Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 24, Issue 12, 2024

Metabolic syndrome (MetS) is now considered a global issue with a growing financial and health impact. Numerous herbal alternatives have been examined and researched due to the ever-increasing demand for new medications to treat metabolic syndrome disorders. People have empirically employed Moringa oleifera (MO), a native plant to several Asian nations, for a variety of diseases. We sought to examine recent research on MO in MetS and its potential mechanism of action in the current review. Four databases, including PubMed, Scopus, Web of Sciences, and Google Scholar, were thoroughly searched, and the data were then compiled. In total, 146 papers covering nonclinical and clinical MO investigations in metabolic syndromerelated disorders are included in this study. Numerous research confirmed MO's positive impact on the control of blood glucose, blood pressure, hyperlipidemia, and obesity. Many molecular processes have been investigated, including increasing glucose transporter type 4 (GLUT4) expression, inhibition of β-Hydroxy-β-methylglutaryl-coenzyme A (HMG-CoA), α-glucosidase inhibiting, AMP-activated protein kinase (AMPK) activation, and other suggested mechanisms. The current review established much data favoring MO's potential advantages in metabolic syndrome. However, further research involving human studies is required in this area to determine whether Moringa can effectively treat metabolic syndrome.

Objective: To investigate the effect of high blood glucose on the decline in the estimated glomerular filtration rate (eGFR) in the elderly. Methods: We compared the decline in eGFR of diabetic and non-diabetic groups in the noninterventional state and analyzed the effect of hyperglycemia on the decline in eGFR among the elderly in a retrospective analysis of 1,223 cases of elderly people aged 65 years or older with a 4-year follow-up period. Results: The prevalence of diabetes in the elderly increased significantly from 12.67% in 2017 to 16.68% in 2021. The rate of decline in eGFR in patients with diabetes was higher than in the population without diabetes, at 9.29% and 5.32%, respectively (both p <0.05). Conclusion: The results of this study revealed that the prevalence of diabetes in the elderly increased significantly, and there is a more rapid decrease in the eGFR levels in those with diabetes than those without diabetes.

Objective: The study aimed to study the differential gene expression and immune cell infiltration in patients with steroid-induced necrosis of the femoral head (SANFH), identify the key genes and immune cells of SANFH, and explore the relationship between immune cells and SANFH. Methods: The high-throughput gene chip dataset GSE123568 was downloaded from the GEO database, and the differential gene expression was analyzed with the R language. The STRING database and Cytoscape software were used to analyze the protein interaction network and screen key genes, and enrichment analysis was carried out on key genes. The infiltration of immune cells in SANFH patients was analyzed and verified by immunohistochemistry. Results: EP300, TRAF6, STAT1, JAK1, CASP8, and JAK2 are key genes in the pathogenesis of SANFH, which mainly involve myeloid cell differentiation, cytokine-mediated signaling pathway, tumor necrosis factor-mediated signaling pathway, and cellular response to tumor necrosis factor through JAK-STAT, NOD-like receptor, toll-like receptor, and other signaling pathways, leading to the occurrence of diseases; immune infiltration and immunohistochemical results have shown the expression of memory B cells and activated dendritic cells as reduced in SANFH patients, while in the same SANFH samples, M1 macrophages have been positively correlated with monocytes, and neutrophils have been negatively correlated with monocytes expression. Conclusion: EP300, TRAF6, STAT1, JAK1, CASP8, and JAK2 have exhibited significant differences in SANFH (spontaneous osteonecrosis of the femoral head). Memory B cells, activated dendritic cells, M1 macrophages, monocytes, and neutrophils have shown abnormal expression in SANFH.

