Tripterygium glycosides (TG), bioactive extracts derived from Tripterygium wilfordii Hook F., possess potent anti-inflammatory and immunomodulatory properties, making them promising therapeutic candidates for a range of autoimmune and inflammatory diseases. This review summarizes recent advances in the pharmacological mechanisms of TG, including their roles in cytokine suppression, autophagy modulation, anti-fibrotic remodeling, and oxidative stress regulation. Evidence from clinical trials and real-world studies supports the therapeutic potential of TG in conditions such as systemic lupus erythematosus, diabetic kidney disease, rheumatoid arthritis, and psoriasis. In addition, we highlight ongoing efforts to overcome TG's narrow therapeutic window through monomer isolation, structural optimization, prodrug strategies, and innovative delivery systems. Emerging derivatives—such as LLDT-8 (5R-5-hydroxytriptolide) and triptonide—exhibit reduced toxicity while retaining robust efficacy, providing new avenues for clinical translation. Furthermore, the integration of systems pharmacology, synthetic biology, and AI-assisted drug design is accelerating the development of next-generation TG-based therapeutics.

Tripterygium wilfordii, a traditional Chinese botanical drug, has emerged as a rich source of bioactive metabolites with promising therapeutic potential. Among its metabolites, diterpenoids and triterpenoids—such as triptolide, triptonide, and celastrol—exhibit potent immunosuppressive, anti-inflammatory, and anti-tumor properties through modulation of key molecular pathways including NF-κB, JAK/STAT, and TGF-β/Smad. This review provides a comprehensive overview of the chemical classification, pharmacological mechanisms, and clinical translation of major metabolites derived from T. wilfordii. It highlights their application in autoimmune diseases, cancer, fibrosis, and metabolic disorders, while addressing current challenges in safety, solubility, and bioavailability. Advancements in drug delivery systems, structural modification, and precision medicine approaches are also discussed. Together, these insights aim to guide future research and translational development of T. wilfordii-based compoundic therapeutics.

Glucose homeostasis, which is critical for maintaining energy supply and health, involves glycogen metabolism, glycolysis, and gluconeogenesis. Lysosomal membrane proteins (LMPs) play core roles in regulating these processes. However, no focused systematic review of the topic has been reported. This review provides an in-depth analysis of the central roles of LMPs in glucose metabolism, focusing on the regulation of glucose homeostasis and their potential effects on metabolic diseases through the regulation of autophagy, signaling networks, specialized transporter functions, and other relevant mechanisms. In general, LMPs play core roles in lysosomal biosynthesis, and an in-depth study of their relationship with glucose metabolism could significantly highlight the important contribution of lysosomes in the development of related diseases.

BACKGROUND:Environmental toxicants are increasingly recognized as potential modifiers of diabetic nephropathy (DN) progression. Aflatoxin B1 (AFB1), a ubiquitous foodborne contaminant, can induce oxidative and fibrotic injury, yet its DN-relevant molecular circuitry has not been systematically mapped. AIM:To define DN-associated, AFB1-responsive pathways and prioritize mechanistically plausible molecular mediators and intercellular communication axes linked to profibrotic remodeling. METHODOLOGY:We integrated bulk transcriptomics with single-cell and spatial transcriptomics, immune deconvolution, cell-cell communication inference, pseudotime trajectory analysis, and structure-informed modeling (molecular docking and molecular dynamics simulations). RESULTS:AFB1-associated signatures were enriched for oxidative stress, xenobiotic metabolism, and extracellular matrix (ECM) remodeling programs. Cross-cohort analyses prioritized ITGA11 and LTBP1 as consistently AFB1-responsive candidates with diagnostic performance (AUC >0.7), and spatial/single-cell mapping localized their expression predominantly to mesangial and fibroblast-like compartments. Pseudotime trajectories suggested distinct dynamics, with transient ITGA11 activation and sustained LTBP1 upregulation, consistent with complementary roles during ECM remodeling. Cell-cell communication analysis highlighted a glomerular PTHLH-PTH1R signaling axis between podocyte- and mesangial-associated states, and immune profiling linked ITGA11/LTBP1-associated programs to innate/adaptive immune reprogramming. In silico modeling supported direct AFB1-protein interactions, with stable binding observed over 100-ns simulations and higher predicted affinity toward ITGA11 (≈-8.4 kcal/mol). CONCLUSION:Collectively, our results suggest that AFB1 may aggravate DN by coupling oxidative/immune stress to mesangial- and fibroblast-centered ECM remodeling. ITGA11/LTBP1 and the glomerular PTHLH-PTH1R signaling axis therefore merit focused investigation as priority nodes to delineate the mechanistic basis of AFB1-driven nephrotoxicity in DN, including intercellular injury amplification within the glomerular unit.

