Browsing by Author "Subhashini"

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Basic overview of human physiology
(Elsevier, 2020) Atul Srivastava; Mrinalini Kumari; Dinesh Prasad Gond; Subhashini
Physiology has been defined as the branch of science dedicated to analyze and understand all the events, activities and functions of the living system. It is the study of normal function and vital processes of living organism. Classified as the sub-section and subdivision of biology and zoology, it covers a range of subject that include organs, anatomy, cells, biological compounds, and how they all interact to make life possible. The different division of physiology are only the various attempts to approach and understand the same problem from different angle. System biology considers all living phenomena as emergent properties due to interface among components of the system. Each system is highly complicated and each functions properly only when it cooperates with the other in maintaining the proper internal environment. The present knowledge of physiology has already assumed gigantic proportion and recent researches are adding everyday something new to it. The present review gives an idea about the major human physiological process like movement, digestion, respiration, blood circulation their composition and functioning and how each system are interrealated affecting functioning of other regulating the body function. © 2020 Elsevier Inc. All rights reserved.
Blocking μ-opioid receptor by naltrexone exaggerates oxidative stress and airway inflammation via the MAPkinase pathway in a murine model of asthma
(Elsevier Inc., 2024) Vinita Pandey; Vandana Yadav; Atul Srivastava; Pratikkumar Gaglani; Rashmi Singh; Subhashini
Opioids regulate various physiological and pathophysiological functions, including cell proliferation, immune function, obesity, and neurodegenerative disorders. They have been used for centuries as a treatment for severe pain, binding to opioid receptors a specific G protein-coupled receptor. Common opioids, like β-endorphin, [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO), and dynorphins, have analgesic effects. The use of a potent antagonist, like naltrexone hydrochloride, to block the effects of mu Opioid Receptor (μOR) may result in the withdrawal of physiological effects and could potentially impact immune responses in many diseases including respiratory disease. Asthma is a respiratory disease characterized by airway hyperresponsiveness, inflammation, bronchoconstriction, chest tightness, stress generation and release of various cytokines. Airway inflammation leads recruitment and activation of immune cells releasing mediators, including opioids, which may modulate inflammatory response by binding to their respective receptors. The study aims to explore the role of μOR antagonist (naltrexone) in regulating asthma pathophysiology, as the regulation of immune and inflammatory responses in asthma remains unclear. Balb/c mice were sensitized intranasally by 1% TDI and challenged with 2.5% TDI. Naltrexone hydrochloride (1 mg/kg body weight) was administered through intraperitoneal route 1 h before TDI induction. Blocking μOR by naltrexone exacerbates airway inflammation by recruiting inflammatory cells (lymphocytes and neutrophils), enhancing intracellular Reactive oxygen species in bronchoalveolar lavage fluid (BALF), and inflammatory mediator (histamine, Eosinophil peroxidase and neutrophil elastase) in lungs. Naltrexone administration modulated inflammatory cytokines (TNF-α, IL-4, IL-5, IL-6, IL-10, and IL-17A), and enhanced IgE and CRP levels. Naltrexone administration also increased the expression of NF-κB, and phosphorylated p-P38, p-Erk, p-JNK and NF-κB by inhibiting the μOR. Docking study revealed good binding affinity of naltrexone with μOR compared to δ and κ receptors. In future it might elucidate potential therapeutic against many respiratory pathological disorders. In conclusion, μOR blocking by naltrexone regulates and implicates inflammation, bronchoconstriction, and lung physiology. © 2023 Elsevier Inc.
