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Background: Rheumatoid arthritis, a chronic autoimmune disease, is characterized by synovial hyperplasia and cartilage erosion. Here, we investigated the potential mechanism of action of quercetin, the main component of flavonoids, in treating rheumatoid arthritis. Object: To examine the anti-arthritic effects of quercetin and elucidate the specific mechanisms that differentiate its metabolic effects on autoimmune and inflammatory responses at the synovial cell level. Methods: We created a collagen-induced arthritis (CIA) model in Wistar rats, which were administered quercetin (50 or 100 mg/kg) continuously for four weeks via stomach perfusion. The arthritis score, histopathological staining, radiological assessment, and serum biochemical parameters were used to study the impact of quercetin on disease improvement. Additionally, immunofluorescence was employed to detect JAK1/STAT3/HIF-1α expression in rat joints. Moreover, the effects of quercetin (20, 40, and 80 µmol/L) on the properties and behavior of synovial fibroblasts were evaluated in an in vitro MH7A cell model using flow cytometry, CCK8, and transwell assays. Further, the mRNA expression levels of inflammatory cytokines IL1β, IL6, IL17, and TNFα were assessed by quantitative real-time PCR. Glucose, lactate, lactate dehydrogenase, pyruvate, pyruvate dehydrogenase, and adenosine triphosphate assay kits were employed to measure the metabolic effects of quercetin on synovial fibroblasts. Finally, immunoblotting was used to examine the impact of quercetin on the JAK1/STAT3/HIF-1α signaling pathway in synovial fibroblasts. Results: In vivo experiments confirmed the favorable effects of quercetin in CIA rats, including an improved arthritis score and reduced ankle bone destruction, in addition to a decrease in the pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in serum. Immunofluorescence verified that quercetin may ameliorate joint injury in rats with CIA by inhibiting JAK1/STAT3/HIF-1α signaling. Various in vitro experiments demonstrated that quercetin effectively inhibits IL-6-induced proliferation of MH7A cells and reduces their migratory and invasive behavior, while inducing apoptosis and reducing the expression of the pro-inflammatory cytokines IL1β, IL6, IL17, and TNFα at the mRNA level. Quercetin caused inhibition of glucose, lactate, lactate dehydrogenase, pyruvate, and adenosine triphosphate and increased pyruvate dehydrogenase expression in MH7A cells. It was further confirmed that quercetin may inhibit energy metabolism and inflammatory factor secretion in MH7A cells through JAK1/STAT3/HIF-1α signaling. Conclusions: Quercetin's action on multiple target molecules and pathways makes it a promising treatment for cartilage injury in rheumatoid arthritis. By reducing joint inflammation, improving joint metabolic homeostasis, and decreasing immune system activation energy, quercetin inhibits the JAK1/STAT3/HIF-1α signaling pathway to improve disease status. [ABSTRACT FROM AUTHOR]

Abstract Mesopelagic species are unexplored novel low‐trophic sources of essential micronutrients and may contribute to combat malnutrition. In this study, common mesopelagic species from the North Sea including Northern krill (Meganyctiphanes norvegica), glacier lanternfish (Benthosema glaciale), and Muller's pearlside (Maurolicus muelleri) were supplemented in mice feed using a Western diet recipe. The metabolic outcomes were subsequently compared to those of ordinary seafood. Consumption of mesopelagic species induced a large variation in weight gain, in the following order: lanternfish (7.1 g) > krill (14.4 g) > control (19.7 g) > pearlside (22.6 g). The lanternfish‐supplemented diet containing wax esters reduced weight gain and obesity and improved insulin sensitivity. The wax esters from the lanternfish‐supplemented diet were efficiently absorbed, with more than 92% of the fatty alcohols being assimilated. The inclusion of lanternfish and pearlside led to improvements in the fatty acid (FA) composition in the mouse liver, evidenced by increased levels of essential long‐chain polyunsaturated FAs and an increased n‐3/n‐6 ratio (0.7 to 1.45 vs. 0.46 in control group). Notably, no adverse effects were found in mice fed pearlside and lanternfish, although an elevated level of fluoride in femur bone was observed in mice fed a diet supplemented with krill followed by reduced sperm concentration and sperm motility. Collectively, our findings underscore the diverse array of metabolic and physiological effects induced by the consumption of mesopelagic species. Furthermore, these species can be considered as good sources of n‐3 FAs and essential vitamins, suggesting their potential value to human nutrition.

Abstract Background Rheumatoid arthritis, a chronic autoimmune disease, is characterized by synovial hyperplasia and cartilage erosion. Here, we investigated the potential mechanism of action of quercetin, the main component of flavonoids, in treating rheumatoid arthritis. Object To examine the anti-arthritic effects of quercetin and elucidate the specific mechanisms that differentiate its metabolic effects on autoimmune and inflammatory responses at the synovial cell level. Methods We created a collagen-induced arthritis (CIA) model in Wistar rats, which were administered quercetin (50 or 100 mg/kg) continuously for four weeks via stomach perfusion. The arthritis score, histopathological staining, radiological assessment, and serum biochemical parameters were used to study the impact of quercetin on disease improvement. Additionally, immunofluorescence was employed to detect JAK1/STAT3/HIF-1α expression in rat joints. Moreover, the effects of quercetin (20, 40, and 80 µmol/L) on the properties and behavior of synovial fibroblasts were evaluated in an in vitro MH7A cell model using flow cytometry, CCK8, and transwell assays. Further, the mRNA expression levels of inflammatory cytokines IL1β, IL6, IL17, and TNFα were assessed by quantitative real-time PCR. Glucose, lactate, lactate dehydrogenase, pyruvate, pyruvate dehydrogenase, and adenosine triphosphate assay kits were employed to measure the metabolic effects of quercetin on synovial fibroblasts. Finally, immunoblotting was used to examine the impact of quercetin on the JAK1/STAT3/HIF-1α signaling pathway in synovial fibroblasts. Results In vivo experiments confirmed the favorable effects of quercetin in CIA rats, including an improved arthritis score and reduced ankle bone destruction, in addition to a decrease in the pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in serum. Immunofluorescence verified that quercetin may ameliorate joint injury in rats with CIA by inhibiting JAK1/STAT3/HIF-1α signaling. Various in vitro experiments demonstrated that quercetin effectively inhibits IL-6-induced proliferation of MH7A cells and reduces their migratory and invasive behavior, while inducing apoptosis and reducing the expression of the pro-inflammatory cytokines IL1β, IL6, IL17, and TNFα at the mRNA level. Quercetin caused inhibition of glucose, lactate, lactate dehydrogenase, pyruvate, and adenosine triphosphate and increased pyruvate dehydrogenase expression in MH7A cells. It was further confirmed that quercetin may inhibit energy metabolism and inflammatory factor secretion in MH7A cells through JAK1/STAT3/HIF-1α signaling. Conclusions Quercetin’s action on multiple target molecules and pathways makes it a promising treatment for cartilage injury in rheumatoid arthritis. By reducing joint inflammation, improving joint metabolic homeostasis, and decreasing immune system activation energy, quercetin inhibits the JAK1/STAT3/HIF-1α signaling pathway to improve disease status.

