Endocrine, metabolic & immune disorders drug targets最新文献

Backgrounds: Postbiotics produced by gut microbiota have exhibited diverse pharmacological activities. Valeric acid, a postbiotic material produced by gut microbiota and some plant species like valerian, has been explored to have diverse pharmacological activities.

Methods: This narrative review aims to summarise the beneficial role of valeric acid for different health conditions along with its underlying mechanism. In order to get ample scientific evidence, various databases like Science Direct, PubMed, Scopus, Google Scholar and Google were exhaustively explored to collect relevant information. Collected data were arranged and analyzed to reach a meaningful conclusion regarding the bioactivity profiling of valeric acid, its mechanism, and future prospects.

Results: Valeric acid belongs to short-chain fatty acids (SCFAs) compounds like acetate, propionate, butyrate, pentanoic (valeric) acid, and hexanoic (caproic) acid. Valeric acid has been identified as one of the potent histone deacetylase (HDAC) inhibitors. In different preclinical in -vitro and in-vivo studies, valeric acid has been found to have anti-cancer, anti-diabetic, antihypertensive, anti-inflammatory, and immunomodulatory activity and affects molecular pathways of different diseases like Alzheimer's, Parkinson's, and epilepsy.

Conclusion: These findings highlight the role of valeric acid as a potential novel therapeutic agent for endocrine, metabolic and immunity-related health conditions, and it must be tested under clinical conditions to develop as a promising drug.

Background: The prevalence of diabetes is rapidly increasing in India, even among young adult individuals. Rare adiponectin gene (ADIPOQ) variants may be predominantly present in Indians and decrease the circulatory levels of APN (Adiponectin). Studies reported that ADIPOQ gene variants were associated with type 2 diabetes mellitus (T2DM) and its complications in the Indian population.

Objectives: To review the association of specific ADIPOQ gene variants with T2DM and its associated complications.

Materials & methods: A search of Pubmed, Chinhal, Medline, Scopus, Web of Science databases, and Google Scholar search engine was performed to retrieve articles by using the following keywords; "ADIPOQ and T2DM", "ADIPOQ and India," "ADIPOQ gene variants and T2DM", "ADIPOQ gene variants and T2DM and India", "SNPs of ADIPOQ gene and T2DM", "SNPs of ADIPOQ gene and India," SNPs of ADIPOQ gene and T2DM and India". Eligibility criteria for the inclusion of articles: Original, Case-Control Study, and Full-Text articles were published in the English language till the end of April 2023.

Results: A total of 540 articles were retrieved. Out of this, only 18 articles were found suitable to include in this systematic narrative review. The most studied ADIPOQ gene variants were found to be +10211T/G (rs17846866), +45T/G (rs2241766), and +276G/T (rs1501299) in different Indian populations.

Conclusion: It was reviewed that ADIPOQ gene variants +10211T/G (rs17846866), +45T/G (rs2241766), and +276G/T (rs1501299) were predominantly present in the Indian population, and decreasing the circulatory levels of APN and significantly associated with T2DM and its complications.<.

Background: International studies have found that the blood triglycerides to highdensity lipoproteins (TG/HDL-C) ratio predicted insulin resistance in children with overweight and obesity. However, there is a lack of such reports on children from China.

Objective: The objective of this study is to explore the ability of the TG/HDL-C ratio as a blood biomarker for insulin resistance (IR) in obese children in Beijing.

Methods: We evaluated 262 children with obesity from our paediatric outpatient clinic in a cross-sectional study. Detailed medical histories of all children were ascertained, as were clinical examination and laboratory test results, including blood lipids, fasting glucose, insulin, and glycated haemoglobin. We divided them into age groups of 6-9 and 10-13.5 years and then into IR and non-IR groups based on the homeostatic model assessment for IR (HOMA-IR). Analysis was accomplished with SPSS software (version 22.0).

