Hypertensive rats show increased renal excretion and decreased tissue concentrations of glycine betaine, a protective osmolyte with diuretic properties

Hypertension leads to water-electrolyte disturbances and end-organ damage. Betaine is an osmolyte protecting cells against electrolyte imbalance and osmotic stress, particularly in the kidneys. This study aimed to evaluate tissue levels and hemodynamic and renal effects of betaine in normotensive and hypertensive rats. Betaine levels were assessed using highperformance liquid chromatography-mass spectrometry (HPLC-MS) in normotensive rats (Wistar-Kyoto, WKYs) and Spontaneously Hypertensive rats (SHRs), a model of genetic hypertension. Acute effects of IV betaine on blood pressure, heart rate, and minute diuresis were evaluated. Gene and protein expression of chosen kidney betaine transporters (SLC6a12 and SLC6a20) were assessed using real-time PCR and Western blot. Compared to normotensive rats, SHRs showed significantly lower concentration of betaine in blood serum, the lungs, liver, and renal medulla. These changes were associated with higher urinary excretion of betaine in SHRs (0.20 ± 0.04 vs. 0.09 ± 0.02 mg/ 24h/ 100g b.w., p = 0.036). In acute experiments, betaine increased diuresis without significantly affecting arterial blood pressure. The diuretic response was greater in SHRs than in WKYs. There were no significant differences in renal expression of betaine transporters between WKYs and SHRs. Increased renal excretion of betaine contributes to decreased concentration of the protective osmolyte in tissues of hypertensive rats. These findings pave the way for studies evaluating a causal relation between depleted betaine and hypertensive organ damage, including kidney injury

Dose-response relationship between arsenic exposure and the serum enzymes for liver function tests in the individuals exposed to arsenic: a cross sectional study in Bangladesh

<p>Abstract</p> <p>Background</p> <p>Chronic arsenic exposure has been shown to cause liver damage. However, serum hepatic enzyme activity as recognized on liver function tests (LFTs) showing a dose-response relationship with arsenic exposure has not yet been clearly documented. The aim of our study was to investigate the dose-response relationship between arsenic exposure and major serum enzyme marker activity associated with LFTs in the population living in arsenic-endemic areas in Bangladesh.</p> <p>Methods</p> <p>A total of 200 residents living in arsenic-endemic areas in Bangladesh were selected as study subjects. Arsenic concentrations in the drinking water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The study subjects were stratified into quartile groups as follows, based on concentrations of arsenic in the drinking water, as well as in subjects' hair and nails: lowest, low, medium and high. The serum hepatic enzyme activities of alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) were then assayed.</p> <p>Results</p> <p>Arsenic concentrations in the subjects' hair and nails were positively correlated with arsenic levels in the drinking water. As regards the exposure-response relationship with arsenic in the drinking water, the respective activities of ALP, AST and ALT were found to be significantly increased in the high-exposure groups compared to the lowest-exposure groups before and after adjustments were made for different covariates. With internal exposure markers (arsenic in hair and nails), the ALP, AST and ALT activity profiles assumed a similar shape of dose-response relationship, with very few differences seen in the higher groups compared to the lowest group, most likely due to the temporalities of exposure metrics.</p> <p>Conclusions</p> <p>The present study demonstrated that arsenic concentrations in the drinking water were strongly correlated with arsenic concentrations in the subjects' hair and nails. Further, this study revealed a novel exposure- and dose- response relationship between arsenic exposure metrics and serum hepatic enzyme activity. Elevated serum hepatic enzyme activities in the higher exposure gradients provided new insights into arsenic-induced liver toxicity that might be helpful for the early prognosis of arsenic-induced liver diseases.</p

Resveratrol prevents angiotensin II-induced hypertrophy of vascular smooth muscle cells through the transactivation of growth factor receptors

