Significant Weight Reduction Research Articles

Effects of canagliflozin on cardiac remodeling and hemodynamic parameters in patients with type 2 diabetes mellitus

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors have demonstrated to reduce cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) in large trials independent of glycemic control. The mechanisms of this cardioprotective property remain uncertain. Evidence suggests positive hemodynamic changes and favorable cardiac remodeling contributing to the clinical outcomes but results were conflicting. We aim to investigate the potential impact on hemodynamic parameters, cardiac structure and functions. This prospective observational study included T2DM patients receiving canagliflozin 100 mg per day in addition to their antidiabetic treatment. We analyzed hemodynamic parameters assessed by echocardiographic measurements and impedance cardiography (ICG) to evaluate systolic and diastolic functions from baseline to 24 weeks after treatment. A total of 47 patients (25 males and 22 females) averaging 64.6 ± 10.9 years had a significant reduction in HbA1c, body weight, and systolic blood pressure. Hematocrit increased significantly, while NT-proBNP remained unchanged. E/e′, left atrium (LA) volume, and LA stiffness were reduced, while left ventricle (LV) global longitudinal strain (GLS) and LA strain rates increased at 24 weeks by conventional and speckle tracking echocardiography. LV mass and ejection fraction showed no differences. ICG suggested significant improvement in hemodynamic parameters with increased stroke volume index and cardiac output index and decreased systemic vascular resistance index at 12 and 24 weeks. Canagliflozin improved hemodynamic parameters and had a favorable impact on LA and LV reverse remodeling. These changes may explain the beneficial effect on cardiovascular outcomes in large clinical trials.

Neuroprotective Potential of Silymarin against Rotenone induced motor deficits in Wistar Rats

AbstractBackgroundParkinson’s disease is a hypokinetic disorder characterized by selective loss of dopaminergic in substantia nigra pars compacta (SNPc) region of mid‐brain. Dopaminergic degeneration of neurons is considered to be due to oxidative stress, neuroinflammation, neurons mitochondrial dysfunction and glutamate excitotoxicity etc. Silymarin was selected as an investigational drug, due to its numerous activities in current research, it possesses substantial antioxidant and neuroprotective functionalities and it has been reported to produce anti‐oxidant, anti‐inflammatory and neuromodulatory actions in previous studies.MethodIn the current study we have investigated the role of Silymarin against rotenone induced motor deficit and biochemical abnormalities in Wistar rats. Rats were treated with 1.5mg/kg rotenone subcutaneously for 35 days. Silymarin (50,100 and 200 mg/kg i.p.) was administered after 30 minutes of rotenone administration from day 7th to 35th day. Rotenone caused significant reduction in motor functions and body weight and produced elevation in striatal oxidative burden.ResultThe biochemical analysis revealed that there is reduction in the level of anti‐oxidants (GSH, Catalase, and SOD) in the animals following rotenone administration. Whereas Silymarin treated rats were stable and regained their body weight. In addition Silymarin significantly attenuated rotenone induced motor deficit and striatal oxidative stressConclusionOutcomes of the current study suggest neuroprotective potential of Silymarin and its ability to correct movement disability and thus could prove to be useful candidate molecule in the management of motor disorders.

In vitro and In vivo evidence demonstrating chronic absence of Ref-1 Cysteine 65 impacts Ref-1 folding configuration, redox signaling, proliferation and metastasis in pancreatic cancer

Ref-1/APE1 (Redox Effector/Apurinic Endonuclease 1) is a multifunctional enzyme that serves as a redox factor for several transcription factors (TFs), e.g., NF-kB, HIF-1α, which in an oxidized state fail to bind DNA. Conversion of these TFs to a reduced state serves to regulate various biological responses such as cell growth, inflammation, and cellular metabolism. The redox activity involves a thiol exchange reaction for which Cys65 (C65) serves as the nucleophile. Using CRISPR editing in human pancreatic ductal adenocarcinoma (PDAC) cells, we changed C65 to Ala (C65A) in Ref-1 to evaluate alteration of Ref-1 redox dynamics as well as chronic loss of Ref-1 redox activity on cell signaling pathways, specifically those regulated by NF-kB and HIF-1α. The redox activity of Ref-1 requires partial unfolding to expose C65, which is buried in the folded structure. Labeling of Ref-1 with polyethylene glycol-maleimide (PEGm) provides a readout of reduced Cys residues in Ref-1 and thereby an assessment of partial unfolding in Ref-1. In comparing Ref-1WT vs Ref-1C65A cell lines, we found an altered distribution of oxidized versus reduced states of Ref-1. Accordingly, activation of NF-kB and HIF-1α in Ref-1C65A lines was significantly lower compared to Ref-1WT lines. The bioinformatic data revealed significant downregulation of metabolic pathways including OXPHOS in Ref-1C65A expressing clones compared to Ref-1WT line. Ref-1C65A also demonstrated reduced cell proliferation and use of tricarboxylic acid (TCA) substrates compared to Ref-1WT lines. A subcutaneous as well as PDAC orthotopic in vivo model demonstrated a significant reduction in tumor size, weight, and growth in the Ref-1C65A lines compared to the Ref-1WT lines. Moreover, mice implanted with Ref-1C65A redox deficient cells demonstrate significantly reduced metastatic burden to liver and lung compared to mice implanted with Ref-1 redox proficient cells. These results from the current study provide direct evidence that the chronic absence of Cys65 in Ref-1 results in redox inactivity of the protein in human PDAC cells, and subsequent biological results confirm a critical involvement of Ref-1 redox signaling and tumorigenic phenotype.

