Endocrine, metabolic & immune disorders drug targets最新文献

{"title":"The Differential Diagnosis between Pseudo Cushing's Syndrome and True Cushing's Syndrome in a Septic Patient in the Pre-Agonal Phase: A Case Report.","authors":"Simone Antonio De Sanctis, Sabrina Chiloiro, Eloisa Sofia Tanzarella, Filippo Bongiovanni, Antonella Giampietro, Amato Infante, Gennaro De Pascale, Laura De Marinis, Massimo Antonelli, Alfredo Pontecorvi, Antonio Bianchi","doi":"10.2174/0118715303346706250206070813","DOIUrl":"https://doi.org/10.2174/0118715303346706250206070813","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis is an illness characterized by a high-stress condition for patients, accompanied by alterations in biochemical processes, behavior, and levels of consciousness. Hormonal alterations that can be seen in this context include increased plasma cortisol values, a condition known as pseudo-Cushing's syndrome (PCS), which in exceptional cases requires a differential diagnosis from true Cushing's syndrome (CS).</p><p><strong>Case presentation: </strong>We report a septic patient with pseudo-Cushing's syndrome in the pre-agonal phase, suggesting that PCS during sepsis is an underestimated condition, as the severity of the patient's clinical condition is compounded by the difficulty of diagnosis itself.</p><p><strong>Conclusion: </strong>In this clinical case, for the severe clinical conditions of the patient and the poor prognosis, we conducted a comprehensive endocrine work-up to rule out an ACTH-dependent hypercortisolism that, if confirmed, could have changed the therapeutic approach and the prognosis of the reported patient.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Bioinformatics Analysis Revealing that the NSDHL Gene Might Be Associated with the Progression of Western HFD/SW-Induced Hepatocellular Carcinoma.","authors":"Jing Hong, Bo Pan, Zhaoxian Yan, Xiao-Feng Zhai, Yongshang Liu","doi":"10.2174/0118715303356256250129063049","DOIUrl":"https://doi.org/10.2174/0118715303356256250129063049","url":null,"abstract":"<p><strong>Background and objective: </strong>Hepatocellular carcinoma (HCC) remains a significant global health concern. However, the etiology and pathogenesis of HCC have yet to be fully elucidated. Previous studies have indicated a close association between obesity and the occurrence and progression of HCC. The objective of this study was to employ bioinformatics strategies in order to explore key genes associated with the clinical diagnosis and prognosis of HCC induced by a Western high-fat diet and sugar water (HFD/SW).</p><p><strong>Materials and methods: </strong>We obtained the expression profile chip data GSE197884 from the Gene Expression Omnibus (GEO) database. Subsequently, \"DESeq\" and \"Limma\" R packages were employed to identify differentially expressed genes (DEGs) while constructing a co-expressed gene network using weighted gene co-expression analysis (WGCNA). Functional enrichment analyses were then carried out, followed by the construction of a protein-protein interaction (PPI) network to uncover core genes. The core genes were confirmed through data retrieved from The Cancer Genome Atlas (TCGA) database in order to determine their status as hub genes. Finally, survival and tumor immune infiltration analyses were performed to unveil the prognostic significance of these hub genes.</p><p><strong>Results: </strong>In total, 126 intersection targets were retrieved through the Venn diagram. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the DEGs were primarily related to the proliferation and apoptosis of HCC cells, the digestion and metabolism of liver cells, the HCC tumor microenvironment, and immune response. The PPI network analysis identified 11 core targets, among which seven hub genes, including NSDHL, MVK, SQLW, GCAT, ALAS2, GLDC, and AGXT, were obtained after TCGA database validation. Furthermore, it was found that NSDHL was closely associated with the clinical diagnosis and prognosis of HCC induced by HFD/SW and also affected the cellular immune infiltration in the HCC tumor microenvironment.</p><p><strong>Conclusion: </strong>The present study demonstrated a significantly elevated expression of NSDHL in HCC tissues, suggesting its potential as a specific biomarker for precise clinical diagnosis and prognosis assessment of HCC induced by HFD/SW.