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Environmental mutagens are chemical and physical substances in the environment that has a potential to induce a wide range of mutations and generate multiple physiological, biochemical, and genetic modifications in humans. Most mutagens are having genotoxic effects on the following generation through germ cells. The influence of germinal mutations on health will be determined by their frequency, nature, and the mechanisms that keep a specific mutation in the population. Early prenatal lethal mutations have less public health consequences than genetic illnesses linked with long-term medical and social difficulties. Physical and chemical mutagens are common mutagens found in the environment. These two environmental mutagens have been associated with multiple neurological disorders and carcinogenesis in humans. Thus in this study, we aim to unravel the molecular mechanism of physical mutagens (UV rays, X-rays, gamma rays), chemical mutagens (dimethyl sulfate (DMS), bisphenol A (BPA), polycyclic aromatic hydrocarbons (PAHs), 5-chlorocytosine (5ClC)), and several heavy metals (Ar, Pb, Al, Hg, Cd, Cr) implicated in DNA damage, carcinogenesis, chromosomal abnormalities, and oxidative stress which leads to multiple disorders and impacting human health. Biological tests for mutagen detection are crucial; therefore, we also discuss several approaches (Ames test and Mutatox test) to estimate mutagenic factors in the environment. The potential risks of environmental mutagens impacting humans require a deeper basic knowledge of human genetics as well as ongoing research on humans, animals, and their tissues and fluids.

Respiratory diseases, both acute and chronic, are reported to be the leading cause of morbidity and mortality, affecting millions of people globally, leading to high socio-economic burden for the society in the recent decades. Chronic inflammation and decline in lung function are the common symptoms of respiratory diseases. The current treatment strategies revolve around using appropriate anti-inflammatory agents and bronchodilators. A range of anti-inflammatory agents and bronchodilators are currently available in the market; however, the usage of such medications is limited due to the potential for various adverse effects. To cope with this issue, researchers have been exploring various novel, alternative therapeutic strategies that are safe and effective to treat respiratory diseases. Several studies have been reported on the possible links between food and food-derived products in combating various chronic inflammatory diseases. Nutraceuticals are examples of such food-derived products which are gaining much interest in terms of its usage for the well-being and better human health. As a consequence, intensive research is currently aimed at identifying novel nutraceuticals, and there is an emerging notion that nutraceuticals can have a positive impact in various respiratory diseases. In this review, we discuss the efficacy of nutraceuticals in altering the various cellular and molecular mechanisms involved in mitigating the symptoms of respiratory diseases.

Nanoemulsions (NMs) are one of the most important colloidal dispersion systems that are primarily used to improve the solubility of poorly water soluble drugs. The main objectives of this study wer...

Introduction:: The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an increased mortality rate across the globe. However, the underlying mechanism of SARS-CoV-2 altering human immune response is still elusive. The existing literature on miRNA mediated pathogenesis of RNA virus viz. Dengue virus, West Nile virus, etc. raises a suspicion that miRNA encoded by SARS-CoV-2 might facilitate virus replication and regulate the host’s gene expression at the post-transcriptional level. Methods:: We investigated this possibility via computational prediction of putative miRNAs encoded by the SARS-CoV-2 genome using a novel systematic pipeline that predicts putative mature-miRNA and their targeted genes transcripts. To trace down if viral-miRNAs targeted the genes critical to the immune pathway, we assessed whether mature miRNA transcripts exhibit effective hybridization with the 3’UTR region of human gene transcripts. Conversely, we also tried to study human miRNA-mediated viral gene regulation to get insight into the miRNA mediated offense and defense mechanism of viruses and their host organisms in toto. Results:: Our analysis led us to shortlist six putative miRNAs that target, majorly, genes related to cell proliferation/differentiation/signaling, and senescence. Nonetheless, they also target immune-related genes that directly/indirectly orchestrate immune pathways like TNF (Tumor Necrosis Factor) signaling and Chemokine signaling pathways putatively serving as the nucleus to cytokine storms. Conclusion:: Besides, these six miRNAs were found to conserved so far across 80 complete genomes of SARS-CoV-2 (NCBI Virus, last assessed 12 April 2020) including Indian strains that are also targeted by 7 human miRNAs and can, therefore, be exploited to develop MicroRNA-Attenuated Vaccines.

An outbreak of “Pneumonia of Unknown Etiology” occurred in Wuhan, China, in late December 2019. Later, the agent factor was identified and coined as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the disease was named coronavirus disease 2019 (COVID-19). In a shorter period, this newly emergent infection brought the world to a standstill. On 11 March 2020, the WHO declared COVID-19 as a pandemic. Researchers across the globe have joined their hands to investigate SARS-CoV-2 in terms of pathogenicity, transmissibility, and deduce therapeutics to subjugate this infection. The researchers and scholars practicing different arts of medicine are on an extensive quest to come up with safer ways to curb the pathological implications of this viral infection. A huge number of clinical trials are underway from the branch of allopathy and naturopathy. Besides, a paradigm shift on cellular therapy and nano-medicine protocols has to be optimized for better clinical and functional outcomes of COVID-19-affected individuals. This article unveils a comprehensive review of the pathogenesis mode of spread, and various treatment modalities to combat COVID-19 disease.

The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities.

Alzheimer’s disease (AD) is a global health concern owing to its complexity, which often poses a great challenge to the development of therapeutic approaches. No single theory has yet accounted for the various risk factors leading to the pathological and clinical manifestations of dementia-type AD. Therefore, treatment options targeting various molecules involved in the pathogenesis of the disease have been unsuccessful. However, the exploration of various immunotherapeutic avenues revitalizes hope after decades of disappointment. The hallmark of a good immunotherapeutic candidate is not only to remove amyloid plaques but also to slow cognitive decline. In line with this, both active and passive immunotherapy have shown success and limitations. Recent approval of aducanumab for the treatment of AD demonstrates how close passive immunotherapy is to being successful. However, several major bottlenecks still need to be resolved. This review outlines recent successes and challenges in the pursuit of an AD vaccine.