Combination Therapy with Curcumin Alone Plus Piperine Ameliorates Ovalbumin-Induced Chronic Asthma in Mice
(Springer New York LLC, 2018) Preeti S. Chauhan; Anju Jaiswal; Subhashini; Rashmi Singh
Allergic asthma is an inflammatory condition accompanied by inflammation as well as oxidative stress. Supplementation of an anti-inflammatory agent having antioxidant properties may have therapeutic effects against this disease. Over the recent decades, the interest in combination therapy as new alternative medication has increased and it offers numerous benefits along with noticeable lack of toxicity as well as side effects. In this study, protective effects of curcumin alone and in combination with piperine were evaluated in mouse model of allergic asthma. Balb/c mice were sensitized on days 0, 7, and 14 and challenged from days 16–30 on alternate days with ovalbumin (OVA). Mice were pretreated with curcumin (Cur; 10 and 20 mg/kg) and piperine (Pip; 5 mg/kg) alone and in combination via the intraperitoneal route on days 16–30 and compared with intranasal curcumin (5 mg/kg) treatment. Blood, bronchoalveolar lavage fluid (BALF), and lungs were collected after mice were sacrificed on day 31st. Mice immunized with OVA have shown significant increase in airway inflammation and oxidative stress as determined by oxidative stress markers. A significant suppression was observed with all the treatments, but intranasal curcumin treatment group has shown maximum suppression. So, among all the treatment strategies utilized, intranasal curcumin administration was most appropriate in reducing inflammation and oxidative stress and possesses therapeutic potential against allergic asthma. Present study may prove the possibility of development of curcumin nasal drops towards treatment of allergic asthma. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
Current and future prospects of nanoparticles to combat bacterial infections
(Elsevier, 2022) Dinesh Prasad Gond; Atul Srivastava; Subhashini; Anjney Sharma; Kumari Mrinalini
Bacterial infections are a major public health problem that result high morbidity and mortality. There are several options for antibacterial therapy, however, their efficacies are limited, particularly due to the developing resistance mechanism. In the past decade, a great advance in nanomedicine has shown promise for the treatment of bacterial infection. In the current perspective for medicine application or medical therapies, nanotechnology using nanoscale materials is increasingly being utilized for clinical applications, especially as a new paradigm to combat bacterial infections. The nanoparticles can act as antibacterial agents or carriers for loading antibacterial drugs to promote the bioavailability and effectiveness of antibiotics. Nanoparticles may penetrate the cell membrane of pathogenic microorganisms and interfere with important molecular pathways, formulating unique antimicrobial mechanisms. These particles have also demonstrated synergy in combination with optimal antibiotics and may aid in limiting the global crisis of emerging bacterial resistance. In the current chapter, we have highlighted and summarized the potentially significant impact of nanoparticles as antibacterial agents, the recent progress on the development of antibacterial nanoparticles, and the subsequent approaches and challenges for clinical applications. This chapter offers an overview of the current and future prospects of antibacterial nanosystems. © 2023 Elsevier Inc. All rights reserved.
Dual blockade of TLR-4 and mu-opioid receptor by very low-dose naltrexone prevents respiratory depression via modulating redox homeostasis and airway inflammation in chronic obstructive pulmonary disease
(Elsevier Inc., 2025) Soni; Vandana Yadav; Vinita Pandey; Atul Kumar Srivastava; Pratikkumar Gaglani; Subhashini
Chronic Obstructive Pulmonary Disease (COPD), is characterized by poorly irreversible airflow obstruction and abnormal inflammatory response in lungs. It represents an innate and adaptive immune response to long term exposure to noxious particles and gases, particularly cigarette smoke (CS). The current pharmacological treatment of COPD is symptomatic and mainly based on the use of bronchodilators reducing the lung function progression. The present study explores a comprehensive exploration into the therapeutic potential of Naltrexone (NTX), an FDA-approved non-peptide opioid antagonist, in managing COPD pathogenesis. NTX exhibits distinct responses across varying dosages where it implies a dose pharmacological profile, with dose-dependent targets yielding diverse effects. The study aims to uncover its efficacy in experimental mice model of COPD by observing redox homeostasis, inflammatory responses, and apoptosis encompassing variable doses. Our findings reveal promising outcomes, particularly