Objective: Traditional denoising algorithms perform less due Limited Directional Selectivity problem and do not adequately capture directional information in pixels. Traditional algorithms' edge representation and texture details are insufficient for the earlier detection of DH. Limited Directional Selectivity leads to inaccurate diagnosis and classification of Disc Herniation (DH) stages. The DH stages are (i) Degeneration (ii) Prolapse (iii) Extrusion and (iv) Sequestration. Moreover, detection of DH size below 2mm using MR image is the major problem.

Methods: To solve the above problem, spinal cord MR images fed to the proposed Parrot optimization tuned Denoising Convolutional Neural Network (Po- DnCNN) algorithm for perspective enhancement of nucleus pulposus region in the spinal cord, vertebrae. The perspective enhancement of Spinal cord image led to the accurate classification of stages and earlier detection of DH by using the proposed Hippopotamus optimization- Fast Hybrid Vision Transformer (Ho–FastViT) algorithm. For this study, spinal cord MR images are obtained from the Grand Challenge website – SPIDER dataset.

Results: The proposed Po-DnCNN method and Ho-FastViT results are analysed quantitatively and qualitatively based on the edge, contrast, classification of the stage, and enhancement of the projected nucleus pulposus region in the spinal cord and vertebrae. The predicted DH results using the proposed method are compared with the manual Pfirrman Grade value of the spinal card method.

Conclusion: Proposed method is better than traditional methods for earlier detection of DH. Po-DnCNN and Ho-FastViat methods give high accuracy of about 98% and 97% compared to traditional methods.

However, these pregnancies carry a high-risk status for both the mother and fetus, with increased rates of maternal and fetal complications.

Case Presentation: We present a series of three women who conceived while on dialysis and delivered successfully. These women were managed with increasing dialysis frequency and developing a clinical protocol early on, with a multidisciplinary approach and close collaboration with obstetricians. Our case series is unique as one of the women had three successful deliveries while on dialysis, and one of them had a positive outcome with twin pregnancies while on dialysis.

Conclusion: Successful outcomes in these high-risk pregnancies while on dialysis suggest that with meticulous care and multidisciplinary approach, conception and successful deliveries are plausible in women who receive dialysis.

Objective: This article aims to review the available literature and recent studies demonstrating the efficacy, safety, mechanism of action and drug-drug interactions of losartan in cardiovascular disease.

Methods: This is a focused literature review with the keywords relevant to the terms performed in PubMed, Scopus and Web of Science through May 28, 2023, according to the PRISMA guidelines. Based on the PICO standard format, fifty-two relevant in-depth consequent guide approaches and evidence-based choices were selected associated with a knowledgeable collection of current, high-quality manuscripts.

Results: After oral administration, time to reach maximum concentration is about 1-2 hours. With a 78% binding to protein, it has a bioavailability of 25-35%. Losartan is not removed by hemodialysis. For the full effect to occur, it may take up to 6 weeks. The drug is mainly prescribed for patients with high blood pressure, diabetic nephropathy, hypertension and left ventricular hypertrophy. The publication reported higher drug exposures and adverse reactions in women than men with antihypertensive medications. Losartan could improve changes in gut microbiota that might be associated with hypertension. In the high-risk group of renal transplant recipients with arterial hypertension, research reported wellcontrolled blood pressure with losartan monotherapy.

Conclusion: In addition to the major losartan interactions with captopril, enalapril, lisinopril, and lithium, there are moderate interactions with aspirin, pregabalin, alprazolam, amitriptyline, baclofen, betamethasone, buspirone. Muscle cramps, respiratory infection, cough, hyperkalemia, anemia and stuffy nose are the main reported side effects. As polypharmacy could hide pharmacokinetics interaction due to cytochrome P450, therefore, the combination of losartan with drugs such as phenobarbital, rifampin or fluconazole needs vigilant attention regarding therapeutic drug monitoring.

Aims: The aim of this investigation was to evaluate clinical and demographic data of kidney transplantation in a main tertiary hospital in Isfahan/Iran.

Objectives: The published articles confirmed that a successful kidney transplant reduces mortality. Consequently, for further challenges associated with the causes and outcomes, preliminary studies are crucial in a large population of kidney transplant.

Methods: From the database of hospital and transplant surgery notebook, the features such as, age, duration of surgery, the number of kidney donors (living person or brain death), and predisposing factors for ESRD were extracted and analyzed.

Results: A total of 688 kidney transplant recipients comprised of males (n= 473M) and females (n= 215) were considered for further analysis. Recipients received kidneys from 482 living and 206 cadaver donors. The mean age of donors versus recipients was 30.4 versus 43.7 years (p≤0.05) respectively. Operation time in the recipients of living versus cadaver donors was 3.7 versus 4 hours. Operation time from 5.5 (the year 2007) reached 3.7 hours (the year 2019). The number of cadaver donors was 3 (the year 2009) which reached at 19 (the year 2019).

Conclusion: In Isfahan, Iran, more than 50% of the population studied needed kidney transplantation around the age of 45 years, and the number of transplanted men was 2.2 times higher than the females. The mean duration of the operation was significantly reduced, and the number of brain death donors steadily increased. Further, remodelling and analyzing the data obtained from this initial investigation could facilitate resourceful decisions regarding practical aspects of kidney transplantation outcome.

Case Presentation: The authors, hereby, highlight varied presentations of tertiary hyperparathyroidism (THPT) by presenting 3 interesting cases, describing their clinical course and outcomes. Through sharing these experiences and insights, we hope to contribute to a better understanding of THPT and its optimal management in patients with ESKD.

Conclusion: THPT can have a significant impact on patient health and quality of life. Despite the widespread use of interventions, such as vitamin D analogues, calcimimetics and parathyroidectomy, THPT remains a significant clinical challenge for patients with ESKD.

Objective: This paper aims to discuss the mechanism of actions, pathways, and metabolites triggered due to the development of neuropathy and nephropathy post-long-haul diabetes in patients. The therapeutic targets are also highlighted, proving to be a potential cure for such conditions.

Methods: Research works were searched from international and national databases with keywords like “diabetes,” “diabetic nephropathy,” “NADPH,” “oxidative stress,” “PKC,” “Molecular mechanisms,” “ cellular mechanisms,” “complications of diabetes,” and “factors.” The databases searched were PubMed, Scopus, Directory of open access journals, Semantic Scholar, Core, Europe PMC, EMBASE, Nutrition, FSTA- Food Science and Technology, Merck Index, Google Scholar, PubMed, Science Open, MedlinePlus, Indian citation index, World Wide Science, and Shodhganga.

Results: Pathways causing protein kinase C (PKC) activation, free radical injury, oxidative stress, and aggravating the conditions of neuropathy and nephropathy were discussed. In diabetic neuropathy and nephropathy, neurons and nephrons are affected to the extent that their normal physiology is disturbed, thus leading to further complications and conditions of loss of nerve sensation in diabetic neuropathy and kidney failure in diabetic nephropathy.

Current treatment options available for the management of diabetic neuropathy are anticonvulsants, antidepressants, and topical medications, including capsaicin. According to AAN guidelines, pregabalin is recommended as the first line of therapy, whereas other drugs currently used for treatment are gabapentin, venlafaxine, opioids, amitriptyline, and valproate.

Drug targets for treating diabetic neuropathy must suppress the activated polyol pathways, kinase C, hexosamine, and other pathways, which amplify neuroinflammation. Targeted therapy must focus on the reduction of oxidative stress and proinflammatory cytokines and suppression of neuroinflammation, NF-κB, AP-1, etc.

Conclusion: Potential drug targets must be considered for new research on the treatment of neuropathy and nephropathy conditions.]]> https://www.benthamscience.comarticle/135222Objective: The potential mechanism underlying the protective effect of Astragaloside IV (AS-IV) co-treatment with 1, 25-dihydroxy-vitamin D (Vit-D) on neuropathy in diabetic high-fat rats was investigated.

Methods: The rat diabetic hyperlipidemia (DH) model was established via streptozotocin and a high-fat diet (HFD). After co-treatment (of AS-IV and Vit-D at respective doses of 50 mg/kg via oral gavage and 30000 IU/kg via intramuscular injection), blood glucose levels, markers of inflammation and oxidative stress, as well as apoptosis and histopathology were evaluated with appropriate techniques.

Results: Co-treatment could effectively reduce blood glucose levels substantially (p< 0.01), improve weight loss, and decrease oral glucose tolerance. Reduced respective sensory and motor nerve conduction velocities in rats were substantially improved (p<0.01) after co-treatment. Also, we observed obvious improvement in DH-induced injured nerve fiber myelin structure and other organ pathologies in co-treated rats. Besides, we observed up-regulated expressions of peroxisomal-proliferator activated receptor-alpha (PPAR-α) and Vit-D receptors (VDR) (p< 0.01) through the western blotting technique. Using the same technique, we also discovered reduced levels of interleukin (IL)1 beta, IL-6, and tumor necrosis factor-alpha, coupled with increased IL-10 and superoxide dismutase levels (p< 0.01). Importantly, co-treatment could effectively exert antioxidative and anti-inflammatory effects. Also, co-treatment resulted in the up-regulation of PPAR-α and VDR expressions, inhibition of the renin–angiotensin–aldosterone system, and promotion of β-cell sensitivity to insulin.

