Dengue virus pathogenesis and host molecular machineries.

Dengue viruses (DENV) are positive-stranded RNA viruses belonging to the Flaviviridae family. DENV is the causative agent of dengue, the most rapidly spreading viral disease transmitted by mosquitoes. Each year, millions of people contract the virus through bites from infected female mosquitoes of the Aedes species. In the majority of individuals, the infection is asymptomatic, and the immune system successfully manages to control virus replication within a few days. Symptomatic individuals may present with a mild fever (Dengue fever or DF) that may or may not progress to a more critical disease termed Dengue hemorrhagic fever (DHF) or the fatal Dengue shock syndrome (DSS). In the absence of a universally accepted prophylactic vaccine or therapeutic drug, treatment is mostly restricted to supportive measures. Similar to many other viruses that induce acute illness, DENV has developed several ways to modulate host metabolism to create an environment conducive to genome replication and the dissemination of viral progeny. To search for new therapeutic options, understanding the underlying host-virus regulatory system involved in various biological processes of the viral life cycle is essential. This review aims to summarize the complex interaction between DENV and the host cellular machinery, comprising regulatory mechanisms at various molecular levels such as epigenetic modulation of the host genome, transcription of host genes, translation of viral and host mRNAs, post-transcriptional regulation of the host transcriptome, post-translational regulation of viral proteins, and pathways involved in protein degradation.

The association between anti-smoking legislation and prevalence of acute respiratory illnesses in Indian children.

Objective: Exposure to tobacco smoke causes numerous health problems in children, and create burden on the population in terms of economy, morbidity and mortality. In order to protect the child from exposure to tobacco smoke in the outdoor environment, sufficient legislative enactments are available in Indian legislation. The objective of the present study is to investigate the fact that in absence of any specific laws stating about protection of children from exposure to tobacco smoke in indoor environment, whether outdoor related legislations are sufficient to protect children from exposureand to explore the scope for enforcement of both state and central laws in improving health of children in India. Study design: The study considered cross-sectional survey data of Demographic and Health Survey Data on India, National Family and Health Survey fourth round (NFHS-4) for the year 2015-16 on Indian children (below age of four). Methods: Both bivariate and multivariate logistic regression models were used to assess the impact of anti-smoking laws on the prevalence of acute respiratory infection (ARI) based on the place of residence, indoor tobacco smoke exposure and age of the child. Results: The results have shown an inclination of ARI among children in association with states having single law, rural area resident, exposure to indoor tobacco smoke and age of the child, both as independent or in combination are quite conspicuous, and are found to be underestimated. The logistic regression also revealed the influence of these factors both as independent and even in interaction with other. Conclusions: Legislative intervention through both at central (or national)and state levels through anti-smoking laws will decrease the indoor tobacco smoke exposure as a result ARI prevalence will also decrease among children in India.

Next-generation therapeutics for rare genetic disorders.

The therapeutic potential of the human genome has been explored through the development of next-generation therapeutics, which have had a high impact on treating genetic disorders. Classical treatments have traditionally focused on common diseases that require repeated treatments. However, with the recent advancements in the development of nucleic acids, utilizing DNA and RNA to modify or correct gene expression in genetic disorders, there has been a paradigm shift in the treatment of rare diseases, offering more potential one-time cure options. Advanced technologies that use CRISPR-Cas 9, antisense oligonucleotides, siRNA, miRNA, and aptamers are promising tools that have achieved successful breakthroughs in the treatment of various genetic disorders. The advancement in the chemistry of these molecules has improved their efficacy, reduced toxicity, and expanded their clinical use across a wide range of tissues in various categories of human disorders. However, challenges persist regarding the safety and efficacy of these advanced technologies in translating into clinical practice. This review mainly focuses on the potential therapies for rare genetic diseases and considers how next-generation techniques enable drug development to achieve long-lasting curative effects through gene inhibition, replacement, and editing.

Circulating plasma miR-23b-3p as a biomarker target for idiopathic Parkinson's disease: comparison with small extracellular vesicle miRNA.