with VLDN (100 μg/kgbw and 50 μg/kgbw), where a significant reduction in ROS, NO and positive impacts on TOS and TAS, was observed which indicates its potential as an oxidative stress modulator. Furthermore, VLDN modulated the antioxidant enzymatic activity thereby reducing the apoptotic phenomenon via caspase-3. VLDN significantly reduced the inflammatory response by inhibiting the inflammatory mediators (histamine, LDH and CRP) and suppressing cytokine production (TNF-α, IFN-γ and IL-6). The study also delved into intricate pathway where mechanistically VLDN exerted anti-inflammatory effect by inhibiting the activation of NF-kB/MAPK signalling via TLR4. These findings collectively highlight VLDN multifaceted impact in mitigating oxidative stress, inflammation influencing apoptosis in COPD management, offering valuable insights for future therapeutic strategies. © 2025
Inhibiting SIRT-2 by AK-7 restrains airway inflammation and oxidative damage promoting lung resurgence through NF-kB and MAP kinase signaling pathway
(Frontiers Media SA, 2024) Vandana Yadav; Vinita Pandey; Pratikkumar Gaglani; Atul Srivastava; Soni; Subhashini
Introduction: Chronic obstructive pulmonary disease (COPD) is a major global cause of mortality with limited effective treatments. Sirtuins (SIRT) are histone deacetylases that are involved in the regulation of redox and inflammatory homeostasis. Hence, the present study aims to investigate the role of SIRT-2 in modulating inflammation in a murine model of COPD. Methods: COPD in mice was established by cigarette smoke (CS) exposure for 60 days, and AK-7 was used as the specific SIRT-2 inhibitor. AK-7 (100 µg/kg and 200 µg/kg body weight) was administered intranasally 1 h before CS exposure. Molecular docking was performed to analyze the binding affinity of different inflammatory proteins with AK-7. Results: Immune cell analysis showed a significantly increased number of macrophages (F4/80), neutrophils (Gr-1), and lymphocytes (CD4+, CD8+, and CD19+) in the COPD, group and their population was declined by AK-7 administration. Total reactive oxygen species, total inducible nitric oxide synthase, inflammatory mediators such as neutrophil elastase, C-reactive protein, histamine, and cytokines as IL4, IL-6, IL-17, and TNF-α were elevated in COPD and declined in the AK-7 group. However, IL-10 showed reverse results representing anti-inflammatory potency. AK-7 administration by inhibiting SIRT-2 decreased the expression of p-NF-κB, p-P38, p-Erk, and p-JNK and increased the expression of Nrf-2. Furthermore, AK-7 also declined the lung injury by inhibiting inflammation, parenchymal destruction, emphysema, collagen, club cells, and Kohn pores. AK-7 also showed good binding affinity with inflammatory proteins. Discussion: The current study reveals that SIRT-2 inhibition mitigates COPD severity and enhances pulmonary therapeutic interventions, suggesting AK-7 as a potential therapeutic molecule for COPD medication development. Copyright © 2024 Yadav, Pandey, Gaglani, Srivastava, Soni and Subhashini.
Intranasal curcumin ameliorates airway inflammation and obstruction by regulating MAPKinase activation (p38, Erk and JNK) and prostaglandin D2 release in murine model of asthma
(Elsevier B.V., 2016) Subhashini; Preeti S. Chauhan; D. Dash; B.N. Paul; Rashmi Singh
Asthma, a multifactorial, chronic inflammatory disease encompasses multiple complex pathways releasing number of mediators by activated mast cells, eosinophils and T lymphocytes, leading to its severity. Presently available medications are associated with certain limitations, and hence, it is imperative to search for anti-inflammatory drug preferably targeting signaling cascades involved in inflammation thereby suppressing inflammatory mediators without any side effect. Curcumin, an anti-inflammatory molecule with potent anti-asthmatic potential has been found to suppress asthmatic features by inhibiting airway inflammation and bronchoconstriction if administered through nasal route. The present study provides new insight towards anti-asthmatic potential of intranasal curcumin at lower doses (2.5 and 5.0 mg/kg) in Balb/c mice sensitized and challenged with ovalbumin (OVA) which is effective in inhibiting airway inflammation. These investigations suggest that intranasal curcumin (2.5 and 5.0 mg/kg) regulates airway inflammation and airway obstruction mainly by modulating cytokine levels (IL-4, 5, IFN-y and TNF-α) and sPLA2 activity thereby inhibiting PGD2 release and COX-2 expression. Further, the suppression of p38 MAPK, ERK 42/44 and JNK54/56 activation elucidate the mechanism behind the inhibitory role of intranasal curcumin in asthma progression. Thus, curcumin could be better alternative for the development of nasal formulations and inhalers in near future. © 2015 Elsevier B.V. All rights reserved.
