Therapeutic Efficacy of Antioxidants in Ameliorating Obesity Phenotype and Associated Comorbidities

Obesity has been a worldwide epidemic for decades. Despite the abundant increase in knowledge regarding the etiology and pathogenesis of obesity, the prevalence continues to rise with estimates predicting considerably higher numbers by the year 2030. Obesity is characterized by an abnormal lipid accumulation, however, the physiological consequences of obesity are far more concerning. The development of the obesity phenotype constitutes dramatic alterations in adipocytes, along with several other cellular mechanisms which causes substantial increase in systemic oxidative stress mediated by reactive oxygen species (ROS). These alterations promote a chronic state of inflammation in the body caused by the redox imbalance. Together, the systemic oxidative stress and chronic inflammation plays a vital role in maintaining the obese state and exacerbating onset of cardiovascular complications, Type II diabetes mellitus, dyslipidemia, non-alcoholic steatohepatitis, and other conditions where obesity has been linked as a significant risk factor. Because of the apparent role of oxidative stress in the pathogenesis of obesity, there has been a growing interest in attenuating the pro-oxidant state in obesity. Hence, this review aims to highlight the therapeutic role of antioxidants, agents that negate pro-oxidant state of cells, in ameliorating obesity and associated comorbidities. More specifically, this review will explore how various antioxidants target unique and diverse pathways to exhibit an antioxidant defense mechanism

Evaluation of serum mineral micronutrients (Zn, Cu, Fe, Mg) and their correlation with clinical parameters (gingival index, probing pocket depth, clinical attachment loss) in chronic periodontitis patients

Background: Nutrition especially micro-mineral nutrients plays a major role in the etiology of chronic periodontitis. Serum levels of micro-mineral nutrients can be used as markers for the incidence of periodontitis and may also be used as indicators for dietary supplementation. Aims and Objectives: The aim of the study was to estimate the serum levels of Zn, Cu, Fe, and Mg of chronic periodontitis patients and normal healthy controls., to measure the clinical parameters (gingival index, probing pocket depth [PPD], and clinical attachment loss) in chronic periodontitis patients and normal healthy controls., to compare the levels of serum Zn, Cu, Fe, and Mg levels of chronic periodontitis patients and healthy controls and to correlate the levels of serum micronutrients with clinical parameters (gingival index, PPD, and clinical attachment loss) in chronic periodontitis patients and healthy controls. Materials and Methods: A total of 110 subjects, 55 subjects with chronic periodontitis and 55 healthy control subjects in the age group 35–65 years were selected for the study. Serum micronutrient levels of Cu, Fe, Zn, Mg, and the clinical parameters were measured. Results: Serum concentrations of Cu and Fe showed statistically significant increase and serum Zn and Mg showed a significant decrease in peridontitis patients as compared to normal healthy controls. Copper and Fe showed a significant positive correlation and Zn and Mg showed a significant negative correlation with clinical parameters (gingival index, PPD, and clinical attachment loss). Conclusion: The present study supports and extends the view that the assessment of serum mineral micronutrient can serve as possible biomarkers or indicators for an inflammatory condition like chronic periodontitis

Processing of aluminum-graphite particulate metal matrix composites by advanced shear technology

Copyright @ 2009 ASM International. This paper was published in Journal of Materials Engineering and Performance 18(9) and is made available as an electronic reprint with the permission of ASM International. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplications of any material in this paper for a fee or for commercial purposes, or modification of the content of this paper are prohibited.To extend the possibilities of using aluminum/graphite composites as structural materials, a novel process is developed. The conventional methods often produce agglomerated structures exhibiting lower strength and ductility. To overcome the cohesive force of the agglomerates, a melt conditioned high-pressure die casting (MC-HPDC) process innovatively adapts the well-established, high-shear dispersive mixing action of a twin screw mechanism. The distribution of particles and properties of composites are quantitatively evaluated. The adopted rheo process significantly improved the distribution of the reinforcement in the matrix with a strong interfacial bond between the two. A good combination of improved ultimate tensile strength (UTS) and tensile elongation (e) is obtained compared with composites produced by conventional processes.EPSR

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Systematic Review of Clinical Insights into Novel Coronavirus (CoVID-19) Pandemic: Persisting Challenges in U.S. Rural Population

