Formulation development of nanostructured lipid carrier-based nanogels encapsulating tacrolimus for sustained therapy of psoriasis.

The goal of this study was to formulate tacrolimus nanogel based on nanostructured lipid carrier (NLC) in order to improve the efficacy, aesthetic, and patient compliance for the treatment of psoriasis. The microemulsion method was used to create phase diagrams and NLCs were prepared using points obtained from the microemulsion region and characterized. The gelling agent carbopol was used to develop an NLC-based nanogel.

Inhibition of Marek's Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In Vitro.

Marek's disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested that MDV suppresses the induction of type I interferons and thus escapes immune control. Cholesterol 25-hydroxylase (CH25H), a gene that encodes an enzyme that catalyses cholesterol to 25-hydroxycholesterol (25-HC), is an interferon-stimulating gene (ISG) known to exert antiviral activities.

A Review: Understanding Molecular Mechanisms of Antibody-Dependent Enhancement in Viral Infections.

Antibody Dependent Enhancement (ADE) of an infection has been of interest in the investigation of many viruses. It is associated with the severity of the infection. ADE is mediated by non-neutralizing antibodies, antibodies at sub-neutralizing concentrations, or cross-reactive non-neutralizing antibodies.

Nanoparticulate drugs and vaccines: Breakthroughs and bottlenecks of repurposing in breast cancer.

Breast cancer (BC) is a highly diagnosed and topmost cause of death in females worldwide. Drug repurposing (DR) has shown great potential against BC by overcoming major shortcomings of approved anticancer therapeutics. However, poor physicochemical properties, pharmacokinetic performance, stability, non-selectivity to tumors, and side effects are severe hurdles in repurposed drug delivery against BC.

Exploring the Evolutionary History and Phylodynamics of Human Immunodeficiency Virus Type 1 Outbreak From Unnao, India Using Phylogenetic Approach.

Certain rural and semiurban settings in the Unnao district, Uttar Pradesh, India observed an unprecedented increase in the detection of HIV cases during July 2017. Subsequent investigations through health camps and a follow-up case-control study attributed the outbreak to the unsafe injection exposures during treatment. In this study, we have undertaken a secondary analysis to understand the phylogenetic aspects of the outbreak-associated HIV-1 sequences along with the origin and phylodynamics of these sequences.

HIV-1 Drug Resistance Among Treatment-Naive Transgenders from India.

Transgenders (TGs) are highly affected by HIV with high prevalence of 3.14% in India. Since 2017, targeted preventive efforts have been initiated by the government and HIV-infected TGs are being provided the antiretroviral (ART) treatment.

Type I IFN signaling limits hemorrhage-like disease after infection with Japanese encephalitis virus through modulating a prerequisite infection of CD11bLy-6C monocytes.

Background: The crucial role of type I interferon (IFN-I, IFN-α/β) is well known to control central nervous system (CNS) neuroinflammation caused by neurotrophic flaviviruses such as Japanese encephalitis virus (JEV) and West Nile virus. However, an in-depth analysis of IFN-I signal-dependent cellular factors that govern CNS-restricted tropism in JEV infection in vivo remains to be elucidated.

Methods: Viral dissemination, tissue tropism, and cytokine production were examined in IFN-I signal-competent and -incompetent mice after JEV inoculation in tissues distal from the CNS such as the footpad.

Neutralization diversity of HIV-1 Indian subtype C envelopes obtained from cross sectional and followed up individuals against broadly neutralizing monoclonal antibodies having distinct gp120 specificities.

Background: The potential use of the broadly neutralizing monoclonal antibodies (bnAbs) towards prophylaxis and treatment to HIV-1 is currently being explored. While a number of promising bnAbs have been discovered and a few of them have progressed towards clinical development, their extent of neutralization coverage with respect to global HIV-1 variants given the existence of genetically distinct subtypes and recombinants circulating globally is not clearly known. In the present study, we examined the variation in the neutralization susceptibility of pseudoviruses expressing 71 full length primary HIV-1 subtype C envs obtained from limited cross-sectional individuals over different time points against four bnAbs that target gp120 with distinct specificities: VRC01, CAP256-VRC26.

