Case Presentation: The present case report briefs the finding of a 60-year-old woman presenting to the gynecological outpatient department for a routine gynaecological check-up. She was a known case of type II diabetes mellitus, hypertension, and asthma. She had no history of postmenopausal bleeding or vaginal discharge. Incidentally, on per speculum examination, a polyp of 2x3 cm was seen protruding through the cervical opening (cervical os). Her transvaginal ultrasound revealed a postmenopausal uterus with a thickened endometrium of 10mm. Her histopathology report of dilatation and curettage with polypectomy revealed serous carcinoma against the background of atrophic endometrium. The patient was managed with staging laparotomy with Wertheim’s hysterectomy with bilateral pelvic lymph node dissection, omentectomy, and parietal peritoneum biopsy. Her final histopathology report revealed Stage 1A1 MUSC with atrophic endometrium.

Conclusion: The case report highlights the clinical significance of recognizing MUSC as an early- stage variant of endometrial cancer. Postmenopausal women, vulnerable to uterine serous carcinoma, require comprehensive sampling of all endometrial biopsies, curettings, and endometrial polyps to ensure early detection and accurate staging.

Materials and Methods: Transcriptome data for PCa were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) websites. Differentially expressed neuroendocrine differentiation related genes (NDGs) were identified. By utilizing multivariate Cox analysis, a neuroendocrine differentiation-related molecular model for predicting prognosis was constructed and validated. The study investigated the novel model’s association with the tumor immune microenvironment, clinicopathological characteristics, tumor stemness, and anticancer treatment sensitivity. Additionally, preliminary experimental verifications of Diencephalon / Mesencephalon Homeobox 1 (DMBX1) were conducted.

Results: Finally, we identified a total of 19 differentially expressed NDGs. A neuroendocrine differentiation-related molecular model was established and successfully validated both internally and externally. The high-risk group exhibited significantly poorer biochemical recurrence-free survival (BCRFS) in the training, testing, and validating cohorts. The areas under the receiver operating characteristic curves for the training, testing, and validating cohorts were 0.825, 0.719, and 0.729, respectively. The tumor immune microenvironment, clinicopathological features, tumor stemness, and anti-cancer drug sensitivity was significantly different between high and low-risk patients. Preliminary experiments revealed that higher expression of DMBX1 significantly enhanced the proliferation, migration, and neuroendocrine differentiation of PCa cells.

Conclusion: This research developed a unique neuroendocrine differentiation-related molecular model that is highly suitable for predicting BCRFS. High DMBX1 expression may promote the development and neuroendocrine differentiation of prostate cancer.

Methods: The methodology involves a review of publicly available data to estimate the prevalence and mortality associated with stomach cancer in the region. Years of life lost (YLLs) and years lived with disability (YLDs) are calculated specifically to provide a nuanced understanding of the disease burden. The Human Development Index (HDI) serves as a primary measure of socioeconomic status, allowing us to explore how disparities in health outcomes correlate with socioeconomic conditions.

Results: Findings indicate a clear correlation: lower HDI values are associated with higher incidence and mortality rates of stomach cancer. Countries exhibiting greater socioeconomic inequality demonstrate a disproportionate burden of diseases, reflected in elevated DALYs, YLLs, and YLDs.

Discussion: These results underscore the pressing need for targeted public health interventions to address these disparities. Addressing socioeconomic inequalities is crucial for reducing the burden of stomach cancer in Asia. Our findings advocate for implementing strategic public health measures that focus on improving access to healthcare, enhancing nutritional education, and promoting preventive strategies in high-risk populations.

Conclusion: This study contributes to the growing body of evidence linking socioeconomic factors to health disparities and emphasizes the importance of equitable healthcare access in combating stomach cancer effectively.

Methods: This study utilized Mendelian Randomization (MR) to investigate the causal impact of GM on the development of myopia. Instrumental variables (IVs) were identified from Genome-Wide Association Studies (GWAS), focusing on genetic variants significantly associated with microbiome composition. A comprehensive array of MR techniques was applied to ensure a robust estimation of causal effects and to adjust for potential confounders and pleiotropy.

Results: The Inverse-Variance Weighted (IVW) method was used to identify significant associations between GM and myopia. Increased risk of myopia was linked to the class Betaproteobacteria (OR=1.01, 95% CI 1.004-1.017, P=0.003), the order Burkholderiales (OR=1.009, 95% CI 1.001-1.016, P=0.02), the family Oxalobacteraceae (OR=1.005, 95% CI 1.001-1.01, P=0.023), and several genera including Eubacterium xylanophilum group (OR=1.007, 95% CI 1.001-1.013, P=0.033), and Bifidobacterium (OR=1.005, 95% CI 1-1.01, P=0.038). Protective effects were noted for the order Mollicutes RF9 (OR=0.994, 95% CI 0.99-0.999, P=0.014), the genus Allisonella (OR=0.996, 95% CI 0.993-0.999, P=0.019), the genus Lachnospiraceae UCG001 (OR=0.994, 95% CI 0.989-1, P=0.045), and the family Enterobacteraceae (OR=0.991, 95% CI 0.982-1, P=0.047) and order Enterobacteriales (OR=0.991, 95% CI 0.982-1, P=0.047). Sensitivity analyses further confirmed the robustness of these findings.

Discussion: This study provides causal evidence for the \"Microbiome-Gut-Eye Axis\" in myopia development, identifying specific gut microbiota that influence myopia risk. These findings suggest potential for microbiota-targeted interventions, warranting further research in diverse populations.

Conclusions: The findings support the \"Microbiome-Gut-Eye Axis\" as a potential factor in myopia pathogenesis and highlight microbiota-targeted interventions as novel therapeutic strategies for managing myopia. This study lays the groundwork for further research on how modifying GM can influence eye health and offers new perspectives on preventive health strategies.

Methods: We analyzed the transcriptomic data of 256 sarcoma patients from The Cancer Genome Atlas (TCGA) to define the network and prognostic value of predefined ubiquitination-related genes and performed subgroup analyses. Additionally, the role of TRIM21 in sarcoma progression was explored using cellular experiments.

Results: We identified two ubiquitination-related clusters, and patients in the two clusters were characterized by different survival outcomes, enriched pathways, and characteristics of the tumor microenvironment. A ubiquitination-related signature involving LRRC41, RNF125, TRIM21, and UBE3D was identified to predict prognoses. The signature was associated with patient prognoses in the public sarcoma cohorts and our independent cohort. Immunohistochemistry analyses revealed that the risk score and CD8 could distinguish patients with different survival outcomes in our cohort. Mechanistically, different risk groups were also characterized by distinct enriched pathways and characteristics of the tumor microenvironment. Cellular experiments revealed that TRIM21 overexpression could suppress tumor progression in sarcomas.

Discussion: This study provided a novel classification for sarcoma patients based on expressions of ubiquitination-related genes. The classification and the prognostic model may facilitate the understanding of sarcoma pathogenesis, the prediction of prognosis and immunotherapy response for sarcoma patients. Meanwhile, it was confirmed that TRIM21 suppressed sarcoma progression and identified it as a potential target for therapeutic interventions.

Conclusion: The classification and signature stratify sarcoma patients for prognosis and immunotherapy response, with TRIM21 representing a promising therapeutic target.]]> https://www.benthamscience.comarticle/145262 https://www.benthamscience.comarticle/147016Introduction: Breast Cancer (BC) is one of the most prevalent malignant tumors in women. The incidence of estrogen receptor-positive (ER⁺) breast cancer is as high as 70%, and it is increasing. Amorphophalli rhizoma (APR) has the potential to be used in breast cancer.

Aims: The objectives of the present study were to explore the impact of different APR extracts on the proliferation, migration, and invasion of ER+BC and to investigate their possible mechanism at the molecular level.

Methods: Various extracts of APR were prepared in different solvents, such as petroleum ether, ethyl acetate, n-butanol, and water. ER⁺ T47D breast cancer cell lines were acquired and utilized to assess the effect of APR extracts on ER+ BC. Cell viability was assessed using the cell counting kit8 (CCk8) method, while anti-invasive and migratory effects were examined by transwell and wound healing assay. All the extracts were initially screened, and the ethyl acetate fraction (APR-EA) was found to be the most effective. Ultra High-Performance Liquid Chromatography (UHPLC) of APR-EAE extract revealed the presence of various phytochemicals, such as succinic acid, 2-methoxy resorcinol, penicillic acid, morphine, salicylic acid, α-linolenic acid, and linolenic acid. Flow cytometry, western blot, and immunohistochemistry were used to explore molecular mechanisms.

Results: APR-EA demonstrated anti-proliferative, anti-migratory, and anti-invasive effects on the ER+ T47D cell line. Thus, APR-EAE might inhibit the expression of P-PI3K/PI3K and PAkt/ Akt proteins, which subsequently represses the expression of ERα. This inhibition affects the downstream expression of the proteins CDK4 and Bcl-2, which are linked to cell growth and apoptosis.

Conclusion: Additionally, APR-EA might increase the expression of P21 and Bax proteins, which are associated with cell cycle arrest and apoptosis. Overall, these effects contribute to the anti-ER+ breast cancer properties of APR-EA.

Methods: In this study, siRNA transfection was used to regulate the expression of GPX4. The effect of GPX4 inhibition on HR-proficient ovarian cancer was determined by CCK-8 assay and flow cytometry. Immunofluorescence and comet assay were used to reflect DNA damage. ROS production was measured using DCFH-DA and flow cytometry. The combination index of PARP inhibitors and RSL3 was calculated using CompuSyn software based on Chou- Talalay methodology.

Results: GPX4 inhibition confers HR-proficient ovarian cancer cells sensitive to PARPi due to ROS generation and oxidative stress caused DNA double-strand breakage. The combination of olaparib and niraparib with GPX4 inhibitor RSL3 also showed a synergistic effect.

Conclusion: Combining GPX4 inhibition with PARP inhibitors resulted in a notable increase in DNA damage, ultimately causing the death of cancer cells with proficient HR pathways. Our findings may provide new therapeutic options for HR-proficient patients to benefit from PARP inhibitors and improve outcomes.

Objective: Ferroptosis is a recently observed cell death modality and has been shown to link to the efficacy of different anti-cancer treatments, thus offering opportunities for the development of novel therapies. This study aims to investigate the potentiating effects of COX-2 inhibitors on ferroptosis in nasopharyngeal cancer.

Methods: The inhibitory effects of COX-2 inhibitors celecoxib and rofecoxib on nasopharyngeal cancer cells were assessed with MTT, colony formation, sphere formation, Transwell, and wound healing assays. The status of COX-2 with celecoxib and rofecoxib treatment was investigated by Western blotting and immunofluorescence experiments. Ferroptosis was induced with the GPX4 inhibitor RSL3 with or without COX-2 inhibition and was monitored by fluorescence microscopy. Transcriptomic profiling was conducted with 5-8F cells treated with DMSO as control or celecoxib, and ferroptosis-related candidates were validated by RT-PCR analysis.

