Background/Objectives: Type 2 diabetes mellitus (T2DM) is a chronic multifactorial metabolic disorder requiring multi-target therapeutic strategies. This study aimed to predict the potential material basis, key targets and molecular mechanisms by which PuRenDan (PRD) may act against T2DM through an integrated network pharmacology and molecular simulation approach. Methods: Active compounds of PRD were screened from TCMSP, HERB 2.0 and the literature, and compound-related targets were predicted using TCMSP, SwissTargetPrediction and PharmMapper. T2DM-associated targets were collected from OMIM, DrugBank, DisGeNET, HPO, ClinPGx and GeneCards to obtain drug-disease intersection targets. Cytoscape was used to construct herb-compound-target and protein-protein interaction (PPI) networks, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was performed using AutoDock Vina1.1.2, and representative ligand-receptor complexes were further assessed by 100 ns molecular dynamics (MD) simulations and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) binding free-energy analysis. Results: A total of 163 active compounds, 597 PRD-related targets, 9138 T2DM-associated targets and 483 intersection targets were identified. β-sitosterol, emodin, quercetin, kaempferol and formononetin were predicted as major active compounds, whereas AKT1, TP53, SRC, IL6, TNF, EGFR and ESR1 were identified as disease-related network hubs. KEGG enrichment highlighted the PI3K-Akt, MAPK, HIF-1, FoxO, mTOR, AGE-RAGE and TNF signalling pathways. Docking predicted a comparatively favourable multi-target binding tendency for β-sitosterol. MD and MM/PBSA analyses further suggested favourable dynamic stability for β-sitosterol-TNF, β-sitosterol-AKT1, β-sitosterol-SRC and emodin-EGFR complexes, with β-sitosterol-TNF showing the lowest predicted binding free energy among the simulated systems. Conclusions: These in silico findings suggest that PRD may regulate T2DM-related inflammatory, insulin-signalling, oxidative-stress and metabolic networks through coordinated multi-compound, multi-target and multi-pathway actions. β-sitosterol may represent an important candidate material basis of PRD, with TNF, AKT1, SRC and EGFR as potential key targets. These conclusions remain predictive and require validation in biochemical, cellular and animal experiments.

The effects of the ketogenic diet (KD) on lipid metabolism remain controversial. We conducted a systematic review and meta-regression analysis of randomized controlled trials (RCTs) to evaluate the impact of KD on lipid profile parameters in adult populations. Five electronic databases (PubMed/MEDLINE, Web of Science, Scopus, Embase, Cochrane Library) were systematically searched from inception through June 2025 for RCTs examining lipid-related outcomes following KD interventions (defined as > 45

Protein arginine methyltransferases (PRMTs) play crucial roles in gene regulation, signal transduction, mRNA splicing, DNA repair, cell differentiation, and embryonic development. Due to its significant impact, PRMTs is a target for the prevention and treatment of various diseases. Among the PRMT family, PRMT1 is the most abundant and ubiquitously expressed in the human body. Although extensive research has been conducted on PRMT1, the reported inhibitors have not successfully passed clinical trials. In this study, deep learning was employed to analyze the characteristics of existing PRMTs inhibitors and to construct a classification model for PRMT1 inhibitors. Through a classification model and molecular docking, a series of potential PRMT1 inhibitors were identified. The representative compound (compound 156) demonstrates stable binding to the PRMT1 protein by molecular hybridization, molecular dynamics simulations, and binding free energy analyses. The study discovered novel scaffolds for potential PRMT1 inhibitors.

Enterovirus A71 (EV-A71), a major etiological agent of hand-foot-mouth disease, can cause severe neurological complications. However, the mechanisms underlying EV-A71-induced cell damage and potential therapeutic strategies remain inadequately understood. Here, we investigated EV-A71 replication dynamics and associated cytopathic effects in nine distinct cell lines, including epithelial, neuronal, immune, and other cell types. Cell viability, membrane integrity, and energy metabolism were assessed using Cell Counting Kit-8 (CCK-8), lactate dehydrogenase (LDH), and adenosine triphosphate (ATP) assays. The antiviral activity of rosmarinic acid (RA), a natural polyphenol, was evaluated by plaque reduction, qPCR, and Western blot. EV-A71 exhibited cell-type-specific replication and cytotoxicity patterns. RA significantly preserved cell viability, reduced LDH release, maintained ATP levels, and suppressed IL-6 expression. Mechanistically, RA inhibited viral replication by downregulating VP1 expression and viral RNA levels. Molecular docking indicated strong binding of RA to the hydrophobic pocket of VP1, potentially disrupting virus-host interactions. Collectively, these findings highlight RA’s combined antiviral and cytoprotective potential, supporting its candidacy as a therapeutic agent against EV-A71 infection.

