Endocrine, metabolic & immune disorders drug targets最新文献

Background: The ketogenic diet, known for its high-fat, low-carbohydrate composition, has been extensively studied in endocrine and metabolic diseases. This study carried out bibliometric analysis to examine the research trends in this field over the past 20 years, aiming to provide insights for future studies.

Methods: We searched the Web of Science Core Collection for all relevant papers. VOSviewer was used for network visualization, the bibliometrix package of R software (version 4.3.0) was utilized for data analysis, and CiteSpace was employed for mapping and trend analysis.

Results: This study encompassed 508 relevant articles spanning from 2003 to 2023, authored by 2827 researchers from 887 institutions across 57 countries/regions. The total number of publications increased from 3 in 2003 to 508 in 2023, showing a steady growth trend. The United States emerged as the predominant contributor in this field, followed by Italy and China. Notably, SAJOUX I consistently exhibited high activity in this field, according to the analysis, with an h-index of 13. The journal Nutrients has consistently made substantial contributions to this field, accounting for 19% of all publications. The keywords "obesity," "ketogenic diet," and "weight loss" appeared most frequently, with "obesity" occurring 163 times.

Conclusion: This study used a bibliometric method to analyze the impact of the ketogenic diet on the endocrine metabolic system. The research identifies recent frontiers and trending directions, providing valuable references for scholars in this field.

Aims and objectives: The purpose of this study was to comprehensively evaluate the association of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) with neurological adverse events using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, with the aim of guiding the rational use of statins.

Methods: The number and clinical characteristics of adverse events (AEs) to statins in the FAERS database between 2012 and March, 2023, were extracted. Neurological AEs were defined by the system organ classes (SOCs) of "Nervous System Disorders (10029205)" and the corresponding PT. Disproportionality was calculated using the reporting dominance ratio (ROR), proportional reporting ratio (PRR), and information component (IC025).

Results: Between January, 2012 and March, 2023, a total of 90,357 AEs were reported for the three statins (atorvastatin, resuvastatin, and simvastatin). The majority of reports on AEs came from the United States (n = 7284). A total of 8409 reports described neurological AEs following the use of the three statins, with atorvastatin accounting for more than half of the reports (n = 4430). The mean age of patients who developed neurological AEs was 55 years and older. The prevalence was similar in female patients (2230/4480) and male patients (1999/4480). Disproportionate analyses showed that at the SOC level, only the correlation between atorvastatin and neurological AEs suggested a positive signal (ROR: 9.77 (9.56-9.99); IC025: 3.28; PRR (χ2): 9.76 (16.07)) and in total, there were 32 PTs with a positive signal. The median time for neurological AEs was 71 days (IQR: 14-559 days), and the most common AEs were other serious effects (important medical event) (OT) (n = 2283) and hospitalization (HO) (n = 715).

Conclusion: This study suggests that atorvastatin may be associated with an increased risk of neurological AEs. This study provides realistic evidence of the potential risk of statin-related adverse events.

Introduction: This study aims to investigate the function and potential mechanism of Tanshinone IIA in uric acid-induced HK-2 fibrosis models.

Materials and methods: An in vitro model of fibrosis was constructed using uric acid stimulation. RT-qPCR and Western blot were used to evaluate the levels of inflammatory cytokines. The detection of ROS and ELISA assay were used to analyze the changes in oxidative stress.

Results: Tanshinone IIA inhibited the increase in inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-18 and the formation of NLRP3 inflammasome induced by uric acid stimulation. In addition, Tanshinone IIA treatment reduced the production of ROS and MDA, promoting the expression of SOD and CAT, thereby protecting HK-2 cells from oxidative stress damage. Besides, the expression of TGF-β, FN, and COL-1 was significantly reduced by the treatment of Tanshinone IIA. Mechanistically, Tanshinone IIA inhibited the expression of inflammatory cytokines and the formation of the NLRP3 inflammasome by targeting NRF2.

