MW assisted synthesis of some heterocyclic compounds and their Mannich bases under solvent free conditions and their biological assay

A highly efficient MW assisted synthesis of different nitrogen containing heterocyclic compounds under solvent free conditions was reported. Their aminomethylation was carried out on acidic alumina under microwave irradiation to give the corresponding Mannich bases. The method is clean, fast, facile, efficient, low cost and environmentally benign. The structure of synthesized compounds has been characterized on the basis of their elemental analysis and spectral data. These compounds were evaluated for their antimicrobial activity against bacteria and fungi

Endothelial Cell-Derived TGF-β Promotes Epithelial-Mesenchymal Transition via CD133 in HBx-Infected Hepatoma Cells

Background: Hepatitis B-X Protein (HBx) encoded in Hepatitis B virus (HBV) is known to play a critical role in development and progression of HBV induced hepatocellular carcinoma (HCC). HBx interacts with and activates various cells in HCC microenvironment to promote tumor initiation, progression and invasion. In this study, we investigated how surrounding stromal cells interact with HBx-infected hepatoma cells by a series of in vitro co-culture studies.Methods: Huh7 hepatoma cells were cultured and transfected with the mammalian expression vector pGFP-HBx. Co-culture assays were performed between HBx-transfected Huh7 cells and conditioned media (CM) from stromal cells [endothelial cell lines (HUVECs) and hepatic stellate cell lines (LX2 cells)]. The effect of these interactions was studied by a series of functional assays like chemotaxis, invasion, and wound healing scratch assays. Also, quantitative real time (RT)-PCRs of the mesenchymal genes was performed in the hepatoma cells with and without the co-cultures. Hep3B cells with an integrated HBV genome were taken as positive controls.Results: HBx-transfected Huh7 cells cultured in presence of CM from HUVECs illustrated enhanced migration and tube formation as compared to HBx-transfected cells cultured alone or co-cultured with LX2 cells. HBx-transfected hepatoma cells incubated with CM from HUVECs also expressed mesenchymal genes including Thy1, CDH2, TGFβR1, VIM, and CD133. ELISAs revealed increased levels of TGF-β in CM from HUVECs. In comparison to unstimulated HBx-transfected Huh7 cells, TGF-β stimulated cells displayed increased invasive properties and mesenchymal gene expression. RT-PCR and flow cytometry analysis further demonstrated that incubation with either CM from HUVECs or TGF-β significantly increased the expression of a stemness marker, CD133 in HBx-infected hepatoma cells. Gene inhibition experiments with CD133 siRNA showed a downregulation of mesenchymal gene expression and properties in TGF-β induced HBx-infected hepatoma cells as compared to that observed in control siRNA treated cells, indicating CD133 as one of the key molecules affecting epithelial to mesenchymal transition (EMT) in HBx-infected cells.Conclusion: The study indicates that secretory factors like TGF-β from neighboring endothelial cells may enhance expression of CD133 and impart an aggressive EMT phenotype to HBx-infected hepatoma cells in HBV induced HCC

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Synthesis of quinozoline and its imino sugars by using NaY zeolite catalyst under microwave condition

734-7373-Amino-2-phenylquinazolin-4-(3H)-one (2) has been synthesized by the treatment of hydrazine hydrate with 2-phenyl-4H-3,1-benzoxazin-4-one (1) using NaY zeolite as a solid support under microwave irradiation. Compound (2) on reaction with various aldoses affords the corresponding imino sugars (3a-h). In this work, NaY zeolite has been found to act both as solid support as well as catalyst

MW assisted synthesis of some pyrazoles containing benzotriazole moiety: An environmentally benign approach

432-439MW assisted synthesis of pyrazoles containing benzotriazole moieties <b style="mso-bidi-font-weight: normal">4a-n has been achieved by cyclocondensation of substituted chalcones 3a-n with hydrazide of benzotriazole 2 in presence of glacial acetic acid (GAA). Thus, synthesized compounds <b style="mso-bidi-font-weight: normal">4a-n have been characterized by their spectral data and evaluated for their antibacterial and antifungal activities against various microbes

Biological decolorization of the synthetic dye RBBR in contaminated soil

Soil contaminated with the synthetic dye Remazol Brilliant Blue R (RBBR) was treated independently with the wheat straw-grown white rot fungus Irpex lacteus, a bacterial consortium isolated from a dye-polluted soil and a coculture comprising both I. lacteus and the bacterial consortium. Both I. lacteus and the coculture removed RBBR (decrease in absorbance at 578 nm) gradually during a 49-day incubation time to 76 and 78%, respectively. The bacterial consortium alone, however, decolorized RBBR starting after 14 days with a final RBBR removal of 89%. Using controls with heat-killed cultures almost no decolorization occurred. The decolorization by the coculture did not show an increased RBBR removal as compared to the individual cultures. This might be explained by the observation that I. lacteus inhibited growth of the bacterial consortium

Depression and health-related quality of life of patients with type 2 diabetes attending tertiary level hospitals in Dhaka, Bangladesh

Abstract Introduction Type 2 diabetes mellitus (T2DM) and depression are closely linked. People with T2DM are at increased risk of developing depression and vice versa. T2DM and depression comorbid conditions adversely affect Health-Related Quality of Life (HRQOL) and management of T2DM. In this study, we assessed depression and HRQOL among patients with T2DM in Dhaka, Bangladesh. Methods A cross-sectional study was conducted in two tertiary-level hospitals in Dhaka, Bangladesh. Data were collected from 318 patients with T2DM. A set of standard tools, PHQ-9 (for assessing depression) and EuroQol-5D-5L (for assessing the HRQOL), were used. Statistical analyses, including Chi-square and Fisher's exact tests, Wilcoxon (Mann–Whitney), and Spearman's correlation coefficient tests, were performed using SPSS (v.20). Results The majority of the patients (58%) were females, with a mean age (standard deviation) of 52 ± 10 years, and 74% of patients lived in urban areas. The prevalence of depression was 62% (PHQ-9 score ≥ 5). Over three-quarters (76%) reported problems in the anxiety/ depression dimension of EQ-5D, followed by pain/discomfort (74%), mobility (40%), self-care (36%), and usual activities (33%). The depression and T2DM comorbid condition were associated with all the five dimensions of EQ-5D (χ2 statistics with df = 1 was 52.33, 51.13, 52.67, 21.61, 7.92 for mobility, self-care, usual activities, pain/discomfort, and anxiety/ depression dimensions respectively, p- < 0.01). The mean EQ-5D index (0.53 vs. 0.75) and the mean EQ-5D VAS (65 vs. 76) both showed lower values in T2DM patients with depression compared to T2DM patients without depression (Wilcoxon test, p- < 0.001). Conclusions We conclude that the majority of the patients with T2DM had comorbid conditions, and the HRQOL was negatively affected by comorbid depression in T2DM patients. This suggests the importance of timely screening, diagnosis, treatment, and follow-up of comorbid depression in T2DM patients to improve overall health and QOL