The novel coronavirus (nCoV) has emerged as a severe public health threat globally in the 21st century. Several therapies were reported towards identifying ligand against coronavirus, including targeting specific functional proteins or enzymes that are crucial to viruses, thereby preventing the synthesis and replication of virus RNA. Our study is mainly focused on targeting the virus's structural proteins, which could further block the binding of the virus to human cell receptors. In our study, we have selected nine Flavonoids for the inhibition of COVID-19 Spike protein, which have already been reported with their antiviral efficacies against other virus-infected diseases. AutoDock and PatchDock were used to study the inhibitory potential of flavonoids against COVID-19. Amongst all the eleven screened compounds, baicalin has depicted the highest binding affinity against 2019-nCoV spike glycoprotein. Additionally, we have also compared its potential with two standard HIV drugs Abacavir and hydroxychloroquine, and the docking results clearly revealed the better inhibitory potential of baicalin in comparison to recently used drug Abacavir and hydroxychloroquine for the treatment of COVID-19. Therefore our experimental findings strongly suggested that baicalin can be used as a potential inhibitor against COVID-19 spike protein, which could inhibit the interaction of the virus with the host cell and thus could provide a potential lead molecule for the development of a drug against COVID-19 disease.

Background: Nowadays, the potential therapeutic role of various bioflavonoids including Curcumin, Luteolin and Resveratrol has currently been well-documented in a vast range of fatal complications including synaptic failure and cancers. These bioflavonoids are widely being implemented for the treatment of various cancers as they possess anti-cancerous, anti-oxidant and anti-inflammatory properties. Moreover, they are also used as a better alternative to conventional therapies since; these are non-toxic to cells and having no or least side effects. Notably, the pertinent therapeutic role of Rutin in cervical cancer is still unsettled however, its anti-cancerous role has already been reported in other cancers including prostate and colon cancer. Rutin (Vitamin P or Rutoside) is a polyphenolics flavonoid exhibiting multi-beneficial roles against several carcinomas. Objective: Despite the evidence for its several biological activities, the anticancer effects of Rutin on human cervical cancer (C33A) cells remain to be explored. In this study, the anticancer potential of Rutin was investigated by employing the key biomarkers such as nuclear condensation reactive oxygen species (ROS), apoptosis, and changes in mitochondrial membrane potential (MMP). Results: Our findings showed that Rutin treatment reduced the cell viability, induced significant increase in ROS production and nuclear condensation in dose-dependent manner. Moreover, Rutin provoked apoptosis by inducing decrease in MMP and activation of caspase-3. Cell cycle analysis further confirmed the efficacy of Rutin by showing cell cycle arrest at G0/G1 phase. Conclusion: Thus, our study is envisaged to open up interests for elucidating Rutin as an anticancerous agent against cervical cancer.

Neoechinulins are fungal and plant-derived chemicals extracted from Microsporum sp., Eurotium rubrum, Aspergillus sp., etc. Two analogues of neoechinulin, i.e., A and B, exerted extensive pharmacological properties described in this review. Neoechinulin is an indole alkaloid and has a double bond between C8/C9, which tends to contribute to its cytoprotective nature. Neoechinulin A exhibits protection to PC12 cells against nitrosative stress via increasing NAD(P)H reserve capacity and decreasing cellular GSH levels. It also confers protection via rescuing PC12 cells from rotenone-induced stress by lowering LDH leakage. This compound has great positive potential against neurodegenerative diseases by inhibiting SIN-1 induced cell death in neuronal cells. Together with these, neoechinulin A tends to inhibit Aβ42-induced microglial activation and confers protection against neuroinflammation. Alongside, it also inhibits cervical cancer cells by caspase-dependent apoptosis and via upregulation of apoptosis inducing genes like Bax, it suppresses LPS-induced inflammation in RAW264.7 macrophages and acts as an antidepressant. Whereas, another analogue, Neoechinulin B tends to interfere with the cellular mechanism thereby, inhibiting the entry of influenza A virus and it targets Liver X receptor (LXR) and decreases the infection rate of Hepatitis C. The present review describes the pharmaceutical properties of neoechinulins with notes on their molecular, cellular, and functional basis and their therapeutic properties.

Lung cancer (LC) is one of the leading causes of mortality accounting for almost 25% of cancer deaths throughout the world. The shortfall of affordable and effective first-line chemotherapeutics, the existence of resistant tumors, and the non-optimal route of administration contribute to poor prognosis and high mortality in LC. Administration of repurposed non-oncology drugs (RNODs) loaded in nanocarriers (NCs) via inhalation may prove as an effective alternative strategy to treat LC. Furthermore, their site-specific release through inhalation route using an appropriate inhalation device would offer improved therapeutic efficacy, thereby reducing mortality and improving patients' quality of life. The current manuscript offers a comprehensive overview on use of RNODs in LC treatment with an emphasis on their inhalation delivery and the associated challenges. The role of NCs to improve lung deposition and targeting of RNODs via inhalation are also elaborated. In addition, information about various RNODs in clinical trials for the treatment of LC, possibility for repurposing phytoceuticals against LC via inhalation and the bottlenecks associated with repurposing RNODs against cancer are also highlighted. Based on the reported studies covered in this manuscript, it was understood that delivery of RNODs via inhalation has emerged as a propitious approach. Hence, it is anticipated to provide effective first-line treatment at an affordable cost in debilitating LC from low and middle-income countries (LMIC).

Publisher Copyright: © 2021 Frontiers in Bioscience. All rights reserved. Alzheimer's, a progressive neurodegenerative disease affects brain and neurons through enormous reduction in nerve cell regenerative capacity. Dementia and impairment of cognitive functions are more prevalent in Alzheimer's disease (AD) patients in both industrialized and non-industrialized countries. Various factors play significant role in molecular cascades that leads to neuronal inflammation, dementia and thereby AD progression. Current medications are symptomatic that alleviates pain while lack in absolute cure, urging researchers to explore targets and therapeutics. Interestingly, nanomedicines developed due to the onset of nanotechnology, are being extensively investigated for the treatment of AD. This review presents the advancement in nanotherapeutic strategies, involving the emergence of nanomaterials that offers advantage to pass through the blood-brain barrier and acts as a therapeutic modality against AD.

