Elevated Blood Glucose Levels Research Articles

Bioassay guided isolation and compounds identification of the anti-diabetic fractions of (rosemary) Rosmarinus officinalis leaves extract

BackgroundDiabetes mellitus is a metabolic disease characterized by prolonged elevated blood glucose levels. It is a common health problem with a high mortality and morbidity to the human race. A number of medicinal plants such as rosemary (Rosmarinus officinalis) have been used for the treatment of diabetes. Most of the anti-diabetic conventional drugs have been found to have some side effects and there is therefore need to explore new sources of anti-diabetic drugs. The aim of the current study was to investigate the possibility of getting anti-diabetic compounds from R. officinalis that can be used as leads for drug discovery.MethodologyR. officinalis leaves were macerated in 50% methanol in dichloromethane and the crude extract fractionated by column chromatography. The obtained fractions were subjected to an in-vitro alpha-amylase inhibition assay. The anti-hyperglycemic potential of the fractions was evaluated in diabetic induced Wistar rats. The most potent fractions were analyzed by gas chromatography-mass spectrophotometry (GC-MS) for identification of the compounds.ResultsA total of 21 chromatographic fractions were assembled with different alpha- amylase inhibition activity. Eleven of the fractions had more than 30% alpha-amylase inhibition activity. The ethyl acetate fraction had the highest inhibition potential (LC50 of 2.8 μg/mL). The anti-diabetic assay in rats showed that fractions (F1) and (F4) had highest blood glucose reduction of 44.5 ± 0.4 and 52.8 ± 1.3%, respectively (p < 0.05). GC-MS analysis of fractions F1 and F4 showed the presence of 21 and 23 compounds in F1 and 23, respectively.ConclusionThis study has demonstrated that R. officinalis crude extract fractions obtained from 50% methanol in dichloromethane possesses alpha-amylase inhibitory and anti-hyperglycemic activities as well as secondary metabolites with varying chemical structures. The hexane and hexane/ethyl acetate (8/2) fractions showed most potent alpha-amylase inhibition with high anti-hyperglycemic activity giving hope of a possibility of obtaining lead compounds for new anti-diabetic drugs.

Exposure to environmental doses of DEHP causes phenotypes of polycystic ovary syndrome

Globally, approximately 6–20 % of women who are of reproductive age suffer from polycystic ovary syndrome (PCOS), with environmental factors believed to be significant contributors. Di-2-ethylhexyl phthalate (DEHP) is known to be an endocrine disruptor, and is also suspected of being associated with the occurrence of PCOS, but in vivo studies to verify this association are lacking. In this study, female SD rats were exposed to DEHP at levels of 0.1, 1.0, and 10 mg/kg/d, which are comparable to daily human exposure, to explore its potential role in the development of PCOS. The findings indicated that DEHP exposure reduced ovarian and uterine coefficients, decreased accumulation of primordial follicles, increased the prevalence of atretic and cystic follicles and fibrosis in ovarian tissues, altered serum hormone levels, elevated blood glucose levels and insulin resistance, disrupted the endocrine system and resulted in significant oxidative damage in the ovarian tissues. These results imply that DEHP exposure may cause lesions resembling PCOS to develop. By analyzing the differential expression of the proteome, and using GO and KEGG enrichment analyses, we found they were mainly enriched in the metabolic pathway and in the PPAR signaling pathway. We confirmed that activation of the PPARγ signaling pathway caused by DEHP exposure, is related to the emergence of PCOS-like lesions. This research provides direct in vivo experimental evidence for the association between DEHP exposure and PCOS.

Skin disorders in patients with type 2 diabetes mellitus in Khartoum Dermatology and Venereology Teaching Hospital

Background: Diabetes is a chronic, metabolic disease characterized by elevated levels of blood glucose, which leads over time to serious damage to the heart, blood vessels, eyes, kidneys and nerves. The most common is type 2 diabetes, usually in adults, which occurs when the body becomes resistant to insulin or doesn't make enough insulin. About 1 in 11 adults worldwide now have diabetes mellitus (DM), 90% of whom have type 2 DM (T2DM). One of the most common manifestations of diabetes are skin complications, such as dryness of the skin, bacterial and fungal infections. Objectives were to study the frequency and pattern of skin disorders in patients with T2DM at Khartoum dermatology and venereology teaching hospital (KDVTH) in Khartoum, Sudan during August 2016 to December 2016. Methods: This was prospective, observation descriptive, cross-sectional hospital-based study used a quantities method. A total convenient sample technique enrolled 100 points during the study period. Results: One hundred diabetic patients (64% male and 36% female) were included in the study. The age group varies between (25 and &gt;70 years), the commonest cutaneous manifestations were xerosis which was found in 45 patients (45%), fungal infection found in 36 patients (36%). Serum HbA1c level was done for each case. Conclusions: The study concluded that the most prevalent cutaneous diseases among patients were xerosis fungal infection, eczema, bacterial infections, and scabies respectively. A significant relationship between duration of DM and level of HB A1C and the presence of cutaneous manifestations was observed.

