The main aim of the present study was to explore health professionals’ reported experiences and approaches to managing children who receive a designation of cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen positive inconclusive diagnosis following a positive NBS result for cystic fibrosis. An online questionnaire was distributed via Qualtrics Survey Software and circulated to a purposive, international sample of health professionals involved in managing children with this designation. In total, 101 clinicians completed the online survey; 39 from the US, six from Canada and 56 from Europe (including the UK). Results indicated that while respondents reported minor deviations in practice, they were cognizant of recommendations in the updated guidance and for the most part, attempted to implement these into practice consistently internationally. Where variation was reported, the purpose of this appeared to be to enable clinicians to respond to either clinical assessments or parental anxiety in order to improve outcomes for the child and family. Further research is needed to determine if these findings are reflective of both a wider audience of clinicians and actual (rather than reported) practice.

This study assessed the associations between host genetic variants and subgingival microbiota in patients with metabolic syndrome (MetS); 103 patients with MetS underwent medical and periodontal examinations and had blood and subgingival plaque samples taken. DNA was extracted and processed (assessing a panel of selected single nucleotide polymorphisms (SNPs) first (hypothesis-testing), and then expanding to a discovery phase. The subgingival plaque microbiome from these patients was profiled. Analysis of associations between host genetic and microbial factors was performed, stratified for periodontal diagnosis. Specific SNPs within RUNX2, CAMTA1 and VDR genes were associated with diversity metrics, with no genome-wide associations detected for periodontitis severity or Mets components at p<10-7. Severe periodontitis was associated with pathogenetic genera and species. Some SNPs correlated with specific bacterial genera, as well as with microbial taxa, notably VDR (rs12717991) with Streptococcus mutans and RUNX2 (rs3749863) with Porphyromonas gingivalis. This is the first study exploring the role of host genotype variation in subgingival microbial dysbiosis in patients with MetS and periodontitis. In conclusion, variation in host genotypes may play a role in the dysregulated immune responses characterizing periodontitis and thus the oral microbiome, suggesting that systemic health-associated host traits further interact with oral health and microbiome.

Type 2 diabetes mellitus (T2DM) is a common metabolic disease characterised by insulin resistance and elevated blood glucose levels, affecting millions of people worldwide. T2DM patients with dyslipidaemia have an increased risk of cardiovascular disease (CVD). A complex interplay of risk factors such as hyperglycaemia, dyslipidaemia, hypertension, obesity, inflammation and oxidative stress favour the development of atherosclerosis, a central mechanism in the pathogenesis of cardiovascular disease. Dyslipidaemia, a hallmark of T2DM, is characterised by elevated triglycerides, decreased high-density lipoprotein (HDL) cholesterol and the presence of small, dense low-density lipoprotein (LDL) particles, all of which promote atherosclerosis. In this article, we have attempted to present various treatment strategies that include pharmacological interventions such as statins, ezetimibe, PCSK9 inhibitors, fibrates and omega-3 fatty acids. We have also tried to highlight the pivotal role of lifestyle modifications, including physical activity and dietary changes, in improving lipid profiles and overall cardiovascular health in T2DM patients. We have also tried to present the latest clinical guidelines for the management of dyslipidaemia in T2DM patients. In conclusion, the treatment of dyslipidaemia in T2DM patients is of great importance as it lowers lipid particle levels, slows the progression of atherosclerosis and ultimately reduces susceptibility to cardiovascular disease.

Secondary movement disorders (SMDs) represent a heterogeneous group of neurological conditions characterized by abnormal, involuntary movements resulting from various underlying causes. This comprehensive review aims to thoroughly understand SMDs, including their epidemiology, pathophysiology, clinical manifestations, diagnostic approach, and management strategies. SMDs encompass a spectrum of movement abnormalities, including dystonia, chorea, athetosis, myoclonus, tics, and tremors. They can arise from a multitude of etiologies, such as drug-induced effects, post-infectious processes, metabolic disturbances, and structural brain lesions. The epidemiology of SMDs varies depending on the underlying cause, with some conditions being more prevalent in specific populations or age groups. Understanding the pathophysiology of SMDs is crucial for accurate diagnosis and targeted management. Diagnosing SMDs requires a comprehensive approach, including a detailed history, physical examination, laboratory investigations, neuroimaging studies, and sometimes electrophysiological studies. Management of SMDs is multifaceted and may involve pharmacological, non-pharmacological, and surgical interventions. Individualized treatment plans are essential, considering the underlying cause, severity of symptoms, and patient preferences. Emerging concepts in the field of SMDs include advancements in genetic research, identification of biomarkers, and development of novel therapeutic approaches. There is a growing focus on patient-centered care and improving the quality of life for individuals with SMDs. In conclusion, SMDs pose diagnostic and therapeutic challenges, requiring a multidisciplinary approach for optimal management. Continued research and collaboration are essential for advancing our understanding and treatment of these complex disorders.

Unhealthy diet can lead to the development of metabolic disorders, and studies have shown strong associations between those conditions, c-reactive protein (CRP) and adiponectin. We report on associations between targeted metabolic markers and active nutrients from diet and Sujiaonori algal supplement (SBM), a natural adiponectin modulation inducer (NAMI) containing 60% of bioactive ulvan-rich fiber, in Japanese women. The study comprised dietary survey and intervention conducted in Kochi, Japan (2016-2017), involving 31 women who completed a dietary survey and provided biospecimen for CRP and adiponectin measurement using ELISA. Sixteen women received 3g SBM daily for one month and 15 others (controls) received 3g of corn starch. In SBM group, mean age was 23.06 (2.21) years [vs. 23.06 (1.55)], BMI was 21.11 (0.59) kg/m2 [vs. 21.43 (0.60) in controls], and daily intake of n3-PUFA [3.83 (0.24) vs. 2.21 (0.33) mg/day; p=0.042] and total fiber [364.12 (2.45) vs. 48.13 (1.57) mg/day in controls; p=0.000] were markedly higher. Furthermore, CRP was inversely associated with total fiber, total n3-PUFA, SBM-n3PUFA, vitamin D and vitamin B6, whereas adiponectin was strongly and positively associated with SBM-fiber and total n3-PUFA. Thus ulvan-rich SBM supplement, which contains ulvan-rich fiber and n3-PUFA, might be beneficial in reducing metabolic risk.

Indirect calorimetry (IC) is a widely used method to study animal energy metabolism by measuring gas exchange. The accuracy of IC depends on detecting variations in signals reflecting the metabolic response, which can be challenging due to measurement noise and external factors. In this study, we propose a methodology to validate IC systems, including an easy-to-use spreadsheet for data computing, to verify accuracy and detect whole-system leaks. We conducted a re-covery test using a simulation of CO2 dynamics in MS Excel and injecting a known CO2 concentration into four respirometry chambers. The clearance rate of CO2 was observed and compared to the expected clearance rate from the simulation. The results from the recovery test in our system show that the proposed methodology is accurate and precise. The proposed methodology and recovery test can be used to standardize the validation of IC systems, providing accurate measurements of animal energy metabolism in different environmental conditions and energy utilization from feeds.

Polyphenols, long-used components of medicinal plants, have drawn great interest in recent years as potential therapeutic agents because of their safety, efficacy, and wide range of biological effects. Approximately 74% of the world's population still uses plant-based medicines, indicating the ongoing significance of phytochemicals for human health. The study emphasizes the growing body of research examining the role of polyphenols in uncovering their anti-adipogenic and anti-obesity properties. Functions of polyphenols including phenylpropanoids, flavonoids, terpenoids, alkaloids, glycosides, and phenolic acids are distinct due to changes in chemical diversity, and structural characteristics. This review methodically investigates the mechanism of how naturally occurring polyphenols mediate obesity and metabolic function. To this end, hormonal control of hunger has the potential to inhibit pro-obesity enzymes such as pancreatic lipase, the promotion of energy expenditure, and the modulation of adipocytokine production. Specifically, polyphenols affect insulin, a hormone that is essential for regulating blood sugar, and they also play a role in part in a complex web of factors that affect the progression of obesity. This review also explores the immunomodulatory properties of polyphenols, providing insight into their ability to improve immune function. The effects of polyphenols on gut health, improving the number of commensal bacteria, cytokine production suppression, and immune cell mediation, including natural killer cells and macrophages. Taken together, continuous studies are required for prudent and precise mechanisms underlying polyphenols' therapeutic potential in obesity and immunomodulation. In the interim, this review emphasizes the holistic approach to health and promotes the consumption of a wide range of foods and drinks high in polyphenols. This review lays the groundwork for future developments, indicating that the components of polyphenols and their derivatives may provide the answer to urgent worldwide health issues. This compilation of the body of knowledge paves the way for future discoveries in the global treatment of pressing health concerns in obesity and metabolic diseases.

Piriform fossa and/or esophageal injuries caused by calibration tubes are relatively rare and re-main unelucidated. Herein, we report the case of a 36-year-old woman with morbid obesity, sleep apnea, and menstrual abnormalities who was scheduled to undergo laparoscopic sleeve gastrectomy (LSG). We inserted a 36-Fr Nelaton catheter made of natural rubber as a calibration tube during the surgery. However, excessive resistance was observed. We confirmed a submuco-sal layer detachment of approximately 5 cm from the left piriform fossa to the esophagus using intraoperative endoscopy. Additionally, LSG was performed using an endoscope as the guiding calibration tube. We inserted a nasogastric tube under endoscopy with a guidewire before com-pleting the surgery, hoping for a guiding effect on saliva flow. After 17 months, the patient suc-cessfully lost weight postoperatively without complaints of neck pain or discomfort during swallowing. Therefore, if the damage is limited to the submucosal layer, as in this case, conserva-tive therapy should be considered, which is similar to the concept of not requiring suture closure in endoscopic submucosal dissection. This case highlights the risk of iatrogenic injuries to the pi-riform fossa and/or esophagus during LSG and the importance of careful calibration tube inser-tion to prevent them.

We aimed to develop a non-linear regression model that could predict the fat fraction of the liver (USFF), similar to magnetic resonance imaging proton density fat fraction (MRI-PDFF), based on quantitative ultrasound (QUS) parameters. We measured and retrospectively collected the ultrasound attenuation coefficient (AC), backscatter-distribution coefficient (BSC-D), and liver stiffness (LS) using shear wave elastography (SWE) in 90 patients with clinically suspected non-alcoholic fatty liver disease (NAFLD) and 51 patients with clinically suspected metabolic-associated fatty liver disease (MAFLD). The MRI-PDFF was also measured in all patients within a month of the ultrasound scan. In the linear regression analysis, only AC and BSC-D showed a significant association with MRI-PDFF. Therefore, we developed prediction models using non-linear least-squares analysis to estimate MRI-PDFF based on the AC and BSC-D parameters. We fitted the models on the NAFLD dataset and evaluated their performance in 3-fold cross-validation repeated five times. We decided to use the model based on both parameters to estimate the ultrasound fat fraction (USFF). The correlation between USFF and MRI-PDFF was strong in NAFLD and very strong in MAFLD. According to a receiver operating characteristics (ROC) analysis, USFF could differentiate between <5% vs. ≥ 5% and < 10% vs. ≥ 10% MRI-PDFF steatosis with excellent, 0.97 and 0.91 area under the curve (AUC) accuracy in the NAFLD and with AUCs of 0.99 and 0.96 in the MAFLD groups. In conclusion, USFF calculated from QUS parameters is an accurate method to quantify liver fat fraction and to diagnose ≥ 5% and ≥ 10% steatosis in both NAFLD and MAFLD. Therefore, USFF can be an ideal non-invasive screening tool for patients with NAFLD and MAFLD risk factors.

Abstract: The brain endothelial cell (BEC) glycocalyx (ecGCx) is a BEC surface coating consisting of a complex interwoven polysaccharide (sweet husk) mesh-like network of membrane-bound proteoglycans, glycoproteins, and glycosaminoglycans (GAGs) covering the apical luminal layer of the brain endothelial cells. The ecGCx may considered as the 1st barrier of a tripartite blood-brain barrier (BBB) consisting of 1) ecGCx; 2) BECs; (3) extravascular compartment of pericytes, extracellular matrix, and perivascular astrocytes, Perturbations of this barrier allow for increased permeability in the postcapillary venule that will be permissive to both fluids, solutes, and proinflammatory peripherally-derived leukocytes into the perivascular spaces (PVS) to result in enlargement as well as increased neuroinflammation. The ecGCx is known to have multiple functions, which include its physical and charge barrier, mechanical transduction, regulation of vascular permeability, modulation of inflammatory response, and anticoagulation functions. This review discusses each of the listed functions in detail and utilizes multiple transmission electron micrographs and illustrations to allow for a better understanding of the ecGCx structural and functional roles as it relates to enlarged perivascular spaces (EPVS). This is the 5th review of a series quintet that discuss the importance of EPVS from the perspective of the cells of brain barriers. Attenuation and/or loss of the ecGCx results in brain barrier disruption with increased permeability to proinflammatory leukocytes, fluids and solutes, which accumulate in the postcapillary venule perivascular spaces. This accumulation results in obstruction and results in EPVS with impaired waste removal of the recently recognized glymphatic system. Importantly, EPVS are progressively being regarded as a marker of cerebrovascular and neurodegenerative pathology.

Studies investigating the acute effect of postprandial exercise (PPE) on glucose responses exhibit significant heterogeneity in terms of participant demographic, exercise protocol, and exercise timing post-meal. As such, this study aimed to further analyze the existing literature on the impact of PPE on glycemic control in individuals with overweight, obesity, and type 2 diabetes (T2D). Literature search was conducted through databases including PubMed, CINAHL, and Google Scholar. Thirty-one original research studies that met the inclusion criteria were selected. The random-effect meta-analysis was performed to compare postprandial glucose area under the curve (AUC) and 24-h mean glucose levels between PPE and the time-matched no-exercise control (CON). Subgroup analysis was conducted to explore whether the glucose-lowering effect of PPE could be influenced by exercise duration, exercise timing post-meal, and disease status of participants. This study revealed significantly reduced glucose AUC (Hedges’ g = -0.317; SE = 0.057; p < 0.05) and 24-hour mean glucose levels (Hedges’ g = -0.328; SE = 0.062; p < 0.05) following PPE than CON. The reduction in glucose AUC was greater (p < 0.05) following PPE lasting >30 min than ≤30 min. The reduction in 24-hour mean glucose levels was also greater (p < 0.05) following PPE initiated ≥60 min than <60 min post-meal and in those with T2D than those without T2D. PPE offers a viable approach for glucose management and can be performed in various forms so long as exercise duration is sufficient. The glucose-lowering effect of PPE may be further enhanced by initiating it after the first hour post-meal. PPE represents a promising strategy, particularly for patients with T2D.