Enabling Population Biology Studies of Stemphylium vesicarium from Onion with Microsatellites.

Stemphylium leaf blight (SLB), caused by the fungus Stemphylium vesicarium, is dominant within the foliar disease complex affecting onion production in New York (NY). The disease causes premature defoliation and significant reductions in bulb weight and quality. Foliar diseases of onion are usually managed by an intensive fungicide program, but SLB management is complicated by resistance to multiple single-site modes of action. The design of integrated disease management strategies is limited by incomplete knowledge surrounding the dominant sources of S. vesicarium inoculum. To facilitate genomic-based studies of S. vesicarium populations, nine microsatellite markers were developed. The markers were multiplexed into two PCR assays containing four and five fluorescently labeled microsatellite markers. Initial testing of the S. vesicarium isolates found the markers were highly polymorphic and reproducible with an average of 8.2 alleles per locus. The markers were used to characterize 54 S. vesicarium isolates from major NY onion production regions in 2016 (n = 27) and 2018 (n = 27). Fifty-two multilocus genotypes (MLGs) were identified between these populations. Genotypic and allelic diversities were high in both the 2016 and 2018 populations. A greater degree of genetic variation was observed within populations than between years. No distinct pattern of MLGs according to population was identified and some MLGs were closely related between 2016 and 2018. The lack of evidence for linkage among loci also was strongly suggestive of clonal populations with only minor differences between the two populations. These microsatellite markers will be a foundational resource for the testing of hypotheses surrounding the population biology of S. vesicarium and therefore informing disease management.

SARS‐CoV‐2 infection worsens Vascular Dementia (VaD)‐associated neuropathology in mice

AbstractBackgroundVascular Dementia (VaD) is the second leading cause of dementia behind Alzheimer’s disease (AD) and has a profound association with the morbidity and mortality of COVID‐19. Recent evidence demonstrates that preexisting vascular dementia is associated with increased COVID‐19 incidence and worsened outcomes after COVID‐19 infection. Collectively, these observations suggest that vascular pathology in VaD such as blood‐brain barrier (BBB) disruption, directly contributes to this association. Previously we and others have demonstrated that SARS‐CoV‐2 binds to the vascular integrin α5β1 receptor and that inhibition of α5β1 integrin with the clinically‐validated peptide ATN‐161 can improve acute SARS‐CoV‐2 infection and reduce SARS‐CoV‐2‐mediated vascular disruption. Furthermore, we have previously demonstrated that ATN‐161 reduces BBB disruption in models of brain ischemia (stroke) and VaD‐modeled chronic bilateral carotid artery stenosis (BCAS), which models reduced blood flow, BBB disruption, neuroinflammation, white matter damage and cognitive decline in VaD. In the present study, we tested the hypothesis that experimental VaD worsens COVID‐19‐associated neuroinflammation and exacerbates subsequent neurovascular damage, which may be targeted therapeutically by ATN‐161.Method10‐week‐old wild‐type (WT) BALB/c male mice were infected with 2×105 PFU mouse‐adapted (MA10) SARS‐CoV‐2 or mock infection 1‐week after BCAS surgery to model the effects of preexisting VaD in mice and subsequent SARS‐CoV‐2 infection. Body weight was monitored daily. The brain was isolated 3‐days post‐infection (dpi) and analyzed for immunohistochemical and mRNA expression of selected markers of neuroinflammation and immune response.ResultBCAS+SARS‐CoV‐2 infected mice exhibited a significant reduction in body weight at 3 dpi compared with the BCAS+mock infected group. Immunohistochemical analysis demonstrated a significant increase in α5 integrin signal in the cortex. SARS‐CoV‐2 infection after BCAS worsened brain and vascular inflammation and glial activation, indicated by increased Iba‐1 (microglia) and GFAP (astrocyte) immunofluorescence and brain (proinflammatory) IL‐1β cytokine transcript levels. Lastly, SARS‐CoV‐2 infection worsens white matter (myelin) integrity as measured by myelin basic protein (MBP) immunofluorescence.ConclusionSARS‐CoV‐2 aggravated VaD‐associated morbidity indicated by elevated white matter damage, glial activation, and neuroinflammation along with increased integrin α5 expression. Integrin α5β1 could, therefore, be a therapeutic target for improving both acute SARS‐CoV‐2 infection, and VaD post‐COVID morbidity and cognitive decline.

