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In this work, we tested the efficacy of yttrium oxide nanoparticles (NY), a promising antioxidant and anti-inflammatory agent, in L-arginine (L-Arg) induced chronic pancreatitis (CP) model. The nanoparticles were characterized using multiple techniques including transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (pXRD), and Energy dispersive X-ray analysis (EDX). The rats were divided into three groups: normal control, L-Arg control, L-Arg + NY (1 mg/kg). We probed the mechanistic effects of the NY by ELISA, multiplex analysis of TGF-β pathway and inflammatory cytokines and immunoblotting. NY treatment significantly reduced pancreatic oxidative-nitrosative stress. In addition, NY intervention also reduced inflammatory cytokines and chemokines resulting in the inhibition of fibrosis signaling. Further, NY treatment suppressed the TGF-β signaling and epithelial-mesenchymal transition (EMT). We conclude that NY shows potential antioxidant, anti-inflammatory, and anti-fibrotic effects against CP and associated fibrosis.

Aim: To assess the mechanistic effects of cerium oxide nanoparticles (CONPs) on Freund’s complete adjuvant (FCA)-induced rheumatoid arthritis in rats. Methods: CONPs were characterized and evaluated in vitro (RAW 264.7 macrophages) and in vivo (FCA-induced rheumatoid arthritis model). Results: In vitro treatment with CONPs significantly reduced lipopolysaccharide-induced oxidative stress (as evident from dichlorodihydrofluorescein diacetate staining), diminished mitochondrial stress (as observed with tetraethylbenzimidazolylcarbocyanine iodide staining) and reduced superoxide radicals. In vivo, CONPs exhibited anti-rheumatoid arthritis activity, as evident from results of paw volume, x-ray, clinical scoring, levels of cytokines (IL-17, IL-1β, TNF-α and TGF-β1) and histology. Conclusion: We provide preclinical proof that CONPs may be a novel futuristic nanoparticle-based approach for therapy of rheumatoid arthritis.

INTRODUCTION: According to the WHO report 2022, 2.21 million new cases and 1.80 million deaths were reported for lung cancer in the year 2020. Therefore, there is an urgent need to explore novel, safe, and effective therapeutic interventions for lung cancer. METHOD: Hence, in the present study, we explored the anticancer potential of vincamine by using network pharmacology, molecular docking, and in vitro approaches. Network pharmacology studies demonstrated that the most common targets of vincamine are G-protein coupled receptors, cytosolic proteins, and enzymes. Among these targets, two targets, ALK and ERBB2 protein, were common between vincamine and non-small cell lung cancer. RESULT: We discovered a link between these two targets and their companion proteins, as well as cancer-related pathways. In addition, a docking investigation between the ligand for vincamine and two targeted genes revealed a strong affinity toward these targeted proteins. Further, the in vitro study demonstrated that vincamine treatment for 72 h led to dose-dependent (0-500 μM) cytotoxicity on the A549 lung cancer cell line with an IC50 value of 291.7 μΜ. The wound-healing assay showed that vincamine treatment (150 and 300 μM) significantly inhibited cell migration and invasion. Interestingly, acridine orange/ethidium bromide dual staining demonstrated that vincamine treatment induces apoptosis in A549 cells. Additionally, the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay showed an increased level of reactive oxygen species (ROS) after the vincamine treatment, indicating ROS-mediated apoptosis in A549 cells. CONCLUSION: Altogether, based on our findings, we hypothesize that vincamine-induced apoptosis of lung cancer cells via ALK and ERBB2 protein modulation may be an attractive futuristic strategy for managing lung cancer in combination with chemotherapeutic agents to obtain synergistic effects with reduced side effects.

