Multi-faceted Anti-obesity Effects of N-Methyl-D-Aspartate (NMDA) Receptor Modulators: Central-Peripheral Crosstalk.

Hypothalamus is central to food intake and satiety. Recent data unveiled the expression of N-methyl-D-aspartate receptors (NMDAR) on hypothalamic neurons and their interaction with GABAA and serotoninergic neuronal circuits. However, the precise mechanisms governing energy homeostasis remain elusive. Notably, in females, the consumption of progesterone-containing preparations, such as hormonal replacement therapy and birth control pills, has been associated with hyperphagia and obesity-effects mediated through the hypothalamus. To elucidate this phenomenon, we employed the progesterone-induced obesity model in female Swiss albino mice. Four NMDAR modulators were selected viz. dextromethorphan (Dxt), minocycline, d-aspartate, and cycloserine. Obesity was induced in female mice by progesterone administration for 4 weeks. Mice were allocated into 7 groups, group-1 as vehicle control (arachis oil), group-2 (progesterone + arachis oil), and group-3 as positive-control (progesterone + sibutramine); other groups were treated with test drugs + progesterone. Various parameters were recorded like food intake, thermogenesis, serum lipids, insulin, AST and ALT levels, organ-to-body weight ratio, total body fat, adiposity index, brain serotonin levels, histology of liver, kidney, and sizing of fat cells. Dxt-treated group has shown a significant downturn in body weight (p < 0.05) by a decline in food intake (p < 0.01), organ-to-liver ratio (p < 0.001), adiposity index (p < 0.01), and a rise in body temperature and brain serotonin level (p < 0.001). Dxt demonstrated anti-obesity effects by multiple mechanisms including interaction with hypothalamic GABAA channels and anti-inflammatory and free radical scavenging effects, improving the brain serotonin levels, and increasing insulin release from the pancreatic ß-cells.

A Placebo-Controlled, Double-Blind Clinical Investigation to Evaluate the Efficacy of a Patented Trigonella foenum-graecum Seed Extract "Fenfuro®" in Type 2 Diabetics.

BACKGROUND: Trigonella foenum-graecum (Fenugreek) is an extensively researched phytotherapeutic for the management of Type 2 diabetes without any associated side effects. The major anti-diabetic bioactive constituents present in the plant are furostanolic saponins, which are more abundantly available in the seed of the plant. However, the bioavailability of these components depends on the method of extraction and hence formulation of the phytotherapeutic constitutes a critical step for its success. OBJECTIVE: The present study reports the efficacy of a novel, patented fenugreek seed extract, Fenfuro®, containing significant amount of furostanolic saponins, in an open-labelled, two-armed, single centric study on a group of 204 patients with Type 2 diabetes mellitus over a period of twelve consecutive weeks. RESULTS: Administration of Fenfuro® in the dosage of 500 mg twice daily along with metformin and/or sulfonylurea-based prescribed antidiabetic drug resulted in a reduction of post-prandial glucose by more than 33% along with significant reduction in fasting glucose, both of which were greater than what resulted for the patient group receiving only Metformin and/or Sulfonylurea therapy. Fenfuro® also resulted in reduction in mean baseline HOMA index from 4.27 to 3.765, indicating restoration of insulin sensitivity which was also supported by a significant decrease in serum insulin levels by >10% as well as slight reduction in the levels of C-peptide. However, in the case of the Metformin and/or Sulfonylurea group, insulin levels were found to increase by more than 14%, which clearly indicated that drug-induced suppression of glucose levels instead of restoration of glucose homeostasis. Administration of the formulation was also found to be free from any adverse side effects as there were no changes in hematological profile, liver function and renal function. CONCLUSION: The study demonstrated the promising potential of this novel phytotherapeutic, Fenfuro®, in long-term holistic management of type-2 diabetes.

The Effects of Ginger (Zingiber Officinale Roscoe) on Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blinded Placebo-Controlled Clinical Trial.