(1) Introduction. A recent viral outbreak of novel coronavirus (CoVID-19) was declared as a pandemic by the World Health Organization (WHO) due to its global public health concern. There has been an aggressive growth in the number of emerging cases suggesting rapid spread of the virus. Since the first reported case of CoVID-19, there has been vast progress in understanding the dynamics of CoVID-19. However, there is an increasing evidence of epidemiological disparity in disease burden between urban and rural areas, with rural areas having minimal pandemic preparedness and their own healthcare challenges. Therefore, this review aims to provide insight on the pathogenesis and the transmission dynamics of CoVID-19 along with pharmacological and non-pharmacological intervention strategies to mitigate the clinical manifestation of this virus. This review also aims to assess existing challenges of the CoVID-19 pandemic in rural areas based on past pandemic experiences and the effect on rural population. (2) Methods. A literature review was conducted using databases such as PubMed, Science Direct, Academic Search Premier, ProQuest, and Google Scholar, along with information from governmental organizations such as Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO). (3) Results. The causative virus, with its likely zoonotic origin, has demonstrated high pathogenicity in humans through increasing human-to-human transmission leading to extensive mitigation strategies, including patient quarantine and mass “social distancing” measures. Although the clinical manifestation of symptoms is mild in majority of the virus-inflicted population, critical patients may present with pneumonia and acute respiratory distress syndrome, exacerbated by pre-existing comorbidities, eventually leading to death. While effective coronavirus disease (CoVID-19)-specific vaccines and drugs are under clinical trials, several pharmacological and non-pharmacological interventions have been adapted to manage symptoms and curtail the effect of the virus to prevent increasing morbidity and mortality. Several persisting challenges have been noted for mitigating CoVID-19 in rural areas, including the poor healthcare infrastructure, health literacy, pandemic preparedness along with the fact that majority of rural population are frail subjects with pre-existing comorbidities. (4) Discussion. The increasing rate of incidence of CoVID-19 presents its own challenges, burdening healthcare institutions and the global economy, and impacting the physical and mental health of people worldwide. Given the clinical insights into CoVID-19 and the challenges presented in this review for the U.S. rural population, mitigation strategies should be designed accordingly to minimize the morbidity and mortality of this contagion

Elucidating Potential Profibrotic Mechanisms of Emerging Biomarkers for Early Prognosis of Hepatic Fibrosis

Hepatic fibrosis has been associated with a series of pathophysiological processes causing excessive accumulation of extracellular matrix proteins. Several cellular processes and molecular mechanisms have been implicated in the diseased liver that augments fibrogenesis, fibrogenic cytokines and associated liver complications. Liver biopsy remains an essential diagnostic tool for histological evaluation of hepatic fibrosis to establish a prognosis. In addition to being invasive, this methodology presents with several limitations including poor cost-effectiveness, prolonged hospitalizations, and risks of peritoneal bleeding, while the clinical use of this method does not reveal underlying pathogenic mechanisms. Several alternate noninvasive diagnostic strategies have been developed, to determine the extent of hepatic fibrosis, including the use of direct and indirect biomarkers. Immediate diagnosis of hepatic fibrosis by noninvasive means would be more palatable than a biopsy and could assist clinicians in taking early interventions timely, avoiding fatal complications, and improving prognosis. Therefore, we sought to review some common biomarkers of liver fibrosis along with some emerging candidates, including the oxidative stress-mediated biomarkers, epigenetic and genetic markers, exosomes, and miRNAs that needs further evaluation and would have better sensitivity and specificity. We also aim to elucidate the potential role of cardiotonic steroids (CTS) and evaluate the pro-inflammatory and profibrotic effects of CTS in exacerbating hepatic fibrosis. By understanding the underlying pathogenic processes, the efficacy of these biomarkers could allow for early diagnosis and treatment of hepatic fibrosis in chronic liver diseases, once validated

Predicting Nonalcoholic Fatty Liver Disease through a Panel of Plasma Biomarkers and MicroRNAs in Female West Virginia Population