Recombinant human growth hormone therapy (rhGH) has been widely accepted as the safe treatment for short stature in children with such genetic syndromes as Prader–Willi syndrome and Turner or Noonan syndrome. Some patients with short stature and rare genetic syndromes are treated with rhGH as growth hormone-deficient individuals or as children born small for their gestational age. After years of experience with this therapy in syndromic short stature, it has been proved that there are some aspects of long-term rhGH treatment beyond growth promotion, which can justify rhGH use in these individuals. This paper summarizes the data of a literature review of the effects of rhGH treatment beyond growth promotion in selected genetic syndromes. We chose three of the most common syndromes, Prader–Willi, Turner, and Noonan, in which rhGH treatment is indicated, and three rarer syndromes, Silver–Russel, Kabuki, and Duchenne muscular dystrophy, in which rhGH treatment is not widely indicated. Many studies have shown a significant impact of rhGH therapy on body composition, resting energy expenditure, insulin sensitivity, muscle tonus, motor function, and mental and behavioral development. Growth promotion is undoubtedly the primary benefit of rhGH therapy; nevertheless, especially with genetic syndromes, the additional effects should also be considered as important indications for this treatment. [ABSTRACT FROM AUTHOR]

The practice of voluntary abstinence from food and drink for 16 to 48 hours is known as intermittent fasting (IF). Jain Ayambil, a type of intermittent fasting, where a special meal of boiled grains without spice, oil, milk, ghee, sugar, curd, fruits, or raw vegetables is taken once during the daytime. The aim of the study was to find out safety and its effect on plasma glucose, lipid profile, anthropometric and psychological parameters. We are reporting first ever scientific study on effect of Aymabil intermittent fasting on health parameters. The present study was carried out on 52 volunteers who did 9 days Ayambil fasting. Physical, and psychological assessment were done on the pre-fasting day (day 0), 4th day, and 9th day whereas biochemical examinations were carried out on pre-fasting (day 0) and 9th day of Ayambil fasting. Out of the total 52 participants (mean age of 52.77 ± 13.51 years), there were 28 (53.85%) females (51.54 ± 12.94) and 24 (46.15%) males (54.21 ± 14.30). A statistically significant reduction was observed for fasting blood glucose (p=0.002), HbA1c (p=0.002), body weight (p=0.001), BMI (p=0.001), diastolic BP (p=0.005), serum creatinine (p= 0.036), and a positive correlation was noted for Hamilton Depression Rating Scale (HDRS) (p=0.001) noted during Ayambil fasting. However, there was no significant change in lipid profile. Our findings suggest that Ayambil fasting is beneficial to metabolic, psychological, and holistic health with no health-related hazards. It is a safe fasting method and exploration of more clinical studies on this can open newer futuristic directions as one of the therapeutic options for a variety of clinical situations. [ABSTRACT FROM AUTHOR]

Farnesoid X receptor (FXR) agonists have emerged as a promising therapeutic strategy for the management of various gastrointestinal (GI) diseases, including primary biliary cholangitis, nonalcoholic fatty liver disease, inflammatory bowel disease, alcohol-related liver disease, and primary sclerosing cholangitis. In this review, we discuss the mechanisms of action of FXR agonists, including their metabolic and immunomodulatory effects, and provide an overview of the clinical evidence supporting their use in the treatment of GI diseases. We also highlight the safety, adverse effects, and potential drug interactions associated with FXR agonists. While these agents have demonstrated efficacy in improving liver function, reducing hepatic steatosis, and improving histological endpoints in primary biliary cholangitis and nonalcoholic fatty liver disease, further research is needed to determine their long-term safety and effectiveness in other GI diseases, such as inflammatory bowel disease, alcohol-related liver disease, and primary sclerosing cholangitis. Additionally, the development of next-generation FXR agonists with improved potency and reduced side effects could further enhance their therapeutic potential.

Background/Objectives: Metallic NPs have been explored for various therapeutic uses owing to utilitarian physicochemical characteristics such as antibacterial, anti-inflammatory, and healing properties. The objective of this study is to evaluate the therapeutic potential of novel silver carbonate nanostructures in promoting wound healing and their antibacterial activity against Pseudomonas chengduensis and Staphylococcus aureus. Methods: In this work, we prepared Ag2CO3 nanoparticles through a two-step methodology that was expected to improve the material’s biomedical performance and biocompatibility. The characterization and assessment of synthesized NPs biocompatibility were conducted using hemolysis assays on the blood of a healthy male human. Further, we performed molecular docking analysis to confirm interactions of silver NPs with biological molecules. Results: In detail, the synthesized NPs showed 2CO3 NPs exhibited high antimicrobial potential against both Pseudomonas chengduensis and Staphylococcus aureus, hence being a potential material that can be used for infection control in biomedical tissue engineering applications. Conclusions: These findings concluded that novel synthesis methods lead to the formation of NPs with higher therapeutic prospects; however, studies of their metaphysical and endocrinological effects are necessary.

Cimicifuga racemosa extracts (CREs) have gained well-established use for the treatment of menopausal symptoms such as hot flushes and excessive sweating, and weight gain. While the clinical effects of CREs have been well documented, the mechanisms underlying these effects are largely unknown. More recently, the metabolic effects of the CRE Ze 450 were demonstrated in cultured cells in vitro and in mouse models of obesity in vivo. At the molecular level, metabolic regulation, enhanced insulin sensitivity, and increased glucose uptake were linked to the activation of AMP-activated protein kinase (AMPK). Therefore, we tested the effects of Ze 450 on AMPK phosphorylation and thus activation in cells from different tissues, i.e., murine C2C12 myoblast cells, human HEPG2 liver cells, mouse HT22 neuronal cells, and in murine 3T3L1 adipocytes. Using a FRET-based HTRF-assay, we found that Ze 450 induced AMPK phosphorylation and the activation of this key enzyme of metabolic regulation in cells from various different tissues including C2C12 (muscle), HEPG2 (liver), HT22 (hippocampal), and 3T3-L1 (adipocyte) cells. In C2C12 muscle cells, enhanced AMPK activation was accompanied by reduced mitochondrial respiration and enhanced glucose uptake. Further, Ze 450 enhanced the resilience of the cells against oxidative death induced by ferroptosis inducers erastin or RSL3. Our findings suggest a general effect of Cimicifuga racemosa on AMPK activation in different tissues and across species. This may have a significant impact on expanded therapeutic applications of Ze 450, since AMPK activation and the related metabolic effects have been previously associated with anti-aging effects and the prevention of the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Sugar consumption is known to be associated with a whole range of adverse health effects, including overweight status and type II diabetes mellitus. In 2015, the World Health Organization issued a guideline recommending the reduction of sugar intake. In this context, alternative sweeteners have gained interest as sugar substitutes to achieve this goal without loss of the sweet taste. This review aims to provide an overview of the scientific literature and establish a reference tool for selected conventional sweeteners (sucrose, glucose, and fructose) and alternative sweeteners (sucralose, xylitol, erythritol, and D-allulose), specifically focusing on their important metabolic effects. The results show that alternative sweeteners constitute a diverse group, and each substance exhibits one or more metabolic effects. Therefore, no sweetener can be considered to be inert. Additionally, xylitol, erythritol, and D-allulose seem promising as alternative sweeteners due to favorable metabolic outcomes. These alternative sweeteners replicate the benefits of sugars (e.g., sweetness and gastrointestinal hormone release) while circumventing the detrimental effects of these substances on human health. [ABSTRACT FROM AUTHOR]

Cinnamic acid, ferulic acid, and the flavonoids quercetin and taxifolin (dihydroquercetin) are naturally occurring compounds found in plants. They are often referred to as polyphenols and are known, among others, for their pharmacological effects supporting health through the inhibition of aging processes and oxidative stress. To improve their bioavailability, pharmacological activities, and safety, the creation of novel flavonoid–phenolic acid hybrids is an area of active research. Previous work showed that such hybridization products of phenolic acids and flavonoids enhanced the resilience of neuronal cells against oxidative stress in vitro, and attenuated cognitive impairment in a mouse model of Alzheimer's disease (AD) in vivo. Notably, the therapeutic effects of the hybrid compounds we obtained were more pronounced than the protective activities of the respective individual components. The underlying mechanisms mediated by the flavonoid–phenolic acid hybrids, however, remained unclear and may differ from the signaling pathways activated by the originating structures of the respective individual phenolic acids or flavonoids. In this study, we characterized the effects of four previously described potent flavonoid–phenolic acid hybrids in models of oxidative cell death through ferroptosis. Ferroptosis is a type of iron-dependent regulated cell death characterized by lipid peroxidation and mitochondrial ROS generation and has been linked to neurodegenerative conditions. In models of ferroptosis induced by erastin or RSL3, we analyzed mitochondrial (lipid) peroxidation, mitochondrial membrane integrity, and Ca2+ regulation. Our results demonstrate the strong protective effects of the hybrid compounds against ROS formation in the cytosol and mitochondria. Importantly, these protective effects against ferroptosis were not mediated by radical scavenging activities of the phenolic hybrid compounds but through inhibition of mitochondrial complex I activity and reduced mitochondrial respiration. Our data highlight the effects of flavonoid–phenolic acid hybrids on mitochondrial metabolism and further important mitochondrial parameters that collectively determine the health and functionality of mitochondria with a high impact on the integrity and survival of the neuronal cells. [ABSTRACT FROM AUTHOR]