IBC-Oxford University2023_BJSPoster_13Short-term outcomes of sleeve gastrectomy for morbid obesity: A single-center experience

Abstract Background Sleeve gastrectomy is a commonly performed procedure for individuals with morbid obesity. Short-term outcomes of sleeve gastrectomy are often assessed in terms of excess body mass index loss (EBMIL). These measures provide an indication of the amount of weight lost relative to the excess weight or excess body mass index prior to surgery. Methods In this study, we evaluated the short-term outcomes of sleeve gastrectomy in patients with morbid obesity. A retrospective analysis was conducted on a series of Laparoscopic Sleeve Gastrectomy (LSG) procedures performed between January 2020 and December 2022. The medical records of all patients who underwent LSG were reviewed and enrolled. Results The study included 162 patients with morbid obesity (mean age: 38 years; 72% female; mean preoperative body mass index: 41 kg/m²). At 6 months postoperatively, the percentage of excess body mass index loss was 69% with a follow-up rate of 81%. At 1 year, it was 83% with a follow-up rate of 72%, and at 2 years, it was 79% with a follow-up rate of 44%. These findings indicate that sleeve gastrectomy leads to substantial weight loss in the short term, as measured by EBMIL. Conclusion Sleeve gastrectomy demonstrates favorable short-term outcomes in terms of excess body mass index loss (EBMIL) for individuals with morbid obesity. These measures provide evidence of significant weight reduction following the procedure, highlighting the effectiveness of sleeve gastrectomy as a treatment option for morbid obesity.

The use of prednisolone during Ramadan fasting in patients with adrenal insufficiency.

Once daily prednisolone taken at predawn has been proposed to be the glucocorticoid replacement of choice in patients with adrenal insufficiency (AI) who intend to fast for the month of Ramadan. However, the effects of prednisolone on metabolic parameters and quality of life during fasting for Ramadan are unknown. Patients with AI on twice-daily hydrocortisone, who had low or moderate risk and intended to fast, were recruited. Patients were converted to prednisolone 5 mg once daily taken at sahur (predawn) and Ramadan education given. Weight, sleep duration, biochemical parametersand quality of life measures (SF-36 questionnaire) were analysed at the end of Ramadan and compared against baseline. Twenty patients (13 men) were recruited, with a mean age of 59.9 ± 15.0 years. All patients were on hydrocortisone 15 mg daily (in divided doses) as pre-Ramadan glucocorticoid replacement. Half had type 2 diabetes with low IDF-DAR risk. Eighty-five percentof patients completed the full 29 days of fasting with no complications. There was a significant reduction in weight (-1.1 ± 1.6 kg, p = .005), with no significant change in blood pressure or sleep duration. There was a significant increase in urea (0.80 ± 1.1 mmol/L, p = .005) and haematocrit, (0.011 ± 0.019 L/L, p = .019) and decrease in serum sodium (-1.6 ± 3.0 mmol/L, p = .028), with no change in serum creatinine or liver function. Quality of life measures were preserved in all domains with significant improvement in role limitation due to physical health (15.3 ± 21.6, p = .005) and bodily pain (8.8 ± 16.3, p = .031). This study has demonstrated that converting patients with AI who are fasting for Ramadan from twice-daily hydrocortisone to prednisolone 5 mg daily at sahur was safe, with no major short-term adverse effects. Despite the higher equivalent glucocorticoid doses, patients experienced weight loss and no clinically significant change in blood pressure, sleep, biochemical parameters or quality of life. This study paves the way to trial even lower doses of prednisolone once daily in patients fasting for Ramadan with AI.

Hypolipidemic, Hypoglycemic, and Ameliorative Effects of Boiled Parsley (Petroselinum crispum) and Mallow (Corchorus olitorius) Leaf Extracts in High-Fat Diet-Fed Rats.

