The cGAS-STING mediated crosstalk between innate immunity and autophagy in leishmaniasis using mathematical modeling: Uncovering new therapeutic avenues.

The present paper deals with the investigation into the cGAS-STING pathway, focusing on the signaling of interferons through mathematical modeling and identifying a significant positive feedback loop regulated by STING for activation of type 1 interferons (IFN-1). Cyclic GMP-AMP synthase (cGAS) is responsible for detecting cytosolic DNA and initiating the STING (stimulator of interferon genes) pathway, which in turn causes the synthesis of pro-inflammatory cytokines and type I interferons. In addition to being crucial for pathogen identification, this route interacts with autophagy, a cellular mechanism that is necessary for immunological homeostasis and pathogen removal.

Mechanistic and structural insights into vitamin B metabolizing enzyme riboflavin kinase from Leishmania donovani.

Leishmania donovani relies on specific vitamins and cofactors crucial for its survival and pathogenesis. Tailoring therapies to disrupt these pathways offers a promising strategy for the treatment of Visceral Leishmaniasis. Current treatment regimens are limited due to drug resistance and high costs.

Soft glassy rheology of single cells with pathogenic protein aggregates.

A correlation between the mechanical properties of cells and various diseases has been emerging in recent years. Atomic force microscopy (AFM) has been widely used to measure a single cell's apparent Young's modulus by treating it as a fully elastic object. More recently, quantitative characterization of the complete viscoelasticity of single cells has become possible.

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication.

Viral infections can cause Endoplasmic Reticulum (ER) stress due to abnormal protein accumulation, leading to Unfolded Protein Response (UPR). Viruses have developed strategies to manipulate the host UPR, but there is a lack of detailed understanding of UPR modulation and its functional significance during HIV-1 infection in the literature. In this context, the current article describes the protocols used in our laboratory to measure ER stress levels and UPR during HIV-1 infection in T-cells and the effect of UPR on viral replication and infectivity.

A high-throughput screen in mESCs to identify the cross-talk between signaling, endocytosis, and pluripotency.

Embryonic stem cell fate is regulated by various cellular processes. Recently, the process of endocytosis has been implicated in playing a role in the maintenance of self-renewal and pluripotency of mouse embryonic stem cells. A previous siRNA-based screen interrogated the function of core components of the endocytic machinery in maintaining the pluripotency of embryonic stem cells, revealing a crucial role for clathrin mediated endocytosis.

Protocol for measuring mechanical properties of live cells using atomic force microscopy.

Atomic force microscope (AFM) is a powerful and versatile tool to determine the physical properties of cells. The force-distance curves obtained from AFM experiments can be used to determine the stiffness and viscoelastic properties of cells. Here, we present a protocol for the determination of viscoelasticity from live cells such as Drosophila hemocytes or mouse embryonic stem cells using AFM.

Targeting peptide based therapeutics: Integrated computational and experimental studies of autophagic regulation in host-parasite interaction.

Cutaneous leishmaniasis caused by the intracellular parasite Leishmania major, exhibits significant public health challenge worldwide. With limited treatment options available, the identification of novel therapeutic targets is of paramount importance. Present study manifested the crucial role of ATG8 protein as a potential target in combating L.

Single-cell ATAC sequencing identifies sleepy macrophages during reciprocity of cytokines in infection.

The hallmark characteristic of macrophages lies in their inherent plasticity, allowing them to adapt to dynamic microenvironments. strategically modulates the phenotypic plasticity of macrophages, creating a favorable environment for intracellular survival and persistent infection through regulatory cytokine such as interleukin (IL)-10. Nevertheless, these effector cells can counteract infection by modulating crucial cytokines like IL-12 and key components involved in its production.

Community characterization of soil from the Central Deccan Plateau dry tropical deciduous forest (Ceddtrof) in central India using 16S rRNA gene amplicon sequencing.

We report a preliminary study of soil from the Central Deccan Plateau dry tropical deciduous forest in India using 16S rRNA gene amplicon sequencing. We report diverse taxa, e.g.

Th17 cell promotes apoptosis of IL-23R neurons in experimental autoimmune encephalomyelitis.

Myelin antigen-reactive Th1 and Th17 cells are critical drivers of central nervous system (CNS) autoimmune inflammation. Transcription factors T-bet and RORγt play a crucial role in the differentiation and function of Th1 and Th17 cells, and impart them a pathogenic role in CNS autoimmune inflammation. Mice deficient in these two factors do not develop experimental autoimmune encephalomyelitis (EAE).

DNAJB8 facilitates autophagic-lysosomal degradation of viral Vif protein and restricts HIV-1 virion infectivity by rescuing APOBEC3G expression in host cells.

HSP40/DNAJ family of proteins is the most diverse chaperone family, comprising about 49 isoforms in humans. Several reports have demonstrated the functional role of a few of these isoforms in the pathogenesis of various viruses, including HIV-1. Our earlier study has shown that several isoforms of HSP40 get significantly modulated at the mRNA level during HIV-1 infection in T cells.

Immunoregulatory framework and the role of miRNA in the pathogenesis of NSCLC - A systematic review.

With a 5-year survival rate of only 15%, non-small cell lung cancer (NSCLC), the most common kind of lung carcinoma and the cause of millions of deaths annually, has drawn attention. Numerous variables, such as disrupted signaling caused by somatic mutations in the EGFR-mediated RAS/RAF/MAPK, PI3K/AKT, JAK/STAT signaling cascade, supports tumour survival in one way or another. Here, the tumour microenvironment significantly contributes to the development of cancer by thwarting the immune response.

