EVALUATION OF WOUND HEALING ACTIVITY OF ACACIA AURICULIFORMIS A. CUNN. STEM BARK

Objective: To evaluate in vivo wound healing activity of ointment containing ethanol and aqueous bark extracts of Acacia auriculiformis A. Cunn. (Family: Mimosaceae).Methods: The presence of phytochemicals like carbohydrates, phenols, flavonoids, tannins and saponins was determined by preliminary phytochemical screening. Wound healing effect of ointment containing 5% w/w ethanol and aqueous stem bark extracts was determined by using excision and incision wound models in Swiss albino mice. Hydroxyproline content determination and histopathological studies of treated groups were carried out.Results: The results showed that both formulations possess significant wound healing activity, which was evidenced by decreased period of epithelialization, increased rate of wound contraction, tensile strength, hydroxyproline content, granulation tissue and collagen fibre formation in all treated animals. The activity may be due to presence of phenols, tannins, and flavonoids.Conclusion: The ointment containing ethanol extract showed better wound healing activity than the ointment containing aqueous extract.Keywords: Acacia auriculiformis, excision wound model, hydroxyproline, incision wound model, tensile strength, wound contractio

Screen Time in Children of Central Nepal: A Parent Reported Cross-sectional Study during COVID-19 Pandemic

Introduction: The insurgence of COVID-19 has affected many aspects of human life and its repercussions on the life of children cannot be undermined. In addition to the serious impact on health and food insecurity, lack of recreational activities, school closure and switch to online learning have pushed children to excessive screen exposure. This study aimed to assess the duration of screen time and parental perspective towards screen viewing in children during the pandemic. Methods: A community-based descriptive cross-sectional study was carried out in Bharatpur Metropolitan City. A total of 384 parents were included purposively. A semi-structured questionnaire was used to interview the parents during the pandemic for one month. During the data collection, appropriate universal precautions for COVID-19 were taken. Results: The median duration of screen exposure was two hours (30 minutes to 9 hours). Most (65%) of the parents stated that their children spent more time on screen compared to pre-COVID-19 times. The majority (82%) of the parents were worried about the possible consequences of excessive screen time. More than two-thirds (72%) of parents thought that screen exposure also has various benefits for children. Conclusion: Most of the children exceeded the duration of screen time recommended by the World Health Organization. Most of the parents were worried about the harmful effects on the health and behavior of children

Electrophilic Aldehyde 4-Hydroxy-2-Nonenal Mediated Signaling and Mitochondrial Dysfunction

Reactive oxygen species (ROS), a by-product of aerobic life, are highly reactive molecules with unpaired electrons. The excess of ROS leads to oxidative stress, instigating the peroxidation of polyunsaturated fatty acids (PUFA) in the lipid membrane through a free radical chain reaction and the formation of the most bioactive aldehyde, known as 4-hydroxynonenal (4-HNE). 4-HNE functions as a signaling molecule and toxic product and acts mainly by forming covalent adducts with nucleophilic functional groups in proteins, nucleic acids, and lipids. The mitochondria have been implicated as a site for 4-HNE generation and adduction. Several studies clarified how 4-HNE affects the mitochondria’s functions, including bioenergetics, calcium homeostasis, and mitochondrial dynamics. Our research group has shown that 4-HNE activates mitochondria apoptosis-inducing factor (AIFM2) translocation and facilitates apoptosis in mice and human heart tissue during anti-cancer treatment. Recently, we demonstrated that a deficiency of SOD2 in the conditional-specific cardiac knockout mouse increases ROS, and subsequent production of 4-HNE inside mitochondria leads to the adduction of several mitochondrial respiratory chain complex proteins. Moreover, we highlighted the physiological functions of HNE and discussed their relevance in human pathophysiology and current discoveries concerning 4-HNE effects on mitochondria

SOD2 Deficiency in Cardiomyocytes Defines Defective Mitochondrial Bioenergetics as a Cause of Lethal Dilated Cardiomyopathy

Electrophilic aldehyde (4-hydroxynonenal; 4-HNE), formed after lipid peroxidation, is a mediator of mitochondrial dysfunction and implicated in both the pathogenesis and the progression of cardiovascular disease. Manganese superoxide dismutase (MnSOD), a nuclear-encoded antioxidant enzyme, catalyzes the dismutation of superoxide radicals (O2•-) in mitochondria. To study the role of MnSOD in the myocardium, we generated a cardiomyocyte-specific SOD2 (SOD2Δ) deficient mouse strain. Unlike global SOD2 knockout mice, SOD2Δ mice reached adolescence; however, they die at ~4 months of age due to heart failure. Ultrastructural analysis of SOD2Δ hearts revealed altered mitochondrial architecture, with prominent disruption of the cristae and vacuole formation. Noninvasive echocardiographic measurements in SOD2Δ mice showed dilated cardiomyopathic features such as decreased ejection fraction and fractional shortening along with increased left ventricular internal diameter. An increased incidence of ventricular tachycardia was observed during electrophysiological studies of the heart in SOD2Δ mice. Oxidative phosphorylation (OXPHOS) measurement using a Seahorse XF analyzer in SOD2Δ neonatal cardiomyocytes and adult cardiac mitochondria displayed reduced O2 consumption, particularly during basal conditions and after the addition of FCCP (H+ ionophore/uncoupler), compared to that in SOD2fl hearts. Measurement of extracellular acidification (ECAR) to examine glycolysis in these cells showed a pattern precisely opposite that of the oxygen consumption rate (OCR) among SOD2Δ mice compared to their SOD2fl littermates. Analysis of the activity of the electron transport chain complex identified a reduction in Complex I and Complex V activity in SOD2Δ compared to SOD2fl mice. We demonstrated that a deficiency of SOD2 increases reactive oxygen species (ROS), leading to subsequent overproduction of 4-HNE inside mitochondria. Mechanistically, proteins in the mitochondrial respiratory chain complex and TCA cycle (NDUFS2, SDHA, ATP5B, and DLD) were the target of 4-HNE adduction in SOD2Δ hearts. Our findings suggest that the SOD2 mediated 4-HNE signaling nexus may play an important role in cardiomyopathy