Obesity is a major health concern associated with serious conditions such as type 2 diabetes and cardiovascular diseases. This study investigated the potential anti-obesity effects of heat-treated parsley and mallow extracts (PE and ME, respectively) in high-fat diet (HFD)-fed rats. The selected herbs underwent three heat treatments (boiling, blanching, and microwaving), and the most effective treatment was orally administered to the HFD rats for eight weeks. All three treatments effectively increased the total phenolic content (TPC) and antioxidant capacity of the herbs, with boiling treatment exhibiting the most significant increase. Boiled herbs demonstrated approximately 29% higher TPC and an impressive 348% increase in antioxidant activity compared to the other treatments. Oral administration of the boiled herb extracts to the HFD rats resulted in significant reductions in body weight, total cholesterol, triglycerides, and LDL cholesterol levels, while elevating the HDL cholesterol levels compared to the positive control rats. Additionally, the boiled herb extracts exhibited antioxidant, hepatoprotective, and nephroprotective effects. Notably, PE displayed more significant anti-obesity properties compared to ME, potentially due to higher TPC and antioxidant activity observed in PE compared to ME. In conclusion, this study highlights the potential positive effects of boiled parsley against obesity and recommends boiling treatment as the preferred method when heat treatment is required for herbs.

SR-18292 Induces Fetal Hemoglobin Synthesis and Reduces Disease Pathology in Sickle Cell Mice

Sickle cell disease (SCD) is a commonly inherited blood disorder, which affects millions around the world. Reactivation of fetal hemoglobin (HbF) synthesis in adult erythroid cells can diminish the severity of many clinical features of the disease. Up-regulation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) has been shown to induce HbF levels in human primary erythroid progenitor CD34 + cells. Here we reported the in vitro and in vivo effects of a small molecular compound, SR-18292, on HbF induction via modulating PGC-1α. To determine whether SR-18292 can induce HbF in human CD34 + cells, we performed RT-qPCR, flow cytometry, and western blot to measure the mRNA and protein levels of PGC-1α and γ-globin. We found that mRNA levels of PGC-1α and γ-globin were significantly increased in cells treated with SR-18292 while β-globin mRNA levels were unaffected. Protein levels of γ-globin and the ratio of F-cells were increased in treated cells. Erythroid cellular differentiation markers (CD71/CD235a) and terminal differentiation markers (CD49d/CD233) were used to examine the differentiation status. There was no significant difference in the population of CD71 +CD235a + cells among all groups. However, SR-18292 treatment increased the percentage of CD49d -CD233 + cells at 5 or 7.5 μM. These results suggest that SR-18292 at higher concentrations can promote erythroid terminal differentiation. To evaluate whether the HbF induction by SR-18292 can reduce the SCD disease pathology in SCD mice or not, we intraperitoneally administered SR-18292 to SCD mice. HbF induction was determined by flow cytometric analysis using an anti-HbF antibody. And it was shown that the HbF-high cell population was induced in SCD mice after 4 weeks of treatment. And we used transferrin receptor CD71 and erythroid-specific marker Ter119 to determine whether SR-18292 could affect erythroid differentiation. There was no significant difference in the CD71 +Ter119 + population after 4 weeks of SR-18192 treatment compared with untreated animals. The mRNA levels of γ-globin and PGC-1α were increased in treated mice. And the increase of PGC-1α and γ-globin protein levels were confirmed by western blot. Reticulocyte is a sign of premature RBC destruction (hemolysis), and the SCD mice usually have high reticulocyte counts (>50%). We measured the reticulocyte in the peripheral blood of SR-18292 treated and untreated SCD mice by flow-cytometric analyses and found that reticulocyte was significantly reduced in SR-18292 treated animals (from 55% to 20%) after 4 weeks of treatment. Complete blood cell counts (CBC) showed that SR-18292 treated mice had slightly elevated numbers of red blood cells (RBCs) and more hemoglobin, but lower counts of white blood cells, lymphocytes, and neutrophils. In addition, the RBC distribution width (RDW) was significantly reduced after SR-18292 treatment, indicating that the size of circulating RBCs was more uniform in treated mice. In addition, erythroid cell morphology was evaluated by blood smears with Wright-Giemsa stain. The number of sickled RBCs were reduced in SCD mice treated with SR-18292 for 4 weeks. This is consistent with our observation that RDW was reduced in SCD mice treated with SR-18292. Furthermore, SR-18292 treated mice had a statistically significant reduction in spleen size and weight in contrast to the spleens of untreated SCD mice. The indices of RBCs were improved in accompany with reduced hemolysis and a higher fraction of circulating mature erythrocytes in treated SCD mice. There were no observable adverse effects on other hematopoietic cell lineages. We also performed single-cell RNA-seqs in human CD34 + cells treated with SR-18292 and found that some known HbF repressors (such as BCL11A and ZBTB7A) were decreased in treated groups. Besides that, there were many differentially expressed genes (DEGs), which might be novel HbF regulators. We are verifying those DEGs genes by qPCR and using CRISPR/cas9 to examine their functions in globin regulation. In summary, our findings suggest that SR-18292 might be a promising therapeutic agent to treat SCD and modulating PGC-1α activity or the signaling pathways that it regulates might benefit therapeutically patients with SCD.