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparative Analysis of COVID-19-Associated and Non-COVID-19-Associated Mucormycosis.","authors":"Süheyla Kömür, Aslıhan Candevira, Ayşe Seza İnala, Ferit Kuşcua, Behice Kurtarana, Funda Memişoğlub, İlkay Karaoğlanc, Yeşim Taşovaa","doi":"10.2174/0118715303335275250116055824","DOIUrl":"https://doi.org/10.2174/0118715303335275250116055824","url":null,"abstract":"<p><strong>Background: </strong>COVID-19-associated Mucormycosis (CAM) has emerged as a significant complication during the COVID-19 pandemic. However, there is a lack of comprehensive comparative studies with non-COVID-associated mucormycosis (NCM).</p><p><strong>Objective: </strong>This study aims to compare the clinical characteristics, risk factors, and outcomes of CAM and NCM to enhance the understanding and management of these infections, particularly during the COVID-19 pandemic.</p><p><strong>Method: </strong>A retrospective multicenter study was conducted at Cukurova University, Malatya İnönü University, and Gaziantep University. We analyzed and compared cases of CAM and NCM diagnosed between January 2018 and February 2022. Data were collected from the infectious diseases and clinical microbiology departments, including demographic details, underlying conditions, treatment regimens, and outcomes.</p><p><strong>Results: </strong>A total of 38 cases were analyzed, with 21 cases of COVID-19-associated mucormycosis (CAM) and 17 cases of non-COVID-19-associated mucormycosis (NCM). The key findings of the study were as follows: CAM was strongly associated with corticosteroid use (p<0.001) and diabetes (p=0.001), while NCM cases were more frequently linked to malignancy and neutropenia (p<0.05). Clinically, CAM cases had a higher incidence of cavernous sinus involvement and bone destruction (p=0.003) compared to NCM cases. However, there was no significant difference in overall survival between the CAM and NCM groups (p=0.201).</p><p><strong>Conclusion: </strong>The study highlights the critical role of corticosteroid use and diabetes as prominent risk factors for CAM. Timely diagnosis and intervention are essential to prevent severe complications, such as cavernous sinus involvement and bone destruction. These findings emphasize the need for tailored management strategies for CAM in the context of COVID-19, with particular attention to these risk factors.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1-Deoxynojirimycin Ameliorates Diabetic Liver Injury by Regulating AMPK/SIRT1 and Oxidative Stress in db/db Mice.","authors":"Yao Li, Yu Cao, Yun-Yuan Tian, Wen-Wen Chen, Juan Wang, Meng-Meng Zhang, Si-Wang Wang, Yan-Hua Xie","doi":"10.2174/0118715303327499250104221937","DOIUrl":"https://doi.org/10.2174/0118715303327499250104221937","url":null,"abstract":"<p><strong>Background: </strong>Patients with diabetic liver injury are in the dilemma of lowering glucose and protecting liver function. This study aimed to uncover the protective effect and mechanism of 1-deoxynojirimycin (1-DNJ), an alpha-glucosidase inhibitor, against diabetic liver injury.</p><p><strong>Methods: </strong>The db/db mice were gavaged with 25 mg/kg, 50 mg/kg, and 100 mg/kg of 1-DNJ for 8 weeks. At the end of the administration, the serum and liver were isolated for further detection. The biochemical indices including TC, TG, LDL-C, AST, ALT, and TBiL were detected in serum. The livers were further analyzed with H&E, oil red, and Masson staining, and the amount of ROS in the liver was detected with probe dihydroethidium. Western blot was used to analyze the levels of proteins involved in fibrosis, oxidative stress, and AMPK/SIRT1 signaling pathway in the liver.</p><p><strong>Results: </strong>1-DNJ administration reduced body weight, liver coefficient, and TC, TG, LDL-C, AST, ALT, and TBiL in db/db mice. H&E and oil red staining showed that 1-DNJ ameliorated hepatocellular ballooning degeneration and lipid deposition in the liver. Moreover, 1-DNJ reduced the hepatic collagen fiber deposition and the protein expression of α-SMA and Collagen I. Further assays revealed that 1-DNJ treatment reduced the ROS level, up-regulated the proteins expression of SOD2, HO-1, NQO-1, p-AMPK/AMPK, p-ACC/ACC, and SIRT1 proteins, and down-regulated the expression of SREBP-1 and SCD-1 proteins in the liver.</p><p><strong>Conclusion: </strong>1-DNJ improves liver function, lipid deposition, and fibrosis of diabetic liver injury in db/db mice by regulating the AMPK/SIRT1 pathway to improve glucose-lipid metabolism and oxidative stress.