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Aim: The cardio-ankle vascular index (CAVI) is a new evaluation indicator for arteriosclerosis. This study investigated the relationship between the CAVI and lipid levels in patients with hypertension in a real clinical environment. Methods: This descriptive study enrolled 2,656 patients (male/female: 1,016/1,640) from the Outpatient Department of Vascular Medicine of Peking University Shougang Hospital and Jinding Street Community Health Service Center. CAVI was measured using a VaseraVS-1000 vascular screening system (Fukuda Denshi, Tokyo, Japan). Results: Age, body mass index (BMI), waist circumference, hip circumference, CAVI, systolic blood pressure (SBP), diastolic blood pressure (DBP), creatinine, fasting plasma glucose (FPG), uric acid (UA), hypersensitive C-reactive protein (hs-CRP), homocysteine, HbA1c, and triglyceride (TG) were significantly higher in the hypertension group than in the non-hypertension group. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were significantly lower in the hypertension group than in the non-hypertension group. The CAVI value was significantly higher in patients with hypertriglyceridemia and normal LDL-C than in those with normal TG and hyper-LDL-C. Age, waist circumference, UA, FPG, HDL-C, hs-CRP, HbA1c, BMI, SBP, and DBP were independently associated with CAVI in all patients. Beta blockers were negatively correlated with CAVI (β = –0.411, P = 0.011). Sex (male) and history of hypertension and diabetes mellitus were positively correlated with CAVI (β = 0.419, P < 0.001; β = 0.247, P = 0.011; β = 0.638, P < 0.001; respectively). Conclusions: The CAVI was significantly higher in patients with hypertension and exhibited differences based on sex. Although we did not find a significant correlation between CAVI and TG, it remains crucial to maintain blood pressure to prevent the development of arteriosclerosis.

Aim. To analyze the relationship between metabolic disorders and obesity with hemodynamic parameters and the severity of the condition of patients with chronic thromboembolic pulmonary hypertension (CTEPH) based on the POLET register. Materials and methods. The study included patients with CTEPH from the POLET register. Data from medical history, lipid profile, glycemia, uric acid level, weight, height, functional class (FC), distance in the 6-minute walk test (6MWT), echocardiography, and right heart catheterization were used for analysis. Results. The study included 84 patients 60±14 years old, including 45 men. The majority of patients had FC III – 51 (65%), which corresponded to 6MWT – 338±113 m. Nineteen (23%) people had experience in taking PAH specific therapy, 37 (46%) had cardiovascular comorbidity. In the general group, the body mass index (BMI) was 25.7±4.5 kg/m2, and normal glycemia, lipid profile, and uric acid levels were also determined. mPAP was 51±12 mmHg, RA area was 25.5 (20; 30) cm2. Correlations were identified between: RA area and the level of total cholesterol (r=0.60; p0.01), triglycerides (r=-0.24; p0.001), LDL cholesterol (r=0.75; p=0.04), uric acid (r=0.75; p=0.03); total cholesterol and 6MWT (r=0.44; p=0.04). Analysis of metabolic disorders, FC and comorbidity revealed differences between FC III and IV groups in the level of HDL cholesterol (p=0.02) and triglycerides (p0.01). Conclusion. The POLET registry includes mainly older patients. Severe FC (87% – III and IV) may be a result of the older age and the presence of concomitant pathology in almost half of the patients. The discovered relationships between the area of RA and FC with lipid and purine metabolism were discovered for the first time, however, they correspond to the direction of the world scientific researches, are important due to the use of these indicators in the scale for calculating the risk of death in patients with PAH and require further development.

Abstract In recent decades, a global shift in lifestyle and the ubiquitous consumption of junk foods have led to dysbiosis and other metabolic disorders significantly impacting human health. Recent studies performed on traditional foods have shown several health benefits and have gained the attention of the scientific community towards ethnic foods. In this regard, the consumption of ethnic foods with symbiotic properties is increasing gradually across the globe. Kefir is one such ethnic food with excellent functional properties. It is a unique traditional fermented drink comprised of kefir grains and probiotic microbes. Kefir grains are a gelatinous consortium of casein, milk solids coupled with yeasts, and lactobacilli-rich microbiota embedded in a poly-saccharide matrix. These components act as starters, initiating fermentation when introduced into fresh milk. This beverage bestows a myriad of symbiotic benefits, encompassing improved gut health and preventing several metabolic and other diseases through various biological mechanisms. Despite its millennia-long history, it has recently gained prominence due to emerging biotechnological and nutraceutical applications and researchers’ burgeoning fascination. In this comprehensive review, we endeavour to provide a meticulous elucidation of the most recent advancements concerning kefir, encompassing its production and processing methodologies for both dairy and water kefir. Furthermore, we delve into the intricate mechanisms underlying its functional properties and the health benefits of kefir as a functional fermented beverage.

Abstract Peroxisomes are dynamic organelles involved in various cellular processes, including lipid metabolism, redox homeostasis, and intracellular metabolite transfer. Accumulating evidence suggests that peroxisomal homeostasis plays a crucial role in human health and disease, particularly in metabolic disorders and ferroptosis. The abundance and function of peroxisomes are regulated by a complex interplay between biogenesis and degradation pathways, involving peroxins, membrane proteins, and pexophagy. Peroxisome-dependent lipid metabolism, especially the synthesis of ether-linked phospholipids, has been implicated in modulating cellular susceptibility to ferroptosis, a newly discovered form of iron-dependent cell death. This review discusses the current understanding of peroxisome homeostasis, its roles in redox regulation and lipid metabolism, and its implications in human diseases. We also summarize the main mechanisms of ferroptosis and highlight recent discoveries on how peroxisome-dependent metabolism and signaling influence ferroptosis sensitivity. A better understanding of the interplay between peroxisomal homeostasis and ferroptosis may provide new insights into disease pathogenesis and reveal novel therapeutic strategies for peroxisome-related metabolic disorders and ferroptosis-associated diseases.

Abstract The world is facing a global nutrition crisis, as evidenced by the rising incidence of metabolic disorders such as obesity, insulin resistance and chronic inflammation. Skeletal muscle is the largest tissue in humans and plays an important role in movement and host metabolism. Muscle fibre formation occurs mainly during the embryonic stage. Therefore, maternal lifestyle, especially nutrition and exercise during pregnancy, has a critical influence on foetal skeletal muscle development and the subsequent metabolic health of the offspring. In this review, the influence of maternal obesity, malnutrition and micronutrient intake on foetal skeletal muscle development is systematically summarized. We also aim to describe how maternal exercise shapes foetal muscle development and metabolic health in the offspring. The role of maternal gut microbiota and its metabolites on foetal muscle development is further discussed, although this field is still in its ‘infancy’. This review will provide new insights to reduce the global crisis of metabolic disorders and highlight current gaps to promote further research.

Senescence-associated secretory phenotype (SASP) is an important feature of cellular senescence and plays an important role in regulating the disease microenvironment. At present, the role of SASP in intervening bone metabolism and inducing bone loss is very limited. Therefore, this paper discusses the regulatory mechanism of SASP in osteoporosis models and summarizes its regulatory characteristics: SASP is fully expressed in senescent bone cells and transmits aging effects to mesenchymal stem cells in an autocrine/paracrine manner, thereby interfering with osteogenic differentiation. SASP activates immune cells and promotes their aging, thus inducing the formation of inflammatory tissue microenvironment and aggravating bone loss. Mitochondrial homeostasis, pathologic hyperglycemia, and obesity-induced fat accumulation all promote SASP expression, thus disrupting microenvironmental homeostasis and transmitting aging effects to bone tissue. To sum up, understanding the role of SASP in osteoporosis lays a solid foundation for us to develop anti-SASP therapy for osteoporosis in the future.