Leonurus japonicas Houtt., has been recorded as "light body and long life" properties in the oldest classical medicinal book Shennong Bencao Jing thousands of years ago. Herba leonuri, also named Chinese Motherwort or Siberian Motherwort, has the effects of activating blood circulation, regulating menstruation, diuresis and detumescence, clearing heat and detoxifying, and is known as the "sacred medicine of gynecology." It has been well known by doctors and usually used in the treatment of common gynecological diseases in clinic. Leonurine is a very important alkaloid in Herba leonuri, which has many biological activities such as anti-oxidation, anti-inflammation, and anti-apoptosis. Diseases of the cardiovascular system and central nervous system are "major health threats" that threaten human life and health worldwide, however, many drugs have certain side effects right now. This paper reviews the potential molecular therapeutic effects of leonurine on cardiovascular system and central nervous system diseases, highlights the current findings of research progress, and focuses on the therapeutic effects of leonurine in various diseases. At present, leonurine is in the stage of clinical experiment, and we hope that our summary can provide guidance for its future molecular mechanism study and clinical application.

Glucagon-like peptide-1 (GLP-1) is a 30-amino acid intestinal insulin-stimulating factor, which is mainly secreted by L cells in the distal ileum and colon. It has various physiological functions, such as promoting insulin secretion and synthesis, stimulating β-cell proliferation, inducing islet regeneration, inhibiting β-cell apoptosis and glucagon release, delaying gastric emptying and controlling appetite, etc. It plays a role through a specific GLP-1 receptor (GLP-1R) distributed in many organs or tissues and participates in the regulation of glucose homeostasis in the body. GLP-1 receptor agonists (GLP-1RAs) has the similar physiological function of GLP-1. Because of its structural difference from natural GLP-1, it is not easy to be degraded by dipeptidyl peptidase-4 (DPP-4), thus prolonging the action time. GLP-1RAs have been recognized as a new type of hypoglycemic drugs and widely used in the treatment of type 2 diabetes mellitus (T2DM). Compared with other non-insulin hypoglycemic drugs, it can not only effectively reduce blood glucose and glycosylated hemoglobin (HbA1c), but also protect cardiovascular system, nervous system and kidney function without causing hypoglycemia and weight gain. Therefore, GLP-1RAs has good application prospects and potential for further development.

ETHNOPHARMACOLOGICAL RELEVANCE:Trigonella foenum-graecum L. (HLB), a widely recognized traditional Chinese medicine, has been historically used for the treatment of diabetes mellitus and its complications. However, the efficacy and mechanism of HLB in the treatment of type 2 diabetes mellitus (T2DM) combined with metabolic-associated fatty liver disease (MAFLD) remain poorly understood. AIM OF THE STUDY:To investigate the therapeutic effects of HLB on T2DM combined with MAFLD in mice and elucidate its underlying mechanisms. MATERIALS AND METHODS:The indices of glucose and lipid metabolism, along with oxidative stress markers, were measured using commercially available assay kits. Histopathological analyses of liver and colon tissues were conducted. Additionally, the mRNA expression levels of genes related to fatty acid metabolism, inflammatory factors, and intestinal tight junction proteins were quantified using reverse transcription polymerase chain reaction (RT-PCR). Microbiome, metabolomic, and transcriptomic analyses were employed to evaluate gut microbiota composition, metabolic profiles, and liver differential genes, respectively. RESULTS:After a 4-week treatment period, HLB effectively ameliorated abnormalities of glucose-lipid metabolism, hepatic oxidative stress, and inflammatory responses. Furthermore, HLB modulated hepatic function and intestinal damage. Through comprehensive multi-omics analysis, the observed improvements were attributed to the remodeling of the gut microbiota and its metabolic alterations, including an increased abundance of beneficial bacteria, regulation of bile acid metabolism. CONCLUSIONS:These findings not only provide a theoretical foundation for the broader application of HLB in traditional Chinese medicine but also offer novel insights into the potential pharmacological mechanisms underlying HLB's efficacy in T2DM and MAFLD treatment.