β-cell dedifferentiation plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). SID1 transmembrane family member 2 (Sidt2) is a lysosomal membrane protein known to regulate hepatic steatosis and lipid metabolism. However, its role in pancreatic β-cell dedifferentiation remains unclear. In this study, we found that Sidt2 expression was significantly decreased in diabetic mice and patients, correlating with impaired glucose metabolism. Through in-vitro and in-vivo experiments, we observed that the loss of Sidt2 accelerated β-cell dedifferentiation, as evidenced by an increase in the number of α cells and a marked reduction in key β-cell markers, such as pancreatic and duodenal homeobox 1 (Pdx1), V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), and glucose transporter 2 (Glut2). Moreover, Sidt2 deficiency disrupted islet function, leading to impaired insulin secretion. Further analyses revealed that the dedifferentiation of β cells induced by Sidt2 deficiency was independent of the Forkhead box protein O1 (FoxO1) pathway, a known regulator of β-cell identity. Instead, the primary mechanism appeared to be related to defects in insulin secretion. In conclusion, our study identified a novel regulatory mechanism of β-cell dedifferentiation and insulin secretion mediated by Sidt2. These findings enhance our understanding of the molecular mechanisms underlying β-cell dedifferentiation and offer new perspectives on the pathogenesis of T2DM, supporting the potential of targeting Sidt2 as an innovative therapeutic strategy to preserve β-cell function and to treat this disease.

Cancer development is influenced by genetic and epigenetic variations, with the interactions between microRNAs (miRNAs) and lysosomal membrane proteins (LMPs) representing key regulatory mechanisms with potential as therapeutic targets. This review focuses on the complex regulatory mechanisms of miRNAs and LMPs in tumor progression, specifically highlighting their roles in tumor suppression, tumor promotion, tumor therapy, and drug resistance and their future application in treatment strategies. Overall, the interactions of LMPs with miRNAs have critical roles in tumor regulation, and studies of these interactions will further highlight their molecular contributions to cancer development.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease (ESRD), and thus, appropriate animal models are critically needed to investigate its pathogenesis and identify new therapeutic targets. DN mouse models are important tools for studying the mechanisms of DN and exploring therapeutic strategies. Common features of the renal pathology in diabetic patients include thickening of the glomerular basement membrane, mesangial expansion, glomerulosclerosis, tubular injury, and interstitial fibrosis. Although DN mouse models generated through pharmacological or genetic approaches demonstrate comparable renal structural changes, the existing DN mouse models fail to replicate the severity of human DN pathology, underscoring the need for further research to develop more precise DN mouse models. Mouse models with renal pathology that better matches the human condition would provide a key platform for identifying potential therapeutic targets and developing new drugs. This review summarizes the advantages and limitations of various DN mouse models, including pharmacological and dietary induction models, genetically engineered models, spontaneous models generated via genetic modification, and models developed by combined modeling approaches. The goal of this review is to provide valuable insights and guidance for the construction of more comprehensive DN models. Clinical trial number Not applicable.

Aim To explore the correlation between estimated glomerular filtration rate (eGFR) and asymptomatic left ventricular diastolic dysfunction (ALVDD) in patients with type 2 diabetes mellitus (T2DM). Methods We performed a retrospective study involving 47 ALVDD and 30 non-ALVDD T2DM patients between October 2023 and March 2024. Patient characteristics, laboratory tests, and echocardiographic measurements were recorded. The relationship between eGFR and ALVDD was examined by Spearman correlation and logistic regression analyses. Receiver operating characteristic curve analysis was conducted to test the diagnostic value of eGFR for ALVDD. Results Patients with ALVDD had lower eGFR but higher echocardiographic measurements than patients without ALVDD (P < 0.05). The eGFR was negatively correlated with echocardiographic measurements (P < 0.05) and was an independent risk factor for ALVDD. Receiver operating characteristic curve analysis demonstrated that eGFR had an area under the ROC curve of 0.766, with a sensitivity of 63.8%, a specificity of 96.7%, and a threshold of 94.02 mL/min/1.73 m2 Conclusions The eGFR was closely correlated with ALVDD and could be applied to estimate the risk of ALVDD in T2DM patients. We recommend the eGFR be considered when evaluating cardiac diastolic dysfunction in T2DM patients at an early stage and thereby guide prompt clinical intervention.

