The HBV web: An insight into molecular interactomes between the hepatitis B virus and its host en route to hepatocellular carcinoma.

Hepatitis B virus (HBV) is a major aetiology associated with the development and progression of hepatocellular carcinoma (HCC), the most common primary liver malignancy. Over the past few decades, direct and indirect mechanisms have been identified in the pathogenesis of HBV-associated HCC which include altered signaling pathways, genome integration, mutation-induced genomic instability, chromosomal deletions and rearrangements. Intertwining of the HBV counterparts with the host cellular factors, though well established, needs to be systemized to understand the dynamics of host-HBV crosstalk and its consequences on HCC progression. Existence of a vast array of protein-protein and protein-nucleic acid interaction databases has led to the uncoiling of the compendia of genes/gene products associated with these interactions. This review covers the existing knowledge about the HBV-host interplay and brings it down under one canopy emphasizing on the HBV-host interactomics; and thereby highlights new strategies for therapeutic advancements against HBV-induced HCC.

Salmonella Typhimurium U32 peptidase, YdcP, promotes bacterial survival by conferring protection against in vitro and in vivo oxidative stress.

YdcP, a U32 peptidase, is characterized as a putative collagenase with a role in several bacterial infections. However, its role in the pathogenesis of Salmonella Typhimurium remains elusive. Here, we investigated the role of U32 peptidase, YdcP, in the intracellular survival of S. Typhimurium (STM). Our study revealed a novel function of YdcP in protecting wild-type Salmonella from in vitro and in vivo oxidative stress. The ydcP knockout strain showed attenuated intracellular proliferation within the murine and human macrophages. Incubation of wild-type Salmonella with H2O2 induced the transcript level expression of ydcP. Moreover, deleting ydcP increased the susceptibility of the bacteria to in vitro oxidative stress. STM ΔydcP showed increased colocalization with the gp91phox subunit of the NADPH phagocytic oxidase in RAW264.7 cells. Further, we observed a reduction in the expression of bacterial anti-oxidant genes in STM ΔydcP growing within the RAW264.7 cells. The delay in the death of BALB/c mice infected with STM ΔydcP proved the association of ydcP with the in vivo pathogenesis of Salmonella. Finally, the attenuated growth of the ydcP mutant in wild-type C57BL/6 mice and the recovery of their growth inhibition in gp91phox-/- C57BL/6 mice endorsed the role of ydcP in protecting Salmonella from in vivo oxidative stress. Together, our study depicts a novel role of Salmonella Typhimurium YdcP, a putative U32 peptidase in rendering protection against oxidative stress.

Risk factors for incident prostate cancer in a cohort of world trade center responders.

BACKGROUND: Despite a relatively young average age and no routine screening, prostate cancer is one of the most common cancers in men who worked at the World Trade Center (WTC) following the 9/11/2001 disaster. This study evaluated whether re-experiencing stressful memories of a traumatic event was associated with prostate cancer incidence. METHODS: Participants were males from one clinical center that monitors the health of first-responders (N = 6857). Monitoring began in July 2002 and occurs annually but does not include prostate cancer screening. Severity of physical exposures and of re-experiencing memories and stress responses were measured at study enrollment using standardized and validated methods in all participants. The outcome was incidence of diagnosed prostate cancer after enrollment (n = 68). Bivariate analyses provided age-adjusted incidence rates (aIR). Cox proportional hazards modeling was used to calculate incidence; hazards ratios (HR) were reported. RESULTS: The mean age of responders on 9/11/2001 was 37.9 years. Prostate cancer incidence was lowest in responders with no re-experiencing stress (aIR = 250.83/100,000 person-years, [233.41-268.25]) and highest in responders with severe re-experiencing stress (aIR = 818.49/100,000 person-years, [801.07-835.91]). Cox proportional hazards regression revealed that re-experiencing the stressful events of 9/11/2001 was associated with increased prostate cancer incidence (HR = 1.96 [1.26-3.05], P = 0.003), even upon adjusting for confounders. CONCLUSIONS: This is the first study to identify a positive association between re-experiencing a traumatic event and prostate cancer incidence. Our results are consistent with recent rodent model evidence demonstrating a direct biological link between stress pathways and prostate tumorigenesis and offer new hypotheses in the causality of prostate cancer.