Persistent respiratory tract inflammation contributes to the pathogenesis of various chronic respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. These inflammatory respiratory diseases have been a major public health concern as they are the leading causes of worldwide mortality and morbidity, resulting in heavy burden on socioeconomic growth throughout these years. Although various therapeutic agents are currently available, the clinical applications of these agents are found to be futile due to their adverse effects, and most patients remained poorly controlled with a low quality of life. These drawbacks have necessitated the development of novel, alternative therapeutic agents that can effectively improve therapeutic outcomes. Recently, nutraceuticals such as probiotics, vitamins, and phytochemicals have gained increasing attention due to their nutritional properties and therapeutic potential in modulating the pathological mechanisms underlying inflammatory respiratory diseases, which could ultimately result in improved disease control and overall health outcomes. As such, nutraceuticals have been held in high regard as the possible alternatives to address the limitations of conventional therapeutics, where intensive research are being performed to identify novel nutraceuticals that can positively impact various inflammatory respiratory diseases. This review provides an insight into the utilization of nutraceuticals with respect to their molecular mechanisms targeting multiple signaling pathways involved in the pathogenesis of inflammatory respiratory diseases.

Outbreak of infectious diseases imposes a serious threat to human population and also causes a catastrophic impact on global economy. Animal coronaviruses remain as one of the intriguing problems, known to cause deadly viral diseases on economically important animal population, and also these infections may spread to other animals and humans. Through isolation of the infected animals from others and providing appropriate treatment using antiviral drugs, it is possible to prevent the virus transmission from animals to other species. In recent times, antiviral drug-resistant strains are being emerged as a deadly virus which are known to cause pandemic. To overcome this, nanoparticles-based formulations are developed as antiviral agent which attacks the animal coronaviruses at multiple sites in the virus replication cycle. Nanovaccines are also being formulated to protect the animals from coronaviruses. Nanoformulations contain particles of one or more dimensions in nano-scale (few nanometers to 1000 nm), which could be inorganic or organic in nature. This review presents the comprehensive outline of the nanotechnology-based therapeutics formulated against animal coronaviruses, which includes the nanoparticles-based antiviral formulations and nanoparticles-based adjuvant vaccines. The mechanism of action of these nanoparticles-based antivirals against animal coronavirus is also discussed using relevant examples. In addition, the scope of repurposing the existing nano-enabled antivirals and vaccines to combat the coronavirus infections in animals is elaborated.

The COVID-19 pandemic has become a serious concern and has negatively impacted public health and the economy. It primarily targets the lungs, causing acute respiratory distress syndrome (ARDS); however, it may also lead to multiple organ failure (MOF) and enhanced mortality rates. Hence, there is an urgent need to develop potential effective therapeutic strategies for COVID-19 patients. Extracellular vesicles (EVs) are released from various types of cells that participate in intercellular communication to maintain physiological and pathological processes. EVs derived from various cellular origins have revealed suppressive effects on the cytokine storm during systemic hyper-inflammatory states of severe COVID-19, leading to enhanced alveolar fluid clearance, promoted epithelial and endothelial recovery, and cell proliferation. Being the smallest subclass of EVs, exosomes offer striking characteristics such as cell targeting, being nano-carriers for drug delivery, high biocompatibility, safety, and low-immunogenicity, thus rendering them a potential cell-free therapeutic candidate against the pathogeneses of various diseases. Due to these properties, numerous studies and clinical trials have been performed to assess their safety and therapeutic efficacy against COVID-19. Hence, in this review, we have comprehensively described current updates on progress and challenges for EVs as a potential therapeutic agent for the management of COVID-19.

Funding Information: The authors sincerely acknowledge the research fund support from ADEK award for Research Excellence (AARE18-194). The authors also acknowledge the research grant (21R075) from Zayed Bin Sultan Al Nahyan Center for Health Sciences (ZCHS), UAE University, UAE. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Myocardium Infarction (MI) is one of the foremost cardiovascular diseases (CVDs) causing death worldwide, and its case numbers are expected to continuously increase in the coming years. Pharmacological interventions have not been at the forefront in ameliorating MI-related morbidity and mortality. Stem cell-based tissue engineering approaches have been extensively explored for their regenerative potential in the infarcted myocardium. Recent studies on microfluidic devices employing stem cells under laboratory set-up have revealed meticulous events pertaining to the pathophysiology of MI occurring at the infarcted site. This discovery also underpins the appropriate conditions in the niche for differentiating stem cells into mature cardiomyocyte-like cells and leads to engineering of the scaffold via mimicking of native cardiac physiological conditions. However, the mode of stem cell-loaded engineered scaffolds delivered to the site of infarction is still a challenging mission, and yet to be translated to the clinical setting. In this review, we have elucidated the various strategies developed using a hydrogel-based system both as encapsulated stem cells and as biocompatible patches loaded with cells and applied at the site of infarction.

Cancer is probably the deadliest human disease in recent years. In the past few years, rapid clinical progress has been made in the field of anticancer drug development. Plant secondary metabolites have been noted as extremely efficacious as promising natural source for anticancer therapy for many years. Camptothecin (CPT) is one of the popularly used anti-tumor drugs possessing clinically proven properties against a plethora of human malignancies that include ovarian and colorectal cancers. For the first time, CPT was obtained from the extracts of a Chinese medicinal tree, Camptotheca acuminata Decne. from the family Cornaceae. Subsequently, CPT was also isolated from the bark of Nothapodytes foetida (Wight) Sleumer (Icacinaceae). However, the availability of enough natural sources for obtaining CPT is a major constraint. Due to overexploitation and harvesting, loss of habitat, excessive trading, and unfavorable environmental factors, the natural source of CPT has become extinct or extremely limited and hence they are red listed under endangered species. Conventional propagation has also failed to meet the ever-expanding demand for CPT production. With this, biotechnological toolkits have constantly been used as a boon to produce sustainable source, utilization, and ex situ conservation of medicinal plants. The approaches serve as a supplement to traditional agriculture in the mass production of plant metabolites with potent bioactivities. Non-availability of enough anticancer medicine and the requirement to satisfy current demands need a sustainable source of CPT. With this background, we present a comprehensive review on CPT discovery, its occurrence in the plant kingdom, biosynthesis, phytochemistry, pharmacological properties, clinical studies, patterns of CPT accumulation, and biotechnological aspects of CPT production in three plants, viz., N. nimmoniana, Ophiorrhiza species, and C. acuminata.Key points• Biotechnological approaches on production of camptothecin from Nothapodytes nimmoniana, Ophiorrhiza species, and Camptotheca acuminata• In vitro propagation of camptothecin-producing plants• Genetic diversity and transgenic research on camptothecin-producing plants.

