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.

Prevalence and factors associated with depression, anxiety, and stress among people with disabilities during COVID-19 pandemic in Bangladesh: A cross-sectional study.

BACKGROUND: The COVID-19 pandemic has had a profound impact on the mental health of individuals across various populations. People with disabilities (PWDs) are particularly vulnerable to these effects, yet there is a lack of studies investigating the mental health of PWDs in Bangladesh. This study aims to investigate the prevalence of and factors associated with depression, anxiety, and stress among PWDs during the COVID-19 pandemic in Bangladesh. METHODS: Data was collected through interviews with 391 PWDs between December 2020 and February 2021. Demographic information, clinical characteristics, and scores from the Depression, Anxiety, and Stress Scale (DASS-21) were obtained. Chi-square tests and logistic regression analyses were conducted to examine the relationship between psychological measures and potential risk factors. RESULTS: The prevalence was found to be 65.7% for depression, 78.5% for anxiety, and 61.4% for stress, respectively. Several factors were identified as associated with these mental health issues, including gender (male), marital status (being married), low education levels, multiple impairments, comorbid medical illnesses, poor sleep quality, rural residency, hearing disability, disability onset later in life, and testing positive for COVID-19. CONCLUSIONS: The prevalence was found to be 65.7% for depression, 78.5% for anxiety, and 61.4% for stress, respectively. Several factors were identified as associated with these mental health issues, including gender (male), marital status (being married), low education levels, multiple impairments, comorbid medical illnesses, poor sleep quality, rural residency, hearing disability, disability onset later in life, and testing positive for COVID-19.

Prevalence, correlates and common conditions associated with adolescent dietary supplement use: a cross-sectional survey in Bangladesh.

OBJECTIVE: There is a broad spectrum of dietary supplements (DS) and their accessibility worldwide. However, little is known about the prevalence of DS use among Bangladeshi adolescents. This study estimates the prevalence, correlates and common conditions related to DS use. DESIGN: A cross-sectional, convenient sampling strategy was adopted using an interviewer-administered, structured questionnaire. SETTING: Kurigram and Patuakhali districts of Bangladesh. PARTICIPANTS: 702 adolescents aged 10-19 years. RESULTS: The overall prevalence of DS use was 83 %. The majority of participants (93·4 %) agreed that DS were good for health, and 28·3 % reported general health and well-being as the reason for using DS. The most frequently used supplements were multivitamins (38·6 %) and Ca (37 %). DS use was more common among adolescents who had ≤5 siblings, good health status, no chronic diseases, a positive impression that DS are good for health and who had the tendency to encourage DS to others. DS use was also higher among those who received DS information from healthcare providers, professional literature, friends, family and relatives. CONCLUSIONS: The prevalence of DS use is relatively higher among Bangladeshi adolescents compared to Bangladeshi adults and adolescents from other countries, highlighting the inclination towards DS use. Guidelines for safe DS use for adolescents are warranted to control DS use and prevent adverse effects.

Suicidal ideation among people with disabilities during the COVID-19 pandemic in Bangladesh: prevalence and associated factors.

BACKGROUND: Evidence from pandemic and pre-pandemic studies conducted globally indicates that people with disabilities (PWDs) have a higher risk for suicidality. However, none of these studies has assessed suicidality among PWDs in Bangladesh. AIMS: The purpose of this study was to determine the prevalence of and factors associated with suicidal ideation among PWDs during the COVID-19 pandemic in Bangladesh. METHOD: Using a snowball sampling technique, a cross-sectional survey was conducted from February to April 2021 among PWDs from six districts in the northern region of Bangladesh. Information related to sociodemographic factors, clinical characteristics, behavioural factors and suicidal ideation was collected. Chi-squared test and logistic regression were used to describe the data and explain the relationship of factors associated with suicidal ideation. RESULTS: The prevalence of COVID-19-related past-year suicidal ideation was 23.9%. The factors associated with suicidal ideation included: age above 35 years, being female, acquiring a disability later in life, lack of sleep and current substance use. In addition, higher education appeared to be a protective factor against suicidal ideation. CONCLUSIONS: This study highlighted that PWDs had an increased risk of suicide; that is, one-fourth of them had past-year suicidal ideation. This may have been because of COVID-19-related restrictions and stressors. Thus, the government and policy makers need to pay more attention to developing effective suicide assessment, treatment and management strategies, especially for at-risk groups, to minimise the impact of the COVID-19 outbreak.

