Migrasomes are a recently discovered class of organelles, typically generated at the intersections and tips of retraction fibers (RFs) in migrating cells. These monolayer vesicular structures encapsulate a variety of bioactive molecules and have been shown to participate in essential physiological processes, including intercellular communication, embryonic development, immune microenvironment modulation, and mitochondrial homeostasis. Beyond their physiological roles, accumulating evidence has revealed that migrasomes are also closely associated with the pathogenesis of various diseases. These include kidney and retinal damage, vascular disorders, as well as the initiation and progression of multiple tumors such as glioma, osteosarcoma, liver cancer, and pancreatic cancer. Given their emerging significance in both normal physiology and disease, migrasomes hold promise as novel biomarkers and therapeutic targets, offering new avenues for research in cell biology and translational medicine.In this review, we summarize recent advances in migrasome research, with a particular emphasis on their involvement in disease mechanisms - an area of growing importance given the current limitations in clinical treatment. We also provide perspectives on future research directions and the potential translational applications of migrasomes.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. The Shen-Kang Recipe (SKR) is a traditional Chinese medicine formula used clinically to slow DKD progression, but its bioactive constituents and molecular targets remain unclear. Solute carrier family 15 member 2 (SLC15A2/PEPT2), a high-affinity peptide transporter expressed in renal proximal tubules, has been implicated in kidney pathophysiology, yet its potential role in mediating the therapeutic effects of the SKR has not been explored. Here, we evaluated the effects of the SKR in db/db mice and found that SKR treatment significantly improved renal function, attenuated glomerulosclerosis, and reduced interstitial collagen deposition. Wide-target metabolomics and quantitative proteomics revealed that the SKR broadly reversed DKD-associated metabolic and proteomic disturbances, particularly in pathways related to energy and amino acid metabolism. Proteomic analysis identified SLC15A2 as a key proximal tubule protein downregulated in DKD and selectively restored by the SKR. UPLC-Q-TOF/MS-based serum pharmacochemistry and network pharmacology highlighted quercetin as a principal bioactive component of the SKR. Molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) confirmed direct, high-affinity binding between quercetin and SLC15A2 (KD = 7.5 µM). In TGF-β1-stimulated HK-2 cells, quercetin suppressed epithelial-mesenchymal transition (EMT), as evidenced by restored E-cadherin and reduced N-cadherin, vimentin, and α-SMA expression; this effect was abrogated by siRNA-mediated SLC15A2 knockdown, demonstrating the functional necessity of this axis. Collectively, these findings identify a quercetin-SLC15A2 axis through which the SKR inhibits EMT and alleviates renal fibrosis in DKD, providing a mechanistic basis for its clinical application and nominating SLC15A2 as a potential therapeutic target.

Glioblastomas (GBM), the most aggressive primary brain tumors, remain challenging to treat due to their rapid proliferation, invasiveness, and resistance to current therapies. Emerging evidence highlights pyroptosis and ferroptosis as critical regulators of tumor progression. This review elucidates the pivotal role of mitochondrial dysfunction in driving these programmed cell death pathways in GBM. Specifically, mitochondrial abnormalities induce overproduction of reactive oxygen species (ROS) and disrupt iron homeostasis, thereby triggering pyroptosis through inflammasome activation and ferroptosis via lipid peroxidation accumulation. Impaired mitochondrial dynamics, such as membrane potential collapse, pro-inflammatory cytokine release, and defective mitophagy, synergistically determine tumor cell fates. We propose novel therapeutic strategies targeting mitochondrial ROS-scavenging systems, iron-sulfur cluster biosynthesis, and mitophagy modulation to overcome resistance to treatment of GBM. These investigations not only advance the understanding of the pathobiology of GBM but also underscore mitochondria as multifaceted therapeutic hubs and offer translational potential for other diseases linked to mitochondrial dysregulation. By integrating cutting-edge research data, this review establishes a foundation for developing precision therapies centered on pyroptosis and ferroptosis modulation, bridging mechanistic discoveries with clinical innovation in neuro-oncology.