Aim: Evaluation of role of supplementation of omega-3 polyunsaturated fatty acids on endothelial function in patients with metabolic syndrome. Methods: Total of 80 patients with metabolic syndrome were enrolled to two groups. We evaluated endothelial function in subjects before and after three-month treatment with omega-3 polyunsaturated fatty acids in dose 2.4g daily (800mg 3 times a day) vs placebo. Using the Endo-PAT2000 device (Itamar Medical Ltd. Caesarea, Israel), reactive hyperemia index – a parameter of endothelial function and augmentation index– a parameter of arterial stiffness were measured. Plasmatic level of glutation peroxidase, homocysteine, apolipoprotein B and lipoprotein (a) were also evaluated. Results: The average values of reactive hyperemia index before the treatment with n-3PUFA was 1.62 ± 0.42 , whereas 1.96 ± 0.62 at the end of the study (p<0.005). Augmentation index changed from 14.66 ± 19.55 to 9.21 ± 15.64 after the treatment (p=0.003). We also observed statistically significant decrease of apolipopotein B (0.94 ± 0.36 vs 1.13 ± 0.35, p = 0.001) and homocysteine (19.31 ± 5.29 vs. 13.78 ± 3.05, p = 0.001) and increase of the glutathion perxidase plasma levels (41.65 ± 8.90 vs. 45.20 ± 8.01), p=0.001. Conclusion: We have observed significant improvement of the endothelial function in subjects with metabolic syndrome treated with omega-3 polyunsaturated fatty acids in dose 2.4g daily.

We evaluated the usefulness of the novel cholesterol-triglyceride subgroup (CTS) indices that potentially reflect the metabolic status regarding risk of coronary heart disease (CHD) using a retrospective longitudinal study of the Japanese general population. We recruited 12,373 individuals from the annual users of our healthcare center. Among them, the first onset of CHD was recorded in 131 individuals between April, 2014 and March, 2020. The multivariate Cox proportional hazards regression analyses for all normalized lipid indices revealed that the CTSqnt index showed a comparable hazard ratio for the CHD outcome to non-high-density lipoprotein cholesterol (nonHDL-c) and triglycerides. The HR of the CTSqlt index was significantly lower than for CTSqnt, but still comparable to that for low-density lipoprotein cholesterol (LDL-c). In comparison with the other indices, CTSqlt is more sensitive to risk increment while the index value increases. Linear regression analyses for the CTS indices and previously known lipid indices suggest that the CTSqnt and CTSqlt indices reflect the quantity of atherogenic lipoproteins and size of smaller and denser LDLs, respectively. Furthermore, the CTSqnt/HDL-c index can be used as a comprehensive risk indicator that may represent the status of lipid metabolism determined by the CTSqlt and CTSqnt indices and thus may be useful for screening. The CTS indices can be used to evaluate the metabolic status of individuals, which may increase the risk of future CHD.

Increasingly, systems biology is gaining relevance in basic and applied research. The combination of computational biology with wet lab produces a synergy that results in an exponential increase in knowledge of biological systems. The study of microorganisms such as Staphylococcus epidermidis RP62A enables the researcher to understand better its metabolic network, which allows the design of effective strategies to treat infections caused by this species or others. S. epidermidis is the second cause of infection in patients with joint implants, so treating its proliferation seems vital for public health. There are different approaches to the analysis of metabolic networks. Flux Balance Analysis (FBA) is one of the most widespread streams. It allows the study of large metabolic networks, their structural properties, the optimization of metabolic flux, and the search for intervention strategies to modify the state of the metabolic network. This work presents the validation of the Staphylococcus epidermidis RP62A metabolic network model elaborated by Díaz-Calvo et al.. Then, we elaborate further on the network analysis’s essential reactions, classifying them. Finally, we introduce some proposals to intervene in the network and design knock-outs.

Bibliometric studies on inherited metabolic diseases(IMDs) didn't exist in the literature.Our research aims to conduct a bibliometric study to determine the current status,trending topics,and missing points of publications on IMDs.Between 1968-2023, we conducted a literature search with keyword "inherited metabolic disease" in the SCOPUS-database.We included research articles in medicine written in English,published in the final section.We created our data pool using VoSviewer, SciMAT, and Rstudio software programs for bibliometric parameters of the articles that met the inclusion criteria.We performed bibliometric analysis of the data with R-package "bibliometrix" and BibExcel programs.We included 2702 research articles published on IMDs.Top three countries that have written the most articles in this field are; USA(n= 501), United Kingdom(n=182), and China(n= 172).The most preferred keywords by the authors were;newborn screening(n=54), mutation(n=43), phenylketonuria(n=42), children(n=35), genetics(n= 34) and maple syrup urine disease(n=32).Trending topics were osteoporosis, computed tomography, bone marrow transplantation in the early years of the study, chronic kidney disease, urea cycle disorders, next-generation sequencing, newborn screening, and familial hypercholesterolemia in the final years of the study. This study provides clinicians with a new perspective showing that molecular and genetic studies in inherited metabolic diseases will play an essential role in diagnosis and treatment in the future.

The pandemic of obesity worldwide has been recognized as a very important challenge. Within its complexity the identification of higher risk patients becomes essential since it seems unsustainable trying to offer access to treatment to all people with obesity. Several new approaches have recently been presented as important tools for risk stratification. This research applied some of these tools in a cross-sectional study involving adults with obesity classes I, II, III and super obesity. The participants had their cardiometabolic risk profile assessed. The study included adults with obesity, aged 18 to 50 years (n=404) who were evaluated for anthropometric, body composition, hemodynamic, physical fitness and biochemical assessments. These variables were used to identify the prevalence of risk factors for cardiometabolic diseases according to the classes of obesity, by gender and age group. The results showed a high prevalence of risk factors, especially among the upper classes of obesity (BMI &gt; 35 kg/m2) using single parameters as the waist circumference with almost 90% above the cut-off point. But there were also smaller numbers as the Glycated Hemoglobin whose prevalence was around 30%. Indexes like the atherogenic index of plasma (AIP) had the highest prevalence, with 100% of the male participants identified with increased risk for cardiovascular diseases.

(1) Background: Metabolic syndrome is associated with cardiovascular complications. Therefore, this study aims to establish cut points for the conicity index based on the components of the metabolic syndrome and to associate it with characteristics sociodemographic, food consumption and occupational factors in Brazilian rural workers; (2) Methods: Cross-sectional study carried out with farmers. The receiver operating characteristic curve was calculated and the cutoff points for the conicity index were identified by the area under the curve, sensitivity and specificity. The variables included in the binary logistic regression analysis were selected by considering p &lt; 0.20 in the bivariate test; (3) Results: The cut points were similar in females according to both criteria, resulting in a single cut-off of 1.269. In males, the cut points showed differences, resulting in 1.272 according to the NCEP-ATP III and 1.252 according to the IDF. We have shown that younger people, those who work more than 40 hours a week and the lowest contribution of culinary ingredients are associated with increased odds of abdominal obesity. While the consumption of the products they sell or produce decreases these chances; (4) Conclusions: The conicity index showed high discriminatory power for the identification of abdominal obesity in rural workers.

Hepatitis B Virus (HBV) is a challenge for global health services, affecting millions and leading hundreds to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. The identification of diverse HBV genotypes reveals distinct geographical distributions and associations with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, further influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.

Background: Abdominal migraine (AM) is a clinical diagnosis specified by Rome IV and ICHD III as a functional gastrointestinal disease (FGID) and a migraine associated syndrome, respectively. AM is undiagnosed and undertreated, and thus far the FDA has not approved any drug for AM treatment. We and others showed that changes in the kynurenine (KYN) pathway of tryptophan (TRP) metabolism played an important role in the pathogenesis and treatment of FIGDs. Changes in the KYN pathway were shown in migraine. Findings: Abdominal migraine reflects impairments in communication within the gut-brain axis. Treatment approaches have not been sufficiently documented and are based on experience of physicians, presenting personal rather than evidence-based practice and including efficacy of some drugs used in adult migraine. Non-pharmacological treatment of AM is aimed preventing or ameliorating AM triggers. Modulations within the KYN pathway of TRP metabolism induced by changes in TRP content in the diet, may ameliorate FGIDs and support their pharmacological treatment. Pharmacological manipulations of brain KYNs in animals have brought promising results for clinical applications. Conclusions: In conclusion, controlled placebo-based clinical trials with dietary manipulation to adjust the amount of the product of the KYN pathway of TRP metabolism are justified in children and adolescents with AM. Further preclinical studies are needed to establish details of these trials.

Prediabetes, a pivotal phase in glucose metabolism between normalcy and diabetes, exerts a profound influence on the aging process and the risk of age-related diseases. This comprehensive review delves into the intricate web of blood-based biomarkers that collectively expedite senescence, marking the transition from a state of health to age-related complications. Key findings underscore the significance of diverse biomarkers, such as telomere length, p16INK4a, senescence-associated secretory phenotype (SASP) factors, DNA methylation clocks, advanced glycation end products (AGEs), inflammatory and oxidative stress markers, circulating hormones, and additional factors like folate, B12, osteocalcin, and more. Not only do these biomarkers serve as indicators of senescence, but they actively fuel chronic inflammation, oxidative stress, and metabolic dysregulation, all of which contribute to accelerated aging. The implications of this understanding are profound, as prediabetes emerges as a critical period in an individual's life, influencing various physiological systems, including the vascular and neural systems, metabolic functions, hormonal regulation, and bone health. Recognizing the profound influence of prediabetes on senescence provides a foundation for personalized intervention strategies to mitigate age-related complications and promote healthy aging. Future research directions call for a more diverse array of biomarkers, in-depth exploration of their roles, and the development of tailored precision medicine strategies to ensure a holistic understanding and effective management of prediabetes-induced senescence and its implications for aging. This knowledge has far-reaching implications for public health and clinical practice, emphasizing the need for early detection and intervention in prediabetic individuals to enhance the quality of life in an aging population with diverse needs.

Endocrine and nervous systems reciprocally interact to manage physiological individual functions and homeostasis. The nervous system modulates hormone release through the hypothalamus, the main cerebrally specialized structure of the neuroendocrine system. Indeed, it is involved in various metabolic processes, administering hormone and neuropeptide release at different levels. This complex activity is affected by neurons of various cerebral areas, environmental factors, peripheral organs, and mediators through feedback mechanisms. Therefore, neuroendocrine pathways have a key role in metabolic homeostasis control, and their abnormalities have been associated with the development of Metabolic Syndrome (MetS) in children. The impaired functioning of genes, hormones, and neuropeptides of various neuroendocrine pathways involved in several metabolic processes has been related to an increased risk of dyslipidaemia, visceral obesity, insulin resistance, type 2 diabetes mellitus, and hypertension. This review examines the neuroendocrine effects on the risk of MetS in children, identifying and underlying the several conditions associated with neuroendocrine pathway disruption. Neuroendocrine systems should be considered in the complex pathophysiology of MetS, and, when genetic or epigenetic mutations in "hot" pathways occur, they could be studied for new potential target therapies in severe and drug-resistant paediatric forms of MetS.

Metabolic-dysfunction associated steatotic liver disease (MASLD) is a chronic liver disease that affects more than a quarter of the global population, and is increasing worldwide, due to the pandemic of obesity. Insulin resistance is closely associated with the development and progression of MASLD. Hepatic entry of increased fatty acids (FA) released from adipose tissue, increase in FA synthesis and reduced FA oxidation in the liver, and hepatic overproduction of triglyceride (TG)-rich lipoproteins may induce the development of MASLD. Since insulin resistance also induces atherosclerosis, the leading cause for death in MASLD patients is cardiovascular disease (CVD). Considering that the development of CVD determines the prognosis of MASLD patients, the ideal therapeutic interventions for MASLD should reduce body weight, improve coronary risk factors, in addition to an improvement in liver functiom. Lifestyle modification such as diet and exercise and surgical interventions such as bariatric surgery and intragastric balloons have shown to improve MASLD by reducing body weight. Sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to improve coronary risk factors and to suppress the occurrence of CVD. Both SGLT2i and GLP-1 have been reported to improve liver enzymes, hepatic steatosis and fibrosis. We recently reported that the selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator, pemafibrate, improved liver function. PPARα agonists have multiple anti-atherogenic properties. Here, we consider the pathophysiology of MASLD and the mechanisms of action of such drugs, and consider whether such drugs and the combination therapy of such drugs could be the ideal treatments for MASLD.

Aims: Medical Nutritional Treatment (MNT) can be complex and associated to potential meta-bolic complications, which has been recently described as Nutritrauma. There is no data on the effect of applying this strategy in clinical practice. The aim of our work is to describe if applica-tion of Nutritrauma concept in real live is useful to detect metabolic complications associated to the prescription of MNT in critically ill patients. Methods: In this descriptive prospective study at a single center, we enrolled 30 consecutive crit-ical ill patients of a 14 beds medical – surgical Intensive Care Unit. The Nutritrauma strategy implementation was based in four M steps: Metabolic screening, MNT prescription, Biochemical Monitoring and Nutritional Management. The primary endpoint was to describe the metabolic complications of the MNT detected with Nutritrauma strategy. Secondary endpoint was to de-scribe the most frequent causes of inappropriate prescription. Results: We analysed 28 patients (mean age 69,7 ± 11,3 years; APACHE II 18,1 ± 8,1, SOFA 7,5 ± 3,7; Nutric Score modified 4,3 ± 2,01 and mean BMI 27,2 ± 3,8). The most frequent disease on admission was sepsis (46,4%). Length of ICU stay was 20,6 ± 15,1 days and 39,3% died during the ICU stay. Enteral nutrition (82,1%) was more frequent than parenteral nutrition (17,9%). During nutritional monitoring 54 specific analytical determinations were made. Hyperglycemia was the most frequent metabolic alteration (83,3% of the determinations). Electrolyte disturbance were hypocalcemia (50%), hypophosphatemia (29,6%) and hypokalemia (27,8%). The most frequent lipid profile abnormality were hypocholesterolemia (64,8%) and hypertriglyceridemia (27,8%). Furthermore, nutritional prescription was modified in the 53,6% of patients: increase protein dosage (25%), increase caloric dosage (21,4%) and change to an organ-specific diet (17,8%). Conclusions: The application of Nutritrauma strategy facilitate the detection of metabolic com-plications and the evaluation of the appropiate prescription of the MNT.

Ludwigia octovalvis (Jacq.) P.H. Raven is widely used in traditional medicine for different illnesses included diabetes and hypertension. However, its impact on lipotoxicity and metabolic syndrome in vivo has not been addressed. Therefore, the aim of this study was to evaluate the effects of this plant on the metabolic syndrome parameters in a C57BL6J mouse hypercaloric diet model. L. octovalvis hydroalcoholic extract and its ethyl acetate fraction (25 mg/kg/day) were used for sub-chronic assessment (10 weeks). Also four subfractions (25 mg/kg) were evaluated in the postprandial triglyceridemia test in healthy C57BL6J mice. The hydroalcoholic extract and ethyl acetate fraction significantly decreased body weight gain (-6.9 g and -1.5 g), fasting glycemia (-46.1 and -31.2 mg/dL), systolic (-26.0 and -22.5mmHg) and diastolic (-8.1 and 16.2 mmHg) blood pressure, free fatty acid concentration (-13.8 and -8.0 μg/mL) and insulin-resistance (measured by TyG index, -0.207 and -0.18) compared to the negative control. Postprandial triglyceridemia test showed that the effects in the sub-chronic model are due, at least in part, to improvement in this parameter. L. octovalvis treatments, particularly the hydroalcoholic extract, improve MS alterations and decrease free fatty acid concentration. These effects are possibly due to high contents of corilagin and ellagic acid.