Objectives: The body fat percentage is an indicator of overall body fat related to metabolism and inflammation. Our study aims to analyze the association between body fat percentage and the risk of cardiometabolic diseases in the general population. Methods: This was a retrospectively cross-sectional study. A total of 5084 participants enrolled from the National Health and Nutrition Examination Survey cycle of 1999-2004 were divided into quartiles according to their body fat percent levels. The body fat percentage was measured from bioelectrical impedance analysis. A history of cardiometabolic diseases, including cardiovascular disease, hypertension and diabetes mellitus, was ascertained from questionnaire, physical or laboratory examination. The association between body fat percentage and cardiometabolic diseases was investigated using multivariate logistic regression. Results: Compared with the lowest quartile of body fat percentage, the multivariate-adjusted odds ratio and 95% confidence interval of the highest quartile was 3.99 (1.58-10.88) for cardiovascular disease, 1.08 (1.04-1.13) for hypertension and 3.08 (1.89-5.11) for diabetes. Body fat percentage independently increased the risk of cardiometabolic diseases as a continuous variable. Conclusion: Higher body fat percentage level was associated with a higher likelihood of cardiometabolic diseases, which could be a powerful predictive factor.

Background: Recognizing the potential of the immune system, immunotherapies have brought about a revolution in the treatment of cancer. Low tumour mutational burden and strong immunosuppression in the peritoneal tumor microenvironment (TME) lead to poor outcomes of immune checkpoint inhibition (ICI) and CART cell therapy in ovarian cancer. Alternative immunotherapeutic strategies are of utmost importance to achieve sound clinical success. Introduction: The development of peptide vaccines based on tumor-associated antigens (TAAs) for ovarian cancer cells can be a potential target to provoke an anti-tumor immune response and subsequent clearance of tumour cells. The purpose of this in silico study was to find potential epitopes for a multi-epitope vaccine construct using the immunopeptidomics landscape of ovarian carcinoma. Methods: The four TAAs (MUC16, IDO1, FOLR1, and DDX5) were selected for potential epitopes prediction. The epitopes for B-cells, helper T-lymphocytes (HTL), and Cytotoxic Tlymphocytes (CTL) were predicted on the basis of antigenic, allergenic, and toxic properties. These epitopes were combined with suitable linkers and an adjuvant to form a multi-epitope construct. Results: Four HTLs, 13 CTLs, and 6 potential B-cell epitopes were selected from the predicted epitope. The designed multi-epitope construct was potentially immunogenic, non-toxic, and non-allergenic. Physicochemical properties and higher-order structural analyses of the final construct revealed a potential vaccine candidate. Conclusion: The designed vaccine construct has the potential to trigger both humoral and cellular immune responses and may be employed as a therapeutic immunization candidate for ovarian malignancies. However, further in vitro and animal experimentation is required to establish the efficacy of the vaccine candidate.

Background: As per the recommendation of the United States Food and Drug Administration, more research is needed to determine the antibody titer against COVID-19 vaccination. Objective: The study aimed to understand the relationship between the antibody titer to the demographics, infection severity, and cycle threshold (CT) values of confirmed COVID-19 patients. Methods: Initially, we obtained consent from 185 populations and included sixty RT-PCRpositive COVID-19 patients from Kamrup District in the Northeast State of Assam, India. The vaccination status was recorded and tested for the level of serum immunoglobulin (IgG). The CT values, gender, and clinical symptoms-based scoring (CSBS) correlated with their IgG value. Results: Around 48% of participants gained an antibody titer more than the threshold value and showed CT values between 18-25. Moreover, the maximum distributed score above the average was found between the CT values 18-25. Conclusion: The IgG titer value differs significantly amongst the vaccinated population, which may depend upon their genetic and demographic variability.