OBJECTIVES:To investigate the therapeutic effect of Jia Wei Qingxin Lotus Seed Drink (QISD) on renal injury in mice with diabetic kidney disease (DKD) and its mechanism. METHODS:The immunogenes differentially expressed in renal tubular epithelial cells (HK-2) induced by late glycosylation end products were screened using GSE193192 dataset from GEO database and the pharmacological mechanisms were predicted. Male ICR mouse models of DKD established by high-fat feeding for 4 weeks and intraperitoneal streptozotocin injection for 5 days were randomized for treatment with low (14.46 g/kg), medium (28.92 g/kg) and high (57.84 g/kg) doses of QISD via gavage for 12 weeks, with dapagliflozin as the positive control drug (n=8). Penal pathologies of the mice were observed by HE, PAS and Masson staining, and renal expression levels of KDM3C, SP1, TNF-α, and MCP-1 mRNAs and proteins were detected using RT-qPCR and Western blotting. In a HK-2 cell model of lipopolysaccharide (LPS)-induced inflammatory injury, the effects of small-molecule inhibitors were tested to explore the therapeutic mechanism of QISD against cell inflammation. RESULTS:QISD treatment significantly lowered serum levels of glycated serum protein, creatinine and urea nitrogen, reduced glycogen accumulation, attenuated glomerular hypertrophy, and decreased renal inflammatory infiltration in DKD mouse models. QISD also reduces the expression levels of KDM3C, SP1, TNF‑α and MCP-1 in the kidney tissues of the mice. In LPS-induced HK-2 cells, the application of JIB-04, an inhibitor of KDM3C, obviously suppressed the expression levels of the inflammatory factors including TNF‑α, MCP-1 and ICAM-1. CONCLUSIONS:QISD can ameliorate renal injury in DKD mice by inhibiting inflammatory response via suppressing excessive activation of the KDM3C/SP1 signaling pathway.

Brown adipose tissue (BAT) thermogenesis combats obesity, but mechanisms linking calcium dynamics to thermogenic programming remain incompletely defined. Here, we identify the calcium channel TRPC6 as an essential BAT-intrinsic regulator of metabolic health. BAT-specific Trpc6 knockout (Trpc6BTKO) mice exhibit spontaneous BAT whitening, mitochondrial dysfunction, and impaired cold tolerance. Upon high-fat diet (HFD) challenge, Trpc6BTKO mice develop exacerbated obesity, hepatic steatosis, and insulin resistance. These phenotypes are driven by increased energy intake and reduced energy expenditure associated with impaired thermogenesis. TRPC6 deficiency suppresses mitochondrial biogenesis and thermogenesis. Mechanistically, TRPC6 mediates calcium influx and interacts directly with BMPR2, thereby selectively activating p38 MAPK signaling to drive thermogenic gene expression. Genetic disruption of the TRPC6-BMPR2 complex abolishes TRPC6-mediated thermogenesis. Thus, we define a non-redundant TRPC6-BMPR2-p38 MAPK signaling axis whose disruption underpins obesity and associated metabolic dysfunction, positioning it as a promising therapeutic target for metabolic disease.

Diabetic kidney disease (DKD) is a common and challenging microvascular complication of diabetes. TGF-β1-mediated epithelial-to-mesenchymal transition (EMT) in renal tubular epithelial cells, characterized by loss of epithelial polarity and intercellular adhesion alongside acquisition of a mesenchymal phenotype, is widely recognized as a key driver of DKD. Here, we reveal that renal interstitial fibrosis (RIF) and EMT constitute important pathological foundations for DKD progression, validated in both clinical DKD patients and DKD mouse models. Concurrently, we confirm the elevated expression of homoeotic domain-interacting protein kinase 2 (HIPK2) in DKD, though its regulatory role in EMT remains unclear. We further established a DKD-EMT cellular model by inducing human renal tubular epithelial cells (HK-2) with TGF-β1 combined with high glucose stimulation. Here, we found that inhibiting HIPK2 expression significantly delayed EMT progression and improved RIF in DKD. Thus, our study provides a novel therapeutic strategy for DKD progression and demonstrates that HIPK2 serves as a potential therapeutic target for DKD-EMT.