ETHNOPHARMACOLOGICAL RELEVANCE:Huidouba (HDB), a traditional Tibetan medicine, has been used for centuries in the Emei Mountain region of Sichuan, China, to treat diabetes and its complications. Known for its efficacy in nourishing kidney-Yin (kidney water) and regulating glucose and lipid metabolism, it is considered a"wonder drug"of Mount Emei.The study of Huidouba holds great significance for elucidating the mechanisms of action by which traditional Chinese and ethnic medicines treat diseases. AIM OF THE STUDY:To investigate the therapeutic effects and underlying mechanisms of Huidouba on diabetic nephropathy (DN) using metabolomic and molecular approaches. MATERIALS AND METHODS:DN rat model was established using high fat diet and streptozotocin (STZ 30 mg/kg) injection. The 65 rats included in the study were divided into normal group, metformin positive control model group, HDB high dose group and HDB low dose group with 13 rats in each group by using random number table method.The rats in HDB treatment group were given a high dose (7.2 g/kg) and a low dose (3.6 g/kg) respectively for 8 weeks. Serum biochemical indices of rats were detected and histopathological analyses of liver, kidney and pancreas were performed. Metabolomics analysis of plasma was performed using UPLC-MS/MS technique. Western blot was used to analyse the expression of key proteins in the bile acid metabolic pathway. RESULTS:HDB administration modulated aberrant metabolic pathways in DN rats, leading to ameliorated hepato-renal functions. Notably, renal dysfunction markers were markedly attenuated: blood urea nitrogen (BUN) declined from 16.27 ± 3.32 mmol/L to 8.95 ± 1.24 mmol/L (HDBL) and 11.80 ± 1.52 mmol/L (HDBH), while serum creatinine (SCr) reduced from 56.00 ± 15.96 μmol/L to 28.75 ± 2.33 μmol/L (HDBL) and 28.01 ± 2.93 μmol/L (HDBH). Albumin-to-creatinine ratio (ACR-8) dropped from 7.68 ± 2.44 mg/g (Model) to 4.39 ± 0.92 mg/g (HDBL) and 5.20 ± 1.80 mg/g (HDBH), indicating preserved glomerular filtration.Hepatoprotective effects were evident, with alanine aminotransferase (ALT) levels decreasing from 148.6 ± 63.73 μmol/L (Model) to 90.45 ± 20.35 μmol/L (HDBL) and 82.67 ± 19.55 μmol/L (HDBH). Aspartate aminotransferase (AST) levels also trended downward (Model: 253.6 ± 225.9 μmol/L vs. HDBH: 147.5 ± 42.18 μmol/L). Histologically, HDB treatment reduced inflammatory infiltration in the liver, kidney, and pancreatic islets, alongside ameliorated tissue degeneration, including a significant reduction in renal fibrosis (renal fibrotic area percentage in the Model group was approx. 13.32 %, which decreased to approx. 7.31 % and 8.68 % in the HDB low and high dose groups, respectively). Untargeted metabolomics revealed upregulated bile acid metabolism pathways (Cholesterol 7alpha-hydroxylase (CYP7A1) and Farnesoid X receptor (FXR/NR1H4)), correlating with improved glucose-lipid homeostasis and attenuated oxidative stress. CONCLUSIONS:The results of the study showed that both high- and low-dose HDB treatments effectively influenced key parameters in DN rats. High-dose HDB demonstrated superior efficacy in reducing total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and ALT levels, while significantly elevating high-density lipoprotein-cholesterol (HDL-C) and insulin (INS) levels compared to the low-dose group. In contrast, low-dose HDB showed a more pronounced reduction in BUN. These findings indicate complex dose-related protective effects. While low-dose HDB showed a more pronounced reduction in BUN and renal fibrosis, high-dose HDB exhibited stronger regulation of glucose-lipid metabolism and insulin secretion. This latter effect involving glucose-lipid homeostasis is likely mediated through its more pronounced modulation of bile acid pathways (e.g., CYP7A1 and NR1H4 upregulation by high-dose HDB). Both doses alleviated liver damage by reducing ALT and AST levels, though high-dose HDB achieved a more significant reduction in hepatic steatosis and inflammatory infiltration. HDB not only improved renal function in DN rats (e.g., BUN decreased from 16.27 mmol/L in the Model group to 8.95 mmol/L in the HDBL group and 11.80 mmol/L in the HDBH group), but also significantly improved renal tissue structure, with quantitative Masson staining analysis showing a reduction in renal fibrotic area from 13.32 % in the Model group to approximately 7.31 % in the HDBL group and 8.68 % in the HDBH group, respectively. HDB demonstrated potential in regulating glucolipid metabolism and protecting the liver. The dose-dependent efficacy observed, particularly concerning these aspects of glucolipid metabolism and certain liver parameters where the high dose showed greater improvements, appears consistent with the trend for high-dose HDB to more strongly modulate bile acid signaling markers (such as CYP7A1 and NR1H4), a key pathway in metabolic regulation, suggesting a potential association.Furthermore, HDB modulates altered metabolic states by modulating the abnormal bile acid metabolism pathway associated with Type 2 Diabetes Mellitus (T2DM). Therefore, we believe that HDB is a promising ethnopharmaceutical for the amelioration of T2DM.