Gestational diabetes mellitus (GDM) is the most frequent complication during pregnancy. This complex disease is characterized by glucose intolerance and consequent hyperglycemia that begins or is first diagnosed in pregnancy, and affects almost 7% of pregnant women. Previous reports have shown that GDM is associated with increased pregnancy complications and might cause abnormal fetal development. At present, treatments are not suitable for the prevention and management of these patients. As an alternative therapeutic opportunity and a leading scientific technique, nanotechnology has helped enlighten the health of these affected women. Theranostic nanomaterials with unique properties and small sizes (at least

Liquid self-nanoemulsifying drug delivery system (L-SNEDDS) of curcumin and quercetin were prepared by dissolving them in isotropic mixture of Labrafil M1944CS®, Capmul MCM®, Tween-80® and Transcutol P®. The prepared L-SNEDDS were solidified using Ganoderma lucidum extract, probiotics and Aerosil-200® using spray drying. These were further converted into pellets using extrusion-spheronization. The mean droplet size and zeta potential of L-SNEDDS were found to be 63.46 ± 2.12 nm and - 14.8 ± 3.11 mV while for solid SNEDDS pellets, these were 72.46 ± 2.16 nm and -38.7 ± 1.34 mV, respectively. The dissolution rate for curcumin and quercetin each was enhanced by 4.5 folds while permeability was enhanced by 5.28 folds (curcumin) and 3.35 folds (quercetin) when loaded into SNEDDS pellets. The Cmax for curcumin and quercetin containing SNEDDS pellets was found 532.34 ± 5.64 ng/mL and 4280 ± 65.67 ng/mL, respectively. This was 17.55 and 3.48 folds higher as compared to their naive forms. About 50.23- and 5.57-folds increase in bioavailability was observed for curcumin and quercetin respectively, upon loading into SNEDDS pellets. SNEDDS pellets were found stable at accelerated storage conditions. The developed formulation were able to normalize the levels of blood glucose, lipids, antioxidant biomarkers, and tissue architecture of pancreas and liver in streptozotocin induced diabetic rats as compared to their naive forms.

The exploration of multiplexed bacterial virulence factors is a major problem in the early stages of Escherichia coli infection therapy. Traditional methods for detecting Escherichia coli (E. coli), such as serological experiments, immunoassays, polymerase chain reaction, and isothermal microcalorimetry have some drawbacks. As a result, detecting E. coli in a timely, cost-effective, and sensitive manner is critical for various areas of human safety and health. Intelligent devices based on nanotechnology are paving the way for fast and early detection of E. coli at the point of care. Due to their specific optical, magnetic, and electrical capabilities, nanostructures can play an important role in bacterial sensors. Another one of the applications involved use of nanomaterials in fighting microbial infections, including E. coli mediated infections. Various types of nanomaterials, either used directly as an antibacterial agent such as metallic nanoparticles (NPs) (silver, gold, zinc, etc.), or as a nanocarrier to deliver and target the antibiotic to the E. coli and its infected area. Among different types, polymeric NPs, lipidic nanocarriers, metallic nanocarriers, nanomicelles, nanoemulsion/ nanosuspension, dendrimers, graphene, etc. proved to be effective vehicles to deliver the drug in a controlled fashion at the targeted site with lower off-site drug leakage and side effects.

The increasing burden of respiratory diseases caused by microbial infections poses an immense threat to global health. This review focuses on the various types of biofilms that affect the respiratory system and cause pulmonary infections, specifically bacterial biofilms. The article also sheds light on the current strategies employed for the treatment of such pulmonary infection-causing biofilms. The potential of nanocarriers as an effective treatment modality for pulmonary infections is discussed, along with the challenges faced during treatment and the measures that may be implemented to overcome these. Understanding the primary approaches of treatment against biofilm infection and applications of drug-delivery systems that employ nanoparticle-based approaches in the disruption of biofilms are of utmost interest which may guide scientists to explore the vistas of biofilm research while determining suitable treatment modalities for pulmonary respiratory infections.

The endocannabinoid system has attracted attention as a pharmacological target for several pathological conditions. Cannabinoid (CB2)-selective agonists have been the focus of pharmacological studies because modulation of the CB2 receptor (CB2R) can be useful in the treatment of pain, inflammation, arthritis, addiction, and cancer among other possible therapeutic applications while circumventing CNS-related adverse effects. Increasing number of evidences from different independent preclinical studies have suggested new perspectives on the involvement of CB2R signaling in inflammation, infection and immunity, thus play important role in cancer, cardiovascular, renal, hepatic and metabolic diseases. JWH133 is a synthetic agonist with high CB2R selectivity and showed to exert CB2R mediated antioxidant, anti-inflammatory, anticancer, cardioprotective, hepatoprotective, gastroprotective, nephroprotective, and immunomodulatory activities. Cumulative evidences suggest that JWH133 protects against hepatic injury, renal injury, cardiotoxicity, fibrosis, rheumatoid arthritis, and cancer as well as against oxidative damage and inflammation, inhibits fibrosis and apoptosis, and acts as an immunosuppressant. This review provides a comprehensive overview of the polypharmacological properties and therapeutic potential of JWH133. This review also presents molecular mechanism and signaling pathways of JWH133 under various pathological conditions except neurological diseases. Based on the available data, this review proposes the possibilities of developing JWH133 as a promising therapeutic agent; however, further safety and toxicity studies in preclinical studies and clinical trials in humans are warranted.

The contagiosity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has startled mankind and has brought our lives to a standstill. The treatment focused mainly on repurposed immunomodulatory and antiviral agents along with the availability of a few vaccines for prophylaxis to vanquish COVID-19. This seemingly mandates a deeper understanding of the disease pathogenesis. This necessitates a plausible extrapolation of cell-based therapy to COVID-19 and is regarded equivalently significant. Recently, correlative pieces of clinical evidence reported a robust decline in lymphocyte count in severe COVID-19 patients that suggest dysregulated immune responses as a key element contributing to the pathophysiological alterations. The large granular lymphocytes also known as natural killer (NK) cells play a heterogeneous role in biological functioning wherein their frontline action defends the body against a wide array of infections and tumors. They prominently play a critical role in viral clearance and executing immuno-modulatory activities. Accumulated clinical evidence demonstrate a decrease in the number of NK cells in circulation with or without phenotypical exhaustion. These plausibly contribute to the progression of pulmonary inflammation in COVID-19 pneumonia and result in acute lung injury. In this review, we have outlined the present understanding of the immunological response of NK cells in COVID-19 infection. We have also discussed the possible use of these powerful biological cells as a therapeutic agent in view of preventing immunological harms of SARS-CoV-2 and the current challenges in advocating NK cell therapy for the same., SARS-CoV-2; COVID-19; Natural killer cells; Cytokines; Pulmonary inflammation.