Conclusion: The combined application of AS-IV and Vit-D exhibited health effects such as anti-oxidation, regulation of inflammatory factors, and promotion of cell repair, which may be considered as the mechanisms underlying treatment of diabetic peripheral neuropathy and improvement in biochemical indicators.

Objective: In this study, a network pharmacology approach and in vivo experiments were adopted to predict the pharmacological effects and mechanisms of Cinn in DN therapy.

Methods: The nephroprotective effect of Cinn on DN was investigated by a streptozotocininduced diabetes mellitus (DM) mouse model. The protein-protein interaction network of Cinn against DN was established by a network pharmacology approach. The core targets were then identified and subjected to molecular docking with Cinn.

Results: Cinn treatment effectively restored body weight, ameliorated hyperglycemia, and reduced kidney dysfunction markers in DM mice, also demonstrating a reduction in tissue injury. Network pharmacology analysis identified 298 DN-Cinn co-target genes involved in various biological processes and pathways. Seventeen core targets were identified, eight of which showed significant differential expression in the DN and healthy control groups. Molecular docking analysis revealed a strong interaction between Cinn and PTEN. Cinn treatment downregulated the PTEN protein expression in DM mice.

Conclusion: This study revealed the multi-target and multi-pathway characteristics of Cinn against DN. Cinn improved renal pathological damage of DN, which was related to the downregulation of PTEN.

Materials and Methods: A total of 1,918 adults older than 18 years of age underwent ultrasonographic (USG) examinations. Participants’ age, sex, height, weight, BMI, liver, spleen, and kidney dimensions, biochemistry and haemogram results were recorded. The relationships between organ measurements and these parameters were examined.

Results: A total of 1,918 patients participated in the study. Of these, 987 (51.5%) were female and 931 (48.5%) were male. The mean age of the patients was 40.74± 15.95 years. The liver length (LL) for men was found to be greater than that for women. The effect of the sex factor on the LL value was statistically significant (p = 0.000). The difference between men and women in terms of liver depth (LD) was statistically significant (p=0.004). The difference between BMI groups in terms of splenic length (SL) was not statistically significant (p=0.583). The difference between BMI groups in terms of splenic thickness (ST) was statistically significant (p=0.016).

Conclusion: We obtained the mean normal standard values of the liver, spleen, and kidneys in a healthy Turkish adult population. Consequently, values exceeding those in our findings will guide clinicians in the diagnosis of organomegaly and will contribute to filling the gap in this regard.

Objective: To investigate the clinical value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in assessing renal pathological injury in patients with immunoglobulin A (IgA) nephropathy compared with a mono-exponential model.

Methods: Altogether, 80 patients with IgA nephropathy were divided into the mild (41 cases) andmoderate–severe (m–s) renal injury groups (39 cases) according to pathology scores, and 20 healthy volunteers were recruited as controls. All participants underwent IVIM-DWI of the kidneys, and renal parenchymal apparent diffusion coefficient (ADC), pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) values were measured. One-way analysis of variance, receiver operating characteristic (ROC) curve analysis, and Pearson correlation analysis were performed for all the DWI-derived parameters.

Results: The DWI-derived parameters of the m–s renal injury group were significantly lower than those of the mild renal injury and control groups (P < 0.01). The ROC analysis revealed that f had the largest area under the ROC curve for differentiation between the m–s and mild renal injury groups and between the m–s renal injury and control groups. The f had the largest correlation coefficient with renal pathology scores (r=−0.81), followed by the D* (−0.69), ADC (−0.54), and D values (−0.53), respectively (all P<0.01).

Conclusion: IVIM-DWI demonstrated better diagnostic performance than the mono-exponential model in assessing renal pathological injury in patients with IgA nephropathy.

Methods: This study was performed at the King Abdul-Aziz University Hospital. We examined 61 patients who underwent SWE. The patients were classified into two groups based on the presence or absence of type 2 Diabetes Mellitus (DM).

Results: The results showed that there was a significant correlation between cortical stiffness and DM duration [p<0.005]. In addition, there was a negative correlation between cortical stiffness and cortical thickness [p=0.147] in patients with DM. Moreover, the eGFR decreased with an increase in cortical stiffness [p=0.499]. The cortical thickness in patients with and without DM was 0.750 ± 0.2 kPa and 0.788 ± 0.4 kPa, respectively. The kidney stiffness in patients with DM and control patients was 8.5 ± 8.6 cm and 14.0 ± 25.16 cm, respectively.

Conclusion: This study showed that kidney p-SWE measurements were reliable. Therefore, further studies assessing kidney stiffness in patients with and without people with diabetes are recommended.

Methods: We have collected the data that supported this idea to conduct a comprehensive review by using scientific databases, such as Pub Med ®, ScienceDirect ®, Google Scholar ®, and MEDLINE ®. An attempt was made to refer to all English-language articles published between 2000 to 2020 using keywords like flavonoids potential in nephrotoxicity and nephrotoxicity treatment approaches with herbal remedies.

Conclusion: This comprehensive review delves into the molecular mechanisms underlying the reno-protective effects of flavonoids. By scavenging reactive oxygen species, inhibiting inflammatory mediators, and modulating intracellular signalling pathways, flavonoids can mitigate oxidative stress and inflammation, thereby preserving renal function and integrity. Preclinical studies have demonstrated the potential of specific flavonoids in ameliorating drug-induced nephrotoxicity, renal ischemia-reperfusion injury, diabetic nephropathy, and other kidney diseases. Furthermore, epidemiological evidence highlights the inverse relationship between flavonoid intake and the risk of developing kidney diseases. Nevertheless, understanding the molecular mechanisms of flavonoids in nephroprotection offers exciting prospects for developing novel therapeutic strategies to combat kidney diseases and promote kidney health.

Methods: We synthesized EF-AuNps using a direct reduction method and characterized the NPs by employing various techniques, including UV-visible spectroscopy, DLS, XRD, EDX, TEM, and FT-IR. The anti-proliferative activity against MDA-MB-231 cells was assessed using MTT and colony formation assays, alongside evaluating cell viability with PI-FACS and live/dead assays. Furthermore, a Western blot was performed to determine the mechanism of action of EFAuNps in TNBC cells.

Result: We successfully synthesized triangular EF-AuNps (<100nm) and observed a substantial inhibition of cell proliferation (IC₅₀ 18μg/ml). Compared to EF alone, EF-AuNps significantly enhanced cell death in TNBC cells, as confirmed by flow cytometry and viability assays. Besides, Western blot analysis verified that the expression of apoptotic-related signal proteins, such as survivin, caspase 3, and caspase 9, were modulated by EF-AuNps.

Conclusion: EF-AuNps showed higher anti-cancer efficacy than EF in the MDA-MB-231 cell line. These findings suggest the therapeutic potential of EF-AuNps for TNBC treatment, advocating for further preclinical and clinical investigations into this promising anti-cancer formulation.

Methods: A rat model of osteoporosis was induced with dexamethasone sodium phosphate. Highly active umbilical cord mesenchymal stem cells (HA-UCMSCs) and UCMSCs were isolated, cultured, identified, and infused intravenously once at a dose of 2.29 × 10⁶ cells/kg. In the 4th week of treatment, bone mineral density (BMD) was evaluated via cross-micro-CT, tibial structure was observed via HE staining, osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was examined via alizarin red staining, and carboxy-terminal cross-linked telopeptide (CTX), nuclear factor-κβ ligand (RANKL), procollagen type 1 N-terminal propeptide (PINP) and osteoprotegerin (OPG) levels were investigated via enzyme-linked immunosorbent assays (ELISAs). BMMSCs were treated with 10^-6 mol/L dexamethasone and cocultured with HA-UCMSCs and UCMSCs in transwells. The osteogenic and adipogenic differentiation of BMMSCs was subsequently examined through directional induction culture. The protein expression levels of WNT, β-catenin, RUNX2, IFN-γ and IL-17 in the bone tissue were measured via Western blotting.

Results: The BMD in the healthy group was higher than that in the model group. Both UCMSCs and HA-UCMSCs exhibited a fusiform morphology; swirling growth; high expression of CD73, CD90 and CD105; and low expression of CD34 and CD45 and could differentiate into adipocytes, osteoblasts and chondrocytes, while HA-UCMSCs were smaller in size; had a higher nuclear percentage; and higher differentiation efficiency. Compared with those in the model group, the BMD increased, the bone structure improved, the trabecular area, number, and perimeter increased, the osteogenic differentiation of BMMSCs increased, RANKL expression decreased, and PINP expression increased after UCMSC and HA-UCMSC treatment for 4 weeks. Furthermore, the BMD, trabecular area, number and perimeter, calcareous nodule counts, and OPG/RANKL ratio were higher in the HA-UCMSC treatment group than in the UCMSC treatment group. The osteogenic and adipogenic differentiation of dexamethasone-treated BMMSCs was enhanced after the coculture of UCMSCs and HA-UCMSCs, and the HA-UCMSC group exhibited better effects than the UCMSC coculture group. The protein expression of WNT, β-catenin, and runx2 was upregulated, and IFN-γ and IL-17 expression was downregulated after UCMSC and HA-UCMSC treatment.

