ANTIHYPERGLYCEMIC AND ANTIDYSLIPIDEMIC POTENTIAL OF IPOMOEA BATATAS LEAVES IN VALIDATED DIABETIC ANIMAL MODELS

Objective: The present study was undertaken to investigate the antidiabetic potential of the leaves of Ipomoea batatas.Methods: The crude powder, 95% ethanolic, 50% ethanolic and aqueous extracts of Ipomoea batatas leaves were administered to normoglycemic and streptozotocin (STZ)-induced diabetic rats in a single dose study. The chloroform, butanol and aqueous fractions of aqueous extract were investigated for their antihyperglycemic on STZ-induced diabetic rats. Multiple dose study of an aqueous fraction was also done in STZ and neonatal STZ-induced diabetic rats. Further, the aqueous fraction was measured against the alpha glucosidase and aldose reductase enzymes, and glucose uptake in L6 myotubes.Results: The aqueous extract showed significant lowering of postprandial hyperglycemia of post sucrose loaded normal rats and significantly declined the blood glucose level of STZ-induced diabetic rats. The aqueous fraction at a single dose of 100 mg/kg b. w in comparison with chloroform and butanol fractions significantly lowered the blood glucose level of STZ-induced diabetic rats. The aqueous fraction in a multiple dose study were found to significantly improved the percent glycated hemoglobin (%HbA1c), fasting blood glucose, oral glucose tolerance (OGTT), serum insulin, lipid profile, liver and kidney parameters in STZ-induced diabetic rats. Marked improvement in OGTT and serum insulin levels was also found in neonatal STZ-induced diabetic rats. In vitro study, the aqueous fraction of I. batatas increased glucose uptake in L6 myotubes and inhibits the α-glucosidase and aldose reductase enzymes.Conclusion: The present study demonstrated the significant antidiabetic activity of the I. batatas leaves by promoting insulin secretion, alpha glucosidase and aldose reductase enzyme inhibition.Â

Makromolekulski prolijekovi. XII. Konjugati primakina: Sinteza i preliminarno ispitivanje antimalarijskog djelovanja

New primaquine conjugates 5-7 with glucosamine and two polymers of polyaspartamide type, poly/a,b-(N-2-hydroxyethyl-DL-aspartamide)/ (PHEA) and poly/a,b-(N-3-hydroxypropyl-DL-aspartamide)/ (PHPA), were synthesized, characterized and screened for their antimalarial activity. The conjugates differed in type of covalent bounding, length of spacer between the polymeric carrier and drug, molecular mass and drug-loading. Blood-schizontocidal activity of the prepared conjugates was tested against Plasmodium berghei infection in Swiss mice. The polymeric conjugates showed better antimalarial activity than glucosamine conjugate.U radu je opisana sinteza, karakterizacija i ispitivanje antimalarijskog djelovanja novih konjugata primakina 5-7 s glukozaminom i dva polimera poliaspartamidnog tipa, poli/a,b-(N-2-hidroksietil-DL-aspartamidom)/ (PHEA) i poli/a,b-(N-3-hidroksipropil-DL-aspartamidom)/ (PHPA). Konjugati su se razlikovali u vrsti kovalentne veze, duljini razmaknice između polimernog nosača i ljekovite tvari, molekulskoj masi i količini vezanog lijeka. Šizontocidno djelovanje pripravljenih konjugata ispitano je na miševima inficiranim Plasmodium berghei. Polimerni konjugati pokazali su jače antimalarijsko djelovanje nego konjugat s glukozamino

Extraction and Characterization of Nanocellulose from Wheat Straw: Facile Approach

The environmental concern occurs due to the extreme use of synthetic materials that have been fortified to develop innovative, multifunctional, and sustainable materials using copious lignocellulosic biomass. In this present study, work was done on the extraction of nanocellulose from wheat straw, and found that wheat straw is an admirable source of cellulose. Chemical processes were used to isolate the cellulose and remove unwanted lignin and hemicellulose from wheat straw followed by sonication, cryo-crushing, and magnetic stirring to achieve nanocellulose. The observed amount of cellulose (36.1%), hemicellulose (30.3%), lignin (17%), and ash content (9.2%) of raw wheat straw. Structural, morphological, and thermal characterization were estimated from FTIR, XRD, FESEM, TEM, DSC, TGA, and AFM for the identification and characterization of extracted cellulose from wheat straw. FTIR showed that the peaks at wavelength 1430.50 cm-1 and 1638.41 cm-1 both show that cellulose is present in the extracted nanocellulose.  Extracted nanocellulose was crystalline and had a 68.96% Crystallinity Index. Morphological analysis, FESEM showed that the untreated wheat straw has an irregular porous structure but the extracted nanocellulose has a regular shape having straight fibers connected. TEM analysis showed that the extracted nanocellulose has a spherical shape structure connected, showing the regular shape, the obtained spherical shape regulates the nanocellulose for further applications. Thermal degradation was observed using TGA which shows that the nanocellulose decomposition was observed around 3600C. AFM determination shows a bell-shaped structure on a smooth surface with a particle height of 3.2 nm and the mean roughness of 110.4 nm was obtained from the extracted nanocellulose. Extracted nanocellulose has a particle size of 58.77 nm