Results: Celecoxib and rofecoxib effectively inhibited the growth and migration of nasopharyngeal cancer cells. Both inhibitors evidently sensitized nasopharyngeal cancer cells to ferroptosis induction by RSL3, with celecoxib outperforming rofecoxib. Celecoxib treatment resulted in significantly differentially expressed genes in 5-8F cells, among which CHAC1 was validated as a ferroptosis-related target.

Conclusion: The COX-2 inhibitor celecoxib effectively sensitized nasopharyngeal cancer cells to ferroptosis induction.

Methods: For cellular studies, flow cytometry, colony formation assay, MTT assay, wound healing assay, and ROS measurement were employed. Western blotting was used to assess the expression levels of apoptotic proteins. A subcutaneous tumor xenograft model was established. The analysis included the evaluation of proteins related to the PI3K/AKT signaling pathway, TUNEL, and Ki-67 staining, as well as HE staining.

Results: L-SeMC caused cell death and, in a concentration-dependent manner, reduced the migration, invasion, and proliferation of esophageal cancer cells. Western blot analysis showed that L-SeMC was associated with a decrease in the anti-apoptotic protein Bcl-2 and an increase in the pro-apoptotic protein Bax. It also triggered the mitochondrial apoptosis pathway, promoting the activation of caspase-3 and subsequent cancer cell death induced by L-SeMC. In a dosedependent manner, L-SeMC decreased the phosphorylation of phosphatidylinositol 3-kinase (PI3K) downstream effector molecules. This suggests that L-SeMC inhibits the PI3K/AKT signaling pathway in esophageal cancer cells, contributing to its anticancer effects.

Discussion: Our results suggest that L-Selenomethylselenocysteine acts as a potential therapeutic pathway in esophageal cancer through the PI3K/AKT signaling pathway. Although the current evidence is limited, we are actively increasing the sample size to conduct further verification.

Conclusion: L-SeMC has a strong anticancer effect on human esophageal cancer cells and promotes apoptosis by inhibiting the PI3K/AKT signaling pathway, suggesting that L-SeMC may represent a novel strategy for the treatment of esophageal cancer.

Methods: To ascertain the potential link between IFI30 expression, clinical data, and overall survival (OS) in ccRCC patients, we employed diverse databases, which include TCGA, Gene Expression Profiling Interaction Analysis (GEPIA), and UALCAN. Furthermore, an in-depth analysis of the link between tumor-infiltrating immune cells (TIIC) and IFI30 was carried out using the TIMER, GEPIA, and TISIDB databases. Immunohistochemistry (IHC) was utilized to identify the IFI30 and PD-1 expression levels in a tissue microarray. Patents about molecular classification and drugs in ccRCC were reviewed through Worldwide Espacenet®.

Results: The expression of IFI30 demonstrated a strong association with sample type, lymph node stage, tumor grade, and cancer stage. Elevated IFI30 expression was linked to unfavorable Disease- Specific Survival (DSS) and Overall Survival (OS) outcomes (p <0.01). Furthermore, overexpression of IFI30 was strongly linked to immunomodulatory molecules, chemokines, and increased infiltration of regulatory T cells (Tregs), natural killer (NK) CD56 cells, T helper 1 (Th1) cells, cytotoxic T cells, and T helper cells. IHC analysis confirmed a robust correlation between IFI30 and PD-1 expression.

Conclusion: IFI30 is a prognostic biomarker for ccRCC patients. Targeting IFI30 may provide new strategies for cancer therapy and improve the prognosis of ccRCC patients.

Methods: The ubiquitination-related gene ubiquitin domain-containing protein 1 (UBTD1) was identified using bioinformatics and single-cell analyses. Subsequently, the ability of UBTD1 to predict CRC prognosis and immune checkpoint correlation was analyzed, the potential drug telatinib targeting UBTD1 was explored, and the correlation between UBTD1 and ferroptosis was analyzed. The role of UBTD1 in CRC and ferroptosis was verified using immunohistochemistry, gene knockout, western blot, cell cloning, and immunofluorescence.

Results: UBTD1 was identified as a significant prognostic and predictive gene for CRC and was involved in regulating immune checkpoint levels and immune cell function of CRC patients with CRC. High UBTD1 expression was found to enhance the presence of immune checkpoints that induce immune escape and inhibit ferroptosis onset. Telatinib may be a potential therapeutic drug targeting UBTD1.

Discussion: This study first identifies UBTD1 as an independent prognostic marker for CRC, with high expression correlating with poor patient survival. Mechanistically, UBTD1 promotes tumor immune escape by upregulating key immune checkpoints and inhibits ferroptosis via regulating GPX4 and lipid peroxidation, thereby facilitating CRC progression. Telatinib shows strong binding affinity with UBTD1 and inhibits CRC cell viability, offering a potential targeted therapy for high UBTD1-expressing CRC. These findings link ubiquitination, immune escape, and ferroptosis in CRC, providing a novel molecular target for precision treatment.

Conclusion: Our study demonstrated that UBTD1 is a prognostic marker for CRC in the regulation of ubiquitination and the tumor immune microenvironment and may serve as a modulator of ferroptosis.

Methods: Utilizing public databases (TCGA, GTEx, TARGET, GEO) and bioinformatics tools, a comprehensive analysis of EGLN genes across various cancer types was conducted. Gene expression, mutation data, stemness scores, and clinical information were integrated to evaluate the mutation landscape, expression levels, and prognostic values of EGLNs. Enrichment and pathway analyses explored EGLN-associated biological processes and functional networks. ssGSEA constructed EGLN scores for prognostic evaluation. Colocalization analysis combined eQTL and GWAS data to investigate genetic variations in cervical cancer. Immunohistochemistry validated EGLN expression in cervical cancer tissues.

Results: EGLN genes showed differential expression across cancer types. EGLN1 overexpression was associated with worse survival in cervical squamous cell carcinoma (CESC), pancreatic adenocarcinoma (PAAD), and neuroblastoma (NB), while EGLN3 was linked to poor survival in CESC, lung adenocarcinoma (LUAD), and kidney cancers. EGLNs also demonstrated varied roles in modulating tumor immune activity and heterogeneity.

Conclusion: This study provides new insights into EGLN biology and identifies EGLN1 as a potential biomarker for cervical cancer.

Methods: This study included NPC patients who experienced RI due to the COVID-19 pandemic. Patient characteristics, details of treatment after RI, compensatory treatment, and survival outcomes were analyzed.

Results: A total of 8 patients were identified, with a median RI duration of 19 days. All patients received an additional fraction of radiotherapy due to the interruption. Following RI, all patients completed the recommended radiotherapy regimen and underwent comprehensive locoregional and systemic assessment three months post-treatment. Complete remission of the nasopharyngeal tumor and cervical lymph nodes was achieved in 7 (87.5%) patients. These patients were administered oral tegafur, gimeracil, and oteracil potassium (S-1) MC. All patients completed one year of MC without experiencing grade 3-4 adverse reactions. With a median follow-up of 34.4 months, no instances of disease recurrence were observed. The 2-year disease-free survival and overall survival were both 100%.

Conclusion: MC may serve as an effective compensatory treatment strategy for NPC patients experiencing RI. These findings offer valuable insights for future clinical trials involving NPC patients with RI due to various reasons.

Methods: Univariable MR analyses were used to determine the causal connection between lipoprotein traits and PC. Instrumental variables corresponding to lipoprotein traits were taken from the Global Lipids Genetics Consortium (GLGC) (n = 188,578). The outcome dataset was created from PC summary-level data (n case = 1896, n control = 1939) from a genome-wide association study of European ancestry. Causal effects were evaluated using the inverse variance weighted (IVW) method. For sensitivity analysis, both the weighted median (WM) and MR-Egger methods, among others, were utilized. We also conducted multivariable MR analyses to examine potential confounders.

Results: In univariable MR, IVWmethods supported evidence that HDL cholesterol (OR = 0.463, 95% CI: 0.313-0.685; p = 1.10×10-4) was linked with a decreased risk of PC. These findings were consistent across other MR methods, including MR-Egger (OR = 0.340, 95% CI: 0.182- 0.638; p = 1.30×10-3) and WM (OR = 0.367, 95% CI: 0.195-0.692; p = 1.90×10-3). Our results displayed no significant heterogeneity or horizontal pleiotropy. Furthermore, these associations persisted in the multivariable MR analysis after adjusting for confounding factors such as smoking, alcohol consumption, and body mass index (BMI).

Conclusion: Our comprehensive MR analyses consistently demonstrate a protective association between higher HDL cholesterol levels and decreased PC risk, even after adjustments for key lifestyle factors and BMI.

Aims: This study aimed to construct nanocomposites that can efficiently support Lenvatinib and target liver cancer tissues and cells.

Objective: In this study, ferric oxide-viral-like mesoporous silica nanoparticles-folic acid (Fe₃O₄-vMSN-FA) nanocomposites loaded with Lenvatinib were constructed, and their antihepatocellular carcinoma effects were evaluated.

Methods: The hydrothermal method was used to synthesize ferric oxide (Fe₃O₄). Ferric oxide- viral-like mesoporous silica nanoparticles (Fe₃O₄-vMSN) were synthesized using a twophase method. Then, Fe₃O₄-vMSN was modified with folic acid (Fe₃O₄-vMSN-FA) to better target tumor cells.

Results: The experimental data showed that Fe₃O₄-vMSN-FA nanocomposites were successfully synthesized and could be loaded with Lenvatinib (Len@ Fe₃O₄-vMSN-FA). Fe₃O₄-vMSN-FA had good stability and biocompatibility, and it can release the loaded Lenvatinib faster in an acidic environment (pH 5.5). CCK8 assay and flow cytometry showed that HepG2 cells in the Len@ Fe₃O₄-vMSN group had the lowest cell viability and the highest apoptosis rate, confirming the anticancer properties of Len@ Fe₃O₄-vMSN-FA in vitro. In addition, transwell experiments showed that the migration and invasion ability of HepG2 cells in the Len@ Fe₃O₄-vMSN-FA group were significantly inhibited. In vivo fluorescence imaging in mice confirmed the enhanced tumor-targeting ability of Fe₃O₄-vMSN-FA. The tumor volume of the Len@ Fe₃O₄-vMSN-FA group was significantly reduced, and there was no significant effect on body weight. Moreover, serum liver function index (ALT and AST) and HE staining showed that Len@ Fe₃O₄-vMSN-FA did not cause obvious damage to organ tissue.

Conclusion: Len@ Fe₃O₄-vMSN-FA has a good anti-liver cancer effect. Fe₃O₄-vMSN-FA can be used as an alternative platform for drug delivery, providing more options for cancer therapy.