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

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.

Trends and determinants of taking tetanus toxoid vaccine among women during last pregnancy in Bangladesh: Country representative survey from 2006 to 2019.

BACKGROUND: Tetanus occurring during pregnancy is still an important cause of maternal and neonatal mortality in developing countries. This study estimated the trend of tetanus toxoid (TT) immunization coverage from 2006 to 2019 in Bangladesh, considering socio-demographic, socio-economic, and geospatial characteristics. METHODS: The dataset used in this study was extracted from Multiple Indicator Cluster Surveys (2006, 2012-13, and 2019) including 28,734 women aged between 15-49 years. Data analysis was performed using cross-tabulation and logistic regression methods. Further, the spatial distribution of TT immunization coverage was also depicted. RESULTS: The trend of TT immunization (81.8% in 2006 to 49.3% in 2019) and that of taking adequate doses of TT (67.1% in 2006 to 49.9% in 2019) has gradually decreased throughout the study period. Among the administrative districts, North and South-West regions had lower coverage, and South and West regions had relatively higher coverage of both TT immunization and that of adequate doses. Antenatal TT immunization (any dosage, inadequate or adequate) was significantly associated with lower age (AOR = 3.13, 1.55-6.34), higher education (AOR = 1.20, 1.03-1.40), living in urban areas (AOR = 1.17, 1.03-1.34), having immunization card (AOR = 5.19, 4.50-5.98), using government facilities for birth (AOR = 1.41, 1.06-1.88), and receiving antenatal care (ANC) (AOR = 1.51, 1.35-1.69). In addition, living in urban areas (AOR = 1.31, 1.10-1.55), having immunization cards (AOR = 1.62, 1.36-1.92), and choosing others' homes for birth (AOR = 1.37, 1.07-1.74) were significantly associated with adequate TT immunization. However, higher education (AOR = 0.57, 0.44-0.74), having poor wealth index (AOR = 0.65, 0.50-0.83), and receiving ANC (AOR = 0.76, 0.63-0.92) had lower likelihood of taking adequate TT immunization. CONCLUSIONS: The gradual decline in the TT immunization rate in the present study suggests the presence of variable rates and unequal access to TT immunization, demanding more effective public health programs focusing on high-risk groups to ensure adequate TT immunization.

Sirtuin1 contributes to the overexpression of Giα proteins and hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats.

BACKGROUND: We earlier demonstrated that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit the overexpression of Giα proteins and hyperproliferation that is attributed to the enhanced levels of endogenous angiotensin II (Ang II). In addition, the implication of Sirtuin1 (Sirt1) a histone deacetylase class III family in Ang II-induced hypertension has also been shown. We recently demonstrated that Ang II increased the expression of Sirt1 in aortic VSMC that contributed to the overexpression of Giα proteins. However, whether Sirt1 is overexpressed in VSMC from SHR and is linked to the enhanced expression of Giα proteins and hyperproliferation remains unexplored. METHOD AND RESULTS: In the present study, we show that Sirt1 is upregulated in VSMC from SHR and this upregulation was attenuated by AT1 receptor antagonist losartan. In addition, the inhibition or knockdown of Sirt1 by specific inhibitors EX 527 and NAM and/or siRNA attenuated the enhanced expression of Giα proteins, cell cycle proteins and hyperproliferation of VSMC from SHR. Furthermore, the enhanced levels of reactive oxygen species (ROS), hydrogen peroxide and NADPH oxidase subunits NOX2 and p47phox, increased phosphorylation of EGFR, ERK1/2 and AKT displayed by VSMC from SHR were also attenuated by knocking down of Sirt1 by siRNA. CONCLUSION: In summary, our results demonstrate that Sirt1 is overexpressed in VSMC from SHR which through augmenting oxidative stress contributes to the enhanced expression of Giα proteins, cell cycle proteins and resultant hyperproliferation of VSMC.