Background/Objectives: Momordica charantia L. (M. charantia), a widely cultivated and frequently consumed medicinal plant, is utilized in traditional medicine. Cucurbitane-type triterpenoids, significant saponin components of M. charantia, exhibit hypoglycemic effects; however, the underlying mechanisms remain unclear. Methods: This study utilized comprehensive network pharmacology to identify potential components of M. charantia cucurbitane-type triterpenoids that may influence type 2 diabetes mellitus (T2DM). Additionally, molecular docking and molecular dynamics studies were performed to assess the stability of the interactions between the selected components and key targets. Results: In total, 22 candidate active components of M. charantia cucurbitane-type triterpenoids and 1165 disease targets for T2DM were identified through database screening. Molecular docking and molecular dynamics simulations were conducted for five key components (Kuguacin J, 25-O-methylkaravilagenin D, Momordicine I, momordic acid, and Kuguacin S) and three key targets (AKT1, IL6, and SRC), and the results demonstrated stable binding. The experimental results indicate that the interactions between momordic acid-AKT1 and momordic acid-IL6 are stable. Conclusions: Momordic acid may play a crucial role in M. charantia’s regulation of T2DM, and AKT1 and IL6 seem to be key targets for the therapeutic action of M. charantia in managing T2DM.

Extracellular matrix (ECM) and integrins are important biological macromolecules. ECM especially collagen IV (COLIV) deposition modulates the integrin-FAK signaling pathway involved in adipogenesis and is strongly associated with insulin resistance. Type 2 diabetes mellitus (T2DM) mice were given swertiamarin (STM) by intragastric administration. STM reduced body weight, blood glucose, and lipid levels and enhanced insulin sensitivity in diabetic mice. The lipid accumulation in liver, gastrocnemius muscle, and inguinal subcutaneous white adipose tissue (igSWAT) were significantly reduced by STM. Bioinformatics analysis revealed a connection between ECM, ITGB1/FAK, and PI3K/Akt signaling pathways. STM downregulated the adipogenesis, IRβ expression, COLIV deposition, ITGB1/FAK, and PI3K/Akt signaling pathways in igSWAT of diabetic mice. In vitro, STM inhibited the glucose uptake and differentiation of adipocytes, and downregulated adipogenesis-related gene and protein expression. STM is bound to ITGB1 and downregulated COLIV deposition, ITGB1/FAK, and PI3K/Akt signaling pathways. When we overexpressed FAK, the effects of STM on downstream PI3K/Akt signaling pathway and adipogenesis were attenuated. In conclusion, STM reduced COLIV deposition and binding with ITGB1 to downregulate ITGB1/FAK signaling pathway, further the downstream PI3K/Akt signaling pathway was inhibited to reduce adipogenesis and ameliorated T2DM. Thus, these signals may be a novel mechanism of STM in treating T2DM.