This study aimed to characterize urinary stress hormones and their metabolites in patients with chronic kidney disease associated with diabetes (CKD with diabetes) and to evaluate their associations with renal function, providing insights into stress-related mechanisms and potential biomarker utility. We enrolled 735 participants, including 449 with type 2 diabetes mellitus(T2D)and 286 with CKD with diabetes. Urinary concentrations of norepinephrine, cortisol, aldosterone, and 17-ketosteroids were analyzed. Statistical methods included correlation and regression analyses, receiver operating characteristic (ROC) curves, and orthogonal partial least squares discriminant analysis (OPLS-DA) to evaluate diagnostic value. Urinary norepinephrine, cortisol, and 17-ketosteroids levels were significantly lower in CKD patients with diabetes than in those with diabetes alone. Norepinephrine was inversely correlated with albumin-to-creatinine ratio, urinary microalbumin, blood urea nitrogen, and serum creatinine, and positively with estimated glomerular filtration rate. Similar trends were observed for cortisol and 17-ketosteroids. Aldosterone was also negatively correlated with urinary microalbumin and creatinine. OPLS-DA showed distinct metabolic profiles between CKD with diabetes and diabetes, suggesting metabolic heterogeneity. Multivariate logistic regression identified norepinephrine as an independent protective factor, while diastolic blood pressure, urinary glucose, and homovanillic acid were risk factors. A composite model integrating norepinephrine, 17-ketosteroids, and homovanillic acid demonstrated high diagnostic performance, with the norepinephrine-based model achieving an AUC of 0.831 in validation. Urinary adrenal hormones and their metabolites provide valuable insights into stress-related mechanisms in CKD with diabetes and may hold potential as complementary noninvasive biomarkers for disease assessment. Not applicable.

C opper is an essential trace element involved in mitochondrial metabolism and redox regulation, and its dysregulation has been increasingly linked to metabolic disorders. However, its specific role in diabetic kidney disease (DKD) remains unclear. In this study, we conducted an integrated analysis combining bulk RNA-seq, single-cell RNA sequencing, and spatial transcriptomics to investigate the involvement of cuproptosis-related genes in DKD. We identified consistent upregulation of FDX1 and LIAS, two key regulators of copper-induced cell death, in the kidneys of diabetic mice. These genes were predominantly localized to metabolically active tubular segments, including the distal convoluted tubule and cortical thick ascending limb. Clinically, urinary copper levels were significantly elevated in DKD patients, indicating systemic copper imbalance. Protein-level validation confirmed increased expression of FDX1 and LIAS as well as decreased expression of cleaved and monomeric form of DLAT in db/db mouse kidney tissue, suggesting impaired mitochondrial lipoylation, a molecular hallmark of cuproptosis. Collectively, these findings provide multi-level evidence that copper overload and activation of cuproptosis-associated pathways may contribute to tubular injury in DKD, offering new insight into trace element-related mechanisms in the pathology of diabetic kidney disease.

Tumor progression is closely related to the complex interactive regulation between autophagy and apoptosis signaling pathways, particularly the molecular mechanisms mediated by lysosomal membrane proteins (LMPs), and their dynamic regulatory processes have become an important direction of current research. However, there is a lack of in-depth and systematic reviews on this topic. This review focuses on the multi-dimensional mechanisms by which LMPs mediate the regulation of the autophagy-apoptosis crosstalk via key molecules like Beclin1, Autophagy-related (ATG), Caspase, PARP, and Bax/Bcl-2 in tumor progression. In addition, it highlights their roles in signaling pathways, drug-mediated cell cycle and combination therapy mechanisms, autophagic and apoptotic crosstalk underlying synergistic and antagonistic effects, and other key biological processes. Overall, as the core hub of the autophagy-apoptosis crosstalk network, the multifactorial synergistic effect mediated by LMPs is crucial in tumor progression. In-depth analysis of this mechanism not only elucidates the molecular pathological basis of tumorigenesis but also provides a theoretical basis for the development of novel anti-tumor intervention strategies targeting LMPs.