(1) Background: Metabolic syndrome is a strong predictor of cardiovascular disease thus the objective of the study was to verify the prevalence of metabolic syndrome in farmers, as well as to verify the association with sociodemographic, work and lifestyle factors. (2) Methods: Cross-sectional, observational study, carried out with 790 individuals. For the diagnosis of metabolic syndrome, the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) and International Diabetes Federation (IDF) criteria were used. Pearson's chi-square test and binary logistic regression were used to verify factors associated with metabolic syndrome (3) Results: The prevalence of MS according to the IDF criteria was 16.3% overall, with 9.7% of women (95% CI: 6.66–16.16) and 6.6% of men (95% CI: 5.17–11.97). According to the NCEP/ATP III criterion, it was 12.3% overall, with 7.5% corresponding to women (95% CI: 6.62 – 13.13) and 4.8% to men (95% CI: 3.5 – 8.70). With regard to the conditions that make up metabolic syndrome, it was found that high density lipoprotein, high blood pressure and high waist circumference were the most prevalent. (4) Conclusions: The prevalence of metabolic syndrome is considerable in the population when compared to other regions, both rural and urban, in Brazil.

Abstract: Astrocytes (ACs) are the most abundant human cell in the brain and importantly, are the master connecting and communicating cells that provide structural and functional support of brain cells at all levels of organization. Further, they are recognized to be the guardians and housekeepers of the brain. Protoplasmic perivascular astrocyte endfeet and their basal lamina form the delimiting outermost barrier (glia limitans) of the perivascular spaces in postcapillary venules and are important for the clearance of metabolic waste and comprise the glymphatic system, which is critically dependent on the proper waste removal by the pvACef polarized aquaporin 4 water channels. Also, the protoplasmic perisynaptic astrocyte endfeet (psACef) are important in cradling the neuronal synapses that serve to maintain homeostasis and serve a functional and supportive role for synaptic transmission. Enlarged perivascular spaces (EPVS) are emerging as important aberrant findings on magnetic resonance imaging (MRI) and associate with white matter hyperintensities, lacunes, aging, accepted to be biomarkers for cerebral small vessel disease, increased in obesity, metabolic syndrome, and type 2 diabetes. Knowledge is exponentially expanding regarding EPVS along with the glymphatic system, since EPVS are closely associated with impaired glymphatic function and waste removal from the brain to the cerebrospinal fluid and systemic circulation. This review intends to focus on how the pvACef play a crucial role in the development of EPVS.

As yin and yang, cancer and diabetes are metabolic disorders characterized by deregulated, yet opposing, metabolic alterations. These metabolic shifts reflect a complex network of defective underlying signaling pathways, which ultimately orchestrate both disease pathogenesis and progression. The Warburg effect portrays the chief metabolic phenotype in cancer and is reflected by the dominance of aerobic glycolysis over minimal-to-no viable oxidative phosphorylation in cancer. Conversely, during the pathogenesis of type 2 diabetes (T2D), oxidative phosphorylation is constantly heightened. In advanced insulin resistance and T2D, the metabolic landscape becomes more complex, with exacerbating metabolic alterations affecting oxidative phosphorylation in a tissue-specific manner. Promising nutritional adjuvants, such as alpha-lipoic acid and flavonoids, can reprogram metabolism and exert antitumor and antidiabetic effects. Other pharmacological agents, such as metformin, have therapeutic effects on cancer and T2D. Herein, we discuss the molecular mechanisms and signaling pathways involved in the metabolic shifts in cancer and T2D, and explore the therapeutic strategies under investigation that aim to reverse the metabolic shift in both disease scenarios.

Polycystic ovary syndrome (PCOS) usually comes along with metabolic disturbances attributed to androgen excess and obesity, but the contribution of each has not been defined, and the occurrence of metabolic disturbances is frequently not investigated. We evaluated 99 PCOS and 41 non-PCOS women. Clinical biomarkers of glucose-, liver-, and endothelial-related metabolic alterations were measured; participants were categorized into four groups according with obesity (OB) and hyperandrogenemia (HA) statuses: Healthy (no-HA, lean), HA (HA, lean), OB (no-HA, OB), and HAOB (HA, OB). Metabolic disturbances were highly frequent in PCOS women (70%). BMI correlated with all biomarkers, while free testosterone (FT) only with glucose- and hepatic-related indicators. Despite insulin sensitivity and liver enzymes were associated with FT, women with obesity exhibited lower M [coeff = 8.56 – 0.080(FT) –3.71(Ob); p &lt;0.001)] and higher aspartate aminotransferase (coeff = 26.27 + 0.532(FT) + 8.08(Ob); p = 0.015)] than lean at the same level of FT. Women with obesity exhibited greater risk of metabolic disorders than lean, independently of hyperandrogenemia. Clinicians are compelled to search for metabolic alterations in PCOS women; obesity must be handled in all cases, but hyperandrogenemia needs to be managed also in those with glucose- or liver-related disturbances.

Lower limb exoskeletons have the potential to reduce the prevalence of work-related musculoskeletal disorders; however, they often lack user-oriented control strategies. Human-in-the-loop (HITL) controls can adapt an exoskeleton’s assistance in real-time, to optimize the user-exoskeleton interaction. This study presents a HITL control for a knee exoskeleton to minimize the users’ physical effort, a parameter innovatively evaluated by their interaction torque with the exoskeleton (a muscular effort indicator) and metabolic cost. This work innovates by estimating the user’s metabolic cost within the HITL control through a machine-learning model. The regression model was able to estimate the metabolic cost, in real-time, with a root-mean-squared error of 0.66 W/kg and a mean absolute percentage error of 26%, making faster (10s) and less noisy estimations than a respirometer (K5, Cosmed) device. The HITL reduced the user’s metabolic cost and interaction torque by 7.3% and 32.3%, respectively, when compared to a zero-torque control. The developed HITL control surpassed both a non-exoskeleton and a zero-torque condition regarding the user’s physical effort, even for a simple task such as slow walking. Furthermore, the user-specific control enabled a lower metabolic cost than the non-user-specific assistance. This proof-of-concept demonstrated the potential for HITL controls in assisted working.

Hyperhomocysteinemia (HHcys) is recognized as an independent risk factor for various significant medical conditions, yet controversy persists around its assessment and management. The diagnosis of disorders affecting homocysteine (Hcys) metabolism faces delays due to insufficient awareness of its clinical presentation and unique biochemical characteristics. In cases of arterial or venous thrombotic vascular events, particularly with other comorbidities, it is crucial to consider moderate to severe HHcys. A nutritional approach to HHcys management involves implementing dietary strategies and targeted supplementation, emphasizing key nutrients like vitamin B6, B12, and folate crucial for Hcys conversion. Adequate intake of these vitamins, along with betaine supplementation, supports Hcys remethylation. Lifestyle modifications, such as smoking cessation and regular physical activity, complement the nutritional approach to enhance Hcys metabolism. For individuals with HHcys, maintaining a plasma Hcys concentration below 50 μmol/L consistently is vital to lower the risk of vascular events. Collaboration with healthcare professionals and dietitians is essential for developing personalized dietary plans addressing specific needs and underlying health conditions. This integrated approach aims to optimize metabolic processes and reduce the associated health risks.

The purpose of this study was to examine the impact of fructose consumption during the peri-pubertal period on the later onset of metabolic syndrome in rats. Additionally, the study sought to explore the potential of moderate-intensity physical training as a non-pharmacological approach to mitigate the fructose effects. Male rats, 30 days old, received 10% fructose, and were submitted to concomitant moderate-intensity training until 60 days old. They were divided into 4 groups: sedentary control (SC), sedentary fructose (SF), trained control (TC), and trained fructose (TF). Fructose consumption mainly affected adult animals, resulting in glucose intolerance, increased periepididymal fat, and increased total cholesterol, triglycerides, and insulin levels. Furthermore, these rats exhibited reduced sympathetic nerve activity. The moderate running led to a decrease in periepididymal and retroperitoneal adipose tissue, as well as a reduction in total cholesterol and improved glucose tolerance. Peri-pubertal rats that received combination treatments exhibited lower levels of glucose and insulin during an intraperitoneal glucose tolerance test. The results indicate that 10% fructose supplementation during peripuberty predisposes to metabolic syndrome in adulthood. However, simultaneous moderate-intensity exercise training attenuates these effects and induces positive changes in glycemic homeostasis, lipid metabolism, and autonomic nervous system activity.

Abstract: Patient blood samples are invaluable in clinical omics databases, yet current methodologies often fail to fully uncover the molecular mechanisms driving patient pathology. While Genome-scale Metabolic Models (GEMs) show promise in systems medicine by integrating various omics data, having only exometabolomic data remains a limiting factor. To address this gap, we introduce a comprehensive pipeline integrating GEMs with patient plasma metabolome. This pipeline constructs case-specific GEMs using literature-based and patient-specific metabolomic data. Novel computational methods, including adaptive sampling and an in-house developed algorithm for the rational exploration of the sampled space of solutions, enhance integration accuracy while improving computational performance. Model characterization involves task analysis in combination with clustering methods to identify critical cellular functions. The new pipeline was applied to a cohort of trauma patients to investigates shock-induced endotheliopathy using patient plasma metabolome data. By analyzing endothelial cell metabolism comprehensively, the pipeline identified critical substrates and contributed to the development of targeted therapeutic strategies. Our study demonstrates the efficacy of integrating patient plasma metabolome data into computational models to analyze endothelial cell metabolism in disease contexts. This approach offers a deeper understanding of metabolic dysregulations and provides insights into diseases with metabolic components and potential treatments.

Metabolic-associated fatty liver disease (MAFLD) and diabetic kidney disease (DKD) share various pathophysiological factors, and epidemiological evidence suggests that these two diseases are associated. Albuminuria and the estimated glomerular filtration rate, which are conventional biomarkers of DKD, are reportedly associated with the risk or severity of MAFLD. Recently, novel DKD biomarkers reflecting renal tubular injury have been introduced to complement conventional DKD markers. In this article, we looked at previous studies that showed an association between MAFLD and DKD and also reviewed the significance of DKD biomarkers as predictive risk factors for MAFLD.

Mucinous breast carcinoma is a rare subtype of mammary neoplasm encountered in medical practice. It represents approximately 1-6% of all breast cancers and is more common in postmenopausal women. There are two subtypes of mucinous breast carcinoma: pure and mixed. We report the case of a 73-year-old Caucasian woman diagnosed with mucinous pancreatic cystadenoma in 2007. She underwent a surgical procedure involving pancreatectomy of the body and tail, along with multiple known cardiovascular and metabolic comorbidities. In November 2019, during a clinical-biological evaluation for associated diseases, a mucinous carcinoma of the right breast was accidentally detected and later confirmed through further investigations. For treatment, a surgical procedure was performed involving lower right quadrantectomy with right axillary lymph node dissection. The postoperative clinical course was favorable. In conclusion, we present the case of a patient diagnosed with mixed mucinous breast carcinoma, without axillary lymph node invasion. Postmenopausal women with diabetes, overweight, and obesity have an increased susceptibility to breast cancer, with our patient having all these risk factors. To date, no study has demonstrated the genetic or radiation implication in the occurrence of mucinous carcinomas, nor the possible development of mucinous carcinomas in series in the same patient. Current data are insufficient to provide recommendations for the screening of malignant mucinous tumors in subjects with significant cardiometabolic risk factors.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has now affected nearly one third of global population and became the number one cause of chronic liver disease in the world because of the obesity pandemic. Chronic hepatitis resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) also remain significant challenges to liver health even in the 21st century. The coexistence of MAFLD and chronic viral hepatitis can markedly alter the disease course of individual diseases and can complicate the management of each of these disorders. Thorough understanding of the pathobiological interlink and interactions between MAFLD and these two chronic viral hepatitis infections are crucial for appropriate management of patients. We update these interlinks in this comprehensive clinical review.

Metabolic bone diseases cover a broad spectrum of disorders that share alterations of bone metabolism leading to a defective skeleton, associated with increasing morbidity, disability, and mortality. There is a close connection between the etiology of metabolic bone diseases and genetic factors, being TP53 one of the genes associated therewith. The single nucleotide polymorphism (SNP) Arg72Pro of TP53 is a genetic factor associated with several pathologies, including cancer, stroke and osteoporosis. Here, we aim to analyze the influence of the TP53 Arg72Pro SNP on bone mass in the humanized Tp53 Arg72Pro knock-in mice. This work reported on the influence of TP53 Arg72Pro polymorphism in bone microarchitecture, OPG gene expression and apoptosis bone status. The results showed that the proline variant of TP53 Arg72Pro polymorphism (Pro72-p53) was associated with deteriorated bone tissue, lower OPG/RANK ratio and lower apoptosis in bone tissue. In conclusion, the TP53 Arg72Pro polymorphism modulates bone microarchitecture and may be a genetic biomarker to identify individuals with an increased risk of suffering metabolic bone alterations

Salidroside, a valuable phenylethanoid glycoside, is obtained from plants belonging to the Rhodiola genus, known for its diverse biological properties. At present, salidroside is still far from large-scale industrial production due to the lower titer and higher process cost. In this study, we constructed a biosynthetic pathway from L-tyrosine to salidroside in Saccharomyces cerevisiae. To increase sali-droside production, we for the first time constructed an in vivo UDP-glucose regeneration system that sucrose synthase GmSUS worked in conjunction with UDP-glucose transferase RrUGT33 to improve the UDP-glucose availability with inexpensive sucrose as the consumed substrate. Finally, the molar conversion rate of L-tyrosine could reach 95%. To further reduce the cost, co-culture with E. coli that synthesized L-tyrosine de novo resulted in an 81% reduction in the final substrate cost per 1 kg of salidroside compared to the initial cost. The final titer of salidroside obtained 3.8 g/L and was the highest titer achieved at the Shake-Flask-Level in the existing reports. And this marked the first successful synthesis of salidroside in an in situ enhanced UDP-glucose system using sucrose. This accomplishment laid a robust groundwork for further investigations into the synthesis of other notable glycosides and natural compounds.