The review is devoted to one of the most controversial issues of modern antihypertensive therapy — the role of new generation sympatholytics — selective I1-imidazoline receptor agonists (AIRs). In modern European recommendations, AIR (moxonidine rilmenidine), along with other centrally acting drugs (reserpine, alpha-methyldopa, clonidine), are mainly intended for additional therapy in rare cases of resistant hypertension, when other treatment options have been ineffective. Nevertheless, AIR invariably finds its place in Russian recommendations for the treatment of arterial hypertension (AH). This class of drugs is recommended for patients with AH in combination with metabolic syndrome and obesity. It is noted that an important property of AIR is its positive effect on carbohydrate and lipid metabolism. This information is based on an analysis of Russian and foreign studies, which convincingly indicate that this class of drugs not only provides adequate and long-term blood pressure control, but also has the above-mentioned positive metabolic effects. At the same time, AIRs are much less likely to cause side effects characteristic of older generation centrally acting drugs. Thus, AIRs have become firmly established in clinical practice in Russia for the treatment of patients with AH in certain clinical situations.

The precise method of action of dienogest on the production and development of endometriosis lesions is unknown, and its controversial effect on endometrial thickness has been under investigation. In the following study the Dienogest's effects on the target animal's histology of female reproductive organs, including the tissues from the Fallopian tubes, ovaries, and uterus, as well as the impact of drug administration on the liver's enzymes and the drug's effects on triglycerides, body weight, and HbA1c, have all been studied. The findings of the following experiment indicated that there was no significant elevation of liver enzymes. The little to no elevation of the liver enzymes indicated that the drug did not induce stress on the hepatic cells and according to the subsequent experiment it is safe for clinical use. Moreover, after 10, 20, and 30 days of blood administration, the level of blood TG significantly decreased, and after 30 days of intake, the level of blood sugar significantly decreased. However, there were no appreciable changes after 10 and 20 days. After 30 days of treatment, the rats' weight also showed a very minor drop. In addition to it, the results of histological changes in the tissue in the following study represented that there were evident changes in the tissues which comprised of decline in blood circulation, fibrosis in tissues, and degeneration of follicles. [ABSTRACT FROM AUTHOR]

Context: Nicotinamide adenine dinucleotide (NAD) levels decline with aging and age-related decline in NAD has been postulated to contribute to age-related diseases. Objective: We evaluated the safety and physiologic effects of NAD augmentation by administering its precursor, β-nicotinamide mononucleotide (MIB-626, Metro International Biotech, Worcester, MA), in adults at risk for age-related conditions. Methods: Thirty overweight or obese adults, ≥45 years, were randomized in a 2:1 ratio to 2 MIB-626 tablets each containing 500 mg of microcrystalline β-nicotinamide mononucleotide or placebo twice daily for 28 days. Study outcomes included safety; NAD and its metabolome; body weight; liver, muscle, and intra-abdominal fat; insulin sensitivity; blood pressure; lipids; physical performance, and muscle bioenergetics. Results: Adverse events were similar between groups. MIB-626 treatment substantially increased circulating concentrations of NAD and its metabolites. Body weight (difference −1.9 [−3.3, −0.5] kg, P=.008); diastolic blood pressure (difference −7.01 [−13.44, −0.59] mmHg, P=.034); total cholesterol (difference −26.89 [−44.34, −9.44] mg/dL, P=.004), low-density lipoprotein (LDL) cholesterol (−18.73 [−31.85, −5.60] mg/dL, P=.007), and nonhigh-density lipoprotein cholesterol decreased significantly more in the MIB-626 group than placebo. Changes in muscle strength, muscle fatigability, aerobic capacity, and stair-climbing power did not differ significantly between groups. Insulin sensitivity and hepatic and intra-abdominal fat did not change in either group. Conclusions: MIB-626 administration in overweight or obese, middle-aged and older adults safely increased circulating NAD levels, and significantly reduced total LDL and non-HDL cholesterol, body weight, and diastolic blood pressure. These data provide the rationale for larger trials to assess the efficacy of NAD augmentation in improving cardiometabolic outcomes in older adults. [ABSTRACT FROM AUTHOR]

Abstract Aim Diet has a profound impact on cardiometabolic health outcomes such as obesity, blood glucose, blood lipids and blood pressure. In recent years, the gut microbiota has emerged as one of several potential key players explaining dietary effects on these outcomes. In this review we aim to summarise current knowledge of interaction between diet and gut microbiota focusing on the gut-derived microbial metabolites short-chain fatty acids and their role in modulating cardiometabolic risk. Findings Many observational and interventional studies in humans have found that diets rich in fibre or supplemented with prebiotic fibres have a favourable effect on the gut microbiota composition, with increased diversity accompanied by enhancement in short-chain fatty acids and bacteria producing them. High-fat diets, particularly diets high in saturated fatty acids, have shown the opposite effect. Several recent studies indicate that the gut microbiota modulates metabolic responses to diet in, e.g., postprandial blood glucose and blood lipid levels. However, the metabolic responses to dietary interventions, seem to vary depending on individual traits such as age, sex, ethnicity, and existing gut microbiota, as well as genetics. Studies mainly in animal models and cell lines have shown possible pathways through which short-chain fatty acids may mediate these dietary effects on metabolic regulation. Human intervention studies appear to support the favourable effect of short-chain fatty acid in animal studies, but the effects may be modest and vary depending on which cofactors were taken into consideration. Conclusion This is an expanding and active field of research that in the near future is likely to broaden our understanding of the role of the gut microbiota and short-chain fatty acids in modulating metabolic responses to diet. Nevertheless, the findings so far seem to support current dietary guidelines encouraging the intake of fibre rich plant–based foods and discouraging the intake of animal foods rich in saturated fatty acids.

Abstract Background Endothelium function is often impaired in patients with type 2 diabetes. We hypothesized that by improving endothelial function using diastole-synchronized compressions/decompressions (DSCD) to the lower body may improve the metabolic profile. The objective of this research was to evaluate the effects of single and multiple DSCD sessions on microcirculation, endothelium function and metabolic parameters of patients with type 2 diabetes. Methods Two monocentric, controlled, randomized cross-over studies (Study 1 and Study 2) were performed. In Study 1, 16 patients received one 20 min DSCD and one simulated (control) session at 2 week intervals; continuous glucose monitoring and cutaneous blood flow were recorded continuously before, during and after DSCD or Control session; other vascular assessments were performed before and after DSCD and control sessions. In Study 2, 38 patients received 60 min DSCD sessions three times/week for three months followed by a 4–6 week washout and 3 month control period (without simulated sessions); vascular, metabolic, body composition, physical activity and quality of life assessments were performed before and after 3 months. Results Both studies showed significant, multiplex effects of DSCD sessions. In Study 1, cutaneous blood flow and endothelium function increased, and plasma and interstitial glucose levels after a standard breakfast decreased after DSCD sessions. In Study 2, cutaneous endothelium function improved, LDL-cholesterol and non-HDL cholesterol decreased, extra-cell water decreased and SF-36 Vitality score increased after 3 months of DSCD sessions. Conclusions Our findings support the beneficial effect of DSCD on the endothelium and show concomitant beneficial metabolic and vitality effects. Future clinical trials need to test whether DSCD use translates into a preventive measure against microvascular diabetic complications and its progression. Trial registration ClinicalTrials.gov identifiers: NCT02293135 and NCT02359461.

