Metabolic Disorders Research Articles

Vasoactive Intestinal Peptide (VIP) and its Receptors in Adipose Tissue: Implications for Cold Stress Adaptation.

Adipose tissue represents an organ that is highly dynamic and contributes toward vital survival events such as immune responses, lactation, metabolism fuel, and thermogenesis. Data emerging from recent studies support the notion of adipose tissue being organized into a complex system characterized by a discrete anatomy, elevated physiological plasticity, and specific vascular and nerve supplies. Vasoactive intestinal peptide (VIP), along with its receptors, type 1 (VPAC1) and type 2 (VPAC2), has been implicated in various physiological and pathophysiological processes. However, studies on VIP and its receptors in adipose tissue are limited. To explore VIP's presence and activity, as well as its adipose tissue-based receptors, we conducted a study on isolated adipocytes and adipose tissue from inguinal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT) in normal and cold-stressed rats. Our findings indicate the presence of the gene expression VIP and VPAC1 in both WAT and BAT under normal conditions, while VPAC2 was absent. In both WAT and BAT, cold exposure upregulated VIP gene expression. However, the response of VIP receptors to cold exposure is controversial. VPAC2 gene expression was induced in both WAT and BAT, while VPAC1 gene expression presented no change of significance in BAT and a slight reduction in WAT. Additionally, VIP, VPAC1, and VPAC2 proteins were identified from Western blot studies on white and brown adipocytes. After exposure to cold there was an increase of significance in the VIP, VPAC1, and VPAC2 protein levels. This study provides novel insights into how VIP and its receptors alter gene expression and protein levels in adipose tissue and adipocytes during cold stress, indicating their potential involvement in adipose tissue regulation. The findings propose VIP's potentially crucial role in adipose tissue's adaptation to cold stress by affecting the metabolic and biochemical functions of subcutaneous and interscapular adipocytes, with potentially significant implications in the context of developing therapies targeting metabolic disorders.

Effectiveness of flaxseed consumption and fasting mimicking diet on anthropometric measures, biochemical parameters, and hepatic features in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): a randomized controlled clinical trial.

Although benefits of flaxseed and fasting mimicking diet (FMD), each alone, have been shown in the management of metabolic dysfunction-associated steatotic liver disease (MASLD), the benefit of combining the two is not clear. This study aimed to investigate the effect of the combination of FMD and flaxseed supplementation on surrogate measures of MASLD. The present study was conducted as a randomized, parallel, open-label controlled clinical trial on a hundred patients with MASLD for 12 weeks. Eligible participants were assigned to four groups including control group (lifestyle modification recommendations); flaxseed group (30 g/day of flaxseed powder consumption); FMD group (16 h of fasting per day), and combination of FMD with flaxseed. Changes in anthropometric parameters, serum levels of lipids, glycemic measures, High-sensitivity C-reactive protein (hs-CRP), and liver enzymes, and hepatic steatosis and fibrosis by transient elastography were assessed. Serum triglycerides, total cholesterol, fasting blood glucose and insulin, hs-CRP and liver enzymes decreased in all intervention groups. Hepatic steatosis score decreased in the intervention groups, but not significantly in comparison to the control group. Hepatic fibrosis score decreased significantly in the intervention groups compared to control. Our data indicate that the combination of FMD with flaxseed consumption is not superior to either of the interventions alone in the management of MASLD.

Occupational stress trajectories and metabolic dysfunction-associated steatotic liver disease among female nurses: a prospective Cohort Study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prominent cause of chronic liver disease, and occupational stress may serve as a potential risk factor. This study aims to assess the association between occupational stress trajectories and incident MASLD among Chinese female nurses. We conducted a prospective longitudinal study using data from the Nurse' Health Cohort Study, involving 1,113 female nurses, free of MASLD at baseline (2018). Occupational stress was measured using the Chinese Nurse Job Stress Scale at four time points. Group-based trajectory modeling was used to identify distinct stress trajectories. Through doctors' diagnoses, we assessed incident MASLD over a subsequent 6-year period from 2019 to 2024. Cox proportional hazards regression models evaluated the association of stress trajectories and MASLD risk, adjusting for demographics, work-related factors, and medical conditions. During follow-up, 256 nurses reported incident physician-diagnosed MASLD. Three occupational stress trajectories were identified: moderate decreasing (36.4%), moderate stable (55.9%), and moderate increasing (7.7%). Participants in the moderate increasing stress trajectory had a significantly higher risk of developing MASLD (adjusted HR: 3.14, 95% CI: 2.19-4.49, p < .001) compared to those in the moderate stable trajectory. This association between stress trajectory and MASLD risk was not modified by age or BMI (pinteraction>0.50). The study concludes that increasing stress levels over time are associated with a higher incidence of MASLD. These findings underscore the importance of stress management interventions in reducing the risk of MASLD progression. Further research is needed to explore the underlying mechanisms and to develop targeted strategies for stress reduction in clinical settings.

