Elevated Hepcidin Expression in Human Carotid Atheroma: Sex-Specific Differences and Associations with Plaque Vulnerability.

Hepcidin is upregulated by increased body iron stores and inflammatory cytokines. It is associated with cardiovascular events, arterial stiffness, and increased iron accumulation in human atheroma with hemorrhage. However, it is unknown whether the expression of hepcidin in human carotid plaques is related to plaque severity and whether hepcidin expression differs between men and women. Carotid samples from 58 patients (38 males and 20 females) were immunostained with hepcidin, macrophages, ferritin, and transferrin receptor. Immunocytochemistry of hepcidin was performed on THP-1 macrophages exposed to iron or 7betahydroxycholesterol. Hepcidin expression significantly increases with the progression of human atherosclerotic plaques. Plaques of male patients have significantly higher levels of hepcidin. Expressions of hepcidin are significantly correlated with the accumulation of CD68-positive macrophages and transferrin receptor 1 (TfR1) and apoptosis. In vitro, hepcidin is significantly increased in macrophages exposed to iron and moderately increased following 7-oxysterol treatment. In the cultured cells, suppression of hepcidin protected against macrophage cell death, lysosomal membrane permeabilization, and oxidative stress. Hepcidin may play a crucial role in the development and progression of atherosclerosis. The differential expression of hepcidin in male and female patients and its significant correlations with plaque severity, highlight the potential of hepcidin as a biomarker for risk stratification and therapeutic targeting in atherosclerosis.

Imidacloprid Induces Lysosomal Dysfunction and Cell Death in Human Astrocytes and Fibroblasts-Environmental Implication of a Clinical Case Report.

Imidacloprid (IMI), a neonicotinoid insecticide, has potential cytotoxic and genotoxic effects on human and experimental models, respectively. While being an emerging environmental contaminant, occupational exposure and related cellular mechanisms are unknown. Herein, we were motivated by a specific patient case where occupational exposure to an IMI-containing plant protection product was associated with the diagnosis of Bell's palsy. The aim was to investigate the toxic effects and cellular mechanisms of IMI exposure on glial cells (D384 human astrocytes) and on human fibroblasts (AG01518). IMI-treated astrocytes showed a reduction in cell number and dose-dependent cytotoxicity at 24 h. Lower doses of IMI induced reactive oxygen species (ROS) and lysosomal membrane permeabilisation (LMP), causing apoptosis and autophagic dysfunction, while high doses caused significant necrotic cell death. Using normal fibroblasts, we found that IMI-induced autophagic dysfunction and lysosomal damage, activated lysophagy, and resulted in a compensatory increase in lysosomes. In conclusion, the observed IMI-induced effects on human glial cells and fibroblasts provide a possible link between IMI cytotoxicity and neurological complications observed clinically in the patient exposed to this neonicotinoid insecticide.

Acidification scenario of Cox's Bazar coast of the Bay of Bengal, Bangladesh and its influence on fish larvae abundance.

Ocean acidification is caused mainly by atmospheric carbon dioxide stored in the ocean. Ocean acidification is considered a major threat to aquatic life, and how it influences the abundance of marine fish larvae is still unclear. This research was designed to measure the current ocean acidification scenario of the Cox's Bazar coast of the Bay of Bengal, Bangladesh, and its probable influence on the abundance of fish larvae. Three research stations were selected: Bakkhali river estuary, Naf river estuary, and Rezu Khal. Monthly sampling was done, and larvae sample was collected from the surface water column (depth: 0.5 m) using a bongo net. Water parameters such as temperature, salinity, total alkalinity, and pH were determined using laboratory protocol. The seacarb package of the R programming language was used to determine ocean acidification factors. The Bakkhali river estuary showed the highest partial carbon dioxide (143.99 ± 102.27 µatm) and the lowest pH (8.27 ± 0.21). A total of 19 larvae families were identified, and the highest larval count was found in Rezu Khal (390 larvae/1000 m3), while the lowest was found in the Bakkhali river (3 larvae/1000 m3). Clupeidae, Myctophidae, and Engraulidae comprised more than 50% of the identified larvae. Blenniidae, Carangidae, Clupeidae, Engraulidae, and Gobiidae were found in all three seasons. Most of the larvae families showed the highest mean abundance under less pCO2. A negative correlation was observed between larvae and acidification factors such as pCO2, HCO3-, and dissolved inorganic carbon (DIC). The study revealed that acidification parameters of the Cox's Bazar coast were not in an acute state for the aquatic organisms' survival, but fish larvae abundance could be declined with raises in the partial carbon dioxide. The results of this study may aid in developing a management plan for conserving Bangladesh's marine and coastal fish.