Tirzepatide, a dual GIP/GLP-1 receptor agonist, produces greater weight loss than semaglutide, but the neural basis of this difference remains unclear. Here we identify, in mice, a tirzepatide-preferential brain–brown adipose tissue (BAT) pathway that promotes weight loss independent of appetite suppression. Located outside the blood–brain barrier, the area postrema (AP) is directly accessible to circulating tirzepatide. Tirzepatide-responsive AP neurons projecting to the dorsal motor nucleus of the vagus (DMV) provide glutamatergic input to raphe pallidus (RPa)-projecting DMV neurons, thereby recruiting an AP→DMV→RPa circuit that drives BAT thermogenesis. Inhibiting RPa neurons, DMV→RPa projections or AP glutamatergic neurons suppresses tirzepatide-induced BAT activation and attenuates weight loss, whereas optogenetic activation of tirzepatide-responsive RPa neurons or DMV→RPa terminals recapitulates these effects. This pathway accounts for approximately 40% of tirzepatide-induced weight loss but is not effectively recruited by semaglutide. Thus, tirzepatide couples appetite suppression with a distinct brainstem thermogenic mechanism, providing a circuit-level basis for its greater anti-obesity efficacy.

BACKGROUND:Erectile dysfunction (ED) is a prevalent male sexual dysfunction that remarkably impacts patients' quality of life and is also recognized as a precursor to cardiovascular disease (CVD) events. Branched-chain amino acids (BCAAs) are derived from dietary intake and mainly involved in energy metabolism. Previous studies have underscored the association between BCAAs and CVD, but the causal link between BCAAs and ED remains uncertain. METHODS:The bidirectional Mendelian randomization (MR) study used the genetic data from genome-wide association studies (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with total BCAAs, leucine, isoleucine, and valine. The genetic data for ED were acquired from the FinnGen study (n = 95,178). The primary method used to assess causal associations was the inverse variance-weighted (IVW) method, supplemented by MR-Egger, weighted median, and simple median analyses. Cochrane's Q test was utilized to evaluate heterogeneity within the results, while the MR-Egger intercept test was utilized to evaluate the Level pleiotropy. A sensitivity analysis was performed employing leave-one-out analysis. RESULTS:The MR analysis results indicate a positive correlation between levels of total BCAA (OR = 1.984, 95 % CI = 1.018-3.868, P = 0.044), leucine (OR = 2.277, 95 % CI = 1.121-4.626, P = 0.023), isoleucine (OR = 2.584, 95 % CI = 1.167-5.722, P = 0.019), valine (OR = 1.894, 95 % CI = 1.119-3.206, P = 0.017), and the risk of ED. Sensitivity tests confirmed the accuracy and robustness of the study findings. Moreover, the reverse MR analysis found no association between ED and the BCAAs. CONCLUSION:The results of this analysis indicate a positive association between the circulating BCAA concentrations and the risk of ED, but their underlying mechanisms require further investigation.

IntroductionFatty acid synthase (FASN) is a key regulator of lipid metabolism, but its role in colorectal cancer (CRC) stemness and ferroptosis remains unclear.MethodsFASN expression in CRC was analyzed using TCGA data and validated in CRC cell lines (CACO-2, HCT116, SW480) and normal HIEC-6 cells via qRT-PCR and Western blot. HCT116 cells (highest FASN expression) were used for experiments. FASN silencing (shRNA) effects on CSCs were assessed via 3D spheroid formation and CD133+CD44+ flow cytometry. In vivo tumor growth was tested in BALB/c nude mice. Mechanistic assays included cholesterol detection, SREBP2 Western blot, fatostatin rescue experiments, ferroptosis markers (ferrous ions, ROS, MDA, 4-HNE, mitochondrial function), and FASN-SREBP2 co-immunoprecipitation.ResultsFASN was overexpressed in CRC tissues (TCGA) and cell lines, with highest levels in HCT116. It was upregulated in 3D spheroids and CD133+CD44+ CSCs. FASN silencing reduced spheroid formation, in vivo tumor growth, and CD133+CD44+ cells. Mechanistically, FASN knockdown decreased cholesterol, activated SREBP2, and induced ferroptosis (elevated ferrous ions, ROS, lipid peroxidation, mitochondrial dysfunction); these effects were reversed by fatostatin. Co-IP confirmed FASN-SREBP2 interaction.DiscussionFASN promotes CRC progression by enhancing CSC stemness and suppressing ferroptosis through SREBP2 inhibition, highlighting its potential as a therapeutic target.