Intradermal Injection of a Thermoresponsive Polymeric Dexamethasone Prodrug (ProGel-Dex) Ameliorate Dermatitis in an Imiquimod (IMQ)-Induced Psoriasis-like Mouse Model.

Psoriasis is a chronic immune-mediated inflammatory skin disease, affecting ∼ 3% of the US population. Although multiple new systemic therapies have been introduced for the treatment of psoriatic skin disease, topical and intralesional glucocorticoids (GCs) continue to be used as effective psoriasis therapies. Their clinical utility, however, has been hampered by significant adverse effects, including skin atrophy and pigmentation as well as elevated blood glucose levels and hypertension. To mitigate these limitations, we have developed a N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based thermoresponsive dexamethasone (Dex) prodrug (ProGel-Dex) and assessed its therapeutic efficacy and safety in an imiquimod (IMQ)-induced psoriasis-like (PL) mouse model. ProGel-Dex was intradermally administered once at three dosing levels: 0.5, 1.0, and 2.0 mg/kg/day Dex equivalent at the beginning of the study. PL mice were also treated with daily topical saline or Dex, which were used as control groups. Treatment of PL mice with ProGel-Dex dosed at 0.5 mg/kg/day resulted in a significant reduction in scaling and erythema. Improvement in gross pathology scores, skin histological scores, and serum cytokine levels was also observed. Interestingly, for mice treated with ProGel-Dex at 1.0 and 2.0 mg/kg/day Dex equivalent, only improvement in skin erythema was observed. GC-associated side effects, such as elevation of serum alanine aminotransferase (ALT) and amylase levels and body weight loss, were not observed in mice treated with ProGel-Dex at 0.5 and 1.0 mg/kg/day Dex equivalent. Collectively, these results demonstrate the efficacy and improved safety of ProGel-Dex in treating psoriatic skin lesions when compared to topical Dex treatment, supporting its translational potential for clinical management of lesional skin psoriasis.

Effect of Zinc Supplementation on Glycemic Control in Newly Diagnosed Patients With Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) is a spectrum of metabolic disorders primarily characterized by elevated blood glucose levels. Type 2 DM (T2DM), the most common form, often requires adjunctive therapies to improve glycemic control and mitigate associated risks. Zinc has been implicated in glucose metabolism and insulin function, prompting this study to evaluate the impact of zinc supplementation on glycemic control in newly diagnosed T2DM patients. A randomized, placebo-controlled trial was conducted involving 80 newly diagnosed T2DM patients. Participants were randomly assigned to receive either zinc supplementation (50 mg/day) or a placebo, in conjunction with standard oral hypoglycemic medication, metformin. Key indicators, including fasting blood glucose (FBG), postprandial blood glucose (PPBG), hemoglobin A1c (HbA1c), and lipid profiles, were measured at baseline and after the 12-month intervention period. The group receiving zinc supplementation demonstrated significant reductions in FBG, PPBG, and HbA1c levels compared to the placebo group. The mean FBG in the intervention group decreased by 21.52 mg/dL, PPBG decreased by 47.53 mg/dL, and HbA1c decreased by 0.79%. Additionally, zinc supplementation led to notable decreases in low-density lipoprotein (LDL) cholesterol by 25.06 mg/dL, triglycerides by 22.2 mg/dL, and total cholesterol levels by 26.67 mg/dL. However, no significant changes were observed in high-density lipoprotein (HDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, or erythrocyte sedimentation rate (ESR). The findings suggest that zinc supplementation may be a beneficial adjunctive therapy in the early management of T2DM, contributing to improved glycemic control and favorable changes in lipid profiles. However, its effect on HDL, VLDL, and ESR was insignificant, indicating the need for further research to better understand the broader implications of zinc in T2DM management.

Effects of dietary supplementation with Vitamin A, D3, E, and Garlic on heat detection, pregnancy rate, and serum profile in anestrus dairy cows