Racial and ethnic differences in the relationship between antenatal stressful life events and postpartum depression among women in the United States: does provider communication on perinatal depression minimize the risk?

OBJECTIVE: Multi-state population-based studies exploring the racial/ethnic differences in the prevalence and correlates of postpartum depression (PPD), which affects 10-20% of women in the US, are rare. The aim of this study was to examine the racial/ethnic disparities in the relationship between antenatal stressful life events and PPD among US women and to explore whether antenatal health care provider communication on perinatal depression was associated with a lower risk. METHODS: Data from the 2009-2011 Pregnancy Risk Assessment Monitoring System (PRAMS) were used. For each racial/ethnic group, the distribution of PPD was compared according to different levels of the stressors and socio-demographic, pre-pregnancy, antenatal, delivery, and neonatal characteristics. Multivariable logistic regression analyses were performed with PPD as the outcome and all variables that were significant in bivariate analyses as predictors. RESULTS: Eleven percent of 87,565 women met the criteria for PPD with the prevalence ranging from 7.9% among Asian/Pacific Islanders to 14% among American Indian/Alaska Natives. Irrespective of race/ethnicity, having many bills to pay and having more than usual arguments with husband/partner were risk factors for PPD. Among non-Hispanic black (NHB) women, having a husband/partner who did not want the pregnancy was associated with PPD (adjusted odds ratio [aOR]: 1.47; 95% confidence interval [CI]: 1.14, 1.90), and among non-Hispanic whites (NHWs), drug/drinking problems of someone close was associated with PPD (aOR: 1.37; 95% CI: 1.21, 1.55). Provider communication was inversely associated with PPD among NHWs (aOR: 0.77; 95% CI: 0.69, 0.85) and NHBs (aOR: 0.74; 95% CI: 0.60, 0.93). CONCLUSION: The protective effect of provider communication on PPD suggests the benefit of a simple conversation about perinatal depression during antenatal care. Furthermore, risk factors for PPD varied by race/ethnicity suggesting that these vulnerabilities should be taken into consideration in identifying women at-risk for PPD.

Missed Opportunities for Preventing Perinatal Transmission of Human Immunodeficiency Virus, Florida, 2007-2014.

OBJECTIVES: Despite declining numbers of perinatally exposed infants, an increase in perinatal human immunodeficiency virus (HIV) infections from 2011 to 2013 prompted this study to identify missed perinatal HIV prevention opportunities. METHODS: Deidentified records of children born from 2007 through 2014, exposed to HIV perinatally, and reported to the Florida Department of Health were obtained. Crude relative risks (RRs) and 95% confidence intervals (CIs) for factors associated with perinatal transmission, nondiagnosis of maternal HIV infection, and nonreceipt of antiretroviral medication were calculated. RESULTS: Of the 4337 known singleton births exposed to maternal HIV infection, 70 (1.6%) were perinatally infected. Among perinatal transmission cases, more than one-third of mothers used illegal drugs or acquired a sexually transmitted infection during pregnancy. Perinatal transmission was most strongly associated with maternal HIV diagnosis during labor and delivery (RR 5.66, 95% CI 2.31-13.91) or after birth (RR 26.50, 95% CI 15.44-45.49) compared with antenatally or prenatally. Among the 29 women whose infection was not known before pregnancy and whose child was perinatally infected, 18 were not diagnosed during pregnancy; 12 had evidence of an acute HIV infection, and 6 had no prenatal care. CONCLUSIONS: Late diagnosis of maternal HIV infection appeared to be primarily the result of acute maternal infections and inadequate prenatal care. In Florida, effective programs to improve utilization of prenatal care and detection and primary prevention of prenatal acute infection are needed.

Racial/Ethnic Disparities in Antenatal Depression in the United States: A Systematic Review.

