Comparing the Efficacy of Topical 4% Benzoyl Peroxide Versus Topical 0.1% Adapalene for Treatment of Acne Vulgaris in Skin of Color Population: A South Asian Perspective.

Introduction Acne vulgaris is one of the most common skin problems encountered in the dermatology department. It is a chronic, inflammatory disease of the pilosebaceous unit, clinically presenting with comedones, papules, pustules, nodules, and cysts. With its particularly high prevalence in the younger population, it has significant adverse sequelae on patient's quality of life. At present, due to an enhanced understanding of the pathogenesis of acne, various therapeutic modalities are available. The current management strategies generally follow a systematic treatment escalation based on disease severity and treatment response. However meticulous choice of appropriate anti-acne medicine for the acne type is the key to the management plan. Starting with mild to moderate types of acne as per the Leeds photometric grading scale, the most useful topical agents include topical retinoids, benzoyl peroxide, and topical antibiotics while systemic therapies such as oral antibiotics or isotretinoin are generally reserved for moderate to severe acne treatment. The skin of color (SOC) population is a relatively neglected group concerning the optimum and safe management strategies in different dermatological conditions and acne is no different, where there remains a need for comparing the available topical modalities for appropriate drug selection in the treatment of mild to moderate acne in SOC population. Objective The objective of this study was to compare the efficacy of topical 4% benzoyl peroxide versus topical 0.1% adapalene in the treatment of acne vulgaris in the SOC population. Methods The participants were divided into two groups, groups A and B. A total of 64 patients of both genders, with acne vulgaris (duration > three months) were included in the study. In group A, 32 patients were administered topical 0.1% adapalene whereas, in group B, 32 patients were given topical 4% benzoyl peroxide. Both medicines were applied at night daily. Patients were called for follow-up after 12 weeks. In both groups, the final efficacy evaluation was done using the Global Acne Grading System (GAGS) score after 12 weeks of treatment period. Results In group A, the age ranged from 15 to 40 years with a mean age of 25.781±3.93 years while the duration of complaint was 5.843±1.27 months. GAGS score was 25.281±2.65 and mean BMI was 23.092±3.51 kg/m2. In group B, the mean age was 25.187± 4.06 years, the duration of complaint was 7.375±2.25 months, the GAGS score was 23.906± 2.60 while the mean BMI was 21.485±3.88 kg/m2. Efficacy in group A was noted in 25 (78.1%) patients as compared to 24 (75%) patients in group B (p =0.768). Conclusion The present study showed that the safety and efficacy of 0.1% adapalene the traditional drug 4% benzoyl peroxide in the SOC population was comparable.

Remediation of organic pollutant from the aqueous environment using in-house fabricated polyaniline-based hybrid composite (PANI-MnPBA/NiCoMnS) materials.

Polyaniline-based hybrid material (PANI-MnPBA/NiCoMnS) was prepared by hydrothermal-solvothermal approach. Synthesized hybrid material was characterized through FTIR-spectroscopy, p-XRD, SEM, EDX, BET, and Zetasizer techniques. Hybrid material as adsorbent for removal of Congo red (CR) from water system showed excellent results such as 98 % removal efficiency and 254 mg/g adsorption capacity. Furthermore, various studies like adsorption isothermal, kinetic, thermodynamic, and statistical analysis were performed to understand the adsorption phenomenon. From various kinetic models, pseudo-first and second-order kinetic models, intra-particle and liquid film diffusion kinetic models, pseudo-first-order kinetic model, and liquid-film diffusion kinetic model both are most suitable for explaining the adsorption phenomenon due to the greater value of R2 (0.955) for CR. According to these kinetic models, physio-sorption and diffusion play a basic role in the adsorption of CR. Moreover, ΔG (-1779.508 kJ mol-1) and ΔH (61,760.889 kJ mol-1) values explained the spontaneous and exothermic nature of the adsorption process, respectively. Furthermore, for support of the adsorption mechanism via electrostatic attractions before and after the adsorption process FTIR results of as-synthesized adsorbent were measured (NH peaks before 3668.88, after 3541.41 cm-1). These results confirm electrostatic attraction for the adsorption process. Finally, the statistical model was added (n < 1), according to this model, adsorption follows a multi-anchorage approach and adsorbent contains enough sites for adsorption of CR.

