Showing papers by "Himanshu Kumar published in 2020"

The interplay between viral-derived miRNAs and host immunity during infection

Abstract: MicroRNAs are short non-coding RNAs that play a crucial role in the regulation of gene expression during cellular processes. The host-encoded miRNAs are known to modulate the antiviral defense during viral infection. In the last decade, multiple DNA and RNA viruses have been shown to produce miRNAs known as viral miRNAs (v-miRNAs) so as to evade the host immune response. In this review, we highlight the origin and biogenesis of viral miRNAs during the viral lifecycle. We also explore the role of viral miRNAs in immune evasion and hence in maintaining chronic infection and disease. Finally, we offer insights into the underexplored role of viral miRNAs as potential targets for developing therapeutics for treating complex viral diseases.

Robust Learning of Multi-Label Classifiers under Label Noise

Abstract: In this paper, we address the problem of robust learning of multi-label classifiers when the training data has label noise. We consider learning algorithms in the risk-minimization framework. We define what we call symmetric label noise in multi-label settings which is a useful noise model for many random errors in the labeling of data. We prove that risk minimization is robust to symmetric label noise if the loss function satisfies some conditions. We show that Hamming loss and a surrogate of Hamming loss satisfy these sufficient conditions and hence are robust. By learning feedforward neural networks on some benchmark multi-label datasets, we provide empirical evidence to illustrate our theoretical results on the robust learning of multi-label classifiers under label noise.

Therapeutic approaches for genetic and infectious diseases.

Abstract: Extrinsic and intrinsic factors perturb the normal structure, function, or structural—functional coordination of the host that results in disease, either infectious or noninfectious. Infectious dis...

Imperative role of particulate matter in innate immunity during RNA virus infection

Abstract: Sensing of pathogens by specialized receptors is the hallmark of the innate immune response. Innate immune response also mounts a defense response against various allergens and pollutants including particulate matter present in the atmosphere. Air pollution has been included as the top threat to global health declared by WHO which aims to cover more than three billion people against health emergencies from 2019-2023. Particulate matter (PM), one of the major components of air pollution, is a significant risk factor for many human diseases and its adverse effects include morbidity and premature deaths throughout the world. Several clinical and epidemiological studies have identified a key link between the PM composition and the prevalence of respiratory and inflammatory disorders. However, the underlying molecular mechanism is not well understood. Here, we investigated the influence of air pollutant, PM10 during RNA virus infections using highly pathogenic avian influenza (HPAI). We thus characterized the transcriptomic profile of lung epithelial cell line, A549 treated with PM10 prior to infection with (HPAI) H5N1 influenza virus, which is known to severely affect the lung and cause respiratory damage. We found that PM10 regulates virus infectivity and enhances overall pathogenic burden in the lung cells. Additionally, the transcriptomic profile highlights the connection of host factors related to various metabolic pathways and immune responses which were dysregulated during virus infection. Overall our findings suggest a strong link between the prevalence of respiratory illness and the air quality.

Metabolic pathways and metabolites shaping innate immunity

Abstract: Synthesis and breakdown of biomolecules through biochemical pathways in the cells for various cellular processes such as cell survival, growth, replication and so on are known as cellular metabolism. The cellular metabolism is not only essential for organization of cellular processes, but it is crucial for tailoring and shaping the host immunity to defend infection and maintain immune homeostasis. Additionally, at cellular and molecular levels, several metabolic intermediates are key deciding factors for many immunological events and induction of cytokines and hence are required to develop appropriate protective responses. Therefore, dysregulation of metabolic pathways may change the susceptibility to disease. This issue of International Reviews of Immunology describes how immunometabolism influences immunological responses, particularly, the macrophage function during vaccination. The issue also provides the possibilities of fine tuning the metabolic pathways or metabolic intermediates to treat different medical conditions (Figure-1). Tuberculosis (TB) is one of the common diseases in developing countries caused by Mycobacterium tuberculosis (Mtb). Mtb broadly causes two kinds of tuberculosis, lung or pulmonary and extrapulmonary TB. Emergence of drug resistant Mtb is a serious threat world-wide and global efforts are going on to understand the complexity of Mtb and develop appropriate drugs and vaccines. Although bacille Calmette-Gu erin (BCG) is a vaccine widely used for TB, the host-BCG interaction is poorly understood. The first review article in this issue by Liu et al. discusses the nonspecific immunity induced by BCG through changing the flux of host metabolic pathways and reestablishing the epigenetic marks (1). The article is useful to the researchers working in TB,

Healthy immunity: it’s all about immune regulation

Abstract: Balanced metabolism, cell signaling, influx or efflux of various biomolecules, metabolites within a cells and regulation of physiological processes are key features of a living entity and are achie...