Nonalcoholic fatty liver disease (NAFLD) is a prominent etiological factor for liver cirrhosis worldwide. It is frequently associated with obesity, diabetes, dyslipidemia, and hypertension. The objective of this study is to assess the efficacy and safety of ginger (Zingiber officinale Roscoe) supplementation in patients with type 2 diabetes mellitus (T2DM) who have NAFLD. In a two-arm, double-blind, placebo-controlled clinical trial, seventy-six patients diagnosed with both T2DM and NAFLD were randomly assigned to receive either ginger powder capsules (1000 mg, twice daily) or placebo capsules (administered in the same manner) for a period of three months. Anthropometric measurements, blood pressure readings, biochemical profiles, and imaging parameters were assessed before and after the intervention. Safety measures were also evaluated. In both the ginger and placebo groups, there was a significant reduction in mean body mass index (BMI), waist and hip circumferences, as well as liver transaminase levels. Moreover, significant improvements in mean systolic and diastolic blood pressures were observed in the ginger group (p = 0.02 and < 0.0001, respectively). Within the ginger group, there was a decrease in serum insulin levels and insulin resistance (HOMA-IR) (p = 0.002 and 0.004, respectively). Furthermore, the ginger group exhibited an improvement in serum HDL-cholesterol level (p = 0.01). However, there were no significant changes in the assessed inflammatory markers or the indices obtained from fibroscan imaging, including steatosis percent and controlled attenuation parameter. This study demonstrates that ginger supplementation can significantly improve mean systolic and diastolic blood pressures. However, it does not have a significant impact on inflammatory markers or fibroscan imaging indices. Nonetheless, the three-month use of ginger improves serum insulin level, insulin resistance (HOMA-IR), and HDL-cholesterol level compared to baseline values. Further investigations with longer durations and larger sample sizes are recommended.

Photobiomodulation in diabetic rats: Effects on morphological, pancreatic parameters, and glucose homeostasis.

Photobiomodulation (PBM) has therapeutic effects on wound healing, diabetic microangiopathy, and retinopathy. However, little is known about the use of PBM for the treatment of diabetes mellitus (DM). In this context, we aimed to evaluate the effects of PBM on pancreas morphology and insulin and glucose tolerance in an experimental model of DM. Thus, DM was induced by streptozotocin (STZ) (60 mg/kg). Subsequently, the rats were treated with PBM (808 nm and 30 J/cm2 ). After euthanasia, morphometric parameters and immunoreactivity for insulin and 8-OHdG were evaluated in the pancreas. The results showed that treated animals had higher values of body mass and higher values in the number of beta cells in the pancreas. In conclusion, PBM resulted in decreased weight loss in STZ-induced diabetic rats and presented a stimulatory effect on the pancreas of the treated animals, highlighting the promising effects of this therapy in the clinical condition of DM.

Repeated oral sucrose dosing after the second wind is unnecessary in patients with McArdle disease: Results from a randomized, placebo-controlled, double-blind, cross-over study.

It is well-established that oral sucrose ingested shortly before exercise improves early exercise tolerance in individuals with McArdle disease. This is by supplying blood-borne glucose for muscle metabolism to compensate for the blocked glycogenolysis. The present study investigated if individuals with McArdle disease could benefit further from repeated sucrose ingestion during prolonged exercise. In this double-blind, placebo-controlled, cross-over study, the participants were randomized to ingest either sucrose or placebo first and subsequently the opposite on two separate days. The participants ingested the drink 10 min before and thrice (after 10, 25, and 40 min) during a 60-min submaximal exercise test on a cycle ergometer. The primary outcome was exercise capacity as indicated by heart rate (HR) and perceived exertion (PE) responses to exercise. Secondary outcomes included changes in blood metabolites, insulin and carbohydrate, and fatty acid oxidation rates during exercise. Nine participants with McArdle disease were included in the study. We confirmed improvement of exercise capacity with oral sucrose vs. placebo during early exercise (pre-second wind) indicated by lower peak HR and PE (p < 0.02). We found no further beneficial effect with repeated sucrose versus placebo ingestion during prolonged exercise, as indicated by no difference in HR or PE post-second wind (p > 0.05). Glucose, lactate, insulin, and carbohydrate oxidation rates increased, and fatty acid oxidation decreased with sucrose versus placebo (p ≤ 0.0002). We can conclude that repeated sucrose ingestion is not recommended during prolonged exercise. This finding can prevent excessive caloric intake and reduce the risk of obesity and insulin resistance.

Evaluation of Antidiabetic and Antioxidant Activities of Fruit Pulp Extracts of Cucurbita moschata Duchesne and Cucurbita maxima Duchesne.