We previously showed that the augmented levels of endogenous angiotensin II (Ang II) contribute to vascular smooth muscle cell (VSMC) hypertrophy through the transactivation of growth factor receptors in spontaneously hypertensive rats. Resveratrol (RV), a polyphenolic component of red wine, has also been shown to attenuate Ang II-evoked VSMC hypertrophy, however, the molecular mechanism mediating this response is obscure. The present study is therefore undertaken to examine if RV could prevent Ang II-induced VSMC hypertrophy through the transactivation of growth factor receptor and associated signaling pathways. Ang II treatment of VSMC enhanced the protein synthesis which was attenuated towards control levels by RV pre-treatment as well as by the inhibitors of NADPH oxidase, c-Src, and growth factor receptors. Furthermore, RV pre-treatment also inhibited the enhanced levels of superoxide anion, NADPH oxidase activity, the increased expression of NADPH oxidase subunits and phosphorylation of c-Src, EGF-R, PDGE-R, ERK1/2 and AKT1/2. In conclusion, these results indicate that RV attenuates Ang II-induced VSMC hypertrophy through the inhibition of enhanced oxidative stress, activation of c-Src, growth factor receptors and MAPK/AKT signaling. It may be suggested that RV could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension and hypertrophy.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Sub-ohm vaping increases the levels of carbonyls, is cytotoxic, and alters gene expression in human bronchial epithelial cells exposed at the air-liquid interface

BACKGROUND: Exposure to electronic-cigarette (e-cig) aerosols induces potentially fatal e-cig or vaping-associated lung injury (EVALI). The cellular and molecular mechanisms underlying these effects, however, are unknown. We used an air-liquid interface (ALI) in vitro model to determine the influence of two design characteristics of third-generation tank-style e-cig devices-resistance and voltage-on (1) e-cig aerosol composition and (2) cellular toxicity. METHODS: Human bronchial epithelial cells (H292) were exposed to either butter-flavored or cinnamon-flavored e-cig aerosols at the ALI in a Vitrocell exposure system connected to a third-generation e-cig device. Exposures were conducted following a standard vaping topography profile for 2 h per day, for 1 or 3 consecutive days. 24 h after ALI exposures cellular and molecular outcomes were assessed. RESULTS: We found that butter-flavored e-cig aerosol produced under \u27sub-ohm\u27 conditions (\u3c 0.5 Ω) contains high levels of carbonyls (7-15 μg/puff), including formaldehyde, acetaldehyde and acrolein. E-cig aerosol produced under regular vaping conditions (resistance \u3e 1 Ω and voltage \u3e 4.5 V), contains lower carbonyl levels (\u3c 2 μg/puff). We also found that the levels of carbonyls produced in the cinnamon-flavored e-cig aerosols were much lower than that of the butter-flavored aerosols. H292 cells exposed to butter-flavored or cinnamon-flavored e-cig aerosol at the ALI under \u27sub-ohm\u27 conditions for 1 or 3 days displayed significant cytotoxicity, decreased tight junction integrity, increased reactive oxygen species production, and dysregulated gene expression related to biotransformation, inflammation and oxidative stress (OS). Additionally, the cinnamon-flavored e-cig aerosol induced pro-oxidant effects as evidenced by increases in 8-hydroxy-2-deoxyguanosine protein levels. Moreover, we confirmed the involvement of OS as a toxicity process for cinnamon-flavored e-cig aerosol by pre-treating the cells with N-acetyl cysteine (NAC), an antioxidant that prevented the cells from the OS-mediated damage induced by the e-cig aerosol. CONCLUSION: The production of high levels of carbonyls may be flavor specific. Overall, inhaling e-cig aerosols produced under \u27sub-ohm\u27 conditions is detrimental to lung epithelial cells, potentially via mechanisms associated with OS. This information could help policymakers take the necessary steps to prevent the manufacturing of sub-ohm atomizers for e-cig devices

Cell-specific toxicity of short-term JUUL aerosol exposure to human bronchial epithelial cells and murine macrophages exposed at the air-liquid interface