Journal of cellular biochemistry 123(10), 1674-1698 (2022). doi:10.1002/jcb.30329 special issue: "Special Issue: Novel therapeutic targets in liver pathology: From basic science to clinical translation / Issue edited by: Stefan Rose-John, Ralf Weiskirchen", Published by Wiley-Liss, New York, NY

Zebrafish is a useful model for understanding human genetics and diseases and has evolved into a prominent scientific research model. The genetic structure of zebrafish is 70% identical to that of humans. Its small size, low cost, and transparent embryo make it a valuable tool in experimentation. Zebrafish and mammals possess the same molecular mechanism of thyroid organogenesis and development. Thus, thyroid hormone signaling, embryonic development, thyroid-related disorders, and novel genes involved in early thyroid development can all be studied using zebrafish as a model. Here in this review, we emphasize the evolving role of zebrafish as a possible tool for studying the thyroid gland in the context of physiology and pathology. The transcription factors nkx2.1a, pax2a, and hhex which contribute a pivotal role in the differentiation of thyroid primordium are discussed. Further, we have described the role of zebrafish as a model for thyroid cancer, evaluation of defects in thyroid hormone transport, thyroid hormone (TH) metabolism, and as a screening tool to study thyrotoxins. Hence, the present review highlights the role of zebrafish as a novel approach to understand thyroid development and organogenesis.

Polysaccharides are biopolymers distinguished by their complex secondary structures executing various roles in microorganisms, plants, and animals. They are made up of long monomers of similar type or as a combination of other monomeric chains. Polysaccharides are considered superior as compared to other polymers due to their diversity in charge and size, biodegradability, abundance, bio-compatibility, and less toxicity. These natural polymers are widely used in designing of nanoparticles (NPs) which possess wide applications in therapeutics, diagnostics, delivery and protection of bioactive compounds or drugs. The side chain reactive groups of polysaccharides are advantageous for functionalization with nanoparticle-based conjugates or therapeutic agents such as small molecules, proteins, peptides and nucleic acids. Polysaccharide NPs show excellent pharmacokinetic and drug delivery properties, facilitate improved oral absorption, control the release of drugs, increases in vivo retention capability, targeted delivery, and exert synergistic effects. This review updates the usage of polysaccharides based NPs particularly cellulose, chitosan, hyaluronic acid, alginate, dextran, starch, cyclodextrins, pullulan, and their combinations with promising applications in diabetes, organ fibrosis and arthritis.

The liver plays an important role in regulating the metabolic processes and is the most frequently targeted organ by toxic chemicals. Acetaminophen (APAP) is a well-known anti-allergic, anti-pyretic, non-steroidal anti-inflammatory drug (NSAID), which upon overdose leads to hepatotoxicity, the major adverse event of this over-the-counter drug.APAP overdose induced acute liver injury is the second most common cause that often requires liver transplantation worldwide, for which N-acetyl cysteine is the only synthetic drug clinically approved as an antidote. So, it was felt that there is a need for the novel therapeutic approach for the treatment of liver diseases with less adverse effects. This review provides detailed analysis of the different plant extracts; phytochemicals and herbal formulations for the amelioration of APAP-induced liver injury.The data was collected using different online resources including PubMed, ScienceDirect, Google Scholar, Springer, and Web of Science using keywords given below.Over the past decades various reports have revealed that plant-based approaches may be a better treatment choice for the APAP-induced hepatotoxicity in pre-clinical experimental conditions. Moreover, herbal compounds provide several advantages over the synthetic drugs with fewer side effects, easy availability and less cost for the treatment of life-threatening diseases.The current review summarizes the hepatoprotective effects and therapeutic mechanisms of various plant extracts, active phytoconstituents and herbal formulations with potential application against APAP induced hepatotoxicity as the numbers of hepatoprotective natural products are more without clinical relativity. Further, pre-clinical pharmacological research will contribute to the designing of natural products as medicines with encouraging prospects for clinical application.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the leading pulmonary inflammatory disorders causing significant morbidity and mortality. Vincamine is a novel phytochemical with promising anti-inflammatory properties. In the current work, the protective effect of vincamine was studied in vitro (Raw 264.7 macrophages) and in vivo against lipopolysaccharide (LPS) induced ALI in Swiss albino mice. Vincamine significantly reduced nitrite and TNF-α release from the LPS stimulated macrophages and increased the levels of IL-10, indicating potent anti-inflammatory effects. It was observed that vincamine at the dose of 40 mg/kg, significantly reduced LPS induced inflammatory cell count in blood and in bronchoalveolar lavage (BAL) fluid. Further, vincamine exerted potent suppression of inflammation by reducing the expression of proinflammatory cytokines, while significantly increased (p 0.001) the expression of anti-inflammatory cytokine (IL-10 and IL-22). Interestingly, histological changes were reversed in vincamine treated groups in a dose-dependent manner. Immunohistochemical analysis revealed significantly enhanced expression of NF-κB, TNF-α and COX-2 while reduced expression of Nrf-2 in disease control group, which were significantly (p 0.001) ameliorated by vincamine. We, to the best of our knowledge, report for the first time that vincamine possesses protective potential against LPS induced inflammation and oxidative stress, possibly by inhibiting the NF-κB cascade, while positively regulating the Nrf-2 pathway. These findings are of potential relevance for COVID-19 management concerning the fact that lung injury and ARDS are its critical features.