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.

Prevalence and factors associated with family planning during COVID-19 pandemic in Bangladesh: A cross-sectional study.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic has negatively impacted health systems worldwide, including in Bangladesh, limiting access to family planning information (FP) and services. Unfortunately, the evidence on the factors linked to such disruption is limited, and no study has addressed the link among Bangladeshis. This study aimed to examine the socioeconomic, demographic, and other critical factors linked to the use of FP in the studied areas during the COVID-19 pandemic. METHODS: The characteristics of the respondents were assessed using a cross-sectional questionnaire survey and descriptive statistics. The variables that were substantially linked with FP usage were identified using a Chi-square test. In addition, a multivariate logistic regression model was used to identify the parameters linked to FP in the study areas during the COVID-19 pandemic. RESULTS: The prevalence of FP use among currently married 15-49 years aged women was 36.03% suggesting a 23% (approximately) decrease compared to before pandemic data. Results also showed that 24.42% of the respondents were using oral contraceptive pills (OCP) which is lower than before pandemic data (61.7%). Multivariate regression analysis provided broader insight into the factors affecting FP use. Results showed that woman's age, education level of the respondents, working status of the household head, locality, reading a newspaper, FP workers' advice, currently using OCP, ever used OCP, husbands' supportive attitude towards OCP use, duration of the marriage, ever pregnant, the number of children and dead child were significantly associated with FP use in the study areas during COVID-19 pandemic. CONCLUSIONS: This study discusses unobserved factors that contributed to a reduction in FP use and identifies impediments to FP use in Bangladesh during the COVID-19 epidemic. This research further adds to our understanding of FP usage by revealing the scope of the COVID-19 pandemic's impact on FP use in Bangladesh's rural and urban areas.

Angiotensin II-induced overexpression of sirtuin 1 contributes to enhanced expression of Giα proteins and hyperproliferation of vascular smooth muscle cells.

Angiotensin II (ANG II) plays an important role in the regulation of various physiological functions including proliferation, hypertrophy of vascular smooth muscle cells (VSMCs) through the overexpression of Giα proteins. Sirtuin 1 (Sirt1), a class III histone deacetylase and epigenetic regulator is implicated in a wide range of cellular functions, including migration and growth of VSMCs and in ANG II-induced hypertension. The present study was undertaken to examine the role of Sirt1 in ANG II-induced overexpression of Giα proteins and hyperproliferation of aortic VSMCs. We show that ANG II treatment of VSMCs increased the expression of Sirt1, which was attenuated by AT1 and AT2 receptor antagonists, losartan, and PD123319, respectively. In addition, the knockdown of Sirt1 by siRNA attenuated ANG II-induced overexpression of Giα-2 and Giα-3 proteins, hyperproliferation of VSMCs and the overexpression of cell cycle proteins, cyclin D1, Cdk4, and phosphorylated retinoblastoma proteins. Furthermore, ANG II-induced increased levels of superoxide anion (O2-) and NADPH oxidase activity and increased phosphorylation of ERK1/2 and Akt that are implicated in enhanced expression of Giα proteins and hyperproliferation of VSMCs were also attenuated to control levels by silencing of Sirt1. In addition, depletion of Sirt1 by siRNA also attenuated ANG II-induced enhanced phosphorylation of platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), and insulin-like growth factor receptor (IGFR) in VSMCs. In summary, our results demonstrate that ANG II increased the expression of Sirt1, which through oxidative stress, growth factor receptor-mediated mitogen-activated protein (MAP) kinase/Akt signaling pathway enhances the expression of Giα proteins and cell cycle proteins and results in the hyperproliferation of VSMCs.NEW & NOTEWORTHY ANG II regulates various physiological functions including proliferation of VSMCs through the overexpression of Giα proteins. Sirt1, a class III histone deacetylase, is implicated in several cellular functions, including VSMC growth and ANG II-induced hypertension. We showed for the first time that ANG II increased the expression of Sirt1, which through oxidative stress, growth factor receptor-mediated MAP kinase/Akt signaling pathway enhances the levels of Giα and cell cycle proteins resulting in the hyperproliferation of VSMCs.