Methods: We evaluated the anticancer effect of Morusin in pancreatic cancer cells, including its impact on pancreatic cancer cell proliferation, colony formation potential, migration, invasion, cell cycle and apoptosis. RNA sequencing (RNA-seq) analysis was employed to identify potential genes involved in the anticancer activity of Morusin. Furthermore, RT-qPCR and Western blot analysis were utilized to verify the findings.

Results: Our results demonstrated that Morusin administration significantly impaired cell proliferation, migration and invasive activity of pancreatic cancer cells. Additionally, Morusin induced apoptosis and disrupted cell cycle progression. Importantly, Morusin was found to co-regulate SLC6A12, HSPA2, P2RY6 and JPH2 in both cell lines by RNA-seq analysis, with the most significant decrease in mRNA levels of SLC6A12 following administration. Mechanistically, Morusin was found to regulate the expression of SLC6A12 and inhibit NF-κB and β-catenin signaling pathways, which may represent the underlying mechanisms of its antitumor activity.

Conclusion: Our findings suggest that Morusin holds potential as an anti-pancreatic cancer agent by targeting SLC6A12 and modulating its associated signaling pathways.

Methods: Bioinformatic analysis was used to identify the key role of TNS4 in PC. CFPAC-1 PC cells were cultured and genetically modified using lentiviral transfection to stably knock down TNS4 expression. Cell proliferation was assessed using the CCK-8 assay, while cell migration and invasion capabilities were evaluated through Transwell assays. Colony formation and flow cytometry were performed to analyze clonogenic potential and cell cycle distribution, respectively. Apoptosis was assessed using tunel staining. Subcutaneous and orthotopic tumor models were established in nude mice to investigate the in vivo effects. Mice were treated with Dahuang Zhechong Pill by oral gavage. Immunohistochemistry and immunofluorescence were employed to detect the expression of key proteins involved in the NF-κB/VEGF pathway, including E-cadherin and Vimentin. ELISA was used to measure circulating IL-17 and amylase levels in mouse serum to test inflammation response.

Results: TNS4 was upregulated in PC and positively associated with PC progression. TNS4 silencing significantly reduced CFPAC-1 cell proliferation, migration, and invasion in vitro. Flow cytometry demonstrated an increase in G0/G1 phase arrest and apoptosis in the TNS4 silencing group. Subcutaneous models showed the anti-tumor effect of TNS4 silencing. Furthermore, Dahuang Zhechong Pill treatment, when combined with TNS4 knockdown, resulted in a marked decrease in tumor size in orthotopic models. Immunohistochemical analysis revealed reduced expression of NF-κB and VEGF in tumor tissues from the combination treatment group. ELISA results indicated lower levels of serum IL-17, and amylase and higher levels of insulin in combination-treated mice.

Discussion: We proposed an innovative therapeutic patent combining traditional Chinese medicine with targeted gene silencing to inhibit PC progression. By investigating the synergistic effects of TNS4 silencing and Dahuang Zhechong Pill in suppressing the NF-κB/VEGF signaling pathway, our findings highlighted a promising strategy that targets tumor proliferation and modulates the inflammatory microenvironment in PC.

Conclusion: Dahuang Zhechong Pill, in combination with TNS4 silencing, effectively inhibits the NF-κB/VEGF pathway and inflammation response, leading to reduced PC progression. These findings suggest a potential therapeutic approach for targeting PC through the combined use of traditional Chinese medicine and gene editing.

Objective: This study aimed to find an effective resistance-reversed agent of ABC transporter. A series of new β-carboline derivatives have been synthesized and are being applied in various invention patents. One of these is B-9-8, a novel harman dimer, which was synthesized to conduct a series of experiments.

Methods: In this study, we investigated whether B-9-8 could reverse ABCG2-mediated drug resistance by using MTT assay, [³H]-mitoxantrone accumulation/efflux assay, western blot analysis, immunofluorescence analysis, ATPase assay, and molecular modeling assay.

Discussion: B-9-8, as a novel harman dimer, exhibits its reversal activity against ABCG2- mediated multidrug resistance without obvious cytotoxicity. Its actions of inhibiting ABCG2 efflux function and down-regulating the protein expression of ABCG2 are crucial for overcoming drug resistance. This makes B-9-8 a possible candidate drug for combined chemotherapy. Its inhibitory effect of ATPase activity and the strong affinity to ABCG2 further demonstrate the potential of B-9-8 as a targeted modulator for drug resistance.

Conclusion: Our findings indicated that B-9-8 could reverse ABCG2-mediated MDR as a potential and reversible modulator in combination with conventional chemotherapeutic drugs.

Materials and Methods: The study was conducted using the NSCLC cell line A549. Small interfering RNA (siRNA)-mediated RhoB knockdown was performed and combined with perifosine (Akt inhibitor) treatment. Cell proliferation was detected by xCELLigence® RTCA. RhoB, pAkt, and Bcl2l11 expressions were analyzed by ELISA. Apoptosis rates were determined by flow cytometry.

Results: We knocked down RhoB in A549 cells using siRNA. According to the results of the 72-hour experiment, RhoB upregulation was observed to reduce the antiproliferative activity of the Akt inhibitor. The pAkt level was significantly lower in the group where the Akt inhibitor was applied to RhoB-silenced cells via siRNA compared to other treatment groups. The percentage of apoptosis in the group where the Akt inhibitor was applied to RhoBsilenced cells was found to be significantly higher than in the RhoB-suppressed group.

Conclusion: Both proliferation and apoptosis tests determined that the RhoB molecule is a negative regulator of the anti-tumor activity of Akt inhibition in non-small cell lung cancer. This study suggests that RhoB expression may play a critical role in the regulation of Akt inhibition in NSCLC, potentially opening new avenues for treatment strategies.

Methods: Overall, 51 HIV-DLBCL patients, 50 DLBCL patients, and 42 Healthy Donors (HD) were enrolled in the study. Data were extracted from outpatient records and the Hospital Information Management System. SPSS 27.0 software was used for statistical analysis of the data.

Results: Significant differences in lymphocyte subsets were observed between groups. HIVDLBCL patients showed decreased CD4⁺ T cell and regulatory T cell (Treg) counts/percentages compared to DLBCL patients and HD, but increased CD8⁺ T cell counts and percentages, as well as Treg percentages. Age-stratified analysis revealed that older HIV-DLBCL patients had lower CD8⁺ T cell counts, reduced CD3⁺ T cell percentages, and elevated CD56⁺CD16⁺ NK cell proportions compared to their younger counterparts.

Discussion: This study revealed a distinct pattern of immune dysregulation in HIV-DLBCL patients, characterized by CD4⁺ T cell depletion and CD8⁺ T cell expansion, which is consistent with previous studies. Age-related immunosenescence may exacerbate the increased proportion of NK cells and the decline in T-cell function, suggesting a poorer prognosis in elderly patients. However, the lack of association between lymphocyte subsets and chemotherapy efficacy may reflect the broad impact of standard regimens on immune reconstitution. Limitations include the small sample size, absence of functional experiments, and failure to assess the influence of coinfections. Future studies should expand the cohort and integrate multiomics data to validate these findings.

Conclusion: Patients with HIV-DLBCL have distinctive alterations in peripheral blood lymphocyte subsets, such as a decreased absolute count and percentage of CD4+ T cells, in comparison to individuals with DLBCL. These alterations appear age-related and showed no significant association with prior antiretroviral therapy. The therapeutic effect of chemotherapy for HIV-DLBCL, however, might not be impacted by the low absolute count and percentage of CD4+ T-cells in peripheral blood, as well as whether or not they had previously received antiretroviral therapy.]]> https://www.benthamscience.comarticle/148923 https://www.benthamscience.comarticle/146744Background: Esophageal Cancer (EC) is a commonly occurring cancer of the digestive tract. The bismuth compounds from thiosemicarbazones have been observed to be active against cancer cells. However, a synthetic nine-coordinate bismuth (III) complex (complex 1) has never been assessed so far for its anticancer in the esophageal squamous cell carcinoma cell line (EC109).

Objectives: Esophageal Cancer (EC) is a commonly occurring cancer of the digestive tract. The bismuth compounds from thiosemicarbazones have been observed to be active against cancer cells. This study aimed to investigate the apoptosis effect of a complex1 in the EC109 cells.

Methods: EC109 cells were treated with complex1. The MTT assay was employed to assess the viability of EC109 cells; the changes in apoptotic and morphological characteristics, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) were examined. The expression levels of proteins associated with apoptosis were assessed using western blotting.

Results: Complex1 was found to inhibit the growth of EC109 cells, exhibiting an IC50 of 0.654 μM through apoptosis depends upon complexation with bismuth(III). In addition, cells exposed to complex1 exhibited a significant increase in the level of intracellular ROS through the suppression of the antioxidant system and caused a reduction in mitochondrial membrane potential(MMP). Co-treatment with N-acetyl-Lcysteine( NAC), an antioxidant agent prevented accumulation of ROS and cell death. Complex1 also led to enhanced Bax expression, and reduced Bcl-2 expression in EC109 cells, thereby enhancing caspase-3/9 activity.

Discussion: This study reported the first use of Complex 1 for treating EC109 cells and demonstrated its superior anticancer activity. Complex 1 triggered apoptosis by significantly increasing reactive oxygen species (ROS) levels. The mechanism involved the downregulation of Bcl-2 and the upregulation of Bax, which resulted in an elevated Bax/Bcl-2 ratio, mitochondrial membrane potential (MMP) disruption, and activation of the caspase cascades. These findings confirmed that mitochondrialmediated apoptosis is the primary pathway for the anticancer effects of Complex 1.

Conclusion: Our study confirmed that complex1 induced apoptosis via enhancing the generation of ROS along with a decline in levels of antioxidant enzymes, subsequently causing MMP loss.

Materials and Methods: Stress testing was performed by exposing Nirogacestat to various degradation conditions, including acid (0.1 and 1N HCl), base (NaOH), oxidative (30% H₂O₂), thermal (105°C), photolytic, and reductive environments. The mobile phase consisted of acetonitrile and 0.1% triethylamine/formic acid, adjusted to pH 2.5 in a 30:70 (v/v) ratio. Chromatographic separation was achieved using an Acquity UPLC BEH Shield RP-18 column (50 × 1.0 mm, 1.7 μ m), with a flow rate of 0.5 mL/min and detection at 251 nm. Linearity was evaluated over a concentration range of 0.25 to 1.5 μg/mL. Validation studies assessed parameters such as selectivity, linearity, accuracy, precision, robustness, and solution stability.

Results: The method demonstrated excellent linearity (r² = 0.999), with peak area directly proportional to concentration within the studied range. All validation parameters were within acceptable limits. Forced degradation studies revealed distinct degradation products under each stress condition. Notably, alkaline degradation resulted in the least degradation, while acid, peroxide, photolytic, thermal, and reductive conditions produced a variety of degradation products. These were effectively separated from Nirogacestat using the developed method. The relative retention times for Nirogacestat and its impurities remained consistent, and mass spectrometry confirmed the identities of the degradation products.

