Establishment of Doxorubicin Resistant Stem-like Cell line from MCF-7 Cells

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Antioxidant, antimicrobial and antiproliferative activities of peel and pulp extracts of red and white varieties of Ipomoea batatas (L) Lam

Purpose: To investigate the antioxidant, antibacterial and anticancer potentials of methanol and ethanol extracts of the peel and pulp of red and white species of Ipomoea batatas (L.) fruit.Methods: Total phenolic contents and flavonoids were determined using chemical assays. Antioxidant studies were carried out using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, inhibition of linoleic acid peroxidation assay and reducing power assay. Antibacterial and antiproliferative activities of extracts were determined using disc diffusion and MDBK cancer cell line inhibition methods, respectively.Results: The extract of peels of red specie (PERS) showed total phenolic contents (TPC) 8.9 mg gallic acid equivalent (GAE)/g dry extract and flavonoids 6.5 mg catechin equivalent (CE)/g dry extract. The extract of PERS also showed promising DPPH free radical scavenging activity, inhibition of linoleic acid peroxidation and reducing power activity. However, mild antibacterial and anti-proliferative activities were noted except that the extract showed significant inhibition of Bacillus subtilis growth.Conclusion: The results indicate that the peel and the pulp of red sweet potato (SP) specie are rich in antioxidants and can potentually be processed as antioxidant food supplements.Keywords: Ipomoea batatas (L.) Lam, Sweet potato, Phenolic content, Antioxidants, Antibacterial activity, Antiproliferative activit

Microwave-assisted solvent free efficient synthesis of 1,3,4-oxadiazole-2(3H)-thiones and their potent in vitro urease inhibition activity

An efficient solvent free microwave assisted synthesis of 5-substituted-1,3,4-oxadiazole-2(3H)-thiones (2a-2r) from hydrazides and carbon disulfide has been accomplished in good to excellent yield. The urease inhibition activity of the resulting compounds was investigated. Preliminary bioassay indicated that the compound 2j bearing 2-bromo substituent is the most active inhibitor exhibiting IC50 12.60 ± 0.92 μM

Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings: Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. Funding: Bill & Melinda Gates Foundation

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

Cytogenetic abnormalities associated with reproductive failure in Pakistani population: experience of a tertiary care hospital

Constitutional chromosomal abnormalities play a significant role in causing reproductive anomalies in individuals of reproductive age. With the rapid advancement of genome engineering techniques, it has now become possible to cure different genetic disorders. However, very limited data is available regarding the prevalence of such aberrations in the Pakistani population. Considering this factor, this retrospective analysis was undertaken to elucidate the type and prevalence rate of such abnormalities in our population. A total of 241 individuals, who were referred to the Liaquat National Hospital, from January 2017 to December 2021, with a history of infertility or miscarriages, were evaluated using the standard GTG banding technique. The results revealed a notably high percentage 44(18.2%) of chromosomal abnormalities in our population. Surprisingly, the frequency of these anomalies was observed to be higher in males than in females. ---Continu

Lack of androgen receptor expression correlates with high expression of ALDH1 and poor overall and 5-year disease free survival in patients with invasive breast cancer

Introduction: A sub-population of cells referred to as cancer stem cells has been identified utilizing specific markers such as aldehyde dehydrogenase 1 (ALDH1) amongst others in solid tumors including breast cancers. Evidence from in vitro studies has shown that high ALDH1 expression identifies tumorigenic cell population which is capable of self-renewal and generating tumors which recapitulate the heterogeneity of the primary tumors. Expression of androgen receptor is present in 70-90% cases of invasive breast cancers at a frequency that is higher than the expression of estrogen or progesterone receptors. However, prognostic relevance of androgen receptor expression in relation to the expression of ALDH1 has not been investigated.Methodology: Immunohistochemical expression of ALDH1 and AR was evaluated in formalin fixed paraffin embedded blocks from 177 invasive breast cancer cases at a single institution in Pakistan from 2006-2010. Clinico-pathological details and follow-up data were collected from patients\u27 medical charts. Data analysis was performed on SPSS version 19. Over-all survival and 5-year disease free survival were estimated by Kaplan Meier.Results: The mean age of the patients was 53.9 (+ 12.40) years. Fifteen percent patients were diagnosed with stage I disease, 52% with stage II, 25% and 8% presented with stage III and stage IV disease, respectively. Twelve percent patients presented with T1 tumors, 49.7% patients presented with T2 tumors whereas 23.7% and 14.6 % patients presented with T3 and T4 tumors respectively. Fifty-seven percent patients were node positive. Estrogen and progesterone receptor expression was present in 62% and 52% of tumors respectively. HER-2/neu was overexpressed /amplified in 30% tumors. Immunohistochemical expression of androgen receptor (AR) was present in 63.8% tumors whereas ALDH1 expression was present in 28.8% tumors. Lack of androgen receptor expression was associated with high expression of ALDH1 ( p= 0.009).Cases were divided into two groups: Group1: ALDH1-/AR+ and Group 2: ALDH1+/ AR-. No significant differences were observed between these groups with respect to age, tumor size, stage of disease, HER-2 neu over-expression/amplification or nodal status. Group 1 phenotype correlated with nuclear grade I and II tumors (p \u3c0.05), estrogen receptor (p \u3c0.05) and progesterone receptor (p \u3c0.05) expression. Group 2 phenotype was associated with nuclear grade III tumors (p \u3c0.05) and estrogen and progesterone receptor negativity (p \u3c0.05). Although not statistically significant, but a trend towards a better over-all survival and 5-year disease free survival was observed in group 1 as compared to group 2.Conclusions:1. Group 1 phenotype correlated with better prognostic features such as well to moderately differentiated and endocrine responsive tumors.2. Group 2 phenotype correlated with poor prognostic features such as higher nuclear grade and lack of expression of hormone receptors.3. Expression of stem cell marker, ALDH1, in group 2 phenotype correlated with poor over-all and 5-year disease free survival