Background: Parkinson's disease (PD) is an increasingly common neurodegenerative condition, which causes movement dysfunction and a broad range of non-motor symptoms. There is no molecular or biochemical diagnosis test for PD. The miRNAs are a class of small non-coding RNAs and are extensively studied owing to their altered expression in pathological states and facile harvesting and analysis techniques. Methods: A total of 48 samples (16 each of PD, aged-matched, and young controls) were recruited. The small extracellular vesicles (sEVs) were isolated and validated using Western blot, transmission electron microscope, and nanoparticle tracking analysis. Small RNA isolation, library preparation, and small RNA sequencing followed by differential expression and targeted prediction of miRNA were performed. The real-time PCR was performed with the targeted miRNA on PD, age-matched, and young healthy control of plasma and plasma-derived sEVs to demonstrate their potential as a diagnostic biomarker. Results: In RNA sequencing, we identified 14.89% upregulated (fold change 1.11 to 11.04, p < 0.05) and 16.54% downregulated (fold change -1.04 to -7.28, p < 0.05) miRNAs in PD and controls. Four differentially expressed miRNAs (miR-23b-3p, miR-29a-3p, miR-19b-3p, and miR-150-3p) were selected. The expression of miR-23b-3p was "upregulated" (p = 0.002) in plasma, whereas "downregulated" (p = 0.0284) in plasma-derived sEVs in PD than age-matched controls. The ROC analysis of miR-23b-3p revealed better AUC values in plasma (AUC = 0.8086, p = 0.0029) and plasma-derived sEVs (AUC = 0.7278, p = 0.0483) of PD and age-matched controls. Conclusion: We observed an opposite expression profile of miR-23b-3p in PD and age-matched healthy control in plasma and plasma-derived sEV fractions, where the expression of miR-23b-3p is increased in PD plasma while decreased in plasma-derived sEV fractions. We further observed the different miR-23b-3p expression profiles in young and age-matched healthy control.

Synergistic correlation between host angiogenin and dengue virus replication.

DENV infection poses a major health concern globally and the pathophysiology relies heavily on host-cellular machinery. Although virus replication relies heavily on the host, the mechanistic details of DENV-host interaction is not fully characterized yet. Here, we are focusing on characterizing the mechanistic basis of virus-induced stress on the host cell. Specifically, we aim to characterize the role of the stress modulator ribonuclease Angiogenin during DENV infection. Our results suggested that the levels of Angiogenin are up-regulated in DENV-infected cells and the levels increase proportionately with DENV replication. Our efforts to knockdown Angiogenin using siRNA were unsuccessful in DENV-infected cells but not in mock-infected control. To further investigate the modulation between DENV replication and Angiogenin, we treated Huh7 cells with Ivermectin prior to DENV infection. Our results suggest a significant reduction in DENV replication specifically at the later stages as a consequence of Ivermectin treatment. Interestingly, Angiogenin levels were also found to be decreased proportionately. Our results suggest that Angiogenin modulation during DENV infection is important for DENV replication and pathogenesis.

Modulation of various host cellular machinery during COVID-19 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) emerged in December 2019, causing a range of respiratory infections from mild to severe. This resulted in the ongoing global COVID-19 pandemic, which has had a significant impact on public health. The World Health Organization declared COVID-19 as a global pandemic in March 2020. Viruses are intracellular pathogens that rely on the host's machinery to establish a successful infection. They exploit the gene expression machinery of host cells to facilitate their own replication. Gaining a better understanding of gene expression modulation in SARS-CoV2 is crucial for designing and developing effective antiviral strategies. Efforts are currently underway to understand the molecular-level interaction between the host and the pathogen. In this review, we describe how SARS-CoV2 infection modulates gene expression by interfering with cellular processes, including transcription, post-transcription, translation, post-translation, epigenetic modifications as well as processing and degradation pathways. Additionally, we emphasise the therapeutic implications of these findings in the development of new therapies to treat SARS-CoV2 infection.

Unravelling the immunobiology of innate lymphoid cells (ILCs): Implications in health and disease.