Thermodynamic Insights into Variation in Thermomechanical and Physical Properties of Isotactic Polypropylene: Effect of Shear and Cooling Rates.

In order to elucidate the effect of shear and cooling process on structural, thermomechanical, and physical properties of polymer melt, excess entropy, a thermodynamic quantity is calculated from radial distribution function generated from equilibrated parts of the molecular simulation trajectories. The structural properties are calculated, which includes the density of polypropylene melt, end to end distance, radius of gyration of the polypropylene polymer chain, and monomer-monomer radial distribution function. Non-equilibrium molecular dynamics simulation was employed to investigate the role of the applied shear rate on the properties of polypropylene. Furthermore, a range of cooling rates were employed to cool the melt. Thermomechanical properties, such as Young's modulus, and physical properties, such as glass transition temperature, were determined for different cases. Results showed that slow cooling and high shear substantially improved the Young's modulus and glass transition temperature of the i-PP. Furthermore, a two-body contribution to the excess entropy was used to elucidate the structure-property relationships in the polymer melt as well as the glassy state and the dependence of shear and cooling rate on these properties. We have used the Rosenfeld excess entropy-viscosity relationship to calculate the viscous behavior of the polymer under a steady shear condition.

Recent Advances in Transition Metal Tellurides (TMTs) and Phosphides (TMPs) for Hydrogen Evolution Electrocatalysis.

The hydrogen evolution reaction (HER) is a developing and promising technology to deliver clean energy using renewable sources. Presently, electrocatalytic water (H2O) splitting is one of the low-cost, affordable, and reliable industrial-scale effective hydrogen (H2) production methods. Nevertheless, the most active platinum (Pt) metal-based catalysts for the HER are subject to high cost and substandard stability. Therefore, a highly efficient, low-cost, and stable HER electrocatalyst is urgently desired to substitute Pt-based catalysts. Due to their low cost, outstanding stability, low overpotential, strong electronic interactions, excellent conductivity, more active sites, and abundance, transition metal tellurides (TMTs) and transition metal phosphides (TMPs) have emerged as promising electrocatalysts. This brief review focuses on the progress made over the past decade in the use of TMTs and TMPs for efficient green hydrogen production. Combining experimental and theoretical results, a detailed summary of their development is described. This review article aspires to provide the state-of-the-art guidelines and strategies for the design and development of new highly performing electrocatalysts for the upcoming energy conversion and storage electrochemical technologies.

Humoral cross-reactivity towards SARS-CoV-2 in young children with acute respiratory infection with low-pathogenicity coronaviruses.

Background: SARS-CoV-2 infection in children frequently leads to only asymptomatic and mild infections. It has been suggested that frequent infections due to low-pathogenicity coronaviruses in children, impart immunity against SARS-CoV-2 in this age group. Methods: From a prospective birth cohort study prior to the pandemic, we identified children with proven low-pathogenicity coronavirus infections. Convalescent sera from these children were tested for antibodies against respective seasonal coronaviruses (OC43, NL63, and 229E) and SARS-CoV-2 by immunofluorescence and virus microneutralization assay respectively. Results: Forty-two children with proven seasonal coronavirus infection were included. Convalescent sera from these samples demonstrated antibodies against the respective seasonal coronaviruses. Of these, 40 serum samples showed no significant neutralization of SARS-CoV-2, while 2 samples showed inconclusive results. Conclusion: These findings suggest that the antibodies generated in low-pathogenicity coronavirus infections offer no protection from SARS-CoV-2 infection in young children.

Metal-Organic Frameworks Derived Electrocatalysts for Oxygen and Carbon Dioxide Reduction Reaction.

The increasing demands of energy and environmental concerns have motivated researchers to cultivate renewable energy resources for replacing conventional fossil fuels. The modern energy conversion and storage devices required high efficient and stable electrocatalysts to fulfil the market demands. In previous years, we are witness for considerable developments of scientific attention in Metal-organic Frameworks (MOFs) and their derived nanomaterials in electrocatalysis. In current review article, we have discussed the progress of optimistic strategies and approaches for the manufacturing of MOF-derived functional materials and their presentation as electrocatalysts for significant energy related reactions. MOFs functioning as a self-sacrificing template bid different benefits for the preparation of metal nanostructures, metal oxides and carbon-abundant materials promoting through the porous structure, organic functionalities, abundance of metal sites and large surface area. Thorough study for the recent advancement in the MOF-derived materials, metal-coordinated N-doped carbons with single-atom active sites are emerging candidates for future commercial applications. However, there are some tasks that should be addressed, to attain improved, appreciative and controlled structural parameters for catalytic and chemical behavior.