Anestrus poses substantial challenges for dairy industries worldwide. This research aims to evaluate the effect of oral supplementation with garlic alone, vitamins A, D3, E alone, and their combination on heat detection, pregnancy rate and serum profile in anestrus dairy cows. Using a completely randomized design, this study, conducted over 327 days, evaluated 72 anestrus-affected cows, which were divided into four groups. T0 (Control) received only normal saline; T1 with vitamin A,D3,E; T2 with Garlic and T3 integrated with A, D3, E + Garlic in drinking water. Results demonstrated that the treatment groups exhibited significantly higher estrus signs (p<0.05) compared to the control. The pregnancy rate was also increased (P=0.059), especially in the T3 group which had the highest heat detection (55.55%), conception (70%), and pregnancy (38.88%). In comparison, the heat detection rate for T1 was 44.44%, while the conception rate for T2 was 66.66%. Additionally, T0 exhibited the least proportion across all parameters. Additionally, the elevated BUN (Blood Urea Nitrogen) and blood glucose levels observed in non-responsive (those not showing signs of heat) cows at 32.51 and 43.65 mg/dl respectively, compared to responsive cows (those showing signs of heat) with levels of 22.40 and 51.34 mg/dl. These findings suggest a potential association between these blood parameters and the cyclicity of dairy cows. These findings highlight that oral supplementation with vitamin AD3E+Garlic significantly improves the heat detection rate and pregnancy rate than only administering vitamin AD3E or Garlic with anestrus in dairy cattle.

A Study to Evaluate the Effect of Alpha-Lipoic Acid on Neuropathic Symptoms in Diabetic Neuropathy Patients on Gabapentin or Pregabalin.

Introduction Chronic hyperglycemia is a key factor in the development of diabetic peripheral neuropathy (DPN), contributing significantly to the progression of this condition through the induction of oxidative stress. Elevated blood glucose levels lead to increased production of reactive oxygen species (ROS), which cause damage to neuronal cells and exacerbate neuropathic symptoms. Alpha-lipoic acid (ALA) is a potent antioxidant that neutralizes ROS and reduces oxidative damage. By addressing the mechanisms of neuropathy, ALA mitigates the effects of chronic hyperglycemia through antioxidant regeneration, inflammation reduction, and endothelial function improvement. As a result, ALA is emerging as a promising intervention for managing oxidative stress and inflammation in DPN. Methods Prospective, double-blind, placebo-controlled study, a total of 52 DPN subjects on gabapentin or pregabalin were randomly assigned to either ALA 600 mg oral once daily or placebo oral once daily for 12 weeks. Treatment outcome was assessed using vibration perception threshold (VPT), Neuropathy Total Symptom Score 6 (NTSS-6), quality of life (QOL) assessed by 12-Item Short Form Health Survey (SF-12) Questionnaire, oxidative stress biomarkers (malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH)) and inflammatory biomarker (high-sensitivity C-reactive protein (hs-CRP)) at baseline and every visit (four, eight, and 12 weeks). Neuron-specific enolase (NSE) levels were done at baseline and 12 weeks. Glycated hemoglobin (HbA1C) and safety parameters were done at screening and 12 weeks. Compliance with the study medication was assessed by pill count. Reported adverse drug reactions were recorded. Results A total of 52 subjects (males = 22; females = 30) with a mean age of 55.63 ± 7.5 years were randomized to receive either ALA or placebo. A significant reduction in VPT was observed with ALA at 12 weeks compared to baseline (from 26.92 ± 3.58 to 22.14 ± 1.94; p < 0.0001). Secondary parameters like NTSS-6, QOL by SF-12 questionnaire, NSE levels, oxidative biomarkers levels, and inflammatory biomarkers showed significant improvement with ALA compared to placebo. No serious adverse events were reported. Conclusion ALA demonstrated a protective effect against DPN by its antioxidant and anti-inflammatory effects and was found to have good safety.

Sodium Butyrate, a Gut Microbiota Derived Metabolite, in Type 2 Diabetes Mellitus and Cardiovascular Disease: A Review.

Type 2 diabetes is characterized by elevated blood glucose levels, leading to an increased risk of cardiovascular diseases. Sodium butyrate, the sodium salt of the short-chain fatty acid butyric acid produced by gut microbiota fermentation, has shown promising effects on metabolic diseases, including type 2 diabetes and cardiovascular diseases. Sodium butyrate demonstrates anti-inflammatory, anti-oxidative, and lipid-lowering properties and can improve insulin sensitivity and reduce hepatic steatosis. In this review, we investigate how sodium butyrate influences cardiovascular complications of type 2 diabetes, including atherosclerosis (AS), heart failure (HF), hypertension, and angiogenesis. Moreover, we explore the pathophysiology of cardiovascular disease in type 2 diabetes, focusing on hyperglycemia, oxidative stress, inflammation, and genetic factors playing crucial roles. The review suggests that sodium butyrate can be a potential preventive and therapeutic agent for cardiovascular complications in individuals with type 2 diabetes.