Balancing immune tolerance and immune responses.

Abstract: Regulation is crucial for streamline function of immunity during infection, controlling growth of transformed cells, tolerance to commensal microbes, and tolerance at immune privilege sites. It is a complex process and takes place at signaling levels as well as the cellular level. The regulation at signaling level is mediated through molecular interactions of various transducer molecules and at the cellular level it is mediated through cell to cell interaction via cytokines or chemokines secreted by them. The breakdown of molecular regulatory circuit results in either low response to invading microbes or unwanted heightened responses or autoimmune diseases. This issue of International Reviews of Immunology describes, how physical workout, lowers inflammatory responses through pattern-recognition receptors of natural immunity and how regulatory B lymphocytes maintain low immune responses during pregnancy and its link with the hormones predominantly secreted during pregnancy. The issue also discusses the link among B cells, antibodies and neurological diseases in the central nervous system (Figure 1). Sensing signature molecules of pathogens, also known as pathogen-associated molecular patterns (PAMPs) by innate immune sensors, induces cytokines and chemokines to develop an antimicrobial state. On another hand, sensing of host molecules, known as damage or danger-associated molecular pattern by innate sensors, result in autoimmune inflammatory diseases. In recent years, the crosstalk among metabolic products produced during different physical states and associated metabolic diseases and innate immunity have been investigated to greater extant. The first review article of this issue by Collaoa et al. discusses how physical or metabolic state is linked with innate immunity, particularly Toll-like receptor-mediated immune responses. The authors also discuss the beneficial aspects of physical activities in light of

Tools for fundamental understanding of systemic lupus erythematosus.

Abstract: The regulated and dynamic interactions of immune cells and its soluble and cellular factor constitute the host immunity, which manages microbial challenges and maintains homeostasis. The onset of a...

Therapeutic management of post-parturient haemoglobunuria in buffalo: A case report

Abstract: A 6 year old buffalo with third parity was presented to Veterinary Clinical complex at College of veterinary and animal sciences, Pantnagar with reddish brown color urine, inappetance, reduced milk production, and constipation. The laboratory examination revealed anemia haemoglobinuria and hypophosphatemia. A phosphorus deficiency is associated with predominantly forage based diet and inadequate mineral supplementation is suspected for probable underlying cause. A course of five days phosphorus supplementation and non specific supportive therapy was immediately initiated based on the tentative diagnosis. It effectively revered the clinical course of the disease and brought significant improvement. The case report indicated that phosphorus supplementation may improve the haematological and serum biochemical parameters and successful therapeutic management of post parturient haemoglobinuria (PPH) in buffaloes.

Integrated role of microRNA-30e-5p through targeting negative regulators of innate immune pathways during HBV infection and SLE

Abstract: Precise regulation of innate immunity is crucial for the development of appropriate host immunity against microbial infections and the maintenance of immune homeostasis. The microRNAs are small non-coding RNA, post-transcriptional regulator of multiple genes and act as a rheostat for protein expression. Here, we identified microRNA(miR)-30e-5p (miR-30e) induced by the hepatitis B virus (HBV) and other viruses that act as a master regulator for innate immune responses. Moreover, pegylated type I interferons treatment to HBV patients for viral reduction also reduces the miRNA. Additionally, we have also shown the immuno-pathological effects of miR-30e in systemic lupus erythematosus (SLE) patients and SLE mouse model. Mechanistically, the miR-30e targets multiple negative regulators namely TRIM38, TANK, ATG5, ATG12, BECN1, SOCS1, SOCS3 of innate immune signaling pathways and enhances innate immune responses. Furthermore, sequestering of endogenous miR-30e in PBMCs of SLE patients and SLE mouse model respectively by the introduction of antagomir and locked nucleic acid based inhibitor significantly reduces type I interferon and pro-inflammatory cytokines. Collectively, our study demonstrates the novel role of miR-30e in innate immunity and its prognostic and therapeutic potential in infectious and autoimmune diseases.

Progresses in immunotherapy

Abstract: Immunotherapy means tailoring the host immune responses using exogeneous or endogenous immune or non-immune cells/molecules to defend against various diseases. It was originally established by Onco...