Structural and Morphological Characterization of Nanocellulose Extracted from Cotton Straw Residue

This study is focused on the synthesis and characterization of cotton straw residue. Nanocellulose was synthesized by chemical method and followed by ultrasonication and cryocrushing. The results of the present study show that the cotton straw residue consists of lignin (27%), hemicellulose (15%), cellulose (32%), and ash content  (2.3%). Nanocellulose was characterized by FTIR, XRD, FESEM, TEM, DSC, TGA, and AFM.  Two aromatic rings were observed at wavelength 1650.47cm-1 and  1436.53 cm-1 which indicates that there is a presence of cellulose in the prepared sample which was characterized by FTIR. The structural analysis shows that the material was amorphous and the nanocellulose crystallinity is 23 %. The morphological analysis using FESEM indicates even elongated fiber with a smooth surface and it contains pore in the nanocellulose of cotton residue. TEM analysis indicates that nanocellulose has an irregular shape with a circular rod-like structure of different sizes. The enthalpy of nanocellulose changes at 168.48℃ due to endothermic transition. TGA results show that the nanocellulose is degraded in the temperature range 300-355℃ and low thermal stability was observed during the experiment. AFM  result shows the needle shape particle ( root square mean roughness = 0.1738nm) and the size of nanocellulose was observed 7.1 nm

E3 ubiquitin ligase Fbw7 negatively regulates granulocytic differentiation by targeting G-CSFR for degradation

AbstractTight control between activation and attenuation of granulocyte colony stimulating factor receptor (G-CSFR) signaling is essential to regulate survival, proliferation and differentiation of myeloid progenitor cells. Previous studies demonstrated negative regulation of G-CSFR through endosomal–lysosomal routing and ubiquitin–proteasome mediated degradation. However, very few E3 ubiquitin ligases are known to target G-CSFR for ubiquitin–proteasome pathway. Here we identified F-box and WD repeat domain-containing 7 (Fbw7), a substrate recognizing component of Skp–Cullin–F box (SCF) E3 ubiquitin Ligase physically associates with G-CSFR and promotes its ubiquitin-mediated proteasomal degradation. Our data shows that Fbw7 also interacts with and degrades G-CSFR-T718 (a truncated mutant of G-CSFR found in severe congenital neutropenia/acute myeloid leukemia (SCN/AML patients)) though at a quite slower rate compared to G-CSFR. We further show that glycogen synthase kinase 3 beta (GSK3β), like Fbw7 also targets G-CSFR and G-CSFR-T718 for degradation; however, Fbw7 and GSK3β are interdependent in targeting G-CSFR/G-CSFR-T718 for degradation because they are unable to degrade G-CSFR individually when either of them is knocked down. We further show that Fbw7 mediated downregulation of G-CSFR inhibits signal transducer and activator of transcription 3 (STAT3) phosphorylation which is required for G-CSF dependent granulocytic differentiation. In addition, our data also shows that inhibition of Fbw7 restores G-CSFR signaling leading to enhanced STAT3 activity resulting in massive granulocytic differentiation. These data indicate that Fbw7 together with GSK3β negatively regulates G-CSFR expression and its downstream signaling

Mapping inequalities in exclusive breastfeeding in low- and middle-income countries, 2000–2018

Exclusive breastfeeding (EBF)—giving infants only breast-milk for the first 6 months of life—is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for example, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization’s Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030

Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019

Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. Methods We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (USMR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. Findings Global U5MR decreased from 71.2 deaths per 1000 livebirths (95% uncertainty interval WI] 68.3-74-0) in 2000 to 37.1 (33.2-41.7) in 2019 while global NMR correspondingly declined more slowly from 28.0 deaths per 1000 live births (26.8-29-5) in 2000 to 17.9 (16.3-19-8) in 2019. In 2019,136 (67%) of 204 countries had a USMR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030,154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9.65 million (95% UI 9.05-10.30) in 2000 and 5.05 million (4.27-6.02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3.76 million 95% UI 3.53-4.021) in 2000 to 48% (2.42 million; 2.06-2.86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0.80 (95% UI 0.71-0.86) deaths per 1000 livebirths and U5MR to 1.44 (95% UI 1-27-1.58) deaths per 1000 livebirths, and in 2019, there were as many as 1.87 million (95% UI 1-35-2.58; 37% 95% UI 32-43]) of 5.05 million more deaths of children younger than 5 years than the survival potential frontier. Interpretation Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve USMR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

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