Morinda citrifolia noni water extract enhances innate and adaptive immune responses in healthy mice,ex vivo,and in vitro

Although Morinda citrifolia (noni) has long been used in traditional medicines for human diseases, its molecular and cellular mechanism of immunostimulatory ability to improve human health under normal healthy conditions is not fully elucidated. This study aimed to investigate the in vitro and in vivo immunostimulatory activity of M. citrifolia fruit water extract treated with enzymes (Mc‐eWE). In vitro studies revealed that Mc‐eWE stimulated the cells by inducing nitric oxide (NO) production and the expression of inflammatory cytokines, such as interleukin (IL)‐1β, IL‐6, IL‐12, tumor necrosis factor‐alpha (TNF‐α), and interferon‐gamma (IFN‐γ). The immunostimulatory activity was mediated by activation of NF‐κB and AP‐1. Ex vivo studies showed that Mc‐eWE stimulated splenocytes isolated from mice by inducing NO production and expression of immunostimulatory cytokines and by downregulating the expression of the immunosuppressive cytokine IL‐10 without cytotoxicity. In vivo demonstrated that Mc‐eWE induced immunostimulation by modulating populations of splenic immune cells, especially by increasing the population of IFN‐γ⁺ NK cells. Mc‐eWE enhanced the expression of inflammatory genes and immunostimulatory cytokines and inhibited the expression of IL‐10 in the mouse splenocytes and sera. Taken together, these results suggest that Mc‐eWE plays an immunostimulatory role by activating innate and adaptive immune responses.     

Delivery of Small Interfering RNA to Inhibit Vascular Endothelial Growth Factor in Zebrafish Using Natural Brain Endothelia Cell-Secreted Exosome Nanovesicles for the Treatment of Brain Cancer

Although small interfering RNA (siRNA) holds great therapeutic promise, its delivery to the disease site remains a paramount obstacle. In this study, we tested whether brain endothelial cell-derived exosomes could deliver siRNA across the blood–brain barrier (BBB) in zebrafish. Natural exosomes were isolated from brain endothelial bEND.3 cell culture media and vascular endothelial growth factor (VEGF) siRNA was loaded in exosomes with the assistance of a transfection reagent. While fluorescence-activated cell flow cytometry and immunocytochemistry staining studies indicated that wild-type exosomes significantly increased the uptake of fluorescence-labeled siRNA in the autologous brain endothelial cells, decreased fluorescence intensity was observed in the cells treated with the tetraspanin CD63 antibody-blocked exosome-delivered formulation (p?<?0.05). In the transport study, exosomes also enhanced the permeability of rhodamine 123 in a co-cultured monolayer of brain endothelial bEND.3 cell and astrocyte. Inhibition at the expression of VEGF RNA and protein levels was observed in glioblastoma-astrocytoma U-87 MG cells treated with exosome-delivered siRNAs. Imaging results showed that exosome delivered more siRNAs across the BBB in Tg(fli1:GFP) zebrafish. In a xenotransplanted brain tumor model, exosome-delivered VEGF siRNAs decreased the fluorescence intensity of labeled cancer cells in the brain of zebrafish. Brain endothelial cell-derived exosomes could be potentially used as a natural carrier for the brain delivery of exogenous siRNA.     

A Longitudinal Survey for Genome-based Identification of SARS-CoV-2 in Sewage Water in Selected Lockdown Areas of Lahore City,Pakistan: A Potential Approach for Future Smart Lockdown Strategy

In 2019, the newly emerged SARS-CoV-2 virus caused pneumonia-like illness. The disease rapidly spread globally, leading to a worldwide outbreak referred to as the COVID-19 pandemic. The affected patients show symptoms of fever, dry cough, respiratory distress, myalgia, and gastrointestinal disturbance. As of April 5, 2021, 132,083,022 people worldwide were affected by COVID-19, while 2,868,454 people died due to the disease[1]. SARS-CoV-2-positive patients may remain asymptomatic or start showing symptoms in 2?14 days after exposure to the virus[2]. The viral infection can be diagnosed from nasopharyngeal, throat, alveolar lavage, lacrimal, blood, and stool samples. The patient starts shedding the virus in stool regardless of being symptomatic or asymptomatic, which makes sewage-based detection of the virus to be more beneficial in the early infection stage.     