Kupyaphores are zinc homeostatic metallophores required for colonization of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) endures a combination of metal scarcity and toxicity throughout the human infection cycle, contributing to complex clinical manifestations. Pathogens counteract this paradoxical dysmetallostasis by producing specialized metal trafficking systems. Capture of extracellular metal by siderophores is a widely accepted mode of iron acquisition, and Mtb iron-chelating siderophores, mycobactin, have been known since 1965. Currently, it is not known whether Mtb produces zinc scavenging molecules. Here, we characterize low-molecular-weight zinc-binding compounds secreted and imported by Mtb for zinc acquisition. These molecules, termed kupyaphores, are produced by a 10.8 kbp biosynthetic cluster and consists of a dipeptide core of ornithine and phenylalaninol, where amino groups are acylated with isonitrile-containing fatty acyl chains. Kupyaphores are stringently regulated and support Mtb survival under both nutritional deprivation and intoxication conditions. A kupyaphore-deficient Mtb strain is unable to mobilize sufficient zinc and shows reduced fitness upon infection. We observed early induction of kupyaphores in Mtb-infected mice lungs after infection, and these metabolites disappeared after 2 wk. Furthermore, we identify an Mtb-encoded isonitrile hydratase, which can possibly mediate intracellular zinc release through covalent modification of the isonitrile group of kupyaphores. Mtb clinical strains also produce kupyaphores during early passages. Our study thus uncovers a previously unknown zinc acquisition strategy of Mtb that could modulate host-pathogen interactions and disease outcome.

Recent Advances in Synthesis and Applications of Single-Atom Catalysts for Rechargeable Batteries.

The rapid development of flexible and wearable optoelectronic devices, demanding the superior, reliable, and ultra-long cycling energy storage systems. But poor performances of electrode materials used in energy devices are main obstacles. Recently, single-atom catalysts (SACs) are considered as emerging and potential candidates as electrode materials for battery devices. Herein, we have discussed the recent methods for the fabrication of SACs for rechargeable metal-air batteries, metal-CO2 batteries, metal-sulfur batteries, and other batteries, following the recent advances in assembling and performance of these batteries by using SACs as electrode materials. The role of SACs to solve the bottle-neck problems of these energy storage devices and future perspectives are also discussed.

Resolution of viral load in mild COVID-19 patients is associated with both innate and adaptive immune responses.

Over 90% of the COVID-19 patients manifest mild/moderate symptoms or are asymptomatic. Although comorbidities and dysregulation of immune response have been implicated in severe COVID-19, the host factors that associate with asymptomatic or mild infections have not been characterized. We have collected serial samples from 23 hospitalized COVID-19 patients with mild symptoms and measured the kinetics of SARS-CoV-2 viral load in respiratory samples and markers of inflammation in serum samples. We monitored seroconversion during the acute phase of illness and quantitated the amount of total IgG against the receptor-binding domain of SARS-CoV-2 and estimated the virus neutralization potential of these antibodies. Viral load decreased by day 8 in all the patients but the detection of viral RNA in saliva samples did not correlate well with viral RNA detection in nasopharyngeal/oropharyngeal swab samples. 25% of the virus-positive patients had no detectable neutralizing antibodies in the serum and in other cases, the efficiency of antibodies to neutralize SARS-CoV-2 B1.1.7 strain was lower as compared to the circulating virus isolate. Decrease in viral load coincided with increase in neutralizing antibodies and interferon levels in serum. Most patients showed no increase in inflammatory cytokines such as IL-1ß or IL-6, however, elevated levels of IL-7 and other inflammatory mediators such as TNF-α and IL-8 was observed. These data suggest that most mild infections are associated with absence of inflammation coupled with an active innate immune response, T-cell activation and neutralizing antibodies.