Objectives More than 10 % of pregnant women in the United States (U.S.) suffer from depression, which has far-reaching consequences on maternal and fetal well-being. There is conflicting evidence regarding the prevalence of antenatal depression among different race and ethnic groups. This systematic review aimed to summarize the existing literature concerning racial/ethnic disparities in the prevalence and correlates of antenatal depression in the U.S. Methods PubMed, CINAHL and PsycINFO databases were searched online for research studies published in English in peer-reviewed journals until March 2015, using a pre-designed search strategy. Eligibility was determined using pre-specified criteria; and quality was assessed. Results Forty-one (41) articles met the criteria; 13 were cross-sectional, and 21 were longitudinal studies. Overall, the prevalence of antenatal depression was 10-30 %; it was higher among non-Hispanic blacks (NHBs) and Hispanics, compared to non-Hispanic whites (NHWs). Few studies looked at the correlates of depression by race/ethnicity. Among employed women, higher depression scores were observed among NHBs, compared to NHWs; while there was no racial difference among unemployed women. Racial difference and race-employment interaction disappeared once discrimination was accounted for. In another study, higher parity, higher stress, and lower self-esteem were significant correlates of depression among NHBs, while less satisfaction with social support, and higher stress predicted higher depression scores among NHWs and Hispanics respectively. Conclusions The findings of our review suggest that not only is antenatal depression a major public health issue that needs to be addressed, but different racial/ethnic groups seem to differ in their vulnerability and risk factors.

Human papillomavirus vaccine acceptability among parents of adolescent girls: obstacles and challenges in Mysore, India.

OBJECTIVE: Worldwide, 530,000 women are diagnosed with cervical cancer and 275,000 die annually. India bears the greatest burden of the disease with 132,000 cases and 74,000 deaths yearly. Widespread uptake of human papillomavirus (HPV) vaccine could reduce incidence and mortality by two-thirds. This study explored obstacles and facilitators of parental acceptability of HPV vaccine. METHODS: In 2010, questionnaires were sent home with a random sample of 800 girls attending 12 schools in Mysore city to be completed by a parent. Data were analyzed using multivariable logistic regression with generalized estimating equation to account for potential clustering by school. RESULTS: Of the 797 completed surveys; 71% reported willingness to accept HPV vaccine for their daughters. The adjusted odds of acceptance was higher among participants who received recommendation from their parents, perceived cervical cancer as a serious disease, believed that HPV vaccine was safe, or felt that vaccination was a good way to protect against cervical cancer. Parents who had concerns about vaccine side-effects or thought that it would cause pain had lower odds of acceptance. CONCLUSION: Future promotion of vaccine should emphasize safety of immunization and involve promotion to the extended family, so that they actively recommend immunization of young adolescent girls.

Mental health issues among pregnant women in correctional facilities: a systematic review.

Incarceration-induced stress makes pregnant women in correctional facilities a high-risk group for mental health problems, resulting in adverse maternal and fetal outcomes. A systematic review was conducted to examine the prevalence and correlates of mental health issues among pregnant inmates. Databases searched included PubMed, Medline, CINAHL Plus, PsycINFO, National Criminal Justice Reference System, Social Work Abstracts, Cochrane and Campbell libraries, which were searched for studies published in English from 1950 till July 2013. Eleven studies were included of pregnant women in correctional facilities and addressed at least one mental illness. Quality score was assigned to these eligible articles. Due to heterogeneity, a narrative review was performed. All of the studies were conducted in the United States, with quality scores ranging from 7 to 10 out of 10. Only one of these studies used mixed methods, the rest were quantitative. Tobacco use among pregnant inmates exceeded 50%, with some studies reporting as high as 84%. Alcohol use was common; 36% of the inmates used illicit drugs in one study. Depression and anxiety levels were high-some studies reported depression among 80% of inmates. Findings suggest that mental health among pregnant prisoners is a huge concern that has not been adequately addressed.

Factors Associated With Gun Possession Among High-School Students in the U.S. Before and During the Pandemic.