Hashimoto's Thyroiditis in Diabetic Patients: A Prospective Study in Nasiriyah City

There is a connection between having Hashimoto's thyroiditis, an autoimmune disease marked by thyroid gland attacks, and an increased risk of type 2 diabetes mellitus, a metabolic disease marked by elevated blood glucose levels. The purpose of this research was to find out how common type 2 diabetes was in Nasiriyah City, Iraq, among individuals suffering from Hashimoto's thyroiditis. Methods: A study using a retrospective cohort was conducted involving thyroiditis caused by Hashimoto's in 100 patients diagnosed between January 2023 and January 2024 at Al Hussein Teaching Hospital. Patients' medical records were reviewed to extract data on demographics, clinical characteristics, and laboratory results, including HbA1c and fasting blood glucose levels. Confirmation of Based on ELISA data indicating positive anti-thyroid peroxidase antibody levels, Hashimoto's thyroiditis was diagnosed. Results: The prevalence of T2DM among the number of Hashimoto's thyroiditis patients was noticeably greater (45%) compared to the general population prevalence of 15%. the number of Hashimoto's thyroiditis patients was noticeably greater HbA1c and FBG levels compared to those without Hashimoto's thyroiditis. Specifically, an investigation of logistic regression revealed that Hashimoto’s thyroiditis was significantly associated with type 2 diabetes individually when OR = 4. 2, 95% CI 2. 1-8. 5). In conclusion, the result of the present investigation, it is clear that, Hashimoto’s thyroiditis has a positive relationship with T2DM in Nasiriyah city of Iraq. Hence, early identification and intervention of T2DM in patients with Hashimoto’s thyroiditis should be a routine practice to avoid complications associated with the two diseases.

Value of Glycemic Indices for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Retrospective Single-Center Study.

Delayed cerebral ischemia (DCI) is a severe complication following aneurysmal subarachnoid hemorrhage (aSAH), linked to poor functional outcomes and prolonged intensive care unit (ICU) stays. Timely DCI diagnosis is crucial but remains challenging. Dysregulated blood glucose, commonly observed after aSAH, may impair the constant glucose supply that is vital for brain function, potentially contributing to DCI. This study aimed to assess whether glucose indices could help identify at-risk patients and improve DCI detection. This retrospective, single-center observational study examined 151 aSAH patients between 2016 and 2019. Additionally, 70 of these (46.4%) developed DCI and 81 did not (no-DCI). To determine the value of glycemic indices for DCI, they were analyzed separately in patients in the period before (pre-DCI) and after DCI (post-DCI). The time-weighted average glucose (TWAG, p = 0.024), mean blood glucose (p = 0.033), and novel time-unified dysglycemic rate (TUDR140, calculated as the ratio of dysglycemic to total periods within a glucose target range of 70-140 mg/dL, p = 0.042), showed significantly higher values in the pre-DCI period of the DCI group than in the no-DCI group. In the time-series analysis, significant increases in TWAG and TUDR140 were observed at the DCI onset. In conclusion, DCI patients showed elevated blood glucose levels before and a further increase at the DCI onset. Prospective studies are needed to confirm these findings, as this retrospective, single-center study cannot completely exclude confounders and limitations. In the future blood glucose indices might become valuable parameters in multiparametric models to identify patients at risk and detect DCI onset earlier.

Risk factors for non-communicable diseases in Afghanistan: insights of the nationwide population-based survey in 2018

BackgroundNoncommunicable diseases (NCDs) account for a substantial number of deaths in Afghanistan. Understanding the prevalence and correlates of major NCD risk factors could provide a benchmark for future public health policies and programs to prevent and control NCDs. Therefore, this study aimed to examine the prevalence and correlates of NCD risk factors among adults aged 18–69 years in Afghanistan.MethodsWe used data from the Afghanistan STEPS Survey 2018. The study population were 3650 (1896 males and 1754 females) adults aged 18–69 years sampled from all 34 provinces through a multistage cluster sampling process. Information on behavioural and biological risk factors was collected. We used STATA (version 18.0) for data analysis.ResultsOf the total participants, 42.8% were overweight or obese, 8.6% were current smokers, 26.9% had insufficient physical activities, 82.6% had low consumption of fruits and vegetables, and only 0.5% had ever consumed alcohol. Approximately 15% of participants had a high salt intake, while 25% and 8% had elevated blood pressure and blood glucose levels, respectively. Similarly, around 18% had elevated total cholesterol. The study revealed a lower prevalence of current smoking among females [AOR = 0.17, 95%CI (0.09–0.30)] compared with males, but a higher prevalence in those who had higher education levels [1.95 (1.13–3.36)] compared with those with no formal education. Insufficient physical activity was higher in participants aged 45–69 years [1.96 (1.39–2.76)], females [4.21 (1.98–8.84)], and urban residents [2.38 (1.46–3.88)] but lower in those with higher education levels [0.60 (0.37–0.95)]. Participants in the 25th to 75th wealth percentiles had higher odds of low fruit and vegetable consumption [2.11 (1.39–3.21)], while those in the > 75th wealth percentile had lower odds of high salt intake [0.63 (0.41–0.98)]. Being overweight/obese was more prevalent in participants aged 45–69 years [1.47 (1.03–2.11)], females [1.42 (0.99–2.01)], currently married [3.56 (2.42–5.21)] or ever married [5.28 (2.76–10.11)], and urban residents [1.39 (1.04–1.86)]. Similarly, high waist circumference was more prevalent in participants aged 45–69 years [1.86 (1.21–2.86)], females [5.91 (4.36–8.00)], those being currently married [4.82 (3.12–7.46)], and those being in 25th to 75th wealth percentile [1.76 (1.27–2.43)]. A high prevalence of elevated blood pressure was observed in participants aged 45–69 years [3.60 (2.44–5.31)] and currently married [2.31 (1.24–4.31)] or ever married [6.13 (2.71–13.8)] participants. Elevated blood glucose was more prevalent in older adults ([1.92 (1.09–3.39)] for 45–69 and [3.45 (2.44–5.31)] for 30–44 years), urban residents [2.01 (1.33–3.03)], and ever-married participants [4.89 (1.48–16.2)]. A higher prevalence of elevated cholesterol was observed in females [2.68 (1.49–4.82)] and those currently married [2.57 (1.17–5.63)] or ever married [4.24 (1.31–13.73)].ConclusionThis study used up-to-date available data from a nationally representative sample and identified the prevalence of NCDs and associated risk factors in Afghanistan. Our findings have the potential to inform and influence health policies by identifying people at high risk of developing NCDs and can assist policymakers, health managers, and clinicians to design and implement targeted health interventions.

