Coumarins as antioxidants Kostova, I; Bhatia, S; Grigorov, P ...
Current medicinal chemistry,
09/2011, Volume:
18, Issue:
25
Journal Article
Peer reviewed
Coumarins, a well-known class of naturally occurring compounds, display a remarkable array of biochemical and pharmacological actions, some of which suggest that certain members of this group of ...compounds may significantly affect the function of various mammalian cellular systems. The development of coumarins as antioxidant agents has attracted much attention in recent years. Coumarins afford an opportunity for the discovery of new antioxidants with truly novel mechanisms of action. This review updates and expands the 2006 review by the same author. The review considers and incorporates the most recently published literature on coumarins as related to their antioxidant properties. A lot of coumarins have been identified from natural sources, especially green plants. These natural compounds have served as valuable leads for further design and synthesis of more active analogues. Beyond doubt, a deep understanding of the mechanisms of existing synthetic and natural coumarins will build the basis for the rational design.
The human papillomavirus (HPV) replication cycle is tightly linked to epithelial cell differentiation. To examine HPV-associated changes in the keratinocyte transcriptome, RNAs isolated from ...undifferentiated and differentiated cell populations of normal, spontaneously immortalized keratinocytes (NIKS) and NIKS stably transfected with HPV16 episomal genomes (NIKS16) were compared using next-generation sequencing (RNA-Seq). HPV16 infection altered expression of 2,862 cellular genes. Next, to elucidate the role of keratinocyte gene expression in late events during the viral life cycle, RNA-Seq was carried out on triplicate differentiated populations of NIKS (uninfected) and NIKS16 (infected). Of the top 966 genes altered (>log
= 1.8, 3.5-fold change), 670 genes were downregulated and 296 genes were upregulated. HPV downregulated many genes involved in epithelial barrier function, which involves structural resistance to the environment and immunity to infectious agents. For example, HPV infection repressed expression of the differentiated keratinocyte-specific pattern recognition receptor TLR7, the Langerhans cell chemoattractant CCL20, and proinflammatory cytokines interleukin 1α (IL-1α) and IL-1β. However, the type I interferon regulator IRF1, kappa interferon (IFN-κ), and viral restriction factors (IFIT1, -2, -3, and -5, OASL, CD74, and RTP4) were upregulated. HPV infection abrogated gene expression associated with the physical epithelial barrier, including keratinocyte cytoskeleton, intercellular junctions, and cell adhesion. Quantitative PCR (qRT-PCR) and Western blotting confirmed changes in expression of seven of the most significantly altered mRNAs. Expression of three genes showed statistically significant changes during cervical disease progression in clinical samples. Taken together, the data indicate that HPV infection manipulates the differentiating keratinocyte transcriptome to create an environment conducive to productive viral replication and egress.
HPV genome amplification and capsid formation take place in differentiated keratinocytes. The viral life cycle is intimately associated with host cell differentiation. Deep sequencing (RNA-Seq) of RNA from undifferentiated and differentiated uninfected and HPV16-positive keratinocytes showed that almost 3,000 genes were differentially expressed in keratinocytes due to HPV16 infection. Strikingly, the epithelial barrier function of differentiated keratinocytes, comprising keratinocyte immune function and cellular structure, was found to be disrupted. These data provide new insights into the virus-host interaction that is crucial for the production of infectious virus and reveal that HPV infection remodels keratinocytes for completion of the virus replication cycle.
