Chemical induced pathognomonic features observed in human vitiligo are mediated through miR-2909 RNomics pathway.

Background: Chemicals like Monobenzyl Ether of Hydroquinone (MBEH) and 4-Tertiary Butyl Phenol (4-TBP) have been widely recognized to induce clinical lesions that resemble vitiligo, but exact molecular pathway through which these chemicals initiate vitiligo is still far from clear.

Objectives: Since vitiligo is widely considered as an autoimmune disease, this study was an attempt to understand miR-2909 RNomics in vitiligo pathogenesis using MBEH treated primary melanocytes as an archetype cellular model because MBEH causes pathological features indistinguishable from clinical vitiligo.

Methods: Primary melanocytes were treated with MBEH and 4-TBP and the role of miR-2909 RNomics at transcriptional and translational level was explored through qRT-PCR, western blot analysis, flow cytometry, immunocytochemistry, immunohistochemistry and in silico binding affinities.

Vitamins (A&D) and Isoprenoid (Chenodeoxycholic acid) molecules are accompanied by Th1 immunostimulatory response and therapeutic cure in vivo: possible antileishmanial drugs.

Investigation of immune modulatory anti-leishmanial molecules is now being strongly encouraged to overcome the immunosuppression manifested during visceral leishmaniasis (VL), resistance, toxicity and high cost associated with conventional therapeutics. In the present study, we explored the protective efficacy of vitamin D, retinoic acid and isoprenoid chenodeoxycholic acid (CDCA) combinations against L. donovani infected BALB/c mice.

Mitochondrial respiration is restricted by miR-2909 within human melanocytes.

Most of the cancer types in general and melanoma in particular exhibit mitochondrial dysfunction leading to the Warburg effect. Our present study stemmed from the observation that human A-375 and melanoma B16 cells displayed overexpression of a novel micro-RNA, miR-2909, shown in our earlier studies to be involved in aerobic glycolysis. Consequently, our study attempts to demonstrate the role of miR-2909 in the regulation of mitochondrial function within human melanocytes.

Tumorigenic PVT-1 gene locus is governed by miR-2909 RNomics.

Genomic regulation and functional significance of PVT-1 gene locus, in the MYC-driven cancers, has remained enigmatic ever since its discovery. With the present study, an attempt is made to establish that cellular AATF genome encoded miR-2909 RNomics pathway involving crucial genes coding for KLF4, Deptor, mTORC1, STAT3, and p53 has the inherent capacity to ensure sustained co-amplification of PVT-1 gene locus together with c-Myc gene. Based upon these results, we propose that miR-2909 RNomics pathway may play a crucial role in the regulation of tumorigenic PVT-1 gene locus.

Human cellular mitochondrial remodelling is governed by miR-2909 RNomics.

Background: There exists a general recognition of the fact that mitochondrial remodelling as a result of aerobic glycolysis ensures human somatic cells to revert to a more primitive-form exhibiting stem-like phenotype. The present study is an attempt to demonstrate that miR-2909 RNomics within human peripheral blood mononuclear cells (PBMCs) has the inherent capacity to re-program these cells to exhibit mitochondrial remodelling paralleled by aerobic glycolysis together with intracellular lipid inclusions. Such re-programmed PBMCs also expressed genes having ability to sustain their de-differentiation state and survival.

Cellular miR-2909 RNomics governs the genes that ensure immune checkpoint regulation.

Cross-talk between coding RNAs and regulatory non-coding microRNAs, within human genome, has provided compelling evidence for the existence of flexible checkpoint control of T-Cell activation. The present study attempts to demonstrate that the interplay between miR-2909 and its effector KLF4 gene has the inherent capacity to regulate genes coding for CTLA4, CD28, CD40, CD134, PDL1, CD80, CD86, IL-6 and IL-10 within normal human peripheral blood mononuclear cells (PBMCs). Based upon these findings, we propose a pathway that links miR-2909 RNomics with the genes coding for immune checkpoint regulators required for the maintenance of immune homeostasis.

Cancer cells govern miR-2909 exosomal recruitment through its 3'-end post-transcriptional modification.

It is widely believed that selective packaging of nucleic acids, especially microRNAs, into exosomes secreted by the cancer cells not only ensures their growth and survival but also helps in the escape from immune surveillance. Keeping in view the fact that human cellular miR-2909 has emerged to regulate genes involved in oncogenesis and immunity, the present study was addressed to reveal the nature of miR-2909 expression within cancer cells of different tissue origin and its incorporation into exosomes secreted by these cells. Post-transcriptional modification, especially 3'-end adenylation and uridylation of miR-2909, exerts opposing effects that may contribute to direct its sorting into exosomes secreted by cancer cells.

An androgen-regulated miR-2909 modulates TGFβ signalling through AR/miR-2909 axis in prostate cancer.