Circulating microRNA panels in subjects with metabolic dysfunction-associated steatotic liver disease after following a 2-year dietary intervention.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) affects one-third of the global population. Despite its high prevalence, there is a lack of minimally non-invasive diagnostic methods to assess this condition. This study explores the potential of circulating microRNAs (miRNAs) as diagnostic biomarkers for MASLD after a 2-year nutritional intervention. Fifty-five subjects with steatosis (MASLD group) from the Fatty Liver in Obesity (FLiO) study (NCT03183193) were analyzed at baseline and after 6, 12 and 24 months. Participants were classified into two groups: those who still had steatosis after the intervention (unhealthy group) and those in whom steatosis had disappeared (healthy group). Hepatic status was evaluated through magnetic resonance imaging (MRI), ultrasonography, elastography and serum transaminases. Circulating miRNA levels were measured by RT-PCR. The dietary intervention was able to modulate the expression of circulating miRNAs after 6, 12, and 24 months. Logistic regression analyses revealed that the most effective panels for diagnosing whether MASLD has disappeared after the nutritional intervention included miR15b-3p, miR126-5p and BMI (AUC 0.68) at 6 months, miR29b-3p, miR122-5p, miR151a-3p and BMI (AUC 0.85) at 12 months and miR21-5p, miR151a-3p and BMI at 24 months (AUC 0.85). Circulating miRNAs were useful in predicting MASLD in subjects with overweight or obesity after following a weight-loss oriented nutritional intervention. These findings highlight the potential role of miRNAs in diagnosing MASLD and underscore the importance of precision nutrition in managing and determining MASLD. Trial registration number: NCT03183193 (www. gov).

Acute tear versus chronic-degenerated rotator cuff pathologies are associated with divergent tendon metabolite profiles

ABSTRACT Purpose/Aim Metabolic disorders are risk factors for rotator cuff injuries, which suggests that the rotator cuff is sensitive to local metabolic fluctuations. However, the link between the metabolic microenvironment and pathologic features of acute tear versus chronic degeneration is currently unknown. The overarching goal of this study was to evaluate alterations in tendon metabolite profiles following acute tear or chronic degeneration of the rotator cuff. We hypothesized that injury types (acute tear vs. chronic degeneration) would result in distinct metabolite profiles relative to clinically unaffected tendon controls. Materials and Methods We utilized untargeted metabolomics to identify pathways that were altered at the time of rotator cuff repair (RCR; acute tear) or reverse total shoulder arthroplasty (rTSA; chronic degeneration) relative to total shoulder arthroplasty controls (TSA; tendon clinically unaffected). Results Acute tears to the rotator cuff were associated with an overall decrease in tendon metabolites. This global decrease was primarily associated with glycolic acid and decreased tricarboxylic acid (TCA) cycle activity. Conversely, chronic tendon specimens from patients undergoing rTSA showed an overall increase in metabolites. Most notably, chronic injury was associated with increased levels of multiple amino acids including alanine, aspartate, lysine, and proline. Conclusions Overall, this study demonstrates that distinct metabolite profiles are associated with injury types, and that therapeutic strategies should address both cellular and matrix components regardless of injury induction. The specific pathways identified paired with validated, established, treatment methods may serve as novel therapeutic targets for patients who suffer from rotator cuff injuries.

