Endocrine, metabolic & immune disorders drug targets最新文献

{"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}

{"title":"Screening Co-Diagnostic Genes for Lung Adenocarcinoma and Myocardial Infarction and Analysis of the Molecular Functions and Drug Value of the Genes.","authors":"Nannan Du, Mengting Liang, Zongjun Liu","doi":"10.2174/0118715303374928250130113050","DOIUrl":"https://doi.org/10.2174/0118715303374928250130113050","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer, and myocardial infarction (MI) is an acute cardiovascular disease resulting from the disruption of coronary blood supply. Recent studies have suggested that these two diseases may share common molecular mechanisms.</p><p><strong>Aim: </strong>The aim of this study was to discover common diagnostic genes for LUAD and MI and analyze their molecular functions and potential drug values by applying bioinformatics analysis.</p><p><strong>Objective: </strong>The objective was to provide a theoretical basis for further research on the pathological mechanisms of LUAD and MI, contributing to the development of novel diagnostic and therapeutic strategies for the two diseases.</p><p><strong>Methods: </strong>In this study, the datasets of LUAD and MI were obtained from TCGA and GEO databases, and differential expression analysis was performed to screen significantly differentially expressed genes (DEGs). Subsequently, disease-related genes were identified using WGCNA analysis, and the biological functions of these genes were explored by functional enrichment analysis. After screening key genes using the protein-protein interaction (PPI) network and the cytoHubba algorithm, biomarkers were determined by LASSO and SVM-RFE machine-learning methods. Finally, immune infiltration analysis and drug prediction were performed, and biomarker expression was verified by single-cell sequencing analysis.</p><p><strong>Results: </strong>A total of 158 differentially upregulated genes were identified between LUAD and MI. WGCNA analysis screened 86 genes that were significantly associated with both diseases and were enriched in an inflammatory response and immune regulation-related pathways, such as the IL-17 signaling pathway. Ten significant genes were identified by the PPI network and cytoHubba and then reduced to 4 using LASSO and SVM-RFE. Noticeably, MMP9 was significantly overexpressed in both diseases. Immune infiltration analysis showed that MMP9 was significantly related to multiple immune cell infiltration. Drug prediction and molecular docking analysis predicted Ilomastat and Osthole as the potential target drugs. Single-cell sequencing analysis revealed that MMP9 was high-expressed in the macrophages in LUAD tissues.</p><p><strong>Conclusion: </strong>This study identified MMP9 as a common diagnostic gene and potential therapeutic target for both LUAD and MI and revealed its role in inflammation and immune regulation through comprehensive bioinformatics analysis. These findings provided a theoretical basis for further research on the pathological mechanisms of LUAD and MI, contributing to the development of novel diagnostic and therapeutic strategies.</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":"143416352","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":"Sars-Cov-2 Infection as Catecholamin Crisis in Pheocreomocitoma: A Case Report.","authors":"Roberto Novizio, Andrea Corsello, Gaetano Emanuele Rizzo, Alfredo Pontecorvi, Pietro Locantore","doi":"10.2174/0118715303348376250103113426","DOIUrl":"https://doi.org/10.2174/0118715303348376250103113426","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The primary presentation of SARS-CoV-2 infection is viral pneumonia, which may be complicated by acute respiratory distress syndrome, although several other manifestations can occur.. Endocrine implications have been described. Pheochromocytomas are rare tumors mainly originating in the adrenal medulla. Symptoms are primarily due to catecholamine overproduction and abrupt release. Catecholamine release is unregulated and could be continuous or paroxysmal. Some conditions (i.e., stress, physical exercise, or specific foods) can trigger catecholamine release. Sars-CoV-2 