Intranasal curcumin and its evaluation in murine model of asthma
(2013) Subhashini; Preeti S. Chauhan; Sharda Kumari; Jarajana Pradeep Kumar; Ruchi Chawla; D. Dash; Mandavi Singh; Rashmi Singh
Curcumin, a phytochemical present in turmeric, rhizome of Curcuma longa, has been shown to have a wide variety of pharmacological activities including anti-inflammatory, anti-allergic and anti-asthmatic properties. Curcumin is known for its low systemic bioavailability and rapid metabolization through oral route and has limited its applications. Over the recent decades, the interest in intranasal delivery as a non-invasive route for drugs has increased as target tissue for drug delivery since nasal mucosa offers numerous benefits. In this study, we evaluated intranasal curcumin following its absorption through nasal mucosa by a sensitive and validated high-performance liquid chromatography (HPLC) method for the determination of intranasal curcumin in mouse blood plasma and lung tissue. Intranasal curcumin has been detected in plasma after 15 min to 3 h at pharmacological dose (5 mg/kg, i.n.), which has shown anti-asthmatic potential by inhibiting bronchoconstriction and inflammatory cell recruitment to the lungs. At considerably lower doses has proved better than standard drug disodium cromoglycate (DSCG 50 mg/kg, i.p.) by affecting inflammatory cell infiltration and histamine release in mouse model of asthma. HPLC detection revealed that curcumin absorption in lungs has started after 30 min following intranasal administration and retained till 3 h then declines. Present investigations suggest that intranasal curcumin (5.0 mg/kg, i.n.) has effectively being absorbed and detected in plasma and lungs both and suppressed airway inflammations at lower doses than the earlier doses used for detection (100-200 mg/kg, i.p.) for pharmacological studies (10-20 mg/kg, i.p.) in mouse model of asthma. Present study may prove the possibility of curcumin as complementary medication in the development of nasal drops to prevent airway inflammations and bronchoconstrictions in asthma without any side effect. © 2013 Elsevier B.V.
Intranasal curcumin attenuates airway remodeling in murine model of chronic asthma
(Elsevier, 2014) Preeti S. Chauhan; Subhashini; D. Dash; Rashmi Singh
Curcumin, phytochemical present in turmeric, rhizome of Curcuma longa, a known anti-inflammatory molecule with variety of pharmacological activities is found effective in murine model of chronic asthma characterized by structural alterations and airway remodeling. Here, we have investigated the effects of intranasal curcumin in chronic asthma where animals were exposed to allergen for longer time. In the present study Balb/c mice were sensitized by an intraperitoneal injection of ovalbumin (OVA) and subsequently challenged with 2% OVA in aerosol twice a week for five consecutive weeks. Intranasal curcumin (5 mg/kg) was administered from days 21 to 55, an hour before every nebulization and inflammatory cells recruitment, levels of IgE, EPO, IL-4 and IL-5 were found suppressed in bronchoalveolar lavage fluid (BALF). Intranasal curcumin administration prevented accumulation of inflammatory cells to the airways, structural alterations and remodeling associated with chronic asthma like peribronchial and airway smooth muscle thickening, sloughing off of the epithelial lining and mucus secretion in ovalbumin induced murine model of chronic asthma. © 2014 Elsevier B.V.
Microbial biofilms and their role in acute and chronic pathogenesis
(Elsevier, 2024) Atul Srivastava; Mrinalini Kumari; Dinesh Prasad Gond; Subhashini
The context of microorganism living within the commune rather than merely as autonomous individual is one of the quickly gaining acceptances. These communities of the organism residing within the extracellular polymeric substance matrix are termed biofilms. A biofilm is an assembly of microbial cells that is irretrievably linked with a surface and covered primarily in a matrix of polysaccharide material. The ability to figure biofilms is a universal attribute of all microorganisms including bacteria. Biofilms may impact human health both positively and negatively. With the tendency to grow anywhere on abiotic as well as biotic surfaces, these act as a potent source of various infections. The rising burden of several diseases caused by microbial infections implies an immense menace to global health. Biofilm formation has been confirmed in numerous pathogens and is evidently mentioned as an important strategy for microbial survival. This chapter provides an overview on biofilms, their structure and formation, and their impact on human health. The current chapter also entails light on the involvement of biofilms in pulmonary infections and existing strategies employed for the treatment. © 2024 Elsevier Inc. All rights reserved.