Background: Compared to Immediate-Release (IR) metformin, Extended-Release (ER) metformin reduces side effects and pill burden while improving adherence; however, there is little real-life data on patient satisfaction with this innovative formulation to guide physicians toward a more holistic approach. Objective: Our goal is to train general practitioners on holistic patient management, with the aim of increasing patient satisfaction and treatment adherence, reducing side effects, and improving quality of life in patients with poor tolerance to metformin-IR. Materials and Methods: We designed an educational program for physicians called SlowDiab, aimed at establishing a holistic patient approach. In this context, adult patients with T2DM who experienced gastrointestinal discomfort with metformin-IR were enrolled and switched to metformin- ER. Data on glycemic control were collected at baseline and 2 months after switching. A survey was carried out on patients to assess their level of satisfaction. Results: In 69 enrolled patients (mean (min-max) age, 68.2 (41-90)), side effects decreased after switching from 61.8% to 16.2% (p < 0.01), and the mean perceived burden of adverse events on a scale of 1 to 10 also decreased (6.17 vs. 3.82; p < 0.05). Among patients previously intolerant to metformin-IR, 74.3% reported no longer experiencing any side effects after the switch. The mean number of tablets taken daily (2.28 vs. 1.66; p < 0.01) and mean plasma glycated hemoglobin (HbA1c) values (7.0% vs. 6.7%; p < 0.05) decreased, while 93.8% of patients were satisfied with the treatment change. Moreover, 84.2% reported an improvement in glycemic control after the switch. Conclusion: In a real-life setting, an educational program for general practitioners confirmed that metformin ER reduces side effects and improves pill burden, therapeutic adherence, and patient satisfaction compared to metformin IR.

Background: Evidence suggested how nurses experienced worse lifestyles than the general population by recording deterioration rates in healthy conditions. Aim: To assess differences between comorbidity, eating behavior, and smartphone addiction according to sex, Body Mass Index (BMI), age, work experience, shift, alcohol assumption, and physical activity in Italian nurses. Methods: An online questionnaire was spread through some professional internet pages. Data included demographic characteristics, the Charlson Comorbidity Index (CCI), the Italian Version of the Dutch Eating Behavior Questionnaire, and the Smartphone Addiction Scale (SAS-SV). Results: A total of 456 nurses were recruited. Significant differences were registered in the smartphone addiction score (p=0.030) and BMI scores and work experience (p=0.001), as underweight participants reported higher scores in the smartphone addiction attitude (2.4714 ± 1.25812) than the other subjects and also participants with the highest number of years in work experience also reported higher smartphone addiction scores (2.8074 ± 1.2022). Significant difference was reported in the CCI scores according to age (p<0.001): subjects aged over 61 years recorded higher scores in the CCI (1.67 ± 1.528) and also according to work experience and CCI scores (p<0.001), as participants employed between 21 and 30 years reported higher scores in the CCI (1.27 ± 1.382) and also to night shift (p=0.037), as participants who worked during the night shift also reported higher scores in the CCI. A significant difference was reported only for restrained eating attitude (p=0.034), as participants who declared to assume alcohol 2-3 times per month recorded higher levels in this eating attitude aspect (32.32 ± 7.181). Conclusion: Female nurses, overweight and obese nurses with low physical activity practice, seemed to spend more time with their smartphones. Healthcare organizations should consider findings to prevent unhealthy lifestyles among nurses, which could negatively influence the whole healthcare system.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is an emerging epidemic; it is a negative diagnosis that depends mainly on the presence of hepatic steatosis with or without inflammation after the exclusion of other chronic liver diseases and excess alcohol intake. However, the new definition of MAFLD is a shift towards a diagnosis of inclusion based on the presence of metabolic dysfunction, regardless of alcohol consumption or other concomitant liver diseases. Given the growing relevance of the disease, data on hepatologists' views and understanding of NAFLD are limited, we aimed to determine hepatologists' awareness and expertise of NAFLD screening, diagnosis, and therapeutic options as well as the influence of changing the NAFLD name to MAFLD on awareness of the fatty liver disease (FLD). Objective: Most of the hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, necessitating a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer better awareness of FLD. Methods: A multicenter online questionnaire of 655 hepatologists was carried out, giving a sample of 207 respondents. A survey composed of 36 questions was used to assess the level of hepatologists' awareness and practices in the screening, diagnosis, and management of NAFLD/MAFLD, as well as their familiarity with the nomenclature change from NAFLD to MAFLD. Results: A total of 207 hepatologists were included, of which 107 (51.4%) were males, with a mean age was 36.4 years. 50.2% (n = 104) of the hepatologists were oriented with NAFLD. Only 41 (19.8%) realized that NAFLD may frequently result in severe hepatic disease. NAFLD is rarely screened by the majority of the participating hepatologists (118, 57%), and (135, 65.2%) of them use liver biopsy for diagnosis of NAFLD. In (104, 50.2%) hepatologists, changing the nomenclature of NAFLD was relatively familiar. Furthermore, 71.9% of hepatologists thought that the new nomenclature offers a better awareness of FLD. Conclusion: A small percentage of hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, and around half of them realize that NAFLD necessitates a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer better awareness of FLD.