ObjectivesTrigonella foenum-graecum L. (HLB) exhibits promising pharmacological properties for the treatment of type 2 diabetic nephropathy (DN). This study aims to enhance the understanding of HLB’s pharmacodynamic effects and elucidate the mechanisms underlying its therapeutic potential in DN.MethodsThe pharmacodynamic effects of HLB were initially evaluated in a murine DN model through the oral administration of an aqueous extract of HLB. The primary bioactive constituents were subsequently identified using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Network pharmacology analysis was integrated with these data to uncover potential molecular targets of HLB in DN. Key renal metabolites were profiled using untargeted metabolomics, followed by metabolic pathway enrichment analysis conducted with the MetaboAnalyst 6.0 platform, which facilitated the identification of relevant metabolic pathways through which HLB modulates DN. Finally, quantitative real-time polymerase chain reaction (QRT-PCR) and Western blot (WB) techniques were employed to validate the expression levels of key genes and proteins, thereby confirming the molecular mechanisms underlying the effects of HLB in DN.ResultsAnimal experiments indicated that HLB significantly improved blood glucose regulation and renal function while reducing oxidative stress and abnormalities in lipid metabolism in diabetic mice. A total of 34 compounds and 159 potential therapeutic targets were identified as key active components of HLB. The untargeted metabolomics analysis revealed 61 critical metabolites, among which the PI3K-Akt-ERK signaling pathway—known to be involved in diabetes—was highlighted as a crucial pathway. QRT-PCR and WB analyses demonstrated that HLB upregulated the expression of MAPK1, MAPK3, AKT1, and PI3K.ConclusionThese results suggest that HLB may alleviate DN by modulating oxidative stress and lipid metabolism. Its effects are likely mediated through the PI3K-Akt-ERK signaling pathway, along with the upregulation of MAPK1, MAPK3, AKT1, and PI3K expression. This study lays the groundwork for further investigations into the molecular mechanisms underlying HLB’s action in DN.

Ethnopharmacological relevance: PuRenDan (PRD) is a traditional Chinese medicine formula comprising five herbs that have been traditionally used to treat type 2 diabetes mellitus (T2DM). While PRD has been shown to be effective in treating T2DM in clinical and animal studies, the mechanisms by which it works on the gut microbiome and metabolites related to T2DM are not well understood. Aim of the study: The objective of this study was to partially elucidate the mechanism of PRD in treating T2DM through analyses of the gut microbiota metagenome and metabolome. Materials and methods: Sprague-Dawley rats were fed high-fat diets (HFDs) and injected with low-dose streptozotocin (STZ) to replicate T2DM models. Then the therapeutic effects of PRD were evaluated by measuring clinical markers such as blood glucose, insulin resistance (IR), lipid metabolism biomarkers (total cholesterol, low-density lipoprotein, non-esterified fatty acids, and triglycerides), and inflammatory factors (tumor necrosis factor alpha, interleukin-6 [IL-6], interferon gamma, and IL-1 beta). Colon contents were collected, and metagenomics, combined with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry metabolic profiling, was performed to evaluate the effects of T2DM and PRD on gut microbiota and its metabolites in rats. Spearman analysis was used to calculate the correlation coefficient among different microbiota, clinical indices, and metabolites. Results: PRD exhibited significant improvement in blood glucose and IR, and reduced serum levels of lipid metabolism biomarkers and inflammatory factors. Moreover, the diversity and abundance of gut microbiota undergo significant changes in rats with T2DM that PRD was able to reverse. The gut microbiota associated with T2DM including Rickettsiaceae bacterium 4572_127, Psychrobacter pasteurii, Parabacteroides sp. CAG409, and Paludibacter propionicigenes were identified. The gut microbiota most closely related to PRD were Prevotella sp. 10 (H), Parabacteroides sp. SN4, Flavobacteriales bacterium, Bacteroides massiliensis, Alistipes indistinctus, and Ruminococcus flavefaciens. Additionally, PRD regulated the levels of gut microbiota metabolites including pantothenic acid, 1-Methylhistamine, and 1-Methylhistidine; these affected metabolites were involved in pantothenate and coenzyme A biosynthesis, histidine metabolism, and secondary bile acid biosynthesis. Correlation analysis illustrated a close relationship among gut microbiota, its metabolites, and T2DM-related indexes. Conclusion: Our study provides insights into the gut microbiota and its metabolites of PRD therapy for T2DM. It clarifies the role of gut microbiota and the metabolites in the pathogenesis of T2DM, highlighting the potential of PRD for the treatment of this disease.

