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.

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.

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.

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.

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.

Phytotherapy for treatment of cytokine storm in COVID-19.

In 2020, a novel strain of coronavirus (COVID-19) has led to a significant morbidity and mortality worldwide. As of the date of this writing, a total of 116 M cases has been diagnosed worldwide leading to 2.5 M deaths. The number of mortalities is directly correlated with the rise of innate immune cells (especially macrophages) in the lungs that secrete inflammatory cytokines (IL-1ß and IL-6) leading to the development of "Cytokine Storm Syndrome" (CSS), multi-organ-failure and death. Given that currently the treatment of this condition is rare and release of effective vaccine might be months away, here, we review the plants and their pharmacologically active-compounds as potential phytopharmaceuticals for the virus induced inflammatory response. Experimental validation of the effectiveness of these natural compounds to prevent or reduce the cytokine storm might be beneficial as an adjunct treatment of SARS-CoV-2.

Histological spectrum of renal disease in HIV/AIDS patients with significant proteinuria: An Indian perspective.

BACKGROUND: Chronic kidney disease (CKD) has become epidemic in HIV/AIDS patients across Western and Eastern countries. HIV-associated nephropathy (HIVAN) has been consistently reported in studies from North America, Europe and African countries. However, studies from Asian countries are very sparse and differ strikingly in histological spectrum of renal disease, particularly in presence of HIVAN. OBJECTIVES: The study was carried out to in a teaching hospital from India to delineate the histological spectrum of renal disease and detect presence HIVAN in those with significant proteinuria (≥1gm/day). PATIENTS AND METHODS: Urine analysis was done in 510 consecutive hospitalised HIV/AIDS patients after screening 640 such patients with age >18years. Patients with dipstick proteinuria ≥1+ were subjected to 24-hour urinary protein estimation. Renal biopsy was done in 10 patients with proteinuria ≥1gm/day. RESULTS: Dipstick proteinuria ≥1+ was present in 29% patients. In patients undergoing kidney biopsy, the most frequent glomerular lesion was mesangial proliferative glomerulonephritis (30%) followed by HIVAN (20%). Tubulo-interstitial lesions were seen in 60% of biopsies. Pooled analysis of all the available kidney biopsy series from India revealed prevalence of HIVAN to be 16.5%. CONCLUSION: Contrary to the popular belief, HIVAN appears to be a common entity in this part of world too. High degree of clinical suspicion is required as diagnosis of HIVAN caries higher morbidity and mortality. Moreover, an early diagnosis and timely management can improve prognosis in such patients.

Polypyrimidine tract-binding protein interacts with coxsackievirus B3 RNA and influences its translation.

We have investigated the possible role of trans-acting factors interacting with the untranslated regions (UTRs) of coxsackievirus B3 (CVB3) RNA. We show here that polypyrimidine tract-binding protein (PTB) binds specifically to both 5' and 3' UTRs, but with different affinity. We have demonstrated that PTB is a bona fide internal ribosome entry site (IRES) trans-acting factor (ITAF) for CVB3 RNA by characterizing the effect of partial silencing of PTB ex vivo in HeLa cells. Furthermore, IRES activity in BSC-1 cells, which are reported to have a very low level of endogenous PTB, was found to be significantly lower than that in HeLa cells. Additionally, we have mapped the putative contact points of PTB on the 5' and 3' UTRs by an RNA toe-printing assay. We have shown that the 3' UTR is able to stimulate CVB3 IRES-mediated translation. Interestingly, a deletion of 15 nt at the 5' end or 14 nt at the 3' end of the CVB3 3' UTR reduced the 3' UTR-mediated enhancement of IRES activity ex vivo significantly, and a reduced interaction was shown with PTB. It appears that the PTB protein might help in circularization of the CVB3 RNA by bridging the ends necessary for efficient translation of the viral RNA.