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Para-coumaric acid (p-CA) is a plant derived secondary metabolite belonging to the phenolic compounds. It is widely distributed in the plant kingdom and found mainly in pizza, vegetables, and cereals. Various in vivo and in vitro studies have revealed its scavenging and antioxidative properties in the reduction of oxidative stress and inflammatory reactions. This evidence-based review focuses on the protective role of p-CA including its therapeutic potential. p-CA and its conjugates possesses various bioactivities such as antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, and anti-melanogenic properties. Due to its potent free radical scavenging activity, it can mitigate the ill effects of various diseases including arthritis, neurological disorders, and cardio-vascular diseases. Recent studies have revealed that p-CA can ameliorate the harmful effects associated with oxidative stress in the reproductive system, also by inhibiting enzymes linked with erectile function.

Funding Information: Acknowledgments: Shreesh Ojha is thankful to the Research Office of the College of Medicine and Health Sciences, United Arab Emirates University, United Arab Emirates, for the support of APC. Funding Information: Funding: This research did not receive any specific grant from the funding agencies in the public, commercial, or not-for-profit sectors. The work in the laboratory of Shreesh Ojha is supported by the grants from United Arab Emirates University, United Arab Emirates. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Limonene is a monoterpene confined to the family of Rutaceae, showing several biological properties such as antioxidant, anti-inflammatory, anticancer, antinociceptive and gastroprotective characteristics. Recently, there is notable interest in investigating the pharmacological effects of limonene in various chronic diseases due to its mitigating effect on oxidative stress and inflammation and regulating apoptotic cell death. There are several available studies demonstrating the neuroprotective role of limonene in neurodegenerative diseases, including Alzheimer’s disease, multiple sclerosis, epilepsy, anxiety, and stroke. The high abundance of limonene in nature, its safety profile, and various mechanisms of action make this monoterpene a favorable molecule to be developed as a nutraceutical for preventive purposes and as an alternative agent or adjuvant to modern therapeutic drugs in curbing the onset and progression of neurodegenerative diseases. This manuscript presents a comprehensive review of the available scientific literature discussing the pharmacological activities of limonene or plant products containing limonene which attribute to the protective and therapeutic ability in neurodegenerative disorders. This review has been compiled based on the existing published articles confined to limonene or limonene-containing natural products investigated for their neurotherapeutic or neuroprotective potential. All the articles available in English or the abstract in English were extracted from different databases that offer an access to diverse journals. These databases are PubMed, Scopus, Google Scholar, and Science Direct. Collectively, this review emphasizes the neuroprotective potential of limonene against neurodegenerative and other neuroinflammatory diseases. The available data are indicative of the nutritional use of products containing limonene and the pharmacological actions and mechanisms of limonene and may direct future preclinical and clinical studies for the development of limonene as an alternativeor complementary phytomedicine. The pharmacophore can also provide a blueprint for further drug discovery using numerous drug discovery tools.

Natural dietary molecules such as flavonoids have been recognized for their immense potential in cancer therapeutics with several health benefits. Hes-1 and Notch-1 overexpression has been associated with the progression of cervical cancer. However, the apoptosis-inducing potential of one such potent flavanol against these two key components of the Notch signaling pathway in cervical cancer has not been elucidated to date. Therefore, in this study, we performed several in vitro assays to gain detailed insight about the apoptotic inducing effect of rutin as well as its modulatory effect on Notch-1 and Hes-1 in cervical cancer cells. The results indicated that rutin led to a dose-dependent antiproliferative effects on Caski cervical cancer cells. DAPI and Mitotracker red staining revealed that rutin induced significant apoptotic effects via caspase-3/9 activation, ROS generation, and alteration in Bax/Bcl2 mRNA expression. Cell cycle analysis resulted in the arrest of cell cycle progression in G0/G1 that was associated with a reduced expression of CDK4 and Cyclin D1. The gene expression analysis further revealed that rutin treatment decreases Notch-1 and Hes-1 mRNA expression. Altogether, these results showed that rutin showed potent anticancer effects in human cervical cancer Caski cells by triggering apoptosis, G0/G1 phase arrest, and downregulating the level of Notch-1 and Hes-1 of the Notch signaling pathway.

