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Fulltext Exosomal mediated signal transduction through artificial microRNA (amiRNA): A potential target for inhibition of SARS-CoV-2

Vadivalagan C, Shitut A, Kamalakannan S, Chen RM, Serrano-Aroca Á, Mishra V, et al.

Cell Signal, 2022 Jul;95:110334.
PMID: 35461900 DOI: 10.1016/j.cellsig.2022.110334

Exosome trans-membrane signals provide cellular communication between the cells through transport and/or receiving the signal by molecule, change the functional metabolism, and stimulate and/or inhibit receptor signal complexes. COVID19 genetic transformations are varied in different geographic positions, and single nucleotide polymorphic lineages were reported in the second waves due to the fast mutational rate and adaptation. Several vaccines were developed and in treatment practice, but effective control has yet to reach in cent presence. It was initially a narrow immune-modulating protein target. Controlling these diverse viral strains may inhibit their transuding mechanisms primarily to target RNA genes responsible for COVID19 transcription. Exosomal miRNAs are the main sources of transmembrane signals, and trans-located miRNAs can directly target COVID19 mRNA transcription. This review discussed targeted viral transcription by delivering the artificial miRNA (amiRNA) mediated exosomes in the infected cells and significant resources of exosome and their efficacy.
Fulltext Gut Microbiota Disruption in COVID-19 or Post-COVID Illness Association with severity biomarkers: A Possible Role of Pre / Pro-biotics in manipulating microflora

Alharbi KS, Singh Y, Hassan Almalki W, Rawat S, Afzal O, Alfawaz Altamimi AS, et al.

Chem Biol Interact, 2022 May 01;358:109898.
PMID: 35331679 DOI: 10.1016/j.cbi.2022.109898

Coronavirus disease (COVID-19), a coronavirus-induced illness attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, is thought to have first emerged on November 17, 2019. According to World Health Organization (WHO). COVID-19 has been linked to 379,223,560 documented occurrences and 5,693,245 fatalities globally as of 1st Feb 2022. Influenza A virus that has also been discovered diarrhea and gastrointestinal discomfort was found in the infected person, highlighting the need of monitoring them for gastro intestinal tract (GIT) symptoms regardless of whether the sickness is respiration related. The majority of the microbiome in the intestines is Firmicutes and Bacteroidetes, while Bacteroidetes, Proteobacteria, and Firmicutes are found in the lungs. Although most people overcome SARS-CoV-2 infections, many people continue to have symptoms months after the original sickness, called Long-COVID or Post COVID. The term "post-COVID-19 symptoms" refers to those that occur with or after COVID-19 and last for more than 12 weeks (long-COVID-19). The possible understanding of biological components such as inflammatory, immunological, metabolic activity biomarkers in peripheral blood is needed to evaluate the study. Therefore, this article aims to review the informative data that supports the idea underlying the disruption mechanisms of the microbiome of the gastrointestinal tract in the acute COVID-19 or post-COVID-mediated elevation of severity biomarkers.
Nutraceuticals and COVID-19: A mechanistic approach toward attenuating the disease complications

Paudel KR, Patel V, Vishwas S, Gupta S, Sharma S, Chan Y, et al.

J Food Biochem, 2022 Dec;46(12):e14445.
PMID: 36239436 DOI: 10.1111/jfbc.14445

Nutraceuticals have emerged as potential compounds to attenuate the COVID-19 complications. Precisely, these food additives strengthen the overall COVID treatment and enhance the immunity of a person. Such compounds have been used at a large scale, in almost every household due to their better affordability and easy access. Therefore, current research is focused on developing newer advanced formulations from potential drug candidates including nutraceuticals with desirable properties viz, affordability, ease of availability, ease of administration, stability under room temperature, and potentially longer shelf-lives. As such, various nutraceutical-based products such as compounds could be promising agents for effectively managing COVID-19 symptoms and complications. Most importantly, regular consumption of such nutraceuticals has been shown to boost the immune system and prevent viral infections. Nutraceuticals such as vitamins, amino acids, flavonoids like curcumin, and probiotics have been studied for their role in the prevention of COVID-19 symptoms such as fever, pain, malaise, and dry cough. In this review, we have critically reviewed the potential of various nutraceutical-based therapeutics for the management of COVID-19. We searched the information relevant to our topic from search engines such as PubMed and Scopus using COVID-19, nutraceuticals, probiotics, and vitamins as a keyword. Any scientific literature published in a language other than English was excluded. PRACTICAL APPLICATIONS: Nutraceuticals possess both nutritional values and medicinal properties. They can aid in the prevention and treatment of diseases, as well as promote physical health and the immune system, normalizing body functions, and improving longevity. Recently, nutraceuticals such as probiotics, vitamins, polyunsaturated fatty acids, trace minerals, and medicinal plants have attracted considerable attention and are widely regarded as potential alternatives to current therapeutic options for the effective management of various diseases, including COVID-19.
Fulltext Polysaccharide-Based Nanomedicines Targeting Lung Cancer