Aims: To examine the association between COVID-19 Shutdown and within-subjects changes in body weight, body mass index (BMI), and glycemic parameters using electronic health record (EHR) data from 23,000 adults with type 2 diabetes (T2DM). Methods: Patients with T2DM with outpatient visit data on body weight, BMI, hemoglobin A1c (HbA1c), and blood glucose (≥ 2 measures before and after 3/16/2020) recorded in the EHR at the University of Pittsburgh Medical Center were included. A within-subjects analysis compared average and clinically significant changes in weight, BMI, HbA1c, and blood glucose during the year POST-Shutdown (Time 2–3) compared to the same interval during the PRE-Shutdown year (Time 0–1) using paired samples t-tests and the McNemar-Bowker test. Results: We studied 23,697 adults with T2DM (51% female; 89% White; mean age = 66 ± 13 years; mean BMI = 34 ± 7 kg/m2; mean HbA1c = 7 ± 2% [53 ± 21.9 mmol/mol]). Weight and BMI decreased during both the PRE- and POST-Shutdown intervals, but the changes were statistically smaller during the year POST-Shutdown relative to PRE (0.32 kg and 0.11 units, p < 0.0001). HbA1c showed statistically greater improvements during the POST-Shutdown interval compared to PRE (− 0.18% [−2 mmol/mol], p < 0.0001), but changes in glucose did not differ for the two intervals. Conclusions: Despite widespread discussion of weight gain in association with the COVID-19 Shutdown, study data showed no evidence of adverse effects of Shutdown on body weight, BMI, HbA1C, or blood glucose in a large sample of adults with T2DM. This information may help to inform future public health decision-making. [ABSTRACT FROM AUTHOR]

Milk is an important food of the daily diet. Many countries include it in their dietary recommendations due to its content in several important nutrients that exert beneficial effects on human health. Human milk is a newborn's first food and plays an important role in the growth, development, and future health of every individual. Cow milk is the type of milk most consumed in the world. However, its relatively high content of saturated fats raises concerns about potential adverse effects on human health, although epidemiological studies have disproved this association. Indeed, dairy consumption appear to be linked to a lower risk of mortality and major cardiovascular disease events. In the last few years many researchers have begun to focus their attention on both the production and quality of cow milk as well as the analysis of milk from other animal species to evaluate their effect on human health. The need to investigate the composition and metabolic effects of milk from other animal species arises from the adverse reactions of individuals in several groups to certain components of cow milk. It has emerged that donkey milk compared with that of other animal species, is the nearest to human milk and an excellent substitute for it. Milk from various animal species shows substantial differences in nutritional composition and distinct metabolic effects. In this review, we discussed the main compositional features and metabolic effects of 3 types of milk: human, cow, and donkey milk. [Display omitted] [ABSTRACT FROM AUTHOR]

This clinical trial aims to compare hormonal and metabolic changes after a 9-week continuous use of oral or vaginal combined hormonal contraceptives (CHCs) in women with polycystic ovary syndrome (PCOS). We recruited 24 women with PCOS and randomized them to use either combined oral (COC, n = 13) or vaginal (CVC, n = 11) contraception. At baseline and 9 weeks, blood samples were collected and a 2 h glucose tolerance test (OGTT) was performed to evaluate hormonal and metabolic outcomes. After treatment, serum sex hormone binding globulin (SHBG) levels increased (p < 0.001 for both groups) and the free androgen index (FAI) decreased in both study groups (COC p < 0.001; CVC p = 0.007). OGTT glucose levels at 60 min (p = 0.011) and AUCglucose (p = 0.018) increased in the CVC group. Fasting insulin levels (p = 0.037) increased in the COC group, and insulin levels at 120 min increased in both groups (COC p = 0.004; CVC p = 0.042). There was a significant increase in triglyceride (p < 0.001) and hs-CRP (p = 0.032) levels in the CVC group. Both oral and vaginal CHCs decreased androgenicity and tended to promote insulin resistance in PCOS women. Larger and longer studies are needed to compare the metabolic effects of different administration routes of CHCs on women with PCOS. [ABSTRACT FROM AUTHOR]

Cimicifuga racemosa extracts (CREs) have gained well-established use for the treatment of menopausal symptoms such as hot flushes and excessive sweating, and weight gain. While the clinical effects of CREs have been well documented, the mechanisms underlying these effects are largely unknown. More recently, the metabolic effects of the CRE Ze 450 were demonstrated in cultured cells in vitro and in mouse models of obesity in vivo. At the molecular level, metabolic regulation, enhanced insulin sensitivity, and increased glucose uptake were linked to the activation of AMP-activated protein kinase (AMPK). Therefore, we tested the effects of Ze 450 on AMPK phosphorylation and thus activation in cells from different tissues, i.e., murine C2C12 myoblast cells, human HEPG2 liver cells, mouse HT22 neuronal cells, and in murine 3T3L1 adipocytes. Using a FRET-based HTRF-assay, we found that Ze 450 induced AMPK phosphorylation and the activation of this key enzyme of metabolic regulation in cells from various different tissues including C2C12 (muscle), HEPG2 (liver), HT22 (hippocampal), and 3T3-L1 (adipocyte) cells. In C2C12 muscle cells, enhanced AMPK activation was accompanied by reduced mitochondrial respiration and enhanced glucose uptake. Further, Ze 450 enhanced the resilience of the cells against oxidative death induced by ferroptosis inducers erastin or RSL3. Our findings suggest a general effect of Cimicifuga racemosa on AMPK activation in different tissues and across species. This may have a significant impact on expanded therapeutic applications of Ze 450, since AMPK activation and the related metabolic effects have been previously associated with anti-aging effects and the prevention of the metabolic syndrome.

Aim: Diet has a profound impact on cardiometabolic health outcomes such as obesity, blood glucose, blood lipids and blood pressure. In recent years, the gut microbiota has emerged as one of several potential key players explaining dietary effects on these outcomes. In this review we aim to summarise current knowledge of interaction between diet and gut microbiota focusing on the gut-derived microbial metabolites short-chain fatty acids and their role in modulating cardiometabolic risk. Findings: Many observational and interventional studies in humans have found that diets rich in fibre or supplemented with prebiotic fibres have a favourable effect on the gut microbiota composition, with increased diversity accompanied by enhancement in short-chain fatty acids and bacteria producing them. High-fat diets, particularly diets high in saturated fatty acids, have shown the opposite effect. Several recent studies indicate that the gut microbiota modulates metabolic responses to diet in, e.g., postprandial blood glucose and blood lipid levels. However, the metabolic responses to dietary interventions, seem to vary depending on individual traits such as age, sex, ethnicity, and existing gut microbiota, as well as genetics. Studies mainly in animal models and cell lines have shown possible pathways through which short-chain fatty acids may mediate these dietary effects on metabolic regulation. Human intervention studies appear to support the favourable effect of short-chain fatty acid in animal studies, but the effects may be modest and vary depending on which cofactors were taken into consideration. Conclusion: This is an expanding and active field of research that in the near future is likely to broaden our understanding of the role of the gut microbiota and short-chain fatty acids in modulating metabolic responses to diet. Nevertheless, the findings so far seem to support current dietary guidelines encouraging the intake of fibre rich plant–based foods and discouraging the intake of animal foods rich in saturated fatty acids. [ABSTRACT FROM AUTHOR]