infections have not been previously described as precipitators of adrenergic crises in pheochromocytoma patients. In this study, we report a case of adrenal crisis of a patient affected by pheochromocytoma in the context of Sars-CoV-2 infection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Case report: &lt;/strong&gt;A 63-year-old Caucasian male known for right adrenal pheochromocytoma waiting for surgical removal was admitted to the Emergency Department (ED) in March 2021 for a fainting episode and hypertensive crisis that he never experienced before. The patient had a known medical history of type 2 mellitus diabetes and hypercholesterolemia treated by slow-release metformin 500 mg/day and atorvastatin 40 mg/day and was not vaccinated for Sars-CoV-2. Two months before, the patient was hospitalized in another hospital for myocardial infarction with non-obstructive coronary arteries, and a chest-abdomen TC scan showed a right adrenal lodge occupied by coarse formation. In the 24-h urine sample, metanephrines were &gt;5000 μg/24h and Normetanephrines &gt;2500 μg/24h. Scintigraphy with 123I-Metaiodobenzylguanidine (MIBG) showed accumulation in right adrenal gland formation, confirming the suspicion of pheochromocytoma. No further areas of pathological uptake were present. Fort that, the patient was started on alpha-blockers (doxazosin 2 mg twice/day). Two weeks later, the patient was also prescribed metoprolol 50 mg twice/day. When admitted to the Emergency Department (ED), Blood Pressure (BP) was 210/108 mmHg with a heart rate of 105 bpm. A routine nasopharyngeal swab for Sars-CoV-2 was performed, resulting positive. After an extra dosage of 2 mg of doxazosin and 20 mg of nifedipine, symptoms addressed to catecholamine release disappeared. Being positive for Sars-CoV-19, the patient was transferred to the infectious diseases department. High mean BP was demonstrated at the control profile. Doxazosin was increased to 4 mg twice a day with a good effect on BP and tachycardia. After 10 days, the SARS-CoV-2 swab result was negative, and the patient was discharged with normal vital parameters and instructions to continue the increased dose of doxazosin. No other crisis was reported until surgery, which was performed without any complications after 1 month.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Since the adrenal crisis is a life-threatening condition, we suggest close BP monitoring and therapeutic adher","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416350","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":"Advances in Sources, Content Determination, and Bioactivity of 20α-Hydroxyprogesterone.","authors":"Liangyun Li, Shujing Yan, Yuexuan Cheng, Chunhong Zhong, Chunli Chen, Xiaoli Gao","doi":"10.2174/0118715303302957250117052100","DOIUrl":"https://doi.org/10.2174/0118715303302957250117052100","url":null,"abstract":"<p><p>20α-hydroxyprogesterone [(20S)-20-hydroxypregn-4-en-3-one, 20α-DHP] is one of the endogenous metabolites of progesterone (Pregn-4-ene-3,20-dione, P4) and a steroid hormone. The literature related to 20α-DHP mainly concentrates on the years from the 1950s to 1970s, and a review of 20α-DHP has not been conducted. In this work, the endogenous and exogenous sources of 20α-DHP are introduced, and methods for determining 20α-DHP in biological samples are described. The biological activities of 20α-DHP are summarized in detail, including the maintenance of pregnancy, endometrial protection, regulation of hormone secretion, ovulation promotion, uterine epithelial cell proliferation, antagonism of breast cancer, and as a diagnostic indicator for psoriasis and polycystic ovarian syndrome. Finally, the pharmacokinetic characteristics of 20α- DHP are briefly introduced to provide a reference for the further development and utilization of 20α-DHP.