Bhat AA, Gupta G, Alharbi KS, Afzal O, Altamimi ASA, Almalki WH, et al.

Pharmaceutics, 2022 Dec 13;14(12).
PMID: 36559281 DOI: 10.3390/pharmaceutics14122788

A primary illness that accounts for a significant portion of fatalities worldwide is cancer. Among the main malignancies, lung cancer is recognised as the most chronic kind of cancer around the globe. Radiation treatment, surgery, and chemotherapy are some medical procedures used in the traditional care of lung cancer. However, these methods lack selectivity and damage nearby healthy cells. Several polysaccharide-based nanomaterials have been created to transport chemotherapeutics to reduce harmful and adverse side effects and improve response during anti-tumour reactions. To address these drawbacks, a class of naturally occurring polymers called polysaccharides have special physical, chemical, and biological characteristics. They can interact with the immune system to induce a better immunological response. Furthermore, because of the flexibility of their structures, it is possible to create multifunctional nanocomposites with excellent stability and bioavailability for the delivery of medicines to tumour tissues. This study seeks to present new views on the use of polysaccharide-based chemotherapeutics and to highlight current developments in polysaccharide-based nanomedicines for lung cancer.
Fulltext Self-nanoemulsifying drug delivery system (SNEDDS) mediated improved oral bioavailability of thymoquinone: optimization, characterization, pharmacokinetic, and hepatotoxicity studies

Rathore C, Hemrajani C, Sharma AK, Gupta PK, Jha NK, Aljabali AAA, et al.

Drug Deliv Transl Res, 2023 Jan;13(1):292-307.
PMID: 35831776 DOI: 10.1007/s13346-022-01193-8

Thymoquinone (TQ) is an antioxidant, anti-inflammatory, and hepatoprotective compound obtained from the black seed oil of Nigella sativa. However, high hydrophobicity, instability at higher pH levels, photosensitivity, and low oral bioavailability hinder its delivery to the target tissues. A self-nanoemulsifying drug delivery system (SNEDDS) was fabricated using the microemulsification technique to address these issues. Its physicochemical properties, thermodynamic stability studies, drug release kinetics, in vivo pharmacokinetics, and hepatoprotective activity were evaluated. The droplet size was in the nano-range (
Lupus Susceptibility Region Containing CDKN1B rs34330 Mechanistically Influences Expression and Function of Multiple Target Genes, Also Linked to Proliferation and Apoptosis

Singh B, Maiti GP, Zhou X, Fazel-Najafabadi M, Bae SC, Sun C, et al.

Arthritis Rheumatol, 2021 Dec;73(12):2303-2313.
PMID: 33982894 DOI: 10.1002/art.41799

OBJECTIVE: In a recent genome-wide association study, a significant genetic association between rs34330 of CDKN1B and risk of systemic lupus erythematosus (SLE) in Han Chinese was identified. This study was undertaken to validate the reported association and elucidate the biochemical mechanisms underlying the effect of the variant.
METHODS: We performed an allelic association analysis in patients with SLE, followed by a meta-analysis assessing genome-wide association data across 11 independent cohorts (n = 28,872). In silico bioinformatics analysis and experimental validation in SLE-relevant cell lines were applied to determine the functional consequences of rs34330.
RESULTS: We replicated a genetic association between SLE and rs34330 (meta-analysis P = 5.29 × 10-22 , odds ratio 0.84 [95% confidence interval 0.81-0.87]). Follow-up bioinformatics and expression quantitative trait locus analysis suggested that rs34330 is located in active chromatin and potentially regulates several target genes. Using luciferase and chromatin immunoprecipitation-real-time quantitative polymerase chain reaction, we demonstrated substantial allele-specific promoter and enhancer activity, and allele-specific binding of 3 histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), CCCTC-binding factor, and a critical immune transcription factor (interferon regulatory factor 1 [IRF-1]). Chromosome conformation capture revealed long-range chromatin interactions between rs34330 and the promoters of neighboring genes APOLD1 and DDX47, and effects on CDKN1B and the other target genes were directly validated by clustered regularly interspaced short palindromic repeat (CRISPR)-based genome editing. Finally, CRISPR/dead CRISPR-associated protein 9-based epigenetic activation/silencing confirmed these results. Gene-edited cell lines also showed higher levels of proliferation and apoptosis.
CONCLUSION: Collectively, these findings suggest a mechanism whereby the rs34330 risk allele (C) influences the presence of histone marks, RNA Pol II, and IRF-1 transcription factor to regulate expression of several target genes linked to proliferation and apoptosis. This process could potentially underlie the association of rs34330 with SLE.
Fulltext The impact of formaldehyde exposure on lung inflammatory disorders: Insights into asthma, bronchitis, and pulmonary fibrosis