Conclusion: HA-UCMSCs have a stronger therapeutic effect on osteoporosis compared with that of UCMSCs. These effects include an improved bone structure, increased BMD, an increased number and perimeter of trabeculae, and enhanced osteogenic differentiation of BMMSCs via activation of the WNT/β-catenin pathway and inhibition of inflammation.

Methodology: In addition to traditional therapies with insulin and oral anti-diabetics, researchers have developed new approaches for treatment, including stem cell (SC) therapy, which exhibits promising outcomes. Besides its significant role in treating type one DM (T1DM) and type two DM (T2DM), it can also attenuate diabetic complications. Furthermore, the development of insulin- producing cells can be achieved by using the different types of SCs, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and multiple types of adult stem cells, such as pancreatic, hepatic, and mesenchymal stem cells (MSC). All these types have been extensively studied and proved their ability to develop insulin-producing cells, but every type has limitations.

Conclusion: This review aims to enlighten researchers about recent advances in stem cell research and their potential benefits in DM and diabetic complications.

Methods: We retrieved all the compound data of AM from the Traditional Chinese Medicine Systems Pharmacology database and screened out the active compounds and their target proteins. Then, a network of candidate compounds and target compounds of AM was constructed using Cytoscape software. Furthermore, hypertensive nephropathy-related genes from the DisGeNET and GeneCards databases were intersected with AM target proteins and hypertensive nephropathy-related genes to determine the potential targets of AM in treating hypertensive nephropathy. Finally, after performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, we conducted molecular docking to verify the interaction between the main active ingredients of AM and the core targets.

Results: A total of 87 effective components of AM were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. According to the network of active compounds and their target proteins, 18 of the 20 effective compounds in AM could act on 210 proteins. Taking the intersection of 274 hypertensive nephropathy-related genes and AM target proteins, 49 potential targets of AM in treating hypertensive nephropathy were identified. Using the median degree value, we determined 25 core targets of AM in treating hypertensive nephropathy. GO enrichment analysis showed that the biological processes of AM on hypertensive nephropathy mainly focused on the inflammatory response, hypoxia response, angiogenesis, cell proliferation, and cell migration. KEGG pathway enrichment analysis mainly involved cancer pathways, the AGE-RAGE signaling pathway in diabetic complications, blood flow shear stress, and atherosclerosis. Molecular docking results showed that quercetin, kaempferol, and 7-O-methylisomucronulatol had strong binding activity with several target proteins and may exert protective effects by stabilizing the interaction between molecules through the intermolecular forces of hydrogen bonds.

Conclusion: This study reveals the targets of AM in treating hypertensive nephropathy using network pharmacology and molecular docking, providing new clues for developing novel drugs for hypertensive nephropathy and basic research development.

Methods: Five original GEO microarray DN and FSGS datasets were evaluated (GSE111154, GSE96804, GSE125779, GSE129973 and GSE121233). Each of the three groups (DN, FSGS, and Controls) had equal renal transcriptome data (n=32) included in the analysis to eliminate bias. The DEGs were identified using TAC4.0. Pathway analysis was performed on the discovered genes aligned to official gene symbols using Reactome, followed by functional gene enrichment analysis using Funrich, EnrichrSTRING and Network analyst investigated PPI, followed by Webgestalt's pathway erichment. Finally, using the Targetscan 7.0 and DIANA tools, filtered differential microRNAs downregulated in DN were evaluated for target identification.

Result: Between the three groups, DN, FSGS, and Control, a total of 194 DEGs with foldchange, >2 & <-2 and P-value 0.01 were found in the renal transcriptome. In comparison to control, 45 genes were elevated, particularly in DN, whereas 43 were upregulated specifically in FSGS. DN datasets were compared to FSGS in a separate analysis. FABP4, EBF1, ADIRF, and ART4 were shown to be among the substantially up-regulated genes unique to DN in both analyses. The transcriptional regulation of white adipocytes was discovered by pathway analysis.

Conclusion: The molecular markers revealed might be employed as specific targets in the aetiology of DN, as well as in T2DM patients' therapeutic care.]]> https://www.benthamscience.comarticle/138879 https://www.benthamscience.comarticle/135908 https://www.benthamscience.comarticle/134598 https://www.benthamscience.comarticle/135912 https://www.benthamscience.comarticle/134759Background: Acute kidney injury (AKI) is characterized by inflammatory infiltration and damage and death of renal tubular epithelial cells (RTECs), in which hypoxia plays an important role. Deferoxamine (DFO) is a well-accepted chemical hypoxia-mimetic agent. Mesenchymal stem cell-conditioned medium (MSC-CM) can reduce local inflammation and repair tissue. In this study, we explored the effect and molecular mechanism of MSC-CM-mediated protection of RTECs under DFO-induced hypoxia.

Methods: Rat renal proximal tubule NRK-52E cells were treated with different concentrations of DFO for 24 hours, followed by evaluation of RTEC injury, using a Cell Counting Kit-8 (CCK-8) to detect cell viability and western blotting to evaluate the expression of transforming growth factor- beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), and hypoxia-inducible factor-1 alpha (HIF-1α) in NRK-52E cells. Then, three groups of NRK-52E cells were used in experiments, including normal control (NC), 25 μM DFO, and 25 μM DFO + MSC-CM. MSC-CM was obtained from the human umbilical cord. MSC-CM was used to culture cells for 12 hours before DFO treatment, then fresh MSC-CM and 25 μM DFO were added, and cells were cultured for another 24 hours before analysis.

Results: Western blotting and cellular immunofluorescence staining showed culture of NRK-52E cells in 25 μM DFO for 24 hours induced HIF-1α and nuclear receptor coactivator-1 (NCoA-1), simulating hypoxia. MSC-CM could inhibit the DFO-induced up-regulation of α-SMA, TGF-β1, HIF-1α and NCoA-1.

Conclusion: Our results suggest that MSC-CM has a protective effect on RTECs by down-regulating HIF-1α and NCoA-1, which may be the harmful factors in renal injury.

Aims: The aim of the study was to review the antihypertensive and vasorelaxant medicinal plants of the Moroccan pharmacopeia.

Objective: To date, no review on Moroccan medicinal plants exhibiting antihypertensive effects has been performed, and their mechanism of action has not been specified. The objective of this review was to collect, analyze, and critically assess published publications on experimental and clinical research that explored the blood pressure-reducing abilities of Moroccan medicinal plant extracts.

Materials and Methods: This study collected, processed, and critically analyzed published studies related to experimental and clinical research that investigated Moroccan herbal derivatives' blood pressure-lowering abilities using a number of scientific databases, including ScienceDirect, Scopus, PubMed, Google Scholar, and others. Plantlist.org was used to validate the right plant names.

Results: The results revealed 22 species of Moroccan medicinal plants belonging to 13 different groups with recognized antihypertensive properties. The species were abundant in a variety of chemical elements. Asteraceae (08 species), Lamiaceae (3 species), Apiaceae (2 species), and 1 species each from the following families: Parmeliaceae, Fabaceae, Cistaceae, Malvaceae, Polygonaceae, Brassicaceae, Myrtaceae, Rutaceae, Amaranthaceae, Rosaceae, and Lauraceae were the most frequently mentioned families for their antihypertensive properties. The most used parts were the leaves and the aerial parts. The two main methods of preparation among Moroccans were decoction and infusion. This study demonstrated the known antihypertensive and vasorelaxant properties of Moroccan medicinal plants in vivo and in vitro, as well as their mechanisms of action. Interestingly, phytochemicals can operate on blood vessels directly via a vasorelaxant impact involving a range of signaling cascades or indirectly by blocking or activating multiple systems, such as an angiotensin-converting enzyme (ACE), renin-angiotensin system (RAS), or diuretic activity.

Conclusion: The review of the available data reveals that more work needs to be done to examine all the Moroccan medicinal plants that have been suggested as antihypertensive in published ethnopharmacological surveys. A review of the literature in this area reveals that methodologies of the experimental study need to be standardized, and purified molecules need to be studied. In addition, mechanistic investigations, when they exist, are generally incomplete. In contrast, only a few advanced clinical investigations have been conducted. However, all studies fail to determine the efficacy/safety ratio.

MicroRNAs (miRNAs), small molecules that regulate gene expression post-transcriptionally, play vital roles in numerous cellular processes, including apoptosis, cell differentiation, development, and proliferation. Their dysregulated expression in urine has been proposed as a potential biomarker for various human diseases, including bladder cancer. To draw reliable conclusions about the roles of urinary miRNAs in human diseases, it is essential to have dependable and reproducible methods for miRNA extraction and profiling.

In this review, we address the technical challenges associated with studying urinary miRNAs and provide an update on the current technologies used for urinary miRNA isolation, quality control assessment, and miRNA profiling, highlighting both their advantages and limitations.

Objectives: The present study aimed to determine the level of miR-124 in patients with lupus nephritis by reverse transcriptase real-time polymerase chain reaction compared to healthy control and correlate its levels with biochemical findings in those patients.

Methods: The study was a case-control study that included fifty patients with lupus nephritis in addition to fifty healthy controls. Blood samples from the participants were subjected to the determination of serological markers of SLE. Moreover, real-time PCR was used for the determination of miR-124.