The traditional processing of Dendrobium officinale (DO) is manufactured through five necessary processing steps: fresh strips, drying at 85 °C, curling, molding, and drying at 35 °C (Fengdou), and the antioxidant activity of DO were increased after processing into Fengdou. To comprehensively analyses the changing functional components, a plant-wide target metabolomics were employed. In total, 739 differential ingredients were identified in five processing treatments, mainly highlighting differences in variation with phenolic acids, flavonoids, lipids, and amino acids and their derivatives, and glycosylation of aglycone result in the up-regulation in flavonoid glycosides levels. Temperature is a key step in DO processing production. In addition, the main enrichment of specific differential ingredients was found in five different metabolic pathways, including glucosinolate biosynthesis, linoleic acid metabolism, flavonoid biosynthesis, phenylpropanoid biosynthesis, ubiquinone and other terpene quinone biosynthesis. Correlation analysis clarified that total phenols and flavonoids showed a significant positive correlation with antioxidant capacity. This study provides new insights into the influence of processing processes on DO quality, which may lead to guidance for the high-quality production of DO.

Obesity is a troubling public health problem worldwide as it increases risks of respiratory complications, systemic arterial hypertension, type 2 diabetes mellitus, sleep disorders, cardiovascular diseases, and metabolic syndrome (MetS). As a measure to counteract comorbidities associated with severe obesity, bariatric surgery stands out. This study aimed to investigate the adiponectin/leptin ratio in women with severe obesity with and without MetS undergone Roux-en-Y Gastric Bypass (RYGB) and to characterize the biochemical, glucose, and inflammatory parameters of blood in women with severe obesity before and after RYGB. Were enrolled female with severe obesity undergoing RYGP with MetS (n=11) and without (n=39). Anthropometric data and blood samples were obtained before and 6 months after RYGB to analyze total cholesterol, low-density lipoprotein (LDL), high- density lipoprotein (HDL), non-HDL total cholesterol, and glucose; and circulating levels of adiponectin and leptin. Significant reductions in weight, body mass index, and glucose, total cholesterol, LDL, and leptin were observed after surgery, with higher levels of HDL, adiponectin, and adiponectin/leptin ratio observed after surgery compared to preoperative values. This study demonstrated that weight loss induced by RYGB in patients with severe obesity with or without MetS improved biochemical and systemic inflammatory parameters, particularly the adiponectin/leptin ratio.

Obesity and metabolic syndrome involve chronic low-grade inflammation called metabolic inflammation as well as metabolic derangements from increased endotoxin and free fatty acids. It is debated whether the endoplasmic reticulum (ER) stress in monocytic cells can contribute to amplify metabolic inflammation; if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 monocytic cells by treatments with lipopolysaccharide (LPS), palmitic acid (PA), or oleic acid (OA), in the presence or absence of ER stressor thapsigargin (TG). Gene expression of tumor necrosis factor (TNF)-α and markers of ER/oxidative stress was determined by qRT-PCR, TNF-α protein by ELISA, ROS by DCFH-DA assay, HIF-1α/p38/ERK-1,2/NF-κB phosphorylation by immunoblotting, and insulin sensitivity by glucose-uptake assay. Regarding clinical analyses, adipose TNF-α was assessed by qRT-PCR/IHC and plasma TNF-α/hs-CRP/MDA/OX-LDL by ELISA. We found that the cooperative interaction between metabolic and ER stresses promoted TNF-α, ROS, CHOP, ATF6, SOD2, and NRF2 expression (P≤0.0183),. However, glucose uptake was not impaired. TNF-α amplification was dependent on HIF-1α/p38/NF-κB phosphorylation, while MAPK/NF-κB inhibitors and antioxidants/ROS scavengers attenuated TNF-α production (P≤0.05). Individuals with obesity displayed increased adipose TNF-α gene/protein expression as well as elevated plasma levels of TNF-α, CRP, MDA, and OX-LDL (P≤0.05). Our findings support a cooperative interaction between metabolic and ER stresses, favoring inflammation by triggering TNF-α production via the ROS/CHOP/HIF-1α and MAPK/NF-κB dependent mechanisms. This study also shows the therapeutic potential of ROS scavengers/anti-oxidants in inflammatory conditions involving metabolic/ER stresses.

Alzheimer's disease (AD) is an incurable neurodegenerative disorder. Early screening, particularly in blood has been regarded as an effective approach for AD diagnosis and prevention. In addition, metabolic dysfunction has been demonstrated to be closely related to AD, which might be reflected in whole blood transcriptome. Hence, we hypothesized that establishment of diagnostic model based on metabolic signatures of blood is a workable strategy. To the end, we initially constructed metabolic pathway pairwise (MPP) signatures to characterize the interplay among metabolic pathways. Then, a series of bioinformatic methodologies, e.g., differential expression analysis, functional enrichment analysis, and network analysis, etc. were used to investigate the molecular mechanism behind AD. Moreover, an unsupervised clustering analysis based on the MPP signature profile via Non-Negative Matrix Factorization (NMF) algorithm was utilized to stratify AD patients. Finally, aimed at distinguishing AD patients from non-AD group, a metabolic pathway-pairwise scoring system (MPPSS) was established using multi-machine learning methods. As a result, many metabolic pathways correlated to AD were disclosed, including oxidative phosphorylation and fatty acid biosynthesis, etc. NMF clustering analysis divided AD patients into two subgroups (S1 and S2), which exhibit distinct activities of metabolism and immunity. Typically, oxidative phosphorylation in S2 exhibits a lower activity than that in S1 and non-AD group, suggesting the patients in S2 might possess a more compromised brain metabolism. Additionally, Immune infiltration analysis showed that the patients in S2 might have phenomena of immune suppression, compared with S1 and non-AD group. These findings indicated that S2 probably have a more severe progression of AD. Finally, MPPSS could achieve an AUC of 0.73 in training dataset, 0.71 in testing dataset and an AUC of 0.82 on weighted average in five external validation datasets. Overall, our study successfully established a novel metabolism-based scoring system for AD diagnosis using blood transcriptome, and provided new insight into the molecular mechanism of metabolic dysfunction implicated in AD.

Ischemic stroke is one of the leading causes of death and permanent disability in the world. Rapid diagnosis and intervention are crucial for reducing its consequences on individuals and societies. Identifying reliable biomarkers for early detection, prognostics and therapy is a criti-cal imperative for improving the stroke patient treatment. Metabolomics has been shown as a promising tool for biomarker discovery since many of the post-ischemic metabolites can found in the plasma or serum of the patient. In this research, we have performed comparative targeted metabolomic analysis of stroke thrombi, patient serums and healthy control serums in order to determine the alteration in the patients’ metabolome. The most statistically altered metabolites characterized in patient compared to control serums were glutamate and serotonin, followed by several lipid metabolites (phospholipids and triacylglycerols) and glucose. In stroke thrombi compared to patient’s serums, the most significantly altered metabolites were classified as li-pids, with choline-containing phospholipids and sphingomyelins having the highest discrimi-natory score. The results of this study could help in understanding the roles of different meta-bolic changes occurring during thrombosis and cerebral ischemia and possibly suggest new metabolic biomarkers of the ischemic stroke.

Metabolic syndrome is a growing global health problem. Evidence suggests that diets rich in phytochemical-containing herbs and spices can contribute to reduced risk of chronic disease. This review assesses the scope of evidence supporting the use of herbs and spices in the diet for prevention or treatment of metabolic syndrome and associated health conditions. A search of PubMed and Scopus databases was carried out to assess the available clinical or cohort evidence for culinary doses of commonly used herbs and spices. Trials that were measuring health factors related to metabolic disorders or the health of individuals with metabolic syndrome or associated diseases were included. Out of a total of 1742 papers identified, there were 146 relevant studies on black pepper, chilli, cardamom, cinnamon, coriander, cumin, fennel, fenugreek, garlic, ginger, Nigella seed, rosemary, sage and turmeric. No relevant research was found for cloves, mint, oregano, parsley or thyme. Cinnamon, fenugreek and ginger were the herbs/spices with the most published trials on them and showed promise for glycaemic control. Cardamom appears to have potential to reduce inflammatory markers, and cinnamon, ginger and turmeric for blood lipids. Patients with type 2 diabetes were the population most likely to be included in studies, but the preventative benefits of herbs/spices in healthy populations were also investigated, particularly for chilli, ginger and cinnamon. There is evidence for the beneficial effect of culinary doses of many common herbs/spices in the prevention and treatment of metabolic syndrome and associated disorders.

Variation in metabolite profiles of under high salinity and nitrogen constraint conditions are the key issues of study at the present. To investigate the optimum NaCl and NaNO3 concentration and the corresponding metabolic pathways of astaxanthin accumulation in H. pluvialis, a 26-day batch culture experiment of H. pluvialis treated under the variable concentration gradients of NaCl and NaNO₃ were conducted. The results indicated that 7.5g•L^-1 and nitrogen-deficient were the optimum NaCl and NaNO₃ concentration for the astaxanthin accumulation according to single factor experiments respectively, under which the highest contents of astaxanthin accumulated in H. pluvialis reached up to 7.51mg•L^-1 and 5.60mg•L^-1. A total of 132 metabolites were analysed using LC-MS/MS technique, among which 30 differential metabolites with statistical significance were highlighted. Subsequently, 18 and 10 differential metabolic pathways in the high salinity and nitrogen-deficient treatments with statistic significance were enriched and annotated respectively. Furthermore, the metabolic networks related to the astaxanthin accumulation were constucted based on the crucial pathways and metabolites. Moreover, the major carbon metabolism in H. pluvialis under the high salinity and nitrogen deficient stress were presented, which exhibited the characteristics in the identified metabolites changes under the different stress conditions. The results did not only demonstrate the differential metabolic networks and the distinct changes in the metabolites involved in the major carbon metabolism, related to the astaxanthin accumulation in H. pluvialis under the different stress factors, but provided the regulation targets for astaxanthin production in practice.

A number of epidemiological studies have implicated elevated iron levels with higher risks of cardiometabolic diseases, including the metabolic syndrome (MetS). MetS is a pathologic clustering of metabolic derangements characterized by central obesity, insulin resistance, hypertension, and dyslipidemia, which can all lead to increased cardiovascular disease morbidity and mortality. However, it remains unclear whether a causal association exists between higher iron status and MetS and its associated risk components. Using the data from the Taiwan Biobank (TWB) (19,012 males; 42,340 females) and of the European Whites from the UK Biobank (UKB) (128,549 males; 142,817 females), we first constructed ethnic- and sex-specific hemoglobin-polygenic risk scores (Hb-PRS) as instrumental variable (IV) for iron status with the Hb-associated SNPs we previously identified from genome-wide association studies (GWAS). We then conducted Mendelian randomization (MR) analyses to elucidate the causal role of elevated iron (either Hb-PRS quintiles or continuous Hb-PRS) on various metabolic components. MR-Egger regressions determined the potential pleiotropic effects of the constructed Hb-PRSs, while the causal relationship of Hb-PRS with anemia served as a control in the analyses. The mean Hb concentration range corresponding to the Hb-PRS quintiles is relatively narrow in both UKB (14.91-15.21 g/dL for males and 13.39-13.71 g/dL for females) and TWB (14.79-15.28 g/dL for males and 12.78-13.21 g/dL for females). In these windows of Hb-PRSs, we found differential associations of Hb-PRS with diabetes (T2D) or hyperglycemia (HGY) as compared to other MetS components. The highest quintiles of Hb-PRSs were causally associated with greater risks of hypertension (HTN) and hypertriglyceridemia (DLP) (i.e., [Taiwanese HC males: Q5 vs. Q1 ORHTN = 1.10 (1.00–1.21), p = 0.0473, Q4 vs. Q1 ORDLP = 1.10 (1.00–1.22), p = 0.0485; European White males: ORHTN = 1.05 (1.01–1.09), p = 0.0194, ORDLP = 1.04 (1.00–1.08), p = 0.0468]). Interestingly, we obtained a consistent negative causal association between increasing Hb-PRS quintiles and T2D or HGY risk across all sex subgroups (i.e., [Taiwanese HC females: ORHGY = 0.89 (0.84–0.95), 0.88 (0.83–0.94), 0.87 (0.82–0.93), 0.86 (0.81–0.92) from Q2 to Q5; European White females: ORHGY = 0.92 (0.87–0.98), 0.91 (0.86–0.97), 0.93 (0.87–0.98), 0.87 (0.82–0.93) from Q2 to Q5; all p &lt; 0.05]. The positive causal relationships between Hb-PRSs and diastolic blood pressure (DBP) and triglycerides (TG) but inverse causal association with glucose (GLU) and glycated hemoglobin (HbA1c) further corroborated such findings. There is, however, a lack of causal association with central obesity (CO), while a U-shaped type of causality was observed for gout (GT) or hyperuricemia (HUA). Sensitivity analyses, which excluded subjects based on self-reports of health conditions or medications and hospital episode statistics data, revealed similar results. Our MR studies confirm a modest causal relationship between propensity of elevated iron status and increased risk of HTN and DLP. We have further observed that modestly lower iron levels causally contribute to the development of T2D. Further validation and elucidation of the underlying biological mechanisms are highly warranted.

A widely discussed topic in the pathophysiology of thyroid nodules is the role of obesity that leads to increased systemic inflammatory markers. Leptin plays a vital role in forming thyroid nodules and cancer through several mechanisms. Together with chronic inflammation, there is an augmentation in the secretion of tumor necrosis factor (TNF) and cytokines interleukin 6 (IL-6), contributing to cancer development, progression and metastasis. In addition, leptin exerts a modulatory action in the growth, proliferation and invasion of thyroid carcinoma cell lines via activating various signal pathways, such as Janus kinase/signal transducer and activator of transcription, mitogen-activated protein kinase (MAPK) and/or phosphoinositide 3-kinase (PI3K) /protein kinase B (Akt). Through several proposed mechanisms, aberrant endogenous estrogen levels have been suggested to play a vital role in the development of both benign and malignant nodules. Metabolic syndrome triggers the development of thyroid nodules by stimulating thyroid proliferation and angiogenesis due to hyperinsulinemia, hyperglycemia and dyslipidemia. Insulin resistance influences the distribution and structure of the thyroid blood vessels. Insulin growth factor -1 (IGF-1) and insulin affect the regulation of the expression of thyroid genes and the proliferation and differentiation of thyroid cells. TSH can promote the differentiation of pre-adipocytes to mature adipocytes, but also, in the presence of insulin, TSH possesses mitogenic properties. This review aims to summarize the underlying mechanisms explaining the role of obesity in the pathophysiology of thyroid nodules and discuss potential clinical implications.