Background and aims:Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. This study aimed to investigate the potential of urinary 11-dehydrothromboxane B2 (U-TXM) as a biomarker for the early detection of DKD. Materials and methods:A total of 690 patients were enrolled, including 422 with diabetes mellitus (DM) and 268 with DKD. Patients with type 1, type 2, and other specific forms of diabetes were consecutively recruited from the Department of Endocrinology, Yijishan Hospital of Wannan Medical College (April-September 2024). U-TXM levels were measured and their clinical relevance to DKD was evaluated using correlation analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis. Results:Urinary U-TXM levels were significantly higher in patients with DKD than in those with DM (median: 1158.05 vs. 960.44 pg/mg Cr; P<0.001). When stratified by renal function, U-TXM remained elevated in DKD regardless of serum creatinine (Cr) level (>70 or ≤70 μmol/L, both P<0.001). Multivariate analysis confirmed the existence of an independent association between DKD and U-TXM (OR=1.778, P=0.001), serum Cr (odds ratio [OR]=2.861, P<0.001), and systolic blood pressure (SBP, OR=1.032, P=0.001). U-TXM correlated positively with the urine albumin-to-Cr ratio (r=0.225, P<0.001), but only weakly with Cr and blood urea nitrogen. ROC analysis showed limited diagnostic value for U-TXM alone (area under the curve [AUC]=0.625), which improved substantially when combined with serum Cr and SBP (AUC=0.803). Conclusion:U-TXM shows potential as a biomarker for DKD, particularly in patients at early disease stages. Validation through longitudinal, multicenter, and comparative studies is required to confirm its clinical utility.

This study aims to evaluate the efficacy and safety of Crisugabalin in patients with diabetic peripheral neuropathic pain (DPNP), with a focus on its rapid onset of action. All the analyses in this study were based on data from a phase 2/3 adaptive randomized clinical trial that enrolled 596 patients. Participants were categorized into four treatment groups according to the intervention received: Crisugabalin 40 mg/day, Crisugabalin 80 mg/day, placebo, and Pregabalin 300 mg/day. The primary endpoint was the change in the average daily pain score (ADPS) over a 13-week treatment period. Secondary endpoints included changes in the Numeric Rating Scale (NRS) and the daily sleep interference score (DSIS) during the first two weeks of treatment. Both Crisugabalin treatment groups (40 mg/day and 80 mg/day) demonstrated statistically significant reductions in ADPS compared to the placebo group starting from week 1 and continuing through week 13 (P < 0.05). Significant differences in pain relief for the Pregabalin group were observed only from week 6. Improvements in NRS and DSIS scores were also noted in both Crisugabalin groups, with statistically significant enhancements evident as early as day 2 of administration. Safety assessments indicated that Crisugabalin was well-tolerated, with a low incidence of serious adverse events and no significant increase in dropout rates among participants. The findings suggest that Crisugabalin offers effective pain relief with an acceptable safety profile, highlighting its rapid onset in patients with DPNP. Clinical trial registration number derived from our parent project, we have retained the original registration identifier: NCT04647773.

ImportanceMany patients with diabetic peripheral neuropathic pain (DPNP) experience inadequate relief, despite best available medical treatments. There are no approved and effective therapies for patients with DPNP in China.ObjectiveTo evaluate the efficacy and safety of capsules containing γ-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP.Design, Setting, and ParticipantsThis phase 2 to 3 adaptive randomized clinical trial was multicenter, double blind, and placebo and pregabalin controlled. The trial started on December 10, 2020, and concluded on July 8, 2022. In stage 1, various doses of HSK16149 were evaluated to determine safety and efficacy for stage 2. The second stage then validated the efficacy and safety of the recommended dose.InterventionIn stage 1, enrolled patients (n = 363) were randomized 1:1:1:1:1:1 to 4 HSK16149 doses (40, 80, 120, or 160 mg/d), pregabalin (300 mg/d), or placebo. In stage 2, patients (n = 362) were randomized 1:1:1 to receive HSK16149, 40 or 80 mg/d, or placebo. The final efficacy and safety analysis pooled data from patients receiving the same treatment.Main Outcomes and MeasuresThe primary efficacy end point in stage 1 was the change from baseline in average daily pain score (ADPS) at week 5. The primary efficacy end point in stage 2 was the change from baseline in ADPS at week 13. When the final statistical analysis was performed, the P values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences.ResultsOf 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d. A total of 644 patients (88.8%) completed the study. The 40- and 80-mg/d doses of HSK16149 were recommended in stage 2. At week 13, the ADPS mean (SD) change from baseline was −2.24 (1.55) for the 40-mg/d and −2.16 (1.79) for 80-mg/d groups and −1.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P < .001). In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common.Conclusions and RelevanceForty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated.Trial RegistrationClinicalTrials.gov Identifier: NCT04647773