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Chrysin Nanocrystal on the Thyroid Gland of Rats Exposed to Chlorpyrifos.","authors":"Tahereh Farkhondeh, Fatemeh Ahrari, Shahnaz Rajabi, Effat Alemzadeh, Behzad Mesbahzadeh, Maryam Rezaei, Sara Ziafati Majidi, Saeed Samarghandian","doi":"10.2174/0118715303329277250120104421","DOIUrl":"https://doi.org/10.2174/0118715303329277250120104421","url":null,"abstract":"<p><strong>Background: </strong>Chlorpyrifos (CPF) is an organophosphate insecticide that is mostly used in agriculture for pest control.</p><p><strong>Aim: </strong>This investigation aimed to evaluate the possible protective role of chrysin nanocrystals on thyroid gland hormones and histology in male rats after exposure to a high dose of chlorpyrifos.</p><p><strong>Method: </strong>Rats were randomly divided into 6 groups (6 rats in each group): 1. healthy control group, 2. treated with chrysin nanocrystal (5 mg/kg), 3. treated with chrysin nanocrystal (10 mg/kg), 4. treated with chrysin nanocrystal (5 mg/kg) + chlorpyrifos, 5. treated with chrysin nanocrystal (10 mg/kg) + chlorpyrifos, and 6. treated with chlorpyrifos (30 mg/kg). After 15 days of intervention, rats were anesthetized, and blood samples were taken from the heart to measure thyroid hormones. Then, the thyroid gland was isolated and stored in 10% formalin for histopathological studies. Thyroid samples were also stored at -80 ° C for measuring oxidative stress parameters.</p><p><strong>Result: </strong>A significant reduction was observed in the serum concentrations of T3 and T4 in all treated groups compared with the control group (p < 0.01). In addition, hormone level examination revealed no statistically significant (p ˃ 0.05) changes in plasma TSH concentration in any of the groups. The treatment with CPF and chrysin nanocrystal did not affect the levels of oxidative biomarkers (MDA, GSH, and NO) in thyroid glands. Photomicrographs of a histological section of the thyroid gland showed vacuolar degenerated follicle epithelium and missing colloids in the histological section of the thyroid gland of all groups.</p><p><strong>Conclusion: </strong>Our findings demonstrated that the oral administration of chrysin nanocrystals could not inhibit the toxic effect of a high dose of CPF on the thyroid gland in the rats.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empagliflozin and Arterial Stiffness in Patients with Type 2 Diabetes: A Real-World Case-Control Study.","authors":"Francesco Tassone, Cinzia Ferreri, Arianna Rossi, Giorgio Borretta, Guido Pastorini, Fabio Anastasio, Mauro Feola","doi":"10.2174/0118715303372020250131060159","DOIUrl":"https://doi.org/10.2174/0118715303372020250131060159","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated beneficial cardiovascular and renal effects in patients with type 2 diabetes mellitus (T2DM).</p><p><strong>Objective: </strong>The objective of this case-control study was to evaluate the efficacy of empagliflozin in modifying the arterial stiffness in type 2 diabetic patients.</p><p><strong>Methods: </strong>Pulse wave velocity (PWV) and other parameters of arterial stiffness were assessed at baseline and after three months of empagliflozin treatment in 16 consecutive outpatients with type 2 diabetes mellitus (T2DM) exhibiting normal left ventricular function and no signs of heart failure. A control group of 16 T2DM outpatients not treated with SGLT2 inhibitors was used for comparison.</p><p><strong>Results: </strong>Duration of diabetes mellitus and sex distribution did not differ between groups. Patients in the empagliflozin group were younger compared to controls (64.1 ± 8.68 vs 74.45 ± 8.13, p < 0.05). At 3-month follow-up, empagliflozin treatment significantly reduced HbA1c (7.9 ± 0.78 vs 7.04 ± 1.09%, p < 0.008). Empagliflozin significantly improved PWV compared to controls (from 13.2 ± 2.0 m/sec to 12.3 ± 1.8 m/sec; P = 0.001; in the control group 12.8 ± 2.3m/s to 13.2 ± 2.4, p = ns, with age and HbA1c as covariates) as well as body weight that significantly reduced (86.75 ± 16.16 kg vs 81.71 ± 16.5 kg, p =0.001) and BMI (30.48 ± 5.4 versus 28.75 ± 5.66 kg/m2, p < 0.002) in comparison to controls. Estimated glomerular filtration rate (eGFR) remained unchanged whereas a significant improvement of urine Albumin to Creatinine ratio with empagliflozin emerged (17.8 ± 46.8 vs 12.2 ± 35.7 mg/mmol, p = 0.049).</p><p><strong>Conclusion: </strong>In this clinical study, mid-term treatment with empagliflozin in patients with type 2 diabetes mellitus (T2DM) resulted in a significant reduction in arterial stiffness. Additionally, the improvement in the urine albumin-to-creatinine ratio suggests a potential enhancement in endothelial function.</p>.