Glucagon-like peptide 1 agonists: a ray of hope for the treatment of polycystic ovarian syndrome

Dear editor, The Glucagon-like-peptide receptor- 1, agonists belong to a class of drugs that have been used to treat type 2 diabetes. Liraglutide and Semaglutide are drugs of this class, commonly sold under the brand names Saxenda and Wegovy respectively. These drugs have also been approved by the FDA for weight loss in diabetic and non-diabetic obese people.1 The mechanism of action of GLP-1 agonists involve stimulating insulin secretion and delaying gastric emptying. Moreover, GLP-1 receptors are found on adipose tissue, where they promote the conversion of stored fat into energy. They also target the appetite center in the hypothalamus which increases satiety and reduces food intake to cause weight loss. A large number of females who struggle with obesity, concomitantly suffer from Polycystic Ovarian syndrome (PCOS) also which is a multifactorial endocrine disorder in women of reproductive age, affecting 4-20% women around the world.2 One of the major manifestations of this syndrome is weight gain and difficulty in losing it. In contemporary medicine, the treatment of PCOS is limited to lifestyle intervention and symptomatic management. Thus, the patients of PCOS are often told by their doctors to simply lose weight. Physicians around the world agree that weight loss is crucial for women with PCOS who are obese to attain better metabolic, reproductive, and cardiovascular outcomes, because if not treated, obesity worsens the presentation of PCOS. But it is noteworthy that the ongoing hormonal imbalances, increased appetite and insulin resistance in this syndrome, all work against the body’s natural mechanism to lose weight and make it extremely difficult for the patient. This creates a dire need for external interventions regarding weight management in PCOS. Where conventional methods like dietary modifications and exercise alone do not provide substantial results, GLP-1 agonists can be a breakthrough for the management of PCOS since recent research and clinical data also provides evidence of correlation between obesity, GLP-1 kinetic alterations, and pathophysiology of PCOS.3 Hence the use of GLP-1 agonists can be a viable option for treatment of PCOS as multiple clinical trials have shown significant weight reduction, decrease in testosterone levels, improvement in insulin sensitivity and menstrual cycles.4 As the prevalence of PCOS continues to rise in Pakistan, the major presenting complaints include; weight gain, facial hair, acne and menstrual irregularities in teenage girls and infertility in married females. ---Continue

Spice Foods effects on Body Weight Reductions between Obese Animal Models

The aim of this study was determination and identification of phenolic and flavonoids fraction in addition to the antioxidant activities of used herbals (curcumin, black pepper and cumin) by HPLC in addition to evaluating the effects of such different spicy food consumptions on body weight reduction between obese animal models. Rats were randomly divided to ten groups fed; Black Papers, Cumin and Curcumin either alone or in different mixtures additionally to groups fed Orlistat (control body weight loss), Non-obese negative control group (C-ve) and Obese control positive group (C+ve). Blood glucose and body weight levels were measured at the beginning and end of the experimental in addition to rats’ lipid profiles (total cholesterol; triglycerides;, high dense lipoprotein cholesterol; low dense lipoprotein cholesterol; and very low dense lipoprotein cholesterol). Results presented that obese models received (Cumin) Cu/( Curcumin ) Cur mixture have the biggest effective significant treatment (about -80% body weight reduction ) followed by both groups fed mixtures of (Curcumin ) Cur/( Black Papers ) Bp and (Curcumin) Cur/( Black Papers ) Bp/( Cumin ) Cu; decreased by -68.0 and -65.6g respectively. The study could be more valuable causing significant body weight reduction between obese models, however human studies are needed.

The effects of pomegranate consumption on obesity indices in adults: A systematic review and meta-analysis.