Effectiveness of ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 infection during the delta (B.1.617.2) variant surge in India: a test-negative, case-control study and a mechanistic study of post-vaccination immune responses.

BACKGROUND: SARS-CoV-2 variants of concern (VOCs) have threatened COVID-19 vaccine effectiveness. We aimed to assess the effectiveness of the ChAdOx1 nCoV-19 vaccine, predominantly against the delta (B.1.617.2) variant, in addition to the cellular immune response to vaccination. METHODS: We did a test-negative, case-control study at two medical research centres in Faridabad, India. All individuals who had a positive RT-PCR test for SARS-CoV-2 infection between April 1, 2021, and May 31, 2021, were included as cases and individuals who had a negative RT-PCR test were included as controls after matching with cases on calendar week of RT-PCR test. The primary outcome was effectiveness of complete vaccination with the ChAdOx1 nCoV-19 vaccine against laboratory-confirmed SARS-CoV-2 infection. The secondary outcomes were effectiveness of a single dose against SARS-CoV-2 infection and effectiveness of a single dose and complete vaccination against moderate-to-severe disease among infected individuals. Additionally, we tested in-vitro live-virus neutralisation and T-cell immune responses to the spike protein of the wild-type SARS-CoV-2 and VOCs among healthy (anti-nucleocapsid antibody negative) recipients of the ChAdOx1 nCoV-19 vaccine. FINDINGS: Of 2379 cases of confirmed SARS-CoV-2 infection, 85 (3·6%) were fully vaccinated compared with 168 (8·5%) of 1981 controls (adjusted OR [aOR] 0·37 [95% CI 0·28-0·48]), giving a vaccine effectiveness against SARS-CoV-2 infection of 63·1% (95% CI 51·5-72·1). 157 (6·4%) of 2451 of cases and 181 (9·1%) of 1994) controls had received a single dose of the ChAdOx1 nCoV-19 vaccine (aOR 0·54 [95% CI 0·42-0·68]), thus vaccine effectiveness of a single dose against SARS-CoV-2 infection was 46·2% (95% CI 31·6-57·7). One of 84 cases with moderate-to-severe COVID-19 was fully vaccinated compared with 84 of 2295 cases with mild COVID-19 (aOR 0·19 [95% CI 0·01-0·90]), giving a vaccine effectiveness of complete vaccination against moderate-to-severe disease of 81·5% (95% CI 9·9-99·0). The effectiveness of a single dose against moderate-to-severe disease was 79·2% (95% CI 46·1-94·0); four of 87 individuals with moderate-to-severe COVID-19 had received a single dose compared with 153 of 2364 participants with mild disease (aOR 0·20 [95% CI 0·06-0·54]). Among 49 healthy, fully vaccinated individuals, neutralising antibody responses were lower against the alpha (B.1.1.7; geometric mean titre 244·7 [95% CI 151·8-394·4]), beta (B.1.351; 97·6 [61·2-155·8]), kappa (B.1.617.1; 112·8 [72·7-175·0]), and delta (88·4 [61·2-127·8]) variants than against wild-type SARS-CoV-2 (599·4 [376·9-953·2]). However, the antigen-specific CD4 and CD8 T-cell responses were conserved against both the delta variant and wild-type SARS-CoV-2. INTERPRETATION: The ChAdOx1 nCoV-19 vaccine remained effective against moderate-to-severe COVID-19, even during a surge that was dominated by the highly transmissible delta variant of SARS-CoV-2. Spike-specific T-cell responses were maintained against the delta variant. Such cellular immune protection might compensate for waning humoral immunity. FUNDING: Department of Biotechnology India, Council of Scientific and Industrial Research India, and Fondation Botnar.

Oxidative stress specifically inhibits replication of dengue virus.