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of the Prognosis and Treatment Responses Based on the Characteristics of Disulfidptosis-Related Genes in Patients with Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma.","authors":"Min Kang, Sha Jiang, Huihui Chen, Youhua Xu, Hui Mo","doi":"10.2174/0118715303374396250129111340","DOIUrl":"https://doi.org/10.2174/0118715303374396250129111340","url":null,"abstract":"<p><strong>Background: </strong>Disulfidptosis is a new type of regulatory cell death (RCD), but the pathophysiological functions and mechanisms of DRGs in CESC remain to be examined.</p><p><strong>Aims: </strong>This study explored the mutation status of disulfidptosis-related genes (DRGs) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC).</p><p><strong>Objective: </strong>After analyzing the mutation profiles of DRGs in CESC, this study established a prognostic model for CESC and also explored the differences in immune infiltration (accumulation of immune system cells in tissues or organs), related enriched pathways, and drug sensitivity between high-risk and low-risk CESC groups.</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) were accessed to source related data. The mutation profiles of DRGs in CESC were analyzed using Mutect2 software, and disulfidptosis scores were calculated by ssGSEA. WGCNA was performed to identify modular genes, which were further filtered and used to formulate a risk model by applying the survival and glmnet packages. Low- and high-risk groups of CESC patients were classified using the survminer package. GSEA was performed to conduct pathway analysis, and immune infiltration was assessed using the MCPcounter package, ESTIMATE, and TIMER algorithms. Finally, immunotherapy response and drug sensitivity were analyzed using the TIDE method and the pRRophetic package, respectively.</p><p><strong>Results: </strong>Except for NDUFA11, ARL6IP5, EPM2AIP1, GBE1, RBM38, ULK4, and ZBTB47 were found to be the DRGs significantly mutated in CESC. The six genes were integrated to develop a RiskScore model with a relatively high Area Under the Curve (AUC) value. Significant differences between the two risk groups were determined, indicating that the model was highly reliable. Notably, the low-risk group was enriched in energy metabolism-correlated pathways, while the high-risk group was primarily enriched in immune-correlated pathways. The high-risk group showed higher immune cell activity, higher TIDE score, and more B cells than the low-risk group. Drug sensitivity study revealed that the high-risk group was more sensitive to chemotherapy drugs.</p><p><strong>Conclusion: </strong>This study provides novel insights into CESC prognosis, immunotherapy, and drug development, contributing to the clinical treatment for CESC.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal Elevation of the Expression of Costimulatory Molecule CD226 in Graves' Disease: Two Cross-Sectional Studies.","authors":"Zhaowei Huang, Xuerong Liu, Tiantian Cai, Yanfei Jiang, Yuqing Wu, Xinwei Zhang, Rong-Hua Song, Jin An Zhang","doi":"10.2174/0118715303337480250107052116","DOIUrl":"https://doi.org/10.2174/0118715303337480250107052116","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore the differential expression of the co-stimulatory molecule CD226 in lymphocytes from patients with New-Onset Graves' Disease (NOGD) and its correlation with clinical indicators.</p><p><strong>Methods: </strong>Sixty-eight participants were recruited for the discovery experiment (NOGD: healthy control (HC) = 39:29). Peripheral Blood Mononuclear Cells (PBMCs) were isolated. Flow cytometry was performed to detect CD226 expression on multiple lymphocyte subtypes. CD226 mRNA expression in PBMCs was detected by qPCR. Fifty-eight participants were recruited for the validation experiment (NOGD: HC=35:23). CD4+ T cells were isolated, and the level of CD226 mRNA in CD4+ T cells was detected. Five cases of each of Graves' disease (GD) thyroid and control thyroid were collected for CD226 immunohistochemical staining.</p><p><strong>Results: </strong>CD226 expression was the highest in monocytes (NOGD: 94.1% vs. HC: 94.8%) and the lowest in CD8+ T cells (NOGD: 65.3% vs. HC: 64.9%). Compared with HC, CD226 expression on the CD4+ T cells increased in the peripheral blood of NOGD patients and correlated with TPO-Ab. Meanwhile, CD226 mRNA levels were elevated in CD4+ T cells and positively correlated with TR-Ab. CD226 expression was significantly increased in the thyroid tissues of GD patients.