Discussion: The validated UPLC-MS method exhibited high sensitivity, selectivity, and robustness in detecting Nirogacestat and its impurities. It effectively distinguishes degradation products even within complex matrices and fully complies with ICH guidelines for analytical method validation. The degradation profile of Nirogacestat under various stress conditions provides critical insights into its stability behavior, which is essential for formulation development and regulatory compliance. The successful separation and identification of degradation products further underscore the method’s applicability as a stability-indicating assay.

Conclusion: The developed UPLC-MS method is the first validated stability-indicating technique for Nirogacestat, offering comprehensive impurity profiling. It is precise, accurate, linear, and robust, making it highly suitable for routine quality control and regulatory submission. This method enables the reliable detection of degradation products, thereby enhancing the safety and efficacy profile of Nirogacestat in pharmaceutical preparations.

Methods: We show that PTEN expression varies significantly in many types of tumors and affects the prognosis of patients with cancer using pan-cancer analysis. Patents were reviewed using the World Intellectual Property Organisation database. We analyzed data from GTEx, CCLE, and TCGA to study the correlation between PTEN expression and prognosis, investigated the correlation between PTEN expression and tumor-infiltrating immune cells using TIMER, analyzed the mutation pattern of PTEN and its correlation with neoantigen expression, TMB, MSI, MMRs, and DNA methyltransferases in tumors, and conducted an enrichment analysis of PTEN in tumors using GSEA.

Results: PTEN expression is related to the levels of infiltrating immune cells, such as B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. PTEN expression is closely related to neoantigen expression, tumor mutational burden, microsatellite instability, and mismatch repair. The results of a functional enrichment analysis of PTEN showed that PTEN has the potential as a biomarker for precision immunotherapy of tumors.

Conclusion: This study suggests that PTEN may be involved in the recruitment and regulation of immune-infiltrating cells, tumor development, metastasis, prognosis, tumor immune escape, and immunotherapy, indicating its importance in tumor diagnosis and treatment.

Background/Introduction: Vulvovaginal Candidiasis (VVC) is an infection caused by Candida species. Although the antimicrobial effects of QIFH have been confirmed, there is no clinical study on its effects on VVC.

Methods: One hundred married women (aged 18-45 years) with complaints of vulvar pruritus or burning were recruited for a triple-blind clinical trial at a health center affiliated with Khorramabad University of Medical Sciences. After a definitive diagnosis of vulvovaginal candidiasis, the eligible women were randomly divided into two groups: one receiving QIFH vaginal suppositories (n=45) and the other receiving Clotrimazole vaginal suppositories (n=45). The patients were instructed to use the medications for 7-10 nights. The symptoms and signs of VVC were compared before and after treatment within each group and between the two groups. The data were analyzed using SPSS 24, employing both parametric and non-parametric tests with a 95 percent confidence interval.

Results: The symptoms and signs of VVC, including pruritus, burning and irritation, vaginal discharge, vaginal redness, and swelling with white, thick discharge, significantly improved in both groups after treatment (p<0.001). There were no significant differences between the two groups of QIFH vaginal suppository users and Clotrimazole users regarding the relief of signs and symptoms after treatment (p>0.05).

Discussion: A study comparing Clotrimazole and QIFH vaginal suppositories found that Quercus infectoria extract effectively treated candida and reduced its growth. Treatment with QIFH significantly improved pruritus symptoms. The tannin ingredient in QIFH's tannins acted through various mechanisms, providing therapeutic and antioxidant effects. QIFH could be an alternative for VVC treatment for women.

Conclusion: The QIFH vaginal suppository was as effective as Clotrimazole in treating the symptoms and signs of VVC without any adverse effects. Given the prevalence of VVC and the similarities in the treatment processes with QIFH and Clotrimazole, it can be concluded that QIFH may be an appropriate alternative for VVC treatment for women who prefer to use herbal medicine.

Clinical Trial Registration No. IRCT20190306042943N2.

Background: Testicular cancer is a frequently diagnosed male tumor. Emerging evidence suggests that Copines family genes are implicated in a variety of cancer phenotypes and cancer progression. Analyzing the expression pattern of Copines family genes in testicular cancer may help improve the treatment efficacy of the cancer.

Objective: This study sought to characterize the expression profiles of Copines family genes in the cellular subpopulations of testicular cancer and to identify key signaling pathways through which they regulate cancer progression.

Methods: Based on single-cell transcriptomic data of testicular cancer, we classified testicular cancer cell subpopulations and analyzed the expressions of Copines family genes in each subpopulation. Cell subpopulations were grouped according to the expression levels of Copines family genes, and differentially expressed Copines family genes between the groups were screened by differential expression analysis. Functional enrichment analysis on the differentially expressed genes (DEGs) was performed with a clusterprofiler package. Functional pathways enriched by the Copines family genes were calculated by AUCell enrichment score. Copy number variation (CNV) analysis was performed using inferCNV to analyze gene mutation patterns across cellular subpopulations, and pseudotime analysis was conducted using Monocle to infer cellular differentiation pathways of cellular subpopulations.

Results: Single-cell clustering identified four major cell subpopulations, namely, NK/T cells, tumor cells, B cells, and macrophages. Notably, the control samples had a relatively small proportion of tumor cells. Further clustering of the tumor cells identified six cell subpopulations, among which multiple Copines genes, especially CPNE1 and CPNE3, showed a high expression. The testicular cancer samples were grouped by the expression patterns of Copines genes, and the DEGs between groups included GNLY, MGP1, CFD2, CCL21, SPARCL13 as well as some other genes involved in the malignant progression of cancer. Pseudotime analysis showed that the upregulated genes were enriched in cell migration and PI3K-Akt pathway, while the downregulated genes were related to immunity. This indicated that the Copines genes regulated the cellular heterogeneity and malignant transformation in testicular cancer.

Conclusion: This study revealed the potential molecular mechanism through which Copines family genes drove the progression of testicular cancer through regulating PI3K-Akt signaling pathway and cell cycle, providing a new target for the development of precision treatment targeting Copines family genes and prognostic assessment of the cancer.

Objective: This systematic review and meta-analysis aimed to determine the effect of the GCKR polymorphisms on GDM susceptibility.

Methods: Seven literature databases were searched (from inception to February 17, 2024) to locate relevant studies included in further meta-analysis. Odds ratio (OR) and 95% confidence intervals (CI) in the pooled population were estimated to assess the effects of the variant allele on GDM risk.

Results: For the rs780094 polymorphism, 13 datasets with 3443 GDM cases and 5930 nondiabetic controls were included. The pooled estimates in the allele model (OR: 1.19, 95% CI: 1.07~1.32), homozygote model (OR: 1.27, 95% CI: 1.10~1.47), dominant model (OR: 1.16, 95% CI: 1.03~1.31), and recessive model (OR: 1.31, 95% CI: 1.09~1.57) suggested that the C allele carriers were prone to GDM. For the rs1260326 polymorphism, five datasets with 1495 cases and 2678 controls were integrated. The statistically significant effect of the C allele was evident in the allele model (OR: 1.12, 95% CI: 1.01~1.24) and the homozygote model (OR: 1.26, 95% CI: 1.03~1.54).

Conclusion: This meta-analysis suggested that the C allele of the rs780094 and rs1260326 polymorphisms in the GCKR gene are significantly associated with increased risk of GDM.

Methods: In a cross-sectional study at a tertiary healthcare facility's endocrinology and metabolism outpatient clinic, participants who had undergone their first thyroid FNAB and attended the clinic to review their results were included. Data collection encompassed demographic information, clinical history, and sonographic features of thyroid nodules. Patient knowledge was assessed using a 6-item questionnaire that evaluated awareness of the indications for thyroid FNAB, potential diagnostic outcomes, and the likelihood of a repeat biopsy.

Results: A total of 423 patients participated in this study, with the majority being female (83.7%). The median age was 54 years. The indication for the biopsy was correctly identified by 68.5% of participants. Awareness of the potential for benign (85.1%) and malignant (84.6%) results was high. However, only 20.4% were informed about non-diagnostic outcomes and 16.6% about indeterminate results. Furthermore, 34.1% understood the need for a repeat biopsy. Participants under 65 years of age demonstrated significantly higher knowledge regarding the reason for the biopsy and the potential for benign or malignant results (p < 0.001). Participants with at least a high school education (38.1%) were more knowledgeable about all aspects of FNAB compared to those with lower educational levels (p < 0.05). Patients with a history of non-thyroidal malignancy (5.7%) demonstrated significantly greater understanding of non-diagnostic and indeterminate results (p < 0.001).

Conclusion: The study reveals substantial knowledge gaps, particularly in understanding thyroid FNAB and its outcomes. Thus, targeted educational interventions are necessary to enhance patient comprehension and improve clinical outcomes.

Methods: This retrospective study analyzed sagittal T2WI from 160 patients with pathologically confirmed stage IB-IIA cervical cancer to predict vaginal invasion. Following an 8:2 training-test split, radiomic features were extracted from manually delineated intratumoral regions and four concentrically expanded peritumoral regions (1-4mm). Features selection by Pearson correlation and LASSO regression. Random forest models incorporating intratumoral and peritumoral (0-4mm) features were constructed, with ROC analysis identifying the optimal model. Subsequently, a 3D-ResNet architecture, enhanced with anisotropic convolutional layers and sophisticated data augmentation, was developed and optimized using the optimal ROI configuration. Model interpretability was facilitated using Grad-CAM, with performance assessed by AUC, sensitivity, specificity, accuracy, and precision.

Results: The AIC-enhanced 3D ResNet-18 model, integrating intratumoral and 3mm peritumoral regions, showed superior test performance (AUC: 0.784, Sensitivity: 0.650, Specificity: 0.765, Accuracy: 0.611, Precision: 0.686) versus the baseline (AUC: 0.742), representing a 6% AUC improvement. Grad-CAM heatmaps identified diagnostically relevant regions within the tumor microenvironment, enhancing biological plausibility and model interpretability.

Discussion: This attention-integrated 3D ResNet-18 framework (AUC=0.784) facilitates non-invasive vaginal invasion detection for fertility-sparing decisions, validated through Grad-CAM tumor localization; however, derivation from a single-center cohort warrants external validation and prospective studies before clinical translation.

Conclusion: This preliminary study demonstrates promising deep learning performance (3D ResNet-18+Grad-CAM+AIC) for vaginal invasion assessment, despite moderate n; however, a single-center retrospective design limits generalizability.

Methods: Through literature review and generalization of our clinical experiences, this review thoroughly described the features, mechanisms, advantages, drawbacks, and prospects of NBI in the treatment of head and neck cancer.

Results: NBI is an emerging endoscopic technology that emits an ambient light at wavelengths of 415 nm (blue) and 540 nm (green) to clearly visualize the details on the mucosal surface. It presents potent efficiencies in the preoperative, intraoperative, and postoperative surveillance and diagnosis of head and neck cancer.