Toxicological effect of sumithion pesticide on the hematological parameters and its recovery pattern using probiotic in Barbonymus gonionotus.

The experiment was conducted to clarify sumithion induced hematoxicity in silver barb (Barbonymus gonionotus) through in vivo exposures (25 % and 50 % of LC50 of sumithion) and subsequent recovery patterns using normal and probiotic treated feed were also assessed. Three treatments each incorporating three replications were used in the experiment for different days (1, 7, 14, 21, and 28). Treatment T1 was control (0 mg/L), and two concentrations, such as 2.61 mg/L (25 % of 96 h LC50), 5.21 mg/L (50 % of 96 h LC50) were used as Treatment T2 and T3, respectively. After 28 days of exposure to pesticide half of the fishes of T2 and T3 were reared in sumithion free water with normal (T2N, T3N) and probiotic treated feed (T2P, T3P). The median lethal concentration (50 %) for 96 h was 10.42 mg/L. In pesticide-treated groups, values of each hematological parameter (blood glucose, red blood cell, hematocrit, and hemoglobin) decreased but prevalence and severity of micronucleus and white blood cells increased significantly (p< 0.05) with concentration and time duration. Other blood indices including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were correspondingly changed in comparison to the control. In the recovery experiment, the silver barb recovered spontaneously, but the recovery rate was significantly higher in probiotic treated groups than normally treated groups in time and duration reliant fashion. In conclusion, persistent sublethal dosages of sumithion caused hematological abnormalities in silver barb. Probiotic supplement can recover the damage but only 28 days of recovery is not enough to recover the total alterations.

CD74 in Apoptotic Macrophages Is Associated with Inflammation, Plaque Progression and Clinical Manifestations in Human Atherosclerotic Lesions.

The aim of this study was to investigate whether CD74 levels in atherosclerotic lesions are associated with inflammation, apoptosis, plaque severity, and clinical symptoms among patients with carotid atherosclerosis. We further studied whether CD74 expression is associated with apoptosis in macrophages induced by 7ketocholesterol (7keto). Sixty-one carotid samples (39 males and 22 females) were immunostained with macrophages, smooth muscle cells, CD74, ferritin, TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling), and thrombin receptors. Double immunocytochemistry of CD74 and caspase 3 or CD74 and Annexin V was performed on THP-1 macrophages exposed to 7keto. In human carotid plaques, CD74 expression is lesion-dependently increased and is associated with necrotic core formation and plaque rupture, clinical symptoms, macrophage apoptosis, ferritin, and thrombin receptors. CD74 levels were inversely correlated to high-density lipoproteins and statin treatment, and positively correlated to triglycerides. In THP-1 macrophages, 7keto induced a significant increase in levels of CD74, ferritin, and apoptotic cell death. This study suggests that CD74 in apoptotic macrophages is linked to inflammation and thrombosis in progression of human atherosclerotic plaques, lipid metabolism, and clinical manifestation in atherosclerosis. Surface CD74 in apoptotic macrophages and ferritin production induced by oxidized lipids may contribute to inflammation and plaque vulnerability in atherosclerosis.

COVID-19 Vaccine Hesitancy and Emerging Variants: Evidence from Six Countries.