Unlocking the promise of MANF in diseases: Mechanistic insights and therapeutic potentials.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a ubiquitous neurotrophic factor that exhibits a variety of physiological functions and plays a critical role in the exploitation of therapeutic potential across a range of diseases, including cardiovascular disorders, nervous system diseases, metabolic imbalances, and cancers. In the context of cardiac diseases, MANF significantly promotes cardiomyocyte survival and improves cardiac functionality. Furthermore, MANF not only provides neuroprotection by shielding neurons from damage and promoting nerve regeneration in neurological disorders, but also involves in insulin resistance, lipid metabolism disturbances and fat-containing liver lesions. However, the oncogenic or tumor suppressive function of MANF in cancer remains unclear, requiring further investigation to elucidate its precise role in the process of cancer initiation and progression. This review aims to summarize the latest advancements in understanding the molecular pathways, intricate mechanisms, and therapeutic potential of MANF in the prevention and treatment of various diseases, emphasizing its multifaceted contributions to health and disease management.

Effects of multidisciplinary therapy on energy balance, inflammation, and metabolic diseases in adolescents with obesity: A narrative review.

Obesity is a consequence of multiple factors, including genetics, lifestyle and nutritional choices, physical activity, sleep duration, screen time, and mood disorders. These behavioral elements can impair the regulation of energy balance and obesity management that link obesity to a constellation of chronic conditions that lead to a high prevalence of cardiometabolic risk factors, metabolic syndrome, and nonalcoholic fatty liver disease. Multidisciplinary therapy is defined as an approach delivered by a multidisciplinary-trained health team covering at least two components of behavior, physical activity/exercise, dietary habits, and/or psychological counseling associated with clinical interventions. This narrative review summarizes the effects of multidisciplinary therapy on neuroendocrine regulation of energy balance, inflammatory biomarkers, cardiometabolic risk factors, metabolic syndrome, nonalcoholic fatty liver diseases, behavior, and quality of life. We found that multidisciplinary therapy, including medical, nutritional, exercise, and behavioral counseling, and/or education, was useful for addressing outcomes such as visceral adiposity, neuroendocrine regulation of energy balance, inflammatory biomarkers, cardiometabolic risk factors, nonalcoholic fatty liver disease, and metabolic syndrome. The effects were mediated by improvements in neuroendocrine regulation of energy balance, downregulation of the pro-inflammatory states, and a reduction in comorbidities. Multidisciplinary therapy also improved mood disorders and quality of life.

Neem seed oil ameliorates diabetic phenotype by suppressing redox imbalance, dyslipidaemia and pro-inflammatory mediators in a rodent model of type 2 diabetes.

The neem plant (Azadirachta indica) has popular ethnomedicinal applications. The anti-diabetic potential and mechanism of neem seed oil (NSO) in a rodent model of type 2 diabetes mellitus was evaluated in the present study. Experimentally-induced diabetic animals were administered NSO (200 and 400 mg/kg) or metformin (150 mg/kg) orally for 30 days, with some animals serving as positive and negative controls. NSO significantly (p < .05) reversed diabetes-induced impaired glucose metabolism, dyslipidaemia, and oxido-inflammatory imbalances typified by changes in the NADH/NAD+ ratio (p < .001) and increases in the mRNA or protein levels of C-reactive protein, 4-hydroxynonenal, and pro-inflammatory cytokines (TNF-α and Il-1β) among others in the hepatic or pancreatic tissues of diabetic animals. The histological evaluation of the pancreatic tissue corroborated the protective effect of NSO. The findings showed that the antidiabetic effect of NSO proceeded through its hypolipidemic effect and modulation of redox and inflammatory signalling events in the tissues of animals.

Uric Acid-HDL Ratio as Predictor of Major Cardiovascular Events in Very High Cardiovascular Risk Patients Treated with High-Intensity Statin Therapy

Introduction: Uric acid levels are positively correlated with cardiovascular disease. High Density Lipoprotein (HDL) cholesterol plays a role in suppressing blood oxidation reactions and protecting vascular endothelial cells. The combination of these two metabolic parameters, the Uric Acid-HDL Ratio (UHR) makes it a very useful predictor marker for metabolic disorders. Statins are known to be the gold standard for raising HDL cholesterol. Some types of statins are also known to reduce serum uric acid levels by involving pleiotropic actions. The aim of this study was to determine baseline UHR as a predictor of MACE after administration of high-intensity statins.Objectives: The Objective of this study was to determine baseline UHR as a predictor of MACE after administration of high-intensity statins.Methods: This study was conducted at the cardiac center of Dr Zainal Abidin Regional General Hospital. This study is an observational study with a prospective cohort design. The target population was patients classified as patients with very high cardiovascular risk and using consecutive sampling techniques.Results: During the study period, a total of 82 patients with ischemic heart disease with very high cardiovascular risk met the inclusion and exclusion criteria. Of these, 49 patients (59.8%) were identified as having major cardiovascular events (MACE) while the remaining 33 patients (40.2%) did not had MACE. The results of this study are that statin therapy may not significantly affect the uric acid-HDL ratio in the context of major cardiovascular events.Conclusions: The uric acid-HDL ratio had no significant predictive ability for major cardiovascular events in patients with very high cardiovascular risk who were treated with high-intensity statin therapy.