Objective: To evaluate the effect of asiaticoside on streptozotocin (STZ) and nicotinamide (NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats. Methods: Asiaticoside (50 and 100 mg/kg body weight) was administered to STZ-NAD-induced diabetic rats for 45 days, and its effects on hyperglycaemic, carbohydrate metabolic, and insulin signaling pathway markers were examined. Results: Asiaticoside increased insulin production, lowered blood glucose levels, and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities. Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity. Furthermore, asiaticoside upregulated the mRNA expressions of IRS-1, IRS-2, and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal. Conclusions: Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis, gluconeogenesis, and insulin signaling pathways.

Abstract Lactoferrin is a natural multifunctional glycoprotein with potential antidepressant-like effects. However, the mechanism of its antidepressant effect has not been explored from the perspective of gut flora metabolism. Therefore, we employed both 16S rDNA gene sequencing and LC–MS metabolomics analysis to investigate the regulatory effects and mechanisms of lactoferrin in a rat model of depression. After one week of acclimatization, twenty-four 7-week-old male Sprague–Dawley rats were randomly and equally assigned into three groups: the control group, the model group, and the lactoferrin intervention group. The control group rats were housed under standard conditions, while the rats in the model and lactoferrin intervention groups were individually housed and exposed to chronic unpredictable mild stress for 44 days simultaneously. The lactoferrin intervention group was provided with water containing 2% lactoferrin (2 g/100 ml). Behavioural tests were conducted at week 7. Upon completion of the behavioral tests, the rats were anesthetized with isoflurane, humanely euthanized using a rat guillotine, and tissue samples were collected for further experiments. The results indicated that lactoferrin intervention led to an increase in sucrose solution consumption, horizontal movement distance, number of cross platforms, and residence time in the target quadrant. Additionally, it resulted in an increase in jejunal tight junction protein ZO-1 expression and a suppression of serum expression of inflammatory factors, Lipopolysaccharide and Diamine oxidase. In summary, lactoferrin can regulate the metabolic disorder of intestinal flora, reduce intestinal permeability, and further regulate the metabolic balance of hippocampal tissues through the microbiota-gut-brain axis. This process ultimately alleviates the depression-like behavior in rats.

Sjögren’s disease (SjD) is a systemic autoimmune disorder characterized by dry eyes and mouth caused by chronic inflammation and is often accompanied by various extra-glandular manifestations, including fatigue and diffuse pain. Although the pathogenesis of the disease remains elusive, several factors (e.g. environmental, genetic and hormonal factors, abnormal metabolic status) are associated with this condition. Accumulating evidence suggests a potential role of cholesterol metabolism in immune and non-immune modulation in various diseases. In this review, we summarize the current findings on the associations between cholesterol metabolism and SjD.

In gestational diabetes mellitus (GDM), adipose tissue undergoes metabolic disturbances and chronic low-grade inflammation. Alternative polyadenylation (APA) is a post-transcriptional modification mechanism that generates mRNA with variable lengths of 3' untranslated regions (3'UTR), and it is associated with inflammation and metabolism. However, the role of APA in GDM adipose tissue has not been well characterized. In this study, we conducted transcriptomic and proteomic sequencing on subcutaneous and omental adipose tissues from both control and GDM patients. Using Dapars, a novel APA quantitative algorithm, we delineated the APA landscape of adipose tissue, revealing significant 3'UTR elongation of mRNAs in the GDM group. Omental adipose tissue exhibited a significant correlation between elongated 3'UTRs and reduced translation levels of genes related to metabolism and inflammation. Validation experiments in THP-1 derived macrophages (TDMs) demonstrated the impact of APA on translation levels by overexpressing long and short 3'UTR isoforms of a representative gene LRRC25. Additionally, LRRC25 was validated to suppress proinflammatory polarization in TDMs. Further exploration revealed two underexpressed APA trans-acting factors, CSTF3 and PPP1CB, in GDM omental adipose tissue. In conclusion, this study provides preliminary insights into the APA landscape of GDM adipose tissue. Reduced APA regulation in GDM omental adipose tissue may contribute to metabolic disorders and inflammation by downregulating gene translation levels. These findings advance our understanding of the molecular mechanisms underlying GDM-associated adipose tissue changes.

Aim: To research the dietary habits of pregnant women living in Bulgaria and to assess the possible health effects for the offspring. Methods: An online anonymous survey of the dietary habits of pregnant women living in Bulgaria was conducted. A questionnaire was developed in Google Forms, collecting information about the demographic profile, diet, frequency of consumption of certain food and drink groups, use of alternative dietary patterns, etc. The questionnaire was spread through social media using the snowball technique. The assessment of the respondents' dietary habits was based on the national dietary recommendations during pregnancy. Descriptive analysis of the results was done using Jamovi software statistical package ver. 2.3.0. Results: 117 pregnant women aged between 21 and 54 years (median - 30 years) were interviewed. Daily consumption of milk and dairy products was found in 41% and 47% of respondents, respectively. Among the women surveyed, all were reported to consume dairy products, except 5.1% who did not consume milk. The relative share of women who rarely or never consumed fish was 58.1% and 12%, respectively, and one woman did not consume both fish and meat. Vegetarians accounted for 6% of the women surveyed, and 6% were on a low carbohydrate diet. Conclusion: Although the majority of pregnant women surveyed followed the recommendations for healthy eating, some rarely or never consumed some of the healthy foods, which put them at risk of deficiency or insufficiency of certain nutrients.

Tao He,1,2,&ast; Xiao-Yu Sun,1,2,&ast; Meng-Han Tong,1,2 Ming-Jie Zhang,1,2 Zhi-Jun Duan1,2 1Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Dalian Central Laboratory of Integrative Neuro-Gastrointestinal Dynamics and Metabolism Related Diseases Prevention and Treatment, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Jun Duan, Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian, 161000, People’s Republic of China, Tel +86 83635963, Email cathydoctor@sina.comBackground and Aim: Obesity is association with elevated risks of erosive esophagitis (EE), and metabolic abnormalities play crucial roles in its development. The aim of the study was to assess the association between metabolic obesity phenotypes and the risk of EE.Methods: This retrospective study enrolled 11,599 subjects who had undergone upper gastrointestinal endoscopy at the First Affiliated Hospital of Dalian Medical University from January 1, 2008, to December 31, 2023. The enrolled individuals were grouped into four cohorts based on their metabolic health and obesity profiles, namely, metabolically healthy non-obesity (MHNO; n=2134, 18.4%), metabolically healthy obesity (MHO; n=1736, 15.0%), metabolically unhealthy non-obesity (MUNO; n=4290, 37.0%), and metabolically unhealthy obesity (MUO; n=3439, 29.6%). The relationships of the different phenotypes of metabolic obesity with the risks of developing EE in the different sexes and age groups were investigated by multivariate logistic regression analysis.Results: The MUNO, MHO, and MUO cohorts exhibited elevated risks of developing EE than the MHNO cohort. The confounding factors were adjusted for, and the findings revealed that the MUO cohort exhibited the greatest risk of EE, with odds ratios (ORs) of 5.473 (95% CI: 4.181– 7.165) and 7.566 (95% CI: 5.718– 10.010) for males and females, respectively. The frequency of occurrence of EE increased following an increase in proportion of metabolic risk factors. Subgroup analyses showed that the individuals under and over 60 years of age in the MHO, MUNO, and MUO cohorts exhibited elevated risks of developing EE. Further analysis suggested that obesity has a stronger influence on the risks of developing EE compared to metabolic disorders.Conclusion: Metabolic disorders and obesity are both related with an elevated risk of EE, in which obesity has a potentially stronger influence. Clinical interventions should target both obesity and metabolic disorders to reduce EE risk. Keywords: metabolic obesity phenotype, erosive esophagitis, metabolic disorders

Diabetes Mellitus (DM) presents a significant global health challenge, with escalating prevalence rates and associated morbidity and mortality. Despite medical advancements, the mortality rates continue to rise, necessitating a deeper understanding of the pathophysiology and potential therapeutic targets. Copper, a vital trace element, plays an important role in various metabolic processes and homeostatic functions within the human body. Dysregulation of copper metabolism has been implicated in the pathogenesis and progression of DM, contributing to oxidative stress, insulin resistance, altered glycemic control, and metabolic abnormalities. The present review provides an illustrative overview of the role of copper in DM, elucidating its impact on oxidative stress, insulin resistance, glycemic control, and metabolic disturbances.