Objective: To evaluate and compare the antidiabetic and antioxidant activities of fruit pulp extracts from Cucurbita moschata (PCMOS) and Cucurbita maxima (PCMAX). Methods: The antidiabetic activity was carried out in vivo by orally and daily giving the extracts at a dose of 500 mg/kg·b.w. to the streptozotocin-induced diabetic male albino Wistar rats for six weeks. After the period of administration, blood glucose levels, body weight, serum insulin, morphology of islets of Langerhans, biochemical parameters, and haematological values of the rats were determined. Meanwhile, the antioxidant activity was carried out in vitro by determination of total phenolic and flavonoid contents, DPPH radical scavenging activity, and ferric reducing antioxidant power. Results: PCMAX significantly (p < 0.05) reduced blood glucose levels but increased the body weight, serum insulin levels, size and number of islets of Langerhans, and ß-cell number of the treated diabetic rats more than PCMOS did. However, they did not alter biochemical parameters and haematological values of the treated diabetic rats. PCMAX possessed total phenolic and flavonoid contents and showed DPPH scavenging and FRAP reducing antioxidant power more significantly (p < 0.05) than PCMOS. Conclusions: According to the obtained results, it is indicated that PCMOS and PCMAX possess antidiabetic and antioxidant activities. PCMAX possesses more potent antidiabetic and antioxidant activities than PCMOS. These are probably due to PCMAX providing polysaccharide and total phenolic and flavonoid contents more than PCMOS.

A multi-omics integrative approach unravels novel genes and pathways associated with senescence escape after targeted therapy in NRAS mutant melanoma.

Therapy Induced Senescence (TIS) leads to sustained growth arrest of cancer cells. The associated cytostasis has been shown to be reversible and cells escaping senescence further enhance the aggressiveness of cancers. Chemicals specifically targeting senescent cells, so-called senolytics, constitute a promising avenue for improved cancer treatment in combination with targeted therapies. Understanding how cancer cells evade senescence is needed to optimise the clinical benefits of this therapeutic approach. Here we characterised the response of three different NRAS mutant melanoma cell lines to a combination of CDK4/6 and MEK inhibitors over 33 days. Transcriptomic data show that all cell lines trigger a senescence programme coupled with strong induction of interferons. Kinome profiling revealed the activation of Receptor Tyrosine Kinases (RTKs) and enriched downstream signaling of neurotrophin, ErbB and insulin pathways. Characterisation of the miRNA interactome associates miR-211-5p with resistant phenotypes. Finally, iCell-based integration of bulk and single-cell RNA-seq data identifies biological processes perturbed during senescence and predicts 90 new genes involved in its escape. Overall, our data associate insulin signaling with persistence of a senescent phenotype and suggest a new role for interferon gamma in senescence escape through the induction of EMT and the activation of ERK5 signaling.

Effect of sesame (Sesamum indicum L.) consumption on glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

Conflicting evidence exists on the effect of sesame consumption on glucose metabolism in patients with type 2 diabetes (T2D). Therefore, this meta-analysis focuses on the relationship between sesame (Sesamum indicum L.) intervention and glycemic control in patients with T2D. Published literature was retrieved and screened from PubMed, Scopus, ISI Web of Science, and the Cochrane Library up to December 2022. Outcome measures included fasting blood sugar (FBS) concentrations, fasting insulin levels, and hemoglobin A1c (HbA1c) percentage. Pooled effect sizes were reported as weighted mean differences (WMDs) and 95% confidence intervals (CIs). Eight clinical trials (395 participants) were eligible for meta-analyses. Overall, sesame consumption significantly reduced serum FBS (WMD: -28.61 mg/dL, 95% CI: -36.07 to -21.16, p˂0.001; I2 = 98.3%) and HbA1c percentage (WMD: -0.99%, 95% CI: -1.22 to -0.76, p ≤ 0.001; I2 = 65.1%) in patients with T2D. However, sesame consumption did not significantly influence fasting insulin levels (Hedges's: 2.29, 95% CI: -0.06 to 4.63, p = 0.06; I2 = 98.1%). In summary, the current meta-analysis showed a promising effect of sesame consumption on glycemic control through reducing FBS and HbA1c, yet additional prospective studies are recommended, using higher doses and longer intervention period, to confirm the impact of sesame consumption on insulin levels in T2D patients.

Arabic gum ameliorates systemic modulation in Alloxan monohydrate-induced diabetic rats.