Association between subjective walking speed and metabolic diseases in individuals with obesity: a cross-sectional analysis.

The association between subjective walking speed and metabolic diseases has received limited attention, particularly in individuals with obesity. We aimed to clarify this association using comprehensive health checkup data of participants with obesity. In total, 8578 individuals with a body mass index ≥ 25.0kg/m2, 9626 individuals with waist circumference ≥ 85cm in men and ≥ 90cm in women, and 6742 individuals who met both criteria of body mass index and waist circumference were included in this cross-sectional analysis. Subjective walking speed was investigated using the question "Is your walking speed faster than the speed of those of your age and sex?" in a health examination questionnaire. Metabolic diseases were defined according to the guidelines for each disease, and modified Poisson regression analyses were performed. In the model adjusted for age and sex, individuals with obesity based on body mass index and fast subjective walking speed showed significantly lower risk of diabetes mellitus (risk ratio [RR] 0.70; 95% CI 0.63-0.77) and dyslipidemia (RR 0.97; 95% CI 0.94-1.00). Similarly, among those with obesity based on waist circumference and both body mass index and waist circumference, fast subjective walking speed showed a significant negative association with hypertension (RR 0.94; 95% CI 0.90-0.97 and RR 0.95; 95% CI 0.92-0.99, respectively), diabetes mellitus (RR 0.70; 95% CI 0.64-0.77 and RR 0.70; 95% CI 0.63-0.77, respectively), and dyslipidemia (RR 0.96; 95% CI 0.94-0.99 and RR 0.96; 95% CI 0.94-0.99, respectively). Thus, among individuals with obesity, the odds of metabolic diseases were lower if their subjective walking speed was fast. This study contributes to earlier prevention of the cascade of diseases that begin with obesity.

Single cell-spatial transcriptomics and bulk multi-omics analysis of heterogeneity and ecosystems in hepatocellular carcinoma.

This study profiled global single cell-spatial-bulk transcriptome landscapes of hepatocellular carcinoma (HCC) ecosystem from six HCC cases and a non-carcinoma liver control donor. We discovered that intratumoral heterogeneity mainly derived from HCC cells diversity and pervaded the genome-transcriptome-proteome-metabolome network. HCC cells are the core driving force of taming tumor-associated macrophages (TAMs) with pro-tumorigenic phenotypes for favor its dominant growth. Remarkably, M1-types TAMs had been characterized by disturbance of metabolism, poor antigen-presentation and immune-killing abilities. Besides, we found simultaneous cirrhotic and HCC lesions in an individual patient shared common origin and displayed parallel clone evolution via driving disparate immune reprograms for better environmental adaptation. Moreover, endothelial cells exhibited phenotypically conserved but executed differential functions in a space-dependent manner. Further, the spatiotemporal traits of rapid recurrence niche genes were identified and validated by immunohistochemistry. Our data unravels the great significance of HCC cells in shaping vibrant tumor ecosystems corresponding to clinical scenarios.

Associations of Metabolic Dysfunction-Associated Fatty Liver Disease With Peripheral Artery Disease: Prospective Analysis in the UK Biobank and ARIC Study.