In recent years, microRNAs (miRNAs) have emerged as promising biomarkers for PCa diagnosis and prognosis. miR-2909 is a novel miRNA that can regulate immunogenomics and oncogenomics. The present study investigated the role of miR-2909 in the pathogenesis of PCa and the potential signalling pathways through which it operates.

miR-2909 regulates ISGylation system via STAT1 signalling through negative regulation of SOCS3 in prostate cancer.

One of the well-document strategies adopted by tumour cells for progression is to evade immune surveillance mechanisms. An understanding of the tight interaction between immunity and progression of cancer can provide novel treatment options for different malignancies including prostate cancer (PCa). Here, we have shown that AATF genome encoded miR-2909, known to play role both in immunity and cancer upregulates various interferon stimulating genes (ISGs) including ISGylation system through STAT1.

APOBEC3G governs the generation of truncated AATF protein to ensure oncogenic transformation.

The oncogenic potential of Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) was recently appreciated by the finding that revealed its ability to downregulate Kruppel-like factor 4 (KLF4) gene translation through its affinity for 3'UTR of KLF4 mRNA. Keeping in view the fact that KLF4 is known to repress apoptosis antagonizing transcription factor (AATF) gene expression, the present study employed stem cells as archetype model to explore the effect of APOBEC3G over-expression upon AATF gene expression within these cells as well as on the genes involved in oncogenic transformation. Such a study revealed that APOBEC3G had the ability to bind AATF mRNA within its third exon to facilitate the generation of truncated 23 kDa AATF translation product which, in turn, had the inherent capacity to be the crucial mediator of APOBEC3G induced oncogenic transformation within such cells.

APOBEC3G has the ability to programme T cell plasticity.

Recently Apolipoprotein B mRNA editing enzyme, Catalytic Polypeptide-like 3G (APOBEC3G) biology has assumed importance because of its role in oncogenesis. In this context, the present study was addressed to understand the immune-modulatory role of APOBEC3G through its effect upon the T-cell plasticity phenomenon. Such an attempt revealed that APOBEC3G has the inherent capacity to regulate genes coding for STAT3, NF-κB, CCL5, IL-6, IL-4, IFN-γ, IL-10 and IL-17 coupled with downregulation of Treg cells within human peripheral blood mononuclear cells (PBMCs) without any noticeable influence upon CD4(+) and CD8(+) cell number.

DNA Ploidy and S-phase Fraction Analysis in Paediatric B-cell Acute Lymphoblastic Leukemia Cases: a Tertiary Care Centre Experience.

DNA ploidy is an important prognostic parameter in paediatric B-ALL, but the significance of the S-phase fraction is unclear. In present study, DNA ploidy was assessed in 40 pediatric B-ALL cases by flow cytometry. The DI (DNA index) and percentage of cells in S-phase were calculated using Modfit software.

Downregulation of host tryptophan-aspartate containing coat (TACO) gene restricts the entry and survival of Leishmania donovani in human macrophage model.

Leishmania are obligate intracellular protozoan parasites of mammalian hosts. Promastigotes of Leishmania are internalized by macrophages and transformed into amastigotes in phagosomes, and replicate in phagolysosomes. Phagosomal maturation arrest is known to play a crucial role in the survival of pathogenic Leishmania within activated macrophages.

APOBEC3G governs to ensure cellular oncogenic transformation.

The oncogenic potential of APOBEC3G gene was recently appreciated by the finding that revealed inhibitory influence of APOBEC3G upon micro-RNA mediated repression of the gene responsible for hepatic metastasis. Here we report for the first time that sustained APOBEC3G expression is the characteristic trait exhibited by various cancer cells of different tissue origins as well as APOBEC3G represses cellular gene coding for tumor suppressor KLF4 by binding to its mRNA. This phenomenon was paralleled by the sustained expression of the cellular SP1 which ensured overexpression of genes coding for c-myc, Bmi-1, BCL-2 and MDM2 coupled with downregulation of tumor suppressor p53 thereby creating a favorable situation for oncogenic transformation.

Microdissecting the role of microRNAs in the pathogenesis of prostate cancer.

MicroRNAs (miRNAs) are naturally occurring, small, non-coding RNA molecules that post-transcriptionally regulate the expression of a large number of genes involved in various biological processes, either through mRNA degradation or through translation inhibition. Since the discovery of miRNAs, a vast amount of research has implicated the deregulated expression of miRNAs in different malignancies, including prostate cancer (PCa). Different miRNA expression profiles are reportedly associated with the development, progression, and emergence of castration-resistant PCa (CRPC), suggesting their use in the diagnosis, prognosis, and development of anti-cancer treatment models directed against this disease.

Mitochondrial uncoupling protein (UCP2) gene expression is regulated by miR-2909.

Reversible decoupling of glycolysis from aerobic-respiration has been widely recognized to be a crucial step in tailoring immune response by the human cells. In this context, the study reported here revealed for the first time that cooperativity between Apoptosis Antagonizing Transcription Factor (AATF) mRNA and miR-2909 within cellular AATF RNome ensures the regulation of mitochondrial uncoupling protein 2 (UCP2) expression in a cyclic fashion and this phenomenon is substantiated when the immune cells face high glucose threat.