High prevalence of the cardiovascular risk factors in Al-Ain, United Arab Emirates. An emerging health care priority

OBJECTIVE: In the United Arab Emirates (UAE) cardiovascular mortality is a leading cause of death. Yet, there is a dearth of data on its risk factors. METHODS: A cross-sectional community based study on established cardiovascular risk factors carried out between February 2004 - February 2005 in Al-Ain City, UAE. Subjects were interviewed, blood pressure, weight, height, fasting blood sugar, and lipid profile measured. Framingham risk scores were used for risk assessment. RESULTS: Eight hundred seventeen subjects (403 males and 414 females) completed the survey, of these 28.4% had a Framingham risk assessment score of more than 20%, 23.3% had diabetes mellitus, 20.8% hypertension, 37.3% obesity, 22.7% metabolic syndrome, and 19.6% of male smoked. Coronary heart disease was reported in 2.4%. Lipid profiles were abnormal in 64% of the males, and in 53.9% of the females, mostly due to low high-density lipoproteins or high triglycerides levels. CONCLUSION: The overall cardiovascular risk assessment of the population screened calls for targeted interventions.     

Protective effect of palm vitamin E and α-tocopherol against gastric lesions induced by water immersion restraint stress in Sprague-Dawley rats

Objective:

Stress can lead to various changes in the gastrointestinal tract of rats. The present study was designed to compare the effect of palm vitamin E (PVE) and α-tocopherol (α-TF) supplementations on the gastric parameters important in maintaining gastric mucosal integrity in rats exposed to water immersion restraint stress (WRS). These parameters include gastric acidity, plasma gastrin level, gastric prostaglandin E₂ (PGE₂), and gastric lesions.

Materials and Methods:

Sixty male Sprague-Dawley rats (200-250 g) were divided into three equal groups: a control group, which received a normal rat diet (RC), and two treatment groups, receiving oral supplementation of either PVE or α-TF at 60 mg/kg body weight for 28 days. Each group was further divided into two groups: the nonstress and stress groups. The stress groups were subjected to 3.5 h of WRS once at the end of the treatment period. Blood samples were then taken to measure the gastrin level, after which the rats were killed. Gastric juice was collected for measurement of gastric acidity and gastric tissue was taken for measurement of gastric mucosal lesions and PGE₂.

Results:

Exposure to stress resulted in the production of gastric lesions. PVE and α-TF lowered the lesion indices as compared to the stress control group. Stress reduced gastric acidity but pretreatment with PVE and α-TF prevented this reduction. The gastrin levels in the stress group were lower as compared to that in the nonstress control. However, following treatment with PVE and α-TF, gastrin levels increased and approached the normal level. There was also a significant reduction in the gastric PGE₂ content with stress exposure, but this reduction was blocked with treatment with both PVE and α-TF.

Conclusion:

In conclusion, WRS leads to a reduction in the gastric acidity, gastrin level, and gastric PGE₂ level and there is increased formation of gastric lesions. Supplementation with either PVE or α-TF reduces the formation of gastric lesions, possibly by blocking the changes in the gastric acidity, gastrin, and gastric PGE₂ induced by stress. No significant difference between PVE and α-TF was observed.     

Association between social capital,health-related quality of life,and mental health: a structural-equation modeling approach