HIV-1 pol gene diversity and molecular dating of subtype C from Sri Lanka.

Background: The first case of HIV infection in Sri Lanka was reported in 1987 and at the end of 2018 there were 3500 people living with HIV. There have been commendable efforts made towards the detection, treatment, and prevention of HIV in the country. Even though the genetic diversity of HIV has been shown to affect the parameters ranging from detection to vaccine development, there is no data available with respect to the molecular epidemiology of HIV-1 in Sri Lanka.

High IL-5 levels possibly contributing to HIV viremia in virologic non-responders at one year after initiation of anti-retroviral therapy.

Lack of viral monitoring in HIV infected patients on anti-retroviral therapy in low income countries may result in missing virologic non-responders (VNR) who show immunologic recovery in spite of unsuppressed viral replication. Biomarkers and drug resistance patterns in these discordant patients in comparison to the concordant treatment failure group need to be studied to understand possible risk factors associated with this condition. HIV infected patients on anti-retroviral therapy for one year were enrolled under three categories namely VNRs (n = 25), treatment failures (n = 18) and treatment responders (n = 40).

Changes in diet composition with urbanization and its effect on the polycystic ovarian syndrome phenotype in a Western Indian population.

Objective: To study the effects of increasingly prosperous diet content on clinical features of polycystic ovary syndrome (PCOS).

Design: A cross-sectional cohort study of 711 women with PCOS from a heterogeneous population spanning a wide spectrum of socioeconomic strata.

Setting: Independent hospital.

Polymeric Mixed Micelles: Improving the Anticancer Efficacy of Single-Copolymer Micelles.

Mixed micelles self-assembled from two or more dissimilar block copolymers provide a direct and convenient approach to improved drug delivery. The present review is focused on mixed micelles (prepared from block copolymers only) for various drug delivery applications along with their merits over single-copolymer micelles. Presented are the physicochemical properties of mixed and single-copolymer micelles, various stimuli-responsive mixed micelles for the treatment of cancer, interesting combinations of multifunctional mixed micelles along with their in vitro and in vivo performance, and the potential of mixed micelles as a gene delivery system.

Gamma radiation degradation of chitosan for application in growth promotion and induction of stress tolerance in potato (Solanum tuberosum L.).

Oligo-chitosan (82.20 kDa) was prepared from chitosan (337.73 kDa) by application of 100 kGy γ-irradiation.

Partial Sequences from Drug Naive HIV-2 Infected Individuals from Maharashtra, India.

HIV-2 is important due to its unique challenges in diagnosis, treatment, and drug resistance. The data on Indian HIV-2 gene as well as resistance to antiretroviral drugs are limited. Here we report sequence data of protease (PR) and reverse transcriptase (RT) genes from HIV-2 infected treatment naive individuals ( = 32) from Maharashtra, India.

PYRE insertion within HIV-1 subtype C p6-Gag functions as an ALIX-dependent late domain.

ALG-2 interacting protein X (ALIX) links HIV-1 Gag to the components of ESCRT-III. HIV-1 engages the ALIX via its nucleocapsid and LYPXnL motif in p6. Overexpression of ALIX corrects the release defect of PTAP deleted HIV-1 via LYPXnL/ALIX pathway.

Dual TLR2/9 Recognition of Herpes Simplex Virus Infection Is Required for Recruitment and Activation of Monocytes and NK Cells and Restriction of Viral Dissemination to the Central Nervous System.

The importance of TLR2 and TLR9 in the recognition of infection with herpes simplex virus (HSV) and HSV-caused diseases has been described, but some discrepancies remain concerning the benefits of these responses. Moreover, the impact of TLR2/9 on innate and adaptive immune responses within relevant mucosal tissues has not been elucidated using natural mucosal infection model of HSV. Here, we demonstrate that dual TLR2/9 recognition is essential to provide resistance against mucosal infection with HSV an intravaginal route.