The kidney is a notable site of glycolysis, gluconeogenesis, and fatty acid oxidation. Loss of a kidney after kidney donation might, therefore, affect the glucose and lipid metabolism of the donors. This matched cohort study investigated the effect of nephrectomy on glucose and lipid metabolisms using Bayesian hypothesis testing. There were 77 pairs of matched donor‐control pairs in the present study. Clinical and laboratory data of the participants, at baseline and 1‐year, were extracted from electronic medical records. Comparisons between donor and control groups were performed using the Bayesian independent samples t‐test or Bayesian Mann–Whitney test. The Bayes Factor for alternative hypothesis over null hypothesis (BF10) was used to compare the two competing hypotheses. The BF10 of 3 or more was considered evidence for the alternative hypothesis. Comparing changes from baseline to 1‐year between donors and controls, the BF10 of triglycerides, high‐density lipoprotein cholesterol (HDL‐C), triglyceride‐glucose (TyG) index of insulin resistance, and estimated glomerular filtration rate (eGFR) were 7.95, 3.96, 30.13, and 1.32 x 1041, respectively signifying that the change of these variables in the donors differed from those in the controls (alternative hypothesis). Triglyceride, HDL‐C, and TyG index of the donors increased more than those of the controls while eGFR of the donor decreased more than that of the controls. Our data suggest that triglycerides and insulin resistance increase after donor nephrectomy. Kidney donors should be informed about these metabolic changes and should adhere to lifestyle recommendations that may mitigate insulin resistance. Summary at a Glance: This matched cohort study investigated the effect of kidney donation on glucose and lipid metabolisms using Bayesian hypothesis testing. Kidney donation increased triglyceride, high‐density lipoprotein cholesterol, and triglyceride‐glucose index of insulin resistance. These metabolic effects of kidney donation should be recognized and appropriately addressed. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: The timing and magnitude of antiretroviral therapy–associated weight change attributions are unclear. Setting: HIV Outpatient Study participants. Methods: We analyzed 2007–2018 records of virally suppressed (VS) persons without integrase inhibitor (INSTI) experience who switched to either INSTI-based or another non–INSTI-based ART, and remained VS. We analyzed BMI changes using linear mixed models, INSTI- and tenofovir alafenamide (TAF) contributions to BMI change by linear mixed models–estimated slopes, and BMI inflection points. Results: Among 736 participants (5316 person-years), 441 (60%) switched to INSTI-based ART; the remainder to non–INSTI-based ART. The mean follow-up was 7.15 years for INSTI recipients and 7.35 years for non-INSTI. Preswitch, INSTI and non-INSTI groups had similar median BMI (26.3 versus 25.9 kg/m2, P = 0.41). INSTI regimens included raltegravir (178), elvitegravir (112), and dolutegravir (143). Monthly BMI increases postswitch were greater with INSTI than non-INSTI (0.0525 versus 0.006, P < 0.001). A BMI inflection point occurred 8 months after switch among INSTI users; slopes were similar regardless of TAF use immediately postswitch. Among INSTI + TAF users, during 8 months postswitch, 87% of BMI slope change was associated with INSTI use, 13% with TAF use; after 8 months, estimated contributions were 27% and 73%, respectively. For non-INSTI+TAF, 84% of BMI gain was TAF-associated consistently postswitch. Persons switching from TDF to TAF had greater BMI increases than others (P < 0.001). Conclusion: Among VS persons who switched ART, INSTI and TAF use were independently associated with BMI increases. During 8 months postswitch, BMI changes were greatest and most associated with INSTI use; afterward, gradual BMI gain was largely TAF-associated. [ABSTRACT FROM AUTHOR]

Cinnamic acid, ferulic acid, and the flavonoids quercetin and taxifolin (dihydroquercetin) are naturally occurring compounds found in plants. They are often referred to as polyphenols and are known, among others, for their pharmacological effects supporting health through the inhibition of aging processes and oxidative stress. To improve their bioavailability, pharmacological activities, and safety, the creation of novel flavonoid–phenolic acid hybrids is an area of active research. Previous work showed that such hybridization products of phenolic acids and flavonoids enhanced the resilience of neuronal cells against oxidative stress in vitro, and attenuated cognitive impairment in a mouse model of Alzheimer’s disease (AD) in vivo. Notably, the therapeutic effects of the hybrid compounds we obtained were more pronounced than the protective activities of the respective individual components. The underlying mechanisms mediated by the flavonoid–phenolic acid hybrids, however, remained unclear and may differ from the signaling pathways activated by the originating structures of the respective individual phenolic acids or flavonoids. In this study, we characterized the effects of four previously described potent flavonoid–phenolic acid hybrids in models of oxidative cell death through ferroptosis. Ferroptosis is a type of iron-dependent regulated cell death characterized by lipid peroxidation and mitochondrial ROS generation and has been linked to neurodegenerative conditions. In models of ferroptosis induced by erastin or RSL3, we analyzed mitochondrial (lipid) peroxidation, mitochondrial membrane integrity, and Ca2+ regulation. Our results demonstrate the strong protective effects of the hybrid compounds against ROS formation in the cytosol and mitochondria. Importantly, these protective effects against ferroptosis were not mediated by radical scavenging activities of the phenolic hybrid compounds but through inhibition of mitochondrial complex I activity and reduced mitochondrial respiration. Our data highlight the effects of flavonoid–phenolic acid hybrids on mitochondrial metabolism and further important mitochondrial parameters that collectively determine the health and functionality of mitochondria with a high impact on the integrity and survival of the neuronal cells.

AimsObesity is associated with progression of chronic kidney disease (CKD). Treatment with bardoxolone methyl in a multinational phase 3 trial, Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), resulted in increases in estimated glomerular filtration rate (eGFR) with concurrent reductions in body weight. We performed post-hoc analyses to further characterize reductions in body weight with bardoxolone methyl.MethodsEligible patients with type 2 diabetes (T2DM) and CKD stage 4 (eGFR 15 to

Background: Endothelium function is often impaired in patients with type 2 diabetes. We hypothesized that by improving endothelial function using diastole-synchronized compressions/decompressions (DSCD) to the lower body may improve the metabolic profile. The objective of this research was to evaluate the effects of single and multiple DSCD sessions on microcirculation, endothelium function and metabolic parameters of patients with type 2 diabetes. Methods: Two monocentric, controlled, randomized cross-over studies (Study 1 and Study 2) were performed. In Study 1, 16 patients received one 20 min DSCD and one simulated (control) session at 2 week intervals; continuous glucose monitoring and cutaneous blood flow were recorded continuously before, during and after DSCD or Control session; other vascular assessments were performed before and after DSCD and control sessions. In Study 2, 38 patients received 60 min DSCD sessions three times/week for three months followed by a 4–6 week washout and 3 month control period (without simulated sessions); vascular, metabolic, body composition, physical activity and quality of life assessments were performed before and after 3 months. Results: Both studies showed significant, multiplex effects of DSCD sessions. In Study 1, cutaneous blood flow and endothelium function increased, and plasma and interstitial glucose levels after a standard breakfast decreased after DSCD sessions. In Study 2, cutaneous endothelium function improved, LDL-cholesterol and non-HDL cholesterol decreased, extra-cell water decreased and SF-36 Vitality score increased after 3 months of DSCD sessions. Conclusions: Our findings support the beneficial effect of DSCD on the endothelium and show concomitant beneficial metabolic and vitality effects. Future clinical trials need to test whether DSCD use translates into a preventive measure against microvascular diabetic complications and its progression. Trial registration ClinicalTrials.gov identifiers: NCT02293135 and NCT02359461. [ABSTRACT FROM AUTHOR]