Results: The comparison of Micro-RNA124 between patients and control subjects revealed a statistically significant decrease in Micro-RNA124 in patients (1.193 ± 0.56) compared to the control (3.36 ± 0.50, p <0.001); the comparison of the level of MicroRNA 124 in the patients with different clinical and serological findings of SLE revealed a significant decrease in the level of MicroRNA 124 in patients with muscular findings (1.02 ± 0.5) compared to the patients with negative manifestations (1.47 ± 0.5, p =0.005).

Conclusion: In the present study, a comparison of MicroRNA-124 in LN patients with different stages compared to normal control showed a statistically significant decrease in Micro-RNA124 in patients with lupus nephritis p <0.001 with significant correlation to the patients’ different clinical and serological findings of SLE. Therefore, it may be used as a new noninvasive therapeutic approach to monitor response to therapy, predict relapses, and identify the degree of the activity of the disease or the progression to the chronic stage.

Method: According to the PRISMA guideline, a systematic search was accomplished to identify all relevant scientific papers on “the role of resveratrol against cisplatin-induced ototoxicity” in different electronic databases up to May 2021. Fifty-five articles were screened based on a predefined set of inclusion and exclusion criteria. Eight eligible studies were finally included in the current systematic review. The in-vitro findings revealed that cisplatin administration significantly decreased the HEI-OC1 cell viability compared to the untreated cells; however, resveratrol co-treatment (in a dose-dependent manner) could protect HEI-OC1 cells against cisplatin-induced decrease in cell viability.

Results: Furthermore, the in-vivo finding showed a decreased value of DPOAE, and increased values of ABR threshold, ABR-I, ABR-IV, and ABR I-IV interval in cisplatin-treated animals; in contrast, resveratrol co-administration demonstrated an opposite pattern on these parameters.

Conclusion: Thus, it can be mentioned that resveratrol co-treatment alleviates cisplatin-induced ototoxicity. Mechanically, resveratrol exerts its otoprotective effects through various mechanisms such as anti-oxidant, anti-apoptosis, and anti-inflammatory.

Aims: The present study tried to find genes selectively expressed in 11 rat organs, including the adrenal gland, brain, colon, duodenum, heart, ileum, kidney, liver, lung, spleen, and stomach.

Materials and Methods: Three normal male Sprague-Dawley (SD) rats were anesthetized, their organs mentioned above were harvested, and RNA in the fresh organs was extracted. Purified RNA was reversely transcribed and sequenced using the Solexa high-throughput sequencing technique. The abundance of a gene was measured by the expected value of fragments per kilobase of transcript sequence per million base pairs sequenced (FPKM). Genes in organs with the highest expression level were sought out and compared with their median value in organs. If a gene in the highest expressed organ was significantly different (p < 0.05) from that in the medianly expressed organ, accompanied by q value < 0.05, and accounted for more than 70% of the total abundance, the gene was assumed as the selective gene in the organ.

Results & Discussion: The Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) pathways were enriched by the highest expressed genes. Based on the criterion, 1,406 selective genes were screened out, 1,283 of which were described in the gene bank and 123 of which were waiting to be described. KEGG and GO pathways in the organs were partly confirmed by the known understandings and a good portion of the pathways needed further investigation.

Conclusion: The novel selective genes and organic functional pathways are useful for scientists to unveil the mechanisms of the organs at the molecular level, and the selective genes’ products are candidate disease markers for organs.

Objective: It aims to provide readers with an understanding of the achievements, developments, and dilemmas of target fishing techniques over the past few years and to provide new ideas for subsequent research.

Methods: Research articles in recent years using target fishing as an entry point are used as a basis to summarize the types of literature based on their principles and characteristics and to discuss the advantages and disadvantages of each method.

Conclusion: This paper summarizes the classification and development of fishing techniques such as ultrafiltration, equilibrium dialysis, cell membrane chromatography, and immobilization of target molecules and target fishing and describes the principles and characteristics of these methods. The applications of these methods in the active ingredients of traditional Chinese medicine are summarized, and the problems and solutions of these methods are discussed.

Objective: The main objective of this review article is to provide a comprehensive and insightful overview of the role of finerenone by mainly focusing on its pharmacological properties, toxicity, uses, bioanalytical technique used for determination, and treatment options.

Materials and Method: Finerenone works by inhibiting the action of the mineralocorticoid receptor. Finerenone is quickly absorbed from the digestive tract after oral treatment and achieves peak plasma concentrations in 1-2 hours.

Result: Finerenone is actively metabolized through oxidation, epoxidation substitution, and direct hydroxylation. Elimination of finerenone is done through urine and feces. Determination of finerenone can be done through HPLC-MS and LSC.

Conclusion: The present review covers the complete picture of ADME properties, bioanalytical techniques, clinical trials, toxicity, and possible avenues in this arena. Finerenone is effective compared to other mineralocorticoid receptor-like spironolactone and eplerenone, for the treatment of chronic kidney disease.

Objectives: The objective of this review was to relate the consumption of probiotic bacteria and its effects on inflammatory diseases, including obesity, type II diabetes and celiac disease.

Methods: A search was carried out in English, between the years 2011 and 2022, for research articles and clinical trials with humans and in vivo studies. Research showed improvement in cardiovascular risk markers, and improvement in insulin sensitivity, lipid profile and plasma atherogenic index, in obesity with the use of probiotics. In type II diabetes, decreased levels of fasting glucose, glycated hemoglobin, insulin and glycemic index, and increased levels of peptide 1, superoxide dismutase and glutathione peroxidase were observed.

Results: In addition to cellular protection of the islets of Langerhans and positive alteration of TNF- α and IL-1β markers. Improvement in the condition of patients with celiac disease was observed, since the neutralization of the imbalance in serotonin levels was observed, reducing the expression of genes of interest and also, a decrease in cytokines.

Conclusion: Therefore, the use of probiotics should be encouraged.

Methods: The arthritis model was induced in rats by injecting Complete Freund’s adjuvant (CFA) into the right hind paw and was subsequently treated with crocin and curcumin. Evaluation of anti- arthritic activity was carried out using paw swelling, hematological parameters, biochemical parameters, inflammatory cytokines, and histopathology of rats.

Results: The results showed increased paw swelling, increased serum markers levels, including CRP, RF, ALP, ALT, and AST, and inflammatory cytokines (ILlβ and TNFα) along with histology changes (cartilage and bone degradation) in arthritic rats when compared to the normal group. Crocin, curcumin and crocin + curcumin administration at different doses (especially combination at 40 mg/kg and 30 mg/kg, respectively), as well as MTX, revealed a suitable therapeutic effect on AIA rats. Moreover, both phytochemicals and their combination at different doses showed effective anti- arthritic effects owing to their anti-inflammatory effects.

Conclusion: Crocin and curcumin, either alone or in combination, can be a suitable treatment modality for rheumatoid arthritis.

Methods: The active ingredients of HS and their potential targets were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the DN-related targets were determined from GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGkb, and Therapeutic Target Database (TTD). The Cytoscape software was used to construct a herb-disease-target network and screen core genes. STRING was employed to generate a protein-protein interaction (PPI) network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the mechanism of action of HS in DN. Animal experiments and molecular docking were used to verify the potential mechanism.

Results: In total, 40 active ingredients and 180 effective targets of HS in DN were identified and 1115 DN-related targets were retrieved. From the PPI network, VEGFA, AKT1, IL6, IL1B, TP53, MMP9, PTGS2, CASP3, EGF and EGFR were identified as core genes. The anti-DN mechanism mainly involved multiple signaling pathways such as AGEs-RAGE. Animal experiments and molecular docking analysis confirmed that HS downregulated the expression of IL-1 and IL-6 via kaempferol-mediated inhibition of JNK1 phosphorylation.

Conclusion: HS exhibits a therapeutic effect in DN through its multiple ingredients that act on several targets and multiple signaling pathways, including AGEs-RAGE.

Objective: The aim of this systematic review was to investigate the association between diabetes microvascular complications, including retinopathy, neuropathy, nephropathy, and gut microbiota composition.

Methods: A systematic search was carried out in PubMed, Scopus, and ISI Web of Science from database inception to March 2023. Screening, data extraction, and quality assessment were performed by two independent authors. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment.

Results: About 19 articles were selected from 590 retrieved articles. Among the included studies, nephropathy has been studied more than other complications of diabetes, showing that the composition of the healthy microbiota is changed, and large quantities of uremic solutes that cause kidney injury are produced by gut microbes. Phyla, including Fusobacteria and Proteobacteria, accounted for the majority of the variation in gut microbiota between Type 2 diabetic patients with and without neuropathy. In cases with retinopathy, an increase in pathogenic and proinflammatory bacteria was observed.

Conclusion: Our results revealed that increases in Bacteroidetes, Proteobacteria and Fusobacteria may be associated with the pathogenesis of diabetic nephropathy, neuropathy, and retinopathy.

In view of the detrimental role of intestinal dysbiosis in the development of diabetes-related complications, gut microbiota assessment may be used as a biomarker in the future and interventions that modulate the composition of microbiota in individuals with diabetes can be used to prevent and control these complications.

In conclusion, the gut microbiome is a critical player in maintaining human health, and its modulation by herbal medicines is a burgeoning area of research. Understanding the complex interactions between herbal compounds and gut microbiota will pave the way for innovative approaches to personalized healthcare and the development of herbal-based therapeutics aimed at promoting gut health and overall well-being.