Investigation of Anti-Diabetic Properties of Ceylon Cinnamon Bark Extracts by In-Vitro α-Amylase and α-Glucosidase Inhibition, Molecular Modeling, and Postprandial Blood Glucose Regulation for Potential Nutraceuticals

Background: Diabetes Mellitus (DM) can appear due to the absence of insulin (DM1- type 1) or poor response of cells to insulin (DM2-type 2). Even though DM1 cannot be controlled using general treatments, DM2 can be easily controlled or prevented using pharmaceuticals, nutraceuticals, or dietary practices. Ceylon cinnamon (Cinnamomum zeylanicum) is one such natural remedy that has been consumed against elevated blood glucose levels in the past. Cinnamon and different types of cinnamon extracts have been scientifically tested for their activities on the inhibition of α-amylase and α-glucosidase enzymes that are responsible for carbohydrate metabolism and are effective in blood glucose regulation. However, the combined effect of aqueous and ethanol extracts of cinnamon bark on blood glucose regulation is still lacking. In this study, Water Extract of Cinnamon (CWE), Ethanol Extracts of Cinnamon (hot ethanol extract of cinnamon-CHEE, cold ethanol extract of cinnamon-CEE, and 50% ethanol extract of cinnamon- CEE-50) were studied for their sugar-controlling properties. Objectives: This study was performed to identify the efficacy of different cinnamon extracts on the inhibition of α-amylase and α-glucosidase enzymes, followed by animal studies to confirm the use of the extracts in nutraceutical formulations. Methods: Water and ethanol-based extraction method was used to prepare cinnamon extracts. These extracts have been scientifically tested for their activities on the inhibition of α-amylase and α-glucosidase enzymes. Molecular docking studies were used to identify the binding of the active molecules to the substrate binding sites of α-amylase and α-glucosidase. In-vivo time dependence postprandial blood glucose regulation studies have been performed with healthy Wistar male rats. Results: Yields of the CHEE, CEE, and CWE were 14±2%, 12±2%, and 8±1% respectively. According to the LCMS data, the major component in the CEE was cinnamaldehyde. Both CWE and CEE were subjected to the Total Polyphenol assay (TPC) and Total Flavonoids (TFC) assays. The TPC of CWE and CEE were 117±1 mg (Gal)/g and 170±10 mg (Gal)/g, while the TFC of CWE and CEE were 359±1 mg (Qc)/g and 254±4 mg (Qc)/g, respectively. In the α-amylase inhibition assay, Acarbose; a known α-amylase inhibitor, and CEE showed IC50 values of 65.4 ppm and 2.6 ppm, while CWE failed to show inhibition against α-amylase. In the α-glucosidase inhibition assay, Acarbose; a known α-amylase inhibitor, CEE, and CWE showed IC50 values of 312 ppm, 4.5 ppm, and 1.3 ppm, respectively. In-vivo time dependence postprandial blood glucose regulation studies that have been performed with healthy Wistar male rats showed a lowering of blood glucose concentrations by 22%, 11%, and 10% of glucose at 30 min, 60 min, and 90 min compared to the control group. Conclusion: The CEE contains polyphenols and flavonoids and is effective in inhibiting both α- amylase and α-glucosidase. The CWE also contains polyphenols and a comparatively higher level of flavonoids and is effective in inhibiting α-glucosidase while not affecting α-amylase inhibition. Overall, the IC50 data, TPC data, and TFC data proposed that the inhibition of carbohydrate hydrolyzing enzymes by polyphenols may depend on the polarity of particular polyphenols. Based on the rat trials, it can be concluded that the 1:1 combination of CWE and CEE may be useful in formulating postprandial blood glucose level-regulating nutraceuticals.