As the world tries to cope with the devastating effects of the COVID-19 pandemic and emerging variants of the virus, COVID-19 vaccination has become an even more critical tool toward normalcy. The effectiveness of the vaccination program and specifically vaccine uptake and coverage, however, is a function of an individual's knowledge and individual opinion about the disease and available vaccines. This study investigated the knowledge, attitudes, and resulting community practice(s) associated with the new COVID-19 variants and vaccines in Bangladesh, Colombia, India, Malaysia, Zimbabwe, and the USA. A cross-sectional web-based Knowledge, Attitudes, and Practices (KAP) survey was administered to respondents living in six different countries using a structured and multi-item questionnaire. Survey questions were translated into English, Spanish, and Malay to accommodate the local language in each country. Associations between KAP and a range of explanatory variables were assessed using univariate and multiple logistic regression. A total of 781 responses were included in the final analysis. The Knowledge score mean was 24 (out of 46), Attitude score 28.9 (out of 55), and Practice score 7.3 (out of 11). Almost 65% of the respondents reported being knowledgeable about COVID-19 variants and vaccination, 55% reported a positive attitude toward available COVID-19 vaccines, and 85% reported engaging in practices that supported COVID-19 vaccination. From the multiple logistic models, we found post-graduate education (AOR = 1.83, 95% CI: 1.23-2.74) and an age range 45-54 years (AOR = 5.81, 95% CI: 2.30-14.69) to be significantly associated with reported COVID-19 knowledge. In addition, positive Attitude scores were associated with respondents living in Zimbabwe (AOR = 4.49, 95% CI: 2.04-9.90) and positive Practice scores were found to be associated with people from India (AOR = 3.68, 95% CI: 1.15-11.74) and high school education (AOR = 2.16, 95% CI: 1.07-4.38). This study contributes to the identification of socio-demographic factors associated with poor knowledge, attitudes, and practices relating to COVID-19 variants and vaccines. It presents an opportunity for collaboration with diverse communities to address COVID-19 misinformation and common sources of vaccine hesitancy (i.e., knowledge, attitudes, and practices).

Determinants of nutrition knowledge, attitude and practices of adolescent sports trainee: A cross-sectional study in Bangladesh.

BACKGROUND: Nutrition is an important predictor of an athlete's performance. It is more important for particularly those athletes who are in the growing stage (adolescents). This study aimed to assess their current level of knowledge, attitude, and practices (KAP) of nutrition and to predict potential factors impacting their level of these KAP. METHODS: A cross-sectional study was conducted among adolescent trainee athletes selected conveniently from 11 sports departments (e.g. cricket, football, hockey, etc.) of Bangladesh Krira Shikkha Protishtan (BKSP). A semi-structured interviewer-administered questionnaire was used for data collection. Anthropometric measurements (e.g. height, weight, BMI, BF %) were taken using appropriate methods. The data were analyzed using R (v3.6.1) and Python Jupyter Notebook. Descriptive statistics, t-test, analysis of variance (ANOVA), and logistic regression were used to determine the relationship between dependent and independent variables. RESULTS: A total number of 260 participants were enrolled in this study, most of them (86%) were male. Their mean age was 15.50 ± 1.83 ranging from 12-19 years. More than half of the participants had good nutrition knowledge (n = 149, 57.3%). Fifty-seven percent of participants had a positive attitude (n = 146) and 57.69% (n = 150) had a good level of practices regarding nutrition. Age (p = 0.007), gender (p = 0.004), department of training (p = 0.0034), and duration of sports training (p = 0.004) of participants were significantly associated with knowledge, while only age and BMI were significantly associated with practices. Athletes with less body fat were more likely to have good nutrition practice behavior (AOR 0.895; 95% CI 0.83, 0.96; p < 0.05) and nutrition knowledge was positively associated with nutrition practice (AOR 2.335; 95% CI 1.405, 3.88; p = 0.001). CONCLUSION: Knowledge, attitude, and practices level observed among many of our participants was satisfactory. Previous nutrition training was found as a potentially modifiable factor of good nutrition knowledge and good nutrition knowledge was found to be a predictor of good practice score. Thus, it is necessary to provide appropriate nutrition information to adolescent athletes through proper educational training and intervention on a regular basis.