Innate lymphoid cells (ILCs), a growing class of immune cells, imitate the appearance and abilities of T cells. However, unlike T cells, ILCs lack acquired antigen receptors, and they also do not undergo clonal selection or proliferation in response to antigenic stimuli. Despite lacking antigen-specific receptors, ILCs respond quickly to signals from infected or damaged tissues and generate an array of cytokines that regulate the development of adaptive immune response. ILCs can be categorized into four types based on their signature cytokines and transcription factors: ILC1, ILC2, ILC3 (including Lymphoid Tissue inducer- LTi cells), and regulatory ILCs (ILCregs). ILCs play key functions in controlling and resolving inflammation, and variations in their proportion are linked to various pathological diseases including cancer, gastrointestinal, pulmonary, and skin diseases. We highlight current advancements in the biology and classification of ILCs in this review. Additionally, we provide a thorough overview of their contributions to several inflammatory bone-related pathologies, including osteoporosis, rheumatoid arthritis, periodontitis, and ankylosing spondylitis. Understanding the multiple functions of ILCs in both physiological and pathological conditions will further mobilize future research towards targeting ILCs for therapeutic purposes.

Alarming Trend in Under-Five Indian Children's Exposure to Indoor Tobacco Smoke.

BACKGROUND AND AIM: Children who are exposed to tobacco smoke (ETS) are at risk for a variety of health issues. There are enough legislative provisions in Indian law to safeguard children from ETS in outdoor settings, but no such specific rules exist to shield them from exposure indoors. This study aimed to examine the trend in under-five children's exposure to indoor tobacco smoke over the course of a decade (from 2005 to 2016) in India. MATERIALS AND METHODS: Data from the National Family and Health Survey (NFHS) for the years 2005-2006 (NFHS-3) and 2015-2016 (NFHS-4) on under-five children have been taken into consideration in cross-sectional analyses of the Demographic and Health Survey on India. Based on different sociodemographic factors, the propensity of indoor ETS among Indian children has been estimated and compared using both bivariate and multivariate logistic regression models. RESULTS: The prevalence of indoor ETS among Indian children under the age of five has greatly risen over the past decade, rising from 4.12% to 52.70%. According to the findings, there has been a noticeable increase in every group of kids, regardless of their age, place of residence, geographic location, socioeconomic status, and literacy level of their mothers. CONCLUSION: In India, the incidence of indoor ETS among children under five has risen by 13 times in the last 10 years, endangering the country. As a result, the Indian government must prepare to take legislative action to safeguard children by passing laws that forbid smoking inside.

Fine-tuning osteoclastogenesis: An insight into the cellular and molecular regulation of osteoclastogenesis.

Osteoclasts, the bone-resorbing cells, are essential for the bone remodeling process and are involved in the pathophysiology of several bone-related diseases. The extensive corpus of in vitro research and crucial mouse model studies in the 1990s demonstrated the key roles of monocyte/macrophage colony-stimulating factor, receptor activator of nuclear factor kappa B ligand (RANKL) and integrin αvß3 in osteoclast biology. Our knowledge of the molecular mechanisms by which these variables control osteoclast differentiation and function has significantly advanced in the first decade of this century. Recent developments have revealed a number of novel insights into the fundamental mechanisms governing the differentiation and functional activity of osteoclasts; however, these mechanisms have not yet been adequately documented. Thus, in the present review, we discuss various regulatory factors including local and hormonal factors, innate as well as adaptive immune cells, noncoding RNAs (ncRNAs), etc., in the molecular regulation of the intricate and tightly regulated process of osteoclastogenesis. ncRNAs have a critical role as epigenetic controllers of osteoclast physiologic activities, including differentiation and bone resorption. The primary ncRNAs, which include micro-RNAs, circular RNAs, and long noncoding RNAs, form a complex network that affects gene transcription activities associated with osteoclast biological activity. Greater knowledge of the involvement of ncRNAs in osteoclast biological activities will contribute to the treatment and management of several skeletal diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, etc. Moreover, we further outline potential therapies targeting these regulatory pathways of osteoclastogenesis in distinct bone pathologies.

The SARS-CoV-2 UTR's Intrudes Host RBP's and Modulates Cellular Splicing.