Results: The TG/HDL-C ratio was higher in children with IR in the 6-9 and 10-13.5-year age groups (p < 0.001). Univariate and multivariate analyses displayed that the TG/HDL-C ratio and HOMA-IR were correlated in the 6-9 and 10-13.5-year-old groups (p < 0.05). In the 6-9-yearold group, IR identified by a TG/HDL-C ratio ≥ 0.645 had a sensitivity, specificity, and an area under the curve (AUC) of 79.1%, 60.9%, and 0.734, respectively. In the 10-13.5-year-old group, IR identified by a TG/HDL-C ratio ≥ 0.725 had a sensitivity, specificity, and an AUC of 79.4%, 62.9%, and 0.724, respectively.

Conclusion: We showed the application of the TG/HDL-C ratio to predict insulin resistance in obese children in Beijing with different diagnostic thresholds based on age (6-9-year-old group with TG/HDL-C ≥ 0.645; 10-13.5-year-old group with TG/HDL-C ≥ 0.725), which were lower compared with the diagnostic threshold for insulin resistance in children reported in other countries.

Obesity is rapidly becoming a global health problem affecting about 13% of the world's population affecting women and children the most. Recent studies have stated that obese asthmatic subjects suffer from an increased risk of asthma, encounter severe symptoms, respond poorly to anti-asthmatic drugs, and ultimately their quality-of-life decreases. Although, the association between airway hyperresponsiveness (AHR) and obesity is a growing concern among the public due to lifestyle and environmental etiologies, however, the precise mechanism underlying this association is yet to establish. Apart from aiming at the conventional antiasthmatic targets, treatment should be directed towards ameliorating obesity pathogenesis too. Understanding the pathogenesis underlying the association between obesity and AHR is limited, however, a plethora of obesity pathologies have been reported viz., increased pro-inflammatory and decreased anti-inflammatory adipokines, depletion of ROS controller Nrf2/HO-1 axis, NLRP3 associated macrophage polarization, hypertrophy of WAT, and down-regulation of UCP1 in BAT following down-regulated AMPKα and melanocortin pathway that may be correlated with AHR. Increased waist circumference (WC) or central obesity was thought to be related to severe AHR, however, some recent reports suggest body mass index (BMI), not WC tends to exaggerate airway closure in AHR due to some unknown mechanisms. This review aims to co-relate the above-mentioned mechanisms that may explain the copious relation underlying obesity and AHR with the help of published reports. A proper understanding of these mechanisms discussed in this review will ensure an appropriate treatment plan for patients through advanced pharmacological interventions.

Aim: The study aimed to examine the association of obesity phenotypes with dental calculus.

Background: Obesity has been recognized as a risk factor for kidney and gallbladder stones formation and periodontitis.

Objective: We have investigated the association between obesity, metabolic risk factors, and dental calculus, which is a sequela following periodontitis.

Methods: This study included 5,281 military members, aged 19-45 years, without antihypertensive medications in Taiwan. Obesity was defined as body mass index ≥27.5 kg/m², and metabolic syndrome (MetS) was defined according to the modified ATP III criteria. Supragingival calculus in any teeth, except for impacted teeth and the third molar, was the outcome of interest. Multiple linear regression analysis with adjustments for age, sex, toxic substance use, brushing teeth frequency, and blood leukocyte counts, was used to determine the association of obesity with dental calculus numbers. Multiple logistic regression analysis was used to assess the association between obesity with or without MetS and the presence of any dental calculus.

Results: BMI was positively correlated to dental calculus numbers [β and confidence intervals (CI) = 0.023 (0.014, 0.032)]. Compared to the obesity(-)/MetS(-) group, there were dosedependent associations for the obesity(-)/MetS(+), obesity(+)/MetS(-), and obesity(+)/MetS(+) groups with the presence of any dental calculus [odds ratios (ORs): 1.08 (0.76, 1.53), 1.31 (1.08, 1.58), and 1.51 (1.20, 1.90), respectively]. Of the metabolic risk factors, abdominal obesity and hypertension were independently associated with dental calculus [ORs: 1.33 (1.13, 1.55) and 1.30 (1.11, 1.52), respectively].