Background: Hashimoto's thyroiditis (HT) is an autoimmune disease characterized by the destruction of thyroid cells through immune processes involving T helper (Th)1 cytokines. This clinical trial investigates the impact of vitamin D supplementation on serum cytokine levels and gene expression in CD4+ T cells from HT patients, aiming to understand its effects on Th-1, Th-2, Th-17, and regulatory T (Treg) cell-associated factors. Methods: Female patients were randomly assigned in a double-blind design to either a vitamin D-supplemented group, which received cholecalciferol (1, 25(OH)2;D3) at a dose of 50,000 IU, or the placebo group, which received a weekly placebo for a duration of three months. Serum cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA), while genes’ expression levels were measured using real-time PCR. Results: Serum 25-hydroxyvitamin D and levels exhibited a significant increase following vitamin D supplementation, in comparison to the placebo group. Additionally, the vitamin D supplementation resulted in a significant elevation of serum calcium (Ca) levels compared to baseline. In the vitamin D group, there was a significant decrease in both serum levels and expression of the interleukin (IL)-17 gene when compared to baseline, although no statistical difference was observed between the placebo and vitamin D groups. The gene expression of transforming growth factor-beta (TGFβ) was significantly increased in the vitamin D group compared to baseline, with no significant difference between the two study groups. Vitamin D treatment had no effect on serum levels of interferon-gamma (IFN) and IL-4. While the gene expression of IL-4 in the vitamin D group did not exhibit a statistically significant increase, the level of GATA3 transcription factor increased significantly when compared to the placebo group. The expression of IFN and transcription factors, T-bet, RORc, and forkhead box protein 3 (FOXP3) in genes did not show significant changes following vitamin D supplementation. Conclusion: The findings suggest that vitamin D supplementation may hold potential benefits for autoimmune diseases, such as HT. However, further longitudinal clinical trials are necessary to gain a more comprehensive understanding of the specific effects of vitamin D on HT.

Background: Pancreatic metastases from medullary thyroid carcinoma (MTC) are exceptional. Imaging and treatment based on somatostatin receptors may play a role, though the evidence is unconvincing. Case Presentation: We have, herein, documented a unique case of metastatic MTC, where pancreatic metastasis was identified by 68Ga-PET/CT, with the disease showing very slow progression during treatment with lanreotide autogel. A 51-year-old woman underwent total thyroidectomy for goiter in 2000, with a postoperative diagnosis of MTC. Due to persistent disease, somatostatin analogues (SSA) treatment commenced in 2005, following a positive acute octreotide test. In 2012, a pathology-confirmed pancreatic metastasis was diagnosed via 68Gallium-positron emission tomography (68Ga-PET/CT). The disease progressed very slowly over 17 years of SSA treatment. Conclusion: This uncommon case of pancreatic metastasis from MTC indicates that nuclear medicine techniques might offer valuable additional information. Extended treatment with lanreotide autogel appears to correlate with very slow disease progression in selected patients.