Decoding systems immunological model of sphingolipids with IL-6/IL-17/IL-23 axes in L. major infection.

IL-6, IL-17, IL-23 and IL-1β are the crucial cytokines controlling inflammatory and immune response during L. major infection. During cutaneous leishmaniasis, an important T helper cell type CD4 Th17 subset plays a deterministic role in lesion formation through channelling infected macrophages and production of IL-1β, IL-6, IL-23 and IFN-γ.

Nested Real-Time PCR Assessment of Vertical Transmission of Sandalwood Spike Phytoplasma ('. Phytoplasma asteris').

The Sandalwood Spike disease (SSD)-related to '. Phytoplasma asteris' has threatened the existence of sandalwood in India. The epidemiology of SSD is still poorly understood despite the efforts to understand the involvement of insect vectors in SSD transmission and alternate plant hosts over the last two decades.

Systems pharmacology aiding benzimidazole scaffold as potential lead compounds against leishmaniasis for functional therapeutics.

Systems pharmacology helps to understand the complex relationships between biological systems, drugs, and infection model; Leishmania major being one of them. It has aided the drug discovery process by addressing the concerns about economic stress, drug toxicity, and the emergence of resistance. Two million new leishmaniasis cases are reported annually, and >350 million people are at risk globally due to the parasite Leishmania.

Mechanobiology of immune cells: Messengers, receivers and followers in leishmaniasis aiding synthetic devices.

Cytokines are influential molecules which can direct cells behavior. In this review, cytokines are referred as messengers, immune cells which respond to cytokine stimulus are referred as receivers and the immune cells which gets modulated due to their plasticity induced by infectious pathogen leishmania, are referred as followers. The advantage of plasticity of cells is taken by the parasite to switch them from parasite eliminating form to parasite survival favoring form through a process called as reciprocity which is undergone by cytokines, wherein pro-inflammatory to anti-inflammatory switch occur rendering immune cell population to switch their phenotype.

MicroRNA-520c-3p impacts sphingolipid metabolism mediating PI3K/AKT signaling in NSCLC: Systems perspective.

Increasing research suggests that sphingolipid metabolism is essential for the progression and metastasis of cancer. The underlying mechanistic insight into the dysregulation of sphingolipid metabolism affecting pathways is poorly investigated. As a result, the goal of the current study was to glean knowledge from the systems biology approach to investigate how the sphingolipid metabolism affects the signal transduction network in non-small cell lung cancer (NSCLC), the most common type of cancer in terms of occurrence and death globally.

Zipper interacting protein kinase (ZIPK) is a negative regulator of HIV-1 replication that is restricted by viral Nef protein through proteasomal degradation.

Human immunodeficiency virus-1 (HIV-1) infection leads to the development of acquired immunodeficiency syndrome (AIDS). To establish a productive infection, HIV-1 hijacks the cellular machinery and modulates various physiological processes to propagate itself. The pathways altered by HIV-1 include cell cycle, autophagy, apoptosis, cell stress pathways, immune response, antiviral response, etc.

Artificial intelligence channelizing protein-peptide interactions pipeline for host-parasite paradigm in IL-10 and IL-12 reciprocity by SHP-1.

Identification of molecular targets in any cellular phenomena is a challenge and a path that one endeavors upon independently. We have identified a phosphatase SHP-1 as a point of intervention of IL-10 and IL-12 reciprocity in leishmaniasis. The therapeutic model that we have developed uniquely targets this protein but the pipeline in general can be used by the researchers for their unique targets.

Deciphering miR-520c-3p as a probable target for immunometabolism in non-small cell lung cancer using systems biology approach.

Background: Non-small cell lung cancer (NSCLC) is considered to have more than 80% of all lung cancer cases, making it the leading cause of cancer-related deaths globally. MicroRNA (miRNA) deregulation has been seen often in NSCLC and has been linked to the disease's genesis, progression, and metastasis via affecting their target genes.

Materials And Methods: Our study focused on the functionality of down-regulated miRNAs in NSCLC.

Evolutionary aspect of Miltefosine transporter proteins in Leishmania major.

Transporter proteins, P-glycoprotein (P-gp) and P4ATPase-CDC50, are responsible for the transport of Miltefosine drug across cell membrane of a protozoan parasite Leishmania major. Mutations or change in activity of these proteins may lead to emergence of resistance in the parasite. Owing to the structural and functional importance of these transporter proteins, we have tried to decipher the evolutionary divergence of these Miltefosine transporter proteins across different forms of life including Protists, Fungi, Plants and Animals.

Neurokinin receptors and their implications in various autoimmune diseases.

Neurokinin receptors belong to the GPCRs family and are ubiquitously expressed throughout the nervous and immune systems. Neurokinin receptors in coordination with neurokinins playing an important role in many physiological processes, including smooth muscle contraction, secretion, proliferation, and nociception. They also contribute to various disease conditions such as inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, psoriasis, and cancer.

Probing the Interactions Responsible for the Structural Stability of Trypanothione Reductase Through Computer Simulation and Biophysical Characterization.

With the necessity to develop antileishmanial drugs with substrate specificity, trypanothione reductase (TryR) has gained popularity in parasitology. TryR is unique to be present only in trypanosomatids and is functionally similar to glutathione in mammals. It protects against oxidative stress exerted by the host defense mechanism.