Ethnopharmacological relevance Black mulberry (Morus nigra L.) is an ancient dual-use plant resource for medicine and food. It is widely used in Uyghur folklore for hypoglycemic treatment and is a folkloric plant medicine with regional characteristics. However, the mechanism of Morus nigra L. treatment in diabetes mellitus has not been fully understood, especially from the perspective of hepatic lipid accumulation is less reported.Objective of this study This study was to explore the potential of Morus nigra L. fruit ethyl acetate extract (MNF-EA) to reduce blood sugar levels by preventing the production of hepatic lipogenesis and to provide more evidence for the use of MNF-EA as an adjuvant therapy for type 2 diabetes mellitus (T2DM).Materials and methods In this study, the chemical composition of MNF-EA was first analyzed and characterized using UPLC-Q-TOF-MS technique. A series of in vitro studies were performed with HepG2-IR cells and oleic acid (OA)-induced HepG2 cells, including MTT assay, glucose uptake assay, oil red O staining and Western blot analysis. The STZ-HFD co-induced T2DM mice were employed for in vivo research, including physical indices, biochemical analysis, histopathological examination, and Western blot analysis.Results The 19 compounds in MNF-EA were identified by UPLC-Q-TOF-MS technique. Insulin resistance (IR) and lipid droplet accumulation in HepG2 cells were greatly improved by MNF-EA treatment, which had no appreciable side effects at the dosage used. In T2DM mice, MNF-EA decreased fasting blood glucose (FBG), saved body weight, and significantly improved oral glucose tolerance (OGTT) and IR status. In addition, MNF-EA treatment also improved lipid metabolism disorders and liver function in T2DM mice. Histopathological sections showed that MNF-EA treatment reduced hepatic steatosis. Mechanistic studies suggest that MNF-EA acted through the AMPK/mTOR pathway.Conclusions These results suggest that MNF-EA has great potential to reverse the metabolic abnormalities associated with T2DM by regulating the AMPK/mTOR signaling pathway. Therefore, we believe that MNF is a promising medicinal and food-homologous agent to improve T2DM.

Cervical cancer is one of the most common cancers that affects middle-aged women and the discovery of new drugs to aid clinical management is needed. As an important member of the protein arginine methyltransferases (PRMTs) family, PRMT1 catalyzes the methylation of protein arginine, which can influence multiple biological processes of cancer cells, such as activating epithelial-mesenchymal transformation (EMT) and acquiring resistance to apoptosis. Therefore, PRMT1 can be considered as a potential drug target for cervical cancer. In the current study, a new sub-binding pocket was discovered by molecular modeling, and by introducing a third substitute on the thiazole group to occupy this pocket, a series of compounds were designed and synthesized as potential PRMT1 inhibitors. Of these, two compounds (ZJG51 and ZJG58) exhibited significant inhibitory activities against PRMT1 without significantly inhibiting PRMT5. Both ZJG51 and ZJG58 displayed potent inhibitory effects on the proliferation of four cancer-derived cell lines and ZJG51 exerted relative selectivity against the cervical cancer cell line, HeLa. Further studies showed that ZJG51 inhibited migration and induce the apoptosis of HeLa cells. Mechanistically, ZJG51 significantly regulated PRMT1 related proteins, and indicated that the induction of apoptosis and inhibition of migration by ZJG51 may involve the activation of Caspase 9 and the inhibition of EMT, respectively. Molecular dynamic simulation and free energy calculation showed that ZJG51 can bind to PRMT1 stably and the binding mode was predicted. These data indicated that introducing the third substitute on the five-membered ring could be a future direction for structure-based optimization of PRMT1 inhibitors, and ZJG51 could be an important lead compound to inform the design of more potent inhibitors.

This study aimed to investigate the effect and potential mechanism of Lychee kernel extract in the intervention of non-alcoholic fatty liver disease (Nonalcoholic fatty liver disease, NAFLD) based on network pharmacology. Methods The components and action targets of litchi nuclei were obtained from the Pharmacology Database and Analysis Platform (TCMSP) within the Chinese Medicine System, the disease targets of NAFLD were obtained using disease target data from GeneCard, the intersection and pathway-target interaction network diagram were obtained through Cytoscape, and the GO bioprocess analysis and KEGG pathway enrichment analysis were performed using Bioinformatics website. We established an animal model with diet-induced obsisity mouse NAFLD and administered LKE via the gastric route. HE staining indicated lipid changes in the liver; the biological kits detect content of TG, TC, ALT, and AST. Results Eighteen potential active ingredients of litchi nuclei were identified, and 52 targets intersected with NAFLD disease. The key targets were INS, TNF, and HSP90AA1. KEGG channel enrichment filtered 20 signal pathways, the main ones include: pathways in cancer、Fluid shear stress and atherosclerosis、AGE-RAGE signaling pathway in diabetic complications;The liver lesions of the mice in the model group were severe, the liver lesions of the mice in the drug group were significantly reduced compared with the model group, and the serum transaminases of the mice in the drug group were also significantly reduced, which was close to the normal group, and the blood lipid metabolism of the drug group also tended to be normal group,and the differences were significant.Conclusion Litchi nuclei may play a role in the treatment of NAFLD by acting on such targets as INS, TNF, and HSP90AA1 and by modulating lipid and atherosclerotic pathways.