Role of the JAK2/STAT3 pathway in angiotensin II-induced enhanced expression of Giα proteins and hyperproliferation of aortic vascular smooth muscle cells.

We earlier showed that angiotensin (Ang) II-induced overexpression of Giα proteins contributes to the hyperproliferation of vascular smooth muscle cells (VSMC). In addition, the implication of the JAK2/STAT3 pathway in Ang II-induced hyperproliferation of VSMC has also been reported. However, the role of the JAK2/STAT3 pathway in Ang II-induced overexpression of Giα proteins and hyperproliferation of VSMC remains unexplored. In the present study, we show that inhibition or knockdown of the JAK2/STAT3 pathway by a specific inhibitor "cucurbitacin I" (CuI) or siRNAs attenuated Ang II-induced overexpression of Giα proteins and hyperproliferation of VSMC. In addition, the enhanced expression of cell cycle proteins induced by Ang II was also attenuated by CuI. Furthermore, Ang II-induced enhanced production of the superoxide anion (O2 -), H2O2, and NADPH oxidase activity, as well as the enhanced expression of NADPH oxidase subunits implicated in enhanced expression of Giα proteins and hyperproliferation, were also attenuated by inhibition of the JAK2/STAT3 pathway. On the other hand, Ang II-induced inhibition and augmentation of the levels of nitric oxide and peroxynitrite, respectively, in VSMC were restored to control levels by CuI. In summary, our results demonstrate that Ang II through the JAK2/STAT3 pathway increases nitroxidative stress, which contributes to the overexpression of Giα proteins and cell cycle proteins and the hyperproliferation of VSMC.

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 'sub-ohm' conditions (< 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 > 1 Ω and voltage > 4.5 V), contains lower carbonyl levels (< 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 'sub-ohm' 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 'sub-ohm' 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.

In utero exposures to electronic-cigarette aerosols impair the Wnt 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 Wnt signaling, which is essential to lung organogenesis. Thus, our data indicate that maternal vaping impairs pregnancy outcomes, alters fetal lung structure, and dysregulates the Wnt signaling. This study provides experimental evidence for future regulations of e-cig products for pregnant women and developmentally vulnerable populations.

Sodium nitroprusside attenuates hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats through the inhibition of overexpression of AT1 receptor, cell cycle proteins, and c-Src/growth factor receptor signaling pathways.

We recently showed that sodium nitroprusside (SNP), a NO donor, attenuated hypertension in spontaneously hypertensive rats (SHR). Since hypertension is associated with enhanced proliferation and hypertrophy of vascular smooth muscle cells (VSMC), the present study examines whether in vivo treatment of SHR with SNP could also inhibit the augmented proliferation of VSMC and explore the signaling mechanisms. Treatment of 8 week old SHR and Wistar Kyoto rats with SNP twice a week for 2 weeks inhibited the enhanced proliferation of VSMC from SHR, the enhanced expression of angiotensin II type 1 (AT1) receptor, and enhanced activation of c-Src and growth factor receptors and ERK1/2 signaling pathways. In addition, SNP also inhibited the overexpression of cell cycle proteins including cyclins D1, Cdk4, and phosphorylated pRB and restored the downregulated Cdk inhibitors p21Cip1 and p27Kip1 expression towards control levels. Furthermore, SNP-induced inhibition of enhanced levels of the AT1 receptor and enhanced proliferation was reversed by L-NAME, an inhibitor of nitric oxide synthase. These results suggest that the SNP-induced antiproliferative effect may be mediated through the inhibition of enhanced expression of the AT1 receptor, cell cycle proteins and activation of c-Src, growth factor receptors, and MAP kinase signaling.

Inhibition of overexpression of Giα proteins and nitroxidative stress contribute to sodium nitroprusside-induced attenuation of high blood pressure in SHR.

