Significance of TLR2 signaling during megakaryocyte development: regulatory cross-talk of miR-125b, cytokine induction, and MAPK pathway during dengue infection.

Objective: Dengue is a viral infection endemic in more than 100 countries as per the WHO reports with approximately 5.2 million patients worldwide that spreads from mosquitoes to humans. Severe form of dengue fever can cause serious bleeding (low platelets) and death.

Design, synthesis and evaluation of 2-aryl quinoline derivatives against 12R-lipoxygenase (12R-LOX): Discovery of first inhibitor of 12R-LOX.

The 12R-lipoxygenase (12R-LOX), a (non-heme) iron-containing metalloenzyme belonging to the lipoxygenase (LOX) family catalyzes the conversion of arachidonic acid (AA) to its key metabolites. Studies suggested that 12R-LOX plays a critical role in immune modulation for the maintenance of skin homeostasis and therefore can be considered as a potential drug target for psoriasis and other skin related inflammatory diseases. However, unlike 12-LOX (or 12S-LOX) the enzyme 12R-LOX did not receive much attention till date.

Milk exosomes elicit a potent anti-viral activity against dengue virus.

Background: Exosomes are nano-sized vesicles secreted by various cells into the intra and extracellular space and hence is an integral part of biological fluids including milk. In the last few decades, many research groups have proved the potential of milk exosomes as a sustainable, economical and non-immunogenic drug delivery and therapeutic agent against different pathological conditions. However, its anti-viral properties still remain to be unearthed.

Tetravalent formulation of polymeric nanoparticle-based vaccine induces a potent immune response against dengue virus.

Dengue is a mosquito-borne disease caused by the four serotypes of the dengue virus (DENV 1-4). It is growing at an alarming rate globally, which could be partly attributed to the lack of an effective therapeutic regimen. Therefore, strategies for developing an effective vaccine have gained more significance in the given scenario.

Equine immunoglobulin fragment F(ab') displays high neutralizing capability against multiple SARS-CoV-2 variants.

Neutralizing antibody-based passive immunotherapy could be an important therapeutic option against COVID-19. Herein, we demonstrate that equines hyper-immunized with chemically inactivated SARS-CoV-2 elicited high antibody titers with a strong virus-neutralizing potential, and F(ab') fragments purified from them displayed strong neutralization potential against five different SARS-CoV-2 variants. F(ab') fragments purified from the plasma of hyperimmunized horses showed high antigen-specific affinity.

Immunogenic profiling of Mycobacterium tuberculosis DosR protein Rv0569 reveals its ability to switch on Th1 based immunity.

Mycobacterium tuberculosis (M.tb) is a multifaceted bacterial pathogen known to infect more than 2 billion people globally. However, a majority of the individuals (>90%) show no overt clinical symptoms of active Tuberculosis (TB) and, it is reported that M.

Leishmanial aspartyl-tRNA synthetase: Biochemical, biophysical and structural insights.

Aminoacyl tRNA synthetases (aaRSs) are integral components of protein biosynthesis along with several non-canonical cellular processes. Inhibition studies of aaRSs presented these enzymes as promising drug targets in many pathogens, however aspartyl tRNA synthetase has not been studied in trypanosomatids despite its essentiality. Hence, full-length ORF of Leishmania donovani aspartyl tRNA synthetase (LdaspRS) was cloned and purified to homogeneity followed by molecular mass determination.

Amino acid sensing pathway: A major check point in the pathogenesis of obesity and COVID-19.

Obesity and obesogenic comorbidities have been associated with COVID-19 susceptibility and mortality. However, the mechanism of such correlations requires an in-depth understanding. Overnutrition/excess serum amino acid profile during obesity has been linked with inflammation and reprogramming of translational machinery through hyperactivation of amino acid sensor mammalian target of rapamycin (mTOR), which is exploited by SARS-CoV-2 for its replication.

Dengue Virus Induced COX-2 Signaling Is Regulated Through Nutrient Sensor GCN2.

Nutrient sensor GCN2 plays a crucial role in the maintenance of cellular homeostasis during the condition of amino acid deprivation. Dysfunction in the GCN2 signaling underlies several chronic metabolic diseases. Recent studies highlight the anti-viral potential of GCN2 against RNA viruses such as Sindbis and HIV.

Anti-dengue infectivity evaluation of bioflavonoid from by dengue virus serine protease inhibition.

Dengue virus (DENV) serine protease enzyme, i.e. NS2B-NS3pro (non-structural protein 2B-non-structural protein 3) has been approved as prime drug target for the drug discovery against dengue infection, because of its essential role in viral replication.

Light-triggered selective ROS-dependent autophagy by bioactive nanoliposomes for efficient cancer theranostics.

Light-responsive nanoliposomes are being reported to induce cancer cell death through heat and reactive oxygen species (ROS). Nanoliposomes (CIR NLPs) encapsulating a near-infrared (NIR) light-sensitive dye, IR780, and a bioactive chlorophyll-rich fraction of Anthocephalus cadamba (CfAc) were synthesized and characterized. These CIR NLPs, when activated by NIR light, displayed localized synergistic cancer cell death under in vitro and in vivo conditions.

Amino acid starvation enhances vaccine efficacy by augmenting neutralizing antibody production.

Specific reduction in the intake of proteins or amino acids (AAs) offers enormous health benefits, including increased life span, protection against age-associated disorders, and improved metabolic fitness and immunity. Cells respond to conditions of AA starvation by activating the amino acid starvation response (AAR). Here, we showed that mimicking AAR with halofuginone (HF) enhanced the magnitude and affinity of neutralizing, antigen-specific antibody responses in mice immunized with dengue virus envelope domain III protein (DENVrEDIII), a potent vaccine candidate against DENV.