Prediabetes is a transitional state between normal blood glucose levels and diabetes, but it is also a reversible process. At the same time, as one of the most important tissues in the human body, the metabolic disorder of skeletal muscle is closely related to prediabetes. Huidouba (HDB) is a clinically proven traditional Chinese medicine with significant effects in regulating disorders of glucose and lipid metabolism. Our study aimed to investigate the efficacy and mechanism of HDB in prediabetic model mice from the perspective of skeletal muscle. C57BL/6J mice (6 weeks old) were fed a high-fat diet (HFD) for 12 weeks to replicate the prediabetic model. Three concentrations of HDB were treated with metformin as a positive control. After administration, fasting blood glucose was measured as an indicator of glucose metabolism, as well as lipid metabolism indicators such as total triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), free fatty acid (FFA), and lactate dehydrogenase (LDH). Muscle fat accumulation and glycogen accumulation were observed. The protein expression levels of p-AMPK, AMPK, PGC-1α, PPAR-α, and GLUT-4 were detected. After HDB treatment, fasting blood glucose was significantly improved, and TG, LDL-C, FFA, and LDH in serum and lipid accumulation in muscle tissue were significantly reduced. In addition, HDB significantly upregulated the expression levels of p-AMPK/AMPK, PGC-1α, PPAR-α, and GLUT-4 in muscle tissue. In conclusion, HDB can alleviate the symptoms of prediabetic model mice by promoting the AMPK/PGC-1α/PPARα pathway and upregulating the expression of GLUT-4 protein.

BACKGROUND:Pancreatic adenocarcinoma (PAAD) is a leading cause of malignancy-related deaths worldwide, and the efficacy of immunotherapy on PAAD is limited. Studies report that long non-coding RNAs (lncRNAs) play an important role in modulating genomic instability and immunotherapy. However, the identification of genome instability-related lncRNAs and their clinical significance has not been investigated in PAAD.METHODS:The current study developed a computational framework for mutation hypothesis based on lncRNA expression profile and somatic mutation spectrum in pancreatic adenocarcinoma genome. We explored the potential of GInLncRNAs(genome instability-related lncRNAs) through co-expression analysis and function enrichment analysis. We further analyzed GInLncRNAs by Cox regression and used the results to construct a prognostic lncRNA signature. Finally, we analyzed the relationship between GILncSig (genomic instability derived 3-lncRNA signature) and immunotherapy.RESULTS:A GILncSig was developed using bioinformatics analyses. It could divide patients into high-risk and low-risk groups, and there was a significant difference in OS between the two groups. In addition, GILncSig was associated with genome mutation rate in pancreatic adenocarcinoma, indicating its potential value as a marker for genomic instability. The GILncSig accurately grouped wild type patients of KRAS into two risk groups. The prognosis of the low-risk group was significantly improved. GILncSig was significantly correlated with the level of immune cell infiltration and immune checkpoint.CONCLUSIONS:In summary, the current study provides a basis for further studies on the role of lncRNA in genomic instability and immunotherapy. The study provides a novel method for identification of cancer biomarkers related to genomic instability and immunotherapy.