Liver fibrosis is one of the major liver complications which eventually progresses to liver cirrhosis and liver failure. Cerium oxide nanoparticles, also known as nanoceria (NC) are nanoparticles with potential antioxidant and anti-inflammatory activities. Herein, we evaluated the hepatoprotective and anti-fibrotic effects of nanoceria (NC) against bile duct ligation (BDL) induced liver injury. NC were administered i.p. for 12 days (0.5 and 2 mg/kg) to C57BL/6J mice. The biochemical markers of liver injury, oxidative and nitrosative stress markers, inflammatory cytokines were evaluated. Fibrosis assessment and mechanistic studies were conducted to assess the hepatoprotective effects of NC. Administration of NC proved to significantly ameliorate liver injury as evident by reduction in SGOT, SGPT, ALP and bilirubin levels in the treated animals. NC treatment significantly reduced the hydroxyproline levels and expression of fibrotic markers. In summary, our findings establish the hepatoprotective and anti-fibrotic effects of NC against BDL induced liver injury and liver fibrosis. These protective effects were majorly ascribed to their potential ROS inhibition and antioxidant activities through catalase, superoxide dismutase (SOD)-mimetic properties and auto-regenerating capabilities.

Chronic liver diseases (CLDs) caused by viral infections, alcohol/drug abuse, or metabolic disorders affect millions of people globally and have increased mortality owing to the lack of approved therapies. Lipoxygenases (LOXs) are a family of multifaceted enzymes that are responsible for the oxidation of polyunsaturated fatty acids (PUFAs) and are implicated in the pathogenesis of multiple disorders including liver diseases. This review describes the three main LOX signaling pathways – 5-, 12-, and 15-LOX – and their involvement in CLDs. We also provide recent insights and future perspectives on LOX-related hepatic pathophysiology, and discuss the potential of LOXs and LOX-derived metabolites as diagnostic biomarkers and therapeutic targets in CLDs.

Aim: The present study was carried out to assess the effect of nanoceria (NC) on pancreatic inflammation caused by cerulein. Methods: NC was characterized and in vitro studies were carried out in murine macrophages. The in vivo effects were tested on cerulein-induced pancreatitis. Results: In vitro treatment with NC remarkably protected macrophages from lipopolysaccharide-induced inflammation and oxidative stress as evident from the results of 2′,7′-dichlorofluorescin diacetate, JC-1 and MitoSox staining. In vivo treatment with NC showed potent superoxide dismutase and catalase mimetic activity, antipancreatitis activity and improved histology. Furthermore, it reduced the expression of p65-NF-κB and acetylation of histone H3 at lysine K14, K56 and K79 residues. Conclusion: We for the first time, demonstrate that NC may be a promising candidate for the therapy of pancreatitis.

This study was performed to study the in vitro and in vivo efficacy of hydroalcoholic extract of curry leaf (CLE) rich in carbazole alkaloids, against LPS-induced inflammation in Raw 264.7 macrophages and cerulein-induced acute pancreatitis, respectively. CLE was characterized by Fourier-transform infrared (FTIR) and liquid chromatography-mass spectrometry. Raw 264.7 cells were stimulated with LPS (2 μg/ml) and treated with CLE. The animals were treated with two doses of CLE (100 and 300 mg/kg). Plasma biochemistry, tissue lipid peroxidation, cytokines, and histological examination were evaluated. CLE was found to decently scavenge the activity of DPPH radical. It dose dependently suppressed nitrite production and oxidative stress in macrophages. CLE alleviated LPS-induced inflammation in macrophages as evident from the results of various inflammatory cytokines (IL-1β, IL-6, and TNF-α). In vivo, CLE reduced cerulein-induced pancreatic edema. CLE significantly abrogated the cerulein-induced lipid peroxidation, nitrite, MPO, and GSH levels. The inflammatory cytokines and p65-NFκB activity were significantly reduced by CLE. Mechanistically, CLE reduced the expression of NT, MPO, IL-1β, ICAM-1, and COX-2, and increased the expression of Nrf2. It reduced distant organ damage markers as well. We report for the first time that CLE holds substantial potential for the prevention of acute pancreatitis.