Background: Adolescents' possession of guns was a matter of concern even before the pandemic. It is pertinent to examine whether students continued possessing guns after schools reopened, and if so, identify factors that might have been associated with such behaviors. Towards this end, the present study examined the relationship between highschool students' experiences and their propensity to possess guns. Methods: This used responses from multiple nationally representative cross-sectional surveys of high school students from the 2019 and 2021 Youth Risk Behavior Survey (YRBS) and the 2021 Adolescent Behaviors and Experiences Survey (ABES). Gun possession within the past year was the main outcome of interest. Experiences of violence, assault, injury, and other adverse experiences were the independent variables. Bivariate and multivariate logistic regressions, adjusting for sample weights, were performed using SAS. Results: Out of a total of more than 25,000 and 38,000 valid responses, respectively in 2019 and 2021 to the question on gun possession, 4.7% and 4.2% reported carrying a gun at least once within the past year. Experiences of sexual violence, involvement in physical fight, perceived lack of safety, and being threatened/injured by weapons, were associated with higher adjusted odds of guns possession among males and females. Among ABES 2021 respondents (more than 7500), those who witnessed violence in the neighborhood were more likely to possess guns. This association was significant among males, whereas parents being informed about whereabouts was significant for females. Conclusion: This study shows that adverse experiences were associated with a higher odds of guns possession among female and male highschool students. Witnessing violent attack on someone in the neighborhood emerged as a risk factor for males. This suggests that social determinants of health as well as adverse experiences are associated with gun possession among high-school students.

Ubiquitin: A double-edged sword in hepatitis B virus-induced hepatocellular carcinoma.

Hepatitis B virus is one of the leading causes behind the neoplastic transformation of liver tissue and associated mortality. Despite the availability of many therapies and vaccines, the pathogenic landscape of the virus remains elusive; urging the development of novel strategies based on the fundamental infectious and transformative modalities of the virus-host interactome. Ubiquitination is a widely observed post-translational modification of several proteins, which either regulates the proteins' turnover or impacts their functionalities. In recent years, ample amount of literature has accumulated regarding the ubiquitination dynamics of the HBV proteins as well as the host proteins during HBV infection and carcinogenesis; with direct and detailed characterization of the involvement of HBV in these processes. Interestingly, while many of these ubiquitination events restrict HBV life cycle and carcinogenesis, several others promote the emergence of hepatocarcinoma by putting the virus in an advantageous position. This review sums up the snowballing literature on ubiquitination-mediated regulation of the host-HBV crosstalk, with special emphasis on its influence on the establishment and progression of hepatocellular carcinoma on a molecular level. With the advent of cutting-edge ubiquitination-targeted therapeutic approaches, the findings emanating from this review may potentiate the identification of novel anti-HBV targets for the formulation of novel anticancer strategies to control the HBV-induced hepato-carcinogenic process on a global scale.

G6PD deficiency mediated impairment of iNOS and lysosomal acidification affecting phagocytotic clearance in microglia in response to SARS-CoV-2.

The glucose-6-phosphate dehydrogenase (G6PD) deficiency is X-linked and is the most common enzymatic deficiency disorder globally. It is a crucial enzyme for the pentose phosphate pathway and produces NADPH, which plays a vital role in regulating the oxidative stress of many cell types. The deficiency of G6PD primarily causes hemolytic anemia under oxidative stress triggered by food, drugs, or infection. G6PD-deficient patients infected with SARS-CoV-2 showed an increase in hemolysis and thrombosis. Patients also exhibited prolonged COVID-19 symptoms, ventilation support, neurological impacts, and high mortality. However, the mechanism of COVID-19 severity in G6PD deficient patients and its neurological manifestation is still ambiguous. Here, using a CRISPR-edited G6PD deficient human microglia cell culture model, we observed a significant reduction in NADPH level and an increase in basal reactive oxygen species (ROS) in microglia. Interestingly, the deficiency of the G6PD-NAPDH axis impairs induced nitric oxide synthase (iNOS) mediated nitric oxide (NO) production, which plays a fundamental role in inhibiting viral replication. Surprisingly, we also observed that the deficiency of the G6PD-NADPH axis reduced lysosomal acidification and free radical production, further abrogating the lysosomal clearance of viral particles. Thus, impairment of NO production, lysosomal functions, and redox dysregulation in G6PD deficient microglia altered innate immune response, promoting the severity of SARS-CoV-2 pathogenesis.

The aftermath of a diagnosis: From resistance to reconciliation.