Network pharmacology and molecular docking insights into Sirtuin-2 inhibitors (AK-7 and AGK-2): A synergistic strategy for COPD treatment
(Elsevier B.V., 2025) Vandana Yadav; Vinita Pandey; Pratikkumar Gaglani; Atul Kumar Srivastava; Soni; Subhashini
Objective: In the present study network pharmacology analysis of AGK-2 and AK-7 (SIRT-2 inhibitors) were performed to elucidate their mechanism in regulating COPD pathogenesis. Methods: Different database (Swiss Target Prediction, GeneCards and DisGeNet) were used for predicting targets of compound and disease. Drug-Target network was constructed using Cytoscape while functional enrichment and pathway analyses were performed using STRING database. ShinnyGo database was utilized for Annotation, Visualization, and Integrated Discovery, along with Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG). Molecular docking was performed to assess the binding affinities of AGK-2 and AK-7 to key proteins. Results: AK-7 and AGK2 revealed 43 and 41 targets while 3392 targets related to COPD were found. Protein-protein interaction (PPI) network revealed 43 nodes and 133 edges for AK-7 and 41 nodes and 110 edges for AGK-2. Enrichment analysis highlighted distinct involvement of AGK-2 and AK-7 in various aspects of respiratory physiology including molecular signaling and neuronal secretions. AGK-2 revealed to influence pathways as EGFR and Ras/Raf/MAPK, while AK-7 targeted pathways like nitric oxide synthatase and tuberculosis, as well as regulating calcium signaling and neuro-immune interactions associated with COPD. Finally molecular docking revealed that AGK-2 showed good binding affinity with MAPK14 and STAT3. Whereas AK-7 with CASP3 and CXCL8. The findings highlight potency of AGK-2 and AK-7 in modulating inflammation, reactive oxygen species, and neuroimmune interactions, suggesting their efficacy in COPD management through SIRT-2 regulation. Conclusion: The study offers novel insights into the potential of SIRT-2 inhibitors to modulate disease mechanisms at a molecular level. © 2024 Elsevier B.V.
Ovalbumin-induced allergic inflammation lead to structural alterations in mouse model and protective effects of intranasal curcumin: A comparative study
(Elsevier Doyma, 2016) Subhashini; P.S. Chauhan; R. Singh
Background: Antigen exposure and persistent inflammation leads to structural changes in the asthmatic airways which are collectively termed as "airway remodelling". Presently available asthma medications ameliorate inflammations but are unable to prevent or reverse the airway remodelling process as most of the treatment strategies are only focused on inflammation instead of remodelling. Methods: Curcumin, a phytochemical present in the rhizome of Curcuma longa is well known for its anti-inflammatory activity; however, the main drawback is its poor bioavailability which limits its therapeutic approval. So, the effect of nasal curcumin on acute and chronic asthma has been studied where short exposure to ovalbumin (4 days) represents acute phase whereas repeated exposures for longer (twice per week till 5 weeks) represents chronic asthma. Disodium cromoglycate (DSCG, 50 mg/kg, i.p.) and dexamethasone (1 mg/kg, i.p.) were used as standard drugs in acute and chronic model of asthma respectively. Results: OVA-induced airway inflammation initiated in acute stage led to remodelling due to persistent inflammation, epithelial and sub epithelial thickening (smooth muscle thickening), extracellular matrix (ECM) deposition, goblet cell hyperplasia and mucus plug formation. Intranasal curcumin is effective in inhibiting airway inflammation and remodelling both by maintaining the structural integrity of lungs in terms of inflammation, airway wall thickening and mucus production. Conclusion: Our findings suggest that curcumin administered through nasal route might prove therapeutically efficient in inhibiting allergic airway inflammations and maintaining structural integrity in the mouse model of allergic asthma. This may lead to the development of curcumin aerosol in near future. © 2016 SEICAP.
Pharmacological inhibition of SIRT-2 by AK-7 modulates redox status and apoptosis via regulating Nrf2 in an experimental model of chronic obstructive pulmonary disease: an invivo and insilico study
(Taylor and Francis Ltd., 2023) Vandana Yadav; Vinita Pandey; Atul Srivastava; Sangita Singh; Subhashini
Chronic obstructive pulmonary disease (COPD) is defined by inflammation and emphysema. Sirtuins (SIRT) are NAD+-dependent histone deacetylases that regulate oxidative stress and inflammation. The present work investigates the modulatory role of SIRT-2 in experimental COPD model. Insilico comparative assessment of SIRT-2 inhibitors (AK-7 and AGK-2) by ADMET and molecular docking revealed AK-7 as suitable candidate for invivo application. COPD in mice was established by cigarette smoke (CS) exposure for 2 months. AK-7 (100 µg/kg and 200 µg/kg body weight) was administered intranasally one hour before CS exposure. The present investigation demonstrates that CS exposure increases total cell count, and free radical production (total reactive oxygen species, total oxidant status, myeloperoxidase, and nitric oxide), which were decreased by AK-7. It also altered antioxidant enzymatic activity (total antioxidant status, catalase, superoxide dismutase, glutathione peroxidase, glutathione-s-transferase, glutathione reductase, and reduced glutathione), hence preserving the redox balance. AK-7 significantly decreases apoptosis, protein carbonylation, lipid peroxidation, TNF-α and IFN-ﻻ levels represent COPD generation in mice and were dramatically decreased by AK-7. Histopathological studies shows that CS exposure damages alveoli and produces peribronchiolar inflammation; both of these events were reduced by AK-7. The antioxidative potency of AK-7 was confirmed by observing Nrf2 and Keap1 proteins. Keap-dependent Nrf2 regulation was observed, with cytosolic Nrf2 and Keap1 expression elevated in COPD and reduced in the AK-7 group while nuclear Nrf2 was reduced in COPD and increased in the AK-7 group. The present study concludes that inhibition of SIRT-2 minimizes COPD severity and mediates therapeutic effects in the lungs. © 2023 Informa UK Limited, trading as Taylor & Francis Group.