The COVID-19 pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a public health emergency with high mortality and disability rates. Given its high mortality rate, there is a serious need for possible effective medications to eliminate the virus, limit the severity, and improve the prognosis (Altay et al., 2020). The management of COVID-19 has continued to rely on drugs repurposed based on their pharmacological effects, including antiviral, antibiotic, anti-inflammatory, and or immunomodulatory, along with availability of numerous vaccines against SARS-CoV-2 in past few months (Fan et al., 2020). Repurposing of drugs has gained enormous attention over identifying novel drug candidates, due to known safety, potency, and multi-targeted pharmacological action as an immunomodulatory, anti-inflammatory, and antimicrobial agent. Studies report that after fever, cough is one of the major symptoms in about 76% patients and sputum production in 28% patients along with 55 and 44% of patients showing dyspnea and myalgia, respectively (Huang et al., 2020). In a study determined the prevalence of asymptomatic cases of COVID-19 and characterized the symptoms of patients with mild COVID-19 report that of the 213 individuals with COVID-19, 19.2% were asymptomatic until admission (Kim et al., 2020). Among the remaining patients with mild COVID-19, cough (40.1%) was the most common symptom followed by hyposmia (39.5%) and sputum (39.5%). In individuals with hyposmia, 90% had accompanying symptoms such as hypogeusia, nasal congestion or rhinorrhoea (Kim et al., 2020). Sputum or productive cough seem a significant symptom in asymptomatic as well as symptomatic (Kim et al., 2020). Cough was observed most common symptom followed by hyposmia and sputum, while fever (>37.5°C) was only observed in 11.6% (Kim et al., 2020). Another study reported that nasal congestion (62%) was the most common symptom in individuals with mild COVID-19 (Chang et al., 2020). The role of mucolytic and bronchodilator administration and tracheal suctioning have been observed beneficial in airway hygiene by reducing the mortality rate of COVID-19 (Farooqi et al., 2020). Therefore, the role of mucolytics, in particular, has been suggested to protect the body from respiratory pathogens ascribed to their expectorant action, and are considered important as an adjuvant in the management of COVID-19 (Esam, 2020). In the purview of the pharmacological basis of therapeutics, we hypothesize that a proteolytic drug of natural origin, serratiopeptidase (SEPD), also known as Serratia E-15 protease or serralysin, serratiaprotease and serrapeptase (Bhagat et al., 2013). SEPD (EC number 3.4.24.40), a serine protease super is derived from the non-pathogenic enterobacteria, which exists in the intestine of the silkworm and facilitates disruption of the cocoon to free the silk moth (Maeda and Morihara, 1995). The forms used in pharmaceutical preparations are isolated from Serratia marcescens or Serratia sp. E 15 based on fermentation or the recombinant production using Escherichia coli (Srivastava et al., 2019). Enzyme drugs are reputed in therapeutics due to their strong target binding and specificity and catalytic behavior to change many target molecules into the desired effectors (Reshma, 2019). Proteolytic enzymes can be useful in the treatment of nosocomial, viral, and resistant infections, especially in pediatric and geriatric age groups due to its relative safety, less tolerance and resistance and its synergic effects (UmaMaheswari et al., 2016). Several proteolytic enzymes act in an orchestrated manner to control and coordinate the entry of virus, replication and diffusion in the host cells. Thus, the proteolytic enzymes could be important in interfering with virus machinery in the host cells and suggested useful in COVID-19 (Gioia et al., 2020). Recently, SEPD has been suggested to be considered in integrative management of COVID-19 (Holloway et al., 2020). One of the case report suggested the role of immunostimulants and proteolytic including SEPD in the treatment of COVID-19 (Kobakova et al., 2020). Our proposition is to repurpose a drug that possesses not only mucolytic property but also potent anti-inflammatory, and antimicrobial properties with a long history of safe clinical use. Herein, we present the possibilities of repurposing SEPD, a mucolytic that could be advantageous over others in COVID-19 treatment due to its wide range of therapeutic effects, including anti-inflammatory, antimicrobial, atheroprotective, antithrombotic, and fibrinolytic properties. Based on these properties, we opined that these properties may provide better therapeutic benefits in limiting the severity and progression of the disease, by reducing the risks of respiratory complications and related death. Serratiopeptidase as A Mucolytic Drug Can Be Useful in COVID-19 In individuals with COVID-19, sputum production, nasal congestion and cough are reported one of the common symptoms after fever (Chang et al., 2020; Huang et al., 2020; Kim et al., 2020). As cough is a major symptom of SARS-CoV-2 infection, the caseinolytic and mucolytic actions of SEPD on the sputum believed to be beneficial. Recently, one of the mucolytic drugs, bromhexine, has been suggested to be repurposed for the possible treatment of COVID-19 (Maggio and Corsini, 2020). Mucolytics either enhance bronchial mucus secretion or reduce mucus viscosity and further facilitate its removal by coughing. The mucus secreted by the goblet cells is an adhesive viscoelastic gel containing high molecular weight mucous glycoproteins and water. The airway mucus is well-known as the first line of airway defense against pathogens, including coronaviruses. The hypersecretion of the airways mucus in a defensive response to the pathogens are believed to cause airway obstruction that leads to respiratory distress (Lu et al., 2021). The mucus in airways traps and keep the microorganisms by a coordinated process of mucociliary clearance which involves release of mucus from the secretory cells controlling the transportation and viscoelasticity by motile cilia on multiciliated cells (Janssen et al., 2016). Mucus accumulation and increase in sputum viscoelasticity reduce mucociliary and cough clearance, thus retaining the sputum and obstructing the airways that enhance inflammation, infection, and progressive lung diseases by neutrophil infiltration (Maggio and Corsini, 2020). SEPD is shown to enhance mucociliary transportability (Maheshwari et al., 2006) and mucociliary clearance by decreasing neutrophils and modulating sputum viscoelasticity in patients with airway diseases (Nakamura et al., 2003). In addition to the mucolytic property, SEPD through oral administration in allergic conditions decreases the viscosity of the nasal mucus by improving rheological properties; thus, it plays a role in mucociliary clearance (Majima et al., 1988; Majima et al., 1990). SEPD has been found bioavailable in the nasal or tracheobronchial mucus, and it exerts proteolytic action even after oral intake (Majima et al., 1988; Majima et al., 1990). Recently, the role of mucins glycoproteins, the structural components of mucus and its interaction with microorganisms particularly SARS-CoV-2 and its pathophysiological and therapeutic relevance has been presented to enhance mucosal defense and control respiratory infections (Chatterjee et al., 2020). The elevated levels of mucin has been reported in the airway mucus of critical ill COVID-19 patients (Lu et al., 2021). The higher levels of mucins are reported in the COVID-19 patients bronchoalveolar lavage fluid (BALF) and lungs of preclinical models of SARS-CoV-2 (Liu et al., 2020). Liu et al. (2020) suggested that during SARS-CoV-2 infection, the rise in the IFN-β and -γ leads higher expression of mucins in alveolar epithelial cells. The mucins stick with the blood-gas barrier and accumulated alveolar mucus affects the blood-gas barrier thereby impeding the gaseous exchange of O2 and CO2 and causing hypoxia, a key factor that initiates COVID-19-induced mortality. Following progression in the diseases, increase in barrier thickness, along with raised inflammatory exudates causes impediment in exchange of O2 and CO2 that leads to the critical illness and complications (Liu et al., 2020). Additionally, SEPD has shown useful in chronic respiratory diseases (Nakamura et al., 2003), chronic sinusitis (Majima et al., 1988), ear, nose and throat disorders (Mazzone et al., 1990), secretory otitis media (Bellussi et al., 1984) and chronic airway disease with troubled expectoration (Nagaoka et al., 1979). Based on the role of SEPD on mucociliary clearance, relieving cough and promoting airway hygiene, it may be useful in delaying pulmonary complications and improving quality of life in COVID-19.