Method: The features used to predict the complications are identified and categorised by scrutinising the standards of electronic health records.

Result: Overall, 102 research articles have been reviewed, resulting in 59 frequent features being identified. Nineteen attributes are recognised as a standard in all four considered complications, which are age, gender, ethnicity, weight, height, BMI, smoking history, HbA1c, SBP, eGFR, DBP, HDL, LDL, total cholesterol, triglyceride, use of insulin, duration of diabetes, family history of CVD, and diabetes. The existence of a well-accepted and updated feature set for health analytics models to predict the complications of diabetes mellitus is a vital and contemporary requirement. A widely accepted feature set is beneficial for benchmarking the risk factors of complications of diabetes.

Conclusion: This study is a thorough literature review to provide a clear state of the art for academicians, clinicians, and other stakeholders regarding the risk factors and their importance.

Introduction: DN has become one of the most prevalent complications of clinical hyperglycemia, with individual-specific variations in the disease spectrum that leads to fatal consequences. Diverse etiologies involving oxidative and nitrosative stress, activation of polyol pathway, inflammasome formation, Extracellular Matrix (ECM) modifications, fibrosis, and change in dynamics of podocyte functional and mesangial cell proliferation adds up to the clinical complexity of DN. Current synthetic therapeutics lacks target-specific approach, and is associated with the development of inevitable residual toxicity and drug resistance. Phytocompounds provides a vast diversity of novel compounds that can become an alternative therapeutic approach to combat the DN.

Methods: Relevant publications were searched and screened from research databases like GOOGLE SCHOLAR, PUBMED and SCISEARCH. Out of 4895 publications, the most relevant publications were selected and included in this article.

Result: This study critically reviews over 60 most promising phytochemical and provides with their molecular targets, that can be of pharmacological significance in context to current treatment and concomitant research in DN.

Conclusion: This review highlights those most promising phytocompounds that have the potential of becoming new safer naturally-sourced therapeutic candidates and demands further attention at clinical level.

Objective: This case-control study aimed to determine the relationship between rs7529229 and rs2228145 polymorphisms of the IL-6R gene with the incidence of nephropathy among T2D patients.

Methods: Fifty-six diabetic patients with nephropathy and 57 T2D patients without nephropathy were included based on inclusion criteria, along with 150 healthy individuals.

Results: The frequencies of AC and CC genotype distributions of the rs2228145 polymorphism in DN patients were significantly higher than in healthy individuals (24.1 and 9.3% versus 10.7 and 6.7%, respectively, P= 0.02). Moreover, the frequency of allele C was higher in DN patients compared to healthy controls (21.30% versus 12%, P=0.025). However, genotype distribution and allele frequencies of the rs7529229 IL-6R polymorphism in DN patients were not statistically significant in comparison with diabetic patients and healthy individuals (P> 0.05).

Conclusion: The results showed that the allele and genotype distribution frequencies of rs2228145 IL-6R gene polymorphism in patients with DN were significantly higher than in healthy individuals. Therefore, the presence of this polymorphism may be involved in the development of diabetic nephropathy in this population.

Methods: A retrospective cohort study was conducted in 108 hospitalized Type 2 diabetes (T2D) patients with renal injury, including 70 with DKD and 38 with NDKD (non-DKD). Clinical features, pathological findings, and follow-up parameters were collected. Serum and urine FABP4 were detected by ELISA. An immunohistochemistry stain was used to determine FABP4 in renal tubulointerstitium. A double immunofluorescence stain was employed to assess FABP4- and CD68-positive macrophages. Correlation analysis, logistic regression models, receiver operating characteristic (ROC), and Kaplan-Meier survival curve were performed for statistical analysis.

Results: DKD patients had increased expression of FABP4 and ectopic fat deposition in tubules. As shown by correlation analyses, FABP4 expression in renal tubules was positively correlated with UNAG (r=0.589, p=0.044) and ESRD (r=0.740, p=0.004). Multivariate regression analysis revealed that UNAG level was correlated with FABP4 expression level above median value (odds ratio:1.154, 95% confidence interval:1.009-1.321, p=0.037). High-expression of FABP4 in renal tubules of DKD was at an increased risk of ESRD. Increased FABP4 expression in inflammatory cells was also associated with ESRD in DKD.

Conclusion: High-expression of FABP4 is involved in the pathogenesis of renal tubular lipid injury and is a risk factor for poor prognosis in DKD patients.

Objective: We investigated the influence of Zam on doxorubicin-induced cardiac toxicity, elucidating its consequential effects on GUT microbiota dysbiosis and hepatic and renal functions.

Methods: Male rats were categorized into four groups: Group 1 as Normal control (NC), Group 2 as Zamzam control (ZC), Group 3 Disease control (DC) and Group 4 as Therapeutic control (DZ) treated with Zam against doxorubicin-induced disease at a dose of 1mg/kg boy weight) intraperitoneally (i.p).

Results: Significant dysbiosis in the composition of GM was observed in the DC group along with a significant decrease (p < 0.05) in serum levels of Zinc, interleukin-10 (IL-10), IL-6 and Angiotensin II (Ang II), while C-reactive protein (CRP), fibrinogen, and CKMB increased significantly (restoration of Zinc ions (0.72 ± 0.07 mcg/mL) compared to NC. Treatment with Zamzam exhibited a marked abundance of 18-times to 72% in Romboutsia, a genus of firmicutes, along with lowering of Proteobacteria in DZ followed by significant restoration of Zinc ions (0.72 ± 0.07 mcg/mL), significant (p ˂ 0.05) reduction in CRP (7.22 ± 0.39 mg/dL), CKMB (118.8 ± 1.02 U/L) and Fibrinogen (3.18 ± 0.16 mg/dL), significant (p < 0.05) increase in IL-10 (7.22 ± 0.84 pg/mL) and IL-6 (7.18 ± 0.40 pg/ml), restoration of Ang II (18.62 ± 0.50 nmol/mL/min), marked increase in renin with normal myocyte architecture and tissue orientation of kidney, and restoration of histological architecture of hepatocyte.

Conclusion: Zam treatment mitigated cardiac toxicity risk through the modulation of GUT microbiota and the renin-angiotensin system and tissue histology effectively.

Purpose: In this review, we aim at various inflammatory mediators and different inflammatory pathways involved in the progression of DN with special emphasis on phytoconstituents which gives protection against DN by acting on these mediators and pathways.

Methods: The literature was searched for the key words: inflammation, anti-inflamatory, phytoconstitutents/ phytochemicals, diabetic nephropathy, clinical and preclinical studies.

Results: The various epidemiological, preclinical, and clinical evidence showed a close relationship between inflammatory response and progression of DN, as such, there is no effective treatment for DN, therefore, there is an unmet need for novel therapeutic approaches to treat them. From ancient times, phytochemicals, also known as phytonutrients, are the bioactive nutrients found in plants and foods, which have proven potentially useful for human well-being. Phytochemicals have demonstrated a promising therapeutic role in nephropathy, principally through the regulation of oxidative stress and inflammation.

Materials and Methods: Different glucose concentrations were used to treat podocytes to mimic the pathology of diabetic nephropathy in vitro. Flow cytometry was used to determine cell apoptosis. Inflammatory cytokines released by podocytes were measured by using an enzymelinked immunosorbent assay (ELISA). Western Blot was used to detect the expression of PRKAB2 protein in podocytes.

Results: Genecard and g: profiler results revealed that miR-29b might be involved in regulating HG-induced cell injury. QRT-PCR indicated that HG-induced downregulation of miR-29b in podocytes. MiR-29b knockdown promoted cell apoptosis and inflammatory response in podocytes. MiR-29b overexpression repressed cell apoptosis and inflammatory response induced by high glucose treatment in podocytes. Luciferase reporter assay and Western Blot showed that miR-29b targeted PRKAB2 to negatively regulate PRKAB2 expression directly. Knockdown of PRKAB2 reversed the increased cell apoptosis and inflammation induced by miR-29b inhibitors.

Conclusion: MiR-29b plays a role in inhibiting inflammation and apoptosis in high glucose (HG) treated podocytes by negatively regulating PRKAB2 expression. This study provides new potential targets and ideas for the treatment of diabetic nephropathy.

Objective: Abuse of alcohol does not occur suddenly. People becoming addicted to various alcoholic beverages is a problem that results from months and years of irresponsible drinking. The process of recovering from the issue in turn includes targeted, particular methods for raising awareness of the negative effects of alcohol usage.

Conclusion: Due to the heightened risks for one's bodily and mental health along with the social issues it generates, alcohol consumption results in these costs. We discuss the three areas of the epidemiology of alcohol's impact on health and diseases, the public health approach for treating problems related to alcohol use, and advancements in alcohol science.

Aim: We aimed to systematically investigate the effect of statins on lipid profiles of patients with CKD by performing a meta-analysis of Randomized Controlled Trials (RCTs).

Methods: Major electronic databases (Scopus, MEDLINE/PubMed, and ISI Web of Science) were searched from inception to August, 2023, to find randomized controlled trials (RCTs) evaluating the effect of different statins on serum lipoproteins in CKD patients. Weighted Mean Difference (WMD) with 95% Confidence Intervals (CI) was used to estimate the effect size. Trial Sequential Analysis (TSA) was performed to confirm the robustness of the evidence.