Emerging infectious disease, the household built environment characteristics, and urban planning: Evidence on avian influenza in Vietnam.

Recent concerns with pandemic outbreaks of human disease and their origins in animal populations have ignited concerns regarding connections between Emerging Infectious Diseases (EID) and development. As disasters, health, and infectious disease become part of planning concern (Matthew & McDonald, 2007), greater focus on household infrastructure and EID disease outbreaks among poultry is warranted. Following Spencer (2013), this study examines the relationship between the mix of household-scale water supplies, sanitation systems, and construction materials, and Highly Pathogenic Avian Influenza (HPAI) among poultry in a developing country: Vietnam. Findings of our multivariate logistic regressions suggest that a non-linear, Kuznets-shaped urban transition (Spencer, 2013) has an independent effect on the outbreak of HPAI, especially as it relates to household-level sanitation infrastructure. We conclude that the Kuznets-shape development of household infrastructure characteristics in Vietnam play a significant role in explaining where poultry outbreaks occur. Using secondary data from the Census of Population and Housing, and the Agricultural Census at the District and Commune levels for the country of Vietnam, we performed logistic regression to test the relationship between outbreaks of HPAI in poultry and newly-developed "coherence indices" (Spencer, 2013) of household water supply, sanitation, and construction materials that measure nonlinear, transitional development. Results show that district-scale coherence indices are negatively and independently correlated with HPAI outbreaks, especially for sanitation. Findings also suggest that community-scale coherence of urban infrastructures is a powerful tool for predicting where HPAI poultry outbreaks are likely to occur, thereby providing health planners new tools for efficient surveillance.

Reproductive health and desire for children among young female sex workers in Bangladesh brothels.

Globally, reproductive health research among female sex workers (FSWs) often focuses on pregnancy prevention, but many women who sell sex aspire to have children in the future. In Bangladesh, where early marriage and parenthood is the norm, we examine reproductive histories and childbearing desires of young women who sell sex in brothels. We interviewed 1061 FSWs aged 18 to 24 in eight brothels in three Bangladesh divisions. Interviewers elicited information on sociodemographic characteristics, contraceptive use, pregnancy history, and childbearing desire. Bivariate and multivariate analyses were conducted to examine correlates of wanting to have a child within 24 months.

Medicinal values of aquatic plant genus Nymphoides grown in Asia: A review

Nymphoides is an aquatic genus consisting about 50 species,of which few were accepted as traditional medicinal plants in Asia.The literature review revealed that Nymphoides species are widely used in Ayurvedic medicine as a popular drug,i.e.Tagara.They are also utilized by the traditional local healers of different Asian countries to treat various diseases,like convulsion,jaundice,fever,headache,etc.According to thein vivo and in vitro pharmacological studies,Nymphoides species have been claimed to possess major biological activities like anticonvulsant,antioxidant,hepatoprotective,cytotoxic,antitumor,etc.Biochemical profiling of different aquatic plants of this genus revealed the presence of some important phytoehemicals as polyphenolic component,flavonoids,triterpenes,carbohydrates,glycosides,etc.Several valuable bioactive compounds including ephedrine,coumarin,secoiridoid glucosides,methyl quercetin,ferulic acid,follamenthoic acid,etc.were also known to be isolated and identified from different Nymphoides species.The aim of this review is to analyze the published report based on the medicinal values of different Asian Nymphoides species,to provide the updlated information about the ethnomedicinal,pharmacological as well as the phytochemical properties for the first time.

Synthesis, crystal structure determination, biological screening and docking studies of N1-substituted derivatives of 2,3-dihydroquinazolin-4(1H)-one as inhibitors of cholinesterases.