To assess the scope for enhancing productivity of soybean (
Glycine max L. Merr.), the CROPGRO-Soybean model was calibrated and validated for the diverse soybean-growing environments of central and ...peninsular India. The validated model was used to estimate potential yields (water non-limiting and water limiting) and yield gaps of soybean for 21 locations representing major soybean regions of India. The average water non-limiting potential yield of soybean for the locations was 3020
kg
ha
−1, while the water limiting potential was 2170
kg
ha
−1 indicating a 28% reduction in yield due to adverse soil moisture conditions. As against this, the actual yields of locations averaged 1000
kg
ha
−1, which was 2020 and 1170
kg
ha
−1 less than the water non-limiting potential and water limiting potential yields, respectively. Across locations the water non-limiting potential yields were less variable than water limited potential and actual yields, and strongly correlated with solar radiation during the season (
R
2
=
0.83,
p
≤
0.01). Both simulated water limiting potential yield (
R
2
=
0.59,
p
≤
0.01) and actual yield (
R
2
=
0.33,
p
≤
0.05) had significant but positive and curvilinear relationships with crop season rainfall across locations. The gap between water non-limiting and water limiting potential yields was very large at locations with low crop season rainfall and narrowed down at locations with increasing quantity of crop season rainfall. On the other hand, the gap between water limiting potential yield and actual farmers yield was narrow at locations with low crop season rainfall and increased considerably at locations with increasing amounts of rainfall. This yield gap, which reflects the actual yield gap in rainfed environment, is essentially due to non-adoption of improved crop management practices and could be reduced if proper interventions are made. The simulation study suggested that conservation of rainfall and drought resistant varieties in low rainfall regimes; and alleviation of water-logging and use of water-logging tolerant varieties in high rainfall regimes will be the essential components of improved technologies aimed at reducing the yield gaps of soybean. Harvesting of excess rainfall during the season and its subsequent use as supplemental irrigation would further help in increasing crop yields at most locations.
Context: Between 1915 and 1950, the infant mortality rate (IMR) in the United States declined from 100 to fewer than 30 deaths per 1,000 live births, prior to the widespread use of medical ...technologies and vaccination. In 2015 the IMR in low- and middle-income countries (LMICs) was 53.2 deaths per 1,000 live births, which is comparable to the United States in 1935 when IMR was 55.7 deaths per 1,000 live births. We contrast the role of public health institutions and interventions for IMR reduction in past versus present efforts to reduce infant mortality in LMICs to critically examine the current evidence base for reducing infant mortality and to propose ways in which lessons from history can inform efforts to address the current burden of infant mortality. Methods: We searched the peer-reviewed and gray literature on the causes and explanations behind the decline in infant mortality in the United States between 1850 and 1950 and in LMICs after 2000. We included historical analyses, empirical research, policy documents, and global strategies. For each key source, we assessed the factors considered by their authors to be salient in reducing infant mortality. Findings: Public health programs that played a central role in the decline in infant mortality in the United States in the early 1900s emphasized large structural interventions like filtering and chlorinating water supplies, building sanitation systems, developing the birth and death registration area, pasteurizing milk, and also educating mothers on infant care and hygiene. The creation of new institutions and policies for infant health additionally provided technical expertise, mobilized resources, and engaged women's groups and public health professionals. In contrast, contemporary literature and global policy documents on reducing infant mortality in LMICs have primarily focused on interventions at the individual, household, and health facility level, and on the widespread adoption of cheap, ostensibly accessible, and simple technologies, often at the cost of leaving the structural conditions that determine child survival largely untouched. Conclusions: Current discourses on infant mortality are not informed by lessons from history. Although structural interventions were central to the decline in infant mortality in the United States, current interventions in LMICs that receive the most global endorsement do not address these structural determinants of infant mortality. Using a historical lens to examine the continued problem of infant mortality in LMICs suggests that structural interventions, especially regarding sanitation and civil registration, should again become core to a public health approach to addressing infant mortality.