Bhat AA, Afzal M, Goyal A, Gupta G, Thapa R, Almalki WH, et al.

Chem Biol Interact, 2024 May 01;394:111002.
PMID: 38604395 DOI: 10.1016/j.cbi.2024.111002

Lung inflammatory disorders are a major global health burden, impacting millions of people and raising rates of morbidity and death across many demographic groups. An industrial chemical and common environmental contaminant, formaldehyde (FA) presents serious health concerns to the respiratory system, including the onset and aggravation of lung inflammatory disorders. Epidemiological studies have shown significant associations between FA exposure levels and the incidence and severity of several respiratory diseases. FA causes inflammation in the respiratory tract via immunological activation, oxidative stress, and airway remodelling, aggravating pre-existing pulmonary inflammation and compromising lung function. Additionally, FA functions as a respiratory sensitizer, causing allergic responses and hypersensitivity pneumonitis in sensitive people. Understanding the complicated processes behind formaldehyde-induced lung inflammation is critical for directing targeted strategies aimed at minimizing environmental exposures and alleviating the burden of formaldehyde-related lung illnesses on global respiratory health. This abstract explores the intricate relationship between FA exposure and lung inflammatory diseases, including asthma, bronchitis, allergic inflammation, lung injury and pulmonary fibrosis.
ncRNAs and their impact on dopaminergic neurons: Autophagy pathways in Parkinson's disease

Thapa R, Moglad E, Afzal M, Gupta G, Bhat AA, Almalki WH, et al.

Ageing Res Rev, 2024 Jul;98:102327.
PMID: 38734148 DOI: 10.1016/j.arr.2024.102327

Parkinson's Disease (PD) is a complex neurological illness that causes severe motor and non-motor symptoms due to a gradual loss of dopaminergic neurons in the substantia nigra. The aetiology of PD is influenced by a variety of genetic, environmental, and cellular variables. One important aspect of this pathophysiology is autophagy, a crucial cellular homeostasis process that breaks down and recycles cytoplasmic components. Recent advances in genomic technologies have unravelled a significant impact of ncRNAs on the regulation of autophagy pathways, thereby implicating their roles in PD onset and progression. They are members of a family of RNAs that include miRNAs, circRNA and lncRNAs that have been shown to play novel pleiotropic functions in the pathogenesis of PD by modulating the expression of genes linked to autophagic activities and dopaminergic neuron survival. This review aims to integrate the current genetic paradigms with the therapeutic prospect of autophagy-associated ncRNAs in PD. By synthesizing the findings of recent genetic studies, we underscore the importance of ncRNAs in the regulation of autophagy, how they are dysregulated in PD, and how they represent novel dimensions for therapeutic intervention. The therapeutic promise of targeting ncRNAs in PD is discussed, including the barriers that need to be overcome and future directions that must be embraced to funnel these ncRNA molecules for the treatment and management of PD.
Revolutionizing lung health: Exploring the latest breakthroughs and future prospects of synbiotic nanostructures in lung diseases

Bani Saeid A, De Rubis G, Williams KA, Yeung S, Chellappan DK, Singh SK, et al.