Pursuing the strategy of developing potent AChE inhibitors, we attempted to carry out the N1-substitution of 2,3-dihydroquinazolin-4(1H)-one core. A set of 32 N-alkylated/benzylated quinazoline derivatives were synthesized, characterized and evaluated for their inhibition against cholinesterases. N-alkylation of the series of the compounds reported previously (N-unsubstituted) resulted in improved activity. All the compounds showed inhibition of both enzymes in the micromolar to submicromolar range. Structure activity relationship (SAR) of the 32 derivatives showed that N-benzylated compounds possess good activity than N-alkylated compounds. N-benzylated compounds 2ad and 2af were found very active with their IC50 values toward AChE in submicromolar range (0.8µM and 0.6µM respectively). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. Computational predictions of ADMET studies reveal that all the compounds have good pharmacokinetic properties with no AMES toxicity and carcinogenicity. Moreover, all the compounds are predicted to be absorbed in human intestine and also have the ability to cross blood brain barrier. Overall, the synthesized compounds have established a structural foundation for the design of new inhibitors of cholinesterase.

Paying for Sex by Young Men Who Live on the Streets in Dhaka City: Compounded Sexual Risk in a Vulnerable Migrant Community.

PURPOSE: Dhaka City is home to thousands of migrants from Bangladesh's rural areas who often live in the streets. Prior studies examine street youth's practice of selling sex as a survival mechanism. We assess their less-studied practice of paying for sex and its association with sexual risk behaviors and outcomes. METHODS: As part of the global Link Up project, trained interviewers recruited 447 young men who live on the streets, ages 15-24, from seven Dhaka City "hotspots" to participate in a survey about sexual health. Among those who ever had sex, we examined frequencies and conducted bivariate analyses of sociodemographic characteristics by paying for sex status. We then conducted bivariate and multivariate logistic regression analyses of paying for sex in the last 12 months and sexual health behaviors and outcomes. RESULTS: Median participant age was 18 years. Among those who ever had sex (N = 321), 80% reported paying for sex in the last 12 months and 15% reported selling sex in the last 12 months. In multivariate analyses, those who paid for sex had significantly increased odds of reporting sexually transmitted infection-related symptoms in the last six months (adjusted odds ratio = 1.76, 95% confidence interval [CI] = 1.17-2.64) and engaging in unprotected last sex with a nonprimary partner (adjusted odds ratio = 2.19, CI = 1.58-3.03). CONCLUSIONS: The adverse factors associated with paying for sex among young men who live on the streets in Dhaka City highlight the need for programs to educate on HIV/sexually transmitted infection prevention and promote condom use, STI screening/treatment, and HIV testing in this population.

Stigma Reduction Training Improves Healthcare Provider Attitudes Toward, and Experiences of, Young Marginalized People in Bangladesh.

PURPOSE: Working with health providers to reduce HIV stigma in the healthcare setting is an important strategy to improve service utilization and quality of care, especially for young people who are sexually active before marriage, are sexual minorities, or who sell sex. A stigma reduction training program for health providers in Bangladesh was evaluated. METHODS: A cohort of 300 healthcare providers were given a self-administered questionnaire, then attended a 2-day HIV and sexual and reproductive health and rights training (including a 90-minute session on stigma issues). Six months later, the cohort repeated the survey and participated in a 1-day supplemental training on stigma, which included reflection on personal values and negative impacts of stigma. A third survey was administered 6 months later. A cross-sectional survey of clients age 15-24 years was implemented before and after the second stigma training to assess client satisfaction with services. RESULTS: Provider agreement that people living with HIV should be ashamed of themselves decreased substantially (35.3%-19.7%-16.3%; p < .001), as did agreement that sexually active young people (50.3%-36.0%-21.7%; p < .001) and men who have sex with men (49.3%-38.0%-24.0%; p < .001) engage in "immoral behavior." Young clients reported improvement in overall satisfaction with services after the stigma trainings (63.5%-97.6%; p < .001). CONCLUSIONS: This study indicates that a targeted stigma reduction intervention can rapidly improve provider attitudes and increase service satisfaction among young people. More funding to scale up these interventions is needed.

Synthesis, biological evaluation and docking studies of 2,3-dihydroquinazolin-4(1H)-one derivatives as inhibitors of cholinesterases.