Dengue virus envelope protein domain III induces pro-inflammatory signature and triggers activation of inflammasome.

Dengue virus poses a considerable clinical problem, with the four closely related serotypes of dengue virus (DENV) infecting around 50-100 million people per year world-wide. The drastic increase in the dengue infection could be partly attributed to geographic expansion of the vector due to increasing urbanization, unavailability of specific antiviral therapies, licensed dengue vaccine, and poor understanding of the host immune responses. It has been reported that the immune-dominant envelope protein (E protein) domain III region (EDIII) of DENV is one of the most potent vaccine candidates because of its ability to trigger host immunity by inducing production of protective neutralizing antibodies.

Activation of integrated stress response pathway regulates IL-1β production through posttranscriptional and translational reprogramming in macrophages.

Immune cells sense and programme its cellular machinery appropriately to the environmental changes through the activation of cytoprotective adaptive pathway so-called the "integrated stress response (ISR)". However, the mechanisms implicated in ISR-induced protective responses are poorly understood. Here, we show that ISR activation by arsenite (Ar) results in suppression of IL-1β production in macrophages and inhibition of DSS-induced colitis in a murine model through a novel posttranscriptional and translation regulatory (PTR) mechanism.

Transcriptome meta-analysis identifies immune signature comprising of RNA binding proteins in ulcerative colitis patients.

Ulcerative colitis (UC) is a persistent inflammatory illness, which is clinically categorised as Inflammatory bowel disease (IBD), affecting millions of people worldwide. The precise cause behind the pathology of the disease remains unknown. However, the involvement of multiple factors including genetic predisposition, immunological deregulations, microbiota imbalance, and environmental triggers has been suggested.

Amino acid starvation sensing dampens IL-1β production by activating riboclustering and autophagy.

Activation of the amino acid starvation response (AAR) increases lifespan and acute stress resistance as well as regulates inflammation. However, the underlying mechanisms remain unclear. Here, we show that activation of AAR pharmacologically by Halofuginone (HF) significantly inhibits production of the proinflammatory cytokine interleukin 1β (IL-1β) and provides protection from intestinal inflammation in mice.

Amino Acid Sensing General Control Nonderepressible-2 Kinase and Immunological Programming.

Metabolic adaptation to the changing nutrient levels in the cellular microenvironment plays a decisive role in the maintenance of homeostasis. Eukaryotic cells are equipped with nutrient sensors, which sense the fluctuating nutrients levels and accordingly program the cellular machinery to mount an appropriate response. Nutrients including amino acids play a vital role in maintaining cellular homeostasis.

Chlorophyll rich biomolecular fraction of A. cadamba loaded into polymeric nanosystem coupled with Photothermal Therapy: A synergistic approach for cancer theranostics.

Development of multifunctional biodegradable nanomaterials to encapsulate hydrophobic drugs and their triggered release in cancer theranostics is a challenge. In the current study, we report the encapsulation of potent anticancer - chlorophyll rich biomolecular fraction from the plant Anthocephalus cadamba into a polymeric nanosystem. The biomolecular fraction was combined with an NIR dye IR-780 to make it photo-thermally active.

Mesoporous ZnO nanocapsules for the induction of enhanced antigen-specific immunological responses.

The application of nanotechnology in vaccinology has fuelled rapid advancement towards the design and development of nanovaccines. Nanoparticles have been found to enhance vaccine efficacy through the spatiotemporal orchestration of antigen delivery to secondary lymphoid organs and antigen-presentation by Antigen Presenting Cells (APCs) synchronized with stimulation of innate and adaptive immune responses. Metal based nanoparticles (MNPs) have been extensively engineered for the generation of nanovaccines owing to their intrinsic adjuvant-like properties and immunomodulatory functions.

A Comprehensive Gene Expression Meta-analysis Identifies Novel Immune Signatures in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA), a symmetric polyarticular arthritis, has long been feared as one of the most disabling forms of arthritis. Identification of gene signatures associated with RA onset and progression would lead toward development of novel diagnostics and therapeutic interventions. This study was undertaken to identify unique gene signatures of RA patients through large-scale meta-profiling of a diverse collection of gene expression data sets.

Cellular Stress Response and Immune Signaling in Retinal Ischemia-Reperfusion Injury.

Ischemia-reperfusion injury is a well-known pathological hallmark associated with diabetic retinopathy, glaucoma, and other related retinopathies that ultimately can lead to visual impairment and vision loss. Retinal ischemia pathogenesis involves a cascade of detrimental events that include energy failure, excitotoxic damage, calcium imbalance, oxidative stress, and eventually cell death. Retina for a long time has been known to be an immune privileged site; however, recent investigations reveal that retina, as well as the central nervous system, elicits immunological responses during various stress cues.

Transcriptome meta-analysis reveals a dysregulation in extra cellular matrix and cell junction associated gene signatures during Dengue virus infection.

Dengue Viruses (DENVs) cause one of the most prevalent arthropod-borne viral diseases affecting millions of people worldwide. Identification of genes involved in DENV pathogenesis would help in deciphering molecular mechanisms responsible for the disease progression. Here, we carried out a meta-analysis of publicly available gene expression data of dengue patients and further validated the meta-profile using in-vitro infection in THP-1 cells.

Mycobacterium tuberculosis Co-operonic PE32/PPE65 Proteins Alter Host Immune Responses by Hampering Th1 Response.

PE/PPE genes, present in cluster with ESAT-6 like genes, are suspected to have a role in antigenic variation and virulence of Mycobacterium tuberculosis. Their roles in immune evasion and immune modulation of host are also well documented. We present evidence that PE32/PPE65 present within the RD8 region are co-operonic, co-transcribed, and co-translated, and play role in modulating host immune responses.