Results: A total of 18 publications were identified. It was found that statins reduced serum levels of Low-Density Lipoprotein (LDL)-C (WMD = -27.81 mg/dl, 95% CI = -34.47 to -21.15, P < 0.001) and total cholesterol (WMD = -25.44 mg/dl, 95% CI = -34.71 to -16.18, P < 0.001) in patients with CKD compared to the control group. Nonetheless, the effect of statins on High-Density Lipoprotein (HDL)-C (WMD = 0.57 mg/dl, 95% CI = -0.71 to 1.85, P = 0.38) and Triglyceride (TG) (WMD = -9.08 mg/dl, 95% CI = -22.22 to 2.06, P = 0.11) was not statistically significant. The results of TSA confirmed the robustness of the evidence and were consistent with the pooled effect size. The findings of subgroup analysis and time response analysis were also significant.

Conclusion: It was found that statin therapy reduced the levels of LDL-C and total cholesterol in patients with CKD.

Objectives: This study aimed to investigate the possible mechanism of CLY in relation to DFU using network pharmacology and molecular docking.

Materials and Methods: Firstly, relevant targets of CLY against DFU were obtained from TCMSP, Swiss Target Prediction database and GEO database. Then, topological analysis was employed by Cytoscape to screen the top 6 core active ingredients and the top 8 hub targets. Furthermore, the OmicShare Tools were applied for gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis. Finally, the results of network pharmacology were verified by molecular docking method.

Results: CLY has 61 active compounds and 361 targets after de-duplication, and the top 8 hub targets were EGFR, TP53, CCND1, IL-1B, CREBBP, AR, PTGS2 and PGR. GO enrichment analysis is mainly related to signal transducer activity, receptor activity, and molecular transducer activity. KEGG pathway analysis indicated that these shared targets were primarily focused on AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, IL-17 signaling pathway, and JAK-STAT signaling pathway. Molecular docking results showed that physciondiglucoside, 2-cinnamoyl-glucose and kinobeon A were well bound with EGFR, IL-1B, AR and PTGS2.

Conclusion: This study demonstrated that CLY has anti-oxidative stress and anti-inflammatory effects in the treatment of DFU through various constituents, multiple targets, and multiple pathways, which provides a valuable point of reference for future investigations on CLY.

Methods: A search was undertaken of the PubMed, Scopus, Web of Science, Embase, and Google Scholar electronic databases up to 15 July 2022. Primary endpoints focused on plasma homocysteine levels. Data were quantitatively analyzed using fixed or random- effect models, as appropriate. Subgroup analyses were conducted based on the drugs and hydrophilic-lipophilic balance of statins.

Results: After screening 1134 papers, 52 studies with a total of 20651 participants were included in the meta-analysis. The analysis showed a significant decrease in plasma homocysteine levels after statin therapy (WMD: -1.388 μmol/L, 95% CI: [-2.184, -0.592], p = 0.001; I2 = 95%). However, fibrate therapy significantly increased plasma homocysteine levels (WMD: 3.459 μmol/L, 95% CI: [2.849, 4.069], p < 0.001; I2 = 98%). The effect of atorvastatin and simvastatin depended on the dose and duration of treatment (atorvastatin [coefficient: 0.075 [0.0132, 0.137]; p = 0.017, coefficient: 0.103 [0.004, 0.202]; p = 0.040, respectively] and simvastatin [coefficient: -0.047 [-0.063, -0.031]; p < 0.001, coefficient: 0.046 [0.016, 0.078]; p = 0.004]), whereas the effect of fenofibrate persisted over time (coefficient: 0.007 [-0.011, 0.026]; p = 0.442) and was not altered by a change in dosage (coefficient: -0.004 [-0.031, 0.024]; p = 0.798). In addition, the greater homocysteine- lowering effect of statins was associated with higher baseline plasma homocysteine concentrations (coefficient: -0.224 [-0.340, -0.109]; p < 0.001).

Conclusion: Fibrates significantly increased homocysteine levels, whereas statins significantly decreased them.

Methods: We performed a systematic review and meta-analysis according to the PRISMA guidelines. Any study that presented the prognostic value of high sensitivity troponin (hs-cTn) of vascular inflammation in stable patients without known cardiac heart disease was considered to be potentially eligible. The Medline (PubMed) database was searched up to April 22, 2021. The main endpoint was the difference in c-index (Δ[c-index]) with the use of hs-cTn for major adverse cardiovascular events (MACEs), cardiovascular and all-cause mortality. We calculated I² to test heterogeneity.

Results: In total, 44 studies and 112,288 stable patients without known coronary heart disease were included in this meta-analysis. The mean follow-up duration of the whole cohort was 6.8 ± 1.1 years. 77,004 (68.5%) of the patients presented at low cardiovascular risk while 35,284 (31.5%) in high. The overall pooled estimate of Δ[c-index] for MACE was 1.4% (95%CI: 0.7-2.1, I²=0%) and for cardiovascular death 1.3% (95%CI: 0.3-2.3, I²=0%). Finally, the overall pooled estimate of Δ[c-index] for all-cause mortality was 3% (95%CI: 1.9-3.9, I²=86%), while high heterogeneity was observed between the studies.

Conclusion: The predictive usefulness of changes in hs-cTn measures in stable individuals with either high or low cardiovascular risk, demonstrates that assessing vascular inflammation in addition to clinical risk factors enhances risk prediction for cardiovascular events and allcause mortality. Further prospective studies are necessary to confirm these findings and assist clinical decision-making regarding the most optimal prevention strategy.

Objective: This paper aims to find the ingredients, the key targets, and the action pathways of PS on DN from the perspective of network pharmacology.

Methods: The databases of network pharmacology, such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Pharmmapper, OMIM, DrugBank, Gene- Cards, TTD, Disgenet, STRING, and Cytoscape software, were used to find the main ingredients and targets. Gene Ontology (GO) function and Kyoto Encyclopedia of Genome and Genomes (KEGG) pathway enrichment analysis were used to reveal the potential pathways of the PS on DN. The GEO database was used to find the targets of DN based on valid experimental research. The molecular docking technology was used to evaluate the combination between ingredients of PS and the targets.

Results: A total of 9 active ingredients and 216 potential therapeutic targets were obtained for PS on DN. Hub targets were discovered by the Cytoscape software analysis. CASP3 was screened by Venn diagram by making intersection between GSE30529 and hub genes. Moreover, CASP3 was combined with one of the nine active ingredients, quercetin, by molecular docking analysis. The KEGG pathways were mainly involved in diabetic nephropathy, and were simultaneously associated with CASP3 as followed: AGE-RAGE signaling pathway in diabetic complications, apoptosis, lipid and atherosclerosis, MAPK signaling pathway, TNF signaling pathway, IL-17 signaling pathway, and p53 signaling pathway.

Conclusion: PS can have the treatment on DN through CASP3. Quercetin, as one of the nine active ingredients, can be bounded to CASP3 to inhibit apoptosis in DN. PS can also take action on DN probably through many pathways. The role of PS on DN through other pathways still needs to be further elaborated.

MicroRNAs (miRNAs) are important in the development and progression of several diseases, including diabetic kidney disease (DKD). These dysregulated miRNAs can impact various cellular processes, including inflammation, fibrosis, oxidative stress, and apoptosis, all of which are implicated during DKD. MiRNAs can alter the course of DKD by targeting several essential mechanisms. Understanding the miRNAs implicated in DKD and their involvement in disease development might lead to identifying possible therapeutic targets for DKD prevention and therapy. Therefore, this review focuses specifically on DKD-associated DN, as well as how in-silico approaches may aid in improving the management of the disease.

Objective: We aim to provide a systematic overview of the mechanisms of Sch in multiple pathways to treat DN in rats.

Methods: Streptozocin was used to build a DN rat model, which was further treated with Sch. The possible mechanism of Sch protective effects against DN was predicted using network pharmacology and was verified by quantitative proteomics analysis.

Results: High dose Sch treatment significantly downregulated fasting blood glucose, creatinine, blood urea nitrogen, and urinary protein levels and reduced collagen deposition in the glomeruli and tubule-interstitium of DN rats. The activities of superoxide dismutase (SOD) and plasma glutathione peroxidase (GSH-Px) in the kidney of DN rats significantly increased with Sch treatment. In addition, the levels of IL-6, IL-1β, and TNF-α were significantly reduced in DN rats treated with Sch. 11 proteins that target both Sch and DN were enriched in pathways such as MAPK signaling, PI3K-Akt signaling, renal cell carcinoma, gap junction, endocrine resistance, and TNF signaling. Furthermore, quantitative proteomics showed that Xaf1 was downregulated in the model vs. control group and upregulated in the Sch-treated vs. model group. Five proteins, Crb3, Tspan4, Wdr45, Zfp512, and Tmigd1, were found to be upregulated in the model vs. control group and downregulated in the Sch vs. model group. Three intersected proteins between the network pharmacology prediction and proteomics results, Crb3, Xaf1, and Tspan4, were identified.

Conclusion: Sch functions by relieving oxidative stress and the inflammatory response by regulating Crb3, Xaf1, and Tspan4 protein expression levels to treat DN disease.