</p><p><strong>Conclusion: </strong>This study demonstrates for the first time the elevated expression of CD226 in CD4+ T cells and thyroid tissue of NOGD. The abnormal elevation of CD226 is correlated with clinical indicators. It suggests that the co-stimulatory molecule CD226 is involved in the pathogenesis of GD.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Analysis of Metabolomic and Transcriptomic Data Reveals Metabolic Signatures and Major Metabolic Pathways in Primary Aldosteronism.","authors":"Xiaomei Lai, Tingting Yang, Chaoping Wei, Shuangbei Zhu, Jianling Li","doi":"10.2174/0118715303361250250119035029","DOIUrl":"https://doi.org/10.2174/0118715303361250250119035029","url":null,"abstract":"<p><strong>Objective: </strong>Primary aldosteronism (PA) is the most common secondary hypertension. In this study, we performed the pathway enrichment analysis based on metabolomics and transcriptomic data to find the metabolic perturbations in PA, which could provide new targets for PA and further understand the biology of PA.</p><p><strong>Methods: </strong>24 PA patients and 24 healthy adults served as the control group in this study. Six participants were chosen from each group to have their peripheral blood and serum samples analyzed for omics investigations. Another eighteen participants' peripheral blood samples were selected for further validation of the RNA-sequencing results.</p><p><strong>Results: </strong>Transcriptomic analyses found 518 differentially expressed genes (DEGs), and 339 remarkably differential metabolites (DMs) were identified by untargeted metabolomics. The pathway enrichment analysis was performed by combining with the omics analysis data. We also focused on analyzing metabolic pathways that repeatedly occur and constructed possible genemetabolic networks. A total of 5 genes and 11 metabolites showed significant changes in altered 3 lipid metabolic pathways. Furthermore, the expressions of these genes were verified by qRT-PCR.</p><p><strong>Conclusion: </strong>The combination of metabolomic and transcriptomic data can give a comprehensive picture of unique illness markers and preliminary knowledge of the molecular abnormalities underpinning PA. These findings may point to viable targets for creating treatments.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transporter Associated with Antigen Processing Proteins (TAP-1 and TAP-2) Gene Expression of MHC-I Downregulated in Oral Squamous Carcinoma.","authors":"Vijay Singh, Shailendra Dwivedi, Ruchika Agrawal, Mohan Raj Ps, Akash Bansal, Akash Agarwal, Sanjeev Misra","doi":"10.2174/0118715303344715241225184322","DOIUrl":"https://doi.org/10.2174/0118715303344715241225184322","url":null,"abstract":"<p><strong>Background: </strong>TAP-1 and TAP-2 are crucial proteins for loading antigenic peptides after proteasome-mediated endogenous processing of the MHC-I (Major Histocompatibility Complex- I) pathway. Our study aimed to explore the Transporter Associated with Antigen Processing proteins (TAP-1 and TAP-2) in oral squamous cell carcinoma and premalignant oral lesions.</p><p><strong>Methods: </strong>We recruited a total of 135 subjects from the outpatient department of the ENT unit of our institute. Real-time Polymerase Chain Reaction (PCR) was used to evaluate the levels of TAP-1 and TAP-2 gene expression in pre-cancerous and oral squamous carcinoma samples. Additionally, we measured the circulating levels of inflammatory markers using an automated biochemistry analyzer.</p><p><strong>Results: </strong>In the current study, we found that the subjects with oral squamous cell carcinoma had lower expressions of the TAP 1 and TAP 2 genes than precancerous oral subjects of OSMF, leukoplakia, and OLP. In oral squamous carcinoma subjects, we found a 1.7- and 2.1-fold change in gene expression of TAP-1 and TAP-2, respectively, compared to control subjects. Furthermore, we observed an increase in levels of metabolic inflammatory biomarkers of CRP, ESR, and ferritin in oral squamous carcinoma subjects compared to premalignant cases and controls, indicating the presence and aggravation of systemic inflammation.</p><p><strong>Conclusion: </strong>The study revealed that subjects with oral squamous cell carcinoma have lower TAP 1 and TAP 2 gene expression than premalignant control subjects, thus affecting MHC-I processing, which ultimately affects the functioning of the immune system. These results have the potential to improve our understanding of disease pathophysiology and provide more targeted treatment options.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}