Medicinal plants are considered an alternative therapy for diabetes mellitus as they regulate glucose levels. Moreover, a variety of plants offer a rich source of bioactive compounds that have potent pharmacological effects without any negative side effects. The present study aimed to clarify the effects of Arabic gum/Gum Acacia (GA) on the biochemical, histopathological, and immunohistochemical changes observed in diabetic rats. Further, the anti-inflammatory activity of GA in response to diabetes, through inflammatory mediators analysis. Male rats were divided into four groups: untreated control, diabetic, Arabic gum-treated, and Arabic gum-treated diabetic rats. Diabetes was induced using alloxan. Animals were sacrificed after 7 and 21 days of treatment with Arabic gum. Body weight, blood and pancreas tissue samples were collected for analysis. Alloxan injection significantly decreased body weight, increased glucose levels, decreased insulin levels, and caused depletion of islets of Langerhans and ß-cell damage in the pancreas. Arabic gum treatment of diabetic rats significantly increased body weight, decreased serum glucose levels, increased insulin levels, exerts anti-inflammatory effect, and improved the pancreas tissue structure. Arabic gum has beneficial pharmacological effects in diabetic rats; therefore, it might be employed as diabetic therapy to reduce the hyperglycemic damage and may be applicable for many autoimmune and inflammatory diseases treatment. Further, the new bioactive substances, such as medications made from plants, have larger safety margins, and can be used for a longer period of time.

Catechins prevent obesity-induced kidney damage by modulating PPARγ/CD36 pathway and gut-kidney axis in rats.

Obesity is an epidemic and a growing public health concern worldwide. It is one of the significant risk factors for developing chronic kidney disease. In the present study, we evaluated the preventive effect of green tea catechins (GTC) against obesity-induced kidney damage and revealed the underlying molecular mechanism of action. Various green tea catechins were quantified in the catechins-rich fraction using HPLC. In vitro, the palmitic and oleic acid-treated NRK-52E cells showed reduced fat accumulation and modulated expressions of PPARγ, CD36, and TGFß after GTC treatment. In vivo, rats were fed with a high-fat diet (HFD), and the effect of GTC was assessed at 150 and 300 mg/kg body weight doses. HFD-fed rats showed a significant reduction in weight gain and improved serum creatinine, urea, and urine microalbumin levels after GTC treatment. The improved adipokines and insulin levels in GTC treated groups indicated the insulin-sensitizing effect. Histopathology revealed reduced degenerative changes, fibrous tissue deposition, and mesangial matrix proliferation in GTC treated groups. GTC treatment also downregulated the gene expressions of lipogenic and inflammatory factors and improved the altered expressions of CD36 and PPARγ in the kidney tissue. Further, GTC prevented gut dysbiosis in rats by promoting healthy microbes like Akkermansia muciniphila and Lactobacillus reuteri. Faecal metabolome revealed reduced saturated fatty acids, and improved amino acid levels in the GTC treated groups, which help to maintain gut health and metabolism. Overall, GTC prevented obesity-induced kidney damage by modulating PPARγ/CD36 signaling and maintaining gut health in rats.

Combining LC-MS/MS profiles with network pharmacology to predict molecular mechanisms of the hyperlipidemic activity of Lagenaria siceraria stand.

ETHNOPHARMACOLOGICAL RELEVANCE: Lagenaria siceraria Stand. (Family: Cucurbitaceae), popularly known as bottle gourd, is traditionally used in Ayurvedic medicine as a food plant, especially in hypertension and obesity. AIM OF THE STUDY: Investigations were undertaken to assign novel lead combinations from this common food plant to multi-molecular modes of actions in the complex disease networks of obesity and hypertension. LC-MS/MS based metabolite screening, in-vivo high fat diet induced hyperlipidemia animal study and network pharmacology explorations of the mechanism of action for lipid lowering effects including a neighbourhood community approach for molecular combinations were performed. MATERIAL AND METHODS: Major chemical constituents of the fruits of LS (LSFE) were analysed by HPLC-DAD-MS/MS-QTOF. Wistar albino rats (n = 36), divided into 6 groups (n = 6) received either no treatment or a high-fat diet along with LSFE or Atorvastatin. Lipid profiles and biochemical parameters were evaluated. In silico cross-validated network analyses using different databases and Cytospace were applied. RESULTS: Profiling of LSFE revealed 18 major constituents: phenolic acids like p-Coumaric acid and Ferulic acid, the monolignolconferyl alcohol, the flavonoid glycosides hesperidin and apigenin-7-glucoside. Hyperlipidemic animals treated with LSFE (200 mg/kg, 400 mg/kg, 600 mg/kg) showed a significant improvement of their lipid profiles after 30 days of treatment. Network pharmacology analyses for the major 18 compounds revealed enrichment of the insulin and the ErbB signalling pathway. Novel target node combinations (e.g. AKR1C1, AGXT) including their connection to different pathways were identified in silico. CONCLUSIONS: The combined in vivo and bioinformatics analyses propose that lead compounds of LSFE act in combination on relevant targets of hyperlipidemia. Perturbations of the IRS→Akt→Foxo1 cascade are predicted which suggest further clinical investigation towards development of safe natural alternative to manage hyperlipidemia.

