Browsing by Author "Kumar, Dhruv"
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- Bracing NK cell based therapy to relegate pulmonary inflammation in COVID-19
A2 Katsausartikkeli tieteellisessä aikakauslehdessä(2021-07) Jeyaraman, Madhan; Muthu, Sathish; Bapat, Asawari; Jain, Rashmi; Sushmitha, E. S.; Gulati, Arun; Channaiah Anudeep, Talagavadi; Dilip, Shirodkar Jaswandi; Jha, Niraj Kumar; Kumar, Dhruv; Kesari, Kavindra Kumar; Ojha, Shreesh; Dholpuria, Sunny; Gupta, Gaurav; Dureja, Harish; Chellappan, Dinesh Kumar; Singh, Sachin Kumar; Dua, Kamal; Jha, Saurabh KumarThe contagiosity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has startled mankind and has brought our lives to a standstill. The treatment focused mainly on repurposed immunomodulatory and antiviral agents along with the availability of a few vaccines for prophylaxis to vanquish COVID-19. This seemingly mandates a deeper understanding of the disease pathogenesis. This necessitates a plausible extrapolation of cell-based therapy to COVID-19 and is regarded equivalently significant. Recently, correlative pieces of clinical evidence reported a robust decline in lymphocyte count in severe COVID-19 patients that suggest dysregulated immune responses as a key element contributing to the pathophysiological alterations. The large granular lymphocytes also known as natural killer (NK) cells play a heterogeneous role in biological functioning wherein their frontline action defends the body against a wide array of infections and tumors. They prominently play a critical role in viral clearance and executing immuno-modulatory activities. Accumulated clinical evidence demonstrate a decrease in the number of NK cells in circulation with or without phenotypical exhaustion. These plausibly contribute to the progression of pulmonary inflammation in COVID-19 pneumonia and result in acute lung injury. In this review, we have outlined the present understanding of the immunological response of NK cells in COVID-19 infection. We have also discussed the possible use of these powerful biological cells as a therapeutic agent in view of preventing immunological harms of SARS-CoV-2 and the current challenges in advocating NK cell therapy for the same. - A comparative cross‐platform meta‐analysis to identify potential biomarker genes common to endometriosis and recurrent pregnancy loss
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä(2021-04-02) Guha, Pokhraj; Roychoudhury, Shubhadeep; Singha, Sobita; Kalita, Jogen C.; Kolesarova, Adriana; Jamal, Qazi Mohammad Sajid; Jha, Niraj Kumar; Kumar, Dhruv; Ruokolainen, Janne; Kesari, Kavindra KumarEndometriosis is characterized by unwanted growth of endometrial tissue in different locations of the female reproductive tract. It may lead to recurrent pregnancy loss, which is one of the worst curses for the reproductive age group of human populations around the world. Thus, there is an urgent need for unveiling any common source of origin of both these diseases and con-nections, if any. Herein, we aimed to identify common potential biomarker genes of these two diseases via in silico approach using meta‐analysis of microarray data. Datasets were selected for the study based on certain exclusion criteria. Those datasets were subjected to comparative meta‐anal-yses for the identification of differentially expressed genes (DEGs), that are common to both diag-noses. The DEGs were then subjected to protein‐protein networking and subsequent functional enrichment analyses for unveiling their role/function in connecting two diseases. From the analyses, 120 DEGs are reported to be significant out of which four genes have been found to be prominent. These include the CTNNB1, HNRNPAB, SNRPF and TWIST2 genes. The significantly enriched pathways based on the above‐mentioned genes are mainly centered on signaling and developmental events. These findings could significantly elucidate the underlying molecular events in endometri-osis‐based recurrent miscarriages. - Crosstalk between long noncoding RNA and microRNA in Cancer
A2 Katsausartikkeli tieteellisessä aikakauslehdessä(2023-08) Bhattacharjee, Rahul; Prabhakar, Neeraj; Kumar, Lamha; Bhattacharjee, Arkadyuti; Kar, Sulagna; Malik, Sumira; Kumar, Dhruv; Ruokolainen, Janne; Negi, Arvind; Jha, Niraj Kumar; Kesari, Kavindra KumarmiRNAs and lncRNAs play a central role in cancer-associated gene regulations. The dysregulated expression of lncRNAs has been reported as a hallmark of cancer progression, acting as an independent prediction marker for an individual cancer patient. The interplay of miRNA and lncRNA decides the variation of tumorigenesis that could be mediated by acting as sponges for endogenous RNAs, regulating miRNA decay, mediating intra-chromosomal interactions, and modulating epigenetic components. This paper focuses on the influence of crosstalk between lncRNA and miRNA on cancer hallmarks such as epithelial-mesenchymal transition, hijacking cell death, metastasis, and invasion. Other cellular roles of crosstalks, such as neovascularization, vascular mimicry, and angiogenesis were also discussed. Additionally, we reviewed crosstalk mechanism with specific host immune responses and targeting interplay (between lncRNA and miRNA) in cancer diagnosis and management. Graphic Abstract: [Figure not available: see fulltext.]. - Evidence of Coronavirus (CoV) Pathogenesis and Emerging Pathogen SARS-CoV-2 in the Nervous System