Reactive oxygen species (ROS) are chemically active species which are involved in maintaining cellular and signalling processes at physiological concentrations. Therefore, cellular components that regulate redox balance are likely to play a crucial role in viral life-cycle either as promoters of viral replication or with antiviral functions. Zinc is an essential micronutrient associated with anti-oxidative systems and helps in maintaining a balanced cellular redox state. Here, we show that zinc chelation leads to induction of reactive oxygen species (ROS) in epithelial cells and addition of zinc restores ROS levels to basal state. Addition of ROS (H2O2) inhibited dengue virus (DENV) infection in a dose-dependent manner indicating that oxidative stress has adverse effects on DENV infection. ROS affects early stages of DENV replication as observed by quantitation of positive and negative strand viral RNA. We observed that addition of ROS specifically affected viral titres of positive strand RNA viruses. We further demonstrate that ROS specifically altered SEC31A expression at the ER suggesting a role for SEC31A-mediated pathways in the life-cycle of positive strand RNA viruses and provides an opportunity to identify drug targets regulating oxidative stress responses for antiviral development.

Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Based Novel Epitopes Induce Potent Immune Responses in vivo and Inhibit Viral Replication in vitro.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiates infection by attachment of the surface-exposed spike glycoprotein to the host cell receptors. The spike glycoprotein (S) is a promising target for inducing immune responses and providing protection; thus the ongoing efforts for the SARS-CoV-2 vaccine and therapeutic developments are mostly spiraling around S glycoprotein. The matured functional spike glycoprotein is presented on the virion surface as trimers, which contain two subunits, such as S1 (virus attachment) and S2 (virus fusion). The S1 subunit harbors the N-terminal domain (NTD) and the receptor-binding domain (RBD). The RBD is responsible for binding to host-cellular receptor angiotensin-converting enzyme 2 (ACE2). The NTD and RBD of S1, and the S2 of S glycoprotein are the major structural moieties to design and develop spike-based vaccine candidates and therapeutics. Here, we have identified three novel epitopes (20-amino acid peptides) in the regions NTD, RBD, and S2 domains, respectively, by structural and immunoinformatic analysis. We have shown as a proof of principle in the murine model, the potential role of these novel epitopes in-inducing humoral and cellular immune responses. Further analysis has shown that RBD and S2 directed epitopes were able to efficiently inhibit the replication of SARS-CoV-2 wild-type virus in vitro suggesting their role as virus entry inhibitors. Structural analysis revealed that S2-epitope is a part of the heptad repeat 2 (HR2) domain which might have plausible inhibitory effects on virus fusion. Taken together, this study discovered novel epitopes that might have important implications in the development of potential SARS-CoV-2 spike-based vaccine and therapeutics.

Assessment of a mass media campaign on giving way to ambulances in five cities of Pakistan.

OBJECTIVE: To determine the contribution of a mass media campaign towards encouraging more vehicles to give way to ambulances, and to identify the factors associated with higher likelihood of giving way to ambulances. METHODS: The three-phase observational study was conducted from December 2017 to March 2018 in Karachi, Lahore, Rawalpindi, Islamabad and Peshawar cities of Pakistan. Six road sites in different areas of each city were selected for observation. The surveys in each city were supervised by academic partners, including APPNA Institute of Public Health, Karachi, University of Health Sciences, Lahore, Al-Nafees Medical College, Rawalpindi and Islamabad, and Khyber Medical University, Peshawar. Three observation surveys were carried out before, during and after the media campaign on right of way for ambulances. Only those ambulances were observed which were rushing through and seeking space. The behaviour of only those vehicles was observed which had the space to change the lane when the space was sought from them. The association of the outcome of vehicles giving way to ambulances immediately or in a few seconds with the campaign was determined using logistic regression analysis. RESULTS: After adjustment for city of observation, timing of the day and type of vehicle, vehicles during and after the campaign were significantly more likely give space to ambulance (p<0.05) compared to cars, buses and vans were significantly less likely to give space (p<0.05). CONCLUSIONS: Media campaign produced better results in encouraging vehicle-owners to give right of way to ambulances to ensure timely medical assistance.

Respiratory Syncytial Virus-Induced Oxidative Stress Leads to an Increase in Labile Zinc Pools in Lung Epithelial Cells.

