Endocrine, metabolic & immune disorders drug targets最新文献

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.

Obesity and associated health impairments are proven to exhibit multifocal health disorders along with increasing co-morbidity. Underlying obesity pathology is linked up with almost every major disease, which may increase the risk of heart disease, hypertension, diabetes, cancer, osteoarthritis, etc. The prevalence of overweight and obesity is on the rise around the world, which enormously affects the life span of individuals. Due to the foggier nature of the underlying pathology, the efficacy is questionable for conventional treatments. The traditional therapy of obesity may involve synthetic moieties and surgical procedures, which have many harmful side effects and chances of recurrent severity. Scientists are continuously focusing on prophylactic remedies alongside maintaining a proper lifestyle. In that context, nature always helped with traditional medications. As per folklore medicine reports, many plants have been used to treat obesity and its associated complications. This review compiles a vast array of datasets, including the impact of obesity and the need for the introduction of phytochemicals in place of conventional pharmacotherapies, the impact of phytochemicals along with the reported mechanisms of action, recent clinical trial reports, and recently explored dietary supplements. The primary objective of this presentation is to chart the future trajectory of phytochemical research for metabolic disorders, establishing a foundational framework for future investigations to build upon.

Introduction/objective: Bioinformatic analysis is a valuable tool that allows us to collect, archive, analyze, and disseminate biological data for further interpretation. Analysis of the IL-23/IL-17A axis and its receptors will provide us with essential information about their functions, interactions, and relationships with various diseases. This review aims to identify the central genes co-expressed in the IL-23/IL-17A axis and their receptors and to understand their ontology and modifying factors.

Methods: We used several databases, including COXPRESdb to obtain the co-expressed genes, ShinyGO and ToppGene platforms to explore gene functional enrichment, and the NetworkAnalyst 3.0 platform for gene expression profiling.

Results: We found that genes encoding IL-23/IL-17A axis proteins and their receptors mainly respond to microbial components, participate in the inflammatory response, and are primarily associated with inflammatory and autoimmune diseases. In addition, we observed an association of the IL-23/IL-17 axis with Behcet's disease, Graft-versus-host disease, and Hodgkin's disease, although there is no direct evidence of their interaction.

Conclusion: The IL-23/IL-17A axis is associated with several inflammatory and autoimmune pathologies. Therefore, we suggest further research to confirm its role in these pathologies and, if possible, use it as a therapeutic target.

Reactive oxygen species production, inflammation, an elevated serum profile, mitochondrial dysfunction, and up-regulation of proapoptotic mediators are the main mechanisms underlying chemotherapy-related hepatotoxicity, which results in hepatocyte disorders such as hepatitis, steatohepatitis, and fibrosis. The article aims to examine a prospective herbal remedy and its bioactive ingredients in terms of its antioxidant, anti-inflammatory, and anti-apoptotic capabilities, which offer superior protection against liver damage during chemotherapy administration. Plants including Silybum marianun, Nelumbo nucifera, Phyllanthus amarus, Plumbago zeylanica, Glycyrrhiza glabra, Citrus limon, and Nigella sativa may have hepatoprotective properties, according to the author. Last but not least, this will give aspiring scientists new knowledge for natural-based development in mitigating liver damage caused by chemotherapy medications.

Introduction: Hypophysitis is a rare inflammatory disorder of the pituitary gland. Symptoms and signs of hypophysitis can be various, progressing insidiously, and its recognition may be challenging.

Case presentation: We report the clinical history and therapeutic management of a 59-year-old man diagnosed with arginine vasopressin deficiency (AVP-D) due to an infundibulo-neurohypophysitis (INH) that occurred after the patient had inhaled spray film containing toluene. In consideration of the clinical signs and radiological imaging suggestive of INH, therapy with desmopressin and corticosteroids was instituted, with gradual improvement of polyuria and resolution of the radiological features of INH.

Conclusion: To our knowledge, we described the first case of INH, manifested with AVP-D, secondary to toluene exposure. In addition, the endocrine effects of toluene inhalation were discussed. Finally, given the scarcity of data available, an overview of all the known toxic substances inducing AVP-D was also provided.

Cancer remains a global health problem that requires constant research for the development of new treatment strategies. Flavonoids, a diverse group of naturally occurring polyphenolic compounds abundant in fruits, vegetables, and other plant sources, have received considerable attention for their potential anticancer properties. This review aimed to provide a comprehensive overview of the current scientific literature on five specific natural flavonoids, namely quercetin, Epigallocatechin Gallate (EGCG), kaempferol, apigenin, and curcumin that have been widely reported in numerous carcinomas and evaluate their effectiveness and mechanisms in fighting different types of cancer. Known for its antioxidant and anti-inflammatory properties, quercetin has shown promise in inhibiting cancer cells and modulating key signaling pathways. EGCG, a prominent catechin found in green tea, has been extensively studied for its ability to induce apoptosis and inhibit angiogenesis, highlighting its potential as an anticancer agent. Kaempferol has antioxidant and anti-inflammatory effects and has shown anticancer potential by modulating cellular processes involved in tumor development. Apigenin, abundant in parsley and chamomile, has been shown to exert anticancer properties by interrupting the cell cycle and inducing apoptosis in cancer cells. Curcumin has shown several anticancer effects, including inhibiting cell proliferation, inducing apoptosis, and modulating inflammatory pathways. Despite these promising findings, it is essential to recognize the complexity of cancer biology and the need for further research to clarify the precise mechanisms of action of these natural flavonoids and optimize their therapeutic applications. Furthermore, understanding flavonoids' potential synergy and interactions with traditional cancer therapies is paramount for developing effective combinatorial strategies. This review thus aimed to summarize the current knowledge on these natural flavonoids and provide insight into their potential role as an adjunctive or stand-alone therapy in the fight against breast, prostate, colon, lung, skin, ovarian, liver, and pancreatic cancer.

Background: The involvement of the larynx in many situations can have a substantial impact on a person's voice, breathing, and general health. Individuals with autoimmune thyroid disorders can experience a variety of conditions affecting the larynx. Autoimmune thyroid disorders, such as Hashimoto's thyroiditis [HT] and Graves' disease [GD], are prevalent conditions affecting the thyroid gland. Beyond their established impact on thyroid function, these disorders have been associated with laryngeal involvement. The current study aims to explore the likelihood of laryngeal involvement in patients with Autoimmune Thyroid Disorders [AITD].

Method: This study involved a retrospective analysis of medical records from patients diagnosed with autoimmune thyroid disorders. Inclusion criteria were a confirmed diagnosis through laboratory investigations and clinical assessment. Patients with pre-existing laryngeal pathologies or other conditions affecting the larynx were not considered. We collected data from 4 research articles and 3 clinical trials from Embase, PubMed, and NCBI-Trials portals, focusing on reported laryngeal symptoms. The severity of laryngeal involvement was assessed and categorized based on its extent and impact on vocal function.

Results: Preliminary analysis of the collected data indicated a significant proportion of patients with autoimmune thyroid disorders reporting laryngeal symptoms. Among these patients, various manifestations of laryngeal involvement were observed, including vocal changes, hoarseness, and throat discomfort.

Conclusion: The findings show that laryngeal symptoms may be an underappreciated feature of these diseases, potentially impacting vocal function and quality of life in affected people. Further research is also needed for more precise projections in this direction.