Polyphenols: Nature's Gift as dietary phytoconstituents against different human ailments

Recently, researches and scientists are showing a lot of interests in bioactive compounds of plants and its products as these constituents are of high valued. Polyphenols are phytochemical constituents which are the integral components in plants and their products that are associated with defensive mechanism against infections and various oxidative stress by free radicals. Green tea, fruits, vegetables, cereals and red wines are rich sources of polyphenolic constituents which attributes prevention from infections and diseases because of its antioxidant properties, anti-diabetic properties, and radical scavenging properties. Oxidative stress which is the primary reason for different ailments in humans is due to the free radicals that are present even during the normal health condition. Polyphenolic acids like cinnamic acid, romarinic acid, stilbenes like resveratrol, flavonoids like catechin, taxifolin, quercetin, and lignans like sesamin, pinoresinol, podophyllotoxin etc. are found to be effective against wide range of human diseases like oxidative stress, cardiovascular disorder, neurodegenerative diseases, aging, and cancer. These phytoconstituents prevent the diseases and provide relieving sensation via different mechanisms. Here, the study shows the importance of polyphenols with respect to the relevance of human health. As there are the promising applications of various bioactive constituents in a wide range of disease, further research should be encouraged on the mechanism of action and bioavailability of polyphenols

The COVID‐19 Pandemic Not Only Poses Challenges, but Also Opens Opportunities for Sustainable Transformation

The COVID-19 pandemic has impacted social, economic, and environmental systems worldwide, slowing down and reversing the progress made in achieving the Sustainable Development Goals (SDGs). SDGs belong to the 2030 Agenda to transform our world by tackling humankind's challenges to ensure well-being, economic prosperity, and environmental protection. We explore the potential impacts of the pandemic on SDGs for Nepal. We followed a knowledge co-creation process with experts from various professional backgrounds, involving five steps: online survey, online workshop, assessment of expert's opinions, review and validation, and revision and synthesis. The pandemic has negatively impacted most SDGs in the short term. Particularly, the targets of SDG 1, 4, 5, 8, 9, 10, 11, and 13 have and will continue to have weakly to moderately restricting impacts. However, a few targets of SDG 2, 3, 6, and 11 could also have weakly promoting impacts. The negative impacts have resulted from impeding factors linked to the pandemic. Many of the negative impacts may subside in the medium and long terms. The key five impeding factors are lockdowns, underemployment and unemployment, closure of institutions and facilities, diluted focus and funds for non-COVID-19-related issues, and anticipated reduction in support from development partners. The pandemic has also opened a window of opportunity for sustainable transformation, which is short-lived and narrow. These opportunities are lessons learned for planning and action, socio-economic recovery plan, use of information and communication technologies and the digital economy, reverse migration and “brain gain,” and local governments' exercising authorities

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017 : A systematic analysis for the global burden of disease study