Conclusion: NBI is a front-edge imaging technology that allows early screening, precise treatment, and postoperative monitoring of head and neck cancer.

Method: A search of the PubMed, Cochrane Library, and Embase datasets from their beginnings from January 2006 to September 2022 was conducted. The authors separately selected and evaluated studies for qualifying criteria and bias risk.

Result and Discussion: Seven studies in total were included. Of them, a total of 387 patients were integrated for the Heterogeneity index (HI), Conformity Index (CI), Equivalent Uniform Dose (EUD), and mean dose (Dmean) comparison analysis, which showed 3D-CRT & IMRT with odd ratio (OR) =1.93; 95% confidence interval (95% CI) =1.63, 2.22; and P value=0.00. For brain tumor patients, CI was higher in IMRT than 3D-CRT with OR= 0.72; 95% CI =0.41, 1.03; p value <0.001. EUD was higher in IMRT than 3D-CRT, resulting in an increased overall survival with OR=-0.86; 95% CI =-1.30, 0.42; and p value<0.001. However, no statistically significant variance was perceived in Dmean between 3D-CRT and IMRT.

Conclusion: Our records suggested that IMRT with conventional linacs results in a meaningfully lower regular percentage of brain tumor volumes compared to 3D-CRT. Finally, this meta-analysis indicated that IMRT is better than 3D-CRT and decreases the average percent irradiated amount of the brain.

Methods: The orthotopic transplantation (OT), IED and IED-based OT (IED-OT) mouse models were established. Expression patterns of Slco4a1 and Slco1b2 were determined using reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting (WB) and immunohistochemistry (IHC) in various tissues, including lung, stomach, liver, spleen, kidney, colon, small intestine, HCC tissues and adjacent non-cancerous tissues.

Results: Animals exhibited symptoms, including weight loss, lethargy, chills, dyspnea, altered hair texture, and gastrointestinal disturbances, confirming the successful establishment of the IED model. The analysis demonstrated differential expression and tissue-specific distribution of Slco4a1 and Slco1b2, which are associated with IED-induced changes. These alterations potentially disrupt organ transport functions, thereby promoting the development of HCC. Additionally, they suggest a role in rebalancing the tumor microenvironment and mitigating damage resulting from abnormal substance accumulation.

Discussion: This study reveals that IED promotes HCC progression by altering the expression and distribution of Slco4a1 and Slco1b2, leading to transport dysfunction in affected organs. Furthermore, IED and OT exhibit synergistic effects in HCC development. These findings enhance the understanding of the underlying mechanisms of IED related HCC. Future studies should establish animal models incorporating both internal and external factors, with cellular experiments needed to further validate the mechanisms.

Conclusion: Changes in SLCO expression and distribution induced by IED may play pivotal roles in the development of HCC. These findings contribute insights that could inform novel therapeutic strategies against HCC.

Aim: This study aimed to develop an applicable prognostic tool capable of addressing the limitations of current methods. We selected AML patients from the clinic and TCGA database to explore the role of ER stress in response to chemotherapy.

Methods: Patients from the TCGA database were employed as the training cohort, and two GEO datasets were used as external validation cohorts. Univariate/multivariate COX and LASSO regression were exemplified to establish the prognostic model. Kaplan-Meier and timedependent ROC were used to assess and compare the efficiency of the model with ELN stratification and other models. In the training cohort, we selected 5 ER stress-related genes to predict chemosensitivity and establish the ERS-5 prognostic model.

Results and Discussion: The model successfully predicted the overall survival of patients (p < 0.0001, HR = 4.86 (2.79-8.44); AUC = 0.83). It was verified in validation cohorts and could further stratify the risk of various AML subgroups. It also enhanced the ability of ELN to predict the response of patients with AML to main chemotherapeutic drugs. Finally, an “ERS-5” risk score was constructed by the nomogram based on the ERS-5 model and age.

Conclusion: Consequently, in this study, the ERS-5 model was constructed, which allowed more rapid (about 3 hours) and accurate risk stratification and complemented the ability of ELN to assess chemosensitivity.

Objectives: In this single-center retrospective study, the relationship between BCL-2 expression and blood venetoclax concentration was analyzed in 35 patients with AML. After that, we explored the differences in curative effect, adverse reactions, and outcomes between patients with different BCL-2 expression levels and patients with different venetoclax concentration levels, respectively.

Methods: BCL-2 mRNA expression levels were examined by reverse transcription quantitative PCR. Blood venetoclax concentrations were measured using high-performance liquid chromatography- tandem mass spectrometry.

Results and Discussion: The results revealed that among patients with AML, those with lower primary BCL-2 expression had a higher complete remission (CR) rate (p =0.005), overall response (OR) rate (p <0.0001), and progression-free survival time (p =0.04). Posaconazole was revealed to be a strong factor that was able to increase blood venetoclax concentration (p <0.001) and CR rate in the venetoclax plus posaconazole group compared to that in the venetoclax monotherapy group (p =0.002); however, no significant difference was identified in the occurrence of adverse reactions between these groups. Among low and high-blood venetoclax concentration groups, the event-free survival of the former group was significantly higher (p =0.013).

Conclusion: Higher levels of BCL-2 expression at initial diagnosis may have adverse effects on the efficacy and prognosis of patients, and higher levels of venetoclax concentration may advance the time of adverse reactions in patients, thus adversely affecting event-free survival (EFS).

Methods: In vitro experiments were performed on the RAW264.7 mouse macrophage line. After the induction of M1-type macrophages with LPS, the effects of Que on cell morphology, M1/M2 surface marker expression, cytokine expression, and JAK2/STAT3 expression were analyzed. In vivo, male SD rats were used as a model of CCL4-induced hepatic fibrosis, and the effects of Que on serum aminotransferase levels, the histopathological structure of liver tissues, and macrophage-associated protein expression in liver tissues were analyzed.

Results: In vitro experiments revealed that Que can suppress the activation of the JAK2/STAT3 signaling pathway, leading to decreases in the expression of M1 macrophage surface markers and cytokines. Additionally, Que was found to increase the expression of M2 macrophage surface markers and cytokines. In vivo, assays demonstrated that Que significantly ameliorated the development of inflammation and fibrosis in a rat liver fibrosis model.

Discussion: These findings identify quercetin as an orally bioavailable small-molecule modulator of macrophage fate and provide preclinical proof-of-concept for targeting JAK2/STAT3 to reverse inflammation-driven fibrosis in chronic liver disease.

Conclusion: Que can inhibit hepatic fibrosis by promoting M1 to M2 macrophage polarization, which could be associated with its ability to suppress the JAK2/STAT3 signaling pathway in macrophages.

Objective: This investigation is aiming to screen covalent inhibitor for LOXL2.

Methods: Covalent molecule libraries of Life Chemical and Enamine were used. The structures of those molecules were optimized by using LigPrep module of Schrödinger. Then optimized by using the LigPrep module of Schrödinger to generate optimal conformations. For covalent docking, CovDock in Glide module was used for the virtual screening. Finally, wound-healing assays were performed to examine the effects of the potential inhibitors.

Results: Eight potential small molecules were selected by covalent docking from the databases (in total 7,908 candidates). ADMET evaluation indicated that all those eight small molecules satisfy the general standard. Furthermore, wound healing experiments showed that the compound (F50972176) significantly inhibits the migration of cancer cells.

Discussion: Through advanced methodologies, namely binding affinity calculations and ADMET prediction, this strategy enables a decrease in time consumption and improves operational efficacy in the rapid screening of LOXL2 covalent inhibitors, which constitutes a crucial research area.

Conclusion: Virtual screening and experimental verification methods were used to screen covalent inhibitors of LOXL2 by targeting functional disulfide bonds. The compound (F50972176) effectively inhibited the migration of esophageal squamous cell carcinoma cells.

Objective: The aim of this review is to identify from the literature the substances and molecules of West African flora involved in the fight against chronic hepatitis B and liver cancer and to provide a summary of their mechanisms of action.

Methods: Pubmed, HAL open science, and Google Scholar literature search engines were used to identify medicinal plants and molecules from the West African flora.

Results and Discussions: Among West African countries, Gambia and Niger had the highest prevalence of hepatitis B virus infection, and 09 West African countries had high rates of liver cancer. A number of studies carried out in Mali, Benin, Senegal, and Burkina Faso enabled us to list anti-HBV and anticancer plants, as well as a number of molecules isolated from plants found in West African regions.

Conclusion: By offering a glimpse into the world of anti-HBV and anticancer molecules from West Africa, this review provides valuable information to support the future development of herbal antiviral and anticancer drugs.

Objective: The aim of this study is to investigate the sensitizing effect of RBF on OX therapy for DGC, as well as to elucidate the potential targets and mechanisms of action. This exploration is of significant importance for the development of sensitizers that can improve the therapeutic efficacy of OX and for the advancement of patentable innovations in this field.

Methods: MTT assay, flow cytometry, Western blotting, and immunofluorescence assays were employed to assess the inhibitory effects of Resibufogenin (RBF) in combination with OX on DGC in vitro. Human DGC cell xenografts were established in a mouse model to evaluate the efficacy and safety of RBF and OX for treating DGC in vivo.

Results and Discussion: It was found that RBF inhibited the proliferation of DGC cells in a timeand dose-dependent manner. When RBF was used in combination with OX, the sensitivity of DGC cells to OX was improved. Significantly, the combination of OX and RBF acts synergistically to induce apoptosis and autophagy while inhibiting migration and invasion of DGC cells in vitro. In vivo, the combination of OX and RBF dramatically inhibited the progression of DGC in the subcutaneous xenograft model without observable toxicity. Mechanistically, RBF significantly inhibited the expression and activation of FAK. OX and RBF synergistically inhibited the phosphorylation of FAK, AKT, and GSK3β to abrogate the entry of β-catenin into the cell nucleus. RBF sensitizes DGC to oxaliplatin via FAK suppression.

Conclusion: RBF exhibits a pronounced suppressive effect on FAK, and its combination with OX synergistically blocks the FAK/AKT/GSK3β/β-catenin signaling cascade, thereby inhibiting the growth and metastasis of DGC. This study provides a novel avenue for future research and patent development of FAK inhibitors, with the potential to enhance the therapeutic efficacy of DGC treatment and overcome drug resistance.

Methods: This study examined the effects of TMAO (100-400 μmol/L) on oocyte maturation, cumulus cell expansion, mitochondrial distribution, and embryonic development in vitro and in a BALB/c mouse model. The involvement of the NF-κB/NLRP3 signaling pathway in TMAO-induced ovarian dysfunction was assessed using Western blotting and gene expression analyses. The potential therapeutic effect of miRNA-146, an NF-κB inhibitor, was also explored.