β-Glucosidases constitute a major group among glycosylhydrolase enzymes. Out of the 82 families classified under glycosylhydrolase category, these belong to family 1 and family 3 and catalyze the ...selective cleavage of glucosidic bonds. This function is pivotal in many crucial biological pathways, such as degradation of structural and storage polysaccharides, cellular signaling, oncogenesis, host-pathogen interactions, as well as in a number of biotechnological applications. In recent years, interest in these enzymes has gained momentum owing to their biosynthetic abilities. The enzymes exhibit utility in syntheses of diverse oligosaccharides, glycoconjugates, alkyl- and amino-glucosides. Attempts are being made to understand the structure-function relationship of these versatile biocatalysts. Earlier reviews described the sources and properties of microbial β-glucosidases, yeast β-glucosidases, thermostable fungal β-glucosidase, and the physiological functions, characteristics, and catalytic action of native β-glucosidases from various plant, animal, and microbial sources. Recent efforts have been directed towards molecular cloning, sequencing, mutagenesis, and crystallography of the enzymes. The aim of the present article is to describe the sources and properties of recombinant β-glucosidases, their classification schemes based on similarity at the structural and molecular levels, elucidation of structure-function relationships, directed evolution of existing enzymes toward enhanced thermostability, substrate range, biosynthetic properties, and applications.
In India, 66% of 8 million married adolescents (~5.3 million) are nulliparous and likely to conceive soon. Among married young women aged 20-24 years about 9.1 million are nulliparous. This group ...remains relatively less reached in maternal nutrition programs. Current estimates of their nutritional status and predictors of body mass index (BMI) are unavailable. Thinness (BMI <18.5 kg/m2), severe thinness (BMI <16 kg/m2), overweight or obesity (BMI ≥ 23kg/m2) prevalence estimates are presented based on a sample of 11,265 married nulliparous adolescents (15-19 years, married, no parity) and 15,358 young women (20-24 years, married, no parity) drawn from the National Family Health Surveys 2005-06 and 2015-16. Trends by age, time and state were analysed. Predictors of BMI were investigated using linear regression. Using BMI for age z score (BAZ) as standard reference, BMI cut-off was calculated for thinness (-2SD) and overweight or obesity (+1SD) among married nulliparous adolescents as recommended for population under 19 years. 35% sampled adolescents and 26% young women were thin; 4%-5% severely thin. Overweight or obesity was higher among married nulliparous young women than married nulliparous adolescents (21% versus 11%). Eight in 1000 were short, thin and young and six in 1000 were short, thin, anemic and young. At 15 years of age, prevalence of thinness based on BMI was 46.5% while based on BAZ, 7.6%. At 24 years of age thinness was 22.5%. Decadal reduction in thinness was half among married nulliparous adolescents (4% points) compared with married nulliparous young women (8% points). Decadal increase in overweight/ obesity ranged from 4% to 5% in both age groups. Western states had high prevalence of thinness; Tamil Nadu had highest prevalence of overweight or obesity. Incremental increase in age and wealth increased BMI among young women more than adolescents. BMI was lower among adolescents and young women wanting a child later than soon β -0.28 (CI -0.49- -0.07), β -0.33(CI -0.56- -0.093), respectively. BMI cut-off 16.49 kg/m2 and 24.12 kg/m2 had a high sensitivity (100%, 99.7%) and specificity (98.9%, 98.5%) to screen thin and overweight or obese adolescents, respectively. Owing to the high prevalence of both thinness and overweight/obesity among nulliparous married adolescents and women, nutritional anthropometry based screening should be initiated for this target group, along with a treatment package in states with high and persistent malnutrition. Family planning services should be integrated in nutrition programs for this target group to achieve normal nutritional status before conception.
Field experiments with soybean were conducted over a period of 1990–1998 in diverse Indian locations ranging in latitude, longitude, and elevation. These locations provided a wide range of ...environments for testing and validation of the crop growth (CROPGRO) model considered in this study with observed changes in soils, rainfall and other weather parameters. Model predicted satisfactorily the trends of days to flowering, maturity and grain yields. The deviations of simulated results were within ±15% of the measurements.
Validated CROPGRO model has been used to simulate the impact of climate change on soybean production in India. The projected scenarios for the Indian subcontinent as inferred from three state-of-the-art global climate models (GCMs) have been used in the present study. There was a decrease (ranging between about 10 and 20%) in soybean yield in all the three future scenarios when the effect of rise in surface air temperature at the time of the doubling of CO
2 concentration was considered. The results obtained on the mitigatory option for reducing the negative impacts of temperature increases indicate that delaying the sowing dates would be favorable for increased soybean yields at all the locations in India. Sowing in the second season would also be able to mitigate the detrimental effects of future increases in surface temperature due to global warming at some locations.