SFRP4 contributes to insulin resistance-induced polycystic ovary syndrome by triggering ovarian granulosa cell hyperandrogenism and apoptosis through the nuclear β-catenin/IL-6 signaling axis

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic ovulation dysfunction and overproduction of androgens. Women with PCOS are commonly accompanied by insulin resistance (IR), which can impair insulin sensitivity and elevate blood glucose levels. IR promotes ovarian cysts, ovulatory dysfunction, and menstrual irregularities in women patients, leading to the pathogenesis of PCOS. Secreted frizzled-related protein 4 (SFRP4), a secreted glycoprotein, exhibits significantly elevated expression levels in obese individuals with IR and PCOS. Whereas, whether it plays a role in regulating IR-induced PCOS still has yet to be understood. In this study, we respectively established in vitro IR-induced hyperandrogenism in human ovarian granular cells and in vivo IR-induced PCOS models in mice to investigate the action mechanisms of SFRP4 in modulating IR-induced PCOS. Here, we revealed that SFRP4 expression levels in both mRNA and protein were remarkably upregulated in the IR-induced hyperandrogenism with elevated testosterone in the human ovarian granulosa cell line KGN. Under normal conditions without hyperandrogenism, overexpressing SFRP4 triggered the remarkable elevation of testosterone along with the increased nuclear translocation of β-catenin, cell apoptosis and proinflammatory cytokine IL-6. Furthermore, we found that phytopharmaceutical disruption of SFRP4 by genistein ameliorated IR-induced increase in testosterone in ovarian granular cells, and IR-induced PCOS in high-fat diet obese mice. Our study reveals that SFRP4 contributes to IR-induced PCOS by triggering ovarian granulosa cell hyperandrogenism and apoptosis through the nuclear β-catenin/IL-6 signaling axis. Elucidating the role of SFRP4 in PCOS may provide a novel therapeutic strategy for IR-related PCOS therapy.

High fat diet consumption and social instability stress impair stress adaptation and maternal care in C57Bl/6 dams

Poor maternal diet and psychosocial stress represent two environmental factors that can significantly impact maternal health during pregnancy. While various mouse models have been developed to study the relationship between maternal and offspring health and behaviour, few incorporate multiple sources of stress that mirror the complexity of human experiences. Maternal high-fat diet (HF) models in rodents are well-established, whereas use of psychosocial stress interventions in female mice are still emerging. The social instability stress (SIS) paradigm, serves as a chronic and unpredictable form of social stress. To evaluate the combined effects of a poor maternal diet and intermittent social stress on maternal health and behaviour, we developed a novel maternal stress model using adult female C57Bl/6 mice. We observed that all HF+ mice demonstrated rapid weight gain, elevated fasting blood glucose levels and impaired glucose tolerance independent of the presence (+) or absence (-) of SIS. Behavioural testing output revealed anxiety-like behaviours remained similar across all groups prior to pregnancy. However, integrated anxiety z-scores revealed a mixed anxious profile amongst HF+/SIS+ females prior to pregnancy. HF+/SIS+ females also did not show reduced plasma ACTH and corticosterone levels that were observed in our other HF+ and HF- stress groups after SIS exposure. Further, HF+/SIS+ females demonstrated significant postpartum maternal neglect, resulting in fewer numbers of live offspring. These findings suggest that prolonged maternal HF diet consumption, coupled with previous exposure to SIS, places a significant burden on the maternal stress response system, resulting in reduced parental investment and negative postpartum behaviour towards offspring.

Association of Elevated Perioperative Blood Glucose With Complications and Postoperative Outcomes Following Traumatic Spine Surgery.

Perioperative blood glucose control has been demonstrated to influence outcomes following spine surgery, though this association has not been fully elucidated in patients with traumatic spine injuries. This study sought to determine the association between perioperative blood glucose levels and complications or outcomes in patients undergoing spine surgery due to injury. A retrospective review was conducted to identify patients who underwent spine surgery due to traumatic injuries between 1 March 2020 and 29 September 2022 at a single academic institution. Descriptive factors, complications, and outcomes were compared between those with a postoperative blood glucose level of <200 mg/dL and those with a preoperative glucose of <200 mg/dL. Patients with a post- and preoperative blood glucose of ≥200 mg/dL had significantly higher odds of respiratory complications (OR = 2.1, 2.1, P = 0.02, 0.03), skin/wound complications (OR = 2.2, 2.8, P = 0.04, 0.03), and increased hospital length of stay (OR = 9.6, 12.1, P = 0.02, 0.03) compared with those with blood glucose of <200 mg/dL. Those with postoperative glucose ≥200 mg/dL also had significantly higher odds of inpatient mortality (OR = 4.5, P = 0.04) when controlling for confounding factors. Neither pre- nor postoperative blood glucose of ≥200 mg/dL was associated with an improvement in American Spinal Injury Association Impairment Scale score at the final follow-up when controlling for multiple confounding factors (P = 0.44, 0.06). Elevated blood glucose both pre- and postoperatively was associated with an increased rate of postoperative complications and negative postoperative outcomes. However, there was no association between elevated blood glucose levels and neurological recovery following traumatic spinal injury.