As a self-degrading and highly conserved survival mechanism, autophagy plays an important role in maintaining cell survival and recycling. The discovery of autophagy-related (ATG) genes has revolutionized our understanding of autophagy. Lysosomal membrane proteins (LMPs) are important executors of lysosomal function, and increasing evidence has demonstrated their role in the induction and regulation of autophagy. In addition, the functional dysregulation of the process mediated by LMPs at all stages of autophagy is closely related to neurodegenerative diseases and cancer. Here, we review the role of LMPs in autophagy, focusing on their roles in vesicle nucleation, vesicle elongation and completion, the fusion of autophagosomes and lysosomes, and degradation, as well as their broad association with related diseases.

The SID1 transmembrane family, member 2, namely, Sidt2 , is a highly glycosylated multichannel lysosomal transmembrane protein, but its specific physiological function remains unknown. Lysosomal membrane proteins are very important for the executive functioning of lysosomes. As an important part of the lysosomal membrane, Sidt2 can maintain the normal morphology of lysosomes and help stabilize them from the acidic pH environment within. As a receptor/transporter, it binds and transports nucleic acids and mediates the uptake and degradation of RNA and DNA by the lysosome. During glucose metabolism, deletion of Sidt2 can cause an increase in fasting blood glucose and the impairment of grape tolerance, which is closely related to the secretion of insulin. During lipid metabolism, the loss of Sidt2 can cause hepatic steatosis and lipid metabolism disorders and can also play a role in signal regulation and transport. Here, we review the function of the lysosomal membrane protein Sidt2 , and focus on its role in glucose and lipid metabolism, autophagy and nucleotide (DNA/RNA) transport.

INTRODUCTION The study aimed to explore the efficacy and safety of low-dose (LD) and regular-dose (RD) prednisone (PDN) for the treatment of subacute thyroiditis (SAT). MATERIAL AND METHODS Patients were randomly allocated using the block randomization method to the 2 groups. The primary outcome was the time required for PDN treatment. Secondary outcomes included percentages of relapse, mean score for the Morisky Medication Adherence Scale-8© (MMAS-8), time required for symptoms to resolve, cumulative PDN dose (mg), and mean erythrocyte sedimentation rate (ESR) at 2 weeks and at baseline. RESULTS The study cohort included 77 patients, randomized 74 participants, and 68 completed the study. There was no significant difference in the treatment duration between the LD and RD groups (55.31 ± 14.05 vs. 61.25 ± 19.95 days, p = 0.053). The mean difference in the time required for PDN treatment between the LD and RD groups was -1.86 [95% confidence interval (CI) = -10.64 to 6.92] days, which was within the non-inferiority margin of 7 days. There was a significant difference in the mean score for MMAS-8 between the LD and RD groups (5.84 ± 0.88 vs. 5.33 ± 1.12, p = 0.031). Also, there was a significant difference in the cumulative PDN dose between the LD and RD groups (504.22 ± 236.86 vs. 1002.28 ± 309.86, p = 0.046). The ESR at 2 weeks was statistically significant compared to baseline values in both groups, with pre-treatment and post-treatment ESRs of 49.91 ± 24.95 and 17.91 ± 12.60/mm/h, (p < 0.0001) in the LD group and 65.08 ± 21.77 and 17.23 ± 13.61/mm/h (p < 0.0001) in the RD group. CONCLUSION Low-dose PDN therapy may be sufficient to achieve complete recovery and better outcomes for SAT. This study is registered with the Chinese Clinical Trial Registry (02/10/2021 ChiCTR2100051762).