Objectives: The objective of this study was to perform a comprehensive pharmacokinetic and pharmacodynamic evaluation of a novel curcumin-tagged solid nanodispersion loaded with telmisartan, with the aim of assessing its potential as a treatment for diabetic nephropathy in an animal model. Specifically, the following objectives will be addressed: formulation and characterization, in vitro evaluation, pharmacokinetics and pharmacodynamics evaluation, and comparative analysis.

Materials and Methods: Telmisartan-loaded curcumin-tagged solid nanodispersion was prepared using the emulsion solvent evaporation method. The optimized formulation was evaluated for pharmacokinetic and pharmacodynamic parameters in an animal model. Wistar rats were divided into 5 groups, with 6 animals in each group. Diabetes was induced using nicotinamide (240 mg/kg) and streptozotocin (55 mg/kg, i.p.) injections in the animals. After 30 to 45 days of introduction, diabetic nephropathy was manifested. The kidneys and pancreas were used for histological analysis and renal and pancreatic damage assessment.

Results: In-vivo studies showed better bioavailability with the t1/2 and Cmax of TLS-15 was 14.92 ± 0.47 hours and 0.32 ± 0.009, respectively, within 2 hours as compared to the t1/2 and Cmax of MP was 4.38 ± 0.19 hours and 0.19 ± 0.008 owing to the better dissolution due to solubility improvement. When compared to the commercially available product, TLS-15 was found to have blood glucose and body weight that were, respectively, 1.01 and 1.03 times higher. Kidney measures, such as serum urea and creatinine, were found to be 0.71 and 1.16 times lower for TLS-15, respectively, and albumin had a value that was 1.13 times higher than for the commercial formulation. Urine indicators, urine albumin, and creatinine estimations, as well as cytokine estimations, revealed that TLS-15 had creatinine levels that were 1.17 times higher and IL-6 levels that were 0.77 times higher than those of a commercial batch.

Conclusion: The findings strongly support the renoprotective and pancreatic protective effects of TLS and Cur (SND-Solid Nanodispersion) combined by lowering levels of cytokines factor (IL- 6), kidney, and lipid parameters. The postulated mechanism might be the combined inhibitory action of TLS and Cur.

Objective: We aim to elucidate the molecular mechanisms linking chronic psychological stress with low-grade neuroinflammation in key brain regions, particularly focusing on the roles of G proteins and serotonin (5-HT) receptors.

Methods: This comprehensive review of the literature employs systematic, narrative, and scoping review methodologies, combined with systemic approaches to general pathology. It synthesizes current research on shared signaling pathways involved in stress responses and neuroinflammation, including calcium-dependent mechanisms, mitogen-activated protein kinases, and key transcription factors like NF-κB and p53. The review also focuses on the role of G protein-coupled neurotransmitter receptors (GPCRs) in immune and pro-inflammatory responses, with a detailed analysis of how 13 of 14 types of human 5-HT receptors contribute to depression and neuroinflammation.

Results: The review reveals a complex interaction between neurotransmitter signals and immunoinflammatory responses in stress-related pathologies. It highlights the role of GPCRs and canonical inflammatory mediators in influencing both pathological and physiological processes in nervous tissue.

Conclusion: The proposed Neuroimmunoinflammatory Stress Model (NIIS Model) suggests that proinflammatory signaling pathways, mediated by metabotropic and ionotropic neurotransmitter receptors, are crucial for maintaining neuronal homeostasis. Chronic mental stress can disrupt this balance, leading to increased pro-inflammatory states in the brain and contributing to neuropsychiatric and psychosomatic disorders, including depression. This model integrates traditional theories on depression pathogenesis, offering a comprehensive understanding of the multifaceted nature of the condition.

Objective: To determine the prevalence and the associated factors of toenail onychomycosis among patients with diabetes in Jordan.

Methods: A cross-sectional study was conducted on 375 patients with diabetes at the National Centre for Diabetes, Endocrinology, and Genetics in Amman, Jordan. Several socio-demographic and health-independent variables including foot self-care practices were collected. Toenail onychomycosis was assessed by a specimen culture and microscopic examinations. Descriptive and inferential statistics were used for data analysis.

Results: The prevalence of toenail onychomycosis was 57.6% (n=216). Multiple logistic regression revealed four significant associated factors; the presence of neuropathy (β=1.87, p=0.02), being an ex-smoker (β=2.69, p=0.01), being treated by both insulin and oral hypoglycemics drugs (β=1.32, p=0.03), and using antibiotics in the last year (β=1.78, p=0.02).

Conclusion: The prevalence of toenail onychomycosis among patients with diabetes in Jordan is high. Regular foot screening and podiatric care are recommended especially among patients with diabetic neuropathy, current treatment by insulin and oral hypoglycemics drugs, previous history of smoking, and previous use of antibiotics.

Method: In the present study, a mouse model of DN was first established to investigate the therapeutic effect of crocin on DN mice. Subsequently, non-targeted metabolomics techniques were used to analyze the mechanisms of action of crocin in the treatment of DN. The effects of crocin on CYP4A11/PPARγ and TGF-β/Smad pathway were also investigated.

Result: Results showed that crocin exhibited significant therapeutic and anti-inflammatory, and anti-oxidative effects on DN mice. In addition, the non-targeted metabolomics results indicated that crocin treatment affected several metabolites in kidney. These metabolites were mainly associated with biotin metabolism, riboflavin metabolism, and arachidonic acid metabolism. Furthermore, crocin treatment upregulated the decreased levels of CYP4A11 and phosphorylated PPARγ, and reduced the increased levels of TGF-β1 and phosphorylated Smad2/3 in the kidneys of DN mice.

Conclusion: In conclusion, our study validated the considerable therapeutic, anti-inflammatory, and antioxidative impacts of crocin on DN mice. The mechanism of crocin treatment may be related to the regulation of biotin riboflavin and arachidonic acid metabolism, the activation of CYP4A11/PPARγ pathway, and the inhibition of TGF-β/Smad pathway in the kidney.

Objective: In this work, we aimed to summarize the interesting results from preclinical and clinical studies that assessed the effects of natural alkaloids (berberine, nigelladine A, piperine, trigonelline, capsaicin, nuciferine, evodiamine, mahanine, and magnoflorine) on impaired insulin sensitivity and worsened insulin resistance, which play a pivotal role in the pathogenesis of type 2 diabetes.

Methods: In the current review, PubMed, ScienceDirect, Springer, and Google Scholar databases were used. The inclusion criteria were based on the following keywords and phrases: insulin sensitivity, insulin resistance, alkaloids and insulin resistance, alkaloids and type 2 diabetes, mechanisms of action, and alkaloids.

Results: The outcomes reported in this review demonstrated that the selected alkaloids increased insulin sensitivity and reduced insulin resistance in vitro and in vivo evidence, as well as in clinical trials, through improving insulin-signaling transduction mainly in hepatocytes, myocytes, and adipocytes, both at cellular and molecular levels. Insulin signaling components (InsR, IRS-1, PI3K, Akt, etc.), protein kinases and phosphatases, receptors, ion channels, cytokines, adipokines, and microRNAs, are influenced by alkaloids at transcriptional and translational levels, also in terms of function (activity and/or phosphorylation). Multiple perturbations associated with insulin resistance, such as ectopic lipid accumulation, inflammation, ER stress, oxidative stress, mitochondrial dysfunction, gut microbiota dysbiosis, and β-cell failure, are reversed after treatment with alkaloids. Furthermore, various indices and tests are employed to assess insulin resistance, including the Matsuda index, insulin sensitivity index (ISI), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT), which are all enhanced by alkaloids. These improvements extend to fasting blood glucose, fasting insulin, and HbA1c levels as well. Additionally, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Homeostasis Model Assessment of β-cell function (HOMA-β) are recognized as robust markers of insulin sensitivity and β-cell function, and it is noteworthy that alkaloids also lead to improvements in these two markers.

Conclusion: Based on the findings of the current review, alkaloids may serve as both preventive and curative agents for metabolic disorders, specifically type 2 diabetes. Nonetheless, there is an urgent need for additional clinical trials to explore the potential benefits of alkaloids in both healthy individuals and those with type 2 diabetes. Additionally, it is crucial to assess any possible side effects and interactions with antidiabetic drugs.

Objectives: This study aimed to investigate the effects of Ang-(1-7) on high glucose-induced islet β-cell dedifferentiation by activating the phosphatidylinositol-3-kinase/Protein kinase B/ Forkhead box transcription factor O1 (PI3K/Akt/FoxO1) signaling pathway.

Methods: The mouse islet β-cell line MIN6 cells were passaged and cultured and randomly divided into five groups: control (Con) group, high glucose (HG) group, HG with Ang-(1-7) group, HG with Ang-(1-7) and specific MasR antagonist A-779 group, and HG with Ang-(1-7) and PI3K inhibitor LY294002 group. After 48 hours, glucose-stimulated insulin secretion (GSIS) was detected by Enzyme-Linked Immunosorbent Assay (ELISA). The mRNA and protein expression levels of β-cell-specific factors (Pancreatic duodenal homeobox-1 (Pdx1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A(MafA)) and endocrine progenitor cell-specific factors (Octamer binding transcription factor 4(Oct4), Nanog) were measured by Real Time-PCR and Western blot. The factors of protein expression levels of PI3K/Akt/FoxO1 signaling pathway (Akt, p-Akt, Fox- O1, p-FoxO1) were determined by Western blot.