The effects of supplementation of Nannochloropsis oculata microalgae on biochemical, inflammatory and antioxidant responses in diabetic rats.

Diabetes is accompanied by inflammation and oxidation. Supplementation of anti-inflammatory and antioxidant compounds can prevent the progression of diabetes. This study aimed to investigate the effects of supplementation of Nannochloropsis oculata microalgae (NOM) on the inflammatory and antioxidant responses in diabetic rats. Sixty male rats were divided into six groups as diabetic and non-diabetic rats receiving 0, 10 and 20 mg/kg of body weight of NOM daily for 21 days. Body weight, the serum concentrations of insulin and glucose and the tissue concentrations of interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), malondialdehyde (MDA), ferric reducing antioxidant power (FRAP), superoxide dismutase (SOD), glutathione peroxidase (GPx) were assessed. The results showed that induction of diabetes significantly reduced the body weight, the serum concentrations of insulin and the tissue concentrations of SOD, FRAP and GPx while increasing the concentrations of glucose, MDA, IL-1ß, IL-6, NF-κB and TNF-α. Daily oral administration of NOM (10 and 20 mg/kg) significantly maintained the body weight, the serum concentrations of insulin and the tissue concentrations of SOD, FRAP and GPx while preventing the increase in the concentrations of glucose, MDA, IL-1ß and TNF-α. In conclusion, diabetes caused inflammation and oxidation while NOM worked as a natural anti-inflammatory and antioxidant compound.

Predictors of acarbose therapeutic efficacy in newly diagnosed type 2 diabetes mellitus patients in China.

BACKGROUND: Acarbose is one of the optimal drugs for patients with the first diagnosis of type 2 diabetes mellitus (T2DM). But what kind of emerging patients has the best therapeutic response to acarbose therapy has never been reported. To this end, we investigated predictors of acarbose therapeutic efficacy in newly diagnosed T2DM patients in China. METHODS: A total of 346 T2DM patients received acarbose monotherapy for 48 weeks as part of participating in the Study of Acarbose in Newly Diagnosed Patients with T2DM in China (MARCH study) from November 2008 to June 2011. Change in glycated hemoglobin (ΔHbA1c) served as a dependent variable while different baseline variables including sex, age, disease duration, weight, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), HbA1c, fasting plasma glucose (FPG), 2-h postprandial blood glucose (2 h PG), fasting insulin (FINS), 2-h postprandial insulin (2 h INS), early insulin secretion index (IGI), homeostasis model assessment of insulin resistance index (HOMA-IR), homeostasis model assessment of beta cell function (HOMA-B), area under the curve (AUC) of glucagon, insulin and GLP-1 were assessed as independent predictors. Step-wise multiple linear regression was employed for statistical analysis. RESULTS: The results suggested that independent predictors of ΔHbA1c at 12 weeks included baseline body weight (ß = - 0.012, P = 0.006), DBP (ß = 0.010, P = 0.047), FPG (ß = 0.111, P = 0.005) and 2 h PG (ß = 0.042, P = 0.043). Independent predictors of ΔHbA1c at 24 weeks included disease duration (ß = 0.040, P = 0.019) and FPG (ß = 0.117, P = 0.001). Finally, independent predictor of ΔHbA1c at 48 weeks was disease duration (ß = 0.038, P = 0.046). CONCLUSIONS: Acarbose may be more effective in newly diagnosed T2DM patients with low FPG, low 2 h PG and obesity. The earlier T2DM is diagnosed and continuously treated with acarbose, the better the response to therapy.

The Effects of Tangning Ziyabitusi on Gut Microbiota and T lymphocyte Subsets in Impaired Glucose Regulation Rats.