Potential of hydroethanolic leaf extract of Ocimum sanctum in ameliorating redox status and lung injury in COPD: an in vivo and in silico study
(Nature Research, 2023) Atul Srivastava; Subhashini; Vinita Pandey; Vandana Yadav; Sangita Singh; Ragini Srivastava
Oxidative stress and inflammation are hypothesised as the main contributor for Chronic Obstructive Pulmonary Disease (COPD). Cigarette smoke (CS), a major cause of COPD leads to inflammation resulting in recruitment of neutrophils and macrophages which are rich sources of oxidants. Activation of these cells produces excess oxidants and depletes antioxidants resulting in stress. Presently, effective drug for COPD is limited; therefore, novel compounds from natural sources, including plants are under exploration. The present study aims to investigate the protective effect of Ocimum sanctum leaf extract (OLE) in CS − induced model of COPD. Exposure to CS was performed thrice a week for 8 weeks and OLE (200 mg/kg and 400 mg/kg) was administered an hour before CS exposure. Control group (negative control) were exposed to ambient air while COPD group was exposed to CS (positive control). Administration of OLE doses reduced inflammation, decreased oxidant concentration and increased antioxidant concentration (p < 0.01). Molecular docking studies between the major phytocompounds of OLE (Eugenol, Cyclohexane and Caryophyllene) and antioxidant enzymes Superoxide dismutase (SOD), Catalase, Glutathione peroxidase (GPx), Glutathione reductase (GR) and Glutathione S Transferase (GST) showed strong binding interaction in terms of binding energy. In vivo and in silico findings for the first time indicates that OLE extract significantly alleviates oxidative stress by its potent free radical scavenging property and strong interaction with antioxidant enzymes. OLE extract may prove to be a therapeutic option for COPD prevention and treatment. © 2023, The Author(s).
Profiling of human genes afflicted with nasopharyngeal carcinoma using microarray data
(Elsevier B.V., 2025) Rupam Raj; Subhashini; Kamalesh Kumar Kumar Patel; Mukesh Sunil Kumar
Background Nasopharyngeal carcinoma (NPC) is the most prevalent malignant carcinoma, and yet the biological mechanisms behind its pathogenesis are still unknown. Objective The objective of the research work was to apply bioinformatics tools to determine the essential expressed genes linked to NPC pathogenesis. Material and methods We retrieved three datasets (GSE12452, GSE13597, and GSE64634), from the Gene Expression Omnibus (GEO) portal. Differentially expressed genes (DEGs) determined between two groups called normal and NPC tissues. Gene ontology enrichment analysis (GO) performed through the online tool DAVID, and Kyoto Encyclopedia of Genes and Genomes (KEGG) online database used to identify pathways and progressions in which DEGs are highly involved in disease progression. Results We identified 77 commonly upregulated, 62 common downregulated in total 140 common DEGs in 3 datasets. The key cancer-causing pathways found in our study were mostly regulating cell adhesion molecules, Akt signalling pathway, cell cycle, cytochrome P450 and one carbon pool by folate. The interaction is shown between these DEGs through a protein protein interaction (PPI) network using STRING software and try to understand the effect these genes have on each other and noticed the most influential genes by studying their topological connectivity. The most influential genes, hub genes were identified by creating modules upon analysis of these modules. Conclusions We got 4 hub genes namely Aurora A (AURKA), Breast cancer susceptibility gene 1 (BRCA1), Fanconi anaemia group I protein (FANCI), and Abnormal spindle microtubule assembly (ASPM). For validation, we performed a survival analysis using GEPIA against the TCGA database, all four hub genes were upregulated in carcinoma cases compared to normal cases. These four biomarkers found can be used as potential therapeutic targets and as molecular signatures for early detection of NPC. © 2024
Protective effect of neem leaf extract and dexamethasone in cigarette-smoke induced liver and kidney injury in Swiss mice: A comparative analysis
(Horticulture and Forestry Society from Transylvania, 2024) Anushree Verma; Subhashini; Vishal Srivashtav; Abhinav Singh