Obesity is strongly associated with nonalcoholic fatty liver disease as well as advanced forms of the disease such as nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. While lifestyle and diet modifications have been the cornerstone of treatment for NASH thus far, they are only effective for less than half of the patients. New endoscopic bariatric therapies (EBTs) have already proved to be safe and effective for the treatment of obesity and type 2 diabetes mellitus, and may provide an intermediate, less invasive, cost-effective option for patients with NASH. In this review, we aim to describe the data and evidence as well as outline future areas of development for endobariatric therapies for the treatment of NASH. In conclusion, EBTs present an effective and safe therapeutic modality for use in the growing pandemic of obesity-related liver disease and should be investigated further with large-scale trials in this patient population. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a promising class of medications for type 2 diabetes (T2D) management. While their glucose-lowering effects are well-established, their long-term impact on cardiovascular outcomes remains a subject of ongoing research and debate. This systematic review aims to assess the long-term cardiovascular effects of GLP-1 RAs in adults with T2D compared to placebo, standard care, or other glucose-lowering medications. We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) and observational studies published from database inception to April 2024. Two independent reviewers screened the studies and extracted the data. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke. Secondary outcomes included individual components of MACE, hospitalization for heart failure, and all-cause mortality. We included 15 studies (eight RCTs and seven observational studies) involving over 180,000 participants. GLP-1 RAs were associated with a significant reduction in MACE compared to placebo or standard care (risk ratio: 0.88, 95% CI: 0.82-0.94, p<0.001). GLP-1 RAs also demonstrated superior cardiovascular protection compared to DPP-4 inhibitors and sulfonylureas. The benefits were particularly pronounced in reducing the risk of stroke and MI. Notably, some studies found larger cardiovascular benefits in frail patients. The effects on heart failure outcomes were mixed, with potential attenuated benefits in patients with baseline heart failure. GLP-1 RAs also showed promising effects on renal outcomes and metabolic parameters. The quality of evidence ranged from moderate to high across outcomes. This systematic review provides strong evidence that GLP-1 RAs offer significant cardiovascular benefits in adults with T2D, particularly in reducing MACE, stroke, and MI. The findings support current guidelines recommending GLP-1 RAs as preferred agents in patients with established cardiovascular disease or high cardiovascular risk. However, the variability in effects across different patient subgroups underscores the need for personalized treatment approaches. Future research should focus on head-to-head comparisons between different GLP-1 RAs, long-term follow-up studies, and investigation of combination therapies to further optimize the use of these agents in clinical practice., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tariq et al.)

Introduction Obesity is a complex condition characterized by excessive accumulation of body fat, which can have multiple causes, including genetic factors, inadequate diet, lack of physical exercise, and socioeconomic factors. Obesity can cause significant respiratory changes, so obese patients present pulmonary complications more frequently than individuals with normal weight. Improving respiratory function is an important aspect of obesity management, as it can reduce the risk of pulmonary complications and improve patients' quality of life. Material and method We conducted a randomized controlled, single-center study that included 70 obese patients, aiming to evaluate the effectiveness of intermittent hypoxia-hyperoxia therapy (IHHT) on metabolic and respiratory effects. Patients were randomly allocated into two equivalent groups: an intervention group, consisting of 35 patients who received IHHT, and a control group, consisting of 35 patients who did not receive this therapy. Results Patients in the intervention group showed a significant increase in exercise tolerance (p < 0.001), improvement in renal function parameters (p = 0.047 for uric acid; p = 0.006 for creatinine), and liver function (p = 0.001 AST; p = 0.030 ALT), compared to the control group. An improvement in the Tiffeneau index was also observed in the intervention group (p < 0.001), indicating an improvement in respiratory function and lung capacity. Conclusions The approach to obesity requires a holistic perspective that takes into account the physical, psychological, and social aspects of this condition. IHHT represents an integrative therapeutic approach that addresses both the metabolic and respiratory aspects of obesity and metabolic syndrome, offering promising prospects for improving patients' health and quality of life. The study results suggest that IHHT may be effective in improving physical performance, renal and hepatic function, as well as respiratory function, with the potential to provide significant benefits in the management and treatment of obese and/or metabolic syndrome patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Balneal and Rehabilitation Sanatorium Ethics Committee of Techirghiol issued approval 6403/28.04.2023. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Uzun et al.)

Astaxanthin (ASX) is a natural product and one of the most powerful antioxidants known. It has significant effects on the metabolism of many animals, increasing fecundity, egg yolk volume, growth rates, immune responses, and disease resistance. A large part of the bioactivity of ASX is due to its targeting of mitochondria, where it inserts itself into cell membranes. Here, ASX stabilizes membranes and acts as a powerful antioxidant, protecting mitochondria from damage by reactive oxygen species (ROS). ROS are ubiquitous by-products of energy metabolism that must be tightly regulated by cells, lest they bind to and inactivate proteins, DNA and RNA, lipids, and signaling molecules. Most animals cannot synthesize ASX, so they need to acquire it in their diet. ASX is easily thermally denatured during extraction, and its high hydrophobicity limits its bioavailability. Our focus in this review is to contrast the bioactivity of different ASX stereoisomers and how extraction methods can denature ASX, compromising its bioavailability and bioactivity. We discuss the commercial sources of astaxanthin, structure of stereoisomers, relative bioavailability and bioactivity of ASX stereoisomers, mechanisms of ASX bioactivity, evolution of carotenoids, and why mitochondrial targeting makes ASX such an effective antioxidant. [ABSTRACT FROM AUTHOR]

More than 422 million people worldwide have diabetes, with 90–95% having type 2 diabetes (T2D). Glycemic control of T2D has demonstrated reductions in microvascular complications but recent data have demonstrated improvements in macrovascular outcomes with sodium–glucose cotransporter 2 (SGLT2) inhibitors. Ertugliflozin is the most recent SGLT2 inhibitor approved in the USA and Europe for the treatment of T2D. This narrative review aims to present and discuss the efficacy, safety, cardiovascular (CV), and renal outcomes related to the use of ertugliflozin in T2D. Ertugliflozin has been evaluated in eight clinical trials (n=5248) with a focus on glycemic control. These trials have demonstrated improvement in glycosylated hemoglobin (0.6–1%), fasting plasma glucose (30–50 mg/dL), 2-hour postprandial glucose (60–70 mg/dL), decreased body weight (2–3 kg), and lowering of blood pressure (3–5 mmHg) in patients with T2D when ertugliflozin is used as monotherapy or in addition to metformin, sitagliptin, insulin, and/or sulfonylureas. The findings from the VERTIS-CV trial (n=8246) were recently published and demonstrated that ertugliflozin use in patients with T2D and atherosclerotic CV disease is safe but did not demonstrate superiority in the lowering of major CV events compared to placebo. Other SGLT2 inhibitors, such as empagliflozin and canagliflozin, have demonstrated this benefit. The VERTIS-CV trial demonstrated that the use of ertugliflozin led to a decrease in the number of hospitalizations for heart failure and this lends further support that this benefit is a class effect of SGLT2 inhibitors.

Abstract Background The disclosure in the media of a benefit with the use of dexamethasone in patients with COVID-19 infection sets precedents for self-medication and inappropriate use of corticosteroids. Methods This is a critical interpretive synthesis of the data available in the literature on the effects of the use of corticosteroids and the impact that their indiscriminate use may have on patients with diabetes. Reviews and observational and experimental studies published until June 18, 2020 were selected. Results Corticosteroids are substances derived from cholesterol metabolism that interfere with multiple aspects of glucose homeostasis. Interactions between corticoid receptors and target genes seem to be among the mechanisms responsible for the critical functions of glucocorticoids for survival and anti-inflammatory effects observed with these medications. Corticosteroids increase hepatic gluconeogenesis, reduce peripheral use of glucose and increase insulin levels. Previous studies have shown that glucocorticoids have a pro-adipogenic function, increasing deposition of abdominal fat, and lead to glucose intolerance and hypertriglyceridemia. In addition, these drugs play a role in controlling liver metabolism and can lead to the development of hepatic steatosis. Glucocorticoids reduce the recruitment of osteoblasts and increase the number of osteoclasts, which results in increased bone resorption and greater bone fragility. Moreover, these medications cause water and sodium retention and increase the response to circulating vasoconstrictors, which results in increased blood pressure levels. Chronic or high-dose use of corticosteroids can, by itself, lead to the onset of diabetes. For those who were already diagnosed with diabetes, studies show that chronic use of corticosteroids leads to a 94% higher risk of hospitalization due to diabetes complications. In addition to the direct effects on glycemic control, the effects on arterial pressure control, lipids and bone metabolism also have a potential for severe consequences in patients with diabetes. Conclusion Fear and uncertainty toward a potentially serious infection may lead people to self-medication and the inappropriate and abusive use of corticosteroids. More than ever, it is necessary for health professionals to be alert and able to predict damages related to the use of these drugs, which is the first step to minimize the potential damages to come.