Chem Biol Interact, 2024 Apr 17;395:111009.
PMID: 38641145 DOI: 10.1016/j.cbi.2024.111009

The escalating prevalence of lung diseases underscores the need for innovative therapies. Dysbiosis in human body microbiome has emerged as a significant factor in these diseases, indicating a potential role for synbiotics in restoring microbial equilibrium. However, effective delivery of synbiotics to the target site remains challenging. Here, we aim to explore suitable nanoparticles for encapsulating synbiotics tailored for applications in lung diseases. Nanoencapsulation has emerged as a prominent strategy to address the delivery challenges of synbiotics in this context. Through a comprehensive review, we assess the potential of nanoparticles in facilitating synbiotic delivery and their structural adaptability for this purpose. Our review reveals that nanoparticles such as nanocellulose, starch, and chitosan exhibit high potential for synbiotic encapsulation. These offer flexibility in structure design and synthesis, making them promising candidates for addressing delivery challenges in lung diseases. Furthermore, our analysis highlights that synbiotics, when compared to probiotics alone, demonstrate superior anti-inflammatory, antioxidant, antibacterial and anticancer activities. This review underscores the promising role of nanoparticle-encapsulated synbiotics as a targeted and effective therapeutic approach for lung diseases, contributing valuable insights into the potential of nanomedicine in revolutionizing treatment strategies for respiratory conditions, ultimately paving the way for future advancements in this field.
Fulltext A global comparison of implementation and effectiveness of materiovigilance program: overview of regulations

Joshi D, Sharma I, Gupta S, Singh TG, Dhiman S, Prashar A, et al.

Environ Sci Pollut Res Int, 2021 Nov;28(42):59608-59629.
PMID: 34515931 DOI: 10.1007/s11356-021-16345-5

Medical devices, being life-saving tools, are considered to be a boon for healthcare system. However, in addition to their therapeutic effects, there are several ill consequences that are caused by these devices. An effective cohort vigilant system was needed to manage such adverse effects. This had led to the introduction of materiovigilance. Materiovigilance is the study and follow-up of occurrences that arise as a result from the usage of the medical equipment. It not only manages adverse events (AE) but also creates harmonization among countries. Keeping these objectives in focus, the principles, perspectives, and practices with regard to materiovigilance that are followed in the USA, Europe, China, Japan, Australia, Canada, and India are being compared. Such a comparison is essential, which will help us to understand the gaps in the current regulatory systems in the above-mentioned countries and furthermore will provide a comprehensive picture to the regulatory authorities to amend any existing laws if required. These amendments may ensure optimal patient safety by providing them a benign experience from the use of medical devices.
Fulltext Expanding Arsenal against Neurodegenerative Diseases Using Quercetin Based Nanoformulations: Breakthroughs and Bottlenecks

Vishwas S, Kumar R, Khursheed R, Ramanunny AK, Kumar R, Awasthi A, et al.

Curr Neuropharmacol, 2023;21(7):1558-1574.
PMID: 35950245 DOI: 10.2174/1570159X20666220810105421

Quercetin (Qu), a dietary flavonoid, is obtained from many fruits and vegetables such as coriander, broccoli, capers, asparagus, onion, figs, radish leaves, cranberry, walnuts, and citrus fruits. It has proven its role as a nutraceutical owing to numerous pharmacological effects against various diseases in preclinical studies. Despite these facts, Qu and its nanoparticles are less explored in clinical research as a nutraceutical. The present review covers various neuroprotective actions of Qu against various neurodegenerative diseases (NDs) such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic lateral sclerosis. A literature search was conducted to systematically review the various mechanistic pathways through which Qu elicits its neuroprotective actions and the challenges associated with raw Qu that compromise therapeutic efficacy. The nanoformulations developed to enhance Qu's therapeutic efficacy are also covered. Various ongoing/completed clinical trials related to Qu in treating various diseases, including NDs, are also tabulated. Despite these many successes, the exploration of research on Qu-loaded nanoformulations is limited mostly to preclinical studies, probably due to poor drug loading and stability of the formulation, time-consuming steps involved in the formulation, and their poor scale-up capacity. Hence, future efforts are required in this area to reach Qu nanoformulations to the clinical level.
Fulltext Recent Progress in Development of Dressings Used for Diabetic Wounds with Special Emphasis on Scaffolds

Awasthi A, Gulati M, Kumar B, Kaur J, Vishwas S, Khursheed R, et al.