Evidence supports the potential application of polyphenols as agents against obesity. Pomegranate is one of the fruits that possess a high content of polyphenols. This systematic review and meta-analysis of randomized controlled trials (RCTs) sought to evaluate the effects of pomegranate consumption on obesity indices, including body mass index (BMI), body weight, waist circumference (WC), fat mass (FM), body fat percentage (BFP), and fat-free mass (FFM) in adults. Relevant RCTs were obtained by searching databases, including PubMed, SCOPUS, and Web of Science, up to May 2023. Heterogeneity tests of the included trials were performed using the I 2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference with a 95% confidence interval. Pooled analysis of 28 trials revealed that pomegranate consumption led to a significant reduction in body weight (WMD: -1.97, 95% CI: -2.91, -1.03, p < .05), and a significant decrease in BMI (WMD: -0.48, 95% CI: -0.76, -0.20, p < .05) in comparison with the control group. However, there were no significant effects on WC, FM, FFM, and BFP in comparison with the control group. Pomegranate consumption may yield a beneficial effect on body weight and BMI in adults. However, there were no significant effects on WC, FM, FFM, and BFP, by pomegranate consumption. Also, pomegranate consumption can reduce body weight, BMI, WC, and BFP in obese adults. Long-term trials with different doses of pomegranate are needed.

Curcumin-loaded chitosan-protamine nanoparticles: A promising approach to ameliorate nicotine-induced reproductive disorders in male rats

Nicotine (NIC) exposure has been shown to impair male fertility, affecting sperm quality and motility. Curcumin (CUR) has been shown to have anti-inflammatory and antioxidant properties and has demonstrated potential in treating a range of health conditions, including infertility. The current study aimed to investigate the effects of curcumin encapsulated in chitosan-protamine nanoparticles (CUR-CPNPs) against nicotine-induced reproductive dysfunction in male rats. CUR-CPNPs were chemically prepared and characterized by TEM imaging, Zetasizer, and FT-IR spectroscopy. eight groups (6 rats per each) of male rats were used: first & second groups acted as control, third group received CUR-CPNPs (250 mg/kg), fourth group received CUR (250 mg/kg), fifth group received CPNPs (250 mg/kg), sixth group received 0.6 mg/kg nicotine (NIC). Finally, seventh and eighth groups are received NIC + CUR, NIC + CUR-CPNPs, respectively. After the end of the treatment period, the rats were anesthetized then the relative weight of the reproductive organs, semen analysis, testosterone levels and oxidative stress biomarkers were assessed, and finally a histopathological analysis of the testicular tissue was performed.The impacts of NIC administration resulted in a significant reduction in relative reproductive organs weights, exacerbated oxidative stress, decreased serum testosterone level, and negatively impacted semen count, motility, and viability. Testicular histopathology revealed extensive degenerative alterations. On the other hand, the ameliorative role of CUR-CPNPs clearly reversed the devastating effect caused by nicotine.

Hepatoprotective Effects of Biochanin A on Thioacetamide-Induced Liver Cirrhosis in Experimental Rats.

The protective effect of biochanin A (BCA) on the histopathology, immunohistochemistry, and biochemistry of thioacetamide (TAA)-induced liver cirrhosis in vivo was investigated. There was a significant reduction in liver weight and hepatocyte propagation, with much lower cell injury in rat groups treated with BCA (25 mg/kg and 50 mg/kg) following a TAA induction. These groups had significantly lower levels of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA). The liver homogenates showed increased antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as decreased malondialdehyde (MDA) levels. The serum biomarkers associated with liver function, namely alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transaminase (GGT), returned to normal levels, comparable to those observed in both the normal control group and the reference control group. Taken together, the normal microanatomy of hepatocytes, the inhibition of PCNA and α-SMA, improved antioxidant enzymes (SOD, CAT, and GPx), and condensed MDA with repairs of liver biomarkers validated BCA's hepatoprotective effect.

Body Mass Index, Quality of Life and Activity Limitation Trajectories over 2 Years in Patients with Knee or Hip Osteoarthritis: A Dual Trajectory Approach Based on 4265 Patients Included in the AktivA Quality Register.

(1) Background: Recent studies claim that weight-neutral approaches emphasizing physical activity might be as effective as weight-loss-centered approaches for improving pain and physical function in patients with knee and hip osteoarthritis. The objectives were to identify distinctive groups of individuals with similar BMI, quality of life and activity limitation trajectories over two years, to compare the overall differences between BMI trajectory groups for baseline variables and to explore the probabilities of the quality of life and activity limitation trajectory groups conditional on the BMI group. (2) Methods: Baseline data for age, gender, BMI, quality of life, activity limitations, pain, general health, knee or hip osteoarthritis and follow-up data on BMI, quality of life and activity limitations at 3, 12 and 24 months were retrieved from the "Active with osteoarthritis" (AktivA) electronic quality register. Group-based trajectory modeling was used to identify distinct trajectories for BMI, quality of life and activity limitations. (3) Results: 4265 patients were included in the study. Four distinct BMI trajectories were identified, normal weight (31%), slightly overweight (43%), overweight (20%) and obese (6%). At baseline, there were highly significant differences between all BMI groups, pain increased and age and general health decreased with higher BMI. Irrespective of weight category, minimal changes in BMI were found over the two-year follow-up period. Over 80% of the participants showed moderate-to-considerable improvements both in quality of life and activity limitations. (4) Conclusions: Almost 70% of the participants belonged to the overweight trajectories. Despite no significant weight reduction over the two years, eight in every 10 participants improved their quality of life and reduced their activity limitations after participating in the AktivA program.