Increasing evidence of sexual dimorphism in pathophysiology of metabolic complications caused by sex steroids is under investigation. The gut microbiota represents a complex microbial ecosystem involved in energy metabolism, immune response, nutrition acquisition, and health of host organisms. Gender-specific differences in composition are present between females and males. The purpose of this study was to use cross-sex fecal microbiota transplantation (FMT) for the detection of sex-dependent metabolic, hormonal, and gut microbiota changes in female and male recipients. Healthy non-obese female and male Wistar rats were divided into donor, same-sex, and cross-sex recipient groups. After a 30-day period of FMT administration, biochemical markers (glucose and lipid metabolism) and sex hormones were measured and gut microbiota was analyzed. Cross-sex male recipients displayed significantly lower testosterone concentration compared to males that received same-sex FMT. Sex-dependent changes caused by cross-sex FMT were detected, while several bacterial taxa correlated with plasma testosterone levels. This study represents the first to study the effect of cross-sex changes in the gut microbiome concerning metabolic and hormonal changes/status in adult non-obese Wistar rats. Herein, we present the cross-sex FMT as a potential tool to modify sex-specific pathologies.

Recently, we isolated and characterized a new pool of mesenchymal stem cells- HPC (Hoof Progenitor Cells), which reside in the coronary corium of equine hooves. We hypothesize, that due to their location, HPC may be involved in the pathogenesis of laminitis, and could possibly be utilized in its treatment. The aim of this study was to compare the newly described HPC to a well-established cell pool-ASC (Adipose Stem Cells). The two cell populations were maintained either in standard culture conditions or under a hyperinsulinemic milieu as hyperinsulinemia is often observed alongside laminitis. Cell cycle dynamics, mitochondrial membrane potential and oxidative stress were analyzed with microcapillary cytometry. Furthermore, the expression of key markers of mitochondrial metabolism, oxidative stress, apoptosis, immunomodulation and insulin signalling were analyzed with the RT-qPCR method. Additionally, a selected panel of miRNA was analyzed with the RT-qPCR method. In standard culture conditions, ASC exhibit higher proliferation than HPC while in hyperinsulinemia a shift towards S phase was observed in both populations. As for the mitochondrial membrane potential, in standard culture conditions, HPC was characterized by a higher percent of live cells. Hyperinsulinemia did not strongly affect the mitochondrial membrane potential of the analyzed populations. Our findings indicate that HPC are characterized by higher activity in terms of mitochondrial dynamics, mitophagy, and mitochondrial biogenesis under standard culture conditions. Yet in both populations, a diminished mitochondrial dynamic and metabolism was observed in hyperinsulinemia. The analysis of oxidative stress revealed, that HPC might possess somewhat higher resistance towards oxidative stress than ASC. Minimal change was observed in the expression of key markers of apoptosis in ASC and HPC under hyperinsulinemia. The analysis of key immunomodulatory markers indicated that HPC may help the cytokine storm for a more effective phenotype change to an immunosuppressing pool of cells with better migratory and healing abilities under hyperinsulinemia than ASC. As for insulin signalling, the obtained data suggests that HPC might be more resistant to hyperinsulinemia and may have greater therapeutic potential in reducing laminitis. Obtained results demonstrated that HPC possesses better potential to modulate the PTEN-AKT pathway by miR-21 and reverse high glucose and high insulin-induced insulin resistance. Taken together, the obtained results indicate that HPC may be a very promising cell pool with therapeutic potential in laminitis treatment, and could be more effective than ASC.

This article explores the relationship between metabolic syndrome and cardiovascular disease, providing a comprehensive overview of its risk factors and prevalence. Metabolic syndrome, characterized by a cluster of interconnected risk factors, significantly increases the likelihood of developing cardiovascular disease and type II diabetes. The study, conducted over a one-year period, involved 117 patients with ages between 30 to 79 years old. Various elements such as gender, age, education level, background, smoking, alcohol consumption, dietary aspects, physical activity, and their contribution in developing the metabolic syndrome, were analysed.Central adiposity and high blood pressure emerged as prominent elements of the condition. The findings underscore the importance of a healthy lifestyle in the prevention and management of metabolic syndrome. Encouraging regular physical activity, maintaining a balanced diet, rich in fresh vegetables and fruits, and avoiding harmful behaviours, such as smoking or alcohol consumption, are essential in reducing the risk of metabolic syndrome and its associated cardiovascular complications. The study highlights the need for public health initiatives, as well as individualized preventive strategies to combat the rising prevalence of metabolic syndrome. Through promoting awareness of its risk factors and implementing effective interventions, healthcare professionals can contribute to better cardiovascular health worldwide. Further research in this area will continue to enhance our understanding of the metabolic syndrome and refine preventive and therapeutic approaches for its management.

In conclusion, the present study demonstrated the safety of practicing WFM at different TOD. Furthermore, it appears that practicing WF in the evening is safer, as indicated by HRR60s, [Gl], and MBP findings. The utilization of digital biomarkers for monitoring health status during WFM has been shown to be efficient.

Soil improvement methods can result in changes in the microbial community in blueberry soil. However, there have been few reports on the impacts of different soil improvement methods on the microbial function, particularly on endophytic microbe. In this study, we analyzed the response of microbial community composition, microbial function and nitrogen (N) cycle to different improvement methods using high throughput sequencing. We aimed to investigate the best soil improvement method from a microbial perspective. The results showed that the highest microbial diversity was observed in the T4 treatment (peat combined with mushroom bran), followed by the T2 treatment (peat combined with acidified rice husk) both in the rhizosphere and roots. The dominant phyla were Proteobacteria and Actinobacteria, which were most abundance in the T4 and T1 (peat combined with sulfur) treatments in the rhizosphere soil, respectively, but showed the opposite trend in the root endophytic bacterial community. Interestingly, Acidobacterium and Paludibaculum, belonging to the Acidobacteria phylum, were found to have the highest influence according to the correlation network analysis. And these bacteria were most abundant in the T2 treatment in the rhizosphere soil. The rhizosphere soil microbial communities were clustered into two categories: one for T1 and T2 treatments, and another for T3 (mushroom bran) and T4 treatments. Compared to the other treatments, the T1 treatment had the most significant impact on microbial functional pathways in the blueberry roots. T2 treatment promoted the growth of N fixation functional bacteria both in the rhizosphere soil and roots. At the module level, the T2 treatment increased the relative abundance of N fixation and decreased the relative abundance of assimilating nitrate reduction reaction (ANRA), dissimilating nitrate reduction reaction (DNRA), denitrification and completed nitrification in the blueberry rhizosphere soil. Additionally, the T2 treatment increased the abundance of root endophytic microbes involved in N fixation. Overall, our findings suggest that the addition of peat combined with acidified rice husk is the optimal soil improvement method for blueberry cultivation.

Gait variability (GV) is a crucial measure of inconsistency of muscular activities or body seg-mental movements during repeated tasks. Hence, GV might serve as a relevant and sensitive measure to quantify adjustments of walking control. However, has not been clarified whether GV is associated with walking speed to exploit effective better coordination level. Fourteen male stu-dents (age 22.4 ± 2.7 years, body mass 74.9 ± 6.8 kg, body height 1.78 ± 0.05 m) took part in this study. After three days of walking 1 km each day at a self-selected speed (SS) on asphalt with Apple Watch S. 7 (AppleTM), the participants were randomly evaluated on a treadmill at three different walking speed intensities for 10 minutes each one, at SS-20% / SS+20% of SS, with 5 minutes of passive recovery in-between. Heart rate (HR) was monitored beat-to beat and nor-malized as HR%MAX, while the rate of perceived exertion (RPE) (CR-10) was asked after each trial. Kinematic analysis was performed assessing the Contact Time (CT), Swing Time (ST), Stride Length (SL), Stride Cycle (SC) and Gait Variability as Phase Coordination Index (PCI). RPE and HR increased with higher walking speed (P = 0.005 and P = 0.035, respectively). CT and SC decreased as the speed increased (P = 0.0001 and P = 0.013, respectively), while ST remained un-changed (P = 0.277). SL increased with higher walking speed (P = 0.0001). Conversely, PCI was 3.81 ± 0.88 % (high variability) at 3.96 ± 0.47 km·h-1, 2.64 ± 0.75 % (low variability) at SS (4.94 ± 0.58 km·h-1), 3.36 ± 1.09 % (high variability) at 5.94 ± 0.70 km·h-1 (P = 0.001). These results indi-cate that while the metabolic demand and kinematics variables changing linearly with increasing speed, the most effective GV was observed at SS. Therefore, SS could be a new methodological approach to choose the individual walking speed, normalize the speed intensity, and avoid a gait pattern alteration.

Purpose of Review Multipotent Mesenchymal stromal cells (MSCs) have recently risen to prominence in regenerative medicine for their powerful intrinsic properties of self-regeneration, immunomodulation, and multi-potency. They exhibited an excellent safety profile in early-phase clinical trials. Nevertheless, MSCs-based therapy suffers reduced efficacy in randomized clinical trials due to a poor understanding of their proper delivery modalities. Here, we intend to explore the current application of MSCs after tissue injuries. We specifically focus on tissue source, delivery routes, metabolic fitness, and cell dose. We further discuss potential approaches to optimize in vivo engraftment. Recent findings MSCs therapeutic effect mediates by paracrine and contact factors, which are cells' intrinsic physiological processes. The cell culture expansion process does not destroy MSCs' intrinsic properties. In vivo persistence of administered MSCs determines their therapeutic potency. Cell viability, fitness, immune match, and delivery route meticulously regulate their in vivo persistency. Different genetic or chemical modification strategies are currently applied to extend their in vivo lifespan and boost their pharmaceutical effect. Summary Improving the in vivo persistence of implanted MSCs could facilitate its clinical translation. This review highlights the pros and cons of different MSCs’ delivery strategies used in clinical or preclinical studies, emphasizing various modification approaches. These can promote prolonged graft cell survival.

Abstract Background: Metabolic syndrome (MetS) is a complex disorder characterized by insulin resistance (IR), central obesity, atherogenic dyslipidemia and higher glucose levels. It increases the risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), imposing an economic burden on the healthcare system. However, the historical origins of MetS as well as the development and evolution of its definitions have not been conclusively documented in the literature. Aim: This study seeks to enhance the understanding of the developmental trends of MetS during the preceding two decades, placing particular emphasis on the definition, diagnosis and prevalence. Methods: An extensive search was performed from 1920 to 2023 across prominent scientific research engines, including Scopus, PubMed, MDPI, and others. Results: Despite advancements, many aspects of MetS remain inadequately understood. As the understanding of the nature and pathophysiology of MetS progresses, the development and refinement of its diagnostic criteria, and assessment and treatment guidelines will continue. Additionally, there exists significant variation in the global prevalence of metabolic syndrome, ranging from 14 to 39%. This prevalence is projected to increase due to the adoption of less healthy dietary patterns and sedentary lifestyles. The observed disparities in metabolic syndrome prevalence can be attributed to multiple factors, including demographic characteristics. Furthermore, the lack of a standardized definition across studies also contributes to the variation in reported prevalence rates. Conclusion: Further studies focusing on the standardization of the MetS definition across different research are crucial. The establishment of consistent criteria would enhance the reliability and validity of research findings, enabling more meaningful comparisons and interpretations.

Modern research achievements support health-promoting effects of natural products and diets rich in polyphenols. Pomegranate (PG) (Punica granatum L.) contain a considerable number of bioactive compounds that exert a broad spectrum of beneficial biological activities, including antimicrobial, antidiabetic, antiobesity, and atheroprotective properties. In this view, the reviewed literature shows that PG intake might reduce insulin resistance, cytokine levels, redox gene expression, blood pressure elevation, vascular injuries and lipoprotein oxidative modifications. Lipid parameters corrective capabilities of PG-ellagitannins are also sufficiently reported to be significantly effective in reducing hyperlipidemia (TC, LDL-C, VLDL-C, and TAGs), plasma HDL-C concentrations, TC/HDL-C and LDL-C/HDL-C ratio. The health benevolent effects of pomegranate consumption appear to be produced through the amelioration of adipose tissue endocrine function, fatty acid utilization, GLUT receptor expression, paraoxonase activity enhancement, PPAR and NFκB modulation. Although the results from animal experiments are encouraging, human findings published in this field are inconsistent and still limited in many points of view. The present review discusses and provides a critical analysis of PG's bioeffects on metabolic syndrome components, type-2 diabetes, obesity, and dyslipidemia, as well as on some cardiovascular-related diseases. A brief overview of the pharmacokinetic properties, safety, and bioavailability of PG-ellagitannins is also included.

Maternal obesity and gestational diabetes predispose to metabolic disturbances in the next generation. Moreover, the lactation phase also stands as critical for metabolic programming. Nevertheless, the precise mechanisms originating these changes remain unclear. Here we investigate the consequences of maternal diet lipid-rich diet during gestation and lactation, and its impact on metabolism and behavior in the offspring. Two experimental groups of Wistar female rats were used: a control group (NC) that fed a standard diet during gestation and lactation periods and an overnutrition group that fed a high-fat diet (HF, 60% lipid-rich) during the same phases. Offspring were analyzed at postnatal days 21, 28, and 2 months-old (PD21, PD28, PD60) for metabolic profile (weight, fasting glycemia insulin sensitivity, glucose tolerance) and euthanized for brain collection to evaluate by western blot markers of synaptic dynamics, metabolism and inflammation in the hypothalamus, hippocampus and prefrontal cortex. At 2 months-old, behavioral tests for anxiety, stress, cognition, and food habits were conducted. We observe that female offspring born from HF mothers exhibited increased weight gain and decreased glucose tolerance that attenuates with age. In offspring males, weight gain increased at P21 and worsened with age, while glucose tolerance remained unchanged. Offspring of HF mothers exhibited elevated levels of anxiety and stress during behavioral tests, displaying decreased predisposition for curiosity compared to the NC group. In addition, offspring from mothers with HF showed increased food consumption and a lower tendency towards food-related aggression. We conclude that exposure to HF diet during pregnancy and lactation induces dysmetabolism in the offspring accompanied by heightened stress and anxiety. There was sexual dimorphism in metabolic traits but not behavioral phenotypes.

Several factors, such as internal algorithm, sensor technology, and obsolescence might skew outcomes when comparing different gas analysers measurements during CPET. Besides aerosol borne infectious disease are a source of contamination during cardiopulmonary exercise tests (CPET). Thus, the main aim of this study was to determine the agreement degree between the Quark RMR and the Jaeger Oxycon Pro, using an antibacterial filter with the latter. Forty-two participants (19-54 years old) performed two non-consecutive maximal graded exercise tests on a cycle-ergometer on two counterbalance and different days using the Oxycon Pro and the Quark RMR in a randomized order. Differences between devices were tested using a generalized linear model adjusted by Bonferroni, and correlation and agreement was assessed using Pearson’s correlation coefficient (R), intraclass coefficient correlation (ICC), Lin’s concordance correlation coefficient (CCC) and Bland-Altman plots. No significant differences were found between devices in any of metabolic or ventilatory parameters for cardiorespiratory fitness assessment (VO_2max: 3131.3±882.1 vs. 3189.8±894.8, p=0.071, VCO_2max: 3436.3±936.0 vs. 3550.3±1043.2, p=0.071, for Quark RMR and Oxycon Pro, respectively). However, Bland-Altman plots showed a trivial tendency towards Oxycon Pro overestimation relative to Quark RMR as air flow volume increases. Both devices showed strong correlation and high level of agreement during maximal and submaximal exercise intensities (Pearson’s R: 0.974 & 0.977; ICC: 0.985 & 0.987; Lin’s CCC: 0.971 & 0.974, for VO₂ and VCO₂, respectively). Therefore, providing consistency to CPET data comparison between both devices, and insight into whether the use of these metabolic carts could be interchangeable or combined when a single device cannot be used for CPET assessment.