Aim. To assess the incidence of glucose metabolism disorders, administered hypoglycemic therapy and its effectiveness in a cohort of patients with previously diagnosed diabetes mellitus (DM) hospitalized for scheduled lower limb joint arthroplasty. Materials and methods. The study included 502 patients. Medical history, information about previously diagnosed DM and prescribed hypoglycemic therapy were collected in all patients according to medical documentation, as well as according to the patients’ survey. Within the preoperative examination, the glucose level was measured, and in patients with previously diagnosed diabetes, measuremaent of the HbA1c level was recommended. Results. The study population included 180 (35.9%) males and 322 females (64.1%). Among them, 99 (19.7%) patients had disorders of glucose metabolism [type 1 diabetes – 1 (0.2%) patient, type 2 diabetes – 90 (17.9%) patients, impaired glucose tolerance (IGT) – 8 (1.6%) patients]. In 8 patients, type 2 diabetes was newly diagnosed during the preoperative examination. HbA1c was measured before hospitalization in 26 patients with diabetes, the mean level was 7.0±1.4%. Regarding the analysis of hypoglycemic therapy, almost half of the patients with DM – 47 (47.5%) – received metformin monotherapy, 8 patients with IGT and 8 patients with newly diagnosed DM did not receive any drug therapy. Target glycemic levels during therapy were achieved in 36 (36.4%) patients, and target HbA1c levels were achieved in 21 patients. Conclusion. The cohort of patients hospitalized for elective lower limb joint arthroplasty is characterized by a relatively high incidence of glucose metabolism disorders, and in some patients, DM was newly diagnosed during the preoperative examination. Metformin is most often used as hypoglycemic therapy, and the target values of glycemia during treatment were achieved in less than half of the patients. The monitoring of the level of glycated hemoglobin is low and requires additional population analysis in order to determine the causes and optimize the strategy of patient management.

Type 2 diabetes mellitus (T2DM) is one of the most common modern “disease of affluence”, characterized by hyperglycemia resulting from defective insulin secretion by pancreatic β cells and/or impaired tissue sensitivity to insulin. In Poland, the incidence of this metabolic disease is 5–8% and is still increasing. The consequences of the development of T2DM include, among others: changes in cardiovascular system, retinopathy, nephropathy and neuropathy. Due to medical progress, it is easier to control glycemia, as well as to predict the occurrence of this disease or the dynamics of its development and consequences. The molecules discussed in the article: growth differentiation factor 15 (GDF-15), mesencephalic astrocyte-derived neurotrophic factor (MANF) and fetuin-A, represent great promise both in the diagnosis and treatment of not only T2DM, but also obesity, which often accompanies T2DM. Most of the studies reported in the literature were performed on animal models, mainly mouse. This article presents arguments supporting the potential usefulness of the above-mentioned paracrine factors for prognostic, diagnostic and therapeutic purposes.

Abstract Myeloid-derived growth factor (MYDGF) is a novel secreted protein with potent antiapoptotic and tissue-repairing properties that is present in nearly 140 human tissues and cell lines, with the highest abundance in the oral epithelium and skin. Initially, MYDGF was found in bone marrow-derived monocytes and macrophages for cardioprotection and repair after myocardial infarction. Subsequent studies have shown that MYDGF plays an important role in other cardiovascular diseases (e.g., atherosclerosis and heart failure), metabolic disorders, renal disease, autoimmune/inflammatory disorders, and cancers. Although the underlying mechanisms have not been fully explored, the role of MYDGF in health and disease may involve cell apoptosis and proliferation, tissue repair and regeneration, anti-inflammation, and glycolipid metabolism regulation. In this review, we summarize the current progress in understanding the role of MYDGF in health and disease, focusing on its structure, function and mechanisms. The graphical abstract shows the current role of MYDGF in different organs and diseases (Fig. 1).

Obesity is a chronic disease that constitutes a global problem and a serious challenge to public health. In the course of this disease, excessive accumulation of fat tissue occurs in the body, which not only leads to an increased risk of health complications, but also negatively affects the quality of life. Fat cells – adipocytes – are responsible for the biosynthesis and release of adipokines, among others, leptin, visfatin, chemerin and omentin-1. They are active biological substances, including mediators of inflammation, which may lead to the development of metabolic disorders in the body. The above-mentioned properties of the described adipokines make it possible to potentially use them as diagnostic and therapeutic factors in the course of obesity and its accompanying disorders such as insulin resistance, type 2 diabetes mellitus, and cardiometabolic complications. Despite significant progress in understanding the role played by the discussed adipokines, further research is necessary to precisely describe the mechanisms of action and to determine the precise relationship between their plasma concentrations and state of diseases.

Abstract Background Various blood metabolites are known to be useful indicators of health status in dairy cattle, but their routine assessment is time-consuming, expensive, and stressful for the cows at the herd level. Thus, we evaluated the effectiveness of combining in-line near infrared (NIR) milk spectra with on-farm (days in milk [DIM] and parity) and genetic markers for predicting blood metabolites in Holstein cattle. Data were obtained from 388 Holstein cows from a farm with an AfiLab system. NIR spectra, on-farm information, and single nucleotide polymorphisms (SNP) markers were blended to develop calibration equations for blood metabolites using the elastic net (ENet) approach, considering 3 models: (1) Model 1 (M1) including only NIR information, (2) Model 2 (M2) with both NIR and on-farm information, and (3) Model 3 (M3) combining NIR, on-farm and genomic information. Dimension reduction was considered for M3 by preselecting SNP markers from genome-wide association study (GWAS) results. Results Results indicate that M2 improved the predictive ability by an average of 19% for energy-related metabolites (glucose, cholesterol, NEFA, BHB, urea, and creatinine), 20% for liver function/hepatic damage, 7% for inflammation/innate immunity, 24% for oxidative stress metabolites, and 23% for minerals compared to M1. Meanwhile, M3 further enhanced the predictive ability by 34% for energy-related metabolites, 32% for liver function/hepatic damage, 22% for inflammation/innate immunity, 42.1% for oxidative stress metabolites, and 41% for minerals, compared to M1. We found improved predictive ability of M3 using selected SNP markers from GWAS results using a threshold of > 2.0 by 5% for energy-related metabolites, 9% for liver function/hepatic damage, 8% for inflammation/innate immunity, 22% for oxidative stress metabolites, and 9% for minerals. Slight reductions were observed for phosphorus (2%), ferric-reducing antioxidant power (1%), and glucose (3%). Furthermore, it was found that prediction accuracies are influenced by using more restrictive thresholds (−log10(P-value) > 2.5 and 3.0), with a lower increase in the predictive ability. Conclusion Our results highlighted the potential of combining several sources of information, such as genetic markers, on-farm information, and in-line NIR infrared data improves the predictive ability of blood metabolites in dairy cattle, representing an effective strategy for large-scale in-line health monitoring in commercial herds.