TLR2/MyD88 pathway-dependent regulation of dendritic cells by dengue virus promotes antibody-dependent enhancement via Th2-biased immunity.

Possible risk mediators in primary dengue virus (DenV) infection that favor secondary DenV infection to life-threatening dengue hemorrhagic fever (DHF) and shock syndrome (DSS) via antibody-dependent enhancement (ADE) have not yet been described. Here, DenV infection enhanced the expression of inflammatory mediators and activation molecules in dendritic cells (DCs) through TLR2/MyD88 pathway. TLR2 appeared to facilitate DenV infection in DCs that were less permissive than macrophages for viral replication.

Antiretroviral resistance following immunological monitoring in a resource-limited setting of western India: A cross-sectional study.

Background: The free antiretroviral therapy (ART) program in India still relies on the clinico-immunological monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following immunological monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART.

HECT Domain and RCC1-Like Domain-Containing Protein 5 (HERC-5) Gene Polymorphisms in HIV-1-Infected Individuals: A Study from India.

HECT domain and RCC1-like domain-containing protein 5 (HERC-5) is one of the novel host restriction factors that is known to inhibit HIV release in vitro. Polymorphisms in other host restriction factors have been associated with HIV infection and disease progression. However, no report is available on the HERC-5 polymorphism in HIV-infected individuals.

Exacerbation of Japanese Encephalitis by CD11c Dendritic Cell Ablation Is Associated with an Imbalance in Regulatory Foxp3 and IL-17CD4 Th17 Cells and in Ly-6C and Ly-6C Monocytes.

Japanese encephalitis (JE) is neuroinflammation characterized by uncontrolled infiltration of peripheral leukocytes into the central nervous system (CNS). We previously demonstrated exacerbation of JE following CD11c dendritic cell (DC) ablation in CD11c-DTR transgenic mice. Moreover, CD11c DC ablation led to abnormal differentiation of CD11bLy-6C monocytes and enhanced permeability of the blood-brain barrier (BBB), resulting in promoting the progression of JE.

Mixed Micelles as Nano Polymer Therapeutics of Docetaxel: Increased In vitro Cytotoxicity and Decreased In vivo Toxicity.

Background: Docetaxel (DTX) has been used to treat several types of cancers, but it has provided pharmaceutical challenges due to its poor water solubility and toxicities associated with the co-solvents (tween-80 and ethanol). Nanopolymer therapeutics can be engineered to deliver anticancer agent specifically to cancer cells, thereby leaving normal healthy cells unaffected by toxic drugs such as DTX. The objective of the present study was to synthesize the polyacrylic acid (PAA)-DTX conjugate (PAADC) and preparation of nanopolymer therapeutics such as PAADC/DSPE-mPEG2000 mixed micelles (PAADC-DP MMs).

A Study of Hepatitis E in Pregnancy: Maternal and Fetal Outcome.

Purpose: HEV infection, a major public health concern, is known to cause large-scale epidemic and sporadic cases of acute viral hepatitis in developing countries. The infection occurs primarily in young adults and is generally mild and self-limiting; however, the case fatality rate is reportedly higher among women, especially during the second or third trimesters of pregnancy.

Methods: This study, a prospective observational study, was conducted at the Dr.

Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs.

CCR5 ameliorates Japanese encephalitis via dictating the equilibrium of regulatory CD4(+)Foxp3(+) T and IL-17(+)CD4(+) Th17 cells.

Background: CCR5 is a CC chemokine receptor involved in the migration of effector leukocytes including macrophages, NK, and T cells into inflamed tissues. Also, the role of CCR5 in CD4(+)Foxp3(+) regulatory T cell (Treg) homing has recently begun to grab attention. Japanese encephalitis (JE) is defined as severe neuroinflammation of the central nervous system (CNS) following infection with mosquito-borne flavivirus JE virus.