The author, a doctor, describes the aftermath of being diagnosed with attention deficit hyperactivity disorder (ADHD) in his late 30s. He was incredulous and immediately resented the diagnosis. He reluctantly agreed to try the prescribed medication but struggled with that as well. Instead of rejecting the ADHD label, he later began reading and watching informative videos about ADHD and the many ways that executive functioning deficits affect behavior, including impulsive outbursts. The communication gap with his psychiatrist widened because of their "virtual" visits during the pandemic. He turned to his primary care physician, with whom he felt less inhibited, and shared his fears and concerns for his family, his career, and himself. As of now, he is looking for the added support of a therapist experienced at helping people with ADHD. Despite everything, he knows he will slip at times. But he is determined to get better at stemming episodes before they reach a tipping point. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Locked, Loaded, and Ready for School: The Association of Safety Concerns With Weapon-carrying Behavior Among Adolescents in the United States.

There is limited, if any, prior research exploring the potential link between adolescents' safety concerns and their predisposition to possess weapons has been limited. This study aimed to examine the relationship between high school students' perceived lack of safety and their weapons carrying behavior in a multiyear nationally representative sample of high school students. Information on self-reported weapons carrying in past month and gun carrying in past year, perceived lack of safety at school or during commute, being bullied and/or threatened, involvement in physical fights, and demographic characteristics were retrieved from Youth Risk Behavior Surveillance Survey data for 1991-2017. Generalized linear mixed models were used to address data clustering by survey year. Sampling design and sample weights were accounted for. Of a total number of 195,280 respondents with valid responses during 1991-2017, 18%, 7%, and 5%, respectively, carried weapon(s) in general, weapon(s) to school, and gun. On an average, 5% skipped school due to safety concerns. Missing ≥2 school days was associated with weapon (adjusted odds ratio [AOR]: 2.25; 95% confidence interval [CI]: 1.94 -2.61) and gun (AOR: 3.18; 95% CI: 1.81 -5.58) possessions, as well as weapons possession in school (AOR: 2.47; 95% CI: 1.96 -3.12). Experiences of weapons-induced injury(ies) or threat(s), and involvement in physical fights were other significant covariates in adjusted analyses. Compared with non-Hispanic whites, students of other racial/ethnic groups had significantly lower odds of possessing weapons. Perceived lack of safety emerged as a potential determinant of weapon carrying, a behavior with far-reaching public health concerns. While future research looking into the psychological motivations of possessing weapons is recommended, our findings offer a unique opportunity to address the crucial problems of school absenteeism induced by experiences of aggression and fears for safety as well as preempt the consequences of weapons-possession by adolescents.

G6PD deficiency: imbalance of functional dichotomy contributing to the severity of COVID-19.

Human COVID-19 has affected more than 491 million people worldwide. It has caused over 6.1 million deaths and has especially perpetrated a high number of casualties among the elderly and those with comorbid illnesses. COVID-19 triggers a pro-oxidant response, leading to the production of reactive oxygen species (ROS) as a common innate defense mechanism. However, ROS are regulated by a key enzyme called G6PD via the production of reduced nicotinamide adenine dinucleotide phosphate (NADPH), which controls the generation and removal of ROS in a tissue-specific manner. Therefore, a deficiency of G6PD can lead to the dysregulation of ROS, which causes a severe inflammatory response in COVID-19 patients. This report highlights the G6PD dichotomy in the regulation of ROS and inflammatory responses, as well as its deficiency in severity among COVID-19 patients.

In Silico Integration of Transcriptome and Interactome Predicts an ETP-ALL-Specific Transcriptional Footprint that Decodes its Developmental Propensity.