Zinc supplementation in cell culture has been shown to inhibit various viruses, like herpes simplex virus, rotavirus, severe acute respiratory syndrome (SARS) coronavirus, rhinovirus, and respiratory syncytial virus (RSV). However, whether zinc plays a direct antiviral role in viral infections and whether viruses have adopted strategies to modulate zinc homeostasis have not been investigated. Results from clinical trials of zinc supplementation in infections indicate that zinc supplementation may be beneficial in a pathogen- or disease-specific manner, further underscoring the importance of understanding the interaction between zinc homeostasis and virus infections at the molecular level. We investigated the effect of RSV infection on zinc homeostasis and show that RSV infection in lung epithelial cells leads to modulation of zinc homeostasis. The intracellular labile zinc pool increases upon RSV infection in a multiplicity of infection (MOI)-dependent fashion. Small interfering RNA (siRNA)-mediated knockdown of the ubiquitous zinc uptake transporter ZIP1 suggests that labile zinc levels are increased due to the increased uptake by RSV-infected cells as an antiviral response. Adding zinc to culture medium after RSV infection led to significant inhibition of RSV titers, whereas depletion of zinc by a zinc chelator, N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) led to an increase in RSV titers. The inhibitory effect of zinc was specific, as other divalent cations had no effect on RSV titers. Both RSV infection and zinc chelation by TPEN led to reactive oxygen species (ROS) induction, whereas addition of zinc blocked ROS induction. These results suggest a molecular link between RSV infection, zinc homeostasis, and oxidative-stress pathways and provide new insights for developing strategies to counter RSV infection.IMPORTANCE Zinc deficiency rates in developing countries range from 20 to 30%, and zinc supplementation trials have been shown to correct clinical manifestations attributed to zinc deficiency, but the outcomes in the case of respiratory infections have been inconsistent. We aimed at understanding the role of zinc homeostasis in respiratory syncytial virus (RSV) infection. Infection of lung epithelial cell lines or primary small-airway epithelial cells led to an increase in labile zinc pools, which was due to increased uptake of zinc. Zinc supplementation inhibited RSV replication, whereas zinc chelation had an opposing effect, leading to increases in RSV titers. Increases in labile zinc in RSV-infected cells coincided with induction of reactive oxygen species (ROS). Both zinc depletion and addition of exogenous ROS led to enhanced RSV infection, whereas addition of the antioxidant inhibited RSV, suggesting that zinc is part of an interplay between RSV-induced oxidative stress and the host response to maintain redox balance.

Zinc Chelation Specifically Inhibits Early Stages of Dengue Virus Replication by Activation of NF-κB and Induction of Antiviral Response in Epithelial Cells.

Zinc is an essential micronutrient which regulates diverse physiological functions and has been shown to play a crucial role in viral infections. Zinc has a necessary role in the replication of many viruses, however, antiviral action of zinc has also been demonstrated in in vitro infection models most likely through induction of host antiviral responses. Therefore, depending on the host machinery that the virus employs at different stages of infection, zinc may either facilitate, or inhibit virus infection. In this study, we show that zinc plays divergent roles in rotavirus and dengue virus infections in epithelial cells. Dengue virus infection did not perturb the epithelial barrier functions despite the release of virus from the basolateral surface whereas rotavirus infection led to disruption of epithelial junctions. In rotavirus infection, zinc supplementation post-infection did not block barrier disruption suggesting that zinc does not affect rotavirus life-cycle or protects epithelial barriers post-infection suggesting the involvement of cellular pathways in the beneficial effect of zinc supplementation in enteric infections. Zinc depletion by N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN) inhibited dengue virus and Japanese encephalitis virus (JEV) infection but had no effect on rotavirus. Time-of-addition experiments suggested that zinc chelation affected both early and late stages of dengue virus infectious cycle and zinc chelation abrogated dengue virus RNA replication. We show that transient zinc chelation induces ER stress and antiviral response by activating NF-kappaB leading to induction of interferon signaling. These results suggest that modulation of zinc homeostasis during virus infection could be a component of host antiviral response and altering zinc homeostasis may act as a potent antiviral strategy against flaviviruses.

Chandipura Virus Utilizes the Prosurvival Function of RelA NF-κB for Its Propagation.