Biomed Res Int, 2022;2022:1659338.
PMID: 35832856 DOI: 10.1155/2022/1659338

Diabetic wound (DW) is a secondary application of uncontrolled diabetes and affects about 42.2% of diabetics. If the disease is left untreated/uncontrolled, then it may further lead to amputation of organs. In recent years, huge research has been done in the area of wound dressing to have a better maintenance of DW. These include gauze, films, foams or, hydrocolloid-based dressings as well as polysaccharide- and polymer-based dressings. In recent years, scaffolds have played major role as biomaterial for wound dressing due to its tissue regeneration properties as well as fluid absorption capacity. These are three-dimensional polymeric structures formed from polymers that help in tissue rejuvenation. These offer a large surface area to volume ratio to allow cell adhesion and exudate absorbing capacity and antibacterial properties. They also offer a better retention as well as sustained release of drugs that are directly impregnated to the scaffolds or the ones that are loaded in nanocarriers that are impregnated onto scaffolds. The present review comprehensively describes the pathogenesis of DW, various dressings that are used so far for DW, the limitation of currently used wound dressings, role of scaffolds in topical delivery of drugs, materials used for scaffold fabrication, and application of various polymer-based scaffolds for treating DW.
Agarwood oil nanoemulsion counteracts LPS-induced inflammation and oxidative stress in RAW264.7 mouse macrophages

Malik R, Paudel KR, Manandhar B, De Rubis G, Shen J, Mujwar S, et al.

Pathol Res Pract, 2023 Nov;251:154895.
PMID: 37879146 DOI: 10.1016/j.prp.2023.154895

PURPOSE: Oxidative stress and inflammation are key pathophysiological features of chronic respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). Agarwood oil obtained from Aquilaria trees has promising antioxidant and anti-inflammatory activities. However, its clinical application is hampered by poor solubility. A viable approach to overcome this involves formulation of oily constituents into emulsions. Here, we have investigated the antioxidant and anti-inflammatory potential of an agarwood oil-based nanoemulsion (DE'RAAQSIN) against lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages in vitro.
METHODS: The antioxidant and anti-inflammatory activity of DE'RAAQSIN was assessed by measuring the levels of ROS and nitric oxide (NO) produced, using the DCF-DA assay and the Griess reagent assay, respectively. The molecular pathways activated by DE'RAAQSIN were investigated via qPCR.
RESULTS: LPS stimulation of RAW264.7 cells increased the production of nitric oxide (NO) and ROS and resulted in the overexpression of the inducible nitric oxide synthase (iNOS) gene. Furthermore, LPS induced the upregulation of the expression of key proinflammatory genes (IL-6, TNF-α, IL-1β, and CXCL1) and of the antioxidant gene heme oxygenase-1 (HO-1). DE'RAAQSIN demonstrated potent antioxidant and anti-inflammatory activity by significantly reducing the levels of ROS and of secreted NO, simultaneously counteracting the LPS-induced overexpression of iNOS, IL-6, TNF-α, IL-1β, and HO-1. These findings were corroborated by in silico activity prediction and physicochemical analysis of the main agarwood oil components.
CONCLUSIONS: We propose DE'RAAQSIN as a promising alternative managing inflammatory disorders, opening the platform for further studies aimed at understanding the effectiveness of DE'RAAQSIN.
Chitosan modified 5-fluorouracil nanostructured lipid carriers for treatment of diabetic retinopathy in rats: A new dimension to an anticancer drug

Sharma DS, Wadhwa S, Gulati M, Kumar B, Chitranshi N, Gupta VK, et al.

Int J Biol Macromol, 2023 Jan 01;224:810-830.
PMID: 36302483 DOI: 10.1016/j.ijbiomac.2022.10.168

Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina.
Fulltext Zerumbone liquid crystalline nanoparticles protect against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro

Paudel KR, Clarence DD, Panth N, Manandhar B, De Rubis G, Devkota HP, et al.

Naunyn Schmiedebergs Arch Pharmacol, 2024 Apr;397(4):2465-2483.
PMID: 37851060 DOI: 10.1007/s00210-023-02760-7

The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1β and Tnf-α, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma.
Nutraceuticals: unlocking newer paradigms in the mitigation of inflammatory lung diseases

Chan Y, Raju Allam VSR, Paudel KR, Singh SK, Gulati M, Dhanasekaran M, et al.

Crit Rev Food Sci Nutr, 2023;63(19):3302-3332.
PMID: 34613853 DOI: 10.1080/10408398.2021.1986467

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.
Fulltext Nutraceuticals and mitochondrial oxidative stress: bridging the gap in the management of bronchial asthma

Allam VSRR, Paudel KR, Gupta G, Singh SK, Vishwas S, Gulati M, et al.