Effect of Short Bouts of Vigorous Stair Climbing on Cardiorespiratory Fitness in Women with Overweight and Obesity: A Pilot Feasibility Study.

We examined the effect of 4 weeks of a brief vigorous stair climbing exercise on cardiorespiratory fitness (CRF) and body composition in women with overweight or obesity. Twenty-six participants (age, 25.4±4.9 years; body mass index [BMI], 25.3±1.8 kg/m2) were randomly assigned to either a stair climbing exercise group (n=13) or a non-exercising control group (n=13). The stair climbing exercise group performed 20 sessions (supervised, five sessions/week over 4 weeks) of brief intermittent stair climbing exercise consisting of a 3-minute warm-up followed by three bouts of 20 seconds of stair climbing (≥80% of age-predicted maximum heart rate) interspersed with 2-minute recovery periods (total exercise duration=10 minutes/session). Peak oxygen uptake (VO2peak) was measured using a graded maximal treadmill test with the use of a standard open-circuit spirometry technique. Body composition was assessed with bioelectrical impedance analysis. All participants, except one who dropped out due to coronavirus disease 2019 (COVID-19) infection, completed the study with 100% attendance rates. There were significant interaction effects (group×time) on body weight, BMI, waist circumference, and CRF such that the stair climbing exercise group had significant (P≤0.01) reductions in body weight (66.5±4.6 to 65.2±4.6 kg), BMI (24.8±1.2 to 24.4±1.1 kg/m2), and waist circumference (78.0±3.7 to 76.5±4.1 cm) and improvements in VO2peak (31.6±2.5 to 34.9±2.6 mL/kg/min) compared with controls. Short bouts of vigorous stair climbing is a feasible and time-efficient exercise strategy for improving CRF in previously sedentary, young women with overweight and obesity.

Effect of Ramadan intermittent fasting on renal and liver function markers among healthy overweight and obese males: A prospective cohort study

Intermittent fasting (IF) has garnered attention for its potential to promote health and combat chronic diseases. This study focused on the effects of Ramadan fasting, a form of IF observed by Muslims, on renal and liver function markers, anthropometric measurements, and dietary intake in healthy overweight and obese men. The study involved 60 participants from Hargeisa, Somaliland, with an average age of 40.01 ± 7.99 years. Results revealed significant reductions in body weight (P ≤ 0.001), waist circumference (P ≤ 0.001), and body mass index (P ≤ 0.001) after Ramadan fasting. Urea levels decreased significantly (P = 0.003), and though creatinine levels showed a non-significant decrease, uric acid levels increased significantly within the normal range (P ≤ 0.001). Serum glutamate oxaloacetate transaminase (GOT) levels decreased significantly (P ≤ 0.001), while glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) levels remained stable. Dietary analysis indicated a significant decrease in total carbohydrates (P = 0.023), proteins (P = 0.006), and dietary cholesterol intake (P ≤ 0.001). These findings suggest that Ramadan fasting positively impacts anthropometric and renal-liver function markers in healthy overweight and obese men. The study contributes to the expanding understanding of intermittent fasting's potential health benefits, emphasizing the importance of considering Ramadan fasting as a preventive approach for metabolic disorders. Further research should explore long-term effects, mechanistic insights, and personalized clinical applications, while public health initiatives could educate individuals about safe and informed fasting practices.

Alterations in the gene expression of SARS-COV-2 entry receptors and enzymes in lungs and hearts of controlled and uncontrolled diabetic mice.

The entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell is carried out by specific receptors and enzymes, including human angiotensin-converting enzyme 2 receptor (ACE2), transmembrane serine protease 2 (TMPRSS2), and cathepsin-L (CTSL). COVID-19 patients with comorbidities, such as diabetes mellitus (DM), are more prone to severe symptoms and have a higher risk of mortality. The present study aimed to investigate the impact of controlled and uncontrolled type 1 DM (T1DM) on the gene expression of mouse Ace2, Tmprss2, and Ctsl and correlate it with the pathological alterations in the lungs and the heart of DM mice. Balb/c mice were administered a single dose of 240 mg/kg streptozocin to induce T1DM. The blood glucose level was measured to confirm the induction of DM. Normalization of blood glucose levels in T1DM mice was achieved using 0.1mL/kg Mixtard® insulin therapy. The mice's lungs and hearts were harvested, and the mRNA was extracted and converted to cDNA. The gene expression of Ace2, Tmprss2, Ctsl, Cyp4a11, and Adrb1 genes, which play a role in the homeostasis of lungs and hearts, were measured using quantitative real-time polymerase chain reaction (RT-PCR). The pathological alterations in the hearts and lungs induced by T1DM were evaluated using the relative heart and lung weights, in addition to the pathohistological examination. After inducing T1DM for 14 days, we observed a significant reduction in the total weight of uncontrolled DM (UDM) mice (P<0.05). Pathohistological examination of UDM lung tissues revealed thickening of the alveolar walls with narrowing of the surface of the alveolar sacs. Additionally, we found that UDM mice exhibited downregulation of Ace2 gene expression (P< 0.05) in their lungs, while both UDM and control DM (CDM) mice showed upregulation of Ctsl gene expression in their hearts (P<0.05). Notably, Cyp4a12 gene expression was significantly downregulated (P<0.05) in UDM mice but returned to normal levels in CDM mice. We conclude from this study that T1DM downregulates Ace2 receptor and Cyp4a12 gene expression, which is correlated with the thickening of alveolar walls and narrowing of the surface of alveolar sacs in the lungs. Insulin administration for controlling T1DM ameliorated these pathological alterations. These results can help increase our understanding of the impact of controlled and uncontrolled T1DM on the lungs and may explain, at least in part, why DM patients with COVID-19 experience exacerbation of symptoms.

Canagliflozin improves hemodynamic parameters by impedance cardiography and left ventricular diastolic function in patients with type 2 diabetes mellitus

Abstract Background Sodium-glucose cotransporter type 2 (SGLT2) inhibitors have been shown to reduce cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) in large trials, independent of glycemic control. The mechanisms behind this cardioprotective effect remain uncertain, although evidence suggests that positive hemodynamic changes and favorable cardiac remodeling may contribute to the clinical outcomes. However, results have been conflicting. The aim of this study was to investigate the potential impact of canagliflozin on hemodynamic parameters, cardiac structure, and function. Methods This prospective observational study included T2DM patients receiving canagliflozin 100mg per day in addition to their antidiabetic treatment. We analyzed hemodynamic parameters assessed by impedance cardiography (ICG) and echocardiographic measurements to evaluate systolic and diastolic functions from baseline to 24 weeks after treatment. Results A total of 47 patients (25 males and 22 females) with an average age of 64.4±10.8 years experienced a significant reduction in HbA1c, hematocrit, body weight, and systolic blood pressure. NT-proBNP levels remained the same. ICG suggested significant improvement in hemodynamic parameters, with increased stroke volume index and cardiac output index and decreased systemic vascular resistance index at 12 and 24 weeks. E/e’, left atrial (LA) volume, and LA stiffness were reduced, while left ventricular (LV) global longitudinal strain (GLS) and LA strain rates increased at 24 weeks, as measured by conventional and speckle tracking echocardiography. LV mass and ejection fraction showed no differences. Conclusions Canagliflozin improved hemodynamic parameters and had a favorable impact on LA and LV reverse remodeling. These changes may explain the beneficial effect on cardiovascular outcomes seen in large clinical trials.

Unravelling the Role of Cancer Cell-Derived Extracellular Vesicles in Muscle Atrophy, Lipolysis, and Cancer-Associated Cachexia.

Cancer-associated cachexia is a metabolic syndrome that causes significant reduction in whole-body weight due to excessive loss of muscle mass accompanied by loss of fat mass. Reduced food intake and several metabolic abnormalities, such as increased energy expenditure, excessive catabolism, and inflammation, are known to drive cachexia. It is well documented that cancer cells secrete EVs in abundance which can be easily taken up by the recipient cell. The cargo biomolecules carried by the EVs have the potential to alter the signalling pathways and function of the recipient cells. EV cargo includes proteins, nucleic acids, lipids, and metabolites. Tumour-secreted EVs have been found to alter the metabolic and biological functions of adipose and muscle tissue, which aids in the development of the cachexia phenotype. To date, no medical intervention or FDA-approved drug exists that can completely reverse cachexia. Therefore, understanding how cancer-derived EVs contribute to the onset and progression of cancer-associated cachexia may help with the identification of new biomarkers as well as provide access to novel treatment alternatives. The goal of this review article is to discuss the most recent research on cancer-derived EVs and their function in cellular crosstalk that promotes catabolism in muscle and adipose tissue during cancer-induced cachexia.