(1) Background: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the presence of fatty liver, hepatic inflammation and fibrogenesis eventually leading to nonalcoholic steatohepatitis (NASH) or cirrhosis. Obesity and diabetes are common risk factors associated with the development and progression of NAFLD, with one of the highest prevalence of these diseased conditions in the West Virginia population. Currently, the diagnosis of NAFLD is limited to radiologic studies and biopsies, which are not cost-effective and highly invasive. Hence, this study aimed to develop a panel and assess the progressive levels of circulatory biomarkers and miRNA expression in patients at risk for progression to NASH to allow early intervention strategies. (2) Methods: In total, 62 female patients were enrolled and blood samples were collected after 8–10 h of fasting. Computed tomography was performed on abdomen/pelvis following IV contrast administration. The patients were divided into the following groups: Healthy subjects with normal BMI and normal fasting blood glucose (Control, n = 20), Obese with high BMI and normal fasting blood glucose (Obese, n = 20) and Obese with high fasting blood glucose (Obese + DM, n = 22). Based on findings from CT, another subset was created from Obese + DM group with patients who showed signs of fatty liver infiltration (Obese + DM(FI), n = 10). ELISA was performed for measurement of plasma biomarkers and RT-PCR was performed for circulating miRNA expression. (3) Results: Our results show significantly increased levels of plasma IL-6, Leptin and FABP-1, while significantly decreased level of adiponectin in Obese, Obese + DM and Obese + DM(FI) group, as compared to healthy controls. The level of CK-18 was significantly increased in Obese + DM(FI) group as compared to control. Subsequently, the expression of miR-122, miR-34a, miR-375, miR-16 and miR-21 was significantly increased in Obese + DM and Obese + DM(FI) group as compared to healthy control. Our results also show distinct correlation of IL-6, FABP-1 and adiponectin levels with the expression of miRNAs in relation to the extent of NAFLD progression. (4) Conclusion: Our results support the clinical application of these biomarkers and miRNAs in monitoring the progression of NAFLD, suggesting a more advanced diagnostic potential of this panel than conventional methods. This panel may provide an appropriate method for early prognosis and management of NAFLD and subsequent adverse hepatic pathophysiology, potentially reducing the disease burden on the West Virginia population

Beneficial Role of HO-1-SIRT1 Axis in Attenuating Angiotensin II-Induced Adipocyte Dysfunction

BACKGROUND: Angiotensin II (Ang II), released by the renin-angiotensin-aldosterone system (RAAS), contributes to the modulatory role of the RAAS in adipose tissue dysfunction. Investigators have shown that inhibition of AngII improved adipose tissue function and insulin resistance in mice with metabolic syndrome. Heme Oxygenase-1 (HO-1), a potent antioxidant, has been demonstrated to improve oxidative stress and adipocyte phenotype. Molecular effects of high oxidative stress include suppression of sirtuin-1 (SIRT1), which is amenable to redox manipulations. The mechanisms involved, however, in these metabolic effects of the RAAS remain incompletely understood. HYPOTHESIS: We hypothesize that AngII-induced oxidative stress has the potential to suppress adipocyte SIRT1 via down regulation of HO-1. This effect of AngII will, in turn, upregulate mineralocorticoid receptor (MR). The induction of HO-1 will rescue SIRT1, hence improving oxidative stress and adipocyte phenotype. METHODS AND RESULTS: We examined the effect of AngII on lipid accumulation, oxidative stress, and inflammatory cytokines in mouse pre-adipocytes in the presence and absence of cobalt protoporphyrin (CoPP), HO-1 inducer, tin mesoporphyrin (SnMP), and HO-1 inhibitor. Our results show that treatment of mouse pre-adipocytes with AngII increased lipid accumulation, superoxide levels, inflammatory cytokine levels, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha), and adiponectin levels. This effect was attenuated by HO-1 induction, which was further reversed by SnMP, suggesting HO-1 mediated improvement in adipocyte phenotype. AngII-treated pre-adipocytes also showed upregulated levels of MR and suppressed SIRT1 that was rescued by HO-1. Subsequent treatment with CoPP and SIRT1 siRNA in mouse pre-adipocytes increased lipid accumulation and fatty acid synthase (FAS) levels, suggesting that beneficial effects of HO-1 are mediated via SIRT1. CONCLUSION: Our study demonstrates for the first time that HO-1 has the ability to restore cellular redox, rescue SIRT1, and prevent AngII-induced impaired effects on adipocytes and the systemic metabolic profile