Curcumin (cur) is a well known plant flavonoid with pleiotropic pharmacological activities. However, due to its poor bioavailability those therapeutic benefits are still out of reach for patient community. The main aim of our study was to prepare sustained release cur microparticles (CuMPs) with Poly (lactic-co-glycolic acid) (PLGA), an FDA approved biodegradable polymer and to assess their pharmacological potential in multiple low doses streptozotocin (MLD-STZ) induced type 1 diabetes mellitus (T1DM). CuMPs were formulated and characterized for size (12.71 ± 4.20 μm) and encapsulation efficiency (85.10 ± 2.33%) with 28% drug loading. In vitro release and in vivo pharmacokinetics studies showed promising results of sustained release of cur from CuMPs. With this here we report a strategy that single administration of CuMPs may fill the therapeutic window that is missing from free drug repeated administration and low bioavailability of cur. Moving forward with this concept, we compared the therapeutic effects of CuMPs (equivalent to 7.5 mg/kg cur with free cur orally (100 mg/kg) and intraperitoneally (7.5 mg/kg) administered daily in MLD-STZ challenged animals). CuMPs exhibited superior effects compared to daily administration free drug given either orally or i.p. in terms of lowering the blood glucose levels, improved glucose clearance as evident from results of i.p. glucose tolerance test (IPGTT). Interestingly, we observed a remarkable reduction in diabetes incidence in CuMPs groups (only one out of six animals i.e. 16.6%). Moreover, plasma and tissue levels of insulin indicated superior effect of CuMPs. In addition, immunohistochemical analysis of insulin in pancreatic β-cells further confirmed the improved therapeutic benefit with significant increase in insulin signal with CuMPs. Amelioration of oxidative stress and inflammation of CuMPs was observed as the molecular mechanism behind the observed superior pharmacological effects with CuMPs. Cumulatively, our sustained release CuMPs formulation may serve as a bridge in overcoming the poor pharmacokinetics issues associated with cur and may hasten the clinical translation of cur.

Non-alcoholic steatohepatitis (NASH) is a progressive form of Non-alcoholic fatty liver disease (NAFLD), which slowly progresses toward cirrhosis and finally leads to the development of hepatocellular carcinoma. Obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome are major risk factors contributing to NAFLD. Targeting these risk factors is a rational option for inhibiting NASH progression. In addition, NASH could be treated with therapies that target the metabolic abnormalities causing disease pathogenesis (such as de novo lipogenesis and insulin resistance) as well with medications targeting downstream processes such as cellular damage, apoptosis, inflammation, and fibrosis. Glucagon-like peptide (GLP-1), is an incretin hormone dysregulated in both experimental and clinical NASH, which triggers many signaling pathways including fibroblast growth factor (FGF) that augments NASH pathogenesis. Growing evidence indicates that GLP-1 in concert with FGF-21 plays crucial roles in the conservation of glucose and lipid homeostasis in metabolic disorders. In line, GLP-1 stimulation improves hepatic ballooning, steatosis, and fibrosis in NASH. A recent clinical trial on NASH patients showed that the upregulation of FGF-21 decreases liver fibrosis and hepatic steatosis, thus improving the pathogenesis of NASH. Hence, therapeutic targeting of the GLP-1/FGF axis could be therapeutically beneficial for the remission of NASH. This review outlines the significance of the GLP-1/FGF-21 axis in experimental and clinical NASH and highlights the activity of modulators targeting this axis as potential salutary agents for the treatment of NASH.