Results: We observed for the first time that high glucotoxicity can induce dedifferentiation of pancreatic islet β-cell, causing a decrease in insulin secretion levels and expression of Pdx1, MafA, p-- FoxO1, and p-Akt and an increase in expression of Oct4 and Nanog. After Ang-(1-7) intervention, insulin secretion levels and expression of Pdx1, MafA, p-FoxO1 and p-Akt were increased, and the levels of Oct4 and Nanog were reduced. However, A-779 and LY294002 could reverse this effect. During these processes, the total Akt and total FoxO1 expression did not change significantly.

Conclusion: Ang-(1-7) may prevent high glucose-induced pathological dedifferentiation of pancreatic β-cell by activating the PI3K/Akt/FoxO1 signaling pathway.

Background: Selenized tripterine phytosomes (Se@Tri-PTs) have been confirmed to undertake synergistic and sensitized effects on inflammation, which may be curatively promising for diabetic nephropathy (DN). However, the mechanisms of Se@Tri-PTs in alleviating podocyte injury, a major contributor to DN, still remain unclear.

Objective: The objective of the study was to find out the underlying mechanisms of Se@Tri-PTs in alleviating podocyte injury in diabetic nephropathy.

Methods: The key components and targets of Tripterygium wilfordii (TW) significant for DN as well as the signaling pathways involved have been identified. A high glucose-induced podocyte injury model was established and verified by western blot. The protective concentration of Se@Tri-PTs was screened by CCK-8 assay. Podocytes cultured with high glucose were treated with Se@Tri-PTs under protective levels. The expression of key protective proteins, nephrin and desmin, in podocytes, was assayed by western blot. Further, autophagy- related proteins and factors, like NLRP3, Beclin-1, LC3II/LC3, P62, and SIRT1, were analyzed, which was followed by apoptosis detection.

Results: Network pharmacology revealed that several monomeric components of TW, especially Tri, act on DN through multiple targets and pathways, including the NLRP3-mediated inflammatory pathway. Se@Tri-PTs improved the viability of podocytes and alleviated their injury induced by high glucose at 5 μg/L or above. High-glucose induction promoted the expression of NLRP3 in podocytes, while a low concentration of Se@Tri-PTs suppressed the expression. A long-term exposure of high glucose significantly inhibited the autophagic activity of podocytes, as manifested by decreased Beclin-1 level, lower ratio of LC3 II/LC3 I, and up- regulation of P62. This abnormality was efficiently reversed by Se@Tri-PTs. Importantly, the expression of SIRT1 was up-regulated and podocyte apoptosis was reduced.

Conclusion: Se@Tri-PTs can alleviate podocyte injury associated with DN by modulating NLRP3 expression through the pathway of SIRT1-mediated autophagy.

Methods: In this review, a systematic search was performed based on PRISMA guidelines for obtaining all relevant studies on “the effects of apigenin against diabetic nephropathy” in various electronic databases up to September 2022. Ninety-one articles were obtained and screened in accordance with the predefined inclusion and exclusion criteria. Seven eligible articles were finally included in this review.

Results: The experimental findings revealed that hyperglycemia led to the decreased cell viability of kidney cells and body weight loss and an increased kidney weight of rats; however, apigenin administration had a reverse effect on these evaluated parameters. It was also found that hyperglycemia could induce alterations in the biochemical and renal function-related parameters as well as histopathological injuries in kidney cells or tissue; in contrast, the apigenin administration could ameliorate the hyperglycemia-induced renal adverse effects.

Conclusion: The results indicated that the use of apigenin could mitigate diabetes-induced renal adverse effects, mainly through its antioxidant, anti-apoptotic, and anti-inflammatory activities. Since the findings of this study are based on experimental studies, suggesting the use of apigenin (as a nephroprotective agent) against diabetic nephropathy requires further clinical studies.

Objectives: This study aimed to investigate the role of exosome miR-30a-5p in high glucose (HG)-induced glomerular endothelial cells (GECs) dysfunction and explore the underlying mechanisms.

Methods: GECs were cultured in normal glucose (5.5 mM) and HG (30 mM) conditions. The recipient GECs were transfected with exosome or miR-30a-5p mimic/inhibitor and then detected by using CCK-8 and flow cytometry assay. Luciferase analysis was used to verify miR-30a-5p acted on notch homolog protein 1 (Notch1). RT-qPCR and Western blot were used to detect the expression of VE-cadherin, α-SMA, vascular endothelial growth factor (VEGF) and Notch1. In vivo, exosome miR-30a-5p was administered to DN mice, and periodic acid-Schiff (PAS) staining, UTP levels, and HbA1c levels were measured.

Results: The expression of miR-30a-5p was downregulated in HG-treated GECs. Exosome miR-30a-5p significantly promoted cell proliferation, and migration and reduced apoptosis of GECs under HG conditions. MiR-30a-5p directly targeted the 3-UTR region of Notch1. Exosome miR-30a-5p reduced the expression levels of Notch1 and VEGF, both at mRNA and protein levels. Furthermore, exosome miR-30a-5p inhibited HG-induced EndMT, as evidenced by increased VE-cadherin and reduced α-SMA. In vivo studies demonstrated that exosome miR-30a-5p reduced serum HbA1c levels and 24-hour urine protein quantification.

Conclusion: This study provides evidence that exosome miR-30a-5p suppresses EndMT and abnormal angiogenesis of GECs by modulating the Notch1/VEGF signaling pathway. These findings suggest that exosome miR-30a-5p could be a potential therapeutic strategy for the treatment of DN.

Background: The development of network pharmacology promotes the process of medicinal transformation of traditional Chinese medicine. This study took Chuanxiong as an example to analyze the active components in the treatment of DN.

Objective: Molecular docking and other technologies have effectively helped the complex find the disease's active ingredients.

Methods: The data of Chuanxiong was collected from the TCPSP database, DN gene expression data were collected through the NCBI database, and DN-related genes were obtained through differential analysis. In addition, the regulatory network of Chuanxiong and the main active components of DN treatment was constructed using String and Cytoscape tools. At the same time, PPI network interaction analysis was performed on core genes and GO. KEGG analysis was performed to predict essential genes using the Auto Dock tool.

Results: Eight active components of Chuanxiong were screened out. NCOA1 and NCOA2 could interact with Angelica lactone A, Myricetin, Chrysophanol, Chuanxiong, naphthalize, and Chrysophanol. Meanwhile, Angelica Lactone A, Myricetin, Chrysophanol, Chuanxiong, naphthafunolide, and Chrysophanol can affect the regulation of estrogen signaling pathway, endocrine and other factors regulating calcium reabsorption and adipogenesis of adipocytes through the regulation of steroid hormone stimulation and regulation of cAMP-dependent protein kinase complex.

Conclusion: NCOA1 and NCOA2 can be used as pharmacodynamic targets of Chuanxiong for improving DN.

Aim: This study aimed to investigate whether newer second-line glucose-lowering treatments are associated with an alternative risk of developing diabetic retinopathy in people with type 2 diabetes.

Methods: A nationwide cohort of people with type 2 diabetes on second-line glucose-lowering treatment regimens in 2008-2018 was extracted from the Danish National Patient Registry. Adjusted time to diabetic retinopathy was estimated with a Cox Proportional Hazards model. The model was adjusted for age, sex, diabetes duration, alcohol abuse, treatment start year, education, income, history of late-diabetic complications, history of non-fatal major adverse cardiovascular events, history of chronic kidney disease, and history of hypoglycaemic episodes.

Results: Treatment regimens of metformin + basal insulin (HR: 3.15, 95% CI: 2.42-4.10) and metformin + glucagon-like peptide-1 receptor agonist (GLP-1-RA, HR: 1.46, 95% CI: 1.09-1.96) were associated with an increased risk of diabetic retinopathy compared with metformin + dipeptidyl peptidase-4 inhibitors (DPP-4i). Treatment with metformin + sodium–glucose cotransporter-2 inhibitor (SGLT2i, HR: 0.77, 95% CI: 0.28-2.11) was associated with the numerically lowest risk of diabetic retinopathy compared with all regimens investigated.

Conclusion: Findings from this study indicate that basal insulin and GLP-1-RA are suboptimal second- line choices for people with type 2 diabetes at risk of developing diabetic retinopathy. However, many other considerations concerning the choice of second-line glucose-lowering treatment for type 2 diabetes patients should be taken into account.

Objective: One of the oldest plant families that have been used medicinally is the Apiaceae family. One of the most important genera of this family is Ferula, which has 170 different species and is distributed in hot and dry regions of the earth and has various therapeutic properties. The purpose of this article is to review the anti-diabetic effects of the Ferula genus on diabetes.

Methods: In this review article, key science databases, including Science Direct, PubMed, and Google Scholar, were searched to find information on Ferula genus using a combination of different keywords, including diabetes, hyperglycemia, and alpha-glucosidase inhibition.

Results: A total of 9 types of Ferula have been reported in the articles that have anti-diabetic properties.

Conclusion: The review of the conducted research shows that the genus Ferula has a high potential in reducing blood sugar and other aspects of diabetes, and additional research should be performed in this field.