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416408","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":"ICPi-Induced Graves' Disease with Pre-existing Autoimmune Thyroid Disorders: A Case Report and Literature Review.","authors":"Xinpan Wang, Doudou Chen, Yun Shi, Tao Yang, Xuqin Zheng","doi":"10.2174/0118715303317264250116095028","DOIUrl":"https://doi.org/10.2174/0118715303317264250116095028","url":null,"abstract":"<p><strong>Background: </strong>Immune Checkpoint Inhibitor (ICPi) therapy has revolutionized cancer treatment but can lead to immune-related adverse events (irAE), including thyroid dysfunction. The impact of ICPi on patients with pre-existing autoimmune thyroid diseases (PATD), particularly the development of Graves' disease, remains poorly understood.</p><p><strong>Case description: </strong>We provide the first complete case of Graves' disease with ICPi therapy in a patient who already had Hashimoto's thyroiditis.. The patient, a 52-year-old male, was diagnosed with lung adenocarcinoma and received Atezolizumab. Clinical evaluation revealed hyperthyroidism, confirmed by elevated thyroid hormones and autoantibodies (TRAb and TSAb). The patient was managed with methimazole and demonstrated a transient hyperthyroid phase followed by persistent hypothyroidism. Only 16 confirmed cases of Graves' disease induced by ICPi were reported. We conducted a review to investigate the clinical characteristics, risk factors, and prognosis trends associated with ICPi-induced Graves disease in PTAD patients. Additionally, changes in thyroid function and autoantibodies during and after ICPi treatment are examined.</p><p><strong>Conclusion: </strong>This case underscores the importance of monitoring thyroid function and autoantibodies in patients with PATD undergoing ICPi therapy. The findings suggest distinct differences in the humoral immune response between ICPi-induced and spontaneous Graves' disease, necessitating further research into autoantibody dynamics and their relationship with cellular immunity in these patients.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416338","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":"Relative Fat Mass Associated with Hyperuricemia in Adults: A Cross-Sectional Study.","authors":"Tian Gu, Zhaoxiang Wang, Qichao Yang, Mengjiao Xu, Xuejing Shao, Bingshuang Xue","doi":"10.2174/0118715303344427241218114648","DOIUrl":"https://doi.org/10.2174/0118715303344427241218114648","url":null,"abstract":"<p><strong>Aims: </strong>There is a close relationship between obesity and hyperuricemia. Relative Fat Mass (RFM) is considered a new indicator for evaluating obesity. We aim to explore the relationship between RFM and the risk of hyperuricemia in adults.</p><p><strong>Methods: </strong>This cross-sectional study included adult participants from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). The RFM was calculated as: RFM =64 - (20 × height/waist circumference) + (12 × sex), where sex is defined as 0 for men and 1 for women. Hyperuricemia was confirmed by using serum uric acid (SUA) levels ≥ 7 mg/dL in men and ≥ 6 mg/dL in women. The relationship between RFM and the risk of hyperuricemia was thoroughly investigated.</p><p><strong>Results: </strong>A total of 29369 participants were enrolled in this study. The RFM levels in the hyperuricemia group were higher than those in the non-hyperuricemia group (P < 0.01). Logistic and linear regression indicated that RFM levels were positively associated with the risk of hyperuricemia (OR=1.08, 95% CI: 1.05-1.11, P < 0.001) and SUA levels (β=0.04, 95% CI: 0.03-0.05, P < 0.001). The relationship remained consistent across subgroups. Smooth curve fitting showed a nonlinear relationship, with an inflection point at 34.22. Above this threshold, the link between RFM levels and hyperuricemia was found to be more remarkable.</p><p><strong>Conclusion: </strong>Higher RFM is associated with an increased risk of hyperuricemia. RFM could act as a cost-efficient and straightforward measure for hyperuricemia risk assessment.