Materials and Methods: We screened differentially expressed genes (DEGs) using mRNA expression profile data from Gene Expression Omnibus (GEO). Then functional and pathway enrichment analyses of DEGs were performed utilizing the database for annotation, visualization, and integrated discovery (DAVID) and the GEO Data Analysis Module within the ACBI Bioinformation tool. Target genes with differential expression of miRNAs were predicted using the miRWalk (Version 3.0) database, and the intersection between these predictions and DEGs was selected as differentially expressed miRNAtarget genes. In addition, a protein-protein interaction (PPI) network and an miRNAmRNA regulatory network were constructed. Finally, L1000CDS2 database analyses were performed to identify the potential therapeutic targets for IAs.

Results: In total, 742 DEGs and 171 DEGs were identified from the GSE13353 and GSE15629 datasets, respectively. The PPI of DEGs consisted of 868 nodes and 618 edges, including 392 upregulated genes and 521 downregulated genes, respectively, while 10 hub genes were identified. Among the top 10 hub genes, justification of CXCR4, IL6, CCR5, CCL5, CXCR2, CXCL1, CCL2, CCL20, CD4, and CXCL10. These hub genes were primarily augmented in the atherosclerosis process, cytokine-cytokine receptor interaction and cell adhesion molecules pathways. Through the miRNAs-hub gene network construction, 7 miRNAs associated with the hub genes were identified. The results suggest that the sensitivity toward simvastatin, curcumin, parthenolide, celastrol, BMS-345541, etc., correlates with the expression of 10 hub genes.

Conclusion: In summary, this study reveals some crucial genes and pathways potentially involved in the pathogenesis of IAs progression. These findings provide a new insight into the research and treatment of IAs.

Methods: Two mRNA expression datasets (GSE58399 and GSE42669) from GEO were analyzed to identify differentially expressed genes (DEGs) between recurrent and primary tumors. Functional enrichment (Gene Ontology, KEGG) characterized implicated processes and pathways. A protein–protein interaction network (STRING and Cytoscape) identified hub genes. miRWalk 3.0, integrating TargetScan, miRDB, and miRTarBase, predicted miRNAs targeting hub genes and defined miRNA–mRNA interactions. The Connectivity Map (CMap) was used to prioritize small molecules predicted to reverse the DEGs signature. Kaplan–Meier survival analyses assessed associations between candidate genes and patient outcomes.

Results: We identified 201 DEGs and constructed a PPI network comprising 180 nodes and 337 edges. Ten hub genes were prioritized. CMap nominated five top candidate compounds— levamisole, chlorzoxazone, ranitidine, atovaquone, and chrysin—as potential therapeutics for glioblastoma recurrence. Synaptotagmin 1 (SYT1) emerged among hub genes and was predicted to be regulated by 12 miRNAs. Elevated SYT1 expression correlated with poorer overall and progression-free survival in recurrent glioblastoma patients.

Discussion: This integrative analysis highlights SYT1 and its upstream miRNAs as candidate biomarkers and potential therapeutic targets in recurrent glioblastoma and proposes several repurposable compounds for experimental validation. Further functional studies and clinical validation are required prior to translation.

Conclusion: Collectively, this study offers valuable insights into the regulatory landscape of recurrent glioblastoma and lays the groundwork for more targeted and personalized therapeutic approaches.]]> https://www.benthamscience.com/article/1487022026-06-02 https://www.benthamscience.com/article/1552552026-06-02Introduction: Non-communicable diseases (NCDs), including metabolic disorders, cardiovascular diseases, liver pathologies, and age-related syndromes, are a major global health challenge. Human placental extract (HPE) and related formulations, such as Laennec and porcinederived extracts, have been investigated as cell-free therapeutic agents capable of modulating physiological and immunological pathways.

Methods: A systematic literature review was conducted using PubMed, MEDLINE, Scopus, Google Scholar, and the National Library of Medicine databases. Only original English-language research articles were included. Data were extracted on the biochemical composition, mechanisms of action, and therapeutic outcomes of placental extracts in preclinical and clinical studies.

Results: HPE was shown to enhance liver function by reducing oxidative stress, promoting hepatocyte regeneration, and regulating apoptosis and autophagy. In metabolic disorders and cachexia, it preserved muscle and adipose tissue and alleviated symptoms of cirrhosis and metabolic dysfunction- associated steatohepatitis. Laennec and porcine extracts improved iron metabolism, reduced hepatic fibrosis, and enhanced glucose regulation in type 2 diabetes and non-alcoholic fatty liver disease. Additional reported effects included anti-aging properties, relief in chronic fatigue syndrome, and dermatological benefits, such as reduced hair loss and improved allergic contact dermatitis.