Environ Sci Pollut Res Int, 2022 Sep;29(42):62733-62754.
PMID: 35796922 DOI: 10.1007/s11356-022-21454-w

Asthma is a chronic inflammatory disease primarily characterized by inflammation and reversible bronchoconstriction. It is currently one of the leading causes of morbidity and mortality in the world. Oxidative stress further complicates the pathology of the disease. The current treatment strategies for asthma mainly involve the use of anti-inflammatory agents and bronchodilators. However, long-term usage of such medications is associated with severe adverse effects and complications. Hence, there is an urgent need to develop newer, novel, and safe treatment modalities for the management of asthma. This has therefore prompted further investigations and detailed research to identify and develop novel therapeutic interventions from potent untapped resources. This review focuses on the significance of oxidative stressors that are primarily derived from both mitochondrial and non-mitochondrial sources in initiating the clinical features of asthma. The review also discusses the biological scavenging system of the body and factors that may lead to its malfunction which could result in altered states. Furthermore, the review provides a detailed insight into the therapeutic role of nutraceuticals as an effective strategy to attenuate the deleterious effects of oxidative stress and may be used in the mitigation of the cardinal features of bronchial asthma.
Nuclear factor-kappa B (NF-κB) inhibition as a therapeutic target for plant nutraceuticals in mitigating inflammatory lung diseases

Alharbi KS, Afzal O, Almalki WH, Kazmi I, Javed Shaikh MA, Thangavelu L, et al.

Chem Biol Interact, 2022 Feb 25;354:109842.
PMID: 35104489 DOI: 10.1016/j.cbi.2022.109842

Nutraceuticals are dietary supplements that are used to improve health, postpone aging, prevent illnesses, and maintain the human body's correct functioning. Nutraceuticals are now garnering a lot of interest because of their nutritional and therapeutic benefits. The research indicating the relevance of nutraceuticals as a possible therapeutic candidate against inflammatory lung disease was covered in this review. Nowadays, inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma, pneumonia, lung cancer, becoming highly dreadful because of their associated fatality. Inflammation is one of the cores and common factors of these diseases which is mainly associated with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, NF-κB p65 and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation, and initiation of the signaling pathway of the NF-κB. The secondary metabolites from natural sources are the active component that attenuates NF-κB and the associated pathway that inhibits inflammation in lung diseases. Nutraceuticals belonging to the chemical category polyphenols, alkaloids, terpenoids, flavonoids, tannins have the potential to combat the NF-κB pathway. Accordingly, this review discusses the medical value of nutraceuticals briefly and their ability to mitigate various inflammatory lung diseases through targeting inhibition of NF-κB.
Fulltext Evidence of Coronavirus (CoV) Pathogenesis and Emerging Pathogen SARS-CoV-2 in the Nervous System: A Review on Neurological Impairments and Manifestations

Jha NK, Ojha S, Jha SK, Dureja H, Singh SK, Shukla SD, et al.

J Mol Neurosci, 2021 Nov;71(11):2192-2209.
PMID: 33464535 DOI: 10.1007/s12031-020-01767-6

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.
Proteostasis disruption and senescence in Alzheimer's disease pathways to neurodegeneration

Thapa R, Ahmad Bhat A, Shahwan M, Ali H, PadmaPriya G, Bansal P, et al.

Brain Res, 2024 Dec 15;1845:149202.
PMID: 39216694 DOI: 10.1016/j.brainres.2024.149202

Alzheimer's Disease (AD) is a progressive neurological disease associated with behavioral abnormalities, memory loss, and cognitive impairment that cause major causes of dementia in the elderly. The pathogenetic processes cause complex effects on brain function and AD progression. The proper protein homeostasis, or proteostasis, is critical for cell health. AD causes the buildup of misfolded proteins, particularly tau and amyloid-beta, to break down proteostasis, such aggregates are toxic to neurons and play a critical role in AD pathogenesis. The rise of cellular senescence is accompanied by aging, marked by irreversible cell cycle arrest and the release of pro-inflammatory proteins. Senescent cell build-up in the brains of AD patients exacerbates neuroinflammation and neuronal degeneration. These cells senescence-associated secretory phenotype (SASP) also disturbs the brain environment. When proteostasis failure and cellular senescence coalesce, a cycle is generated that compounds each other. While senescent cells contribute to proteostasis breakdown through inflammatory and degradative processes, misfolded proteins induce cellular stress and senescence. The principal aspects of the neurodegenerative processes in AD are the interaction of cellular senescence and proteostasis failure. This review explores the interconnected roles of proteostasis disruption and cellular senescence in the pathways leading to neurodegeneration in AD.

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