SARS-CoV-2 is a novel coronavirus that causes a potentially fatal respiratory disease known as coronavirus disease (COVID-19) and is responsible for the ongoing pandemic with increasing mortality. Understanding the host-virus interaction involved in SARS-CoV-2 pathophysiology will enhance our understanding of the mechanistic basis of COVID-19 infection. The characterization of post-transcriptional gene regulatory networks, particularly pre-mRNA splicing, and the identification and characterization of host proteins interacting with the 5' and 3'UTRs of SARS-CoV-2 will improve our understanding of post-transcriptional gene regulation during SARS-CoV-2 pathogenesis. Here, we demonstrate that either SARS-CoV-2 infection or exogenous overexpression of the 5' and 3'UTRs of the viral genomic RNAs, results in reduced mRNA levels possibly due to modulation of host cell pre-mRNA splicing. Further, we have investigated the potential RNA-binding proteins interacting with the 5' and 3'UTRs, using in-silico approaches. Our results suggest that 5' and 3'UTRs indeed interact with many RNA-binding proteins. Our results provide a primer for further investigations into the UTR-mediated regulation of splicing and related molecular mechanisms in host cells.

Long-term implications of COVID-19 on bone health: pathophysiology and therapeutics.

BACKGROUND: SARS-CoV-2 is a highly infectious respiratory virus associated with coronavirus disease (COVID-19). Discoveries in the field revealed that inflammatory conditions exert a negative impact on bone metabolism; however, only limited studies reported the consequences of SARS-CoV-2 infection on skeletal homeostasis. Inflammatory immune cells (T helper-Th17 cells and macrophages) and their signature cytokines such as interleukin (IL)-6, IL-17, and tumor necrosis factor-alpha (TNF-α) are the major contributors to the cytokine storm observed in COVID-19 disease. Our group along with others has proven that an enhanced population of both inflammatory innate (Dendritic cells-DCs, macrophages, etc.) and adaptive (Th1, Th17, etc.) immune cells, along with their signature cytokines (IL-17, TNF-α, IFN-γ, IL-6, etc.), are associated with various inflammatory bone loss conditions. Moreover, several pieces of evidence suggest that SARS-CoV-2 infects various organs of the body via angiotensin-converting enzyme 2 (ACE2) receptors including bone cells (osteoblasts-OBs and osteoclasts-OCs). This evidence thus clearly highlights both the direct and indirect impact of SARS-CoV-2 on the physiological bone remodeling process. Moreover, data from the previous SARS-CoV outbreak in 2002-2004 revealed the long-term negative impact (decreased bone mineral density-BMDs) of these infections on bone health. METHODOLOGY: We used the keywords "immunopathogenesis of SARS-CoV-2," "SARS-CoV-2 and bone cells," "factors influencing bone health and COVID-19," "GUT microbiota," and "COVID-19 and Bone health" to integrate the topics for making this review article by searching the following electronic databases: PubMed, Google Scholar, and Scopus. CONCLUSION: Current evidence and reports indicate the direct relation between SARS-CoV-2 infection and bone health and thus warrant future research in this field. It would be imperative to assess the post-COVID-19 fracture risk of SARS-CoV-2-infected individuals by simultaneously monitoring them for bone metabolism/biochemical markers. Importantly, several emerging research suggest that dysbiosis of the gut microbiota-GM (established role in inflammatory bone loss conditions) is further involved in the severity of COVID-19 disease. In the present review, we thus also highlight the importance of dietary interventions including probiotics (modulating dysbiotic GM) as an adjunct therapeutic alternative in the treatment and management of long-term consequences of COVID-19 on bone health.