Abstract Background Obesity is a metabolic syndrome where allelic and environmental variations together determine the susceptibility of an individual to the disease. Caloric restriction (CR) is a nutritional dietary strategy recognized to be beneficial as a weight loss regime in obese individuals. Preconceptional parental CR is proven to have detrimental effects on the health and development of their offspring. As yet studies on maternal CR effect on their offspring are well established but paternal CR studies are not progressing. In current study, the impact of different paternal CR regimes in diet-induced obese male Wistar rats (WNIN), on their offspring concerning metabolic syndrome are addressed. Methods High-fat diet-induced obese male Wistar rats were subjected to caloric restriction of 50% (HFCR-I) and 40% (HFCR-II) and then they were mated with normal females. The male parent’s reproductive function was assessed by sperm parameters and their DNMT’s mRNA expression levels were also examined. The offspring’s metabolic function was assessed by physiological, biochemical and molecular parameters. Results The HFCR-I male parents have shown reduced body weights, compromised male fertility and reduced DNA methylation activity. Further, the HFCR-I offspring showed attenuation of the AMPK/SIRT1 pathway, which is associated with the progression of proinflammatory status and oxidative stress. In line, the HFCR-I offspring also developed altered glucose and lipid homeostasis by exhibiting impaired glucose tolerance & insulin sensitivity, dyslipidemia and steatosis. However, these effects were largely mitigated in HFCR-II offspring. Regarding the obesogenic effects, female offspring exhibited greater susceptibility than male offspring, suggesting that females are more prone to the influences of the paternal diet. Conclusion The findings highlight that HFCR-I resulted in paternal undernutrition, impacting the health of offspring, whereas HFCR-II largely restored the effects of a high-fat diet on their offspring. As a result, moderate caloric restriction has emerged as an effective weight loss strategy with minimal implications on future generations. This underscores the shared responsibility of fathers in contributing to sperm-specific epigenetic imprints that influence the health of adult offspring.

Abstract In the present scenario, obesity is a challenging health problem and its prevalence along with comorbidities are on the rise around the world. Ingestion of fish becomes trendy in daily meals. Recent research has shown that marine fish oil (FO) (found in tuna, sardines, and mackerel) may offer an alternative method for reducing obesity and problems associated with it. Marine FO rich in long‐chain omega‐3 polyunsaturated fatty acids (LC n‐3 PUFA) and long‐chain omega‐6 polyunsaturated fatty acids (LC n‐6 PUFA) plays an important role in reducing abnormalities associated with the metabolic syndrome and has a variety of disease‐fighting properties, including cardioprotective activity, anti‐atherosclerotic, anti‐obesity, anti‐cancer, anti‐inflammatory activity. Studies in rodents and humans have indicated that LC n‐3 PUFA potentially elicit a number of effects which might be useful for reducing obesity, including suppression of appetite, improvements in circulation, enhanced fat oxidation, energy expenditure, and reduced fat deposition. This review discusses the interplay between inflammation and obesity, and their subsequent regulation via the beneficial role of marine FO, suggesting an alternative dietary strategy to ameliorate obesity and obesity‐associated chronic diseases.

As medical research advances and technology rapidly develops, auricular acupuncture has emerged as a point of growing interest. This paper delves into the intricate anatomy of auricular points, their significance and therapeutic principles in traditional Chinese medicine (TCM), and the underlying mechanisms of auricular acupuncture in contemporary medicine. The aim is to delve deeply into this ancient and mysterious medical tradition, unveiling its multi-layered mysteries in the field of neurostimulation. The anatomical structure of auricular points is complex and delicate, and their unique neurovascular network grants them a special status in neurostimulation therapy. Through exploration of these anatomical features, we not only comprehend the position of auricular points in TCM theory but also provide a profound foundation for their modern medical applications. Through systematic review, we synthesize insights from traditional Chinese medical theory for modern medical research. Building upon anatomical and classical theoretical foundations, we focus on the mechanisms of auricular acupuncture as a unique neurostimulation therapy. This field encompasses neuroregulation, pain management, psychological wellbeing, metabolic disorders, and immune modulation. The latest clinical research not only confirms the efficacy of auricular stimulation in alleviating pain symptoms and modulating metabolic diseases at the endocrine level but also underscores its potential role in regulating patients’ psychological wellbeing. This article aims to promote a comprehensive understanding of auricular acupuncture by demonstrating its diverse applications and providing substantial evidence to support its broader adoption in clinical practice.

The worldwide surge in obesity and associated metabolic disorders is emerging as a significant public health issue for societies and healthcare systems. Available evidence has shown that alterations in the gut microbiota could be implicated in the pathogenesis of obesity and associated disorders. A healthy gut microbiome is characterized by richness and high microbial diversity. Gut microbiota affect how the host responds to diet, and conversely, the host may modify the gut microbiota through changes in dietary habits. Diet can impact and alter the composition, diversity, and species richness of the gut microbiota over time. An unhealthy diet, high in fat and sugar, may lead to decreased microbial diversity, reduced synthesis of metabolites that maintain gut permeability, damage to the mucus layer, increased bacterial translocation and lipopolyssacharide which can trigger endotoxemia, chronic subclinical inflammation and metabolic disorders. Currently, the impact of diet on gut microbial composition and its involvement in the pathogenic mechanisms underlying metabolic disorders is one of the most promising areas of research in nutrition. This special issue has gathered original research articles in topics related to diet patterns, gut microbiota, obesity and associated metabolic disorders as well as brief reports, reviews and perspectives in the wider field of translational and clinical metabolic research. In particular, the aim of this Special Issue was to present evidence connecting gut microbiota with metabolic disorders, explore the underlying mechanisms of this association, and examine how diet patterns may influence this relationship.

Nonketotic hyperglycinemia (NKH) is a rare, autosomal recessive metabolic disorder usually associated with mutations in genes AMT, GLDC or GCSH involved in the glycine cleavage complex. Other genes have been linked with less severe NKH, associated with deficiency of lipoate cofactor such as GLRX5, LIAS, BOLA3. We identified a new case of GLRX5-mediated NKH who presented at 2-month with severe developmental delay and seizures. The initial suspicion was raised by the MRI and then confirmed by glycine measurements in cerebrospinal fluid and blood. Genetic analysis revealed a previously undescribed homozygous variant in the GLRX5 gene [NM_016417.3:c.367G>C; p. (Asp123His)]. Despite medication and supportive care, he died at the age of 4 months after a sudden neurological deterioration. It was decided to limit therapeutic interventions due to the severity of the prognosis. The case was more severe than the previous GLRX5-mediated NKH described, regarding the early age at onset and the severity. Moreover, the genetic variant was located at a potentially crucial site for glutathione binding in the GLRX5 protein. This report, thereby, expands our understanding of NKH’s genetic underpinnings and phenotypic variability, highlighting the crucial role of GLRX5 and other related genes in variant NKH.

Microbial interactions are widespread and important processes that support the link between disease and microbial ecology. The gut microbiota is a major source of microbial stimuli that can have detrimental or beneficial effects on human health. It is also an endocrine organ that maintains energy homeostasis and host immunity. Obesity is a highly and increasingly prevalent metabolic disease and the leading cause of preventable death worldwide. An imbalance in the gut microbiome is associated with several diseases including obesity-related metabolic disorders. This review summarizes the complex association between the gut microbiome and obesity-associated metabolic diseases and validates the role and mechanisms of ecological dysregulation in the gut in obesity-associated metabolic disorders. Therapies that could potentially alleviate obesity-associated metabolic diseases by modulating the gut microbiota are discussed.

PurposeOur study utilizes Mendelian Randomization (MR) to explore the causal relationships between a range of risk factors and preeclampsia, a major contributor to maternal and perinatal morbidity and mortality.MethodsEmploying the Inverse Variance Weighting (IVW) approach, we conducted a comprehensive multi-exposure MR study analyzing genetic variants linked to 25 risk factors including metabolic disorders, circulating lipid levels, immune and inflammatory responses, lifestyle choices, and bone metabolism. We applied rigorous statistical techniques such as sensitivity analyses, Cochran’s Q test, MR Egger regression, funnel plots, and leave-one-out sensitivity analysis to address potential biases like pleiotropy and population stratification.ResultsOur analysis included 267,242 individuals, focusing on European ancestries and involving 2,355 patients with preeclampsia. We identified strong genetic associations linking increased preeclampsia risk with factors such as hyperthyroidism, BMI, type 2 diabetes, and elevated serum uric acid levels. Conversely, no significant causal links were found with gestational diabetes, total cholesterol, sleep duration, and bone mineral density, suggesting areas for further investigation. A notable finding was the causal relationship between systemic lupus erythematosus and increased preeclampsia risk, highlighting the significant role of immune and inflammatory responses.ConclusionThis extensive MR study sheds light on the complex etiology of preeclampsia, underscoring the causal impact of specific metabolic, lipid, immune, lifestyle, and bone metabolism factors. Our findings advocate for a multidimensional approach to better understand and manage preeclampsia, paving the way for future research to develop targeted preventive and therapeutic strategies.