Polycystic ovarian syndrome (PCOS) is the primary cause of female infertility affecting several women worldwide. Changes in hormonal functions such as hyperandrogenism are considered a significant factor in developing PCOS in women. In addition, many molecular pathways are involved in the pathogenesis of PCOS in women. To have better insights about PCOS, it is data from clinical studies carried on women suffering from PCOS should be collected. However, this approach has several implications, including ethical considerations, cost involved and availability of subject. Moreover, during the early drug development process, it is always advisable to use non-human models mimicking human physiology as they are less expensive, readily available, have a shorter gestation period and less risk involved. Many animal models have been reported that resemble the PCOS pathways in human subjects. However, the models developed on rats and mice are more preferred over other rodent/non-rodent models due to their closer resemblance with human PCOS development mechanism. The most extensively reported PCOS models for rats and mice include those induced by using testosterone, letrozole and estradiol valerate. As the pathophysiology of PCOS is complex, none of the explored models completely surrogates the PCOS related conditions occurring in women. Hence, there is a need to develop an animal model that can resemble the pathophysiology of PCOS in women. The review focuses on various animal models explored to understand the pathophysiology of PCOS. The article also highlights some environmental and food-related models that have been used to induce PCOS.

Neurodegeneration is a distinguishing feature of many age related disorders and other vector borne neuroinflammatory diseases. There are a number of factors that can modulate the pathology of these disorders. ATP-binding cassette (ABC) transporters are primarily involved in the maintenance of normal brain homeostasis by eliminating toxic peptides and compounds from the brain. Also, ABC transporters protect the brain from the unwanted effects of endogenous and exogenous toxins that can enter the brain parenchyma. Therefore, these transporters have the ability to determine the pathological outcomes of several neurological disorders. For instance, ABC transporters like P-glycoprotein (ABCB1), and BCRP (ABCG2) have been reported to facilitate the clearance of peptides such as amyloid-β (Aβ) that accumulate in the brain during Alzheimer’s disease (AD) progression. Other members such as ABCA1, ABCA2, ABCC8, ABCC9, ABCG1 and ABCG4 also have been reported to be involved in the progression of various brain disorders such as HIV-associated dementia, Multiple sclerosis (MS), Ischemic stroke, Japanese encephalitis (JE) and Epilepsy. However, these defective transporters can be targeted by numerous botanical compounds such as Verapamil, Berberine and Fascalpsyn as a therapeutic target to treat these neurological outcomes. These compounds are already reported to modulate ABC transporter activity in the CNS. Nonetheless, the exact mechanisms involving the ABC transporters role in normal brain functioning, their role in neuronal dysfunction and how these botanical compounds ensure and facilitate their therapeutic action in association with defective transporters still remain elusive. This review therefore, summarizes the role of ABC transporters in neurological disorders, with a special emphasis on its role in AD brains. The prospect of using botanical/natural compounds as modulators of ABC transporters in neurological disorders is discussed in the latter half of the article.

Cancer kills millions of people worldwide every year. The main form of treatment at this point is chemotherapy, which comprises of systemic drug delivery so that they can kill the cancerous cells more effectively. But most of these drugs cause severe side effects in patients and, therefore there is a strong need to focus on identifying natural compounds as a potent phytoinhibitors using various in silico and in vitro approaches. Natural compounds pose low toxicity, hence render them to be an excellent alternative to the basis for the development of new anti-cancerous drugs. Our study considers an effective therapeutic target, Jab1 (c-Jun activation domain-binding protein-1) or a c-Jun coactivator, which has been implicated in multiple protein interactions that play a significant role in various stages of carcinogenesis. Hence we have performed screening of 1500 natural compounds having anticancerous activity by applying various in silico approaches including Lipinski rule of five, ADME, and various Molecular Docking tools. In this study, we have identified two potent phytoinhibitors against Jab1 which needs to be further validated through in vitro approaches.

Coronavirus disease (COVID-19), caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic and presents a public health emergency. It has affected millions of people and continues to affect more, despite tremendous social preventive measures. Identifying candidate drugs for the prevention and treatment of COVID-19 is crucial. The pathogenesis and the complications with advanced infection mainly involve an immune-inflammatory cascade. Therefore, therapeutic strategy relies on suppressing infectivity and inflammation, along with immune modulation. One of the most promising therapeutic targets for the modulation of immune-inflammatory responses is the endocannabinoid system, particularly the activation of cannabinoid type 2 receptors (CB2R), a G-protein coupled receptor which mediates the anti-inflammatory properties by modulating numerous signaling pathways. To pharmacologically activate the CB2 receptors, a naturally occurring cannabinoid ligand, beta-caryophyllene (BCP), received attention due to its potent anti-inflammatory, antiviral, and immunomodulatory properties. BCP is recognized as a full selective functional agonist on CB2 receptors and produces therapeutic effects by activating CB2 and the nuclear receptors, peroxisome proliferator-activated receptors (PPARs). BCP is regarded as the first dietary cannabinoid with abundant presence across cannabis and non-cannabis plants, including spices and other edible plants. BCP showed tissue protective properties and favorably modulates numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. Based on its pharmacological properties, molecular mechanisms, and the therapeutic potential of BCP as an immunomodulator, anti-inflammatory, organ-protective, and antiviral, we hypothesize that BCP could be a promising therapeutic and/or preventive candidate to target the triad of infection, immunity, and inflammation in COVID-19. In line with numerous studies that proposed the potential of cannabinoids in COVID-19, BCP may be a novel candidate compound for pharmaceutical and nutraceutical development due to its unique functional receptor selectivity, wide availability and accessibility, dietary bioavailability, nonpsychoactivity, and negligible toxicity along with druggable properties, including favorable pharmacokinetic and physicochemical properties. Based on reasonable pharmacological mechanisms and therapeutic properties, we speculate that BCP has potential to be investigated against COVID-19 and will inspire further preclinical and clinical studies.

The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.