The review is devoted to selective I1-imidazoline-receptor agonists. An analysis of Russian and foreign studies is presented, the results of which indicate that this drug class not only provides adequate and long-term control of blood pressure, but also has a number of favorable metabolic effects. Therefore, it contributes to reducing insulin resistance (weight loss) and has organ protective properties (endothelial function improvement, left ventricular hypertrophy regression, microalbuminuria reduction). At the same time, selective I1-imidazoline-receptor agonists are much less likely to cause side effects characteristic of old-generation sympatholytic agents. This class of drugs is invariably included in Russian guidelines for the diagnosis and treatment of hypertension.

Background: Long-term administration of dexamethasone induces adverse effects such as muscle catabolism, hyperplasia, increased adiposity, and insulin resistance (IR). In view of these data, many authors tried to induce IR with different individual dose ranges with a varied induction periods. In this study, dexamethasone was used to find the dose to induce maximum insulin resistance in rodents. Materials and methods: A sum of 42 healthy male Wistar albino rats were categorized into six groups of dexamethasone treatment and one control group (n=6/group). In a 6-day study period, all treatment groups received respective graded doses of dexamethasone starting from low - (0.5 mg/kg and 1 mg/kg), intermediate - (2 mg/kg and 4 mg/kg) and high-dose (8 mg/kg and 16 mg/kg). Results: Graded doses of dexamethasone treatment for 6 days produced hyperglycemia and hyperinsulinemia in a dose-dependent manner and the maximum effect was noted with high doses of dexamethasone compared to intermediate and low (p<0.05). The profound reduction in insulin sensitivity was caused by high-doses of dexamethasone treatment evidenced by sustained elevation of homeostatic model assessment of insulin resistance (HOMA-IR) which was strongly associated with a declined homeostatic model assessment of insulin sensitivity (HOMA-IS), The peripheral sensitivity indices, Gutt and Matsuda, were markedly elevated in high dexamethasone groups compared to intermediate- and low-dose groups (p<0.05). Serum lipids and creatinine (p<0.05), whereas high-density lipoprotein cholesterol (HDL-CH) was markedly reduced and resulted in the subsequent rise in the atherogenic index (AGI) (p<0.05). Moderate to severe glycosuria and ketonuria were noted in intermediate- and high-dose treatment groups only. However, there is no significant difference in metabolic effects between 8 mg/kg and 16 mg/kg treatments (p>0.05). Conclusion: Administration of 8 mg/kg dexamethasone for 6 days would be sufficient for the induction of maximum insulin resistance in Wistar albino rats. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of older versus younger age on change in anthropometric and metabolic measures during extended treatment of psychotic depression with sertraline plus olanzapine.Methods: Two hundred and sixty-nine men and women aged 18-85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo. Weight, waist circumference and plasma lipids, glucose, HbA1c, and insulin were measured at regular intervals during the acute, stabilization and randomized phases of the study. Linear mixed models were used to analyze the trajectories of anthropometric and metabolic measures.Results: Participants aged 60 years or older experienced less weight gain and less increase in cholesterol during the combined acute and stabilization phases of the study compared with those aged 18-59 years. At the acute-stabilization termination visit, mean weight in older participants was 6.5 lb. less than premorbid weight, whereas it was 17.9 lb. more than premorbid weight in younger participants. In the RCT, there was a significant interaction of treatment and age group for the trajectory of weight, but the post hoc tests that compared age groups within each treatment arm were not statistically significant. There were no clinically significant differences between younger and older participants in glycemic measures.Conclusion: Older patients with psychotic depression experienced less increase in weight and total cholesterol than their younger counterparts during acute and stabilization treatment with sertraline plus olanzapine. In the older group, weight gained during the acute and stabilization phases appeared to be partial restoration of weight lost during the index episode of depression, whereas weight gain in younger participants was not. [ABSTRACT FROM AUTHOR]

Sleep is essential for every living organism. Humans spend about one-third of their lives sleeping. Sleep has been studied extensively, and the role of sleep in psychological, mental, and physical well-being is established to be the best. The rhythm of the brain between wakefulness and sleep is called the circadian rhythm, which is mainly controlled by melatonin and the pineal gland. The imbalance of this rhythm can lead to devastating effects on health. Vigorous workouts close to bedtime can interfere with falling asleep. Meal timing and composition can significantly affect sleep quality. It is advised to avoid large meals, caffeine, and alcohol before bedtime. Heavy meals close to bedtime can lead to poor sleep and hormone disruption. By following these guidelines enumerated in the article, individuals can improve sleep quality and overall health. Sleep cycles, especially rapid eye movement sleep, have a profound influence on mental and physical health. Adhering to recommended sleep practices enhances bodily restoration, fortifies the immune system, and upholds metabolic equilibrium. Sleep hygiene aligned with circadian rhythms is crucial for disease prevention and well-being. Healthcare professionals should prioritize sleep optimization strategies for patient care and public health., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Desai et al.)

This study aimed to evaluate the effects of addition of yacon flour on the quality parameters of goat milk yogurt and investigate the metabolic effects of its regular consumption on high fat diet-fed Wistar rats (30 days). The formulation containing 7% (w/v) yacon flour had higher nutritional values, acceptable sensory attributes and higher count (107 cfu/g) of viable probiotic microorganisms, with shelf life of at least 30 days. 7% yacon flour addition improved goat yogurt sugar profile, reducing lactose (0.94%) and increasing prebiotic fructooligosacharides (4.55%) content in the final product. Supplementation of goat yogurt + yacon to a high fat diet resulted in lower body weight, body mass index, fasting glucose levels, HOMA-IR and atherogenic indices of rats, improving the effects of goat yogurt or yacon flour alone (P

The article provides a review of the topical issues of beta-blockers use in the clinical practice. Attention of practitioners is drawn to the possibility of using these or other beta-blockers in various clinical situations. Some beta-blockers, especially non-selective ones, have negative effects and cannot be used in certain clinical situations (metabolic syndrome, type 2 diabetes mellitus). Modern super-selective beta-blockers do not have these negative effects and can be widely used in clinical practice, including metabolic syndrome and type 2 diabetes. The review focuses on metoprolol tartrate, which has the most extensive evidence base for efficient treatment of various cardiovascular diseases. Another problem related to beta-blockers is their infrequent use or use at inadequate doses. In this connection, a practitioner should prescribe them at the recommended therapeutic doses in various clinical situations, according to the instructions for use of the drug.

Objective We investigated direct effects of a therapeutic growth hormone dose on lipolysis, glucose and amino acid metabolism. Methods This crossover microdialysis trial involved six healthy male volunteers receiving single subcutaneous injections of both growth hormone (0.035 mg/kg) and placebo (0.9% sodium chloride). The investigation comprised three test days with standard diet. The first day served for adaptation, the second and third one for determining study data during 9 night hours with or without growth hormone. Abdominal subcutaneous microdialysate and blood were continuously collected and forwarded to a separate room next door where hourly taken samples were centrifuged and frozen until analysed. Results Growth hormone achieved the peak serum level after 3 h followed by a plateau-like course for the next 6 h. Glycerol in microdialysate started to rise 2 h following growth hormone injection achieving significance compared to placebo after 9 h (P <0.05). Serum glycerol increased 4 h after growth hormone administration achieving significance after 6 h (P <0.05). Glucose and amino acid concentrations showed neither in microdialysate nor in serum significant differences between growth hormone and placebo. Serum values of insulin and C-peptide revealed no significant difference between growth hormone and placebo. Summary and Conclusion As the result of a high single subcutaneous dose of GH, persistent lipolysis can be shown in continuously collected microdialysate and blood, but no indication for gluconeogenesis or protein anabolism. [ABSTRACT FROM AUTHOR]