BACKGROUD: JUUL, an electronic nicotine delivery system (ENDS), which first appeared on the US market in 2015, controled more than 75% of the US ENDS sales in 2018. JUUL-type devices are currently the most commonly used form of ENDS among youth in the US. In contrast to free-base nicotine contained in cigarettes and other ENDS, JUUL contains high levels of nicotine salt (35 or 59 mg/mL), whose cellular and molecular effects on lung cells are largely unknown. In the present study, we evaluated the in vitro toxicity of JUUL crème brûlée-flavored aerosols on 2 types of human bronchial epithelial cell lines (BEAS-2B, H292) and a murine macrophage cell line (RAW 264.7). METHODS: Human lung epithelial cells and murine macrophages were exposed to JUUL crème brûlée-flavored aerosols at the air-liquid interface (ALI) for 1-h followed by a 24-h recovery period. Membrane integrity, cytotoxicity, extracellular release of nitrogen species and reactive oxygen species, cellular morphology and gene expression were assessed. RESULTS: Crème brûlée-flavored aerosol contained elevated concentrations of benzoic acid (86.9 μg/puff), a well-established respiratory irritant. In BEAS-2B cells, crème brûlée-flavored aerosol decreased cell viability (≥ 50%) and increased nitric oxide (NO) production (≥ 30%), as well as iNOS gene expression. Crème brûlée-flavored aerosol did not affect the viability of either H292 cells or RAW macrophages, but increased the production of reactive oxygen species (ROS) by ≥ 20% in both cell types. While crème brûlée-flavored aerosol did not alter NO levels in H292 cells, RAW macrophages exposed to crème brûlée-flavored aerosol displayed decreased NO (≥ 50%) and down-regulation of the iNOS gene, possibly due to increased ROS. Additionally, crème brûlée-flavored aerosol dysregulated the expression of several genes related to biotransformation, inflammation and airway remodeling, including CYP1A1, IL-6, and MMP12 in all 3 cell lines. CONCLUSION: Our results indicate that crème brûlée-flavored aerosol causes cell-specific toxicity to lung cells. This study contributes to providing scientific evidence towards regulation of nicotine salt-based products

Knowledge, Attitudes, and Practices towards COVID-19 among Pregnant Women in Northern Bangladesh: A Community-Based Cross-Sectional Study

Background: COVID-19, caused by SARS-CoV-2, remains a global public health concern despite the availability of effective antiviral treatment against multiple strains. Studies have shown that pregnant women are more susceptible to COVID-19 due to altered physiology and immunological features. Therefore, this study was designed to investigate pregnant women’s knowledge, attitudes, and practice (KAP) to prevent COVID-19 and determine the factors associated with KAP. Methods: A community-based cross-sectional study was conducted among 425 pregnant women in Northern Bangladesh. The samples were obtained using a simple random sampling technique from 5 April to 15 June 2020. The data were collected by face-to-face survey with a structured and pre-tested questionnaire and analyzed using SPSS version 25. Bivariable and multivariable logistic regression analyses were performed, and p-values < 0.05 at 95% CI were considered statistically significant. Results: Overall, the score of KAP among the respondents was 47.76%, 49.41%, and 56.24%, respectively. Participants’ area of residence, educational status of the husband, and antenatal care (ANC) visit were significantly associated with the level of knowledge, whereas age, educational status of the husband, number of living children, and knowledge were significant predictors of attitude. The knowledge of COVID-19 was the only predictor associated with the practice. Conclusion: Our study shows that almost half of the participants had poor knowledge, a negative attitude, and poor practices regarding COVID-19. Additional health education programs by healthcare professionals and different media, coordinated and combined efforts of government and individuals’ participation will be required to fight the spread of the infection

Protective effects of Moringa oleifera Lam. leaves against arsenic–induced toxicity in mice

Objective: To evaluate the protective role of leaves of Moringa oleifera (M. oleifera) Lam. against arsenic-induced toxicity in mice. Methods: Swiss albino male mice were divided into four groups. The first group was used as non-treated control group while, the second, third, and fourth groups were treated with M. oleifera leaves (50 mg/kg body weight per day), sodium arsenite (10 mg/kg body weight per day) and sodium arsenite plus M. oleifera leaves, respectively. Serum indices related to cardiac, liver and renal functions were analyzed to evaluate the protective effect of Moringa leaves on arsenic-induced effects in mice. Results: It revealed that food supplementation of M. oleifera leaves abrogated the arsenic-induced elevation of triglyceride, glucose, urea and the activities of alkaline phospatase, aspartate aminotransferase and alanine aminotransferase in serum. M. oleifera leaves also prevented the arsenic-induced perturbation of serum butyryl cholinesterase activity, total cholesterol and high density lipoprotein cholesterol. Conclusions: The results indicate that the leaves of M. oleifera may be useful in reducing the effects of arsenic-induced toxicity

In utero exposures to electronic-cigarette aerosols impair the signaling during mouse lung development