Carotid intima-media thickness predicted the presence but not the severity or complexity of coronary artery disease in a South Asian population / El grosor de íntima media carotídeo predijo la presencia aunque no la gravedad ni complejidad de la enfermedad de las arterias coronarias en la población del sur de Asia

Background: Carotid intima-media thickness (CIMT) is considered a marker of atherosclerosis, but the data is lacking from the South Asian population. We aimed to study the relation of CIMT with the presence and severity of coronary artery disease (CAD) in this population. Methods: This was a prospective, single-center study of consecutive patients undergoing elective coronary angiography. Participants with >50% luminal stenosis in any major coronary artery were included in the CAD group and those with normal coronaries in the non-CAD group. Multivariate linear regression analysis was done to determine independent predictors of CAD. Pearson's correlation coefficients assessed correlations between CIMT and Syntax and Gensini score. Results: The mean CIMT was significantly much higher in the CAD group when compared to the non-CAD group (0.83±0.16 vs 0.61±0.14mm, p<0.001). On multivariable linear regression analysis only diabetes (β=0.208 and p=0.024), waist–hip ratio (β=0.178 and p=0.043), current smoker (β=0.293 and p=<0.001) and CIMT (β=0.217 and p=0.031) were independent predictors of CAD. The mean Gensini score in the CAD group was 48.59±34.25 and the mean Syntax score was 19.45±10.24. No significant relation was found between CIMT and Gensini score (r=0.009 and p=0.89), and Syntax score (r=−0.087 and p=0.171). Conclusion: Mean CIMT is an independent predictor of CAD along with diabetes, waist–hip ratio, and smoking. However, CIMT was not related to the severity and complexity of the CAD as assessed by the Gensini score and Syntax score, respectively. (AU)

Antecedentes: El grosor de íntima media carotídeo (GIM) está considerado un marcador de la aterosclerosis, aunque se carece de datos relativos a la población del sur de Asia. Nuestro objetivo fue estudiar la relación de GIM con la presencia y gravedad de la enfermedad de las arterias coronarias (EAC) en esta población. Métodos: Estudio prospectivo y unicéntrico de pacientes consecutivos sometidos a angiografía coronaria electiva. Se incluyó en el grupo EAC a los participantes con >50% estenosis luminal en cualquier arteria coronaria mayor, y en el grupo no EAC a los participantes con arterias coronarias normales. Se realizó un análisis de regresión lineal multivariante para determinar los factores predictivos independientes de EAC. Los coeficientes de correlación de Pearson evaluaron las correlaciones entre GIM y las puntuaciones de Gensini y Syntax. Resultados: El GIM medio fue significativamente mayor en el grupo EAC en comparación con el grupo no EAC (0,83±0,16 vs. 0,61±0,14mm, p<0,001). En el análisis de regresión lineal multivariante solo la diabetes (β=0,208 y p=0,024), el índice cintura-cadera (β=0,178 y p=0,043), y el tabaquismo actual (β=0,293 y p=<0,001) y GIM (β=0,217 y p=0,031) fueron factores predictivos independientes de EAC. La puntuación Gensini media en el grupo EAC fue de 48,59±34,25, y la puntuación Syntax media fue de 19,45±10,24. No se encontró relación significativa entre GIM y la puntuación de Gensini (r=0,009 y p=0,89) y la puntuación Syntax (r=−0,087 y p=0,171). Conclusión: El GIM medio es un factor predictivo independiente de EAC, junto con la diabetes, el índice cintura-cadera y el tabaquismo. Sin embargo, GIM no guardó relación con la gravedad y complejidad de EAC, según la evaluación de las puntuaciones de Gensini y Syntax, respectivamente. (AU)

Bifidobacterium longum Ameliorates Ovariectomy-Induced Bone Loss via Enhancing Anti-Osteoclastogenic and Immunomodulatory Potential of Regulatory B Cells (Bregs).