Arsenic Trioxide Exerts Antimyeloma Effects by Inhibiting Activity in the Cytoplasmic Substrates of Histone Deacetylase 6

Arsenic trioxide (As2O3) has shown remarkable efficacy for the treatment of multiple myeloma (MM). Histone deacetylases (HDAC) play an important role in the control of gene expression, and their dysregulation has been linked to myeloma. Especially, HDAC6, a unique cytoplasmic member of class II, which mainly functions as α-tubulin deacetylase and Hsp90 deacetylase, has become a target for drug development to treat cancer due to its major contribution in oncogenic cell transformation. However, the mechanisms of action for As2O3 have not yet been defined. In this study, we investigated the effect of As2O3 on proliferation and apoptosis in human myeloma cell line and primary myeloma cells, and then we studied that As2O3 exerts antimyeloma effects by inhibiting activity in the α-tubulin and Hsp90 through western blot analysis and immunoprecipitation. We found that As2O3 acts directly on MM cells at relatively low concentrations of 0.5∼2.5 µM, which effects survival and apoptosis of MM cells. However, As2O3 inhibited HDAC activity at the relatively high concentration and dose-dependent manner (great than 4 µM). Subsequently, we found that As2O3 treatment in a dose- and time-dependent fashion markedly increased the level of acetylated α-tubulin and acetylated Hsp90, and inhibited the chaperone association with IKKα activities and increased degradation of IKKα. Importantly, the loss of IKKα-associated Hsp90 occurred prior to any detectable loss in the levels of IKKα, indicating a novel pathway by which As2O3 down-regulates HDAC6 to destabilize IKKα protein via Hsp90 chaperone function. Furthermore, we observed the effect of As2O3 on TNF-α-induced NF-κB signaling pathway was to significantly reduced phosphorylation of Ser-536 on NF-κB p65. Therefore, our studies provide an important insight into the molecular mechanism of anti-myeloma activity of As2O3 in HDAC6-Hsp90-IKKα-NFκB signaling axis and the rationale for As2O3 can be extended readily using all the HDAC associated diseases

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

The Molecular Origin and Taxonomy of Mucinous Ovarian Carcinoma

Mucinous ovarian carcinoma (MOC) is a unique subtype of ovarian cancer with an uncertain etiology, including whether it genuinely arises at the ovary or is metastatic disease from other organs. In addition, the molecular drivers of invasive progression, high-grade and metastatic disease are poorly defined. We perform genetic analysis of MOC across all histological grades, including benign and borderline mucinous ovarian tumors, and compare these to tumors from other potential extra-ovarian sites of origin. Here we show that MOC is distinct from tumors from other sites and supports a progressive model of evolution from borderline precursors to high-grade invasive MOC. Key drivers of progression identified are TP53 mutation and copy number aberrations, including a notable amplicon on 9p13. High copy number aberration burden is associated with worse prognosis in MOC. Our data conclusively demonstrate that MOC arise from benign and borderline precursors at the ovary and are not extra-ovarian metastases

Preparation and studies of electrical properties of cobalt substituted Li-Zn ferrites by sol-gel auto combustion method

A series of Co substituted lithium zinc ferrite powders with different content of Co (0.00 to 0.1 in steps of 0.02) were prepared by a novel sol-gel auto combustion process using citric acid. Their spinel structure was confirmed by XRD. The variation in lattice parameter and density with cobalt concentration was studied which showed an increasing trend. A decreasing pattern was observed in variation of porosity with increasing Co. Room temperature dielectric constant and resistivity were studied as a function of composition at 10 KHz. The room temperature dielectric constant decreases with successive addition of Co2+ in the series. The observed variation in dielectric constant has been explained on the basis of space charge polarization and Koops two layer model. Resistivity is observed to increase with increasing concentration and the observed variation in resistivity has been explained by Verwey hopping mechanism.Author Affiliation: Ibetombi Soibam1, Sumitra Phanjoubam1, H B Sharma1, H N K Sarma1 and Chandra Prakash2 1Department of Physics, Manipur University, Canchipur, Imphal-795 003, Manipur, India 2Directorate of ER & IPR, DRDO Bhawan, Rajaji Marg, New Delhi-110 011, India E-mail : [email protected] of Physics, Manipur University, Canchipur, Imphal-795 003, Manipur, India 2Directorate of ER & IPR, DRDO Bhawan, Rajaji Marg, New Delhi-110 011, Indi