Discussion: Placental extracts, such as HPE, Laennec, and porcine formulations, show promise for treating NCDs, including metabolic disorders, liver pathologies, and age-related syndromes. Preclinical and clinical studies highlight their mechanisms, which involve reducing oxidative stress, promoting hepatocyte regeneration, regulating apoptosis/autophagy, and improving iron metabolism and glucose control. Benefits include alleviating cirrhosis, type 2 diabetes, cachexia, chronic fatigue, and dermatological issues like hair loss. While the evidence is encouraging, largescale trials are needed to confirm their efficacy and the underlying molecular pathways.

Conclusion: Placental extracts exhibited diverse therapeutic effects across multiple NCDs, mediated by immunomodulatory, antioxidative, and metabolic regulatory mechanisms. While current evidence from preclinical and clinical studies is promising, large-scale, rigorously designed trials are needed to validate efficacy and clarify molecular pathways.

Materials and Methods: In the present investigation, AD was induced in control, exercise, empagliflozin (10 mg/kg BW, PO), and combined intervention groups using intrahippocampal injections of an amyloid-beta (Aβ) prepared solution via stereotaxic surgery. The therapeutic effects of each treatment, exercise alone, empagliflozin alone, and exercise plus empagliflozin, were studied. After 28 days, spatial memory tests were used to assess memory and learning. Furthermore, histopathological (H&E and Congo red) and immunohistochemical (GFAP) analyses were performed, and the ADP/ATP ratio in isolated brain mitochondria was measured by HPLC.

Results: Our results showed that the combined program of physical training and empagliflozin treatment in the Aβ-induced AD model drastically improved cognitive functions and neurological parameters, including target-finding time, traveled distance, time spent in the target quadrant, and ADP/ATP ratios in brain mitochondria. Additionally, it diminished necrotic cell death and reduced Aβ plaques but did not notably affect astrocyte activity.

Discussion: Exercise and empagliflozin, by affecting mitochondrial energy balance and reducing amyloid deposition, play key roles in mitigating AD pathophysiology.

Conclusion: The combined effects of the treatments used in this experimental method yielded significant improvements in cognitive functions. These findings provide a basis for further clinical studies for the exploration of the synergistic impact of the aforementioned therapeutic methods.

Methods: SPF-grade SD rats were divided into groups, and a PCPA-induced insomnia rat model was established. Mongolian medical warm acupuncture was applied to acupoints such as “Dinghui”, “Heyi”, and “Heart”. General behavior, spontaneous activity, and pentobarbital-induced sleep tests were observed before and after treatment; Western blot and IHC were used to analyze the expression of Clock, Bmal1, Per1, and Per2 proteins in the hypothalamus; Realtime Quantitative PCR was used to analyze mRNA expression of Clock, Bmal1, Per1, and Per2 in the hypothalamus; HE staining was used to observe morphological changes in hypothalamic neurons.

Results: After intervention with Mongolian medical warm acupuncture, insomniac rats showed quiet behavior and reduced activity, with drinking, eating, and mental state gradually returning to normal; Western blot results showed that, compared to the blank group, Clock and Bmal1 protein expression in the hypothalamus of the model group rats was significantly decreased (p<0.05), while Per1 and Per2 expression was significantly increased (p<0.05). Compared to the model group, the warm acupuncture group showed significantly increased Clock and Bmal1 protein expression (p<0.05), and significantly decreased Per1 and Per2 protein expression (p<0.05). IHC results showed that Clock and Bmal1 positive expression in the model group was significantly reduced, while expression in the warm acupuncture group and drug group was significantly increased; PCR results showed that, compared to the blank group, Clock and Bmal1 expression in the hypothalamus of the model group rats was significantly decreased (p<0.05), while Per1 and Per2 expression was significantly increased (p<0.05). Compared to the model group, the warm acupuncture group showed significantly increased Clock and Bmal1 expression (p<0.05), and significantly decreased Per1 and Per2 expression (p<0.05). HE staining results showed that in the blank group, cell membranes were intact, nuclei were located centrally, and nucleoli were clearly visible; in the model group, cell numbers were significantly reduced, boundaries were unclear, cells were swollen, and many nuclei were displaced; in the warm acupuncture group and drug group, hypothalamic cells were densely and orderly arranged, structures were clear, and cell damage was significantly restored.

Discussion: The findings suggest that Mongolian medical warm acupuncture exerts a regulatory effect on hypothalamic biological clock gene expression, which may contribute to the restoration of circadian rhythm balance and reduction of hyperarousal in insomnia rats.

Conclusion: Mongolian medical warm acupuncture significantly reduces excitability in insomniac rats. The sleep-promoting mechanism of Mongolian medical warm acupuncture is closely related to its regulation of hypothalamic expression of biological clock genes Clock, Bmal1, Per1, and Per2 in insomniac rats.

Methods: Potential pazopanib targets were identified from multiple databases. Differential expression analysis was conducted using microarray data from hepatocyte-like cells treated with pazopanib and from matched control samples. Genes that overlapped between pazopanib targets and differentially expressed genes (DEGs) were considered potential pathogenic targets for hepatotoxicity. Multiple machine learning algorithms were employed for gene selection to improve accuracy and predictive capability. Molecular docking was used to evaluate the binding affinity of pazopanib to core proteins. Functional enrichment analysis was conducted to elucidate the potential toxic mechanisms.