Conclusion: Tanshinone IIA exerts a protective role in uric acid-induced HK-2 fibrosis models by targeting the NRF2-NLRP3 signaling pathway to reduce the occurrence of inflammation and oxidative stress.

Background: Senna leaf is a commonly used medication for treating constipation, and long-term use can cause damage to the intestinal mucosa and lead to drug dependence. But the exact mechanism remains unclear.

Objective: Using non-targeted metabolomics technology to study the mechanism of senna leaf ethanol extract (EESL) inducing inflammation and oxidative stress in mice and causing side effects.

Methods: EESL was administered to mice by gavage to detect inflammation and oxidative stressrelated factors in mice, and the EESL components and differential metabolites in mouse plasma were analyzed using non-targeted metabolome techniques.

Results: 23 anthraquinone compounds were identified in the EESL, including sennoside and their derivatives. Administration of EESL to mice resulted in a significant increase in pro-inflammatory factors, IL-1β, and IL-6 in the plasma, while the levels of IgA significantly decreased. The levels of oxidative stress significantly increased, and the intestinal mucosal integrity was impaired. 21 endogenous in plasma metabolites were identified as differential metabolites related with taurine and taurine metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, tryptophan metabolism, and sphingolipid metabolism. These metabolic pathways are related to oxidative stress and inflammation.

Conclusion: Senna leaf can inhibit the expression of tight junction proteins in the intestinal mucosa and disrupt intestinal mucosal barrier integrity, exacerbating oxidative stress and inflammation induced by bacterial LPS entering the bloodstream. In addition, the impact of Senna leaf on tryptophan metabolism may be linked to the occurrence of drug dependence.

Objective: This study aimed to uncover biomarkers associated with fibroblasts to diagnose ulcerative colitis (UC) and predict sensitivity to TNFα inhibitors.

Methods: We identified fibrosis-related genes by analyzing eight bulk RNA and one single-cell RNA sequencing dataset from UC patients. Three machine learning algorithms were employed to identify common significant genes. We utilized five machine learning models, namely Random Forest (RF), Support Vector Machine (SVM), Xgboost, Multilayer Perceptron (MLP), and Logistic Regression, to develop diagnostic models for UC. Following hyperparameter tweaking using grid search, we evaluated Matthew's Correlation Coefficient (MCC) of each model on the validation set. Finally, we identified five hub genes in UC patients and evaluated their response to infliximab or golimumab.

Results: We identified 23 genes associated with fibroblasts. Further analysis using three ML models revealed BIRC3, IFITM2, ANXA1, ISG20, and MSN as critical fibroblast genes. Following hyperparameter adjustment, the SVM model exhibited the most favorable characteristics in the validation set, achieving an MCC of 0.7. ANXA1 contributed the most to the model that predicts UC. The optimal model was implemented on the website. Among UC patients receiving TNFα inhibitor treatment, the ineffective group showed considerably increased expression of the five critical genes than the responsive group.

Conclusion: BIRC3, IFITM2, ANXA1, ISG20, and MSN may serve as potential diagnostic biomarkers in UC. Through the interaction between characteristic biomarkers and immune infiltrating cells, the immune response mediated by these characteristic biomarkers plays a crucial role in the occurrence and development of UC.

Background: The diagnostic workup of an adrenal mass should always rule out the possibility of an adrenal metastasis, especially in a patient followed-up for a known primitive cancer. Sometimes, however, the incidental finding of a bulky lesion in a cancer patient can lead to the unexpected diagnosis of metastasis from a second occult cancer. Here, we report the case of a voluminous, isolated left adrenal metastasis from unknown and persistently occult hepatocellular carcinoma (HCC), incidentally found during the follow-up for squamous carcinoma of the tongue.