Conclusion: This study suggests general obesity as an independent risk factor for dental calculus formation, and MetS, particularly the components of abdominal obesity, and hypertension may also increase the prevalence of dental calculus. Diet control and regular exercise might be preventive measures for the development of both obesity and dental calculus.

Mitochondria are essential organelles for the survival of a cell because they produce energy. The cells that need more mitochondria are neurons because they perform a variety of tasks that are necessary to support brain homeostasis. The build-up of abnormal proteins in neurons, as well as their interactions with mitochondrial proteins, or MAM proteins, cause serious health issues. As a result, mitochondrial functions, such as mitophagy, are impaired, resulting in the disorders described in this review. They are also due to mtDNA mutations, which alter the heritability of diseases. The topic of disease prevention, as well as the diagnosis, requires further explanation and exploration. Finally, there are treatments that are quite promising, but more detailed research is needed.

Introduction: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people, causing the COVID-19 global pandemic. The use of novel technologies led to the development of different types of SARS-CoV-2 vaccines that have reduced severe disease courses and related deaths. Besides the positive impact of vaccination on the pandemic, local and systemic side effects have been reported; they are usually mild to moderate, although also serious adverse events have been described.

Case presentation: A 21-year-old female was referred to our hospital for the recent onset of severe polyuria and polydipsia, with the need for about 8 liters of daily water intake. The symptoms developed seven days after the administration of the second dose of the mRNA-based (Pfizer-BioNTech^® BNT162b2) SARS-CoV-2 vaccine. In the suspicion of central diabetes insipidus (DI) development, she started treatment with desmopressin (Minirin^® tablets) 60 mg/day with an improvement of symptoms and thirst. A thickening of the pituitary stalk was observed at the pituitary MRI with loss of the posterior pituitary bright spot on T1 weighted images. To confirm the diagnosis of central DI, both the water deprivation test and arginine stimulated copeptin test were performed; whilst the former gave no clear-cut indication of DI, the latter showed a reduced copeptin peak after arginine infusion consistent with the diagnosis of partial central DI. Furthermore, the development of symptoms right after the second dose of the vaccine strengthened the hypothesis that DI was related to the vaccination itself. After our evaluation, there was a progressive reduction of desmopressin dose to a complete discontinuation with the maintenance of a normal hydroelectrolytic balance. Clinical and biochemical follow-up was performed by repeating a pituitary MRI and a second arginine-stimulated copeptin test 15 months after the diagnosis. This time, copeptin levels reached a significantly higher peak after arginine stimulation that completely excluded central DI and at pituitary MRI, the thickening of the pituitary stalk previously described was no longer visible.

Conclusion: Neurohypophysitis can have an abrupt onset independently of the etiology. Central DI is a rather exceptional event after SARS-CoV-2 vaccination but should be recalled in case of sudden polyuria and polydipsia. DI is indeed reported even after SARS-CoV-2 infection, thus, this report should not discourage the use of mRNA-based vaccines. Furthermore, our case demonstrates that full recovery of posterior pituitary function is possible after immunization with anti-Covid-19 BNT162b2 vaccine. Further studies are needed to clarify the possible mechanism relating to SARS-CoV-2 vaccination and this rare adverse event.

Background: Obesity-linked insulin resistance (IR) is an important risk factor for metabolic diseases, and anthropometric indices are commonly used for risk assessment.

Aim: The study aimed to assess possible differences between women and men in the predictive value and association of nine obesity indices with IR, as assessed by HOMA-IR, in a nondiabetic adult population.

Methods: The cross-sectional study included individuals recruited from a hospital in Mexico City. Indices evaluated were waist circumference (WC), hip circumference (HC), body mass index (BMI), waist-to-hip ratio, waist-to-height ratio, visceral adiposity index, body adiposity index (BAI), relative fat mass (RFM), and conicity index (CI). Fasting plasma glucose and insulin were measured to calculate HOMA-IR. Correlation analysis was performed between obesity indices and HOMA-IR. Receiver operating characteristics curve analyses were performed to determine predictive accuracy and cut-off values of obesity indices for IR. A binary logistic regression (BLR) analysis with OR calculation was performed to determine the strength of association with HOMA-IR.