Doxorubicin (Dox) is a secondary metabolite of the mutated strain of Streptomyces peucetius var. Caesius and belongs to the anthracyclines family. The anti-cancer activity of Dox is mainly exerted through the DNA intercalation and inhibiting topoisomerase II enzyme in fast-proliferating tumors. However, Dox causes cumulative and dose-dependent cardiotoxicity, which results in increased risks of mortality among cancer patients and thus limiting its wide clinical applications. There are several mechanisms has been proposed for doxorubicin-induced cardiotoxicity and oxidative stress, free radical generation and apoptosis are most widely reported. Apart from this, other mechanisms are also involved in Dox-induced cardiotoxicity such as impaired mitochondrial function, a perturbation in iron regulatory protein, disruption of Ca2+ homeostasis, autophagy, the release of nitric oxide and inflammatory mediators and altered gene and protein expression that involved apoptosis. Dox also causes downregulation of DNA methyltransferase 1 (DNMT1) enzyme activity which leads to a reduction in the DNA methylation process. This hypomethylation causes dysregulation in the mitochondrial genes like peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1-alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) unit in the heart. Apart from DNA methylation, Dox treatment also alters the micro RNAs levels and histone deacetylase (HDAC) activity. Therefore, in the current review, we have provided a detailed update on the current understanding of the pathological mechanisms behind the well-known Dox-induced cardiotoxicity. Further, we have provided some of the most plausible pharmacological strategies which have been tested against Dox-induced cardiotoxicity.

COVID-19 is a respiratory infection that has been declared as a global health crisis by the WHO. It mainly affects the respiratory system. Apart from respiratory system, it also affects other organs as well including the brain. Numerous emerging reports have demonstrated that the COVID-19 has detrimental effects on neurological functions, and can lead to severe impairment of the central nervous system (CNS). The neurological manifestations linked with COVID-19 include headache, anosmia, encephalitis, epileptic seizures, Guillain-Barre syndrome, stroke and intracerebral hemorrhage alongwith multiple others complications. The CNS related complications may be severe and are linked with poor diagnosis which may worsen the condition. Therefore, there is a need to precisely understand the neurological sequelae along with upcoming clinical outcomes. Here, we present a brief review of the neurological complications and symptoms associated with COVID-19 along with brain imaging findings. Further, we have discussed about the emerging biosensing approaches which may aid in rapid, precise and mass diagnosis of COVID-19.

Development of scaffold from biopolymers can ease the requirements for donor skin autograft and plays an effective role in the treatment of burn wounds. In the current study, a porous foam based, bilayered hydrogel scaffold was developed using gelatin, hyaluronic acid and chondroitin sulfate (G-HA-CS). The fabricated scaffold was characterized physicochemically for pre- and post-sterilization efficacy by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA).In-vitrostudies proved that the scaffold promoted cellular proliferation. The efficacy of G-HA-CS scaffold was compared with Integra™ at different time points (7, 14, 21 and 42 days), in a swine second degree burn wound model. Remarkable healing potential of the scaffold was evident from the wound contraction rate, reduction of IL-6, TNF-αand C3. The expression of healing markers TGF-β1 and collagen 1 revealed significant skin regeneration with regulated fibroblast activation towards the late phase of healing (p< 0.001 at day 21 and 42 vs. control). Expression of Vascular Endothelial Growth Factor A (VEGFA), vimentin and N-cadherin were found to favor angiogenesis and skin regeneration. Mechanistically, scaffold promoted wound healing by modulation of CD-45, cyclooxygenase-2 and MMP-2. Thus, the promising results with foam based scaffold, comparable to Integra™ in swine burn injury model offer an innovative lead for clinical translation for effective management of burn wound.

Bilirubin has been proven to possess significant anti-inflammatory, antioxidant and antiviral activities. Recently, it has been postulated as a metabolic hormone. Further, moderately higher levels of bilirubin are positively associated with reduced risk of cardiovascular diseases, diabetes, metabolic syndrome and obesity. However, due to poor solubility the therapeutic delivery of bilirubin remains a challenge. Nanotechnology offers unique advantages which may be exploited for improved delivery of bilirubin to the target organ with reduced risk of systemic toxicity. Herein, we postulate the use of intravenous administration or inhalational delivery of bilirubin nanomedicine (BNM) to combat systemic dysfunctions associated with COVID-19, owing to the remarkable preclinical efficacy and optimistic results of various clinical studies of bilirubin in non-communicable disorders. BNM may be used to harness the proven preclinical pharmacological efficacy of bilirubin against COVID-19 related systemic complications.