Newborn Screening (NBS) is one of the most significant and successful public health initiatives globally. Implemented in various capacities across most developed countries, NBS programs vary in scope and focus, with the most comprehensive screening for over 50 conditions. In Slovenia, NBS is a vital component of the public health system, initiated in 1979 with screenings for phenylketonuria. The program has evolved and expanded with the introduction of new technologies such as mass spectrometry for metabolic diseases and immunoreactive and genetic tests for conditions like cystic fibrosis, spinal muscular atrophy, and primary immune deficiencies. Dried blood spots on filter paper facilitate easy transportation to the University Children’s Hospital Ljubljana for the analysis. Professional sample collection by maternity ward staff ensures sample quality, which is critical for successful laboratory testing. Participation in the program is universal for all newborns, with an option for parental refusal. Hundreds of Slovenian newborns have been successfully diagnosed and treated, underscoring the program’s importance. With the advent of new medicines and therapies, the scope of NBS is set to expand. The program’s success relies on the synergy between participating groups - maternity hospitals, the pediatric clinic, and the laboratory.

Abstract Background Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood. Method Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene–exposure dataset. The 14 clinical factors were categorized into three groups: metabolic laboratory markers, blood pressure, and the MetS diagnostic factors. The causal relationship between metabolic factors and PTB were analyzed using two-sample Mendelian Randomization (MR). Additionally, the direct effects on the risk of PTB were investigated through multivariable MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test. Results According to the two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. According to the multivariable MR, HDL-C (IVW: OR 2.798, 95% CI 1.484–5.274, P = 0.001), LDL (IVW: OR 4.027, 95% CI 1.140–14.219, P = 0.03) and TG (IVW: OR 2.548, 95% CI 1.269–5.115, P = 0.009) were positively correlated with the occurrence of PTB. TC (OR 0.131, 95% CI 0.028–0.607, P = 0.009) was negatively correlated with the occurrence of PTB. We selected BMI, DM, HDL-C, SBP, and TG as the diagnostic factors for metabolic syndrome. DM (IVW, OR 1.219, 95% CI 1.040–1.429 P = 0.014) and HDL-C (IVW, OR 1.380, 95% CI 1.035–1.841, P = 0.028) were directly correlated with the occurrence of PTB. Conclusions This MR study demonstrated that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.

Abstract Background Maintaining good health is vital not only for own well-being, but also to ensure high-quality patient care. The aim of this study was to evaluate the prevalence of dyslipidaemia and to determine the factors responsible for the development of this disorder among Polish nurses. Lipid profile disorders are the most prevalent and challenging risk factors for the development of cardiovascular disease. Nurses have significant potential and play a crucial role in providing care and treatment services. Methods This cross-sectional study involved nurses and included measurements of body weight composition (Tanita MC-980), body mass index, waist circumference, blood pressure (Welch Allyn 4200B), lipid profile, and fasting blood glucose (CardioChek PA). Results The results revealed that more than half of the nurses (60.09%) were overweight or obese, with 57.28% exhibiting elevated blood pressure, 32.25% having fasting glucose levels, and 69.14% experiencing dyslipidaemia. Multiple model evaluation using ROC curves demonstrated that multiple models accurately predicted hypercholesterolemia (AUC = 0.715), elevated LDL (AUC = 0.727), and elevated TC (AUC = 0.723) among Polish nurses. Conclusion Comprehensive education programmes should be implemented that include the latest advances in cardiovascular disease prevention. Regular check-ups, as well as the promotion and availability of healthy food in hospital canteens, are essential.

Introduction: Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, typically inherited as a recessive trait, is a genetic condition predominantly observed in Central and Eastern Europe, with birth prevalence in Poland amounting to 1/118,336. In most European countries, e.g., in Poland since 2014, this disorder is included in newborn screening. Case Presentation: This paper presents the ophthalmic symptoms of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency in three pediatric patients. Visual acuity testing, fundus photography, and optical coherence tomography (OCT) were performed and data were collected over several years (2017–2022). In case 1, a female born in 2010, exhibited abnormalities in the central part of the posterior pole, mainly in the macula, and included choriocapillaris atrophy and severe disruption of the outer retinal layer. Case 2, a female born in 2012, presented with progressive shortsightedness and choroid atrophy documented with angio-OCT. Case 3, a male born in 2013, experienced recurrent hospitalizations due to metabolic decompensations and presented with mild myopia, thinning of the choroid layer, and slight pigment dispersion with macular sparing. Conclusion: The main ophthalmic symptoms of LCHAD deficiency were choroidal atrophy, disorganization of the outer retinal layer, and myopia. Choroidal atrophy and pigment dispersion were consistently the earliest signs of LCHAD-associated chorioretinopathy. Although the progression of chorioretinopathy in each case resulted from metabolic decompensation, one documented case revealed that not every metabolic crisis results in ophthalmological changes. Nonetheless, strict adherence to a low-fat, high-carbohydrate diet remains crucial to prevent gradual deterioration and vision loss.

Abstract Background In the present systematic review and meta-analysis, the association of maternal exposure to the endocrine disrupting chemicals (EDCs) with cardio-metabolic risk factors in children during childhood for the first time. Method The PubMed, Scopus, EMBASE, and Web of Science databases were systematically searched, up to Feb 2023. In total 30 cohort studies had our inclusion criteria. A random-effects model was used for the variables that had considerable heterogeneity between studies. The Newcastle–Ottawa Scale (NOS) tool was used to classify the quality score of studies. All statistical analyses were conducted using Stata 14 and P-value

Abstract As one of the most attractive next‐generation probiotics, mucin‐degrading Akkermansia muciniphila has emerged as an essential and integral factor in maintaining human health and affecting pathological outcomes. Its abundance is inversely associated with various metabolic diseases (e.g., obesity and type 2 diabetes), cardiovascular diseases, and intestinal inflammation. Supplementing A. muciniphila to restore the gut microbiota ecosystem is a promising approach for treating metabolic disorders. However, the direct utilization of this probiotic is limited by technological and regulatory hurdles, such as the in vitro bulk culture of A. muciniphila and the need for expensive animal‐derived materials. Therefore, enrichment of A. muciniphila using nutraceutical supplements is a feasible strategy. Dietary supplements, especially medicinal herbs, offer a vast and valuable resource as potential prebiotics for promoting the growth of A. muciniphila in the gut, ensuring reliable safety and efficacy. In this study, we first systemically reviewed the dietary substances and medicinal foods known to promote A. muciniphila from over 100 literature sources, aiming to establish a candidate basis for future exploration of prebiotics targeting A. muciniphila. Furthermore, we summarized and discussed the major regulatory factors and mechanisms responsible for the beneficial effect of A. muciniphila on metabolic disorders, hoping to open up exciting directions for in‐depth research on the pharmacological mechanism of A. muciniphila and pave the way for its clinical therapeutics.

Abstract Background Children with various metabolic disorders are considered a high-risk group for different developmental delays. Delayed language development (DLD) and autism spectrum disorder (ASD) have a common incidence in children with metabolic disorders which negatively impact their social and academic life. So, early assessment of this high-risk group for the presence of DLD and/or ASD is of great significance and providing better prognosis through starting therapy as early as possible. Aim of the work It aims to detect the presence of DLD and ASD among children with metabolic disorders. Methods This is an analytical (observational) cross-sectional study. The subjects of this study comprised a convenient sample of 100 children diagnosed as having different metabolic disorders with age range between 24 and 48 months. The Modified Preschool Language Scale, Fourth Edition–Arabic version and the Childhood Autism Rating Scale were applied for all children, to detect the presence of DLD and ASD. Results Assessment of 100 children with unequal distribution of 13 types of metabolic disorders found that 86% of cases had DLD and 16% had ASD. Regarding different metabolic disorders, we found both DLD and ASD in nine types and only DLD in four types of metabolic disorders. Conclusion Children with metabolic disorders are at a high risk for DLD and ASD. Early detection of these cases provides early intervention and better outcome.