Case description: A 72-year-old HBV/HCV-negative male patient with a history of alcohol abuse was referred to our hospital for gastric bleeding. Some weeks before, the patient was operated on for a locally advanced squamous cell carcinoma of the tongue, which required cervical lymph node neck dissection, temporary tracheostomy, jejunostomy, and plastic reconstruction. Subsequent diagnostic imaging revealed a left adrenal mass sized 9x15 cm with suspicious features. The hormonal workout was negative for pheochromocytoma and a hyperfunctioning adrenal lesion. The patient underwent laparotomic left adrenalectomy. The exploration of the liver was compatible with alcoholic cirrhosis and did not reveal any other palpable lesion. The adrenal mass histologically turned out to be a poorly differentiated G3 HCC. Subsequent radiological exams were unable to identify the primary liver lesion or any other neoplasms. Conversely, α-FP levels were initially high but reduced after treatment with sorafenib. After 2 years of follow-up, the patient is alive and well, albeit with evidence of locoregional inter-aortocaval lymphadenopathy. The primary HCC has never been identified, thus suggesting the hypothesis of a diffuse cirrhosis-like HCC.

Conclusion: The suspicion of an adrenal metastasis in a patient with primary cancer with a low potential for adrenal metastatic spreading must raise the diagnostic suspect for another synchronous occult cancer beyond that for primary adrenal cancer. HCC can rarely first manifest as a metastatic adrenal lesion.

Objective: Analysis of Traditional Chinese Medicine (TCM) constitution type general medical patients and the relationship between the metabolic index.

Methods: A cohort of 1,029 general individuals who underwent a physical examination at the Affiliated Hospital of Changchun University of Chinese Medicine for identification of their TCM constitution between January 2021 and April 2023 were included in this study. Their data were sorted and analyzed using Microsoft Excel and SPSS26.0 statistical software.

Results: Among the 1029 study participants, the balanced constitution (BC) type was the most prevalent (33.24%), and the blood stasis constitution (BSC) type was the least prevalent (2.62%). Compared with BC, phlegm-dampness constitution (PDC) (P=0.000), yang-deficiency constitution (YADC) (P=0.000) and BSC (P=0.008) had significant differences in body mass index (BMI) (P<α). The systolic blood pressure (SBP) of PDC was different (P=0.042, P<α). There was a significant difference in diastolic blood pressure (P=0.001, P<α). The diastolic blood pressure (DBP) of YADC was significantly different (P=0.001, P<α). Yin-deficiency constitution (YIDC) (P = 0.007) and YADC differences between fasting blood glucose (FBG) (P = 0.025) were significantly (P<α). There were significant differences in uric acid (UA) of YADC (P=0.000), BSC (P=0.004), PDC (P=0.007) and qi-stagnation constitution (QSC) (P=0.012, P<α). The triglyceride (TG) of YADC (P=0.000) and PDC (P=0.005) were significantly different (P<α). There was a difference in total cholesterol (TC) between PDC (P=0.046) and BC (P<α). BSC (P = 0.028) and PDC (P = 0.023) of low-density lipoprotein cholesterol (LDL-C) also had a significant difference (P<α).

Conclusion: People with PDC, YADC and BSC had more abnormal metabolic indexes than people with BC, and the metabolic indexes of people with YIDC constitution were different from those with BC. Individuals with these four TCM constitution types should pay attention to making appropriate changes in lifestyles and dietary habits and take required measures to prevent the incidence and development of metabolic diseases.

Background: Recurrent Pregnancy Loss (RPL) and Polycystic Ovary Syndrome (PCOS) are both common diseases involving women of childbearing age, and their pathogenesis is still not sufficiently known.

Objective: This study aimed to explore the relationship between RPL and PCOS in bioinformatics.