Results: Our analysis identified 162 target genes for pazopanib and 291 DEGs, revealing seven shared genes as potential pathogenic targets for pazopanib-induced hepatotoxicity. Using machine learning, we further detected four core target genes: CYP1A1, DDR2, FGF1, and PLK4. Molecular docking confirmed that pazopanib stably bound to these core proteins. Functional enrichment analysis indicated that the hepatotoxicity associated with pazopanib may involve p53 signaling, impaired cell cycle, and immune modulation.

Conclusion: This study enhances our understanding of the molecular mechanisms underlying pazopanib-induced hepatotoxicity, which is essential for developing protective strategies and therapeutic interventions. By integrating network toxicology, microarray analysis, and machine learning, this study provides a comprehensive framework for investigating the complex toxicological processes of specific compounds and offers insights that could improve the clinical applications and regulatory safety of targeted therapies.

Methods: We modelled endothelial dysfunction through TNFα stimulation in human umbilical vein endothelial cells (HUVECs) and examined the role of betanin and its possible mechanism of action by MTT assay, western blotting, and immunofluorescence staining. A systemic inflammation model of mice was built through LPS to investigate the protective roles of betanin.

Results: Betanin pre-treatment increased cell viability, inhibited the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM- 1), and improved endothelial tight junction by upregulating the expression of occludin and zonula occludens-1 (ZO-1) after TNFα stimulation in HUVECs. In terms of endothelial-mesenchymal transition, betanin up-regulated the expression of endothelial phenotypes VE-cadherin and CD31, whereas it inhibited the expression of mesenchymal phenotype N-cadherin, indicating that betanin reduced endothelial-mesenchymal transition in TNFα-stimulated HUVECs. In addition, betanin increased the expression of LC3 and decreased the expression of p62, two central proteins in autophagy. Betanin also reversed the abnormal autophagic flux after TNFα exposure. However, the specific autophagy inhibitor, 3-methyladenine, blocked the protective effect of betanin. Finally, betanin was found to greatly decrease ICAM-1 and VCAM-1 expression, and upregulate occludin and ZO-1 levels in a systemic inflammation model of mice.

Conclusion: The above results collectively suggested that betanin may improve endothelial dysfunction by promoting autophagy, thus exerting beneficial effects on cardiovascular health.]]> https://www.benthamscience.com/article/1482982026-06-02

Objective: We aimed to explore the role of MXDs in GC.

Methods: The Wilcoxon rank sum test and t-test were employed to evaluate the differential expression of the MXD gene family members in GC tissues compared to non-paired normal gastric tissues. cBioPortal was utilized for examining genetic alterations within the MXD gene family. R software, specifically version 3.6.3, was used to scrutinize the expression patterns of MXD genes in GC, their correlation with clinical parameters, and to generate a correlation heat map. The survival package (v3.2-10) and the Cox regression model were implemented to evaluate the prognostic significance of the MXD gene family. The pROC package (v1.17.0.1) was applied to assess the diagnostic potential of the MXD gene family. R software (v3.6.3) was also used to explore potential regulatory networks involving members of the MXD gene family and related genes. The GSVA package (v1.34.0) was leveraged to investigate the link between the expression of the MXD gene family and immune cell infiltration. Visualization was facilitated by the ggplot2 (v3.3.3), survminer (v0.4.9), and clusterProfiler (v3.14.3) packages. Gene Set Cancer Analysis (GSCA) was employed to determine the sensitivity of the MXD gene family's expression to drugs from the GDSC database. The expression levels of MXD genes were validated across various cell lines using quantitative real-time PCR (qRT-PCR).

Results: MXD1 was significantly upregulated in GC, while MXD3 and MXD4 were significantly downregulated. Significant correlations were identified between the expression levels of MXD3 and the T stage (p = 0.041) and age (p = 0.001) of GC patients. Additionally, a notable association was observed between MXD4 expression and the histologic grade (p = 0.006) in GC patients. Low MXD3 expression was associated with a poor prognosis in GC. Low MXD3 expression was an independent prognostic factor for poor outcomes in GC patients. MXD3 demonstrated some accuracy in predicting tumor and normal tissue outcomes (AUC = 0.884). MXDs mediate gastric carcinogenesis and progression by regulating immune cells and pathways, including endocytosis, cell cycle, and apoptosis. The expression of the MXD gene family was associated with immune cell infiltration and drug sensitivity. MXD3 and MXD4 expression levels were significantly downregulated in GC cell lines, while MXD1 expression was significantly upregulated.

Conclusion: The MXD gene family may serve as novel biomarkers of poor prognosis and as potential immunotherapeutic targets for GC.]]>