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.Peer reviewe

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

UNVEILING NOVEL GENES: EXPLORING THEIR POTENTIAL ROLES IN HUMAN ENDOMETRIAL STROMAL FIBROBLAST CELL DECIDUALIZATION

In the secretory phase of the menstrual cycle, a notable transformation occurs within the uterine endometrium. Specifically, the elongated fibroblast-like mesenchymal cells change and take a different form, resembling polygonal epithelioid-like cells. This transformation is referred to as decidualization and provides the immune-privileged nutritive support required for establishing pregnancy and placental development. Though it is evident that decidualization is under the control of the hormone progesterone and estrogen and is a complex interplay of various protein-coding genes and long noncoding RNA’s (lncRNA’s), precise mechanisms involved during decidualization are not fully understood. This study was carried out to explore the roles of various protein-coding genes and long noncoding RNAs (lncRNAs) in human endometrial stromal fibroblast (hESF) decidualization. RNA sequencing of in vitro decidualization of hESF cells isolated from term placenta was compared with RNA sequencing analysis of in vitro decidualization from cells isolated from non-pregnant human endometrial stromal cells (HESC). The NR4A2, NR4A3, and ATOH8 genes, along with 17 selected lncRNAs, were chosen from differential expression analysis from RNA-Seq. All of them were significantly upregulated ( except LncAL121578.3 and LINC01605, which were downregulated) during hESF decidualization. The RNA-Seq data were confirmed with RT-qPCR analysis. NR4A2, NR4A3, and ATOH8 protein abundance were also significantly upregulated during hESF decidualization. Modulating ATOH8 expression influenced the decidualization markers genes, cell size, and shape morphology. In addition, ATOH8 displayed a potential role in EMT/MET transition, glucose metabolism, FST/INHBB meditated IL4 regulation, cell cycle, and apoptosis. Lentivirus-mediated knockdown and overexpression of ATOH8 reveals ATOH8 to be an upstream regulator of the WNT/FZD-FOXO1 pathway, previously shown to be critical for hESF decidualization. We also explored possible regulators of ATOH8 expression during hESF decidualization. BMP2 significantly enhanced ATOH8 mRNA and protein expression when cells were stimulated to undergo decidualization. DHM1, an ALK2/3 inhibitor, significantly reduced ATOH8 mRNA and protein expression. In addition, the cAMP analog alone represented the primary effect of ATOH8 expression when cells were stimulated to undergo decidualization.Interestingly, targeting NR4A2 and NR4A3 with lentivirus-mediated shRNA gene delivery reduced the expression of ATOH8 mRNA, indicating that NR4A2 and NR4A3 are somehow involved in the upstream regulation of ATOH8. In addition, targeting LncAC027288.3 with lentivirus altered the decidualization marker genes and reduced the expression of ATOH8 mRNA expression levels, indicating that LncAC027288.3 acts as an upstream regulator of ATOH8 expression. Our research suggests decidualization is a complicated yet coordinated interplay of events involving transcription factors, bHLH transcription factors, and LncRNAs.Keywords: ATOH8, Decidualization, LncRNA

Enzyme-mediated formulation of stable elliptical silver nanoparticles tested against clinical pathogens and MDR bacteria and development of antimicrobial surgical thread

Abstract Background Silver nanoparticles (AgNPs) are believed to be emerging tool against various infectious diseases including multi-drug resistant (MDR) bacteria. In the present study, in vitro synthesis of AgNPs was optimized using 1:50 ratio of macerozyme (25 μg/μl) and 1 mM AgNO3 incubated at 80 °C for 8 h. AgNPs were characterized by UV–Visible spectroscopy, dynamic light scattering (DLS), scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy (TEM) and X-ray diffraction (XRD). Results Characterization studies suggest the synthesis of elliptical, stable and crystalline AgNPs with an average size of 38.26 ± 0.4 nm calculated using TEM. The XRD pattern revealed the face-centered-cubic (fcc) form of metallic silver. Good shape integrity and dispersion of AgNPs after 1 year of incubation confirmed their stability. AgNPs were exibited the antimicrobial property against ten pathogenic bacteria, three molds and one yeast. The AgNPs also revealed remarkable antimicrobial activity against three MDR strains i.e. Extended spectrum beta-lactamase positive Escherichia coli, Staphylococcus aureus (MRSA) and Teicoplanin resistant Streptococcus Pneumoniae. The AgNPs coated surgical threads (suture) were revealed the remarkble antibacterial activity against three MDR strains. This is the first report to synthesize antimicrobial elliptical AgNPs using enzymes. Conclusion The results suggest the possibilities to develop the nanoparticles coated antimicrobial medical fabric to combat against MDR infection

Erasmus syndrome: A rare case report of silicosis and systemic sclerosis

Abstract People with silicosis may develop Erasmus syndrome, a condition characterized by the emergence of systemic sclerosis (SSc) after silica exposure. This case study emphasizes the significance of understanding the connection between occupational silica exposure, silicosis, and SSc. A 24‐year‐old male stonecutter got silicosis and a form of SSc following 8 years on his job as a stonecutter. The signs and symptoms the patient experienced were Raynaud's phenomenon, cutaneous fibrosis, arthralgia, digital pitting, and respiratory distress. High‐resolution computed tomography (HRCT) revealed interstitial lung disease and calcified mediastinal lymph nodes. This case study demonstrates the clinical importance of the relationship between occupational silica exposure, silicosis, SSc, and Erasmus syndrome. Healthcare providers need to be aware of the possible difficulties and issues that may result from silica exposure. They should prioritize quick detection and efficient treatment plans for those who have been exposed to silica while on the job

MOESM1 of Enzyme-mediated formulation of stable elliptical silver nanoparticles tested against clinical pathogens and MDR bacteria and development of antimicrobial surgical thread

Additional file 1. UV–Vis spectra of AgNPs synthesized at 37 °C, 60 °C, 80 °C and 90 °C temperature