Jianmei Lu,1,2,&ast; Yongzhu Zeng,1,&ast; Huashuai Zhong,1 Wei Guo,1 Yuyan Zhang,1 Wanting Mai,3 Yucui Qin,4 Xiaodan Su,3 Bo Zhang,5 Weisen Wu,1 Yu Zhu,1 Qiujie Huang,6 Yong Ye1,7– 9 1Department of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China; 2The Second Nanning People’s Hospital, Nanning, People’s Republic of China; 3The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 4Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 5Scientific Research Center, Guilin Medical University, Guilin, People’s Republic of China; 6Department of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China; 7Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Nanning, People’s Republic of China; 8Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening, Nanning, People’s Republic of China; 9Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Education Department, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiujie Huang, Department of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China, Email hqj8@163.com Yong Ye, Department of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China, Email yong-ye@163.comBackground and Purpose: Nitidine chloride (NC) is a botanical drug renowned for its potent anti-inflammatory, antimalarial, and hepatocellular carcinoma-inhibiting properties; however, its limited solubility poses challenges to its development and application. To address this issue, we have devised a colon-targeted delivery system (NC-CS/PT-NPs) aimed at modulating the dysbiosis of the gut microbiota by augmenting the interaction between NC and the intestinal microbiota, thereby exerting an effect against nonalcoholic fatty liver disease.Methods: The NC-CS/PT-NPs were synthesized using the ion gel method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behavior of the NC-CS/PT-NPs were characterized. Furthermore, the impact of NC-CS/PT-NPs on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice was investigated through serum biochemical analysis, ELISA, and histochemical staining. Additionally, the influence of NC-CS/PT-NPs on intestinal microbiota was analyzed using 16S rDNA gene sequencing.Results: The nanoparticles prepared in this study have an average particle size of (255.9± 5.10) nm, with an encapsulation rate of (72.83± 2.13) % and a drug loading of (4.65± 0.44) %. In vitro release experiments demonstrated that the cumulative release rate in the stomach and small intestine was lower than 22.0%, while it reached 66.75% in the colon. In vivo experiments conducted on HFD-induced NAFLD mice showed that treatment with NC-CS/PT-NPs inhibited weight gain, decreased serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and lipid levels, improved liver and intestinal inflammation, and altered the diversity of gut microbiota in mice.Conclusion: This study provides new evidence for the treatment of NAFLD through the regulation of gut microbiota using active ingredients from traditional Chinese medicine.Keywords: nanoparticles, colonic targeting, metabolic disorders, gut microbiota

Abstract Determination of long COVID requires ruling out alternative diagnoses, but there has been no report on the features of alternative diagnoses. This study was a single-center retrospective study of outpatients who visited our clinic between February 2021 and June 2023 that was carried out to determine the characteristics of alternative diagnoses in patients with post-COVID-19 symptoms. In a total of 731 patients, 50 patients (6.8%) were newly diagnosed with 52 diseases requiring medical intervention, and 16 (32%) of those 50 patients (2.2% of the total) were considered to have priority for treatment of the newly diagnosed disorders over long COVID treatment. The proportion of patients with a new diagnosis increased with advance of age, with 15.7% of the patients aged 60 years or older having a new diagnosis. Endocrine and metabolic diseases and hematological and respiratory diseases were the most common, being detected in eight patients (16%) each. Although 35 of the 52 diseases (67%) were related to their symptoms, endocrine and metabolic diseases were the least associated with specific symptoms. Other disorders that require attention were found especially in elderly patients with symptomatic long COVID. Thus, appropriate assessment and differentiation from alternative diagnoses are necessary for managing long COVID.

Yuanli Ai,1,&ast; Kun Peng,2,&ast; Chunli Li,1,&ast; Jun Zhang,1 Gang Wang,3,4 Bin Wang,1 Enyi Huang3,4 1Institute of Life Sciences, College of Basic Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Medical and Pharmaceutical College, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education College of Stomatology, College of Stomatology, Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Wang; Enyi Huang, Email bwang@cqmu.edu.cn; enyihuang@hospital.cqmu.edu.cnIntroduction: Bone, a pivotal structural organ, is susceptible to disorders with profound health implications. The investigation of gene expression in bone tissue is imperative, particularly within the context of metabolic diseases such as obesity and diabetes that augment the susceptibility to bone fractures. The objective of this study is to identify a set of internal control genes for the analysis of gene expression.Methods: This study employs reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) to assess gene expression in bone tissue. We selected fourteen housekeeping genes and assessed their stability in the cortical bone of mouse models for obesity and diabetes using four well-established algorithms (GeNorm, BestKeeper, NormFinder, and the comparative Delta Ct method).Results and Conclusion: We identified Rpl13a as the mostly stably expressed reference gene in cortical bone tissue from mouse models of obesity and diabetes (db/db), while Gapdh was found to be the most stable reference gene in another diabetes model, KKAy mice. Additionally, Ef1a, Ppia, Rplp0, and Rpl22 were identified as alternative genes suitable for normalizing gene expression in cortical bone from obesity and diabetes mouse models. These findings enhance RT-qPCR accuracy and reliability, offering a strategic guide to select reference gene for studying bone tissue gene expression in metabolic disorders.Keywords: reference genes, Rpl13a, Gapdh, cortical bone, metabolic disorders

Background and aim: Phytoformulation therapy is a pioneering strategy for the treatment of metabolic disorders and related diseases. The aim of the present study was to investigate the protective effect of a phytoformulation consisting of hydroxycitric acid and capsaicin against obesity-related cardiomyopathy. Experimental procedure: Sprague-Dawley rats were fed HFD for 21 weeks, and phytoformulation (100 mg/kg body weight) was administered orally for 45 days starting at week 16. Results and conclusion: We found that HFD supplementation resulted in significant hyperglycemia and caused an increase in cardiac lipid deposition, inflammation and apoptosis in the heart. Phytoformulation therapy not only significantly decreased blood levels of glucose, cholesterol, triglycerides, free fatty acids, and inflammatory cytokines in obese rats, but also protected cardiac tissue, as shown by histological analysis. Conversely, phytoformulation therapy decreased mRNA levels for sterol regulatory element-binding factor 1, fatty acid synthase, acetyl-CoA carboxylase, and fatty acid binding protein 1 genes involved in fatty acid synthesis and absorption in obese rats. It increased the levels of lysosomal acid lipase, hormone-sensitive lipase, and lipoprotein lipase genes involved in fatty acid degradation in the heart. In addition, the phytoformulation improved cardiac inflammation and apoptosis by downregulating the genes nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB), tumour necrosis factor α, interleukin-6, toll-like receptor-4 (TLR-4), BCL2-associated X and caspase-3. In conclusion, our results show that the phytoformulation improved insulin sensitivity and attenuated myocardial lipid accumulation, inflammation, and apoptosis in the heart of HFD-induced obese rats by regulating fatty acid metabolism genes and downregulating NF-kB/TLR-4/caspase-3.