There is currently limited evidence comparing the association between metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic fatty liver disease (NAFLD), and the risk of peripheral artery disease (PAD). This study aims to analyze the associations of MAFLD and NAFLD with incident PAD. Two longitudinal studies, the UKB (UK Biobank) study (n=372 216) and the ARIC (Atherosclerosis Risk in Communities) study (n=4681), categorized participants into MAFLD/non-MAFLD groups and NAFLD/non-NAFLD groups. Subsequently, participants were classified into 4 groups: non-fatty liver disease, MAFLD-only, NAFLD-only, and both MAFLD and NAFLD groups. Cox proportional hazard model estimated associations of MAFLD/NAFLD status, subtypes, and liver fibrosis severity with PAD risk. The MAFLD group had a higher risk of incident PAD compared with the non-MAFLD group, and similarly, the NAFLD group had a higher risk compared with the non-NAFLD group. Among these 4 groups, the MAFLD-only group had the strongest association with the risk of incident PAD, while the NAFLD-only group was not independently associated. Diabetic MAFLD subtype was significantly associated with increased PAD risk, and higher level of liver fibrosis scores correlated with elevated PAD risk. Both MAFLD and NAFLD are significantly associated with an increased incidence of PAD, with stronger associations in MAFLD and diabetic MAFLD population. These findings emphasize that the need for screening and prevention strategies for PAD in this high-risk population is warranted. The assessment of MAFLD and its subtypes should be considered as an integral component of cardiovascular risk assessment.

Ethanol extract of cassia seed alleviates metabolic dysfunction-associated steatotic liver disease by acting on multiple lipid metabolism-related pathways

Abstract Background and objective In northern China’s cold regions, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) exceeds 50%, significantly higher than the national and global rates. MASLD is an important risk factor for cardiovascular and cerebrovascular diseases, including coronary heart disease, stroke, and tumors, with no specific therapeutic drugs currently available. The ethanol extract of cassia seed (CSEE) has shown promise in lowering blood lipids and improving hepatic steatosis, but its mechanism in treating MASLD remains underexplored. This study aims to investigate the therapeutic effects and mechanisms of CSEE. Methods MASLD models were established in male Wistar rats and golden hamsters using a high fat diet (HFD). CSEE (10, 50, 250 mg/kg) was administered via gavage for six weeks. Serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), as well as liver TC and TG, were measured using biochemical kits. Histopathological changes in the liver were evaluated using Oil Red O staining, Hematoxylin-eosin (H&amp;E) staining, and transmission electron microscopy (TEM). HepG2 cell viability was assessed using the cell counting kit-8 (CCK8) and Calcein-AM/PI staining. Network pharmacology was used to analyze drug-disease targets, and western blotting was used to confirm these predictions. Results CSEE treatment significantly reduced serum levels of TC, TG, LDL-C, ALT, and AST, and improved liver weight, liver index, and hepatic lipid deposition in rats and golden hamsters. In addition, CSEE alleviated free fatty acid (FFA)-induced lipid deposition in HepG2 cells. Molecular biology experiments demonstrated that CSEE increased the protein levels of p-AMPK, p-ACC, PPARα, CPT1A, PI3K P110 and p-AKT, while decreasing the protein levels of SREBP1, FASN, C/EBPα, and PPARγ, thus improving hepatic lipid metabolism and reducing lipid deposition. The beneficial effects of CSEE were reversed by small molecule inhibitors of the signaling pathways in vitro. Conclusion CSEE improves liver lipid metabolism and reduces lipid droplet deposition in Wistar rats and golden hamsters with MASLD by activating hepatic AMPK, PPARα, and PI3K/AKT signaling pathways.

Association Between Metabolic Disorders and Cognitive Domains in Community-Dwelling Older Adults

ABSTRACT Objectives evaluate the association between Metabolic Syndrome (MetS) and cognitive performance (global and in each domain) in community-dwelling older adults. Methods cross-sectional study with 544 participants (≥60 years). Cognition was assessed using the Cognitive Abilities Screening Instrument – Short (CASI-S), evaluating four domains: memory, orientation, executive function, recall. MetS was identified considering five components: abdominal obesity, diabetes, hypertriglyceridemia, low HDL, and hypertension. Mann–Whitney test and Poisson regression models adjusted for age and education were used to assess the differences in cognition scores. Results Hypertensive participants had lower global cognition, and those with hypertriglyceridemia had lower memory scores; obese individuals reached lower executive function and higher recall scores. Diabetes was associated with worse recall in men, and low HDL to lower memory scores; hypertensive women had worse recall. In adjusted models, association between abdominal obesity, executive function and recall (total sample) remained significant (p = .003 and p = .048, respectively). Conclusions Global cognition was not associated to metabolic disorders, but obesity was associated to lower executive function and higher recall. Clinical Implications Assessing each cognitive domain may be more sensitive in subjects with MetS components, and interaction between components, sex and education also must be considered to establish adequate care strategies for the older adults.

Recent advances in the toxicological effects of difenoconazole: A focus on toxic mechanisms in fish and mammals.