Early T precursor acute lymphoblastic leukemia (ETP-ALL) exhibits poor clinical outcomes and high relapse rates following conventional chemotherapeutic protocols. Extensive developmental flexibility of the multipotent ETP-ALL blasts with considerable intra-population heterogeneity in terms of immunophenotype and prognostic parameters might be a target for novel therapeutic interventions. Using a public gene expression dataset (GSE28703) from NCBI GEO DataSets with 12 ETP-ALL and 40 non-ETP-ALL samples, such heterogeneity was found to be reflected in their transcriptome as well. Hub genes were identified from the STRING-derived functional interaction network of genes showing differential expression between ETP-ALL and non-ETP-ALL as well as variable expression across ETP-ALL. Nine genes (KIT, HGF, NT5E, PROM1, CD33, ANPEP, CDH2, IL1B, and CXCL2) among the hubs were further validated as possible diagnostic ETP-ALL markers using another gene expression dataset (GSE78132) with 17 ETP-ALL and 27 non-ETP-ALL samples. Linear dimensionality reduction analysis with the expression levels of the hub genes in ETP-ALL revealed their divergent inclinations towards different hematopoietic lineages, proposing them as novel indicators of lineage specification in the incompletely differentiated ETP-ALL blasts. This further led to the formulation of a personalized lineage score calculation algorithm, which uncovered a considerable B-lineage-bias in a substantial fraction of ETP-ALL subjects from the GSE28703 and GSE78132 cohorts. In addition, STRING-derived physical interactome of the potential biomarkers displayed complete segregation of the B-lineage-skewed markers from other lineage-associated factors, highlighting their distinct functionality and possible druggability in ETP-ALL. A panel of these biomarkers might be useful in pinpointing the dominant lineage specification programmes in the ETP-ALL blasts on a personalized level, urging the development of novel lineage-directed precision therapies as well as repurposing of existing therapies against leukemia of different hematopoietic lineages; which might overcome the drawbacks of conventional chemotherapy.

Dynamic Palmitoylation of Red Cell Membrane Proteins Governs Susceptibility to Invasion by the Malaria Parasite, Plasmodium falciparum.

Phosphorylation and other post-translational modifications of red blood cell (RBC) proteins govern membrane function and have a role in the invasion of RBCs by the malaria parasite, Plasmodium falciparum. Furthermore, a percentage of RBC proteins are palmitoylated, although the functional consequences are unknown. We establish dynamic palmitoylation of 118 RBC membrane proteins using click chemistry and acyl biotin exchange (ABE)-coupled LC-MS/MS and characterize their involvement in controlling membrane organization and parasite invasion. RBCs were treated with a generic palmitoylation inhibitor, 2-bromopalmitate (2-BMP), and then analyzed using ABE-coupled LC-MS/MS. Only 42 of the 118 palmitoylated proteins detected were palmitoylated in the 2-BMP-treated sample, indicating that palmitoylation is dynamically regulated. Interestingly, membrane receptors such as semaphorin 7A, CR1, and ABCB6, which are known to be involved in merozoite interaction with RBCs and parasite invasion, were found to be dynamically palmitoylated, including the blood group antigen, Kell, whose antigenic abundance was significantly reduced following 2-BMP treatment. To investigate the involvement of Kell in merozoite invasion of RBCs, a specific antibody to its extracellular domain was used. The antibody targeting Kell inhibited merozoite invasion of RBCs by 50%, implying a role of Kell, a dynamically palmitoylated potent host-derived receptor, in parasite invasion. Furthermore, a significant reduction in merozoite contact with the RBC membrane and a consequent decrease in parasite invasion following 2-BMP treatment demonstrated that palmitoylation does indeed regulate RBC susceptibility to parasite invasion. Taken together, our findings revealed the dynamic palmitoylome of RBC membrane proteins and its role in P. falciparum invasion.

Complementary crosstalk between palmitoylation and phosphorylation events in MTIP regulates its role during Plasmodium falciparum invasion.

Post-translational modifications (PTMs) including phosphorylation and palmitoylation have emerged as crucial biomolecular events that govern many cellular processes including functioning of motility- and invasion-associated proteins during Plasmodium falciparum invasion. However, no study has ever focused on understanding the possibility of a crosstalk between these two molecular events and its direct impact on preinvasion- and invasion-associated protein-protein interaction (PPI) network-based molecular machinery. Here, we used an integrated in silico analysis to enrich two different catalogues of proteins: (i) the first group defines the cumulative pool of phosphorylated and palmitoylated proteins, and (ii) the second group represents a common set of proteins predicted to have both phosphorylation and palmitoylation. Subsequent PPI analysis identified an important protein cluster comprising myosin A tail interacting protein (MTIP) as one of the hub proteins of the glideosome motor complex in P. falciparum, predicted to have dual modification with the possibility of a crosstalk between the same. Our findings suggested that blocking palmitoylation led to reduced phosphorylation and blocking phosphorylation led to abrogated palmitoylation of MTIP. As a result of the crosstalk between these biomolecular events, MTIP's interaction with myosin A was found to be abrogated. Next, the crosstalk between phosphorylation and palmitoylation was confirmed at a global proteome level by click chemistry and the phenotypic effect of this crosstalk was observed via synergistic inhibition in P. falciparum invasion using checkerboard assay and isobologram method. Overall, our findings revealed, for the first time, an interdependence between two PTM types, their possible crosstalk, and its direct impact on MTIP-mediated invasion via glideosome assembly protein myosin A in P. falciparum. These insights can be exploited for futuristic drug discovery platforms targeting parasite molecular machinery for developing novel antimalarial therapeutics.