Chandipura virus (CHPV), a cytoplasmic RNA virus, has been implicated in several outbreaks of acute encephalitis in India. Despite the relevance of CHPV to human health, how the virus interacts with the host signaling machinery remains obscure. In response to viral infections, mammalian cells activate RelA/NF-κB heterodimers, which induce genes encoding interferon beta (IFN-ß) and other immune mediators. Therefore, RelA is generally considered to be an antiviral transcription factor. However, RelA activates a wide spectrum of genes in physiological settings, and there is a paucity of direct genetic evidence substantiating antiviral RelA functions. Using mouse embryonic fibroblasts, we genetically dissected the role of RelA in CHPV pathogenesis. We found that CHPV indeed activated RelA and that RelA deficiency abrogated the expression of IFN-ß in response to virus infections. Unexpectedly, infection of Rela-/- fibroblasts led to a decreased CHPV yield. Our investigation clarified that RelA-dependent synthesis of prosurvival factors restrained infection-inflicted cell death and that exacerbated cell death processes prevented multiplication of CHPV in RelA-deficient cells. Chikungunya virus, a cytopathic RNA virus associated also with epidemics, required RelA, and Japanese encephalitis virus, which produced relatively minor cytopathic effects in fibroblasts, circumvented the need of RelA for their propagation. In sum, we documented a proviral function of the pleiotropic factor RelA linked to its prosurvival properties. RelA promoted the growth of cytopathic RNA viruses by extending the life span of infected cells, which serve as the replicative niche of intracellular pathogens. We argue that our finding bears significance for understanding host-virus interactions and may have implications for antiviral therapeutic regimes.IMPORTANCE RelA/NF-κB participates in a wide spectrum of physiological processes, including shaping immune responses against invading pathogens. In virus-infected cells, RelA typically induces the expression of IFN-ß, which restrains viral propagation in neighboring cells involving paracrine mechanisms. Our study suggested that RelA might also play a proviral role. A cell-autonomous RelA activity amplified the yield of Chandipura virus, a cytopathic RNA virus associated with human epidemics, by extending the life span of infected cells. Our finding necessitates a substantial revision of our understanding of host-virus interactions and indicates a dual role of NF-κB signaling during the course of RNA virus infections. Our study also bears significance for therapeutic regimes which alter NF-κB activities while alleviating the viral load.

Matrine ameliorates anxiety and depression-like behaviour by targeting hyperammonemia-induced neuroinflammation and oxidative stress in CCl4 model of liver injury.

Acute or chronic liver injury is associated with hyperammonemia which induced neuroinflammation and oxidative stress in the brain. Neuroinflammation, oxidative stress, reduced neurogenesis, and apoptosis are critical factors for the development of anxiety and depression. The present study was aimed to evaluate the anxiolytic and antidepressant properties of matrine against acute liver injury in the rodent model. Acute liver injury in mice was induced by administration of the acute hepatotoxic dose of carbon tetrachloride (CCl4) (1 ml/kg, i.p.). Pretreatment of mice with matrine (50 mg/kg i.p.) remarkably ameliorated CCl4-induced anxiety and depression-like behavior as evident from the results of open field test (OFT), elevated plus maze test (EPM), light-dark box test (LDB), forced swimming test (FST), and tail suspension test (TST). Moreover, matrine significantly inhibited CCl4-induced neuroinflammation in mice by reducing pro-inflammatory cytokines such as interleukins (IL-1ß, IL-6) and tumor necrosis factor-α (TNF-α) levels in the hippocampus (HC) and prefrontal cortex (PFC). CCl4-induced oxidative stress was reduced by matrine due to its potential to enhance the levels of reduced glutathione (GSH), catalase (CAT), glutathione-S-transferase (GST), and decreased the malondialdehyde (MDA), and nitrite level in the PFC and HC of mice brain. Matrine remarkably reduced the levels of corticosterone, ammonia, AST, ALT, and creatinine. Matrine pretreatment remarkably ameliorated CCl4-induced morphological liver injury. Acute pretreatment of matrine enhanced neurogenesis by increasing the number of GFAF (glial fibrillary acidic protein) positive astrocyte, BDNF (brain-derived neurotrophic factor), and VEGF (vascular endothelial growth factor) in the hippocampus of CCl4-treated mice. Pretreatment of matrine inhibited apoptosis and DNA damage in the hippocampus. The present data revealed that hyperammonemia produced due to liver injury induced oxidative stress, neuroinflammation, reduced neurogenesis and apoptosis in the hippocampus, thus, resulting in anxiety and depression. Taken together, the present results suggested that matrine has a significant antidepressant and anxiolytic effects through modulation of neuroinflammation, oxidative stress, reduced neurogenesis and apoptosis induced by CCl4 administration.