In search of potent inhibitors of cholinesterases, we have synthesized and evaluate a number of 2,3-dihydroquinazolin-4(1H)-one derivatives. The synthetic approach provided an efficient synthesis of the target molecules with excellent yield. All the tested compounds showed activity against both the enzymes in micromolar range. In many case, the inhibition of both enzymes are higher than or comparable to the standard drug galatamine. With the selectivity index of 2.3 for AChE, compound 5f can be considered as a potential lead compound with a feature of dual AChE/BChE inhibition with IC50=1.6±0.10µM (AChE) and 3.7±0.18µM (BChE). Binding modes of the synthesized compounds were explored by using GOLD (Genetic Optimization for Ligand Docking) suit v5.4.1. The computed binding modes of these compounds in the active site of AChE and BChE provide an insight into the mechanism of inhibition of these two enzyme.

Autophagy dysfunction and regulatory cystatin C in macrophage death of atherosclerosis.

Autophagy dysfunction in mouse atherosclerosis models has been associated with increased lipid accumulation, apoptosis and inflammation. Expression of cystatin C (CysC) is decreased in human atheroma, and CysC deficiency enhances atherosclerosis in mice. Here, we first investigated the association of autophagy and CysC expression levels with atheroma plaque severity in human atherosclerotic lesions. We found that autophagy proteins Atg5 and LC3ß in advanced human carotid atherosclerotic lesions are decreased, while markers of dysfunctional autophagy p62/SQSTM1 and ubiquitin are increased together with elevated levels of lipid accumulation and apoptosis. The expressions of LC3ß and Atg5 were positively associated with CysC expression. Second, we investigated whether CysC expression is involved in autophagy in atherosclerotic apoE-deficient mice, demonstrating that CysC deficiency (CysC(-/-) ) in these mice results in reduction of Atg5 and LC3ß levels and induction of apoptosis. Third, macrophages isolated from CysC(-/-) mice displayed increased levels of p62/SQSTM1 and higher sensitivity to 7-oxysterol-mediated lysosomal membrane destabilization and apoptosis. Finally, CysC treatment minimized oxysterol-mediated cellular lipid accumulation. We conclude that autophagy dysfunction is a characteristic of advanced human atherosclerotic lesions and is associated with reduced levels of CysC. The deficiency of CysC causes autophagy dysfunction and apoptosis in macrophages and apoE-deficient mice. The results indicate that CysC plays an important regulatory role in combating cell death via the autophagic pathway in atherosclerosis.

Autophagy Induction Protects Against 7-Oxysterol-induced Cell Death via Lysosomal Pathway and Oxidative Stress.

7-Oxysterols are major toxic components in oxidized low-density lipoprotein and human atheroma lesions, which cause lysosomal membrane permeabilization (LMP) and cell death. Autophagy may function as a survival mechanism in this process. Here, we investigated whether 7-oxysterols mixed in an atheroma-relevant proportion induce autophagy, whether autophagy induction influences 7-oxysterol-mediated cell death, and the underlying mechanisms, by focusing on cellular lipid levels, oxidative stress, and LMP in 7-oxysterol-treated macrophages. We found that 7-oxysterols induced cellular lipid accumulation, autophagy dysfunction, and cell death in the form of both apoptosis and necrosis. Exposure to 7-oxysterols induced autophagic vacuole synthesis in the form of increased autophagy marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and LC3-phosphatidylethanolamine conjugate (LC3-II) and autophagic vacuole formation. This led to an accumulation of p62, indicating a reduction in autophagic vacuole degradation. Importantly, autophagy induction significantly reduced 7-oxysterol-mediated cell death by diminishing LMP and oxidative stress. Moreover, autophagy induction minimized cellular lipid accumulation induced by 7-oxysterols. These findings highlight the importance of autophagy in combating cellular stress, LMP, and cell death in atherosclerosis. Therefore, activation of the autophagy pathway may be a potential therapeutic strategy for prevention of necrotic core formation in atherosclerotic lesions.

A computational study of base-catalyzed reactions of cyclic 1,2-diones: cyclobutane-1,2-dione.