Multiple pharmacologic strategies are currently available to lower blood pressure (BP). Renin-angiotensin system (RAS)-inhibitors, calcium channel blockers and diuretics are widely recommended as first line therapies. Sympathetic activation is an important contributor to BP elevation but remains unopposed or is even increased by some of these drug classes. Selective imidazoline receptor agonists (SIRAs) reduce increased central sympathetic outflow and are considered as add-on therapy in most guidelines. We conducted an international survey to evaluate contemporary hypertension management strategies in countries with high prescription rates of SIRAs to better understand the rationale and practical indications for their use in a real-world setting. Physicians from seven countries (India, Jordan, Lebanon, Russia, Saudi Arabia, South Africa, United Arab Emirates) were asked to complete a web-based questionnaire and comment on clinical case scenarios to provide information on their current practice regarding antihypertension strategies, underlying rationale for their choices, and adherence to relevant guidelines. 281 physicians completed the questionnaire including mainly cardiologists (35%) and general practitioners (32%). 96% reported using European (60%) or local (56%) guidelines in their daily practices. The majority of responding physicians (83%) had knowledge of SIRAs and 70% prescribed SIRAs regularly typically as a third line antihypertensive strategy (63%). The preferred combination partners for SIRAs were RAS-inhibitors (72%). Contemporary hypertension management varies between countries and therapeutic approaches in a real-world setting are not always in line with recommendations from available guidelines. In the countries selected for this survey prescription of SIRAs was common and appeared to be guided predominantly by considerations relating to the underlying pathophysiologic mechanism of sympathetic inhibition. [ABSTRACT FROM AUTHOR]

This study aims to better characterize the metabolic effects of antipsychotics in the early stage of treatment in first-episode patients with schizophrenia. We performed a retrospective real-world study in a naturalistic setting that included inpatients with first-episode drug-naïve schizophrenia; metabolic profiles were measured at baseline and 2 weeks and 4 weeks after antipsychotic treatment. The metabolic profiles of medicated patients with first-episode schizophrenia were also included. Insulin resistance, based on the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C), increased significantly after 2 weeks of antipsychotic treatment, whereas fasting glucose (FG) decreased significantly. Regarding lipid metabolism, triglycerides (TG), cholesterol (CHOL) and low-density lipoprotein cholesterol (LDL-C) increased significantly after 2 weeks of antipsychotic treatment; however, high-density lipoprotein cholesterol (HDL-C) decreased significantly after 4 weeks of antipsychotic treatment. There were no statistically significant differences between the antipsychotic groups in any of the metabolic parameters evaluated. Our study revealed that insulin resistance and lipid metabolic abnormalities occurred as early as two weeks after the initiation of antipsychotic treatment. Our findings suggest that metabolic profiles should been monitored in the early stage of antipsychotics treatment in clinical practice. Further research is needed to explore the underlying mechanisms of the short-term effects of antipsychotics on metabolic parameters. [ABSTRACT FROM AUTHOR]

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• The effects of glucose-lowering drugs in patients with type 2 diabetes (T2D) are potentially mediated by gut microbiota, and these drugs may also directly influence microbiome composition. • It has not been ascertained whether either dapagliflozin or gliclazide influences microbiome composition in patients with T2D. • This study found that microbiome composition was not altered by either dapagliflozin or gliclazide treatment. • Thus, the metabolic effects of either treatment are not likely to be driven by changes in colonic microbiome composition. Patients with type 2 diabetes (T2D) are usually treated with (combinations of) glucose-lowering medication. The effects of these drugs can be influenced by intestinal microbiota and vice versa, as these drugs can also influence microbiome composition. However, as there is currently little clinical insight into this bug–drug interaction, our study aimed to evaluate the effects of 12-week treatment with the SGLT2 inhibitor dapagliflozin and sulphonylurea gliclazide on gut microbiome composition in T2D patients treated with metformin. A total of 44 patients were randomized to either dapagliflozin or gliclazide treatment for 12 weeks. At baseline and after 12 weeks, faecal samples and 24-h urine were collected. During study visits, anthropometric data were measured and blood samples drawn after an overnight fast. Microbiome composition was determined by 16S rRNA gene sequencing. Plasma glucose, insulin, HbA 1c and urinary glucose excretion were measured using conventional methods. While dapagliflozin and gliclazide similarly improved glycaemic control, dapagliflozin reduced and gliclazide increased fasting insulin. Dapagliflozin also greatly increased urinary glucose excretion whereas gliclazide did not, while body mass index, fat mass percentage and waist circumference were reduced by dapagliflozin, but increased by gliclazide. However, neither treatment significantly affected either gut microbiome alpha diversity or composition and, after treatment, no associations were found between microbiome composition and other clinical parameters. Even though gliclazide and dapagliflozin have different metabolic actions in patients with T2D, neither treatment altered the faecal microbiome, thereby suggesting that the observed metabolic changes are not mediated by their effects on the microbiota. [ABSTRACT FROM AUTHOR]

Prostate cancer has the second highest incidence of all cancers amongst men worldwide. Androgen deprivation therapy (ADT) remains a common form of treatment. However, in reducing serum testosterone to castrate levels and rendering men hypogonadal, ADT contributes to a myriad of adverse effects which can affect prostate cancer prognosis. Physical activity is currently recommended as synergistic medicine in prostate cancer patients to alleviate the adverse effects of treatment. Progressive resistance training (PRT) is an anabolic exercise modality which may be of benefit in prostate cancer patients given its potency in maintaining and positively adapting skeletal muscle. However, currently, there is a scarcity of RCTs which have evaluated the use of isolated PRT in counteracting the adverse effects of prostate cancer treatment. Moreover, although physical activity in general has been found to reduce relapse rates and improve survival in prostate cancer, the precise anti-oncogenic effects of specific exercise modalities, including PRT, have not been fully established. Thus, the overall objective of this article is to provide a rationale for the in-depth investigation of PRT and its biological effects in men with prostate cancer on ADT. This will be achieved by (1) summarising the metabolic effects of ADT in patients with prostate cancer and its effect on prostate cancer progression and prognosis, (2) reviewing the existing evidence regarding the metabolic benefits of PRT in this cohort, (3) exploring the possible oncological pathways by which PRT can affect prostate cancer prognosis and progression and (4) outlining avenues for future research. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a chronic endocrine/metabolic disorder characterized by elevated postprandial and fasting glycemic levels that result in disturbances in primary metabolism. In this study, we evaluated the metabolic effects of thiazolidine-2,4-dione derivatives in Wistar rats and Swiss mice that were fed a high-fat diet (HFD) for 4 weeks and received 90 mg/kg of streptozotocin (STZ) intraperitoneally as a T2DM model. The HFD consisted of 17% carbohydrate, 58% fat, and 25% protein, as a percentage of total kcal. The thiazolidine-2,4-dione derivatives treatments reduced fasting blood glucose (FBG) levels by an average of 23.98%–50.84%, which were also improved during the oral starch tolerance test (OSTT). Treatment with thiazolidine-2,4-dione derivatives also improved triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and total cholesterol levels (P < 0.05). The treatment intake has also shown a significant effect to modulate the altered hepatic and renal biomarkers. Further treatment with thiazolidine-2,4-dione derivatives for 28 days significantly ameliorated changes in appearance and metabolic risk factors, including favorable changes in histopathology of the liver, kidney, and pancreas compared with the HFD/STZ-treated group, suggesting its potential role in the management of diabetes. Thiazolidine-2,4-dione derivatives are a class of drugs that act as insulin sensitizers by activating peroxisome proliferator-activated receptor-gamma (PPAR-γ), a nuclear receptor that regulates glucose and lipid metabolism. The results of this study suggest that thiazolidine-2,4-dione derivatives may be a promising treatment option for T2DM by improving glycemic control, lipid metabolism, and renal and hepatic function. • Thiazolidine-2,4-dione showed in vivo hypoglycemic effects in diabetic mice. • Effectively lowers hyperglycemia in STZ-induced type 2 diabetic mice. • The impact of derivatives on biochemical and hematological analyses was carried out. [ABSTRACT FROM AUTHOR]