The toxicological study of pesticides at sub-lethal and environment-relevant concentrations has become increasingly crucial for human and environmental health. Toxic mechanisms of agrochemicals contribute to discovering green pesticides, assessing the hazards of pesticides comprehensively, and supporting legitimate regulatory decisions. However, the toxicological effects of difenoconazole are not yet fully understood despite being frequently detected in fruits, vegetables, waters, and soils and posing hazards to humans and the environment. This lack of knowledge could lead to flawed risk assessment and administrative oversight. Thus, the review aimed to provide some investigation perspectives for clarifying the toxicological effects of difenoconazole by synthesizing the toxic data of difenoconazole on various organisms, such as bees, Daphnia magna, fish, earthworms, mammals, and plants and summarizing the toxicological mechanisms of difenoconazole, especially in fish and mammals from peer-reviewed publications. Evidence revealed that difenoconazole caused multiple toxicological effects, including developmental toxicity, reproductive toxicity, endocrine disruption effects, neurotoxicity, and transgenerational toxicity. The toxic mechanisms involved in metabolic disturbance, oxidative stress, inflammation, apoptosis, and autophagy by activating reactive oxygen species-mediated signaling pathways and mitochondrial apoptosis routes, disturbing amino acids, lipid, and nucleotide metabolism, and regulating gene transcription and expression in mammals and fish. Based on the review, further studies better focus on the toxic differences of difenoconazole stereoisomers, the toxicological effects of transformation products of difenoconazole, and the mechanism of action of difenoconazole on sex-specific endocrine disruption effects, intestinal damage, and gut dysbacteriosis for its hazard assessment and management synthetically.

Prevalence of cardiometabolic outcomes in women who underwent salpingo-oophorectomy to prevent hereditary breast and ovarian cancer: a meta-analysis.

Risk reduction salpingo-oophorectomy (RRSO) is usually performed in women with hereditary breast and ovarian cancer (HBOC) syndrome for BRCA1 and BRCA2 gene mutation carriers, resulting in surgical menopause, which is more associated with a high risk of cardiovascular and metabolic disease than in premenopausal and natural menopausal women. This study assessed the prevalence of cardiovascular and metabolic outcomes in women who underwent salpingo-oophorectomy as a preventive measure against HBOC. This meta-analysis assessed prevalence rates for four metabolic/cardiovascular conditions: myocardial infarction, hypertension, hypercholesterolemia, and type 2 diabetes mellitus. DerSimonian and Laird random-effects models were applied to all analyses, with 95% confidence interval (CI). Heterogeneity was assessed with I². We used OpenMeta Analyst software for statistical analysis. A total of five retrospective studies and one observational study involving 1,320 patients were included. The average body mass index (BMI) was 25.97kg/m2 and the average waist circumference was 87.94cm. The analysis across a mean 4.94-year follow-up revealed prevalence rates for acute myocardial infarction of 1.5% (95% CI 0.3-2.7; P = 0.077; I²=56.25%), hypertension of 28% (95% CI 6.9-49.1; P < 0.001; I2 = 98.42%), hypercholesterolemia of 27.2% (95% CI 6.8-47.6; P < 0.001; I²=98.67%), and type 2 diabetes mellitus of 3.3% (95% CI 1.1-5.5; P < 0.001; I²=82.44%). Our findings suggest that there is no marked increase in cardiovascular risk among women with HBOC undergoing RRSO.

The regulatory effects of bioactive polysaccharides on intestinal function and bile acids: chemical structures, bioactivities, and mechanisms

Polysaccharides are one of the important components of the human diet, offering a wide range of biological activities, especially in improving inflammation in the digestive system and addressing metabolic diseases. Among all the reported bioactivities of polysaccharides, their regulation effects on intestinal function and bile acids (BAs) are gradually attracting the attention of more researchers. Bile acids, the main components of intestinal lipid digestive fluid, are also key signal factors for metabolic homeostasis and impact overall health. Polysaccharides usually interact directly or indirectly with the gut and gut microbiota to participate in the regulation process of reabsorption, metabolism, and excretion of bile acids in humans, thereby exerting their role in the intervention of human diseases. In this review, we comprehensively reviewed the effects of bioactive polysaccharides on the regulation of intestinal function and bile acids. The chemical structures, bioactivities, and potential mechanisms for their activities were also reviewed. This study aimed to provide a comprehensive reference for future research on the activities and mechanisms of polysaccharides, as well as to offer important strategies and insights for the development of bioactive polysaccharides to prevent inflammatory and metabolic diseases.