AimTo explore the association(s) between demographic factors, socioeconomic status (SES), social capital, health-related quality of life (HRQoL), and mental health among residents of Tehran, Iran.MethodsThe pooled data (n = 31 519) were extracted from a population-based survey Urban Health Equity Assessment and Response Tool-2 (Urban HEART-2) conducted in Tehran in 2011. Mental health, social capital, and HRQoL were assessed using the 28-item General Health Questionnaire (GHQ-28), social capital questionnaire, and Short-Form Health Survey (SF-12), respectively. The study used a multistage sampling method. Social capital, HRQoL, and SES were considered as latent variables. The association between these latent variables, demographic factors, and mental health was determined by structural-equation modeling (SEM).ResultsThe mean age and mental health score were 44.48 ± 15.87 years and 23.33 ± 11.10 (range, 0-84), respectively. The prevalence of mental disorders was 41.76% (95% confidence interval 41.21-42.30). The SEM model showed that age was directly associated with social capital (P = 0.016) and mental health (P = 0.001). Sex was indirectly related to mental health through social capital (P = 0.018). SES, HRQoL, and social capital were associated both directly and indirectly with mental health status.ConclusionThis study suggests that changes in social capital and SES can lead to positive changes in mental health status and that individual and contextual determinants influence HRQoL and mental health.Mental health is defined by World Health Organization (WHO) as “a state of well-being in which every individual realizes his/her own potential, can cope with the normal pressures of life, can work productively, and is able to make a contribution to his/her community” (1,2). Mental health and associated disorders have received increasing attention worldwide, largely due to their impact on socio-economic and overall health status of patients (3). Mental health problems remain a global concern, and account for a large fraction of diseases (4,5).The overall prevalence of mental disorders in Iran between 2000 and 2008 ranged from 12.5% to 38.9% and was similar in urban (20.9%) and rural areas (21.3%) (6). Anxiety and depression were more prevalent than somatization and social dysfunction (7). The provinces with the highest prevalence of mental problems were Chaharmahal with 38.3% and Golestan with 37.3% (8).Mental health is usually determined by a complex interaction of sociocultural, psychological, environmental, and demographic factors (9). The prevalence of mental health disorders is significantly associated with age, marital status, educational level, employment, and health-related to quality of life (HRQoL) (10). HRQoL incorporates physical and socio-emotional functioning and is used to measure individual''s perception of health status, welfare, and well-being in a society (11). A frequently used psychometrical tool for the assessment of HRQoL is Short-Form Health Survey (SF-12). Its two main components are physical component summary (PCS) and mental component summary (MCS), both of which are associated with mental health (12). Previous studies have confirmed a bidirectional association between physical health and depression (as one of the main dimensions of mental health) (13). However, it is not clear whether there is a causal relationship between them (13,14).The suggested mechanisms by which depression could lead to physical disability and decreased HRQoL are poor health behaviors, increased risk of physical disease, and characteristics of depression (eg, decreased pain threshold) (15). On the other hand, physical disability can lead to depression and deterioration of mental health due to restriction of social activities and loss of social capital (15). Ultimately, this bilateral association between depression and poor physical health can lead to increasing health risks (14).Mental disorders such as depression and anxiety are also influenced by socioeconomic status (SES) (16). SES is commonly conceptualized as an individual or group’s relative social standing or class (16,17). The main predictors of SES are education level, income, and occupation (15,17,18). The correlations between SES and mental health have been explained by various mechanisms. It has been found that negative impact of low SES on mental health (19) can be reduced by the mediating effect of social capital and physical health (4,18).Social capital has been defined as individual’s social networks and social interactions, shared norms, values, and understandings that facilitate collective action within or among groups. It can act as a protective factor, promoting mental health status by reducing socioeconomic inequalities (4,20) and play an important role in reducing the prevalence of mental disorders (4). Previous studies have found that social ties and support significantly improve mental health (9). Nonetheless, the association between social capital, mental health, quality of life, and SES is not consistently reported (21,22). This population-based study aims to explore the association between demographic factors, SES, social capital, HRQoL, and mental health among Tehran residents using structural-equation modeling (SEM).     

Collagen-chitosan 3-D nano-scaffolds effects on macrophage phagocytosis and pro-inflammatory cytokine release

Macrophages are effector cells in the innate and adaptive immune systems and in situ exist within three-dimensional (3-D) microenvironments. As there has been an increase in interest in the use of 3-D scaffolds to mimic natural microenvironments in vitro, this study examined the impact on cultured mice peritoneal macrophages using standard 2-D plates as compared to 3-D collagen-chitosan scaffolds. Here, 2-D and 3-D cultured macrophages were evaluated for responses to lipopolysaccharide (LPS), dexamethasone (Dex), BSA (bovine serum albumin), safranal (herbal component isolated from safranal [Saf]) and Alyssum homolocarpum mucilage (A. muc: mixed herbal components). After treatments, cultured macrophages were evaluated for viability, phagocytic activity and release of tumor necrosis factor (TNF)-α and interleukin (IL)-1β pro-inflammatory cytokines. Comparison of 2-D vs 3-D cultures showed that use of either system – with or without any exogenous agent – had no effect on cell viability. In the case of cell function, macrophages cultured on scaffolds had increases in phagocytic activity relative to that by cells on 2-D plates. In general, the test herbal components Saf and A. muc. had more impact than any of the other exogenous agents on nanoparticle uptake. With respect to production of TNFα and IL-1β, compared to the 2-D cells, scaffold cells tended to have significantly different levels of production of each cytokine, with the effect varying (higher or lower) depending on the test agent used. However, unlike with particle uptake, here, while Saf and A. muc. led to significantly greater levels of cytokine formation by the 3-D culture cells vs that by the 2-D plate cells, there was no net effect (stimulatory) vs control cultures. These results illustrated that collagen-chitosan scaffolds could provide a suitable 3-D microenvironment for macrophage phagocytosis and could also impact on the formation of pro-inflammatory cytokines.