Ethnopharmacological relevance: Myristica fragrans (Nutmeg) is a commonly used Chinese herbal medicine and edible spice. According to Pharmacopoeia of People's Republic of China, it has the effects of warming the middle and promoting qi, astringent intestines, and antidiarrheal. In the record of Compendium of Materia Medica, it is the myristica fragrans water extract (MFWE) that is utilized for therapeutic purposes of gastrointestinal disorders frequently. Research purpose: This study is to investigate the pharmacodynamic material foundation and molecular mechanism of myristica fragrans on gastric ulcers using UHPLC-Q-Orbitrap-MS/MS with network pharmacology and experimental verification. This may provide theoretical guidance for the clinical use of myristica fragrans, and support a theoretical foundation for its future advancement into natural functional products that can relieve acute gastric ulcers. Materials and methods: Using UHPLC/MS technology and network pharmacology, we identified possible active chemicals molecules, screened out core targets and core pathways, and simulated drug target binding through molecular docking situations. Acute gastric ulcer was caused by intragastric administration of absolute ethanol (0.075 ml/10g). Myristica fragrans water extract (182 mg/kg and 364 mg/kg) was administered orally 14 days in advance. The same method was used to distribute 0.5% carboxymethyl cellulose solution into the Model and Control group. The mice were murdered on the 15th day. Following the sacrifice, the gastric tissue was removed for histological analysis. The tissue needs to detect levels of IL-1 beta, TNF-alpha, IL-10, and IL-6 as well as the activity of SOD, GSH-Px, MDA, and MPO. In addition, H&E staining and the TUNEL method were used to observe the effect on the gastric mucosa of mice. Western blot was used to detect apoptosis, ferroptosis, and antioxidation-related proteins.

Diabetic kidney disease (DKD) is highly prevalent worldwide, and its incidence continues to rise annually. Hyperglycemia, fatty acids, and other damage-related molecules are detected by specific pattern recognition receptors (PRRs), thereby triggering pyroptosis, leading to kidney damage and functional decline. However, the main pathways and underlying mechanisms remain unclear. Here, we confirm that the pyroptosis signal transduction pathway is intimately associated with the pathogenesis of DKD. Furthermore, CUEDC2, a protein involved in cell cycle, cellular stress response, inflammatory response, and tumorigenesis and regulation, was found to be downregulated in the kidneys of DKD mice and exhibited a negative correlation with glomerular endothelial cell (GEC) injury and pyroptosis. In the GEC pyroptosis model, inhibition of CUEDC2 expression facilitated the activation of the NLRP3 inflammasome, exacerbating pyroptosis. Conversely, CUEDC2 overexpression inhibited NLRP3 inflammasome activation, thereby improving pyroptosis. CUEDC2 exerted a protective effect by attenuating lipo polysaccharide-induced NLRP3 inflammasome activation and pyroptosis. Mechanistically, CUEDC2 interacted with NLRP3 during inflammasome activation, thereby inhibiting IL-1β maturation and caspase-1 activation. This study provides a new mechanism underlying the progression of DKD and identifies CUEDC2 as a potential therapeutic target.

During diabetic kidney disease (DKD), tubulointerstitial fibrosis persists, although several methods have been applied to reduce albuminuria levels. In this research, we found that bovine serum albumin (BSA)-induced renal tubular cell injury could also spread to normal tubular cells through exosomes, which may explain why tubulointerstitial fibrosis persists. Our previous studies revealed that SESN2 overexpression alleviates tubular dysfunction. In this study, we showed that SESN2 overexpression in donor HK2 cells interrupted this "doom loop" and confirmed that SESN2 may mediate this process by reducing exosome secretion. By using RNA-seq and IP-MS, we found that SESN2 could inhibit BSA-induced Rab-7a ubiquitination, thus promoting autophagosome and lysosome fusion and accelerating MVB degradation. We also showed that SESN2 promotes the nuclear translocation of TFEB through the mTOR pathway, thus further alleviating lysosomal function and promoting MVB degradation. We also found that SESN2 not only slowed DKD progression but also promoted renal tubular cell secretion of protective exosomes, which also slowed DKD progression. In conclusion, SESN2 can interrupt the progression of albuminuria-induced tubular injury by inhibiting exosome secretion and promoting MVB degradation. Thus, SESN2 may be a new therapeutic target for DKD treatment.