Objective: Acute liver injury (ALF) is a potential factor of many serious hepatopathies. Carbon tetrachlo-ride (CCl4) is a possible environmental toxicant that can induce ALF. Portulaca oleracea (PO) is one of the most popular edible herbs and has several biological activities such as antioxidant, antimicrobial, anti-inflammatory effects. We explored the significance of PO in regulating inflammatory function in animal models and cultured hepatocytes during liver damage caused by CCl4.Methods: The effect of PO on ALF was evaluated by CCl4-induced mice models in vivo. Hepatic levels of transaminase activities and inflammatory factors were examined. The gene and protein expression of S100A8 and S100A9 were measured by RT-PCR and Western blot analysis. Meanwhile, the efficacy of PO was certified by HepG2 cells in vitro. The transaminase activities, inflammatory factors, and the pro-tein expression of S100A8 and S100A9 were also detected.Results: Animal tests showed that pretreatment with PO reduced the liver pathological tissue damage and the serum levels of ALT, AST, ALT and LDH, as well as reducing the pro-inflammatory cytokines (IL-1b, IL-6, TNF-a) secretion in CCl4-induced liver injury mice. Simultaneously, HepG2 cells pretreated with PO exhibited a significant decrease in the activities of ALT and AST. Moreover, PO resulted in a sig-nificant downregulation of the pro-inflammatory markers S100A8, S100A9 gene and protein expression on CCl4 induced acute liver injury was demonstrated entirely in vivo and vitro experiments.Conclusion: PO may down-regulate S100A8 and S100A9 and inhibit pro-inflammatory cytokines' release, indicating a potential clinical effect for controlling the disease.(c) 2022 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background:Iron is an essential nutrient element, and iron metabolism is related to many diseases. Ferroptosis is an iron-dependent form of regulated cell death associated with ischemic stroke (IS). Hence, this study intended to discover and validate the possible ferroptosis-related genes involved in IS.Materials and methods:GSE16561, GSE37587, and GSE58294 were retrieved from the GEO database. Using R software, we identified ferroptosis-related differentially expressed genes (DEGs) in IS. Protein-protein interactions (PPIs) and enrichment analyses were conducted. The ROC curve was plotted to explore the diagnostic significance of those identified genes. The consistent clustering method was used to classify the IS samples. The level of immune cell infiltration of different subtypes was evaluated by ssGSEA and CIBERSORT algorithm. Validation was conducted in the test sets GSE37587 and GSE58294.Results:Twenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls. Enrichment analysis shows that the 21 DEGs are involved in monocarboxylic acid metabolism, iron ion response, and ferroptosis. Moreover, their expression levels were pertinent to the age and gender of IS patients. The ROC analysis demonstrated remarkable diagnostic values of LAMP2, TSC22D3, SLC38A1, and RPL8 for IS. Transcription factors and targeting miRNAs of the 21 DEGs were determined. Vandetanib, FERRIC CITRATE, etc., were confirmed as potential therapeutic drugs for IS. Using 11 hub genes, IS patients were categorized into C1 and C2 subtypes. The two subtypes significantly differed between immune cell infiltration, checkpoints, and HLA genes. The 272 DEGs were identified from two subtypes and their biological functions were explored. Verification was performed in the GSE37587 and GSE58294 datasets.Conclusion:Our findings indicate that ferroptosis plays a critical role in the diversity and complexity of the IS immune microenvironment.

Objective: Sarcopenia causes loss of skeletal muscle and function, thus seriously affecting the physical function and quality of life in the elderly. This article discusses the specific molecular mechanism and ameliorating effects of Tudangshen (TDS) on sarcopenia in elderly rats with type 2 diabetes mellitus (T2DM).Methods: Elderly Sprague-Dawley (SD) rats were randomly selected and fed with a high-fat diet combined with intraperitoneal injection of streptozotocin to establish T2DM model. The model rats were stratified and randomly divided into model group, metformin group, TDS high-dose group, TDS medium-dose group, and TDS low-dose group according to blood glucose combined with body weight, and the same batch of old SD rats were set as normal control group. The effects of TDS in an elderly T2DM sarcopenia rat model were evaluated by observing body positions of the rats, analyzing blood biochemistry, testing exercise capacity, and pathologically staining sectioned gastrocnemius muscle tissues. The molecular mechanisms of the effects were analyzed using quantitative real-time polymerase chain reaction and western blotting.Results: TDS has no statistically significant effect on blood glucose, insulin and glycosylated serum protein in aged rats with T2DM, but it can reduce levels of glycosylated serum protein, total cholesterol, triglycerides, and low-density lipoprotein; it improves pathological changes in rat gastrocnemius muscle tissues, and increases muscle cell activity in elderly rats with T2DM and sarcopenia. TDS also promoted the upregulation of the expression of mammalian target of rapamycin (mTOR)/protein kinase B (PKB/Akt)/phosphatidylinositol 3-kinase (PI3K)/ribosomal protein S6 kinase/eukaryotic initiation factor 4E binding rotein1 mRNA in rats and triggered an increase in corresponding protein levels.Conclusions: TDS alleviated muscle decline in elderly rats with T2DM by activating the PI3K/AKT/mTOR signaling pathway and regulating the synthesis of corresponding proteins.