Results: Western blotting confirmed that TMAO activates the NF-κB signaling pathway and induces the synthesis of caspase 3 and NLRP3 complexes. However, pretreatment with miRNA-146, an NF-κB inhibitor, significantly reduced inflammation and inflammatory gene expression during TMAO therapy. Additionally, miRNA-146 pretreatment promoted oocyte maturation by suppressing NF-κB/NLRP3 activation, OGCs apoptotic inflammatory factor expression, and the gene expression of NF-κB, caspase 3, and NLRP3.

Conclusion: Findings demonstrate that TMAO disrupts oocyte development through NF- κB/NLRP3 activation, contributing to ovarian dysfunction. Notably, targeting TMAO and its downstream signaling could serve as a novel therapeutic strategy for premature ovarian insufficiency (POI).

Objective: In this study, we aimed to elucidate the regulatory role and the underlying mechanisms controlling the activity of exosomes derived from cancer stem cells (CSCs).

Methods: Our group isolated exosomes from CSCs and non-CSCs to examine their regulatory mechanisms using Transwell migration, Cell Counting Kit-8 (CCK-8), and 5-ethynyl- 2′-deoxyuridine (EdU) assays.

Results: The role of Eukaryotic Translation Initiation Factor 3 Subunit B (EIF3B) in CRC was examined using an in vivo tumorigenesis mouse model. It was found that treatment with exosomes isolated from CD133⁺ cells (CD133+Exos) promoted the proliferation and migration of SW480 cells. The downregulation of EIF3B reduced the proliferation and migration- promoting effects of CD133+ Exos on SW480 cells. Furthermore, CD133⁺ Exos treatment promoted the tumorigenesis of SW480 cells.

Conclusion: Our findings demonstrate that CSC-derived exosomes transport EIF3B into CRC cells to initiate epithelial-to-mesenchymal transition (EMT) and promote metastasis.

Objective: In this study, arylhydrazonopyrazole derivatives (3a-c) were employed in a series of multicomponent reactions to synthesize 3,5,6,7,8,9-hexahydropyrazolo[1,5-a]quinoline and pyran derivatives. Pyrazolo[1,5-a]quinoline derivatives, due to their structural properties, are considered valuable scaffolds for the development of novel drugs targeting similar biological pathways, with the potential for improved therapeutic efficacy. This study aimed to demonstrate the use of simple arylhydrazonopyrazole derivatives in multicomponent reactions with cyclic ketones and aromatic aldehydes. The resulting compounds were then assessed for their cytotoxic and antiproliferative activities. Following these reactions, further heterocyclization processes were conducted, incorporating the quinoline moiety into the final structures. These findings underscore the potential of pyrazolo[ 1,5-a]quinoline derivatives as promising candidates for drug discovery, offering new avenues for targeting diseases with related molecular mechanisms.

Methods: The key starting compound in this study was 3,5-dimethyl-4-(2-phenylhydrazono)-4Hpyrazole, which has been utilized in numerous heterocyclization reactions. These reactions, involving various reagents, such as cyclic ketones and diketones in the presence of aromatic aldehydes, led to the formation of fused tetracyclic compounds. Arylhydrazonopyrazole derivatives (5a-c) were employed in multicomponent reactions to synthesize 3,5,6,7,8,9-hexahydropyrazolo[1,5- a]quinoline and pyran derivatives. The reactions were carried out using both conventional catalysts and ionic liquid-immobilized catalysts. Notably, the use of ionic liquid-immobilized catalysts resulted in higher yields of the desired compounds.

Results: In this study, new compounds were synthesized, characterized, and evaluated for their cytotoxicity against six cancer cell lines: A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460. Additionally, the cytotoxic effects of the synthesized compounds were assessed against hepatocellular carcinoma (HepG2) and cervical carcinoma (HeLa) cell lines. Morphological studies of selected compounds were also conducted to further understand their effects on the cancer cells. Moreover, the cytotoxicity of the selected compounds was tested against seventeen different cancer cell lines, categorized by disease type. Morphological analyses of these selected compounds were also performed to gain deeper insights into their potential as anticancer agents.

Conclusion: The inhibition assays of the tested compounds demonstrated significant activity against c-Met enzymatic activity, with IC₅₀ values ranging from 0.25 to 10.30 nM. Additionally, potent inhibition was observed in the prostate PC-3 cell line, with IC₅₀ values ranging from 0.19 to 8.62 μM. These promising results highlight the potential of these compounds and encourage further research to explore their therapeutic applications in the future.

The Hypoxia-inducible Factor (HIF) pathway is central to the pathophysiology of ccRCC and von Hippel-Lindau (VHL) disease. As part of the VHL-HIF-VEGF axis, the HIF-2α inhibition has been identified as a rationale target for mRCC treatment. Indeed, one such agent called belzutifan is already approved for VHL-associated RCC and other VHLassociated neoplasms, and a series of trials have indicated encouraging efficacy and good tolerability in sporadic mRCC as well. The potential inclusion of belzutifan into the mRCC treatment armamentarium either as a single agent or as combination therapy could cover the lack of therapeutic options as well as the need for a new combination in mRCC; therefore, this drug has the potential to be largely used in mRCC.

In this review, we have recapitulated the clinical data supporting the use of belzutifan in mRCC as monotherapy and the background for combination with other agents as well as its safety profile.

Methods: A platinum-resistance-related gene model was built by bioinformatics analysis. Then, its predictive power was internally validated. Continually, a nomogram was constructed to confirm the model's predictive ability. Afterward, GSEA was used to explore our model's potential functions. The ESTIMATE, CIBERSORT, TIMER, and ssGSEA were applied to estimate immune conditions. Then, somatic mutation and drug sensitivity were also analyzed. Finally, to gain insights into the roles of targeted genes in drug sensitivity, patient-derived tumor organoids (PDOs) validation was performed.

Results: Nine platinum-resistance-related genes, including SLC22A2, TAP1, PC, MCM3, GTF2H2, FXYD5, SUPT6H, IGKC, and MATN2, were anchored to build the predictive model, which was well internally validated. Subsequently, GSEA unveiled that our model genes enriched in the Hedgehog signaling pathway. The predictive signature was associated with immune checkpoint inhibitors such as PD-1, PD-L1, and CTLA4, guiding immunotherapy applications for OC patients. Drugs such as dasatinib, midostaurin, metformin, MK-2206, and mitomycin C might also benefit OC patients with different risk scores. PDOs showed patients with high-risk scores were more resistant to cisplatin than patients with low-risk scores.

Conclusion: The platinum-resistance-related gene signature (SLC22A2, TAP1, PC, MCM3, GTF2H2, FXYD5, SUPT6H, IGKC, and MATN2) is valuable for prognosis prediction and guidance of treatment choices for OC patients.

Methods: DHPPT was produced via C. lunata fermentation of Rg1, isolated by n-butanol extraction and column chromatography, and characterized using FT-IR and ¹H-NMR spectroscopy. Cytotoxicity was assessed against A549 cells (MTT assay). In vivo studies involved plasma lipid analysis (TC, TG, and HDL-C), lung oxidative stress markers (GSH, CAT, GPx, and MDA), inflammatory mediators, including IL-6, NF-κB, and matrix metalloproteinases (MMP-2 & MMP-12), and NADPH oxidase gene expression (NOX-2, NOX-4). Moreover, histopathology was performed using H&E staining.

Results: DHPPT showed potent anticancer activity (IC₅₀ = 67.66 μg/mL) with low toxicity (LD₅₀ = 780 mg/kg). In B[a]P-exposed mice, DHPPT (39 mg/kg) significantly increased HDL-C (87.5%) and antioxidant markers (GSH 162%, CAT 74.6%, GPx 79.8%), decreased TC (28.9%), TG (26.7%), and MDA (60.5%), reduced inflammatory markers (IL-6 32.9%, NF-κB 36.0%, MMP-2 53.3%, MMP-12 40.5%), and downregulated NOX-2 (52.7%) and NOX-4 (63.5%). Histopathology revealed a preserved alveolar structure with reduced inflammation.

Discussion: The therapeutic effects of DHPPT involve multiple mechanisms, such as antioxidant activity through increased GSH, CAT, and GPx levels enhanced free radical scavenging, while decreased MDA indicated reduced lipid peroxidation. Anti-inflammatory action via reduced IL-6 and NF-κB suppressed cytokine signaling pathways, while decreased MMP-2/MMP-12 limited tissue remodeling. Additionally, NOX-2/NOX-4 downregulation reduced reactive oxygen species generation. The superior efficacy of DHPPT against tamoxifen suggests its unique ability to simultaneously target oxidative stress, inflammation, and genetic pathways disrupted by B[a]P. Furthermore, the biotransformation by C. lunata enhanced bioavailability by removing glucose moieties, while preserving the active aglycone structure.

Conclusion: DHPPT demonstrates significant chemopreventive potential against B[a]P-induced lung damage through coordinated antioxidant, anti-inflammatory, and gene-regulatory mechanisms. These findings support further development of microbial-transformed ginsenosides as multifaceted therapeutic agents, with future studies needed to evaluate clinical applications and potential synergies with conventional treatments.

Methods: We performed an exhaustive search across electronic databases such, as PubMed, EMBASE, and the Cochrane CENTRAL, spanning from their inception to December 15, 2023. Only English-published articles evaluating the effectiveness and safety of DOACs in managing cancer- associated VTE were considered. Evaluation criteria encompassed recurrent VTE, major bleeding (MB), clinically significant non-major bleeding (CSNMB), and clinically relevant bleeding (CRB). Statistical analyses were conducted utilizing Comprehensive Meta-Analysis software.

Results: From the 1195 records, 8 studies with 3913 patients were included. DOACs demonstrated a significant reduction in recurrent VTE risk (OR: 0.73, CI 95%: 0.57-0.93, p =0.01) compared to traditional anticoagulants. However, there was a marginal increase in MB risk (OR: 1.24, CI 95%: 0.90-1.69, p =0.17) with DOACs, though not statistically significant. Notably, DOACs were associated with a higher risk of CRNMB (OR: 1.64, CI 95%: 1.24-2.17, p <0.001) and CRB (OR: 1.22, CI 95%: 1.00-1.52, p =0.04). No publication bias was observed. Gastrointestinal cancer, Rivaroxaban/ apixaban use, switching from dalteparin, improved physical function with DOACs, specific tumor sites, and older age subgroups were predictors for bleeding complications in cancer patients on anticoagulant therapy.

Conclusion: This meta-analysis provides evidence supporting the efficacy of DOACs in reducing VTE recurrence in cancer patients. However, the increased risk of bleeding complications warrants careful consideration in personalized treatment decisions. Ongoing research is necessary to refine therapeutic strategies in this complex clinical landscape.

