Endocrine, metabolic & immune disorders drug targets最新文献

Introduction: The objective of this study was to evaluate the demographic, clinical, laboratory, and ultrasonographic characteristics of patients diagnosed with subclinical hypothyroidism, with a particular emphasis on the anti-thyroid peroxidase (anti-TPO) antibody and inflammatory biomarkers.

Methods: The study included 157 patients diagnosed with subclinical hypothyroidism, categorised into anti-TPO-positive and anti-TPO-negative groups. A retrospective comprehensive evaluation comprising demographic data, thyroid medication status, ultrasonographic characteristics, and laboratory parameters was conducted and statistically analysed between the groups.

Results: Of 157 patients, 48.4% were anti-TPO positive. This group was significantly associated with increased levothyroxine (LT4) use and sonographic parenchymal heterogeneity. However, there were no significant differences in nodule presence, number, size, or structure. A positive correlation was found between anti-TPO and ferritin levels. In addition, a positive correlation was observed between the thyroid-stimulating hormone (TSH)/free T4 ratio and the solidity of nodules, as well as between TSH and the neutrophil-to-lymphocyte ratio (NLR). Surprisingly, a negative correlation was found between anti-TPO levels and the number of nodules, as well as the cystic characterisation of the nodules.

Discussion: In our study, higher levels of anti-TPO and TSH were associated with inflammatory markers such as ferritin and NLR, suggesting a possible link with systemic inflammation. Furthermore, anti-TPO and the TSH/T4 ratio also showed associations with specific sonographic features of the thyroid gland.

Conclusion: TSH and anti-TPO levels might be associated with systemic inflammation and thyroid sonographic findings in patients with subclinical hypothyroidism. More studies on larger patient populations should confirm the same results to suggest their clinical significance.

Introduction: Severe acute pancreatitis (SAP) is characterized by systemic inflammation and gut microbiota dysbiosis. However, the interplay between microbial alterations, host metabolism, and gene expression remains unclear. This study aimed to investigate how monoacylglycerol lipase (MAGL) inhibition by JZL184 alleviates SAP by modulating the gut microbiota- metabolite-target gene network.

Methods: A rat model of SAP was developed, with rats assigned into three groups for comparison: the Control group (CON), the untreated SAP group (SAP), and the SAP group treated with JZL184 (JZL184). Fecal samples underwent 16S rRNA sequencing to assess microbial diversity and composition. Functional annotation was performed using KEGG pathways. Integrated analyses of intestinal microbiota, metabolomics, and pancreatic transcriptomics (GSE161945) were conducted to construct a microbiota-metabolite-target gene regulatory network, which was validated by qRT-PCR.

Results: SAP rats exhibited decreased Bacteroidetes, increased Proteobacteria, and enrichment of Escherichia-Shigella. JZL184 treatment restored microbial balance, reducing Escherichia-Shigella and enhancing Lactobacillus and Bacteroides. It also suppressed NOD-like receptor and MAPK signaling pathways. Network analysis revealed positive correlations between Escherichia-Shigella, arachidonic acid, and HMOX1 expression, and negative correlations between Lactobacillus, aspartic acid, and ACE expression. qRT-PCR confirmed normalization of ACE expression in JZL184- treated pancreatic tissues.

Discussion: JZL184 mitigated SAP by reshaping microbial composition, reducing pro-inflammatory taxa, restoring beneficial microbes, and altering key metabolites. These changes collectively modulated inflammatory pathways, including MAPK and NOD-like receptor signaling. The therapeutic benefit may also be mediated through the microbial control of metabolites that influence gene expression.

Conclusion: JZL184 effectively mitigates SAP by reshaping the gut microbiota-metabolite-gene network, suppressing pathogenic bacteria and inflammatory pathways while restoring beneficial microbes and metabolic homeostasis. These findings support MAGL inhibition as a promising microbiota- targeted therapeutic strategy for SAP.

Background: Patients with GAD65 antibody-associated autoimmune encephalitis who also have diabetes are usually considered to have type 1 diabetes mellitus (T1DM). However, previous reports often lacked β-cell function assessments, relying solely on anti-GAD65 positivity for diagnosis, which is insufficient for accurate classification.

Case presentation: We present a 30-year-old Chinese woman diagnosed with GAD65-associated autoimmune encephalitis, hyperthyroidism, and diabetes. Her peak C-peptide level was 3.99 ng/mL, inconsistent with the β-cell dysfunction typical of classic T1DM. The combination of high GAD65 antibody titers and preserved β-cell function made it challenging to determine her diabetes type.

Conclusion: This case suggests that clinicians should pay more attention to assessing and monitoring β-cell function when GAD65-associated autoimmune encephalitis is accompanied by diabetes.

Neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, ischemic stroke, and other related conditions, significantly impact the quality of life, particularly in low-income nations. The pathogenesis of these diseases is driven by neuroinflammation, oxidative stress, apoptosis, mitochondrial dysfunction, and regulation of autophagy. To date, no therapies or medications can fully reverse the progression of these diseases. Natural polysaccharides have demonstrated significant therapeutic potential in the treatment of neurodegenerative diseases. Lycium barbarum polysaccharide, derived from the traditional Chinese medicine Lycium barbarum L., has attracted considerable attentionfor its diverse biological activities, biodegradability, ease of modification, and low toxicity. This review aims to systematically evaluate the neuroprotective effects of Lycium barbarumpolysaccharides and their mechanisms in various neurodegenerative disease models. For this study, we used multiple scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar. We verified the correct plant name through the website plantlist.org. The search results were interpreted and documented based on the retrieved bibliographic information. Lycium barbarum polysaccharide has shown significant therapeutic potential for the treatment of neurodegenerative diseases. Experimental evidence reveals its neuroprotective effects through various mechanisms, including reducing neuroinflammation, alleviating oxidative stress, inhibiting apoptosis, improving mitochondrial function, and regulating autophagy. The current review established that Lycium barbarum polysaccharide holds promise as a therapeutic agent for neurodegenerative diseases. However, further research is required to address the limitations identified in previous studies and to guide future experimental investigations and clinical applications.

Introduction: Sarcopenia is a degenerative musculoskeletal disease affecting the elderly, significantly impairing patients' quality of life and challenging modern medicine. This study innovatively combines Traditional Chinese Medicine (TCM) theories with modern medical research to explore the mechanisms by which Gushukang granules address sarcopenia.

Methods: The research integrated multi-dimensional research methods, including network pharmacology, metabolomics, and animal experiments, to comprehensively investigate the scientific mechanisms of Gushukang granules' intervention in sarcopenia.

Results: Network pharmacology analysis identified multiple potential targets related to muscle growth and repair. UPLC-Q-TOF MS technology tracked metabolic pathways, while animal experiments verified that Gushukang granules precisely regulate muscle metabolic balance by modulating key signaling pathways involved in protein synthesis and degradation.

Discussion: The findings demonstrate the potential of integrating traditional and modern medical approaches in addressing age-related muscle degradation, providing scientific validation for TCM treatment of sarcopenia.

Conclusion: This study establishes a model for modernizing TCM research, offering solid scientific evidence for comprehensive intervention of chronic diseases in the elderly and highlighting the TCM concept of "preventing disease before its onset" in modern medical translation.

Introduction: Irritable Bowel Syndrome (IBS) and hypothyroidism are both common conditions that significantly affect patient health. This study examines the link between IBS and hypothyroidism, focusing on how IBS impacts hypothyroidism.

Methods: A retrospective cohort study using data from the UK Biobank (UKB) and a cross-sectional analysis from the National Inpatient Sample (NIS) were conducted. Propensity score matching was applied to control for confounding factors. Cox proportional hazards models (UKB) and logistic regression models (NIS) were used to evaluate the association between IBS and hypothyroidism. Subgroup analyses by age and sex were performed.

Results: The UKB cohort included 22,970 IBS patients (mean age 56.1 ± 7.94 years, 72.2% female) with a hypothyroidism prevalence of 4.1%, compared to 438,094 non-IBS participants (mean age 56.4 ± 8.12 years, 51.9% female) with a prevalence of 2.9%. In the NIS, 183,738 IBS patients had a hypothyroidism prevalence of 20.6%, compared to 10.3% in 20,298,589 non-IBS participants. After PSM, the hazard ratio (HR) for hypothyroidism in IBS patients was 1.21 (95% CI: 1.12-1.30, P < 0.001) in the UKB, and the odds ratio (OR) was 1.25 (95% CI: 1.23-1.27, P < 0.001) in the NIS. Subgroup analyses showed a higher risk for hypothyroidism in IBS patients, particularly those aged ≤65 years and females.

Conclusions: IBS is associated with an increased risk of hypothyroidism. Clinicians should consider screening for thyroid dysfunction in IBS patients to improve patient outcomes.

Introduction: The interplay between LncRNA MALAT1 and hsa-miR-1 plays a crucial role in Myocardial Ischemia-Reperfusion Injury (MIRI), offering insights into the molecular mechanisms underlying cardiovascular pathologies. This study sought to elucidate their regulatory relationship and functional impact on MIRI progression.