BACKGROUND: Impaired glucose regulation (IGR) represents the prediabetic state and is associated with gut microbiota (GM) dysbiosis and chronic inflammation. Tangning Ziyabitusi Tablet (TZT) is a Chinese Uyghur herbal medicine with preventative and therapeutic effects on diabetes, but its hypoglycemic mechanisms are unclear. METHODS: Thirty-six male Wistar rats were divided into the normal diet (ND) and IGR groups. The IGR group was given a high-fat diet (HFD). After the IGR model establishment, the ND group was divided into ND and ND+TZT groups, and the IGR group into IGR and IGR+TZT groups. After 8 weeks of TZT administration, 16S rRNA sequencing and untargeted metabolomics were performed on fecal samples. Mesenteric lymph nodes were also collected, and T lymphocytes separated after rats were sacrificed. Flow cytometry was used to characterize different CD4+ T cell subsets in mesenteric lymph nodes. Finally, we analyzed the correlation between GM and characteristic fecal metabolites. RESULTS: Impaired glucose tolerance and insulin resistance were improved in the IGR+TZT group when compared with the IGR group. Bacterial 16S rRNA sequencing results showed that Sobs and Chao1 indices in the IGR group were significantly decreased, but were increased in the IGR+TZT group. The relative abundance of Bacteroidetes was decreased while the relative abundance of Firmicutes was increased in the IGR group. Adlercreutzia abundance was decreased after TZT administration, while the abundance of Christensenellaceae_R-7_group, norank_f_norank_o_Clostridia_UCG-014, UCG-005, and Eubacterium_nodatum_group was increased in the IGR+TZT group. Lymph node CD4+ T cell proportions in the IGR group were significantly increased, while they were significantly decreased in the IGR+TZT group. Correlation analysis showed that tumor necrosis factor-α, interleukin-6, T helper cells (Th1, Th2, Treg), and insulin had a greater impact on GM community structure. CONCLUSIONS: TZT improved glucose tolerance and ameliorated GM dysbiosis in IGR rats. Additionally, TZT significantly modulated CD4+ T cell subset proportions in rat mesenteric lymph nodes and fecal metabolism. Moreover, correlation analysis showed that key microbiota was closely related to IGR indices. Thus, TZT modulated GM composition and immune functions of the intestinal mucosa. We provide useful information for the investigation of active mechanisms and the clinical application of TZT.

The effects of selenium supplementation on glycemic control, serum lipoproteins and biomarkers of oxidative stress in infertile women diagnosed with polycystic ovary syndrome undergoing in vitro fertilization: A randomized, double-blind, placebo-controlled trial.

OBJECTIVES: This study aimed to evaluate the effects of selenium consumption on metabolic profile among infertile females diagnosed with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: The current randomized, double-blind, placebo-controlled trial was conducted among 40 infertile females with PCOS aged between 18 and 40 years. Patients were randomly allocated to two groups of intervention to receive selenium supplements (200 µg/day) or placebo (starch). Fasting blood samples were taken at baseline and after 8 weeks of intervention. RESULTS: Selenium administration significantly decreased fasting glucose (P = 0.03), homeostasis model assessment for insulin resistance (P = 0.007) and fasting insulin levels (P = 0.006), and elevated quantitative insulin sensitivity check index (P < 0.001). In addition, selenium supplementation significantly reduced malondialdehyde (MDA) levels (P = 0.006). We did not observe any significant effect of selenium supplementation on pregnancy rate, lipid profiles, total antioxidant capacity (TAC) and total glutathione (GSH) levels. CONCLUSIONS: Overall, our study demonstrated that selenium supplementation for 8 weeks in infertile women with polycystic ovary syndrome undergoing IVF had beneficial effects on glycemic control and MDA levels, but did not affect pregnancy rate, lipid profiles, TAC and GSH levels. CLINICAL TRIAL REGISTRATION NUMBER: This trial was registered at www.irct.ir as http://www.irct.ir: IRCT201701025623N100.

Effects of a Novel Amino Acid Formula on Nutritional and Metabolic Status, Anemia and Myocardial Function in Thrice-Weekly Hemodialysis Patients: Results of a Six-Month Randomized Double-Blind Placebo-Controlled Pilot Study.