Exploring stevioside binding affinity with various proteins and receptors actively involved in the signaling pathway and a future candidate for diabetic patients.

Introduction and Background: Diabetes is a chronic metabolic disease characterized by elevated blood glucose levels and is one of the main global health concerns. Synthetic sugar substrate has many side effects such as leukemia, bladder cancer, hepatotoxicity, breast cancer, headache, and brain toxicity. The WHO and FDA has recently banned some of the synthetic sugar alternatives due to their carcinogenic effects. Objective and Methodology: Therefore, the main objective of the current study was to investigate the safety and binding affinity of Stevioside with Glucose Transpoter-4 (GLUT-4), Akt, Insulin Receptor (IR) and Insulin Receptor Substrate-1 (IRS-1) to confirmed that Stevioside is one the potent natural sweetener/drug for diabetes. This study delves into the molecular interaction between Stevioside and key diabetic proteins: GLUT-4, Akt, IR and IRS-1. A precise molecular docking approach was used to simulate the binding affinity of Stevioside to these proteins. The pharmacokinetic properties of the molecule should be taken into consideration as important variables throughout the virtual screening process. Results: The result of active site analysis of GLUT-4, Akt, IR and IRS-1 showed a zone of 2158.359 Ǻ2, 579.259 Ǻ2, 762.651 Ǻ2, and 152.167 Ǻ2 and a volume of 2765.094 Ǻ³, 355.567 Ǻ³, 686.806 Ǻ³, and 116.874 Ǻ³, respectively. Docking analysis of the Stevioside compound showed the highest docking energy with scores of -9.9 with GLUT-4, -6.7 with Akt, -8.0 with IR and -8.8 with IRS-1. Studies indicated that it remains undigested by stomach acids and enzymes and is not absorbed in the upper small intestine. Further, tests revealed no hepatotoxicity, AMES toxicity, or skin sensitivity, making it a promising candidate for safe consumption as drug metabolism. Conclusion and Recommendations: Instead of other sugar alternatives, Stevioside will help diabetic patients with a lower chance of infections, lowered blood pressure/blood sugar, and increased glucose uptake in diabetic muscles. Stevioside is a natural sweetener, and the current study recommends its usage in various dietary products for diabetic patients.

Okra (Abelmoschus esculentus L. moench) fruit powder standardized in flavonoids improves glycemic control and metabolic memory in acute and chronic hyperglycemia

Type 2 diabetes mellitus (T2DM) is a chronic disease with high global prevalence characterized by persistent hyperglycemia. Elevated blood glucose levels are associated with constant oxidative stress and increased protein glycation, establishing a metabolic memory state. Therefore, the efficacy of the Okra (Abelmoschus esculentus L. moench) Fruit Powder Standardized in Flavonoids (OFP-SF) was evaluated in glucose homeostasis, oxidative stress, and metabolic memory, using zebrafish models of acute and chronic hyperglycemia. The OFP-SF was produced from dried fresh fruits and subsequently subjected to characterization regarding its antioxidant potential and chemical composition. Finally, the product was standardized to contain 1.6% flavonoids. In acute hyperglycemia, OFP-SF at doses of 125 μg and 250 μg demonstrated the ability to normalize blood glucose levels, reaching levels of 94.56 ± 5.9 mg/dL and 76.88 ± 8.9 mg/dL, respectively, when administered prior to glucose overload. The same doses were tested in a chronic hyperglycemia model, where after a seven-day treatment, animals receiving 125 and 250 μg of OFP-SF exhibited glycemic values of 73.45 ± 15.67 mg/dL and 33.96 ± 5.31 mg/dL, respectively, comparable to those observed in the Control group (49.48 ± 2.77 mg/dL). Furthermore, OFP-SF was able to mitigate metabolic memory by reducing oxidative stress and protein glycation in the brain, liver, and eye tissues of hyperglycemic zebrafish. These findings provide a basis for developing new products that utilize the phytochemical potential of A. esculentus fruits for the prevention and adjunctive treatment of T2DM.