Currently, more than 9 million American adults, including women of childbearing age, use electronic-cigarettes (e-cigs). Further, the prevalence of maternal vaping now approaching 10% is similar to that of maternal smoking. Little, however, is known about the effects of fetal exposures to nicotine-rich e-cig aerosols on lung development. In this study, we assessed whether in utero exposures to e-cig aerosols compromised lung development in mice. A third-generation e-cig device was used to expose pregnant BALB/c mice by inhalation to 36 mg/mL of nicotine cinnamon-flavored e-cig aerosols for 14-31 days. This included exposures for either 12 days before mating plus during gestation (preconception groups) or only during gestation (prenatal groups). Respective control mice were exposed to filtered air. Subgroups of offspring were euthanized at birth or at 4 wk of age. Compared with respective air-exposed controls, both preconception and prenatal exposures to e-cig aerosols significantly decreased the offspring birth weight and body length. In the preconception group, 7 inflammation-related genes were downregulated, including 4 genes common to both dams and fetuses, denoting an e-cig immunosuppressive effect. Lung morphometry assessments of preconception e-cig-exposed offspring showed a significantly increased tissue fraction at birth. This result was supported by the downregulation of 75 lung genes involved in the signaling, which is essential to lung organogenesis. Thus, our data indicate that maternal vaping impairs pregnancy outcomes, alters fetal lung structure, and dysregulates the signaling. This study provides experimental evidence for future regulations of e-cig products for pregnant women and developmentally vulnerable populations

A multi-population-based genomic analysis uncovers unique haplotype variants and crucial mutant genes in SARS-CoV-2

Abstract Background COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rigorous detection and treatment strategies against SARS-CoV-2 have become very challenging due to continuous evolutions to the viral genome. Therefore, careful genomic analysis is sorely needed to understand transmission, the cellular mechanism of pathogenicity, and the development of vaccines or drugs. Objective In this study, we intended to identify SARS-CoV-2 genome variants that may help understand the cellular and molecular foundation of coronavirus infections required to develop effective intervention strategies. Methods SARS-CoV-2 genome sequences were downloaded from an open-source public database, processed, and analyzed for variants in target detection sites and genes. Results We have identified six unique variants, G---AAC, T---AAC---T, AAC---T, AAC--------T, C----------T, and C--------C, at the nucleocapsid region and eleven major hotspot mutant genes: nsp3, surface glycoprotein, nucleocapsid phosphoprotein, ORF8, nsp6, nsp2, nsp4, helicase, membrane glycoprotein, 3′-5′ exonuclease, and 2′-O-ribose methyltransferases. In addition, we have identified eleven major mutant genes that may have a crucial role in SARS-CoV-2 pathogenesis. Conclusion Studying haplotype variants and 11 major mutant genes to understand the mechanism of action of fatal pathogenicity and inter-individual variations in immune responses is inevitable for managing target patient groups with identified variants and developing effective anti-viral drugs and vaccines

Self-Medication Practices among Adult Population in Bangladesh: A Cross-Sectional Study

Background: The practice of self-medication (SM) is common worldwide and is an important component of medical self-care. However, improper practice can be dangerous. This study aimed to estimate the prevalence of SM and the factors associated with it among Bangladeshi adults. Methods: A cross-sectional survey was conducted between April and June 2021 among Bangladeshi adults (aged > 19 years) using convenient sampling. A total of 1320 subjects were collected through face-to-face interviews using a standardized questionnaire. Multivariable logistic regression analysis was used to identify factors associated with the practice of SM. Results: Overall, 41% of adults in our survey reported SMP. The most common illnesses that prompted SM were common cold/flu (66.4%), gastric problems (65%), and headache (64.4%). The most frequent reasons for SM were to get better-perceived quality of care (30.6%), perceiving SM without side effects (23.3%), and saving time with effectiveness (14.56%). Potential risk factors included 10 years (AOR = 1.91; 95% CI: 1.04–3.50) and >12 years of schooling (AOR = 5.03; 95% CI: 2.27–11.15), being a businessman (AOR = 4.64; 95% CI: 1.74–12.37), having ≤6 family members (AOR = 2.13; 95% CI: 1.40–3.24), being a member of a social group (AOR = 1.53; 95% CI: 1.10–2.12), a health status check after every six months (AOR = 1.52; 95% CI: 1.08–2.13), and current ill-health (AOR = 1.41; 95% CI: 1.06–1.87). Protective factors identified included ≤30 years of age (AOR = 0.40; 95% CI: 0.17–0.93), and practice of modern (AOR = 0.39; 95% CI: 0.22–0.69) and herbal (AOR = 0.45; 95% CI: 0.21–0.97) treatment modality. Conclusion: More than one-third of the study participants reported practicing SM. Increasing the community’s awareness of the adverse outcomes of SM and not just the average experience might sway individuals away from SM, and implementing strict jurisdiction could be a way to minimize inappropriate SM