(1) Background: Chronic Kidney Disease (CKD) induces metabolic derangement of amino acid (AA) kinetics, eliciting severe damage to the protein anabolism. This damage is further intensified by a significant loss of AAs through hemodialysis (HD), affecting all tissues with a high metabolic turnover, such as the myocardium and body muscle mass. (2) Aim: to illustrate the effects of a novel AA mixture in boosting mitochondrial energy production. (3) Methods: A strict selection of 164 dialysis patients was carried out, allowing us to finally identify 22 compliant patients who had not used any form of supplements over the previous year. The study design envisaged a 6-month randomized, double-blind trial for the comparison of two groups of hemodialysis patients: eleven patients (67.2 ± 9.5 years) received the novel AA mix (TRG), whilst the other eleven (68.2 ± 10.5 years) were given a placebo mix that was indistinguishable from the treatment mix (PLG). (4) Results: Despite the 6-month observation period, the following were observed: maintenance of target hemoglobin values with a reduced need for erythropoiesis-stimulating agents in TRG > 36% compared to PLG (p < 0.02), improved phase angle (PhA) accompanied by an increase in muscle mass solely in the TRG group (p < 0.05), improved Left Ventricular Ejection Fraction (LVEF > 67%) in the TRG versus PLG group (p < 0.05) with early but marked signs of improved diastolic function. Increased sensitivity to insulin with greater control of glycemic levels in TRG versus PLG (p = 0.016). (5) Conclusions: the new AA mix seemed to be effective, showing a positive result on nutritional metabolism and cardiac performance, stable hemoglobin levels with the need for lower doses of erythropoietin (EPO), insulin increased cell sensitivity, better muscle metabolism with less loss of mass.

Effect of sodium alginate supplementation on weight management and reproductive hormones in polycystic females.

Dietary fiber is getting attention these days due to its tendency to improve the reproductive performance in human beings. Sodium alginate (SA) is one of the natural dietary fibers. The present study aimed to evaluate the effect of SA on serum insulin, blood sugar, lipid profile, estrogen and testosterone in polycystic (PCOS) females. A single in vivo trial was conducted on thirty adult PCOS females (25 ± 5 years old) with a body mass index (BMI) of 27.5 ± 3.5 kg m-2. Blood samples of all PCOS females were drawn for the initial biochemical analysis and considered as the negative control (NC). A complete randomized design was used to divide the NC group into three equal subgroups (n = 9) i.e. SA3: with 0.03 g; SA6: with 0.06 g per kg body weight per day of sodium alginate; the positive control (PC): metformin 500 mg day-1 for 60 days (two months). A significant reduction (p < 0.05) in the body weight, BMI, blood sugar, serum insulin, lipids and testosterone was observed, while a significant incremental effect (p < 0.05) was observed in the high-density lipoprotein level. The percentages of some physical parameters were also improved like obesity, menstrual cycle, physical activity, psychological issues and hirsutism. Therefore, the study concluded that SA exhibited therapeutic potential for weight management and the improvement of serum testosterone in PCOS females.

Natural 8-C-ascorbyl-(-)-epigallocatechin as antidiabetic agent: α-glucosidase and PTP-1B signaling pathway dual regulators.

α-Glucosidase and protein tyrosine phosphatase 1B (PTP1B) signaling pathway dual regulators decrease postprandial blood glucose levels and improve insulin sensitivity, making it a new treatment strategy for type 2 diabetes. This study examined in vitro antidiabetic activities of 8-C-ascorbyl-(-)-epigallocatechin (AE), found in oolong tea. AE inhibited α-glucosidase (IC50 = 142.8 µM) with activity higher than that of acarbose (IC50 = 250.2 µM). AE significantly promoted glucose-consumption and activated the insulin signaling pathway through enhancing the protein levels of p-GSK3ß and p-Akt and inhibiting the expression of PTP1B, along with slightly inhibitory activity against PTP1B. Docking analysis showed AE inhibited α-glucosidase activity via binding to the catalytic site through hydrogen bonds and Pi-Pi interactions, as well as a good shape match to the active pocket. In addition, AE could relieve oxidative damage and possessed good antioxidant capacity. Taken together, the results of this study indicate that AE exhibits antidiabetic activity in vitro, making it a potential functional food ingredient and drug candidate for management of type 2 diabetes.

Probiotics and synbiotics supplementation improve glycemic control parameters in subjects with prediabetes and type 2 diabetes mellitus: A GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials.