Materials and Methods: Eligible studies were identified in Web of Science, Google Scholar, GLOBOCAN data base, PubMed, Science Direct, Scopus, ScieLo, and HAL to find the relevant ones published up to September 2024. Then, the relevant studies were analyzed using the keywords such as “risk factor or lung cancer” and “lung cancers or lung tumor”. Finally, the supplementary studies were addressed by the data provided by the Health Department at the Ministry of Health and Medical Education of the Islamic Republic of Iran.

Results: Smoking cigarette increases the cases which are at risk as secondhand smokers. The pattern of smoking in Iran is increasing, especially among women at young ages. There is scattered and vague information about gas, air pollution, nutrition and obesity, genetics, occupational exposure, and lifestyle in LC.

Discussion: Based on peer-reviewed published articles and reports from around the world, including a recent investigation into critical factors and risk assessment of lung cancer, we discuss this issue in more detail in the current manuscript discussion section.

Conclusion: Smoking is regarded as the most vital risk factor for LC. However, other risk factors exist, which should be considered in this disease. This study seeks to present the promise of prevention, as well as providing suggestions to healthcare workers.

Objective: The aim of this scoping review is to provide an overview of the role of ZFAS1 in gliomagenesis, outline existing research on its mechanisms in glioma, and identify any knowledge gaps.

Methods: A literature search was carried out using Scopus, PubMed, and Web of Science (WoS) using a specified search string, and the data gathered was discussed and reported.

Results: This scoping review comprised five original research papers that study ZFAS1 and its roles in gliomagenesis. ZFAS1 was found to be highly upregulated in glioma. and overall survival was revealed to be significantly associated with ZFAS1 status and regulated via several pathways and interactions, such as miRNA signalling, Epithelial to Mesenchymal transition (EMT) and Notch signalling pathway. Furthermore, ZFAS1 knockdown decreased cell proliferation, migration, and invasion while promoting cell death, implying that ZFAS1 is involved in glioma cancer progression.

Conclusion: The evaluation of their diagnostic importance and therapeutic potential may aid in the development of novel therapies for glioma cancer.

Methods: A comprehensive literature review was conducted using databases such as PubMed, Google Scholar, and ScienceDirect. The study adopted a multidisciplinary approach to assess genetic, hormonal, and environmental contributors to BPH. Conventional treatment modalities, including pharmacological and surgical interventions, were analysed alongside their limitations. The pharmacological potential of medicinal plants traditionally used in Ayurveda and Homeopathy was examined, focusing on their bioactive compounds and mechanisms of action.

Results: Findings highlight the growing interest in plant-based therapies due to their favorable safety profiles and potential multi-targeted mechanisms. Several medicinal plants, such as Serenoa repens, Withania somnifera, and Urtica dioica, demonstrate anti-inflammatory, anti-androgenic, and antioxidant activities beneficial in BPH management. The review underscores the therapeutic value of integrating phytotherapy with conventional care to enhance treatment efficacy and patient outcomes.

Discussion: Bridging traditional knowledge systems with evidence-based research may offer novel insights into BPH therapy. While challenges persist in standardizing herbal formulations and conducting rigorous clinical trials, preliminary findings are encouraging.

Conclusion: Integrating traditional medicinal knowledge with modern scientific validation may lead to safe, effective, and innovative therapies for BPH, ultimately improving the quality of life for affected individuals.

Objective: The objective of the present research was to identify the most suitable counterpart for celecoxib, which would produce synergistic effects and improve the selectivity index, safety, and efficacy of targeting cancer cells.

Methods: The HOPE-62 cancer cell line and noncancerous LLC-MK2 cell line were used to analyze the activity of the prepared formulations. The effectiveness was compared by calculating the half-maximal inhibitory concentration (IC50) values of carrageenan, celecoxib, and celecoxib embedded with carrageenan. The release pattern of celecoxib from the carrageenan matrix was also determined by using a trans-diffusion cell; moreover, the binding sites of carrageenan and celecoxib were also evaluated through in silico molecular docking studies.

Results: Carrageenan showed promising anticancer activity, with an IC₅₀ value of 17.3±2 μM against the HOPE- 62 cell line. When blended with celecoxib (15.6±2 μM), the combination achieved enhanced efficacy and improved selectivity over celecoxib alone (IC₅₀ of 10.3±1.5 μM). In noncancerous LLC-MK2 cells, the IC₅₀ values were observed to be significantly higher: 1484 ±6 μM in the combined formulation and with IC₅₀ values of 559±3 μM and 878±4 μM, respectively, in celecoxib and carrageenan alone.

Conclusion: The carrageenan-embedded celecoxib exhibited a significant increase in the selectivity index from 32 to 144, which suggests enhanced anticancer activity with a favorable safety profile. Initially, sustained release of celecoxib from the blend was at a higher rate, but steadily maintained rates were. The In-silico docking studies also supported the synergistic activity of the combined form through separate interaction patterns without interfering with others. These findings underscore the therapeutic potential of excipient–drug blending strategies to achieve synergistic effects, excellent selectivity, and reduced toxicity in cancer treatments.

Objective: This review encapsulates recent progress in ACTA2-AS1 research, examining its expression profile, biological functions, molecular mechanisms, and anticipated influence on cancer diagnosis, treatment, and prognosis, emphasizing its potential as a novel therapeutic target based on lncRNA and its prognostic utility as a biomarker.

Methods: Based on a comprehensive search of the PubMed database for the biological function of lncRNA ACTA2-AS1 in malignant tumors, the current research is systematically summarized and critically analyzed.

Results: ACTA2-AS1 plays a complex role in various biological processes in tumor cells, encompassing proliferation, apoptosis, and cell cycle arrest. It also contributes to migration, invasion, epithelial-mesenchymal transition (EMT), and drug resistance. Mechanistically, ACTA2-AS1 influences oncogenic or tumor-suppressive effects via a complex regulatory network. It can adsorb specific 5 miRNAs as competitive endogenous RNAs (ceRNAs), thereby mitigating the suppression of downstream mRNA targets implicated in tumorigenesis (e.g., SOX7, KLF9, CXCL2, BCL2L11, etc.) and modulating their downstream signaling pathways (e.g., Wnt5a/PKC, SMAD3, mTOR, etc.), demonstrating a broad spectrum of dual roles in carcinogenesis and tumor suppression.

Conclusion: ACTA2-AS1 is a promising biomarker and molecular target for the treatment of cancer.

Objective: To verify the relationship between the expression of PD-L1 in CTCs in HLC and the consistency in tissue and the preliminary clinical application.

Methods: A laboratory-based experimental study was carried out at Fujian Medical University Union Hospital. CTCs were identified using an immunomagnetic positive sorting methodology. Simultaneous detection was conducted on the CTC levels among PD-L1 positive patients, aiming to ascertain the dynamic relationship between real-time CTC fluctuations and the clinicopathological indices of the patients. This investigation encompassed a cohort of 38 individuals, wherein PD-L1 expression analysis was executed to delineate CTC variations in PD-L1- positive patients.

Results: The constructed immunolipid magnetic nano-beads demonstrated pronounced efficacy in capturing CTCs, and the lipid nanoparticles exhibited noteworthy capture efficiency coupled with minimal cytotoxic effects. The assessment of PD-L1 expression consistency between CTCs and tissue specimens revealed a substantial agreement surpassing 70%. Furthermore, inhibition of PD-L1 yielded a significant elevation in the cytokine TNF- α levels, accompanied by a concomitant reduction in IL-10 levels.

Conclusion: The CTC sorting system devised in this investigation boasts attributes of remarkable specificity and sensitivity. By virtue of PD-L1 expression analysis, it holds the potential to offer instructive implications for tailoring individualized treatments in clinical scenarios.

Methods: ZnO-NPs were synthesized extracellularly using A. biplanus fungal extract. The nanoparticles were characterized through UV-Vis spectrophotometry, showing an absorbance peak at 375 nm, and scanning electron microscopy (SEM), which determined their morphology and size. The anticancer activity was evaluated in vitro using HCT-116 cells. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were assessed to understand the mechanism of cytotoxicity. In vivo studies were proposed for further validation.

Results: The synthesized ZnO-NPs appeared pale white and exhibited a characteristic absorbance at 375 nm. SEM revealed spherical particles ranging from 35–150 nm. The ZnO-NPs showed strong anticancer activity with an IC₅₀ value of 40.6 μg/mL. ROS levels increased significantly in treated cells, while the MMP decreased to 77.25% compared to 100% in controls.

Discussion: ZnO-NPs exerted cytotoxic effects via ROS generation and mitochondrial dysfunction. These results underscore the nanoparticles’ ability to induce apoptosis in cancer cells through oxidative stress pathways.

Conclusion: Biogenically synthesized ZnO-NPs from A. biplanus show promise as eco-friendly anticancer agents. Further in vivo studies are recommended to confirm their therapeutic potential.

Aim: This study aimed to evaluate the cytotoxic effects, apoptosis induction, changes in cell cycle progression, and gene expression alterations of new heterocyclic compounds and their precursors against the acute monocytic leukemia cell line THP-1 through in vitro experimentation and computational approaches.

Methods: The study employed cytotoxicity assays, flow cytometry analyses, gene expression evaluations, oral bioavailability studies, and molecular modeling. Among the compounds tested, 6, 25, and 26 demonstrated the greatest potency and selectivity, exhibiting substantially increased cytotoxicity (1.18 μM < IC₅₀ < 7.66 μM) against the THP-1 cell line. Investigations into apoptosis induction and cell cycle changes revealed that these compounds primarily caused an increase in the number of THP-1 cells undergoing apoptosis after 48 hours of treatment. Additionally, compounds 6 and 25 induced an accumulation of cells in the G0/G1 phase in the same cell line.

Results: Regarding gene expression, a shift in the expression profile of genes associated with apoptotic mechanisms was observed. Furthermore, in silico analysis revealed that these three active compounds potentially interact with histone deacetylase 8 (HDAC8), a protein known to be associated with cancer.

Conclusion: These findings underscore the potential of these compounds as candidates for the development of novel therapeutic approaches in oncology.

Objectives: Although CDK4/6 inhibitors class of therapy has revolutionized the treatment of metastatic breast cancer, some patients showed resistance and decreased efficacy. This study is the first to propose innovative computational strategies to improve the effectiveness and pharmacokinetic properties of existing HER2/CDK4/6 inhibitors anti-cancer agents. Through computer-aided drug design, the activity of existing breast cancer drug candidates has been tested. Structural modifications have been applied for in-silico optimization of their biological activity.

Methods: In this research, twenty-two analogues of the tested compounds have been proposed. Their biological activity and pharmacokinetic properties (ADMET) have been tested using BIOVIA Discovery Studio software.

Results: Out of the designed analogous compounds, seven proposed structures demonstrated superior efficacy compared to the original drugs. The research study docking studies revealed that modifications to lapatinib and tucatinib improved binding affinity to HER2 by 15-25%, with docking scores of -18.34 kcal/mol and -1.04 kcal/mol, respectively. Similarly, CDK4/6 inhibitors exhibited enhanced selectivity, with abemaciclib showing the highest binding energy of -13.2 kcal/mol. ADMET predictions suggested improved solubility and reduced toxicity risks compared to the original drugs.