Effect of 25-methoxy hispidol A isolated from Poncirus trifoliate against bacteria-induced anxiety and depression by targeting neuroinflammation, oxidative stress and apoptosis in mice.

Neuroinflammation, oxidative stress and apoptosis are implicated in the pathogenesis of neuropsychiatric diseases like anxiety and depression. 25-Methoxyhispidol A (25-MHA) is a triterpenoid isolated from the immature fruit of Poncirus trifoliate. Recently, its crude extracts have been shown to exhibit anti-bacterial and anti-inflammatory activities. The current study investigated the effect of 25-MHA (1, 5 and 10 mg/kg) against bacteria-induced anxiety and depression-like behaviors in mice. Mice were challenged intraperitoneally (i.p.) with LPS (0.83 mg/kg), S. aureus and E. coli after 30 min of 25-MHA treatment. 25-MHA (10 mg/kg) significantly mitigated the anxiety-like behavior as indicated by the results of elevated plus maze test, open field test, and light-dark box test. It also demonstrated the anti-depressant like effect by significantly reducing the immobility time in tail suspension test and forced swim test. The oxidative stress was reduced by pretreatment with 25-MHA, improving the antioxidant enzymes level such as glutathione, glutathione sulfo-transferase, and catalase. Similarly, 25-MHA attenuated the bacterial infection induced neuroinflammation by inhibiting the interleukin- 6 (IL-6), interleukin-1 beta (IL-1ß), and tumor necrosis factor-α (TNF-α) levels in prefrontal cortex and hippocampus regions. Pretreatment of 25-MHA also decreased the cortisol level and prevented changes in the thickness of the granular layer in the dentate gyrus. It also inhibited the DNA damage in hippocampus region as analyzed by comet assay. Hence, present results demonstrated that 25-MHA possesses anti-anxiety and anti-depressant activities due to the ability to reduce neuroinflammatory, oxidative stress and apoptosis induced by the administration of LPS, E. coli, and S. aureus.

Evaluation of facial divine proportion in North Indian Population.

OBJECTIVE: To evaluate the facial divine proportion and its relationship with facial attractiveness in North Indian population. MATERIALS AND METHODS: For evaluation of various facial proportions, standardized frontal facial photographs of total 300 subjects between 18 and 30 years of age were obtained. Black and white copies of these photographs were presented in front of an evaluation jury for assigning scores of facial attractiveness and finally 130 attractive subjects were selected. These subjects were divided into two groups, Group I (attractive females n = 65) and Group II (attractive males n = 65) and they were further analyzed for various parameters of facial proportions. Unpaired Student's t-test was used to compare both groups. RESULTS: Group I showed that five of seven vertical facial proportions were close to divine proportion (1.618) whereas only two vertical proportions in Group II were close to it. Transverse facial proportions in both groups deviated more from divine proportion (1.618) and were closer to silver proportion (1.414). CONCLUSIONS: Most of the facial proportions of attractive females in the North-Indian population were close to the divine proportion. Thus, facial divine proportion could be an important factor in the perception of facial attractiveness of North-Indian attractive females.

Identification and characterization of the role of c-terminal Src kinase in dengue virus replication.

We screened a siRNA library targeting human tyrosine kinases in Huh-7 cells and identified c-terminal Src kinase (Csk) as one of the kinases involved in dengue virus replication. Knock-down of Csk expression by siRNAs or inhibition of Csk by an inhibitor reduced dengue virus RNA levels but did not affect viral entry. Csk partially colocalized with viral replication compartments. Dengue infection was drastically reduced in cells lacking the three ubiquitous src family kinases, Src, Fyn and Yes. Csk knock-down in these cells failed to block dengue virus replication suggesting that the effect of Csk is via regulation of Src family kinases. Csk was found to be hyper-phosphorylated during dengue infection and inhibition of protein kinase A led to a block in Csk phosphorylation and dengue virus replication. Overexpression studies suggest an important role for the kinase and SH3 domains in this process. Our results identified a novel role for Csk as a host tyrosine kinase involved in dengue virus replication and provide further insights into the role of host factors in dengue replication.