The reaction of cyclobutane-1,2-dione with hydroxide was studied by a variety of ab initio (MP2, SCS-MP2, CCSD(T), CEPA/1) and density functional (M06-2X) methods. Three possible reaction paths of the initially formed tetrahedral adduct leading to either 1-hydroxycyclopropane-1-carboxylate (benzilic acid type rearrangement, path A), α-oxobutanoate (path B) or γ-oxobutanoate (path C) were considered. Although the latter two products show similar or even more negative Gibbs free energies of reaction than calculated for the benzilic acid type rearrangement, the Gibbs free energies of activation are substantially higher. According to the calculations, the only feasible reaction appears to be the formation of 1-hydroxycyclopropane-1-carboxylate, which is corroborated by previous experimental observations.

Cell death induced by 7-oxysterols via lysosomal and mitochondrial pathways is p53-dependent.

Oxysterol accumulation and p53 expression mainly in macrophages have been associated with cell death and necrotic core formation in human atheroma progression. Oxidative stress and lysosomal membrane permeabilization (LMP) in macrophages are important causes of macrophage apoptosis. However, it is not understood how p53 and oxysterols interact in the process. We show here that 7-oxysterols induce endogenous full-length p53 and phospho-p53 (p53-Ser15) in both nucleus and cytoplasm of THP1 and J774 cells, which is followed by cellular oxidative stress and apoptotic cell death. The role of p53 in 7-oxysterol-mediated cell death is further investigated in temperature sensitive p53-transfected (M1-t-p53) and in p53-deficient (M1) cells. These results reveal that 7-oxysterols induce induction and nuclear translocation of p53 in M1-t-p53 cells, which in turn enhances LMP, mitochondrial translocation of Bax, mitochondrial membrane permeabilization, cytosolic release of cytochrome c, and cell death. Most importantly, the above effects of 7-oxysterols were not observed in p53-deficient M1 cells. The findings reveal that 7-oxysterol-induced cell death occurs via p53-dependent pathways. Subsequent p53 nuclear translocation and induction of wild-type and phosphorylated p53 are early steps in oxysterol-induced lysosomal-mitochondrial pathways involved in cell death.

A substrate-driven approach to determine reactivities of α,ß-unsaturated carboxylic esters towards asymmetric bioreduction.

The degree of C=C bond activation in the asymmetric bioreduction of α,ß-unsaturated carboxylic esters by ene-reductases was studied, and general recommendations to render these "borderline-substrates" more reactive towards enzymatic reduction are proposed. The concept of "supported substrate activation" was developed. In general, an additional α-halogenated substituent proved to be beneficial for enzymatic activity, whereas ß-alkyl or ß-aryl substituents were detrimental for the reactivity of nonhalogenated substrates, and α-cyano groups showed little effect. The alcohol moiety of the ester functionality was found to have a strong influence on the reaction rate. Overall, activities were determined by both steric and electronic effects.

Pesticides exposure in Pakistan: a review.

This is the first systematic review of studies done since 1960, and to give an integrated picture of pesticides exposure to humans, animals, plants, waters, soils/sediments, atmosphere etc. in Pakistan. Authors have extracted data from different departments, published literature in research journals and National reports. Although the wide-spread usage of pesticides in Pakistan has controlled the pests, but like other countries, it has started causing environmental problems in the area. In some areas of Punjab and Sindh groundwater has been found contaminated and is constantly being under the process of contamination due to pesticide use. There is considerable evidence that farmers have overused and misused pesticides especially in cotton-growing areas. It is evident from the biological monitoring studies that farmers are at higher risk for acute and chronic health effects associated with pesticides due to occupational exposure. Furthermore, the intensive use of pesticides (higher sprays more than the recommended dose) in cotton areas involves a special risk for the field workers, pickers, and of an unacceptable residue concentration in cottonseed oil and cakes. The authors have also discussed the merits and demerits of different studies. The review will set the future course of action of different studies on pesticide exposure in Pakistan. Data limitations are still the major obstacle towards establishing clear environmental trends in Pakistan. The authors suggest that a reliable monitoring, assessment and reporting procedures shall be implemented in accordance with appropriate environmental policies, laws and regulations in order to minimize the pesticides exposure.