Environmental exposure to heavy metals, particularly lead (Pb) and nickel (Ni), is implicated in chronic metabolic diseases, including diabetes mellitus (DM). This cross-sectional study assessed the Pb and Ni levels in groundwater using ICP-OES and urine samples collected from 2688 participants using ICP-MS. We aimed to establish the associations between Pb and Ni exposure and risk factors for DM and metabolic disorders. Groundwater analysis revealed the elevated levels of total dissolved solids, electrical conductivity, hardness, turbidity, Ni, and Pb, exceeding the WHO guidelines. The mean concentration of Pb in groundwater samples of study area was 0.025 mg/L which was higher than the WHO permissible limit of 0.01 mg/L. Similarly the mean concentration of Ni in groundwater samples of study area was 0.038 mg/L which was also higher than the WHO permissible limit of 0.02 mg/L. In human study, participants, categorized into Pb-detected and Ni-detected groups, exhibited significantly higher Pb and Ni levels and non-exposed non-diabetic groups. Ni-detected diabetics showed elevated Ni levels compared to non-exposed non-diabetics. Similarly, Pb-detected diabetics showed elevated Pb levels compared to non-exposed non-diabetics. These findings suggest a potential contribution of Pb and Ni exposure to DM development. The study also identified associations between heavy metal exposure and disruptions in various biomarkers related to DM, lipid profile, inflammation, oxidative stress, liver function, and kidney function. Pb-detected diabetics demonstrated elevated levels of glycemic index biomarkers, including fasting blood glucose (P

Chronic kidney disease (CKD) with high morbidity and mortality all over the world is characterized by decreased kidney function, a condition which can result from numerous risk factors, including diabetes, hypertension and obesity. Despite significant advances in our understanding of the pathogenesis of CKD, there are still no treatments that can effectively combat CKD, which underscores the urgent need for further study into the pathological mechanisms underlying this condition. In this regard, animal models of CKD are indispensable. This article reviews a widely used animal model of CKD, which is induced by adenine. While a physiologic dose of adenine is beneficial in terms of biological activity, a high dose of adenine is known to induce renal disease in the organism. Following a brief description of the procedure for disease induction by adenine, major mechanisms of adenine-induced CKD are then reviewed, including inflammation, oxidative stress, programmed cell death, metabolic disorders, and fibrillation. Finally, the application and future perspective of this adenine-induced CKD model as a platform for testing the efficacy of a variety of therapeutic approaches is also discussed. Given the simplicity and reproducibility of this animal model, it remains a valuable tool for studying the pathological mechanisms of CKD and identifying therapeutic targets to fight CKD.

This retrospective study aimed to evaluate the metabolic and biochemical abnormalities in children with nephrocalcinosis to identify its important risk factors and better understand the disease pathophysiology. Data were collected from the medical records of 163 children diagnosed with nephrocalcinosis. Their clinical and laboratory characteristics at admission were recorded, and a 24-hour urinalysis was performed to measure parameters such as calcium, oxalate, citrate, uric acid, magnesium, and cystine. Family history of kidney stones and parental consanguinity were present in 58.8% and 58.2% of patients, respectively. The most common underlying conditions were hyperparathyroidism (24%), distal renal tubular acidosis (16.6%), and medullary sponge kidney (12.9%). The main abnormalities included hypocitraturia (65.2%), hypercalciuria (51.9%), hypomagnesuria (44.6%), hyperoxaluria (39.1%), hyperuricosuria (31.5%), vitamin D deficiency (30.06%), and metabolic acidosis (27%). Patients with kidney stones and failure to thrive had higher rates of hypercalciuria. Metabolic acidosis was more common in those with parental consanguinity and vitamin D deficiency. Renal failure at final follow-up was more evident in older patients, those with parental consanguinity, hypokalemia, acidosis, and hyperparathyroidism. End-stage renal disease was more frequent in patients with consanguineous parentage, hyperparathyroidism, hypokalemia, and acidosis. Parental consanguinity, family history of kidney stones, and urinary metabolic disorders are important risk factors for pediatric nephrocalcinosis. This highlights the need for genetic counseling, screening, and monitoring of biochemical abnormalities. Early diagnosis and timely treatment are crucial to maintain glomerular function and prevent kidney failure.

The field of nanophotonics has advanced and can be utilized as a method to detect different infectious diseases. The introduction of multiplex nanophotonic diagnostics has enabled the speedy and simultaneous detection of viral infections and specific biomarkers. The quick reaction times, high sensitivity, and specificity of multiplex nanophotonic diagnostics enable real-time identification of viruses without the need for nucleic acid amplification. This review presents an overview of nanophotonic tools used to identify diseases and particular biomarkers. The paper also examines possible research areas for the development of unique, cutting-edge multiplex nanophotonic diagnostics capable of concurrently detecting various diseases or biomarkers/biomolecules. Furthermore, it discusses barriers to further advancement and offers insight into anticipated trends.

Abstract Metabolic disorders, including obesity, dyslipidemia, diabetes, nonalcoholic fatty liver disease, and metabolic syndrome, are characterized by insulin resistance, abnormalities in circulating cholesterol and lipid profiles, and hypertension. The most common pathophysiologies of metabolic disorders are glucose/lipid metabolism dysregulation, insulin resistance, inflammatory response, and oxidative stress. Although several agents have been approved for the treatment of metabolic disorders, there is still a strong demand for more efficacious drugs with less side effects. Natural products have been critical sources of drug research and discovery for decades. However, the usefulness of bioactive natural products is often limited by incomplete understanding of their direct cellular targets. In this review, we highlight the current understanding of the established and emerging molecular mechanisms of metabolic disorders. We further summarize the therapeutic effects and underlying mechanisms of natural products on metabolic disorders, with highlights on their direct cellular targets, which are mainly implicated in the regulation of glucose/lipid metabolism, insulin resistance, metabolic inflammation, and oxidative stress. Finally, this review also covers the clinical studies of natural products in metabolic disorders. These progresses are expected to facilitate the application of these natural products and their derivatives in the development of novel drugs against metabolic disorders.

Metabolic disorders include obesity, nonalcoholic fatty liver disease, insulin resistance and type 2 diabetes. It has become a major health issue around the world. Ubiquitin-proteasome system (UPS) is essential for nearly all cellular processes, functions as a primary pathway for intracellular protein degradation. Recent researches indicated that dysfunctions in the UPS may result in the accumulation of toxic proteins, lipotoxicity, oxidative stress, inflammation, and insulin resistance, all of which contribute to the development and progression of metabolic disorders. An increasing body of evidence indicates that specific dietary polyphenols ameliorate metabolic disorders by preventing lipid synthesis and transport, excessive inflammation, hyperglycemia and insulin resistance, and oxidative stress, through regulation of the UPS. This review summarized the latest research progress of natural polyphenols improving metabolic disorders by regulating lipid accumulation, inflammation, oxidative stress, and insulin resistance through the UPS. In addition, the possible mechanisms of UPS-mediated prevention of metabolic disorders are comprehensively proposed. We aim to provide new angle to the development and utilization of polyphenols in improving metabolic disorders.

Polycystic ovarian syndrome (PCOS) is a common heterogeneous reproductive endocrine metabolic disorder in women of reproductive age characterized by clinical and biochemical hyperandrogenemia, ovulation disorders, and polycystic ovarian morphology. Ferroptosis is a novel type of cell death driven by iron accumulation and lipid peroxidation. Ferroptosis plays a role in maintaining redox balance, iron metabolism, lipid metabolism, amino acid metabolism, mitochondrial activity, and many other signaling pathways linked to diseases. Iron overload is closely related to insulin resistance, decreased glucose tolerance, and the occurrence of diabetes mellitus. There is limited research on the role of ferroptosis in PCOS. Patients with PCOS have elevated levels of ferritin and increased reactive oxygen species in ovarian GCs. Studying ferroptosis in PCOS patients is highly important for achieving personalized treatment. This article reviews the progress of research on ferroptosis in PCOS, introduces the potential connections between iron metabolism abnormalities and oxidative stress-mediated PCOS, and provides a theoretical basis for diagnosing and treating PCOS.