BackgroundGlioma is one of the most common tumors, characterized by a high incidence rate and mortality, posing a formidable global health challenge. Palmitoylation represents a significant post-translational modification that holds a pivotal role in the progression of glioma. However, the biological mechanisms underlying palmitoylation-related genes (PRGs) in glioma remain elusive to date.MethodsThis study utilized an unsupervised clustering algorithm based on the TCGA-GBMLGG cohort to identify palmitoylation-related molecular subtypes and comparatively analyzed the differences between the two subtypes in terms of clinicopathological characteristics, tumor microenvironment (TME), response to immunotherapy, and somatic mutations. Subsequently, through LASSO Cox regression analysis, a palmitoylation-related risk score (PRRS) model for predicting the prognosis of glioma patients was developed and validated. Additionally, the differences in chemotherapeutic drug sensitivity and response to immunotherapy among different PRRS groups were evaluated. Ultimately, potential drugs targeting palmitoylation-related proteins for the treatment of glioma were explored through molecular docking studies, molecular dynamics simulations, and in vitro drug experiments.ResultsThis study found that compared with glioma patients in Cluster 2, those in Cluster 1 had a higher World Health Organization (WHO) grade and a worse prognosis. Additionally, the infiltration levels of M2-type macrophages and regulatory T cells were higher in Cluster 1 than in Cluster 2. Immune checkpoint genes, major histocompatibility complex (MHC), and T-cell stimulators were also upregulated in Cluster 1. The PRRS model shows promising prospects in predicting the prognosis of glioma patients, and patients with lower PRRS values are more likely to benefit from immunotherapy. Molecular docking, molecular dynamics simulations, and in vitro drug experiments have confirmed that AT-7519, BIX02189, and THZ-2-101-1 can inhibit glioma cell migration while promoting cell apoptosis.ConclusionsA significant correlation exists between palmitoylation and tumor microenvironment in glioma. The PRRS emerges as a dependable prognostic biomarker, offering therapeutic advantages in the context of chemotherapy and immunotherapy, and potentially aiding in clinical decision-making for glioma patients. The identified compounds, AT-7519, BIX02189, and THZ-2-101-1, may potentially exert inhibitory effects on the malignant progression of glioma by targeting palmitoylation-related proteins.

BACKGROUND:Apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) plays a crucial role in DNA base excision repair, cell apoptosis, cell signaling, and the regulation of transcription factors through redox modulation and the control of reactive oxygen species (ROS). However, the connection between APE1 and acute liver injury (ALI) remains enigmatic. This study aims to unravel the molecular mechanisms underlying ALI and shed light on the role of APE1 in this context.METHOD:We induced acute liver injury (ALI) in mice by lipopolysaccharide/D-galactosamine (LPS/GalN) and intervened with the APE1 inhibitor E3330. We examined the expression of APE1 in ALI mice and ALI patient tissues after E3330 intervention, Additionally, we measured hepatic oxidative stress, ferroptosis, and autophagy marker proteins and genes. In establishing an AML-12 liver cell injury model, we utilized the Nrf2 activator tert-butylhydroquinone (TBHQ) as an intervention and examined APE1, Nrf2, ferroptosis-related proteins, and autophagy marker proteins and mRNA.RESULTS:Both ALI patients and ALI mice exhibited reduced APE1 expression levels. After E3330 intervention, there was a significant exacerbation of liver injury, oxidative stress, and a reduction in the expression of proteins, including GPX4, X-CT, ATG3, ATG5, and LC3 (LC3I/II). Consistent results were also observed in AML-12 cells. With TBHQ intervention, Nrf2 expression increased, along with the expression of proteins associated with iron death and autophagy. Mechanistically, APE1 activation regulates Nrf2 to inhibit ferroptosis and promote autophagy in hepatocytes.CONCLUSION:The data suggest that APE1 is a pivotal player in ALI, closely linked to its regulation of Nrf2. Strategies involving APE1 activation to modulate Nrf2, thereby inhibiting hepatocyte ferroptosis and promoting autophagy, may represent innovative therapeutic approaches for ALI. Additionally, tert-butylhydroquinone (TBHQ) holds significant promise in the treatment of acute liver injury.

The incidence rate and mortality rate of cardiovascular disease rank first in the world. It is associated with various high-risk factors, and there is no single cause. Epigenetic modifications, such as DNA methylation or histone modification, actively participate in the initiation and development of cardiovascular diseases. Histone lysine methylation is a type of histone post-translational modification. The human Jumonji C domain (JMJD) protein family consists of more than 30 members. JMJD proteins participate in many key nuclear processes and play a key role in the specific regulation of gene expression, DNA damage and repair, and DNA replication. Importantly, increasing evidence shows that JMJD proteins are abnormally expressed in cardiovascular diseases, which may be a potential mechanism for the occurrence and development of these diseases. Here, we discuss the key roles of JMJD proteins in various common cardiovascular diseases. This includes histone lysine demethylase, which has been studied in depth, and less-studied JMJD members. Furthermore, we focus on the epigenetic changes induced by each JMJD member, summarize recent research progress, and evaluate their relationship with cardiovascular diseases and therapeutic potential.