Materials and methods: Using an H9C2 cardiomyocyte cell line subjected to ischemia-reperfusion (I/R) modeling, we analyzed alterations in LncRNA MALAT1 and hsa-miR-1 expression and their downstream effects on apoptosis, reactive oxygen species (ROS) accumulation, and myocardial injury markers.

Results: Our findings demonstrated that siRNA-mediated knockdown of MALAT1 or modulation of hsa-miR-1 (via mimics and inhibitors) effectively attenuated oxidative stress and reduced cardiomyocyte apoptosis. Furthermore, in vivo experiments using a murine MIRI model corroborated the regulatory roles of MALAT1 and hsa-miR-1, identifying them as potential therapeutic targets for mitigating reperfusion injury.

Discussion: Our findings highlight the importance of the MALAT1/miR-1 axis in MIRI pathogenesis. The observed reduction in ROS and apoptosis upon modulation of these molecules suggests their involvement in key cellular stress responses. These results align with previous studies on lncRNA- miRNA interactions in cardiovascular diseases.

Conclusion: These results not only highlight the significance of the MALAT1/miR-1 axis in MIRI but also propose novel molecular intervention strategies for the treatment of cardiovascular disease.

Introduction: This study investigated the hepatoprotective effects and mechanisms of 17β-estradiol (E2) in a mouse model of type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD).

Methods: Male C57BL/6J mice (n = 6/group) were fed a high-fat diet for 8 weeks and injected with streptozotocin (60 mg/kg for 3 days) to induce T2DM + NAFLD. Animals were randomized into control, model, E2 (20 μg/kg/day, i.p., 8 weeks), E2 + siNC, and E2 + siPGC-1α groups. Metabolic indices, liver enzymes, body weight, liver index, and pre-specified cholestasis-related safety endpoints (alkaline phosphatase [ALP], total bile acids [TBA], total bilirubin [TBil]) were quantified. H&E and Oil Red O staining were used to assess hepatic injury and steatosis. PGC-1α/ERRα signaling was evaluated by Western blotting, immunofluorescence, and ChIPqPCR.

Results: Compared with the model group, E2 reduced fasting blood glucose by 54.7%, insulin by 36.3%, HOMA-IR by 71.1%, cholesterol by 25.9%, triglycerides by 46.2%, LDL-C by 36.6%, ALT by 47.2%, and AST by 39.9% (all P < 0.05). Body weight, liver index, hepatocyte injury, and lipid deposition were also decreased. E2 restored hepatic PGC-1α and ERRα expression and their co-localization; ChIP-qPCR confirmed ~7-fold enrichment of ERRα promoter regions by PGC-1α. For cholestasis-related indices, ALP and TBA exhibited only small, non-concerted changes while TBil remained stable; all values stayed within reference limits, indicating no cholestatic phenotype under our dosing paradigm. PGC-1α knockdown (E2 + siPGC-1α) blunted or abolished these metabolic, histological, and signaling benefits.

Discussion: The study demonstrates that 17β-estradiol exerts hepatoprotective and metabolic regulatory effects in diabetic fatty liver via modulation of the PGC-1α/ERRα pathway.

Conclusion: This study demonstrates that E2 alleviates metabolic dysfunction and hepatic injury in T2DM-NAFLD mice by activating the PGC-1α/ERRα axis, while preserving cholestatic safety, as evidenced by non-concerted ALP/TBA/TBil changes within reference limits. PGC-1α is essential for mediating these effects, highlighting the PGC-1α/ERRα pathway as a promising therapeutic target for metabolic liver disease.

Background: Anti-LGI1 antibody-associated encephalitis is a rare autoimmune neurological disorder, and primary Sjögren's syndrome is a systemic autoimmune disease with multisystem involvement. The coexistence of these conditions with acute cerebral infarction is extremely rare and highlights complex interactions between autoimmune and vascular mechanisms.

Case presentation: This case report describes a middle-aged female patient diagnosed with LGI1 antibody-associated encephalitis, complicated by Sjögren's syndrome and acute cerebral infarction. The patient presented with an acute onset of symptoms, including delayed response, cognitive impairment, and right-sided weakness. Brain MRI revealed a fresh infarction in the left basal ganglia region. Blood and cerebrospinal fluid tests confirmed the presence of LGI1 antibodies, with blood anti-SS-A antibody levels at +++ and anti-SS-B antibody levels at +, as well as anti- Ro-52 antibody levels at +++.

Conclusions: This report emphasizes the importance of recognizing the overlap between these conditions, as timely diagnosis and intervention can lead to better outcomes in similar cases. By examining the relationship between anti-LGI1 antibody-associated encephalitis, primary Sjögren's syndrome, and acute cerebral infarction, this paper aims to expand the understanding of the complex interactions between autoimmune encephalitis and systemic disorders.