Nuclear factor-kappa B, involved in inflammation, host immune response, cell adhesion, growth signals, cell proliferation, cell differentiation, and apoptosis defense, is a dimeric transcription factor. Inflammation is a key component of many common respiratory disorders, including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and acute respiratory distress syndrome. Many basic transcription factors are found in NF-κB signaling, which is a member of the Rel protein family. Five members of this family c-REL, NF-κB2 (p100/p52), RelA (p65), NF-κB1 (p105/p50), RelB, and RelA (p65) produce 5 transcriptionally active molecules. Proinflammatory cytokines, T lymphocyte, and B lymphocyte cell mitogens, lipopolysaccharides, bacteria, viral proteins, viruses, double-stranded RNA, oxidative stress, physical exertion, various chemotherapeutics are the stimulus responsible for NF-κB activation. NF-κB act as a principal component for several common respiratory illnesses, such as asthma, lung cancer, pulmonary fibrosis, COPD as well as infectious diseases like pneumonia, tuberculosis, COVID-19. Inflammatory lung disease, especially COVID-19, can make NF-κB a key target for drug production.

Nuclear factor κB (NFκB) is a unique protein complex that plays a major role in lung inflammation and respiratory dysfunction. The NFκB signaling pathway, therefore becomes an avenue for the development of potential pharmacological interventions, especially in situations where chronic inflammation is often constitutively active and plays a key role in the pathogenesis and progression of the disease. NFκB decoy oligodeoxynucleotides (ODNs) are double-stranded and carry NFκB binding sequences. They prevent the formation of NFκB-mediated inflammatory cytokines and thus have been employed in the treatment of a variety of chronic inflammatory diseases. However, the systemic administration of naked decoy ODNs restricts their therapeutic effectiveness because of their poor pharmacokinetic profile, instability, degradation by cellular enzymes and their low cellular uptake. Both structural modification and nanotechnology have shown promising results in enhancing the pharmacokinetic profiles of potent therapeutic substances and have also shown great potential in the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. In this review, we examine the contribution of NFκB activation in respiratory diseases and recent advancements in the therapeutic use of decoy ODNs. In addition, we also highlight the limitations and challenges in use of decoy ODNs as therapeutic molecules, cellular uptake of decoy ODNs, and the current need for novel delivery systems to provide efficient delivery of decoy ODNs. Furthermore, this review provides a common platform for discussion on the existence of decoy ODNs, as well as outlining perspectives on the latest generation of delivery systems that encapsulate decoy ODNs and target NFκB in respiratory diseases.

Hypogonadism is an endocrine disorder characterized by inadequate serum testosterone production by the Leydig cells of the testis. It is triggered by alterations in the hypothalamic–pituitary–gonadal axis. Erectile dysfunction (ED) is another common disorder in men that involves an alteration in erectile response–organic, relational, or psychological. The incidence of hypogonadism and ED is common in men aged over 40 years. Hypogonadism (including late-onset hypogonadism) and ED may be linked to several environmental factors-induced oxidative stresses. The factors mainly include exposure to pesticides, radiation, air pollution, heavy metals and other endocrine-disrupting chemicals. These environmental risk factors may induce oxidative stress and lead to hormonal dysfunctions. To better understand the subject, the study used many keywords, including “hypogonadism”, “late-onset hypogonadism”, “testosterone”, “erectile dysfunction”, “reactive oxygen species”, “oxidative stress”, and “environmental pollution” in major online databases, such as SCOPUS and PUBMED to extract relevant scientific information. Based on these parameters, this review summarizes a comprehensive insight into the important environmental issues that may have a direct or indirect association with hypogonadism and ED in men. The study concludes that environmental factors-induced oxidative stress may cause infertility in men. The hypothesis and outcomes were reviewed critically, and the mechanistic approaches are applied through oxidant-sensitive pathways. This study also provides reccomendations on future therapeutic interventions and protective measures against such adverse environmental factors-induced hypogonadism and ED.

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. Endometriosis is characterized by unwanted growth of endometrial tissue in different locations of the female reproductive tract. It may lead to recurrent pregnancy loss, which is one of the worst curses for the reproductive age group of human populations around the world. Thus, there is an urgent need for unveiling any common source of origin of both these diseases and con-nections, if any. Herein, we aimed to identify common potential biomarker genes of these two diseases via in silico approach using meta‐analysis of microarray data. Datasets were selected for the study based on certain exclusion criteria. Those datasets were subjected to comparative meta‐anal-yses for the identification of differentially expressed genes (DEGs), that are common to both diag-noses. The DEGs were then subjected to protein‐protein networking and subsequent functional enrichment analyses for unveiling their role/function in connecting two diseases. From the analyses, 120 DEGs are reported to be significant out of which four genes have been found to be prominent. These include the CTNNB1, HNRNPAB, SNRPF and TWIST2 genes. The significantly enriched pathways based on the above‐mentioned genes are mainly centered on signaling and developmental events. These findings could significantly elucidate the underlying molecular events in endometri-osis‐based recurrent miscarriages.

The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has led to a global crisis by infecting millions of people across the globe eventually causing multiple deaths. The prominent player of the virus has been known as the spike protein which enters the host system and leads to the infection. The S2 subunit is the most essential in this process of infection as it helps the SARS-CoV-2 to infect the host by binding to the human angiotensin converting enzyme 2 (hACE2), with the help of the receptor binding domain found at the S2 subunit of the virus. Studies also hypothesize that the S glycoproteins present in the virus interacts with different hosts in different ways which might be due to the mutations taking place in the genome of the virus over time. This work aims to decipher the similarities and differences in the sequences of spike proteins from samples of SARS-CoV-2 acquired from different infected individuals in different countries with the help of in silico methods such as multiple sequence alignment and phylogenetic analysis. It also aims to understand the differential infection rates among the infected countries by studying the amino acid composition and interactions of the virus with the host.

Non-communicable, chronic respiratory diseases (CRDs) affect millions of individuals worldwide. The course of these CRDs (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) are often punctuated by microbial infections that may result in hospitalization and are associated with increased risk of morbidity and mortality, as well as reduced quality of life. Interleukin-13 (IL-13) is a key protein that regulates airway inflammation and mucus hypersecretion. There has been much interest in IL-13 from the last two decades. This cytokine is believed to play a decisive role in the exacerbation of inflammation during the course of viral infections, especially, in those with pre-existing CRDs. Here, we discuss the common viral infections in CRDs, as well as the potential role that IL-13 plays in the virus-induced disease pathogenesis of CRDs. We also discuss, in detail, the immune-modulation potential of IL-13 that could be translated to in-depth studies to develop IL-13-based therapeutic entities.