Conclusion: The research study results demonstrate that the synthesis of more lipophilic analogues of lapatinib or tucatinib and, likewise designing of fluorinated derivatives of CDK4/6 inhibitors play a crucial role in improving the efficacy of these anti-cancer agents. These findings highlight the potential of the proposed modifications as promising candidates for further pharmacological and in vitro and in vivo clinical validation.

Materials and Methods: This multi-center, randomized, double-blind, placebo-controlled trial enrolled 136 NSCLC patients scheduled for carboplatin-based chemotherapy. Participants were randomly assigned to the treatment group (JPYW with standard antiemetic drugs) and the control group (placebo with standard antiemetic drugs). The complete control rate of nausea and vomiting was assessed using the Visual Analog Scale (VAS) and patient diaries. Control of anorexia, bloating, constipation, and quality of life was measured using the Functional Living Index-Emesis scale and the Brief Fatigue Inventory (BFI).

Results: The primary objective of this study was to assess the efficacy of JPYW in alleviating non-vomiting digestive symptoms, such as nausea and anorexia, in NSCLC patients receiving carboplatin-based chemotherapy. The secondary objective was to evaluate its effect on improving bloating, constipation, quality of life, and safety.

Discussion: Previous studies have shown that Chinese herbs, such as ginger, are effective in treating chemotherapy- induced nausea and vomiting (CINV). JPYW, a multi-component TCM formula, contains active compounds from Codonopsis pilosula and Atractylodes macrocephala. JPYW exerts anti-inflammatory and prokinetic effects that can synergistically regulate gastrointestinal functions. Preliminary observations confirmed the safety of JPYW combined with standard chemotherapy.

Conclusion: The current findings contribute to the treatment of adverse reactions to tumor chemotherapy and are expected to improve the quality of life for chemotherapy patients.

Objective: The present work was undertaken to evaluate the anticancer potential of aurone based test compounds AU3, AU4, AU5, AU7, and AU10 in breast cancer cell lines MCF-7.

Methods: The azaindole based aurones were synthesized by the condensing 4,6-dimethoxybenzofuran-3(2H)-one derivative with various indole aldehydes in the presence of sodium hydroxide. The MCF-7 breast cancer cell line was used to assess the cytotoxic effects of these compounds. Molecular docking studies of the synthesized compounds against the Cyclin-dependent kinase 2 (CDK2)/Cyclin A complex were conducted.

Results: Our experimental findings demonstrated that AU3, AU4, AU5, AU7, and AU10 elicited significant effects on MCF-7 by virtue of its minimum cell viability, with IC50 values of 70.14 μM, 87.85 μM, 133.21 μM, 52.79 μM, and 99.55 μM, respectively, thus, exhibits potential anticancer action. Further, to corroborate the anticancer potential, we investigated mechanisms of action through molecular docking studies with the CDK2/Cyclin A complex (PDB: 6GUC) and their findings demonstrated that test compounds showed robust binding through various interactions, including hydrogen bonds, Pi-interactions, and Alkyl bonds with key residues such as Lys129, Asp127, Gln131, and Asp145. Test compounds AU3 and AU7, exhibited better binding affinities and diverse interaction profiles, suggesting a potent disruption of CDK2/Cyclin A activity.

Conclusion: Thus, in conclusion, our findings revealed that AU3, AU4, AU5, AU7, and AU10 elicited anticancer action and their effects through CDK2/Cyclin A disruption.

Methods: In the current research, A549 and Hcc1833 cells were treated with different doses of oridonin, and cell proliferation and migration were detected using CCK8, EdU, Transwell, and wound healing assays. A subcutaneous tumor and caudal vein metastasis model was generated to verify the inhibitory effects of oridonin on Hcc1833 tumor growth and metastasis in vivo. Proteomics analyses then were performed to examine the regulatory mechanism. LiP-SMap combined with microscale thermophoresis and molecular docking analyses were used to validate the relationship between oridonin and S100A11.

Results: Data showed that oridonin suppressed cell proliferation and migration depending on dose and suppressed tumor growth and invasion. LiP-SMap and molecular docking analyses confirmed that oridonin interacted with the Asn-53 residue of S100A11, which inhibited the activation of oridonin. S100A11 overexpression reversed the inhibitory effects of oridonin on cell proliferation and migration.

Conclusion: In conclusion, the data indicate that oridonin suppresses LC malignant progression by targeting S100A11.

Methods: We tested the effects of luteolin and PX-478, both alone and in combination, on HIF-1α level in breast cancer cells under hypoxia using the cell viability assay. To determine the rationale for the cell growth inhibition induced by the luteolin+PX-478 combination, we conducted experiments to assess cell survival, apoptosis, cell cycle, invasion, and migration under both normoxic and hypoxic conditions. Furthermore, we evaluated the effect of this combination on DNA damage response under hypoxic stress via Comet assay and immunofluorescence staining.

Results: Our findings revealed that the luteolin+PX-478 combination significantly suppressed the growth of MDA-MB-231 cells. In addition, we assessed time-dependent expression of HIF1α in MDA-MB-231 cells and observed that the combination of luteolin and PX-478 down-regulated the HIF-1α level. Finally, we found that the luteolin+PX-478 combination induced apoptosis and G2 cell cycle arrest and enhanced DNA damage response. This combination also sensitized breast cancer cells to ionizing radiation in hypoxic stress.

Discussion: The findings suggested that targeting HIF-1α with a combination of luteolin and PX-478 may provide a synergistic approach to suppressing tumor growth and enhancing therapeutic response under hypoxic conditions. The observed effects on apoptosis, cell cycle arrest, and DNA damage response indicated that this combination could be a promising strategy for overcoming hypoxia-induced resistance in breast cancer therapy.

Conclusion: Collectively, our results suggested the combination of luteolin and PX-478 to enhance the anticancer effects of PX-478 in breast carcinoma cells by impeding the cell growth and inducing DNA damage response under hypoxia.

Methods: Firstly, a drug resistance model was established, and the expression levels of related RTK were detected by qPCR. Western blot was used to detect the protein expression levels of Akt and MAPK signaling pathways in the control group, single-drug group and two-drug combination group. The gene silencing of SHP2 was achieved by transfection of siRNA and verified by Western blot. CCK8 kit and clone formation assay were used to detect cell proliferation activity. In vivo model of mutant thyroid cancer cells was established by subcutaneous injection of mice and then divided into four groups. Tumor diameter was measured every two days. Immunohistochemistry was used to evaluate the expression of p-ERK, p-AKT and Ki67 in mouse tumors.

Results: In this study, dabrafenib-resistant ATC cells were first constructed, and the response of RTKs in drugresistant cells was upregulated to activate Akt and MER/ERK pathways. The activation of Akt and MEK/ERK pathways in the combination group was significantly inhibited, and the proliferation ability of tumor cells was significantly reduced compared with Dabrafenib, SHP099 group and DMSO group. To verify that SHP099 was not off-target, we also silenced SHP2 expression by transfection with siRNA and obtained the same results. Finally, by building a mouse drug resistance model, we confirmed that dabrafenib and SHP099 can also play a powerful anti-cancer effect in vivo.

Conclusion: The SHP2 inhibitor SHP099 can effectively reverse the drug resistance of dabrafenib through inhibiting the reactivated RAS signaling pathway in anaplastic thyroid cancer.The combination of dabrafenib with SHP2 inhibitor has shown significant tumor suppressive effects for dabrafenib-resistant cells and it may be a new therapeutic strategy with longer lasting therapeutic benefits.

Methods: A comprehensive literature search was conducted using PubMed, ScienceDirect, and Google Scholar with search terms like \"Cancer and proteomics\" and \"Mass spectrometry in oncology,\" utilizing Boolean operators for refinement. Selection criteria included peer-reviewed articles in English on MS-based biomarker detection, tumor-specific proteins, and drug resistance markers, excluding non-peer-reviewed works and pre-2000 publications unless foundational. Extracted data focused on MS methodologies, biomarker sensitivity, and clinical applications, particularly advances in detecting low-abundance biomarkers and monitoring treatment response. Methodological quality was assessed using PRISMA, evaluating study design, sample size, reproducibility, and statistical analysis. Ethical approval was not required, but adherence to systematic review guidelines and proper citation were ensured.

Results: In this review, we highlighted the advanced analytical technique for cancer diagnosis and management of cancer, and described the objective of novel cancer biomarkers. Mass spectrometry (MS) is transforming cancer diagnostics and personalized medicine by enabling precise biomarker detection and monitoring. Unlike traditional antibody-based methods, MS provides high-throughput, quantitative analysis of tumor-specific proteins in clinical samples like blood and tissue. Advanced MS techniques improve sensitivity, allowing for the identification of low-abundance biomarkers and tumor-associated proteoforms, including post-translational modifications and drug resistance markers. In research, MS-based proteomics supports multi-center biomarker validation studies with standardized protocols, enhancing reproducibility. The integration of proteomic data with genomic and transcriptomic datasets through proteogenomics is refining precision oncology strategies. These advancements are bridging the gap between research and clinical application, making MS a critical tool for early cancer detection, prognosis, and therapy selection.

Conclusion: Advancements in technology and analytical techniques have helped to produce more accurate and sensitive cancer-specific biomarkers. These methods are advancing rapidly, and developing high-throughput platforms has yielded great results. However, the substantial variation in protein concentrations makes cancer protein profiling extremely complicated. This shows that more technical developments are required in the future to improve proteome broad screening of cancer cells.

Objective: To assess the clinical features and prognostic factors of HZ in cancer patients through systematic review and meta-analysis. The study aimed to calculate the relative risk of HZ in malignancy and analyze factors affecting prognosis, such as age, gender, tumor type, and treatment.

Methods: A systematic search in PubMed (2016-2024) identified studies on HZ and malignancy. Two reviewers independently screened and selected studies, extracting data on study characteristics, population demographics, and outcomes. Statistical heterogeneity across the studies was addressed using random-effects models, while subgroup analyses were performed to identify potential sources of heterogeneity.

Results: Out of the 633 records reviewed, 13 studies satisfied the eligibility criteria and were incorporated into the meta-analysis. The combined relative risk for any type of cancer was found to be 1.82(95% CI: 1.29,2.57). The combined relative risk for any solid tumors was 1.63(95% CI: 1.08,2.46). The combined relative risk for any haematological cancer was 3.43(95% CI: 1.33,8.86). The combined analysis of all treatment modalities (including Radiotherapy, Chemotherapy, Immunosuppression, HSCT) shows a significant overall effect with a risk ratio of 1.78(95%CI: 1.59,2.00).

Conclusion: Cancer patients have increased HZ risk due to immunosuppression from the malignancy and its treatment, especially in hematological cancers and those undergoing stem cell transplantation.