Objective: Interleukin (IL)-22 is a potential therapeutic protein for the treatment of metabolic diseases such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease due to its involvement in multiple cellular pathways and observed hepatoprotective effects. The short serum half-life of IL-22 has previously limited its use in clinical applications; however, the development of mRNA-lipid nanoparticle (LNP) technology offers a novel therapeutic approach that uses a host-generated IL-22 fusion protein. In the present study, the effects of administration of an mRNA-LNP encoding IL-22 on metabolic disease parameters was investigated in various mouse models. Methods: C57BL/6NCrl mice were used to confirm mouse serum albumin (MSA)-IL-22 protein expression prior to assessments in C57BL/6NTac and CETP/ApoB transgenic mouse models of metabolic disease. Mice were fed either regular chow or a modified amylin liver nonalcoholic steatohepatitis–inducing diet prior to receiving either LNP-encapsulated MSA-IL-22 or MSA mRNA via intravenous or intramuscular injection. Metabolic markers were monitored for the duration of the experiments, and postmortem histology assessment and analysis of metabolic gene expression pathways were performed. Results: MSA-IL-22 was detectable for ≥8 days following administration. Improvements in body weight, lipid metabolism, glucose metabolism, and lipogenic and fibrotic marker gene expression in the liver were observed in the MSA-IL-22–treated mice, and these effects were shown to be durable. Conclusions: These results support the application of mRNA-encoded IL-22 as a promising treatment strategy for metabolic syndrome and associated comorbidities in human populations.

By replacing and removing defective or infected cells, programmed cell death (PCD) contributes to homeostasis maintenance and body development, which is ubiquitously present in mammals and can occur at any time. Besides apoptosis, more novel modalities of PCD have been described recently, such as necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death. PCD not only regulates multiple physiological processes, but also participates in the pathogenesis of diverse disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is mainly classified into metabolic dysfunction-associated steatotic liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), and the latter putatively progresses to cirrhosis and hepatocellular carcinoma. Owing to increased incidence and obscure etiology of MASH, its management still remains a tremendous challenge. Recently, hepatocyte PCD has been attracted much attention as a potent driver of the pathological progression from MASL to MASH, and some pharmacological agents have been proved to exert their salutary effects on MASH partly via the regulation of the activity of hepatocyte PCD. The current review recapitulates the pathogenesis of different modalities of PCD, clarifies the mechanisms underlying how metabolic disorders in MASLD induce hepatocyte PCD and how hepatocyte PCD contributes to inflammatory and fibrotic progression of MASH, discusses several signaling pathways in hepatocytes governing the execution of PCD, and summarizes some potential pharmacological agents for MASH treatment which exert their therapeutic effects partly via the regulation of hepatocyte PCD. These findings indicate that hepatocyte PCD putatively represents a new therapeutic point of intervention for MASH.

The widespread adoption of high-calorie, high-fat, high-sucrose diets (HFHSD) has become a global health concern, particularly due to their association with cardiovascular diseases and metabolic disorders. These comorbidities increase susceptibility to severe outcomes from viral infections and trauma, with trauma-related incidents significantly contributing to global mortality rates. This context underscores the critical need for a reliable blood supply. Recent research has focused on high molecular weight (MW) polymerized human hemoglobin (PolyhHb) as a promising alternative to red blood cells (RBCs), showing encouraging outcomes in previous studies. Given the overlap of metabolic disorders and trauma-related health issues, it is crucial to assess the potential toxicity of PolyhHb transfusions, particularly in models that represent these vulnerable populations. This study evaluated the effects of PolyhHb exchange transfusion in guinea pigs that had developed metabolic disorders due to a 12-week HFHSD regimen. The guinea pigs, underwent a 20 % blood volume exchange transfusion with either PolyhHb or the lower molecular weight polymerized bovine hemoglobin, Oxyglobin. Results revealed that both PolyhHb and Oxyglobin transfusions led to liver damage, with a more pronounced effect observed in HFHSD-fed animals. Additionally, markers of cardiac dysfunction indicated signs of cardiac injury in both the HFHSD and normal diet groups following the Oxyglobin transfusion. This study highlights how pre-existing metabolic disorders can exacerbate the potential side effects of hemoglobin-based oxygen carriers (HBOCs). Importantly, the newer generation of high MW PolyhHb showed lower cardiac toxicity compared to the earlier generation low MW PolyhHb, known as Oxyglobin, even in models with pre-existing endothelial and metabolic challenges.

Studying the metabolic health of population around the world is becoming a priority area of modern medicine. This is associated with an increase in the prevalence of overweight and obesity, which leads to a significant increase in related metabolic diseases, which are actually complications of obesity, primarily visceral. According to 2019 data, overweight and obesity are associated with 5 million deaths and 160 million disability-adjusted life years, more than half of which are due to cardiovascular diseases. This challenge requires the development of cardiometabolic medicine and the training of new specialists.

Aberrant epigenetic modifications, particularly DNA methylation, play a critical role in the pathogenesis and progression of human diseases. The current review aims to reveal the role of aberrant DNA methylation in the pathogenesis and progression of diseases and to discuss the original data obtained from international research laboratories on this topic. In the review, we mainly summarize the studies exploring the role of aberrant DNA methylation as diagnostic and prognostic biomarkers in a broad range of human diseases, including monogenic epigenetics, autoimmunity, metabolic disorders, hematologic neoplasms, and solid tumors. The last section provides a general overview of the possibility of the DNA methylation machinery from the perspective of pharmaceutic approaches. In conclusion, the study of DNA methylation machinery is a phenomenal intersection that each of its ways can reveal the mysteries of various diseases, introduce new diagnostic and prognostic biomarkers, and propose a new patient-tailored therapeutic approach for diseases.

IntroductionTo explore whether blood flow-restrictive resistance exercise (BFRE) can be used as an alternative strategy to moderate-intensity resistance training (RT) to improve metabolic disorder and body composition in older adults with type 2 diabetes (T2DM).MethodsThis is a single-blind, randomized, controlled trial. Ninety-eight older adults with T2DM were randomly divided into three groups: BFRE group (n = 34), RT group (n = 31) and control group (n = 33). Two exercise groups received supervised collective training for a period of six months, each lasting 50 min, three times a week. The primary outcomes included fasting plasma glucose (FPG), Glycosylated hemoglobin (HbA1c), blood lipids, blood pressure, and body composition. The secondary outcome was muscle performance.ResultsAfter six months of intervention, the FPG, HbA1c, blood lipids, diastolic blood pressure, body composition, and muscle performance of the two exercise groups were significantly improved relative to the control group and baseline measurements (P < 0.05). There was no significant increase in lean mass between the two exercise groups compared to the control group and baseline (p > 0.05). There was no significant decrease in systolic blood pressure between the two exercise groups compared to the control group (p > 0.05), but it was significantly lower than their baseline (P < 0.05). There was no significant difference in all indicators between the two exercise groups at the baseline, third and sixth months of intervention (p > 0.05).DiscussionBFRE can safely and effectively improve the metabolic disorder and body composition of older adults with T2DM. For elderly exercise beginners, BFRE can be used as an alternative strategy to moderate-intensity resistance training.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=178886, identifier ChiCTR2300074357.

Abstract Migraine is a disabling neurovascular disorder among people of all ages, with the highest prevalence in the fertile years, and in women. Migraine impacts the quality of life of affected individuals tremendously and, in addition, it is associated with highly prevalent metabolic diseases, such as obesity, diabetes mellitus and thyroid dysfunction. Also, the clinical response to drugs might be affected in patients with metabolic disease due to body composition and metabolic change. Therefore, the efficacy of antimigraine drugs could be altered in patients with both migraine and metabolic disease. However, knowledge of the pharmacology and the related clinical effects of antimigraine drugs in patients with metabolic disease are limited. Therefore, and given the clinical relevance, this article provides a comprehensive overview of the current research and hypotheses related to the influence of metabolic state and body composition on the action of antimigraine drugs. In addition, the influence of antimigraine drugs on metabolic functioning and, vice versa, the influence of metabolic diseases and its hormonal modulating medication on migraine activity is outlined. Future exploration on personalizing migraine treatment to individual characteristics is necessary to enhance therapeutic strategies, especially given its increasing significance in recent decades.