Hinokitiol is a natural bio-active tropolone derivative with promising antioxidant and anti-inflammatory properties. This study was conducted to evaluate the ameliorative effects of hinokitiol against acute pancreatitis induced by cerulein. Mice were pre-treated with hinokitiol intraperitoneally for 7 days (50 and 100 mg/kg), and on the final day of study, cerulein (6 × 50 μg/kg) was injected every hour for six times. Six hours after the last dose of cerulein, blood was collected from the mice through retro-orbital plexus for biochemical analysis. After blood collection, mice were euthanized and the pancreas was harvested for studying effects on oxidative stress, pro-inflammatory cytokines, immunohistochemistry and histopathology of tissue sections. Hinokitiol treatment significantly reduced edema of the pancreas and reduced the plasma levels of lipase and amylase in mice with cerulein-induced acute pancreatitis. It also attenuated the oxidative and nitrosative stress related damage as evident from the reduced malondialdehyde (MDA) and nitrite levels, which were significantly increased in the mice with acute pancreatitis. Furthermore, hinokitiol administration significantly reduced the pancreatitis-evoked decrease in the activity of catalase, glutathione (GSH) and superoxide dismutase (SOD) in the pancreatic tissue. Pre-treatment with hinokitiol significantly reduced the elevated levels of pro-inflammatory cytokines like interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) as well as increased the levels of anti-inflammatory cytokine interleukin-10 (IL-10) in the pancreatic tissue of mice with acute pancreatitis. The immunohistochemical expression of nuclear factor kappa light chain enhancer of activated B cells (NF-κB), cyclooxygenase (COX-2) and TNF-α were significantly decreased by hinokitiol in mice with cerulein-induced acute pancreatitis. In conclusion, the results of the present study demonstrate that hinokitiol has significant potential to prevent cerulein-induced acute pancreatitis.

Coronavirus disease 2019 (COVID-19) is one of the worst pandemics to have hit the humanity. The manifestations are quite varied, ranging from severe lung infections to being asymptomatic. Hence, there is an urgent need to champion new tools to accelerate the end of this pandemic. Compromised immunity is a primary feature of COVID-19. Allium sativum (AS) is an effective dietary supplement known for its immune-modulatory, antibacterial, anti-inflammatory, anticancer, antifungal, and anti-viral properties. In this paper, it is hypothesized that carbon dots (CDs) derived from AS (AS-CDs) may possess the potential to downregulate the expression of pro-inflammatory cytokines and revert the immunological aberrations to normal in case of COVID-19. CDs have already been explored in the world of nanobiomedicine as a promising theranostic candidates for bioimaging and drug/gene delivery. The antifibrotic and antioxidant effects of AS are elaborated, as demonstrated in several studies. It is found that the most active constituent of AS, allicin has a highly potent antioxidant and reactive oxygen species (ROS) scavenging effect. The antibacterial, antifungal, and anti-viral effects along with their capability of negating inflammatory effects and cytokine storm are discussed. The synthesis of theranostic CDs from AS may provide a novel weapon in the therapeutic armamentarium for the management of COVID-19 infection and, at the same time, could act as a diagnostic agent for COVID-19.

Annals of translational medicine : ATM 9(8), 728 (2021). doi:10.21037/atm-20-2948, Published by AME Publishing Company, Shatin, NT

Asthma is a chronic inflammatory disease described by impaired lung function, airway hyperresponsiveness, episodic wheezing, and dyspnea. Asthma prevalence has risen drastically, and it is estimated that more than 339 million individuals worldwide had asthma with marked heterogeneity in pathophysiology and etiology. Several factors involved in the progression and development of asthma include allergens, pollutants, obesity, viruses, antigens, and many more, eliciting strong inflammatory and immune responses, causing airflow obstruction, and tightening of respiratory smooth muscle causing the characteristic asthma symptoms. Multiple complex molecular pathways are involved in asthma pathophysiologies such as immunoglobulin E, cytokines, nitric oxide, dendritic cells, leukotrienes, oxidative stress, and inflammatory infiltrate of mast cells, neutrophils, eosinophils, lymphocytes, innate immunity, and many more. The current chapter focuses on illustrating the various molecular pathways that contribute to asthma development and its progression.