We earlier showed that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit enhanced expression of Giα proteins which was attributed to the decreased levels of nitric oxide (NO), because elevation of the intracellular levels of NO by NO donors; sodium nitroprusside (SNP) and S-Nitroso-N-acetyl-DL-penicillamine (SNAP), attenuated the enhanced expression of Giα proteins. Since the enhanced expression of Giα proteins is implicated in the pathogenesis of hypertension, the present study was undertaken to investigate if treatment of SHR with SNP could also attenuate the development of high blood pressure (BP) and explore the underlying molecular mechanisms. Intraperitoneal injection of SNP at a concentration of 0.5 mg/kg body weight twice a week for 2 weeks into SHR attenuated the high blood pressure by about 80 mmHg without affecting the BP in WKY rats. SNP treatment also attenuated the enhanced levels of superoxide anion (O2- ), hydrogen peroxide (H2 O2 ), peroxynitrite (ONOO- ), and NADPH oxidase activity in VSMC from SHR to control levels. In addition, the overexpression of different subunits of NADPH oxidase; Nox-1, Nox-2, Nox-4, P22phox , and P47phox , and Giα proteins in VSMC from SHR were also attenuated by SNP treatment. On the other hand, SNP treatment augmented the decreased levels of intracellular NO, eNOS, and cGMP in VSMC from SHR. These results suggest that SNP treatment attenuates the development of high BP in SHR through the elevation of intracellular levels of cGMP and inhibition of the enhanced levels of Giα proteins and nitroxidative stress.

Natriuretic peptide receptor-C activation attenuates angiotensin II-induced enhanced oxidative stress and hyperproliferation of aortic vascular smooth muscle cells.

We showed previously that natriuretic peptide receptor-C (NPR-C) agonist, C-ANP4-23, attenuated the enhanced expression of Giα proteins in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) through the inhibition of enhanced oxidative stress. Since the enhanced levels of endogenous angiotensin II (Ang II) contribute to the overexpression of Giα proteins and augmented oxidative stress in VSMC from SHR, the present study was undertaken to investigate if C-ANP4-23 could also attenuate angiotensin II (Ang II)-induced oxidative stress and associated signaling. Ang II treatment of aortic VSMC augmented the levels of superoxide anion (O2-), NADPH oxidase activity, and the expression of NADPH oxidase subunits and C-ANP4-23 treatment attenuated all these to control levels. In addition, Ang II-induced enhanced levels of thiobarbituric acid-reactive substances (TBARS) and protein carbonyl content were also attenuated toward control levels by C-ANP4-23 treatment. On the other hand, Ang II inhibited the levels of nitric oxide (NO) and augmented the levels of peroxynitrite (OONO-) in VSMC which were restored to control levels by C-ANP4-23 treatment. Furthermore, C-ANP4-23 treatment attenuated Ang II-induced enhanced expression of Giα proteins, phosphorylation of p38, JNK, and ERK 1,2 as well as hyperproliferation of VSMC as determined by DNA synthesis, and metabolic activity. These results indicate that C-ANP4-23, via the activation of NPR-C, attenuates Ang II-induced enhanced nitroxidative stress, overexpression of Giα proteins, increased activation of the p38/JNK/ERK 1,2 signaling pathways, and hyperproliferation of VSMC. It may be suggested that C-ANP4-23 could be used as a therapeutic agent in the treatment of vascular remodeling associated with hypertension and atherosclerosis.

Resveratrol attenuates hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats: Role of ROS and ROS-mediated cell signaling.