Objective
Deficiency of adenosine deaminase 2 (DADA2) is a potentially fatal monogenic syndrome characterized by variable manifestations of systemic vasculitis, bone marrow failure, and ...immunodeficiency. Most cases are diagnosed by pediatric care providers, given the typical early age of disease onset. This study was undertaken to describe the clinical phenotypes and treatment response both in adults and in children with DADA2 in India.
Methods
A retrospective analysis of pediatric and adult patients with DADA2 diagnosed at various rheumatology centers across India was conducted. Clinical characteristics, diagnostic findings, and treatment responses were analyzed in all subjects.
Results
In total, 33 cases of DADA2 were confirmed in this cohort between April 2017 and March 2020. Unlike previous studies, nearly one‐half of the confirmed cases presented during adulthood. All symptomatic patients exhibited features of vasculitis, whereas constitutional symptoms and anemia were more common in pediatric patients. Cutaneous and neurologic involvement were common, and 18 subjects had experienced at least one stroke. In addition, the clinical spectrum of DADA2 was expanded by recognition of novel features in these patients, including pancreatic infarction, focal myocarditis, and diffuse alveolar hemorrhage. Treatment with tumor necrosis factor inhibitors (TNFi) was initiated in 25 patients. All of the identified disease manifestations showed marked improvement after initiation of TNFi, and disease remission was achieved in 19 patients. Two cases were complicated by tuberculosis infection, and 2 deaths were reported.
Conclusion
This report presents the first case series of patients with DADA2 from India, diagnosed by adult and pediatric care providers. The findings raise awareness of this syndrome, particularly with regard to its presentation in adults.
During the COVID-19 pandemic, the total number of hospital beds in the National Capital Region (NCR) of Delhi was 54,321 (roughly 300 beds per one lakh population), which was inadequate for the ...patients. Therefore, the Indian government initiated the construction of a 1,000-bedded greenfield hangar-based hospital to bridge the healthcare gap. As a result, Intensive Care Unit (ICU) beds in the facility augmented the COVID-19 care ICU beds in the city by 11%. The authors were involved in the planning, developing, and initiating the functioning of 1,000-bedded Dedicated COVID-19 Hospital (DCH). The hospital was conceptualized, built, and operationalized in 12 days only. Lessons learned from this experience would be of benefit should similar situations arise in future. Coordinating structural designing early with the entire project team—from facility administrators and medical practitioners to architects, consultants, and contractors—can result in a structure that better matches the facility’s long-term needs and often saves construction time and costs. This article enumerates various challenges faced and the way they were addressed. This hangar-based hospital can be rapidly constructed and deployed on a massive scale. While structural integrity is essential, the planning team was particularly aware of the patient-centric modality of healthcare. Many modifications were carried out in the structure based on patient inputs. Informal discussions with discharged patients and relatives revealed that the human-centric approach was the mainstay of the therapy.
A 1 Tb 4-b/cell 162-layer 3-D flash memory achieves 15-Gb/mm2 areal density and delivers program throughput up to 60 MB/s and the best case tR of 65 <inline-formula> <tex-math notation="LaTeX">\mu ...\text{s} </tex-math></inline-formula> by employing 8-kB wordline (WL) central stair structure and contact-through-WL (CTW) architecture. IO speed of 2.4 Gb/s with low tapped termination/center tapped termination (LTT/CTT) combo driver is supported. This article also discusses data transfer energy reduction using VCCQ domain design and data bus inversion (DBI) technique. Novel time division peak power management (TD-PPM) feature can reduce system peak current while maximizing system performance. Cache and IO discrete Fourier transform (DFT) enable a high-speed testing at wafer level for test cost reduction.
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