目的:分析雷公藤多苷(multi-glycosides of tripterygium wilfordii hookf,GTW)治疗糖尿病肾脏病(diabetic kidney disease,DKD)临床病例资料,探讨GTW治疗DKD的有效性和安全性.方法:回顾性分析2019年6月至2022年10月皖南医学院弋矶山医院门诊进行GTW治疗的51例DKD患者的随访及治疗情况,分析治疗6个月后,GTW服药前后实验室疗效指标变化以及药物不良反应情况.结果:经治疗6个月后,患者白蛋白为(40.72±4.87)g/L,与治疗前(35.86±7.90)g/L相比明显升高(P<0.05).治疗前尿白蛋白与肌酐比值(urea albumin creatinine ratio,UACR)为(2 145±253)mg/g,治疗后为(1 263±238)mg/g,治疗后有明显下降(P<0.05);尿常规尿蛋白半定量重度(3+、4+)患者总人数较前下降,治疗前后差异具有统计学意义(P<0.05).治疗 6 个月后患者空腹血糖(fasting blood-glu-cose,FPG)及糖化血红蛋白(glycosylated hemo-globin,HbA1c)分别为(8.42±3.31)mmol/L、(7.41±1.48)%,与基线FPG(7.20±1.95)mmol/L、HbA1c(6.63±1.00)%相比下降(P<0.05);治疗过程中,患者肾小球滤过率(glomerular filtration rate,eGFR)≥3a期血肌酐(Scr)倍增人数为1人(3.80%),UACR倍增人数为2人(7.70%),eGFR≤3b期分别为0人和1人(4.00%),两组差异无统计学意义(P>0.05);3例(5.90%)出现肝功能异常、1例(2.00%)出现白细胞减少,给予护肝、升白药物治疗后情况好转.其他血糖、血脂、血压等指标治疗后与治疗前相比差异无统计学意义(P>0.05).结论:DKD患者采用GTW治疗能够显著减少尿蛋白,提高白蛋白,改善患者肾功能,值得临床推广运用.

OBJECTIVE:To explore the regulatory mechanism of human hepatocyte apoptosis induced by lysosomal membrane protein Sidt2 knockout.METHODS:The Sidt2 knockout (Sidt2-/-) cell model was constructed in human hepatocyte HL7702 cells using Crispr-Cas9 technology.The protein levels of Sidt2 and key autophagy proteins LC3-II/I and P62 in the cell model were detected using Western blotting, and the formation of autophagosomes was observed with MDC staining.EdU incorporation assay and flow cytometry were performed to observe the effect of Sidt2 knockout on cell proliferation and apoptosis.The effect of chloroquine at the saturating concentration on autophagic flux, proliferation and apoptosis of Sidt2 knockout cells were observed.RESULTS:Sidt2-/- HL7702 cells were successfully constructed.Sidt2 knockout significantly inhibited the proliferation and increased apoptosis of the cells, causing also increased protein expressions of LC3-II/I and P62(P < 0.05) and increased number of autophagosomes.Autophagy of the cells reached a saturated state following treatment with 50 μmol/L chloroquine, and at this concentration, chloroquine significantly increased the expressions of LC3B and P62 in Sidt2-/- HL7702 cells.CONCLUSION:Sidt2 gene knockout causes dysregulation of the autophagy pathway and induces apoptosis of HL7702 cells, and the latter effect is not mediated by inhibiting the autophagy-lysosomal pathway.

Objective:To screen highly expressed inflammatory factors in diabetic nephropathy models using protein microarray, analyze differential genes and their regulatory networks, and predict potential therapeutic small molecular compounds.Methods:The inflammatory factor microarray was used to screen the inflammatory factors with the same tendency in the cell model and animal model of diabetic nephropathy. The differential genes screened by R language were enriched and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). STRING builds a protein interaction network online, Cytoscape software analyzes the core subnetwork, and Connectivity Map searches for and predicts small molecule compounds.Results:Diabetic nephropathy model was established using 16-week-old db/db mice and mesangial cells stimulated with high glucose, and the expression of C-X-C motif chemokine ligand 1(CXCL1) was elevated in both models. Multiple GEO datasets indicated a strong association between the high expression of CXCL1 and diabetic nephropathy. Specifically, GSE30122 showed an upregulation of 30 genes and a downregulation of 23 genes. GO enrichment analysis focused on biological processes such as humoral immunity and lipopolysaccharide response; While KEGG enrichment was mainly in pertussis and coagulation cascade pathways. CytoHubba identified 10 hub genes, such as ALB, LUM, and CXCL1. In addition, 10 small molecule compounds were predicted as potential therapeutic drugs using Connectivity Map.Conclusions:CXCL1 may serve as a key gene in the occurrence and development of diabetic nephropathy. ALB, LUM, CXCL1, MMP7, TGFBI, CCL2, S100A4, SOX9, VCAN, and CLU may participate in the regulatory network centered around CXCL1. There are 10 small molecular compounds demenestrating the potential to be therapeutic agents.