Background and Aims: Metabolic Syndrome (MetS), a global problem, predisposes to an increased risk for Type 2 diabetes and premature cardiovascular disease. While MetS is associated with central obesity, there is scanty data on adipocyte hypertrophy, increased fat cell size (FCS), in MetS. The aim of this study was to investigate FCS status in gluteal adipose tissue biopsy of patients with nascent MetS without the confounding of diabetes, cardiovascular disease, smoking or lipid therapy . Methods and Results: Fasting blood and subcutaneous gluteal adipose tissue (SAT) biopsy were obtained in MetS (n=20) and controls (n=19). Cardio metabolic features, FFA levels, hsCRP and HOMA-IR were significantly increased in patients with MetS. Waist-circumference adjusted-FCS was significantly increased in patients with MetS and increased with increasing severity of MetS. Furthermore, there were significant correlations between FCS with glucose, HDL-C and the ratio of TG: HDL-C. There were significant correlations between FCS and FFA, endotoxin and monocyte TLR4 abundance. Also, FCS correlated with readouts of NLRP3 Inflammasome activity. Most importantly, FCS correlated with markers of fibrosis and angiogenesis. Conclusions: In conclusion, in patients with nascent MetS, we demonstrate WC-adjusted increase in FCS from gluteal AT that correlated with cellular inflammation, fibrosis and angiogenesis. While these preliminary observations were in gluteal fat, future studies are warranted to confirm these findings in visceral and other fat depots.

Porphyrinic photosensitizers (PSs) and their nano-sized polymer-based carrier systems are required to exhibit low dark toxicity, avoid side effects, and ensure high in vivo tolerability. Yet, little is known about the intracellular fate of PSs during the dark incubation period and how it is af-fected by nanoparticles. In a systematic study, high resolution magic angle spinning NMR spectroscopy combined with statistical analyses was used to study the metabolic profile of cultured HeLa cells treated with different concentrations of the PS chlorin e4 (Ce4) alone or encapsulated in carrier systems. For the latter, either polyvinylpyrrolidone (PVP) or the micelle forming polyethylene glycol (PEG)-polypropylene glycol triblock copolymer Kolliphor P188 (KP) were used. Diffusion edited spectra indicated Ce4 membrane localization evidenced by Ce4 concentration dependent chemical shift perturbation of the cellular phospholipid choline resonance. The effect was also visible in the presence of KP and PVP, but less pronounced. The appearance of the PEG resonance in the cell spectra pointed towards cell internalization of KP whereas no conclusion could be drawn for PVP that remained NMR-invisible. Multivariate statistical analyses of the cell spectra (PCA, PLS-DA and oPLS) revealed a concentration-dependent metabolic response upon exposure to Ce4 that was attenuated by KP and even more by PVP. Significant Ce4-concentration dependent alterations were mainly found for metabolites involved in the tricarboxylic acid cycle and the phosphatidylcholine metabolism. The data underline an important protective role of the polymeric carriers following cell internalization. Moreover, the current study allowed - to our knowledge for the first time - to trace the intracellular PS localization on an atomic level by NMR methods.

(1) Introduction: The COVID-19 pandemic presented unique challenges for patients and healthcare providers, especially for those working with obesity and related health problems. E-health has emerged as a crucial tool for the follow-up of users undergoing bariatric surgery during this period, allowing remote monitoring of users' health status and providing access to virtual consultation with health professionals. This study aims to analyze the impact of the use of telemedicine during the COVID-19 pandemic on the results of bariatric surgery and user satisfac-tion with this follow-up. (2) Method: Observational study with retrospective data collection. The variables were divided into several groups: health data, associated comorbidities, quality of life, quality of sleep and satisfaction with telemedicine monitoring. (3) Results: Surgery significantly affected weight loss, in general more than 75% loss of excess weight. Comorbidities, like the qual-ity of life, were reversed over time, with 50% of subjects maintaining excellent levels. Although most users were satisfied with the monitoring, the variables had no relationship. (4) Conclusions: The follow-up assured by telemedicine did not alter the results of bariatric surgery, which may allow us to infer that it may be an option to consider for regular monitoring of the post-bariatric surgery process.

Adenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabo-lism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, albeit 10-year clinical trial data in Duchenne muscular dystrophy patients suggests a chronically safe drug. In this study, we tested the toxicity of ASA to cultured myoblasts in vitro and acute systemic toxicity in mice. ASA is a non-toxic small molecule with an LD50> 5000mg/kg. Some background necrotic foci in the liver, kidney and gastrointestinal tract were shown that are likely incidental but warrant follow-up sub-/chronic oral exposure studies.

Intratumoral immune cytolytic activity (CYT), measured as the geometric mean of the expression of Granzyme-A (GZMA) and Perforin-1 (PRF1), has emerged as a critical factor in cancer immunotherapy, with significant implications for patient prognosis and treatment outcomes. Here, we review how different immune checkpoint pathways, the composition of Tumor Microenvironment (TME), antigen presentation and metabolic pathways, all regulate CYT. We also discuss the various methods through which CYT can be assessed. The detection and analysis of tumor-infiltrating lymphocytes using flow cytometry or immunohistochemistry provide important information on the immune cell populations within the TME. Gene expression profiling and spatial analysis techniques, such as multiplex immunofluorescence and imaging mass cytometry, allow researchers to study CYT in the context of the TME. We further report the significant clinical implications that CYT has, as its increased levels are associated with positive clinical outcomes and a favorable prognosis. Moreover, CYT can be used as a prognostic biomarker and aid in patient stratification. Measuring CYT through different methods offers promising paths for improving treatment responses. Overall, we highlight that the understanding and modulation of CYT levels is critical for improving cancer immunotherapy. Research into CYT and the factors that influence it has the potential to transform cancer treatment and improve patient outcomes.

The current view of the mitochondrial respiratory chain complexes I, III and IV foresees the oc-currence of their assembly in supercomplexes providing additional functional properties as compared with randomly colliding isolated complexes. According to the plasticity model, these two structural states of the respiratory chain may interconvert influenced by the intracellular prevailing conditions and in previous studies we candidated the mitochondrial membrane po-tential as a factor controlling their dynamic balance. Here, we extended those studies investigating if and how the cAMP/PKA-mediated signalling influences the aggregation state of the respiratory complexes. Analysis of inhibitory-titration profiles of the endogenous oxygen consumption rates in intact HepG2 cells with specific inhibitors of the respiratory complexes was performed to quantify, in the framework of the metabolic flux theory, the corresponding control coefficients. The results attained inhibiting pharmacologically either PKA and sAC indicate that the reversible phosphorylation of the respiratory chain complexes/supercomplexes influences their assembly state in response to the membrane potential. This conclusion is supported by scrutiny of the available structure of the CI,CIII2,CIV respirasome enabling to map several PKA-target serine residues exposed to the matrix side of the complexes I, III and IV at the contact interfaces of the three complexes.

The aim of this study was to determine the association of metabolic syndrome (MetS) with kidney cancer and the impact of age and gender on such association. Using Korean National Health Insurance Service database, 9,932,670 subjects who had check-up in 2009 were followed up until the diagnosis of kidney cancer or death or until 2019. Kidney cancer was significantly associated with MetS (HR 1.56). This association was higher in the younger age group (HR: 1.82, 1.5, and 1.37 in 20-39 years, 40-64 years, and ≥65 years, respectively). In terms of the association of kidney cancer with obesity and central obesity, young-aged males showed higher HR for kidney cancer than old-aged ones (HR of obesity: 1.96, 1.52, and 1.25; HR of central obesity: 1.94, 1.53, and 1.3 in 20-39 years, 40-64 years, ≥65 years, respectively), while young-aged females showed lower HR. Kidney cancer was associated with obesity and MetS. The association was higher in younger aged population than in older ones. Regarding gender, MetS, obesity, and central obesity showed higher associations with kidney cancer in younger aged male population, while there was no significant difference in such association according to age in females.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Evidence from large epidemiological studies has shown that obesity may predispose to increased Th2 inflammation and increase the odds of developing asthma. On the other hand, there is growing evidence suggesting that metabolic dysregulation that occurs with obesity, and more specifically hyperglycemia and insulin resistance, may modify immune cell function and in some degree systemic inflammation. Insulin resistance seldom occurs on its own, and in most cases constitutes a clinical component of metabolic syndrome, along with central obesity and dyslipidemia. Despite that, in some cases, hyperinsulinemia associated with insulin resistance has been proven a stronger risk factor than body mass in developing asthma. This finding has been supported by recent experimental studies showing that insulin resistance may contribute to airway remodeling, promotion of airway smooth muscle (ASM) contractility and proliferation, increase of airway hyper-responsiveness and release of pro-inflammatory mediators from adipose tissue. All these effects indicate the potential impact of hyperinsulinemia on airway structure and function, suggesting the presence of a specific asthma phenotype with insulin resistance. Epidemiologic studies have found that individuals with severe and uncontrolled asthma have a higher prevalence of glycemic dysfunction, whereas longitudinal studies have linked glycemic dysfunction to an increased risk of asthma exacerbations. Since the components of metabolic syndrome interact with one another so much, it is challenging to identify each one's specific role in asthma. This is why, over the last decade, additional studies have been conducted to determine whether treatment of type 2 diabetes mellitus affects comorbid asthma as shown by the incidence of asthma, asthma control and asthma-related exacerbations. The purpose of this review is to present the mechanism of action, and existing preclinical and clinical data, regarding the effect of insulin resistance in asthma.

The aim was to determine the effect of Sechium edule var. nigrum spinosum (chayote) on gene ex-pression related to antioxidant protection mechanisms and the inflammatory process in older adults with metabolic syndrome (MetS). A quasi-experimental study was carried out in a con-venience sample of 46 older adults diagnosed with MetS: (i) placebo group (PG; n=20), (ii) ex-perimental group (EG; n=26). Clinical, biochemical, and anthropometric parameters, SOD, GPx, and CAT enzyme activity, total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), cytokines (IL-6, IL-8 and TNF-α) and mRNA expression of (SOD, GPx, CAT, IL-6, IL-8, TNF-α, Nrf2, NFkB p50 and NFkB p65), were measured at baseline and 6 months post-intervention. A statistically significant decrease was observed in TOS (baseline, 28.9 ± 3.6 vs. post, 23.7 ± 3.4, p < 0.01) and OSI (baseline, 24.1 ± 3.8 vs. post, 17.7 ± 4). As well as the increase in IL-6 (baseline, 10.7 ± 1.1 vs. post, 12.3 ± 2, p = 0.03), SOD activity (baseline, 167.1 ± 11.9 vs. post, 180.6 ± 7.6, p < 0.05), CAT activity (baseline, 1.0 ± 0.2 vs. post, 1.3 ± 0.2, p < 0.01) and TAS (baseline, 1.1 ± 0.1 vs. post, 1.4 ± 0.1, p < 0.01) in the EG compared to the PG. Regarding the expression of Nrf2, SOD and IL-6, the EG showed a significant increase vs basal levels (47%, 44% and 43%, re-spectively). Our findings suggest that Sechium edule supplementation promotes the antioxidant response and decreases oxidative stress via Nrf2.

This review is focused on synephrine, the principal phytochemical found in bitter orange and other medicinal plants, and widely used as a dietary supplement for weight loss/body fat reduction. We examine different aspects of synephrine biology, delving into its established and potential molecular targets, as well as its mechanisms of action. We present an overview of the origin, chemical composition, receptors, and pharmacological properties of synephrine, including its anti-inflammatory and anti-cancer activity in various in vitro and animal models. Additionally, we conduct a comparative analysis of the molecular targets and effects of synephrine with those of its metabolite, selective glucocorticoid receptor agonist (SEGRA) Compound A (CpdA), which shares a similar chemical structure with synephrine. SEGRA, including CpdA, have been extensively studied as glucocorticoid receptor activators that have a better benefit/risk profile than glucocorticoids due to the reduced adverse effects. We discuss the potential of synephrine usage as a template for the synthesis of new generation of non-steroidal SEGRA. The review also provides insights into the safe pharmacological profile of synephrine.

Chondroitin is a glycosaminoglycan that has gained widespread use in nutraceuticals and pharmaceuticals, mainly for treating osteoarthritis. Traditionally, it has been extracted from animal cartilage but recently, biotechnological processes have emerged as a commercial alternative to avoid the risk of viral or prion contamination and offer a vegan-friendly source. Typically, these methods involve producing the chondroitin backbone using pathogenic bacteria and then modifying it enzymatically through the action of sulfotransferases. Despite the challenges of expressing active sulfotransferases in bacteria, the use of eukaryotic microorganisms is still limited to a few works using Pichia pastoris. To create a safer and efficient biotechnological platform, we have constructed a biosynthetic pathway for chondroitin production in S. cerevisiae as a proof-of-concept. Up to 125 mg/L and 200 mg/L of intracellular and extracellular chondroitin were produced, respectively. Furthermore, as genome-scale models are valuable tools for identifying novel targets for metabolic engineering, a stoichiometric model of chondroitin-producing S. cerevisiae has been developed and used in optimization algorithms. Our research has yielded several novel targets, such as uridine diphosphate(UDP)-N-acetylglucosamine pyrophosphorylase (QRI1), glucosamine-6-phosphate acetyltransferase (GNA1) or N-acetylglucosamine-phosphate mutase (PCM1) overexpression that might enhance chondroitin production, which will guide future experimental research to develop more efficient host organisms for the biotechnological production process.

Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015-22 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0 - 9.6) and 4.0 (1.8 - &gt;70) µmol/L respectively and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C, in ‘asymptomatic’ individuals (n=17), demonstrating a median (range) C5C of 3.0 (1.8 – 7.1) whilst ‘clinically affected’ patients (n=7), showed a median (range) C5C of 13.9 (7.7 - &gt; 70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those &gt; 2.0 and &lt; 5.0 µmol/L prompting 2nd tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder.