Discoveries in the last few years have emphasized the existence of an enormous breadth of communication between osteo-immune systems. These discoveries fuel novel approaches for the treatment of several bone pathologies including osteoporosis. Bifidobacterium longum (BL) is a preferred probiotic of choice due to its varied immunomodulatory potential in alleviating various inflammatory diseases. Here, we evaluate the effect of BL in an ovariectomy (ovx)-induced post-menopausal osteoporotic mouse model. Our in vitro findings reveal that BL suppresses the differentiation and functional activity of RANKL-induced osteoclastogenesis in both mouse bone marrow cells and human PBMCs. Strikingly, BL-induced Bregs were found to be significantly more efficient in suppressing osteoclastogenesis and modulating Treg-Th17 cell balance with respect to control Bregs in vitro. Our in vivo µCT and bone mechanical strength data further confirm that BL supplementation significantly enhanced bone mass and bone strength, along with improving the bone microarchitecture in ovx mice. Remarkably, alterations in frequencies of CD19+CD1dhiCD5+IL-10+ Bregs, CD4+Foxp3+IL-10+ Tregs, and CD4+Rorγt+IL-17+ Th17 cells in distinct lymphoid organs along with serum-cytokine data (enhanced anti-osteoclastogenic cytokines IFN-γ and IL-10 and reduced osteoclastogenic-cytokines IL-6, IL-17, and TNF-α) strongly support the immunomodulatory potential of BL. Altogether, our findings establish a novel osteo-protective and immunomodulatory potential of BL in augmenting bone health under osteoporotic conditions.

Anti-proliferative Activity of Labdane Diterpenes Isolated from Polyalthia cerasoides and their Molecular Interaction Studies.

BACKGROUND: Polyalthia cerasoides is well known for its therapeutic effects and is extensively used by the tribal people of South India and Africa to treat infertility, toothache, inflammation, rheumatism, fever, and to combat stress. OBJECTIVE: In the present research, the anti-proliferative potential of two bioactive compounds isolated from the stem bark of P. cerasoides (Roxb.) Bedd. of the Annonaceae family was investigated. METHODS: The dried stem bark was powdered and subjected to extraction using methanol and further partitioned using petroleum ether. Yellow viscous oil was isolated from the petroleum ether fraction using column and preparative thin-layer chromatography. The chromatographic fractions were characterized using GC-MS. The anti-proliferative effect of the isolated compounds was assessed against HepG2 Cells using MTT- Cytotoxicity test. Furthermore, comparative in-silico docking studies were performed to predict the binding pattern of isolated molecules individually, as well as simultaneously with α, ß-tubulin, a critical protein involved in the molecular mechanism of microtubule formation. RESULTS: GC-MS analysis of yellow viscous oil from petroleum fraction confirmed the presence of two labdane diterpenes that were identified as 12E-3,4-Seco-labda-4(18),8(17),12,14-tetraen-3-oic acid, and methyl harvadate C by mass fragmentation analysis. The MTT-cytotoxicity assay showed the dose-dependent cytotoxic effect on HepG2 Cells. The comparative docking studies of the isolated compounds exhibited strong interactions with the α, ß-tubulin protein. CONCLUSION: The prominent anti-proliferative effect exhibited by the isolated compounds, along with effective binding to α, ß-tubulin protein, encourages their future utilization as prominent anti-cancer molecules.

Maternal and fetal outcomes of COVID-19 infection in pregnant women with chronic rheumatic heart disease in a South Asian population: A case series.

Rheumatic heart disease (RHD) is associated with an increased risk of adverse maternal, fetal, and neonatal outcomes, particularly in developing countries. The current COVID-19 pandemic has also affected pregnant women, probably increasing the adverse effects. It is speculated that COVID-19 infection in pregnant women would further increase the risk of complications. However, factual data is still lacking, especially from resource-constrained countries. We conducted a case series of 20 pregnant women with RHD and COVID-19 infection and compared their outcomes with 40 with RHD but without COVDI-19. We observed a high risk of adverse cardiac and pregnancy effects across the whole cohort of 60 patients. However, the comparative study between the two groups failed to show any incremental risk of complications due to COVID-19 infection. Although the sample size was limited; the results are encouraging, particularly for developing countries.

Carotid intima-media thickness predicted the presence but not the severity or complexity of coronary artery disease in a South Asian population.