Graphical abstract, Highlights • Nanoceria is a unique rare earth nanomedicine with catalase and SOD mimetic activity. • It possesses promising anti-inflammatory and TGF-β inhibitory activity. • Nanoceria may reduce the complications of COVID-19 by inhibition of MAPKs and NFκB signaling. • It may be nebulized at very low concentration with beneficial pharmacological effects. • It may halt lung fibrosis and prove to be a useful tool for the management of COVID-19., The COVID-19 pandemic has emerged as an unprecedented global healthcare emergency and has devastated the global economy. The SARS-CoV-2 virus replicates in the host cells and is seemingly much more virulent compared to other flu viruses, as well as the SARS-CoV-1. The respiratory complications of the disease include acute respiratory distress syndrome (ARDS), cytokine storm, systemic inflammation, and pulmonary fibrosis. Nanoceria (NC) is a versatile rare earth nanoparticle with remarkable catalase and superoxide dismutase mimetic redox regenerative properties. Interestingly, NC possesses promising anti-inflammatory, antioxidant and anti-fibrotic properties, making it an attractive tool to fight against the SARS-CoV-2 as well as the associated systemic complications. Until now, there is no clinically approved vaccine or drug for the treatment of COVID-19, and the conquest to find a novel therapy for this global havoc is being undertaken at a warlike pace. Herein, based on preclinical evidence, we hypothesize that NC owing to its unique pharmacological properties, might be an attractive preclinical candidate to win the battle over COVID-19. Further, it may be used as a prevention or treatment strategy in combination with other drugs.

The COVID-19 pandemic is the most devastating health emergency that humans have seen over the past century. The war against the disease has been handicapped by unavailability of effective therapeutic options. Till date, there is no clinically approved vaccine or drug for the treatment of COVID-19, and the ongoing search to find a novel therapy is progressing at pandemic pace. Herein, we propose a novel hypothesis based on sound research evidence that electric stimulation can be a potential adjuvant to the currently used symptomatic therapies and antiviral drugs. Based on preclinical evidence, we propose that electric stimulation can improve respiratory functions, inhibit SARS-CoV-2 growth, reduce pain, boost immunity and improve the penetration of antiviral drugs. We envisage that our hypothesis, if used clinically as an adjuvant, may significantly improve the therapeutic outcomes of the current treatment regimen being used around the globe for the management of COVID-19.

Gene therapy is the product of man's quest to eliminate diseases. Gene therapy has three facets namely, gene silencing using siRNA, shRNA and miRNA, gene replacement where the desired gene in the form of plasmids and viral vectors, are directly administered and finally gene editing based therapy where mutations are modified using specific nucleases such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regulatory interspaced short tandem repeats (CRISPR)/CRISPR-associated protein (Cas)-associated nucleases. Transfer of gene is either through transformation where under specific conditions the gene is directly taken up by the bacterial cells, transduction where a bacteriophage is used to transfer the genetic material and lastly transfection that involves forceful delivery of gene using either viral or non-viral vectors. The non-viral transfection methods are subdivided into physical, chemical and biological. The physical methods include electroporation, biolistic, microinjection, laser, elevated temperature, ultrasound and hydrodynamic gene transfer. The chemical methods utilize calcium- phosphate, DAE-dextran, liposomes and nanoparticles for transfection. The biological methods are increasingly using viruses for gene transfer, these viruses could either integrate within the genome of the host cell conferring a stable gene expression, whereas few other non-integrating viruses are episomal and their expression is diluted proportional to the cell division. So far, gene therapy has been wielded in a plethora of diseases. However, coherent and innocuous delivery of genes is among the major hurdles in the use of this promising therapy. Hence this review aims to highlight the current options available for gene transfer along with the advantages and limitations of every method.

Aim: The present study was designed to probe the cardioprotective effects of nanoyttria (NY). Materials & methods: NY was characterized using various techniques. Isoproterenol (ISO)-induced cardiotoxicity challenged mice were treated with NY for 28 days at two doses (0.4 and 4 mg/kg, intraperitoneally). Results: NY demonstrated free radical scavenging activity as shown by a 2,2-diphenyl-1-picrylhydrazyl assay. NY treatment showed alleviation of ISO-induced cardiotoxicity as evident from the reduction in biochemical parameters. The expression of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) showed significant decrease upon NY treatment. Histopathology and ECG showed protection in histoarchitecture and rhythm of heart, respectively. Reduction in hydroxyproline and TGF-β1 expression indicated antifibrotic activity. Conclusion: We report for the first time that NY ameliorates ISO-induced cardiac remodeling.