Role of glucose 6-phosphate dehydrogenase (G6PD) deficiency and its association to Autism Spectrum Disorders.

Autism Spectrum Disorder (ASD) is a common group of neurodevelopmental disorders which causes significant alterations in social and communication skills along with repetitive behavior and limited interests. The physiological understanding of ASD is ambiguous. Several reports suggested that environmental, genetic and epigenetic changes, neuroinflammation, mitochondrial dysfunction and metabolic alterations orchestrate the pathological outcomes of ASD. A recent report from Saudi Arabia found a mutation in X-chromosomal housekeeping glucose 6-phosphate dehydrogenase (G6PD) gene in two male ASD patients. Although, the involvement of G6PD-deficiency in the pathogenesis of ASD is poorly understood. Several reports suggested that G6PD deficiency impedes cellular detoxification of reactive oxygen species (ROS), which may result in neuronal damage and neuroinflammation. A deficiency of G6PD in newborn children may play a fundamental role in the pathogenesis of ASD. In this review, we will discuss the implications of G6PD deficiency in pathogenesis, male biasness and theranostics in ASD patients.

Familiarity Breeds Strategy: In Silico Untangling of the Molecular Complexity on Course of Autoimmune Liver Disease-to-Hepatocellular Carcinoma Transition Predicts Novel Transcriptional Signatures.

Autoimmune liver diseases (AILD) often lead to transformation of the liver tissues into hepatocellular carcinoma (HCC). Considering the drawbacks of surgical procedures in such cases, need of successful non-invasive therapeutic strategies and treatment modalities for AILD-associated-HCC still exists. Due to the lack of clear, sufficient knowledge about factors mediating AILD-to-HCC transition, an in silico approach was adopted to delineate the underlying molecular deterministic factors. Parallel enrichment analyses on two different public microarray datasets (GSE159676 and GSE62232) pinpointed the core transcriptional regulators as key players. Correlation between the expression kinetics of these transcriptional modules in AILD and HCC was found to be positive primarily with the advancement of hepatic fibrosis. Most of the regulatory interactions were operative during early (F0-F1) and intermediate fibrotic stages (F2-F3), while the extent of activity in the regulatory network considerably diminished at late stage of fibrosis/cirrhosis (F4). Additionally, most of the transcriptional targets with higher degrees of connectivity in the regulatory network (namely DCAF11, PKM2, DGAT2 and BCAT1) may be considered as potential candidates for biomarkers or clinical targets compared to their low-connectivity counterparts. In summary, this study uncovers new possibilities in the designing of novel prognostic and therapeutic regimen for autoimmunity-associated malignancy of liver in a disease progression-dependent fashion.

Disparities, desperation, and divisiveness: Coping with COVID-19 in India.

India enforced one of the world's largest lockdowns in the last quarter of March 2020 to minimize the impact of the COVID-19 pandemic. This commentary focuses on the mental health implications of the ongoing pandemic as well as the lockdown that lasted for more than two months and is still in place in certain areas. Whereas loneliness, stress, anxiety, and depression have been widespread, vulnerable sections of the population, including daily wage workers, migrant laborers, religious minorities, women and children, and the elderly, have been facing various forms of economic, sociopolitical, and familial stigma, racism, and violence. By and large, the COVID-19 pandemic has widened all forms of societal disparities in India. (PsycInfo Database Record (c) 2020 APA, all rights reserved).