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401126","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 Role of the Toll-Like Receptor Signaling Pathway in Autoimmune Diseases and Treatment with Traditional Chinese Medicine: A Literature Review.","authors":"Yaru Wang, Lin Bao, Mingying Liu, Xintian Tang, Hui Liu, Xiaodong Liang, Yifan Liu","doi":"10.2174/0118715303340093241227094242","DOIUrl":"https://doi.org/10.2174/0118715303340093241227094242","url":null,"abstract":"<p><p>Toll-Like Receptors (TLRs) is a pattern recognition receptor that connects innate and adaptive immunity and participates in inflammatory responses play a key role in common autoimmune diseases such as Rheumatoid Arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, and Sjögren's syndrome (SS) by participating in antigen recognition, immune cell activation, and inflammatory factor release. Due to the multi-component and multi-target characteristics of traditional Chinese medicine (TCM), the role of TCM active ingredients acting on TLRs has been widely studied. This article describes the relationship between TLR and four autoimmune diseases, as well as a review of the efficacy of TLR intervention by active ingredients of traditional Chinese medicine. To provide some basis for the future clarification of the mechanism of action of drugs for autoimmune diseases and to assist in the development of new medicines.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026187","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":"Treatment of Primary Hypothyroidism by Slow-Release Liothyronine Monotherapy.","authors":"Fereidoun Azizi, Atieh Amouzegar, Hengameh Abdi, Safdar Masoumi, Ladan Mehran","doi":"10.2174/0118715303321830241227112420","DOIUrl":"https://doi.org/10.2174/0118715303321830241227112420","url":null,"abstract":"<p><strong>Background: </strong>Combination therapy with levothyroxine (L-T4) and slow-release T3 (SRT3) in the treatment of hypothyroidism results in a normal triiodothyronine/thyroxine (T3/T4) ratio above that of L-T4 monotherapy. No clinical study has been reported with SRT3 monotherapy for hypothyroidism.</p><p><strong>Methods: </strong>This study was conducted in two parts. In part one, 20 patients with primary hypothyroidism and serum thyrotropin (TSH) >30 mU/L were randomized into 3 groups receiving 1.6 μg/kg L-T4, equivalent doses of SRT3 or L-T3 of 0.55 μg/kg for 4 weeks and fasting serum free T4 (fT4), T3 and TSH were measured weekly, before taking medication, up to 4 weeks. In part two, in 9 hypothyroid patients on L-T4 therapy and normal serum TSH, L-T4 therapy was discontinued and a once daily dose of SRT3 0.55 μg/kg was replaced. Serum fT4, T3 and TSH were measured weekly.</p><p><strong>Results: </strong>Part One; in patients treated with L-T3 and L-T4 serum TSH decreased to normal values after 4 weeks of intervention. In 7 patients on SRT3, serum T3 increased from 47±12 at baseline to 110±16 ng/dL and serum TSH decreased from 60±11 at baseline to 24±10 and 26±7 mU/L, respectively, at 14 and 21 days after intervention. At the end of 28 days, mean serum T3 was 110±16, 168±74 and 96±18 ng/dL in SRT3, L-T3 and L-T4 groups, respectively, p<0.001. Part Two: serum fT4 decreased from 1.43±0.7 to 0.41±0.14 ng/dLand serum T3 increased from 86±21 to 113±27 ng/dL by 21 days. Mean serum TSH remained in the normal range until 14 days but increased to 15.1±7.6 mU/L at 21 days. At the end, mean serum fT4, T3 and TSH were 0.35±0.17 ng/dl, 77.4±8.9 ng/dL and 35±11 mU/L.</p><p><strong>Conclusion: </strong>In patients with primary hypothyroidism SRT3 monotherapy with an equivalent dose to L-T4 maintains normal serum T3, but is unable to sustain normal serum TSH concentration.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026189","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":"Metabolomic Analysis of the Effects of Canagliflozin on HFpEF Rats and Its Underlying Mechanism.","authors":"Guorui Zhang, Qingjuan Zuo, Sai Ma, Lili He, Zhongli Wang, Jianlong Zhai, Tingting Zhang, Yan Wang, Yifang Guo","doi":"10.2174/0118715303373321250108174111","DOIUrl":"https://doi.org/10.2174/0118715303373321250108174111","url":null,"abstract":"<p><strong>Background: </strong>Heart failure with preserved ejection fraction (HFpEF) represents a challenging cardiovascular condition characterized by normal systolic function but impaired diastolic performance. Despite its increasing prevalence, therapeutic options remain limited. This study investigated the metabolic effects of canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on cardiac function and energy metabolism in HFpEF.