Methods: Two expression chips, GSE86241 (obtained from 8 PCOS patients and 9 healthy controls) and GSE73025 (obtained from 5 RPL patients and 5 healthy controls), were downloaded from the Gene Expression Omnibus (GEO) database. We used the GEO database to analyze the gene expression profiles of PCOS and RPL to identify the intersection of abnormal miRNA expression, predicted the target genes of the intersecting miRNAs from miRDB, miRTarBase, and TargetScan databases, and then incorporated the miRNA-mRNA modulation network. By using the string database, the PPI network was built, which could screen the Hub genes and enrich them for analysis. Ultimately, the critical miRNA-mRNA regulatory network was set on the basis of the relationship between hub genes and miRNA.

Results: A total of 39 significantly altered miRNAs of PCOS and 137 significantly altered miRNAs of RPL were obtained, three miRNAs (miR-767-5p, miR-3196, and miR-187-3p), five signaling pathways (PI3K-Akt, p53, Toll-like receptor, C-type lectin receptor, and TNF signaling pathways), and six Hub genes (CASP8, PIK3R1, ADAMTS2, ADAMTS3, COL3A1, and MDM2) were found to be related to the development and progression of two diseases. More importantly, all Hub genes were regulated by miR-767-5p.

Conclusion: This research clarifies the possible relationship between miRNA and mRNA with PCOS and RPL for the first time. It provides a basis for illustrating the pathogenic mechanism and a target of therapies for these two diseases.

Objective: Cinnamomi cortex (CC), a traditional Chinese herbal medicine, exhibits antidiabetic properties, yet the underlying mechanisms are not fully understood. Our study combined network pharmacology, molecular docking, and experimental validation to elucidate the antidiabetic mechanisms of CC.

Methods: Active components of CC and their potential antidiabetic targets were identified through TCMSP, DisGeNET, and GeneCards. The PPI networks were constructed with STRING and analyzed with Cytoscape, while GO and KEGG analyses utilized the DAVID database. Molecular docking with core targets was performed using Autodock Vina. The efficacy of CC in diabetes mellitus was evaluated through H&E staining, qPCR, and Western blot in the T2DM mouse.

Results: Eleven active components and sixty-six potential antidiabetic targets of CC were identified. The enrichment analysis revealed 288 GO terms and 37 pathways. The molecular docking showed high affinity for PPAR-γ and IL-6 receptors. In vivo studies further confirmed CC's ability to modulate PPAR-γ and IL-6, contributing to its antidiabetic effects.

Conclusion: CC manages diabetes by regulating the PPAR-γ pathway and suppressing associated inflammation, providing a multi-pathway therapeutic approach.

Background: Chronic Kidney Disease (CKD) is a common chronic disease that is a threat to human health. Accumulating evidence showed that long noncoding RNAs (lncRNAs) are associated with various diseases and can function as competing endogenous RNAs (ceRNAs). However, the roles and functions of the lncRNA‒miRNA-mRNA network in CKD are still unclear.

Methods: In this study, we performed differential expression analysis of lncRNAs, miRNAs, and mRNAs in CKD using the datasets GSE66494 and GSE80247 from the Gene Expression Omnibus. A total of 33 lncRNAs, 20 miRNAs, and 240 mRNAs were differentially expressed between CKD patients and healthy controls. Two ceRNA interaction modules composed of 11 hub nodes, namely, 2 lncRNAs (LINC01086, LINC01094), 2 miRNAs (hsa-miR-197-3p, hsamiR- 513b-5p) and 7 mRNAs (CENPF, TOP2A, ARHGAP11A, CEP55, MELK, DTL, and ANLN) were constructed. In vitro knockdown of LINC01094 expression in renal tubular epithelial HK2 cells significantly attenuated the phenotype of TGFβ1-induced cell fibrosis.

Results: The results of RNA immunoprecipitation (RIP) experiments and dual-luciferase reporter experiments based on constructed mutants confirmed that LINC01094 could mediate MELK expression by sponging miR-513b-5p.

Conclusion: Our observations indicated that lowering the expression of LINC01094 can significantly attenuate the TGFβ1-induced fibrosis phenotype in HK2 cells and renal inflammation through the miR-513b-5p/MELK/Smad3 signalling axis.