Ethnopharmacological relevance: Exocarpium Citri grandis (ECG, Huajuhong in Chinese), the epicarp of C. grandis 'Tomentosa', has been used for hundreds of years as an anti-inflammatory, expectorant, hypoglycemic, and lipidlowering medication in China. Nevertheless, there have been few papers that have explored the mechanism behind ECG's hypolipidemic characteristics from the perspective of treating nonalcoholic fatty liver disease (NAFLD). Aim of study: The purpose of our study was to confirm the therapeutic and preventative effects of ECG in NAFLD by regulating lipid accumulation and iron metabolism, and to explore the specific mechanism of ECG in enhancing hepatic iron transport and excretion capabilities. Study design: We constructed a NAFLD model by feeding male C57BL/6 J mice with a high-fat diet for 12 weeks. Mice were gavaged with ECG beginning in the seventh week of modeling, and three dosage gradients were established: low dose group (2.5 g/kg/d), medium dose group (5 g/kg/d) y, and high dose group (10 g/kg/d) until the end of model construction in week 12. Materials and methods: We used network pharmacology to analyze the relationship between ECG and NAFLD. In addition, we constructed a nonalcoholic fatty liver disease model by feeding male C57BL/6 J mice a high-fat diet for 12 weeks. Finally, lipid accumulation, iron accumulation, inflammation and oxidative stress were evaluated by serological index detection, histological detection, immunofluorescent and immunohistochemical staining, and western blotting. Results: Network pharmacology confirmed the treatment effect of ECG in NAFLD. Three active components of ECG, including Naringenin, Naringin and Neohesperidin, were detected by UHPLC-HRMS analysis. The results of serum TC, TG, LDL concentration, HE staining, Oil red staining and Nile red staining demonstrated that ECG could improve lipid metabolism disorders. The results of serum iron concentration, liver tissue iron

Background: Obesity is a complex condition that is affected by a variety of factors, including the environment, behavior, and genetics. However, the genetic mechanisms underlying obesity remains poorly elucidated. Therefore, our study aimed at identifying key genes for human obesity using bioinformatics analysis.Methods: The microarray datasets of adipose tissue in humans were downloaded from the Gene Expression Omnibus (GEO) database. After the selection of differentially expressed genes (DEGs), we used Lasso regression and Support Vector Machine (SVM) algorithm to further identify the feature genes. Moreover, immune cell infiltration analysis, gene set variation analysis (GSVA), GeneCards database and transcriptional regulation analysis were conducted to study the potential mechanisms by which the feature genes may impact obesity. We utilized receiver operating characteristic (ROC) curve to analysis the diagnostic efficacy of feature genes. Finally, we verified the feature genes in cell experiments and animal experiments. The statistical analyses in validation experiments were conducted using SPSS version 28.0, and the graph were generated using GraphPad Prism 9.0 software. The bioinformatics analyses were conducted using R language (version 4.2.2), with a significance threshold of p < 0.05 used.Results: 199 DEGs were selected using Limma package, and subsequently, 5 feature genes (EGR2, NPY1R, GREM1, BMP3 and COL8A1) were selected through Lasso regression and SVM algorithm. Through various bioinformatics analyses, we found some signaling pathways by which feature genes influence obesity and also revealed the crucial role of these genes in the immune microenvironment, as well as their strong correlations with obesity-related genes. Additionally, ROC curve showed that all the feature genes had good predictive and diagnostic efficiency in obesity. Finally, after validation through in vitro experiments, EGR2, NPY1R and GREM1 were identified as the key genes.Conclusions: This study identified EGR2, GREM1 and NPY1R as the potential key genes and potential diagnostic biomarkers for obesity in humans. Moreover, EGR2 was discovered as a key gene for obesity in human adipose tissue for the first time, which may provide novel targets for diagnosing and treating obesity.

There is a lack of research regarding the relationship between creatinine to cystatin C to waist circumference ratio (CCR/WC ratios) and the development of type 2 diabetes mellitus (T2DM). We aimed to evaluate the association between CCR/WC ratios and incident T2DM in Chinese adults.