</p><p><strong>Methods: </strong>We established a rat model of HFpEF using Dahl salt-sensitive rats and evaluated three experimental groups: control (A), HFpEF (B), and canagliflozin-treated HFpEF (C). This study carried out comprehensive analyses of cardiac structure and function, metabolomic profiling, and detailed assessment of myocardial energy metabolism, including mitochondrial respiratory capacity and ATP synthesis. Additionally, we validated our findings using H9C2 cardiomyocytes under controlled conditions.</p><p><strong>Results: </strong>Canagliflozin treatment significantly improved cardiac remodeling markers, including reduced myocardial volume and fibrosis area, while enhancing diastolic function (E/A ratio). Metabolomic analysis revealed normalization of hypermetabolic states, with significant reductions in key metabolites, including L-lysine, D-glucose, and uridine. The treatment restored balance in multiple metabolic pathways, particularly affecting β-alanine metabolism, pyrimidine metabolism, and the citrate cycle. Notably, canagliflozin enhanced mitochondrial respiratory function, increased ATP synthesis, and optimized fatty acid utilization, as evidenced by reduced free fatty acid content.</p><p><strong>Conclusion: </strong>Our findings demonstrated that canagliflozin exerts cardioprotective effects through multiple metabolic pathways, suggesting its potential as a therapeutic option for HFpEF. The ability of the drug to optimize energy metabolism and improve mitochondrial function represents a novel mechanism for treating this challenging condition.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019450","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":"Protective Effects of Monoacylglycerol Lipase Inhibition in Rats with Severe Acute Pancreatitis and Its Possible Mechanism.","authors":"Tong Su, Hongwei Xu, Ruixia Wang, Tong Xiao, Jing Wang, Shulei Zhao","doi":"10.2174/0118715303335207241225091132","DOIUrl":"https://doi.org/10.2174/0118715303335207241225091132","url":null,"abstract":"<p><strong>Background and aim: </strong>In the context of gastrointestinal diseases, the role of monoacylglycerol lipase (MAGL) is significant. Therefore, the objective of this study was to examine the protective effects of MAGL inhibition using JZL184 in rat models of severe acute pancreatitis (SAP) and to explore its mechanism.</p><p><strong>Methods: </strong>In this study, a rat model of SAP was established, and the rats were divided into three groups for treatment: the Control group (CON), the SAP group (SAP), and the SAP group treated with JZL184 (JZL184). The serum levels of amylase (AMS), alanine aminotransferase (ALT), creatinine (Cr), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), and phosphodiesterase (PDE) were measured using enzyme-linked immunosorbent detection kits. The ascites volume was determined using the cotton ball weighing method. The levels of reactive oxygen species (ROS) were detected using the ROS Kit. Additionally, histological tissue changes were assessed through hematoxylin and eosin staining.</p><p><strong>Results: </strong>The SAP group showed increased levels of AMS, ALT, Cr, ROS, and ascites volume compared to the CON group. Additionally, the SAP group exhibited congested and edematous lung and pancreatic tissues with inflammation. However, the JZL184 group, when compared to the SAP group, showed decreased levels of AMS, ALT, Cr, and ROS, reduced ascites volume, and significantly reduced lung tissue and pancreatic histopathology scores. In the NO/cGMP/PDE system, compared with the CON group, the levels of NO and PDE in the SAP group were higher and the levels of cGMP were lower. Compared with the SAP group, the JZL184 group decreased NO and PDE levels and increased cGMP levels.</p><p><strong>Conclusions: </strong>Indeed, the inhibition of MAGL with JZL184 has been found to have a protective effect on rats with SAP. Specifically, it has shown significant improvement in the pathological damage of lung and pancreatic tissues. Furthermore, JZL184 has also exhibited protective effects on the liver and kidney. The mechanism may be related to the effect of JZL184 on the NO/cGMP/ PDE signaling pathway.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019454","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}