Probiotics and synbiotics have been proposed to exhibit an important role in glucose homeostasis and maintain the balance of the gut microbiota. However, clinical trials have shown mixed findings. Therefore, we conducted a systematic review and meta-analysis of all eligible randomized controlled trials (RCTs) examining the effects of probiotics and synbiotics intake on glycemic outcomes among individuals with prediabetes and type 2 diabetes mellitus (T2DM). The PubMed/Medline, Scopus, ISI Web of Science, and Cochrane library were searched up to March 2022 for published RCTs exploring the effectiveness of probiotics and synbiotics compared to control on glycemic outcomes. The random-effects model was applied in order to the estimation of 95 % confidence interval (CI) and the weighted mean difference (WMD) for each endpoint. Meta-analysis of forty-six RCTs (3067 participants) showed that probiotics and synbiotics supplementation significantly reduced fasting plasma glucose (FPG) (weighted mean difference (WMD): - 11.18 mg/dl, 95 % CI: - 13.60, - 8.75, p ˂0.001), fasting insulin serum level (WMD: -1.23 µIU/ml, 95 % CI: -1.76, -0.71, p ˂0.001), hemoglobin A1c (HbA1c) (WMD: -0.35 %, 95 % CI: -0.44, -0.26, p˂0.001), and homeostatic model assessment of insulin resistance (HOMA-IR) (WMD: -0.87, 95 % CI: -1.09, -0.65, p˂0.001). Additionally, probiotics and synbiotics intake resulted in an increase in values of quantitative insulin-sensitivity check index (QUICKI) (WMD: 0.01, 95 % CI: 0.00, 0.01, p˂0.001). However, probiotics and synbiotics consumption did not change glucose values following oral glucose tolerance test (OGTT). Our findings suggest that probiotic and synbiotic intake has favorable effects on glycemic profile in patients with prediabetes and T2DM.

Therapeutic Role of Curcumin in Diabetes: An Analysis Based on Bioinformatic Findings.

BACKGROUND: Diabetes is an increasingly prevalent global disease caused by the impairment in insulin production or insulin function. Diabetes in the long term causes both microvascular and macrovascular complications that may result in retinopathy, nephropathy, neuropathy, peripheral arterial disease, atherosclerotic cardiovascular disease, and cerebrovascular disease. Considerable effort has been expended looking at the numerous genes and pathways to explain the mechanisms leading to diabetes-related complications. Curcumin is a traditional medicine with several properties such as being antioxidant, anti-inflammatory, anti-cancer, and anti-microbial, which may have utility for treating diabetes complications. This study, based on the system biology approach, aimed to investigate the effect of curcumin on critical genes and pathways related to diabetes. METHODS: We first searched interactions of curcumin in three different databases, including STITCH, TTD, and DGIdb. Subsequently, we investigated the critical curated protein targets for diabetes on the OMIM and DisGeNET databases. To find important clustering groups (MCODE) and critical hub genes in the network of diseases, we created a PPI network for all proteins obtained for diabetes with the aid of a string database and Cytoscape software. Next, we investigated the possible interactions of curcumin on diabetes-related genes using Venn diagrams. Furthermore, the impact of curcumin on the top scores of modular clusters was analysed. Finally, we conducted biological process and pathway enrichment analysis using Gene Ontology (GO) and KEGG based on the enrichR web server. RESULTS: We acquired 417 genes associated with diabetes, and their constructed PPI network contained 298 nodes and 1651 edges. Next, the analysis of centralities in the PPI network indicated 15 genes with the highest centralities. Additionally, MCODE analysis identified three modular clusters, which highest score cluster (MCODE 1) comprises 19 nodes and 92 edges with 10.22 scores. Screening curcumin interactions in the databases identified 158 protein targets. A Venn diagram of genes related to diabetes and the protein targets of curcumin showed 35 shared proteins, which observed that curcumin could strongly interact with ten of the hub genes. Moreover, we demonstrated that curcumin has the highest interaction with MCODE1 among all MCODs. Several significant biological pathways in KEGG enrichment associated with 35 shared included the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, PI3K-Akt signaling pathway, TNF signaling, and JAK-STAT signaling pathway. The biological processes of GO analysis were involved with the cellular response to cytokine stimulus, the cytokine-mediated signaling pathway, positive regulation of intracellular signal transduction and cytokine production in the inflammatory response. CONCLUSION: Curcumin targeted several important genes involved in diabetes, supporting the previous research suggesting that it may have utility as a therapeutic agent in diabetes.