Nuclear receptors (NRs) constitute a superfamily of ligand-activated transcription factors with a paramount role in ubiquitous physiological functions such as metabolism, growth, and reproduction. Owing to their physiological role and druggability, NRs are deemed attractive and valid targets for medicinal chemists. Pentacyclic triterpenes (PTs) represent one of the most important phytochemical classes present in higher plants, where oleanolic acid (OA) is the most studied PTs representative owing to its multitude of biological activities against cancer, inflammation, diabetes, and liver injury. PTs possess a lipophilic skeleton that imitates the NRs endogenous ligands. Herein, we report a literature overview on the modulation of metabolic NRs by OA and its semi-synthetic derivatives, highlighting their health benefits and potential therapeutic applications. Indeed, OA exhibited varying pharmacological effects on FXR, PPAR, LXR, RXR, PXR, and ROR in a tissue-specific manner. Owing to those NRs modulation, OA exhibited prominent hepatoprotective properties comparable to ursodeoxycholic acid (UDCA) in a bile duct ligation mice model and antiatherosclerosis effect as simvastatin in a model of New Zealand white (NZW) rabbits. It also demonstrated a great promise in alleviating non-alcoholic steatohepatitis (NASH) and liver fibrosis, attenuated alpha-naphthol isothiocyanate (ANIT)-induced cholestatic liver injury, and controlled blood glucose levels, making it a key player in the therapy of metabolic diseases. We also compiled OA semi-synthetic derivatives and explored their synthetic pathways and pharmacological effects on NRs, showcasing their structure-activity relationship (SAR). To the best of our knowledge, this is the first review article to highlight OA activity in terms of NRs modulation.

Introduction Urolithiasis, a prevalent urological condition (8-13% globally) exhibits regional variations, influenced by water quality, climate, health factors and diet. Sri Lanka with its tropical climate and dietary patterns is part of the "Stone Belt" of Asia. This study in Northern Sri Lanka examines urinary stone compositions and assesses the prevalence of metabolic disorders among urolithiasis patients. Methods This prospective cross-sectional study, conducted at tertiary urology centre from July 2022 to June 2023, focused on surgically treated urolithiasis patients. Institutional ethical clearance was obtained. Patient details and investigational findings were collected through questionnaires and data extraction forms. Stone analysis utilized Fourier transform infrared spectroscopy and detailed metabolic evaluation of 24 hour urine collection sample is carried out. Results This study followed 153 surgically treated urolithiasis patients, primarily male (64.3%), mean age 48.64. Ureteric colic (48.4%) was common, with kidney stones (45.8%) prevalent; 57.52% had recurrent stones. Diabetes mellitus (DM=23.5%) was the top comorbidity. Calcium oxalate monohydrate (COM) stones (78.4%) were most frequent, followed by uric acid (12.4%). COM predominated in 40-59 age group. No significant gender-stone type association. 86.9% had metabolic abnormalities, notably hypocitraturia (60.1%). 23% had both hypocitraturia and hypomagnesuria. Some metabolic disorders showed gender differences, with a marginal age-metabolic disorders association (p < 0.061). Urine oxalate levels were normal with higher variability in males. Conclusion Middle-aged males with urolithiasis commonly presented with ureteric colic and predominantly had calcium oxalate monohydrate stones. Recurrent stones were common, often accompanied by metabolic abnormalities such as hypocitraturia and hypomagnesuria, with diabetes mellitus as the primary comorbidity.

Previous investigations have illuminated the significant association between the gut microbiome and a broad spectrum of health conditions, including obesity, diabetes, cardiovascular diseases, and psychiatric disorders. Evidence from certain studies suggests that dysbiosis of the gut microbiota may play a role in the etiology of obesity and diabetes. Moreover, it is acknowledged that dietary habits, pharmacological interventions, psychological stress, and other exogenous factors can substantially influence the gut microbial composition. For instance, a diet rich in fiber has been demonstrated to increase the population of beneficial bacteria, whereas the consumption of antibiotics can reduce these advantageous microbial communities. In light of the established correlation between the gut microbiome and various pathologies, strategically altering the gut microbial profile represents an emerging therapeutic approach. This can be accomplished through the administration of probiotics or prebiotics, which aim to refine the gut microbiota and, consequently, mitigate the manifestations of associated diseases. The present manuscript evaluates recent literature on the relationship between gut microbiota and metabolic syndrome published over the past three years and anticipates future directions in this evolving field.

The use of recombinant bovine somatotropin (rbST) leads to an increase, in variable amounts, of milk production in buffalo, but there is a lack of information on the influence of rbST on their metabolism. This study looked at the effects of a single 500 mg dose of rbST on lipid profile, liver and kidney function and physical, chemical and cellular constitution of milk in 14 buffalo over 14 days, from the 100th day of lactation, and compared them with 14 animals in a control group. From the 1st day after rbST, there was a rise in beta hydroxybutyrate (β-HBO), possibly due to the higher dry matter intake or by biotransformation of NEFA into β-HBO. Treatment did not influence blood glucose, non-esterified fatty acids (NEFA), triglycerides, cholesterol, total protein, albumin, AST, GGT, bilirubin, urea or creatinine. In 71.3% of the buffalo there was a gradual increase in milk production with maximal response in the first week that was then followed by a gradual decrease, whilst in 21.4%, the increase in production occurred between 7 and 10 days, and only 7.1% of animals did not respond. On the 3rd, 5th, 7th and 10th days after treatment, an increase was found in milk production between the two groups equal to 1.04, 1.52, 1.42 and 1.06 liters, respectively. In relative terms this means an increase in milk production, respectively, of 15.1%; 21.0%; 19.8 % and 15.1 %. The constitution of the milk showed no difference in the amounts of fat, lactose, total solids or somatic cell count; however, on the 3rd day after rbST, there was a decrease in protein; notably, from the 5th day, protein values show no statistical difference. It can be concluded that the application of rbST in buffalo from the 100th day of lactation is metabolically safe, since the treatment neither caused imbalances in fat metabolism nor overloaded the liver or renal function, and the changes in milk composition were transient and limited to a decrease in milk protein.

Sleep fragmentation (SF) can increase inflammation and production of reactive oxygen species (ROS), leading to metabolic dysfunction. SF is associated with inflammation of adipose tissue and insulin resistance. Several studies suggested that melatonin may have beneficial metabolic effects by activating AMP-activated protein kinase (AMPK). However, it is unclear whether melatonin affects the AMPK signaling pathway in SF-induced metabolic dysfunction. Therefore, we hypothesize that SF induces metabolic impairment and inflammation in white adipose tissue (WAT), as well as altered intracellular homeostasis. We further hypothesize that these conditions could be improved by melatonin treatment. We conducted an experiment using adult male C57BL/6 mice, which were divided into three groups: control, SF, and SF with melatonin treatment (SF+Mel). The SF mice were housed in SF chambers, while the SF+Mel mice received daily oral melatonin. After 12 weeks, glucose tolerance test, insulin tolerance test, adipose tissue inflammation, and AMPK assessments were performed. The SF mice showed increased weight gain, impaired glucose regulation, inflammation, and decreased AMPK in WAT compared to the controls. Melatonin significantly improved these outcomes by mitigating SF-induced metabolic dysfunction, inflammation, and AMPK downregulation in adipose tissue. The therapeutic efficacy of melatonin against cardiometabolic impairments in SF may be due to its ability to restore adipose tissue homeostatic pathways.

FLH 13-11 is an F1 interspecific hybrid muscadine grape genotype that was developed to produce new anthocyanins for pigment color stability. This hybrid resulted from a cross between ‘Marsh’ (Vitis munsoniana) and ‘Magoon’ (V. rotundifolia). This report characterizes the anthocyanins produced in fully ripe berries, and reveals a significant difference in total anthocyanin contents from two continuous cropping seasons. High-performance liquid chromatography with a diode array detector (HPLC-DAD) and HPLC-quadrupole time-of-flight tandem mass spectrometry (HPLC-qTOF-MS/MS) were used to profile anthocyanins in berries. The resulting data showed that fourteen anthocyanins were detected, six from 2011 and nine from 2012, with only one produced in both seasons. However, the anthocyanidin profiles of berries were the same. Five anthocyanins were annotated as diglucosides of anthocyanidins based on MS/MS features, including delphinidin 3,5-diglucoside produced in both seasons, cyanidin 3,5-diglucoside mainly formed in 2011, petunidin 3,5-diglucoside, malvidin 3,5-diglucoside, and peonidin 3,5-glucoside only detected in 2012. Also, three anthocyanidin-diglucoside like anthocyanins and three monoglucosides including peonidin 3- glucoside, delphinidin 3- glucoside like, and pelargonidin 3- glucoside like anthocyanins, were detected in 2011 and 2012, respectively. These results indicate that FLH 13-11 can produce both anthocyanidin-diglucosides and -monoglucosides, and their biosynthesis is closely dependent on cropping years.

Prolylcarboxypeptidase (PRCP, PCP, Lysosomal Pro-X-carboxypeptidase, Angiotensinase C) controls angiotensin - and kinin- induced cell signaling. Elevation of PRCP appear to be activated in chronic inflammatory diseases (cardiovascular disease (CVD), diabetes) in proportion to severity. Vascular endothelial cell senescence and mitochondrial dysfunction have consistently been shown in models of CVD in aging. The cellular senescence, a driver of age-related dysfunction, can differentially alter the expression of lysosomal enzymes due to lysosomal membrane permeability. There is a lack of data demostrating the effect of age-related dysfunction on the expression and function of PRCP. To explore the changes in PRCP, PRCP-dependent prekallikrein (PK) pathway was charcterized in early – and late-passage human pulmonary artery endothelial cells (HPAECs). Detailed kinetic analysis of cells treated with high molecular weight kininogen (HK), a precursor of bradykinin (BK), and PK revealed a mechansim by which senescent HPAECs activate the generation of kallikrein upon the assembly of the HK-PK complex on HPAECs in parallel with an upregulation of PRCP and endothelial nitric oxide (NO) synthase (eNOS) and NO formation. The NO production and expression of both PRCP and eNOS increased in early-passage HPAECs while decreased in late-passage HPAECs. Low activity of PRCP in late passage HPAECs was associated with rapid decreased telomerase reverse transcriptase mRNA levels. We also found that, with an increase in the passage number of HPAECs, reduced PRCP altered respiration rate. These results indicated that aging dysregulates PRCP protein expression, and further studies will shed light into the complexity of PRCP-dependent signling pathway in aging.

Background: The pandemic caused by the SARS-CoV-2 virus demonstrated the importance of prevention through a healthy diet and lifestyle, the most vulnerable people being those with severe chronic conditions, those who are overweight, and those with an unbalanced immune system. Methods: The evaluation of the eating habits and lifestyle of the Romanian population in the post-pandemic period was carried out based on a cross-sectional observational study with the help of a questionnaire. Results: 4704 valid answers were registered (3136 female and 1568 male respondents). Among the respondents, most of them belong to the young population, 2892 between the ages of 18 and 40, i.e., 61.5%. Most male respondents are overweight (1400) and obese (780). Most respondents indicated a tendency to consume 1-2 meals per day irregularly (p=0.6167). Only 974 respondents adopted a healthy diet, and 578 a healthy lifestyle. Conclusion: The present study reports low adherence to a healthy diet (20.7%) and healthy lifestyle (12.28%), especially among the young population (&lt; 30 years). In the current context, it reports a reduced tendency to consume vegetables and fruits among the population, below the daily average recommended by the nutrition guidelines, a tendency towards sedentary behavior, and even deficient hydration of some of the respondents; these negative aspects can create a long term a series of nutritional and psycho-emotional imbalances. Our results evidence that complex surveys among the population are regularly required to investigate nutritional or lifestyle deficiencies; moreover, it could be helpful in further educational measures in nutrition, food, and environmental safety.

Osteoarthritis (OA) is a pathology of great impact worldwide which its physiopathology is not completely known and usually diagnosed by imaging techniques performed at advanced stages of the disease. The aim of this study was to evaluate early serum metabolome changes and identify the main metabolites involved in an inflammatory OA animal model. The study was performed with thirty rats, OA in all animals was induced by intra-articular injection of monoiodoacetate into the knee joint. Blood samples were taken from all animals and analyzed by mass spectrometry before OA induction, and 28, 56 and 84 days following induction. Histological study confirmed OA in all samples. The results of this study allow the identification of several changes in the serum metabolome over time, including organic acids, benzenoids, heterocyclic compounds and lipids at T28, organic acids at T56 and lipid classes at T84. We conclude that OA induces serological changes in the metabolome and, more specifically, 18 metabolites which could serve as potential biomarkers. However, it was not possible to establish a relationship between the identified metabolites and the time at which the samples were taken. Therefore, these findings should be confirmed in future OA studies.

We present the case of a 28-year-old male with a history of alcohol dependency and smoking, who presented with chest pain, shortness of breath, and altered sensorium. He exhibited severe metabolic acidosis, low platelet count, and acute kidney injury. Alcoholic ketoacidosis (AKA) was suspected due to ketonuria, metabolic acidosis, and ketonemia, compounded by electrolyte abnormalities and radiographic findings of pneumonia.Prompt intervention included electrolyte correction, thiamine supplementation, broad-spectrum antibiotics, and diuretics. Thiamine played a pivotal role in the patient's recovery, with significant improvement in consciousness observed within a day. After six days, the patient was discharged in stable condition, showing normal renal and hepatic function during follow-up.This case emphasizes the need for early recognition and comprehensive management in AKA, highlighting thiamine's crucial role in treatment success.

The microglia, displaying diverse phenotypes, play a significant regulatory role in the development, progression, and prognosis of Parkinson's disease. Research has established that glycolytic reprogramming serves as a critical regulator of inflammation initiation in pro-inflammatory macrophages. Furthermore, the modulation of glycolytic reprogramming has the potential to reverse the polarized state of these macrophages. Previous studies have shown that levetistilide A (LA), a phthalide component derived from Angelica sinensis, possesses a range of pharmacological effects, including anti-inflammatory, antioxidant, and neuroprotective properties. In our study, we have examined the impact of LA on inflammatory cytokines and glucose metabolism in microglia induced by lipopolysaccharide (LPS). Furthermore, we explored the effects of LA on the AMPK/mTOR pathway and assessed its neuroprotective potential both in vitro and in vivo. The findings revealed that LA notably diminished the expression of M1 pro-inflammatory factors induced by LPS in microglia, while leaving M2 anti-inflammatory factor expression unaltered. Additionally, it reduced ROS production and suppressed IκB-α phosphorylation levels as well as NF-κB p65 nuclear translocation. Notably, LA exhibited the ability to reverse microglial glucose metabolism reprogramming and modulate the phosphorylation levels of AMPK/mTOR. In vivo experiments further corroborated these findings, demonstrating that LA mitigated the death of TH-positive dopaminergic neurons and reduced microglia activation in the ventral SNpc brain region of the midbrain and the striatum. In summary, LA exhibited neuroprotective benefits by modulating the polarization state of microglia and altering glucose metabolism, highlighting its therapeutic potential.