Methylglyoxal induces death in human brain neuronal cells (SH-SY5Y), prevented by metformin and dapagliflozin

Diabetes mellitus is a metabolic disorder caused by a dysfunction in insulin action or secretion, leading to an elevation in blood glucose levels. It is a highly prevalent condition and as a result, the NHS spends 10 % of its entire budget on diabetes mellitus care, that is equivalent to £10 billion a year. Diabetes mellitus has been linked with vascular and neurological complications which may be associated with the progression of neurodegeneration and Alzheimer's disease. Chronic hyperglycaemia increases the production of the reactive oxidant species (ROS) such as methylglyoxal (MGO). MGO has been linked with vascular complications, neuropathy and cytotoxicity. The main aim of this study was to investigate the potential beneficial effect of antidiabetic agents such as metformin and dapagliflozin on human brain neuronal cells (SH-SY5Y) treated with MGO. SH-SY5Y cells were cultured in DMEM/F12 media and subjected overnight incubation with one of the following treatment conditions: Control (untreated); MGO (1 μM); MGO (100 μM); metformin (100 μM) + MGO (100 μM); and dapagliflozin (10 μM) + MGO (100 μM). Several assays were conducted to explore the effect of the treatment groups on the SH-SY5Y cells. These included: MTT assay; LDH assay, peroxynitrite fluorescence assay, and laser scanning confocal microscopy. MGO (100 μM) led to significant cell injury and damage and significantly reduced the survival of the cells by approximately 50–75 %, associated with significant increase in peroxynitrite. The addition of metformin (100 μM) or dapagliflozin (10 μM) represented significant protective effects on the cells and prevented the cell damage caused by the high MGO concentration. As a result, the findings of this research reveal that MGO-induced cell damage may partly be mediated by the generation of peroxynitrite, while the antidiabetic agents such as metformin and dapagliflozin prevent brain cell death, which potentially may play prophylactic roles against the risk of dementia in diabetic patients.

Protective effects of spermidine levels against cardiovascular risk factors: An exploration of causality based on a bi-directional Mendelian randomization analysis

The study investigated the causal relationships between spermidine levels and CVD risk factors using a bi-directional MR approach. Employing genetic variants from extensive GWAS datasets as IVs, the study aimed to determine whether spermidine levels can influence CVD risk factors such as blood pressure, blood glucose, and lipid profiles, and vice versa. The findings suggest a protective role of elevated spermidine levels against hypertension, elevated blood glucose, and lipid profiles (LDL-C and HDL-C). Specifically, increased spermidine levels were significantly associated with lower risk of hypertension (IVW beta = -0.0013453913, p = 0.01597648) and suppression risk of elevated blood glucose (IVW beta = -0.08061330, p = 0.02450205). Additionally, there was a notable association with lipid modulation, showing a decrease in LDL-C (IVW beta = -0.01849161, p = 0.01086728) and an increase in HDL-C (IVW beta = 0.0044608332, P = 0.01760051). Conversely, the influence of CVD risk factors on spermidine levels was minimal, with the exception that elevated blood glucose levels resulted in reduced spermidine levels. (IVW beta = -0.06714391, P = 0.01096123). These results underline the potential of spermidine as a modifiable dietary target for the prevention and management of cardiovascular diseases. Further investigations are warranted to explore the underlying biological mechanisms and the applicability of these findings in broader and diverse populations.

Impact of Lactobacillus acidophilus and Its Combination with Isoflavone Products on Calcium Status, Calcium Transporters, and Bone Metabolism Biomarkers in a Post-Menopausal Osteoporotic Rat Model.

Osteoporosis in menopausal women requires alternatives to current medications, considering their adverse effects. In this context, probiotics and isoflavone products are promising dietary interventions. The objective of our study was to examine the impacts of Lactobacillus acidophilus and its combination with daidzein and tempeh on calcium status, calcium transporters, and bone metabolism biomarkers in a post-menopausal osteoporotic rat model. A total of 48 female Wistar rats were exposed to a two-stage experiment involving calcium deficit induction and subsequent dietary interventions across six groups. Calcium levels, the gene expression of TRPV5 and TRPV6 calcium transporters, bone histopathology, serum bone metabolism markers, and blood biochemistry were evaluated. The results revealed that, while decreasing serum calcium levels, the groups that received the probiotic L. acidophilus and isoflavone combination exhibited increased bone metabolism biomarkers and decreased calcium transporter expressions, akin to the effects of bisphosphonate. Additionally, significant improvements in bone histopathology were observed in these groups. However, the group receiving probiotic L. acidophilus alone did not exhibit significant changes in bone resorption biomarkers, calcium transporter expression, or various blood parameters. Meanwhile, the combination of probiotic L. acidophilus with tempeh positively influenced hematological parameters and reduced cholesterol and triglyceride levels, but it led to elevated blood glucose levels. Correlation analyses highlighted associations between serum calcium levels, calcium transporter expression, and bone metabolism biomarkers. In conclusion, our findings suggest that the daily consumption of probiotic L. acidophilus in combination with isoflavone products may improve bone health in ovariectomized rats, warranting further research to elucidate potential interactions with other nutrients.