Results: We included 378 individuals (59% females, mean age 46.38 ±12.25 years). The highest Pearson coefficient value was observed for BMI among women, while among men, the highest values were found for BMI and BAI. WC among women, and BAI and RFM among men showed the highest sensitivity, while the highest specificity was observed for WHR among women and WC among men with respect to insulin prediction. In the adjusted BLR model, BMI, WC, and WHR among women and WC and RFM and BAI among men were independently associated with IR, showing the highest odds ratio (OR).

Conclusion: In Mexican adults, WC, WHR, RFM and BAI could be complementary tools for BMI in screening for IR.

Background: Kidney stones and thyroid disease are two common diseases in the general population, with multiple common risk factors. The associations between kidney stones and thyroid disease are unclear.

Aim: This study aims to assess the association between 'once had a thyroid disease' and the odds of kidney stones.

Methods: Adult participants from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 with reliable kidney stone and thyroid disease data were included. Adjusting for age, gender, race, education level, and marital status, diabetes, hypertension, gout, angina pectoris, stroke, and asthma, logistic regression was used to examine the relationship between kidney stones and thyroid illness.

Results: Using stratified analysis, the association between thyroid illness and kidney stones was investigated further. Among the participants, 4.9% had kidney stones, and 10.1% had thyroid disease. Kidney stone was associated with thyroid disease (OR=1.441, (95% CI:1.294-1.604), p <0.01), which remained significant (OR=1.166, (95% CI:1.041-1.305), p <0.01) after adjustments with age, gender, race, education level and marital status, diabetes, hypertension, gout, angina pectoris, stroke, and asthma. Stratified by blood lead, blood cadmium, and blood urea nitrogen levels in the human body, the odds of kidney stones still increased with once having a previous thyroid disease.

Conclusions: In this large nationally representative survey over 10 years, kidney stone was strongly associated with thyroid disease. In this cross-sectional study, we explored the association between thyroid disease and kidney stones, which may help clinicians intervene in them early.

Background: This study aimed to assess the diagnostic capability of insulin surrogate measurements in identifying individuals with metabolic syndrome (MetS) and propose applicable indices derived from fasting values, particularly in large study populations.

Methods: Data were collected from the datasets of the Surveillance of Risk Factors of NCDs in Iran Study (STEPS). MetS was defined based on the National Cholesterol Education Program (NCEP) criteria. Various insulin surrogate indices, including Homeostasis Model Assessment (HOMA), Quantitative Insulin Sensitivity Check Index (QUICKI), Fasting glucose to insulin ratio (FGIR), Reynaud, Reciprocal insulin, McAuley, Metabolic Score for Insulin Resistance (METS-IR), Triglyceride-glucose index (TyG), TG/ HDL-C, TG/ BMI, and TG/ WC ratio were assessed. Receiver Operating Characteristic (ROC) curves were used to assess pathologic conditions and determine the optimal cut-off through the highest score of the Youden index. Also, Area Under the Curve (AUC) values were established for each index totally and according to sex, age, and BMI differences.

Results: The study population consisted of 373 individuals (49.9% women; 75.1% middle age, 39.1% obese, and 27.3% overweight), of whom 117 (31.4%) had MetS. The METS-IR (AUC: 0.856; 95% CI: 0.817-0.895), TG/ HDL-C (AUC: 0.820; 95% CI: 0.775-0.886), TyG (AUC: 0.808; 95% CI: 0.759-0.857), and McAuley (AUC: 0.804; 95% CI: 0.757-0.852) indices provided the greatest AUC respectively for detection of MetS. The values of AUC for all the indices were higher in men than women. This trend was consistent after data stratification based on BMI categories, middle age, and senile individuals.

Conclusion: The present study indicated that indices of insulin, including METS-IR, TG/HDLC, TyG, and McAuley, have an equal or better capacity in determining the risk of MetS than HOMA-IR, are capable of identifying individuals with MetS and may provide a simple approach for identifying populations at risk of insulin resistance.