Short-Term Adjuvant Therapy with Terminalia arjuna Attenuates Ongoing Inflammation and Immune Imbalance in Patients with Stable Coronary Artery Disease: In Vitro and In Vivo Evidence.

The present study evaluated the cardioprotective effects of Terminalia arjuna on classical and immuno-inflammatory markers in coronary artery disease (CAD) as an adjuvant therapy. One hundred sixteen patients with stable CAD were administered placebo/T. arjuna (500 mg twice a day) along with medications in a randomized, double-blind clinical trial.

Functional nature of a novel mutant CYLD observed in pediatric lymphoblastic B-cell leukemia.

The Deubiquitinating enzyme, Cylindromatosis (CYLD), has been established as a crucial regulator of B-cells. The present study was addressed to identify the nature of CYLD-dependent RNomics in patients of pediatric age group with B-ALL. The study revealed the presence of a novel mutant CYLD of 55 kDa in these patients.

High glucose-induced human cellular immune response is governed by miR-2909 RNomics.

Regulation of NFkB family member RelA translocation by tumour suppressor genes encoding p53 and KLF4, has been widely recognized as the critical for human peripheral blood mononuclear cells (PBMCs) to meet their energy requirement for tailoring their immune response against any perceived threat. Our study was addressed to understand as to how human PBMCs respond to high glucose threat in terms of their genomics-directed immune response. The results of such a study revealed for the first time that NFkB induced miR-2909 RNomics is crucial for the regulation of RelA translocation within human PBMCs exposed to high glucose thereby enabling these epigenetically programmed cells to tailor immune response involving genes coding for CCL5; IFN-γ and IL-17.

AATF RNome has the potential to define post mortem interval.

Keeping in view the fact that the circadian rhythm governs human behavioral characteristics, metabolism and body function, the present study was directed to explore whether or not there exists any cooperativity between AATF RNome (comprising AATF mRNA and its encoded microRNA miR-2909) rhythmicity and post mortem interval (PMI). Such a study unambiguously revealed that circadian rhythm exhibited by AATF RNome has a direct correlation with PMI in Balb/c mice. AATF RNome has the potential to act as biomarker for PMI with reasonably good accuracy and hence may turn out to be of crucial importance in forensic investigation.

MALT1 induced immune response is governed by miR-2909 RNomics.

The paracaspase mucosa-associated lymphoid tissue 1 (MALT1) has been widely recognized to play crucial role in lymphocyte activation, development and the generation of lymphomas through the modulation of innate and adaptive immune responses. Our results reported here provide evidence for the first time to support the view that MALT1 exerts its effect upon immune response involving genes coding for retinoic acid-inducible gene 1 (RIG1); interferon-β (IFN-β); apo-lipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G (APOBEC3G); IFN-γ; chemokine (C-C motif) ligand 5 (CCL5) and interleukin-17 (IL-17) through the initiation of cellular miR-2909 RNomics. This ensures sustained expression of specificity protein 1 (SP1)-dependent regulation of genes that in-turn governs MALT1 induced immune response.

Interleukin-18-induced atherosclerosis involves CD36 and NF-κB crosstalk in Apo E-/- mice.

Objective: Interleukin (IL)-18 is a pleotropic cytokine involved in various inflammatory disorders. The transcription factor, nuclear factor kappa-B (NF-κB), is thought to play an important role in IL-18 signaling. The present study proposes a novel role for IL-18 in cholesterol efflux and plaque stability and demonstrates that pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor blocks IL-18 signaling in apolipoprotein (Apo) E-/- mice.

Conventional therapies fail to target inflammation and immune imbalance in subjects with stable coronary artery disease: a system-based approach.

Objective: Cardiovascular diseases are the leading cause of morbidity and mortality. In spite of improved pharmacological interventions, the clinical outcome or response to therapy is poorly linked with the reversal of signs and symptoms of the disease.

Material And Results: Keeping this in view, we evaluated the post-treatment effect of standard therapies on traditional risk factors as well as inflammatory markers in 116 non-diabetic subjects with stable CAD undergoing treatment with conventional drugs for >3 months (Group-II) and 50 normal healthy controls (Group-I).

Modulation of LXR-α and the effector genes by Ascorbic acid and Statins in psoriatic keratinocytes.

Recent studies have revealed critical roles that nuclear receptors like LXR-α (Liver X Receptor- alpha) plays as a class of post-transcriptional gene regulator in skin development and diseases. Keeping in view the fact that LXR-α plays crucial role in keratinocyte proliferation and differentiation, it becomes imperative to dissect the pathways and role of LXR-α genomics in the pathogenesis of psoriasis with ultimate aim to explore novel preventive/therapeutic strategies as treatment options. To explore the effects of agonists and activators of LXR-α on its own gene expression and the putative targets in psoriatic keratinocytes.