In a 24-week-long experiment, 31 rats were assigned to one of 3 groups: a Control group receiving standard chow and water, a Fructose group receiving standard chow and a 20% fructose solution, or an STZ+lipids group that received a fat-enriched diet following a single 25 mg/kg streptozotocin injection at the onset of the diet. Both groups experienced significantly increased caloric intake but did not gain weight above the Control group level. Adipocytes in subcutaneous and visceral adipose depots of both groups had smaller size compared to control and higher density in tissue. Respirometric analyses unveiled a substantial increase in mitochondrial respiration across all adipose tissue types in both dietary intervention groups, with greater changes observed in the Fructose group. Correlation analyses demonstrated that in both experimental groups high tissue respiration is associated with better biochemical profile and closer to control adipose tissue morphology. Increased tissue respiration in adipose depots could be an important mechanism of resilience to excessive caloric intake.

Populational aging is marked by chronic non-communicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarity, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

Long-term storage may reduce the nutritional quality of brown rice, so the present study was aimed to evaluate the nutritive values and application in pig diets. In Exp.1, 18 Landrace × Yorkshire (L × Y) barrows with initial body weight (IBW) of 25.48 ± 3.21 kg were randomly assigned to three treatments, which included corn diet, one-year stored brown rice (BR1) diet and six-year stored brown rice (BR6) diet, to determine the digestible energy (DE) and metabolisable energy (ME) value of stored brown rice. In Exp. 2, 24 barrows (L × Y; IBW: 22.16 ± 2.42 kg) fixed with ileal T-cannula were randomly allotted to four dietary treatments, including corn diet, two stored brown rice diets and nitrogen-free diet, to evaluate the amino acid (AA) digestibility of stored brown rice. In Exp. 3 and 4, 108 crossbred weaned piglets (L × Y; IBW: 9.16 ± 0.89 kg) and 90 crossbred growing pigs (L × Y; IBW: 48.28 ± 3.51 kg) were allotted to 3 treatment diets, including control diet and two stored brown rice diets, respectively, to investigate the application of stored brown rice in weaned piglet and growing-finishing pig diets. Results showed that: 1) The DE and ME of corn and stored brown rice showed no significant differences (P > 0.05), while the apparent ileal digestibility (AID) of arginine, histidine, aspartic acid, and the standardized ileal digestibility (SID) of arginine and histidine were higher in stored brown rice compared to corn (P < 0.05). 2) Compared with the control diet, the stored brown rice diets showed no significant effects on growth performance, nutrient apparent total tract digestibility (ATTD) and serum biochemical indices (P > 0.05), but decreased digestive enzymes activities in duodenum, jejunum and ileum of piglets (P < 0.05). 3) Compared with the control diet, the stored brown rice diets showed no significant effects on growth performance, carcass traits, meat quality, fatty acids profiles in the longissimus dorsi muscle of growing-finishing pigs (P > 0.05). In conclusion, the brown rice stored for 6 years under good conditions has no obvious changes in available energy and nutrient values. Although it may reduce digestive enzyme activity in small intestine of the piglets, the stored brown rice showed no obvious adverse effect on growth performance and meat quality, and can be effectively used in pig diet.

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses metabolic dysfunction-associated fatty liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), with MASH posing a risk of progression to cirrhosis and hepatocellular carcinoma (HCC). The global prevalence of MASLD is estimated at approximately a quarter of the population, with significant healthcare costs and implications for liver transplantation. The pathogenesis of MASLD involves intrahepatic liver cells, extrahepatic components, and immunological aspects, particularly the involvement of macrophages. Hepatic macrophages are a crucial cellular component of the liver and play vital roles in liver function, contributing significantly to tissue homeostasis and swift responses during pathophysiological conditions. Recent advancements in technology have revealed the remarkable heterogeneity and plasticity of hepatic macrophage populations and their activation states in MASLD, challenging traditional classification methods like the M1/M2 paradigm and highlighting the coexistence of harmful and beneficial macrophage phenotypes that are dynamically regulated during MASLD progression. This complexity underscores the importance of considering macrophage heterogeneity in therapeutic targeting strategies, including their distinct ontogeny and functional phenotypes. This review provides an overview of macrophage involvement in MASLD progression, combining traditional paradigms with recent insights from single-cell analysis and spatial dynamics. It also addresses unresolved questions and potential therapeutic targets in this area.

Glioblastoma is a highly malignant brain tumor consisting of heterogeneous cellular population. The transformed metabolism of glioblastoma cells supports their growth and division on the background of their milieu. One might hypothesize that the transformed metabolism of a primary glioblastoma could be well adapted to limitations in the variety and number of substrates imported into the brain parenchyma and present it their microenvironment. Additionally, the phenotypic heterogeneity of cancer cells could promote the variations among their metabolic capabilities regarding the utilization of available substrates and release of metabolic intermediates. With the aim to identify the putative metabolic footprint of different types of glioblastoma cells, we exploited the possibility for separation of polar and ionic molecules present in culture media or cell lysates by hydrophilic interaction liquid chromatography (HILIC). The mass spectrometry (MS) was then used to identify and quantify the eluted compounds. The introduced method allows the detection and quantification of more than 150 polar and ionic metabolites in single run, those may be present either in culture media or cell lysates and provide data for polaromic studies within metabolomics. The method was applied to analyze the culture media and cell lysates derived from two types of glioblastoma cells, T98G and U118. The analysis revealed that even the both types of glioblastoma cells share several common metabolic aspects, they also exhibit differences in their metabolic capability. This finding agrees with the hypothesis about metabolic heterogeneity of glioblastoma cells. Furthermore, the combination of both analytical methods, HILIC-MS, provides a valuable tool for metabolomic studies based on the simultaneous identification and quantification of a wide range of polar and ionic metabolites - polaromics.

Graft injury affects over 50% of liver transplant (LT) recipients, but non-invasive biomarkers to diagnose and guide treatment are currently limited. We aimed to develop a biomarker of graft injury by integrating serum metabolomic profiles with clinical variables. Serum from 55 LT recipients with biopsy confirmed metabolic-dysfunction associated steatohepatitis (MASH), T-cell mediated rejection (TCMR) and biliary complications was collected and processed using a combination of LC-MS/MS assay. The metabolomic profiles were integrated with clinical information using a multi-class Machine Learning (ML) classifier. The efficacy of the model was assessed through the evaluation of the Out-of-Bag (OOB) error estimate. Our ML model yielded an overall accuracy of 79.66% with an OOB estimate of the error rate at 19.75%. The model exhibited a maximum ability to distinguish MASH, with an OOB error estimate of 7.4% compared to 22.2% for biliary and 29.6% for TCMR. The metabolites serine and serotonin emerged as the topmost predictors. When predicting binary outcomes using 3 models: Biliary (biliary vs. rest), MASH (MASH vs. rest) and TCMR (TCMR vs. rest), the AUCs were 0.882, 0.972 and 0.96 respectively. Our ML tool integrating serum metabolites with clinical variables shows promise as a non-invasive, multi-class serum biomarker of graft pathology.

We report the case of a four-year-old male patient with a complex medical history born prematurely as the result of intrauterine growth restriction due to placental insufficiency. His clinical manifestations include severe neurodevelopmental deficits, global developmental delay, Pierre-Robin sequence, and intractable epilepsy with both generalized and focal features. The proband’s low levels of citrulline and lactic acidosis provoked by administration of depakoke are evocative of a mitochondrial etiology. However, the genotype-phenotype correlation remains undefined in the absence of nuclear and mitochondrial pathogenic variants detected by deep sequencing of both genomes. However, live-cell mitochondrial metabolic investigations provide evidence of a deficient oxidative phosphorylation pathway responsible for ATP synthesis, leading to chronic energy crisis in the proband. In addition, our metabolic analysis reveals metabolic plasticity in favor of glycolysis for ATP synthesis. Our mitochondrial morphometric analysis by transmission electron microscopy confirms the suspected mitochondrial etiology, as the proband’s mitochondria exhibit an immature morphology with poorly developed and rare cristae. Thus, our results support the concept that sub-optimal levels of intrauterine oxygen and nutrients alter fetal mitochondrial metabolic reprogramming toward OXPHOS leading to a deficient postnatal mitochondrial energy metabolism. In conclusion, our collective studies shed light on the long-term postnatal mitochondrial pathophysiology caused by intrauterine growth restriction due to idiopathic placental insufficiency and its negative impact on the energy-demanding development of fetal and postnatal brain.

This review focuses on the emerging evidence for the association between estimated cardiorespiratory fitness (eCRF) and metabolic risk factors. Given the challenges associated with directly measuring cardiorespiratory fitness (CRF) in large populations, eCRF presents a practical alternative for predicting metabolic health risks. A literature search identified six relevant cohort studies from 2021 to 2024 that investigated the association of eCRF with hypertension, hyperglycemia, dyslipidemia, and obesity. The review findings highlight a consistent inverse relationship between higher eCRF and lower incidence of metabolic risks in line with CRF cohort studies. This review highlights the importance of low eCRF as a primordial indicator for metabolic risks and underscores the need for broader application. Future research directions should include exploring eCRF's predictive accuracy across diverse populations and health outcomes and testing its real-world applicability in healthcare and public health settings.

Objective: To analyze the relation between alterations in the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis during the first 6 months of life and weight in children born in the Lower Middle São Francisco region. Methods: This is an analytical cohort, with a quantitative approach and a translational perspective. Thirty children with low and normal birth weight were initially identified in a hospital and reapproached at 3 and 6 months of age. Birth weight and alterations in GH/IGF-1 curves at birth, third month, and sixth month of life. Results: Weight gain during the 6 months of follow-up in newborns with low birth weight was greater compared to newborns with normal birth weight. All children who were born with low birth weight had an altered GH/IGF-1 curve at birth (p = 0.002). Most newborns with low birth weight maintained the alteration in the GH/IGF-1 curve at the third month of life (p = 0.027). Regarding the GH/IGF-1 curve at the sixth month, alteration persisted in greater proportion among children with low birth weight. Conclusion: Alterations in insulin resistance markers, demonstrated by increased GH without a proportional increase in IGF-1, were observed to be significant in children with low birth weight, with greater adiposity in this group, which may increase the risk of metabolic diseases in later life.

Background: Cardiovascular (CV) morbidity and mortality are many times higher in chronic kidney disease (CKD), as well as IgA nephropathy (IgAN), than in the general population. The occurrence of metabolic syndrome (MetS) and metabolic risk factors are independent risk factors for CV disease and renal progression. The study aimed to determine the prognostic role of metabolic profiles in a homogenous group of CKD patients. Methods: One hundred and forty-five IgA nephropathy patients (92 male, 53 female, age 54.7 ± 13 years) with CKD stage 1-4 were investigated and followed for a median of 190 months. The composite (CV and renal) endpoints included all-cause mortality and any CV event such as stroke, myocardial infarction, revascularization (CV), end-stage renal disease, and renal replacement therapy (renal). Results: Patients with MetS had significantly more endpoint events (16/27 patients vs. 15/98 patients, p = 0.001) compared to the nonMetS group. Of the secondary endpoints (CV or renal separately), the rate of the renal and CV endpoints was significantly higher in the MetS group (p = 0.001 and p = 0.029). The primary endpoint independent predictors of survival were dyslipidemia, eGFR, hemoglobin, urine albuminuria, and diabetes mellitus, as determined by Cox regression analysis. Independent predictors of secondary renal endpoint were dyslipidemia, hemoglobin, urine albumin, and eGFR. Predictors of secondary cardiovascular endpoints were gender, BMI, and diabetes. Kaplan-Meier curves showed significant differences in MetS and non-MetS when examined at the combined endpoints (CV and renal) or at each endpoint separately. The primary endpoint rate increased significantly with the increased number of MetS components (MetS comp. 0 vs. MetS comp. 2+, primary endpoints, p = 0.012). Conclusion: Our results showed that the metabolic profile has a prognostic role not only for renal endpoints but also for CV endpoints in IgAN. BMI, hyperuricemia, hypertension, and diabetes have a predictive value for the prognosis of IgA nephropathy.

Ever since Varela and Maturana proposed the concept of autopoiesis as the minimal requirement for life, there has been a focus on cellular systems that erect topological boundaries to separate themselves from their surrounding environment. Here we reconsider whether the existence of such a spatial boundary is strictly necessary for self-producing entities. This work presents a novel computational model of a minimal autopoietic system inspired by dendrites and molecular dynamics simulations in three-dimensional space. A series of simulation experiments where the metabolic pathways of a particular autocatalytic set are successively inhibited until autocatalytic entities that could be considered autopoietic are produced. These entities maintain their distinctness in an environment containing multiple identical instances of the entities without the existence of a topological boundary. This gives rise to the concept of a metabolic boundary which manifests as emergent self-selection criteria for the processes of self-production without any need for unique identifiers. However, the adoption of such a boundary comes at a cost, as these autopoietic entities are less suited to their simulated environment than their autocatalytic counterparts. Finally, this work showcases a generalized metabolism-centered approach to the study of autopoiesis that can be applied to both physical and abstract systems alike.

A growing body of research has identified fetal risk factors associated with adult diseases that form the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. This theory proposes a critical developmental period during which the fetus is highly susceptible to specific environmental influences that significantly impact health from short to long term. Maternal stress and T2DM during pregnancy are among these influences, likely leading to fetal overexposure to glucocorticoids and suggesting a shared pathway between maternal dysregulated HPA axis and fetal environmental insults. Studies demonstrate that prenatal glucocorticoid exposure alters fetal HPA axis function, affecting brain function, tissue glucocorticoid availability, and fetal growth in utero. These programmed changes, such as altered HPA axis function and reduced fetal growth, contribute to metabolic disorders persisting into adulthood. T2DM is preceded by a prediabetic state, often asymptomatic, which shares similar pathophysiological complications with T2DM, including HPA axis dysregulation observed in animals. Therefore, investigating prediabetes during pregnancy alongside maternal HPA axis function and its effects on fetal outcomes is crucial, as these areas remain understudied. This review aims to synthesize existing literature on pre-existing T2DM during pregnancy, its links to fetal programming via HPA axis changes, and possible links to pregestational prediabetes.

The human gastrointestinal gut contains about 100 trillion of microorganisms including up to 5000 different types of bacteria called the "gut microbiome". Alterations in the composition of gut microorganisms (dysbiosis) can cause threatening for life diseases. This present seeks to evaluate if finally diet and more specifically functional foods affect the intestinal microbiome, and if obesity and the metabolic syndrome (Mets) are associated with the intestinal microbiome. This systematic review was accomplished according to PRISMA guidelines mostly using the key words functional foods, microbiome, obesity, Mets, Mediterranean diet. The search was carried out of recent scien-tific articles from the databases Pubmed, Scopus, and Google Scholar. The most studies discussed in this review showed a potential therapeutic effect of the Mediterranean diet rich in beneficial nutrients, on body weight, fat deposition, in correlation with modulation of the synthesis of gut microbiome. This literature review demonstrates a possible relationship between the metabolites of the microflora, the endotoxemia, obesity and Mets. The role of probiotics, prebiotics, and polyphe-nols in the prevention of obesity and Mets is of high importance in promoting healthy aging. The future challenge is to understand how different dietary patterns can regulate the composition of the gut microflora and whether these changes could be long-term.