Cigarette smoke (CS) is one of the leading causes of lung injury where co-morbidity in different organs including liver and kidney can be observed. CS contributes as one of the causes of mortality across the globe. Dexamethasone, a corticosteroid is widely used as an anti-inflammatory medication despite being associated with several side effects with long-term usage. Therefore, the present study focused on the comparison between dexamethasone and Azadirachta indica leaf extract (AILE) for treating hepatic and renal injury caused by CS in mice. The phytochemical screening of AILE revealed the abundance of phytocompounds as sterols, proteins, alkaloids, flavonoids and diterpenes that might have antioxidant and anti-inflammatory activity. In this context, Swiss mice were treated with CS, dexamethasone and AILE. CS-induced mice expressed elevated inflammatory cells, Reactive Oxygen Species (ROS) with higher levels of both liver and kidney function markers: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and creatinine respectively which was reversed by AILE. No mortality was observed in CS or AILE-treated group while dexamethasone-treated mice exclusively resulted in 20% mortality. Moreover, CS-induced mice also exhibited declined SOD levels in the liver and kidney and higher Eosinophil peroxidase (EPO) which was modulated by AILE treatment. This is the first report demonstrating in vivo the effects of A. indica ethanolic leaf extract in treating CS-induced hepatic and renal chronic inflammation in an animal model which gave better results when compared to dexamethasone. © Articles by the authors; Licensee SMTCT, Cluj-Napoca, Romania.
Recent applications of nanomedicine in lung disease
(Elsevier, 2022) Atul Srivastava; Mrinalini Kumari; Dinesh Prasad Gond; Subhashini
Lung diseases include a wide spectrum of illnesses, such as asthma, COPD (chronic obstructive pulmonary disease), pneumonia, tuberculosis, lung cancers, and the recent COVID-19 pandemic, and have been a huge threat to human health and life. However, the treatment and diagnosis of various lung diseases are challenging. Among the several treatment strategies and diagnostic techniques, the adverse effect to chemotherapy in cancers, multidrug resistance in tuberculosis, side effects, toxicity, poor drug delivery, and metabolism require the development of novel and promising alternative treatments. Nanotechnology provides a promising tool for the development of innovative treatment overcoming many drug challenges. Nanotechnology being widely studied in medicinal field has given rise to the interdisciplinary nanomedicine field allowing fundamental changes in the diagnosis, treatment, and prevention of disease. Lungs provide a good target organ for drug delivery via an aerosol inhalation mode. Lungs provide a large surface area for local drug action and systemic drug absorption and hence nanomedicines have been a boon in treating many of the lung diseases without leading to any side effects or toxicity. The present chapter aims to review nanoparticles-based drug delivery systems studied over the last decade as therapeutic agents in lung diseases. © 2023 Elsevier Inc. All rights reserved.
Screening of essential oils of angiospermic plants for their fungitoxicity against Aspergillus Flavus and Aspergillus Niger
(International Journal of Pharma and Bio Sciences, 2015) Atul Srivastava; Pradeep Kumar Shukla; Ashwini Kumar Mishra; Subhashini; Suchit John
Essential oils obtained from plants have recently gained a great scientific interest as a potent source of antimicrobials of natural origin. The present study highlights the antifungal activity of essential oils against Aspergillus flavus and Aspergillus niger. During screening of essential oils of six selected Angiospermic plants at 2000 ppm (mg/l) against the test fungus, Mentha arvensis and Citrus aurantifolia, being most effective was selected for further study. The selected oils were subsequently standardized through physicochemical and fungitoxic properties. The MIC values of Mentha arvensis and Citrus aurantifolia were found to be 1000 and 2000 ppm (mg/l) respectively. Fungitoxicity of both oils represents fungicidal, as well as fungistatic behavior at their respective MIC(s). Study also revealed that oil of Mentha arvensis and Citrus aurantifoila are highly thermo stable (up to 80°C) and had the potency to withstand high inoculum density. The fungitoxicity of both the oils remained unaltered up to 180-210 days at room temperature. The antifungal potency of oils was found greater when compared with some prevalent synthetic commercial fungicides. Therefore oils could be recommended as a potential source of ecofriendly herbal fungicide and might have role as pharmaceutical and preservatives.