Resveratrol, a natural polyphenolic compound has been reported to attenuate angiotensin II -induced vascular smooth muscle cell (VSMC) hypertrophy; however, whether resveratrol could also inhibit hyperproliferation of VSMC from spontaneously hypertensive rats (SHR) is unexplored. The present study investigates the effect of resveratrol on hyperproliferation of VSMC from SHR and the underlying molecular mechanisms responsible for this response. For these studies, aortic VSMC from SHR and Wistar-Kyoto (WKY) rats were used. The proliferation of VSMC was determined by [3H] thymidine incorporation and the levels of proteins were determined by Western blotting. The enhanced proliferation exhibited by VSMC from SHR was attenuated by resveratrol. In addition, resveratrol attenuated the overexpression of cyclin D1, cyclin E, cyclin dependent kinase 4 (Cdk4), Cdk2, phosphorylated retinoblastoma protein (pRb), Giα proteins and enhanced phosphorylation of ERK1/2 and AKT in VSMC from SHR. Furthermore, the overproduction of superoxide anion, increased NADPH oxidase activity, overexpression of Nox2, Nox4 and p47phox proteins, increased phosphorylation of EGFR, IGF-IR, and c-Src were all abrogated by resveratrol. These results suggest that resveratrol attenuates the hyperproliferation of VSMC from SHR through the inhibition of ROS, c-Src, growth factor receptor activation, MAPK/PI3K, Giα and cell cycle proteins that are implicated in VSMC hyperproliferation.

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

We previously showed that augmented levels of endogenous angiotensin II (AngII) 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 AngII-evoked VSMC hypertrophy; however, the molecular mechanism mediating this response is obscure. The present study was therefore undertaken to examine whether RV could prevent AngII-induced VSMC hypertrophy through the transactivation of growth factor receptor and associated signaling pathways. AngII treatment of VSMC enhanced the protein synthesis that was attenuated towards control levels by RV pretreatment as well as by the inhibitors of NADPH oxidase, c-Src, and growth factor receptors. Furthermore, RV pretreatment also inhibited enhanced levels of superoxide anion, NADPH oxidase activity, 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 AngII-induced VSMC hypertrophy through the inhibition of enhanced oxidative stress and activation of c-Src, growth factor receptors, and MAPK/AKT signaling. We suggest that RV could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension and hypertrophy.

High-resolution 400K oligonucleotide array comparative genomic hybridization analysis of neurofibromatosis type 1-associated cutaneous neurofibromas.

Neurofibromatosis type 1 (NF1) is a genetic disorder where affected individuals develop benign or malignant nervous system tumors. To date, NF1 is caused by mutations in the NF1 tumor suppressor gene located at chromosome band 17q11.2. In this study, we aimed to characterize novel recurrent regional chromosomal imbalances and tumor-related candidate genes in NF1-associated cutaneous neurofibromas. Nine cutaneous neurofibromas from NF1 patients were screened for recurrent chromosomal imbalances using high-resolution 400K oligonucleotide array comparative genomic hybridization (aCGH). All the cases exhibited at least one sub-microscopic abnormality. Regions of recurrent chromosomal imbalances in a least one third of cases were loss of 1q13.2 (33%, FAM19A3), 1q21.1 (44%, RABGAP1L), 2q37.1 (56%, INPP5D), 3p25.1 (67%, CHCHD4), 4p15.32 (56%, FGFBP1), 5q11.2 (56%, ARL15), 6q22.31 (56%, NKAIN2), 6q22.33 (67%, ARHGAP18), 6q25.1 (67%, UST), 7q13 (56%, ADCY1), 12q13.13 (44%, KRT71), 19q13.32 (56%, GRLF1), and 20p11.21 (56%, NLP) and gain of 2p23.3 (76%, C2orf53), 8q22.3 (44%, ODF1) and 8q24.3 (67%, ARC). Several chromosomal imbalances, including loss of 7q11.23, 13q14.1, 14q32.13, 17p12, and 17q11.2 were detected at a lower frequency. We also confirmed that these chromosomal imbalances were not detected in the patient-matched lymphocyte DNAs. Amongst the 6 tumor-related candidate genes (RABGAP1L, ADCY1, SLIT2, GRLF1, UST, and ARC) identified in the regions of recurrent chromosomal imbalances, the gene expression changes of UST (down-regulation) and ARC (up-regulation) were found to be significantly associated with copy number alterations. The novel recurrent chromosomal imbalances and the altered expression levels of the tumor-related candidate genes may be associated with the development of NF1-associated benign cutaneous neurofibromas.