Study on gut microbiota and metabolomics in postmenopausal women.

Menopausal syndrome, occurring during the menopausal stage in women, manifests as symptoms stemming from decreased estrogen levels, such as hot flashes, insomnia, mental disorders (anxiety, depression), and osteoporosis. The bulk of studies have indicated alterations in the gut microbiota of those experiencing menopause syndrome compared to healthy women. However, This article focuses on the alterations in gut microbiota in perimenopausal women. Our study utilized 16s rRNA sequencing to determine the differences in the gut microbiota and metabolites among 44 menopausal syndrome women. The distribution of gut microbiota in postmenopausal women varies based on the level of follicle stimulating hormone, with changes in gut microbiota abundance taking precedence over symptom onset. Fecal metabolites reveal changes in several metabolites, including Amino acid metabolism (Tyrosine, Tryptophan), Lipid metabolism (Alpha linolenic acid metabolism), and other metabolites. Disturbances in lipid metabolism, triggered by hormonal level fluctuations, can contribute to the development of osteoporosis.

The dopamine hypothesis for ADHD: An evaluation of evidence accumulated from human studies and animal models

Multiple lines of evidence indicate that altered dopamine signaling may be involved in neuropsychiatric disorders and common behavioral traits. Here we critically review evidence collected during the past 40-plus years supporting the role of dopamine dysfunction in attention deficit hyperactivity disorder (ADHD). We recapitulate the basic components of dopaminergic signaling in the central nervous system, focusing on core enzymes, transporters and receptors involved in monoaminergic functions, particularly in striatal and cortical regions. We summarize key human brain imaging and genetic studies reporting associations between dopaminergic neurotransmission and behavioral traits, with an emphasis on ADHD. We also consider ADHD in the context of animal models and single gene, metabolic, and neurological disorders with established dysfunction of the dopaminergic system. Examining the evidence in this way leads us to conclude that there is evidence for the involvement of dopamine but limited evidence for a hypo-dopaminergic state per se as a key component of ADHD. We propose a path forward to increase our understanding of dopamine signaling in human behavioral traits and disorders that should particularly focus on its role in clinical subgroups, during brain development and how it interacts with other neurotransmitter systems.

Exam quality of ultrasound and dynamic contrast-enhanced abbreviated MRI and impact on early-stage HCC detection.

MRI is a potential alternative to ultrasound for hepatocellular carcinoma (HCC) detection. We evaluated the impact of ultrasound and dynamic abbreviated MRI (AMRI) exam quality on early-stage HCC detection. We conducted a multicenter case-control study among patients with cirrhosis (cases with early-stage HCC per Milan Criteria; controls without HCC) who underwent both a liver ultrasound and dynamic contrast-enhanced (DCE) AMRI within 6 months in 2012-2019. Two radiologists performed independent, blinded interpretations of both exams for HCC detection and scored exam quality as no/mild, moderate, or severe limitations. Associations between exam quality, patient characteristics, and HCC detection were assessed by odds ratios (OR). Of 216 cases and 432 controls, severe limitations were reported in 7% and 8% of ultrasounds and DCE-AMRIs, respectively. Severe limitations at ultrasound were associated with obesity (OR 2.08, 95%CI [1.32-3.32]) and metabolic dysfunction-associated steatotic liver disease (MASLD) (OR 1.98 [1.12-3.44]) but not for DCE-AMRI. Decompensated cirrhosis (Child-Pugh C) was associated with severe limitations for both ultrasound (OR 2.54 [1.37-4.58]) and DCE-AMRI (OR 3.96 [2.36-6.58]). Compared to exams with no/mild limitations, exams with severe limitations had lower sensitivity for ultrasound (79.6% vs. 21.7%, P < 0.001) and AMRI (86.1% vs. 50.0%, P = 0.001). In patients in whom ultrasound was severely limited, DCE-AMRI had significantly higher odds of early-stage HCC detection than ultrasound (OR 8.23 [1.25-54.02]). HCC detection by DCE-AMRI may be preferred in patients with severe limitations at ultrasound due to obesity and MASLD. Both modalities remain limited for patients with decompensated cirrhosis, for whom alternative strategies may be needed.