SIRT-2 inhibition by AK-7 orchestrates fibrotic cascades in airways through neuroimmune interaction via TRPA1, TRPM8 and TGF-β signalling
(Elsevier Inc., 2025) Vandana Yadav; Vinita Pandey; Pratikkumar Gaglani; Atul Kumar Srivastava; Soni; Subhashini
Chronic obstructive pulmonary diseases (COPD) is characterized by airflow limitation, chronic inflammation and airway remodeling (AR) in airways and lung parenchyma. AR, a lung response, involves mucus production, airflow issues, and structural changes. It is exacerbated by neurogenic inflammation from activated sensory nerves, highlighting the interplay between neuronal and immune regulation in COPD. Sirtuins play a crucial role in lung remodeling, with SIRT-2 being the least studied. Present study explores how SIRT-2 regulates neurogenic inflammation and fibrosis in experimental BALB/c mice with cigarette smoke-induced COPD. Mice from each group, except the control, were exposed to CS for 60 days and AK-7 (100ug/kg and 200ug/kg) was administered intranasally. The study evaluated lung injury and inflammation marked by increased Cortisol, ACTH, COX-2 and LDH in COPD group with its attenuation by SIRT-2 inhibition. Additionally, CS exposure exhibited neurogenic inflammation represented by activated TPRV1 and TRPM8, elevated neuromediators levels (dopamine, acetylcholine, substance P, serotonin) and their respective receptors which were mitigated by AK-7. CS exposure enhanced fibrosis by targeting the fibrotic cascade, enhancing MMP-9, total collagen, hydroxyproline, and upregulating αSMA, MUC5AC, TGF-β, PKA, GATA-3, FOXO3, and STAT-6. SIRT-2 inhibition effectively reversed all these factors suppressing fibrosis further supported by downregulated SIRT-2 expression and histopathological studies where collagen deposition and mucus production were also attenuated by AK-7. Molecular docking revealed strong binding affinity of certain protein such as COX-2, D5DR and 5HT with AK-7. Overall, targeting SIRT-2 to modulate neuro-immune interplay presents a promising therapeutic approach for addressing AR in COPD. © 2024 Elsevier Inc.
β-Endorphin (an endogenous opioid) inhibits inflammation, oxidative stress and apoptosis via Nrf-2 in asthmatic murine model
(Nature Research, 2023) Vinita Pandey; Vandana Yadav; Rashmi Singh; Atul Srivastava; Subhashini
Asthma, a chronic respiratory disease is characterized by airway inflammation, remodelling, airflow limitation and hyperresponsiveness. At present, it is considered as an umbrella diagnosis consisting several variable clinical presentations (phenotypes) and distinct pathophysiological mechanisms (endotypes). Recent evidence suggests that oxidative stress participates in airway inflammation and remodelling in chronic asthma. Opioids resembled by group of regulatory peptides have proven to act as an immunomodulator. β-Endorphin a natural and potent endogenous morphine produced in the anterior pituitary gland play role in pain modulation. Therapeutic strategy of many opioids including β-Endorphin as an anti‑inflammatory and antioxidative agent has not been yet explored despite its promising analgesic effects. This is the first study to reveal the role of β-Endorphin in regulating airway inflammation, cellular apoptosis, and oxidative stress via Nrf-2 in an experimental asthmatic model. Asthma was generated in balb/c mice by sensitizing with 1% Toulene Diisocyanate on day 0, 7, 14 and 21 and challenging with 2.5% Toulene Diisocyanate from day 22 to 51 (on every alternate day) through intranasal route. β-Endorphin (5 µg/kg) was administered through the nasal route 1 h prior to sensitization and challenge. The effect of β-Endorphin on pulmonary inflammation and redox status along with parameters of oxidative stress were evaluated. We found that pre-treatment of β-Endorphin significantly reduced inflammatory infiltration in lung tissue and cell counts in bronchoalveolar lavage fluid. Also, pre-treatment of β-Endorphin reduced reactive oxygen species, Myeloperoxidase, Nitric Oxide, Protein and protein carbonylation, Glutathione Reductase, Malondialdehyde, IFN-γ, and TNF-α. Reversely, β-Endorphin significantly increased Superoxide dismutase, Catalase, glutathione, Glutathione-S-Transferase, and activation of NF-E2-related factor 2 (Nrf-2) via Kelch-like ECH-associated protein 1 (Keap1), independent pathway in the lung restoring architectural alveolar and bronchial changes. The present findings reveal the therapeutic potency of β-END in regulating asthma by Keap-1 independent regulation of Nrf-2 activity. The present findings reveal the therapeutic potency of β-Endorphin in regulating asthma. © 2023, The Author(s).