BACKGROUND: Carotid intima-media thickness (CIMT) is considered a marker of atherosclerosis, but the data is lacking from the South Asian population. We aimed to study the relation of CIMT with the presence and severity of coronary artery disease (CAD) in this population. METHODS: This was a prospective, single-center study of consecutive patients undergoing elective coronary angiography. Participants with >50% luminal stenosis in any major coronary artery were included in the CAD group and those with normal coronaries in the non-CAD group. Multivariate linear regression analysis was done to determine independent predictors of CAD. Pearson's correlation coefficients assessed correlations between CIMT and Syntax and Gensini score. RESULTS: The mean CIMT was significantly much higher in the CAD group when compared to the non-CAD group (0.83±0.16 vs 0.61±0.14mm, p<0.001). On multivariable linear regression analysis only diabetes (ß=0.208 and p=0.024), waist-hip ratio (ß=0.178 and p=0.043), current smoker (ß=0.293 and p=<0.001) and CIMT (ß=0.217 and p=0.031) were independent predictors of CAD. The mean Gensini score in the CAD group was 48.59±34.25 and the mean Syntax score was 19.45±10.24. No significant relation was found between CIMT and Gensini score (r=0.009 and p=0.89), and Syntax score (r=-0.087 and p=0.171). CONCLUSION: Mean CIMT is an independent predictor of CAD along with diabetes, waist-hip ratio, and smoking. However, CIMT was not related to the severity and complexity of the CAD as assessed by the Gensini score and Syntax score, respectively.

COVID-19: Immunology, Immunopathogenesis and Potential Therapies.

The Coronavirus Disease-2019 (COVID-19) imposed public health emergency and affected millions of people around the globe. As of January 2021, 100 million confirmed cases of COVID-19 along with more than 2 million deaths were reported worldwide. SARS-CoV-2 infection causes excessive production of pro-inflammatory cytokines thereby leading to the development of "Cytokine Storm Syndrome." This condition results in uncontrollable inflammation that further imposes multiple-organ-failure eventually leading to death. SARS-CoV-2 induces unrestrained innate immune response and impairs adaptive immune responses thereby causing tissue damage. Thus, understanding the foremost features and evolution of innate and adaptive immunity to SARS-CoV-2 is crucial in anticipating COVID-19 outcomes and in developing effective strategies to control the viral spread. In the present review, we exhaustively discuss the sequential key immunological events that occur during SARS-CoV-2 infection and are involved in the immunopathogenesis of COVID-19. In addition to this, we also highlight various therapeutic options already in use such as immunosuppressive drugs, plasma therapy and intravenous immunoglobulins along with various novel potent therapeutic options that should be considered in managing COVID-19 infection such as traditional medicines and probiotics.

Regulatory roles of tRNA-derived RNA fragments in human pathophysiology.

Hundreds of tRNA genes and pseudogenes are encoded by the human genome. tRNAs are the second most abundant type of RNA in the cell. Advancement in deep-sequencing technologies have revealed the presence of abundant expression of functional tRNA-derived RNA fragments (tRFs). They are either generated from precursor (pre-)tRNA or mature tRNA. They have been found to play crucial regulatory roles during different pathological conditions. Herein, we briefly summarize the discovery and recent advances in deciphering the regulatory role played by tRFs in the pathophysiology of different human diseases.

Role of non-coding RNAs in Dengue virus-host interaction.

Dengue is potentially a life-threatening arthropod-borne viral infection for which there are no known therapeutic agents till date. Early stage diagnosis of dengue infection is still lacking. Diagnosis is only made after severe manifestations and later stages of infection. Timely prognosis can prevent dengue related mortalities. The nucleic acid-based therapy has potential to emerge as a promising approach for early diagnosis and treatment of this viral infection. Many studies have been carried out suggested the regulatory role of ncRNAs thereby revealing the importance of protein-RNA and RNA-RNA interactions during infection. Various regulatory RNAs are either expressed by mammalian cells or generated by viral RNA have reported to play important roles in viral life cycle including dengue virus. Thus exploring host-virus interaction will pave the novel path for understanding the pathophysiology of febrile infection in dengue. Rapid advances in sequencing techniques along with significant developments in the field of RNA studies has made RNA therapeutics as one of the promising approaches as antiviral targets. The idea of RNA based therapies has been greatly backed by a Hepatitis C virus drug, Miravirsen which has successfully completed phase II clinical trial. In the present review, we will discuss the implications of different non-coding RNAs in dengue infection. Differential expression of small ncRNA may serve as a reliable biomarker of disease severity during different stages of infection and can also play regulatory roles in disease progression.