A2 Katsausartikkeli tieteellisessä aikakauslehdessä(2021-11) Jha, Niraj Kumar; Ojha, Shreesh; Jha, Saurabh Kumar; Dureja, Harish; Singh, Sachin Kumar; Shukla, Shakti D.; Chellappan, Dinesh Kumar; Gupta, Gaurav; Bhardwaj, Shanu; Kumar, Neeraj; Jeyaraman, Madhan; Jain, Rashmi; Muthu, Sathish; Kar, Rohan; Kumar, Dhruv; Goswami, Vineet Kumar; Ruokolainen, Janne; Kesari, Kavindra Kumar; Singh, Sandeep Kumar; Dua, KamalThe 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. - Investigation of precise molecular mechanistic action of tobacco-associated carcinogen `NNK´ induced carcinogenesis: A system biology approach
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä(2019-08-01) Anukriti; Dhasmana, Anupam; Uniyal, Swati; Somvanshi, Pallavi; Bhardwaj, Uma; Gupta, Meenu; Haque, Shafiul; Lohani, Mohtashim; Kumar, Dhruv; Ruokolainen, Janne; Kesari, Kavindra KumarCancer is the second deadliest disease listed by the WHO. One of the major causes of cancer disease is tobacco and consumption possibly due to its main component, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). A plethora of studies have been conducted in the past aiming to decipher the association of NNK with other diseases. However, it is strongly linked with cancer development. Despite these studies, a clear molecular mechanism and the impact of NNK on various system-level networks is not known. In the present study, system biology tools were employed to understand the key regulatory mechanisms and the perturbations that will happen in the cellular processes due to NNK. To investigate the system level influence of the carcinogen, NNK rewired protein–protein interaction network (PPIN) was generated from 544 reported proteins drawn out from 1317 articles retrieved from PubMed. The noise was removed from PPIN by the method of modulation. Gene ontology (GO) enrichment was performed on the seed proteins extracted from various modules to find the most affected pathways by the genes/proteins. For the modulation, Molecular COmplex DEtection (MCODE) was used to generate 19 modules containing 115 seed proteins. Further, scrutiny of the targeted biomolecules was done by the graph theory and molecular docking. GO enrichment analysis revealed that mostly cell cycle regulatory proteins were affected by NNK. - Metabolic regulation in HPV associated head and neck squamous cell carcinoma
A2 Katsausartikkeli tieteellisessä aikakauslehdessä(2020-10-01) Chandel, Vaishali; Raj, Sibi; Kumar, Prabhat; Gupta, Shilpi; Dhasmana, Anupam; Kesari, Kavindra Kumar; Ruokolainen, Janne; Mehra, Pravesh; Das, Bhudev C.; Kamal, Mohammad Amjad; Kumar, DhruvCancer cells exhibit distinct energy metabolic pathways due to multiple oncogenic events. In normoxia condition, the anaerobic glycolysis (Warburg effect) is highly observed in head and neck squamous cell carcinoma (HNSCC). HNSCC is associated with smoking, chewing tobacco, consumption of alcohol or Human Papillomavirus (HPV) infection primarily HPV16. In recent years, the correlation of HPV with HNSCC has significantly expanded. Despite the recent advancement in therapeutic approaches, the rate of HPV infected HNSCC has significantly increased in the last few years, specifically, in lower middle-income countries. The oncoproteins of High-risk Human Papillomavirus (HR-HPV), E6 and E7, alter the metabolic phenotype in HNSCC, which is distinct from non-HPV associated HNSCC. These oncoproteins, modulate the cell cycle and metabolic signalling through interacting with tumor suppressor proteins, p53 and pRb. Since, metabolic alteration represents a major hallmark for tumorigenesis, HPV acts as a source of biomarker linked to cancer progression in HNSCC. The dependency of cancer cells to specific nutrients and alteration of various metabolic associated genes may provide a unique opportunity for pharmacological intervention in HPV infected HNSCC. In this review, we have discussed the molecular mechanism (s) and metabolic regulation in HNSCC depending on the HPV status. We have also discussed the possible potential therapeutic approaches for HPV associated HNSCC through targeting metabolic pathways. - Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer
A2 Katsausartikkeli tieteellisessä aikakauslehdessä(2022-01-26) Raj, Sibi; Kesari, Kavindra Kumar; Kumar, Arun; Rathi, Brijesh; Sharma, Ashok; Gupta, Piyush Kumar; Jha, Saurabh Kumar; Jha, Niraj Kumar; Slama, Petr; Roychoudhury, Shubhadeep; Kumar, DhruvHead and neck cancer is the sixth most common cancer across the globe. This is generally associated with tobacco and alcohol consumption. Cancer in the pharynx majorly arises through human papillomavirus (HPV) infection, thus classifying head and neck squamous cell carcinoma (HNSCC) into HPV-positive and HPV-negative HNSCCs. Aberrant, mesenchymal-epithelial transition factor (c-MET) signal transduction favors HNSCC progression by stimulating proliferation, motility, invasiveness, morphogenesis, and angiogenesis. c-MET upregulation can be found in the majority of head and neck squamous cell carcinomas. c-MET pathway acts on several downstream effectors including phospholipase C gamma (PLCγ), cellular Src kinase (c-Src), phosphotidylinsitol-3-OH kinase (PI3K), alpha serine/threonine-protein kinase (Akt), mitogen-activated protein kinase (MAPK), and wingless-related integration site (Wnt) pathways. c-MET also establishes a crosstalk pathway with epidermal growth factor receptor (EGFR) and contributes towards chemoresistance in HNSCC. In recent years, the signaling communications of c-MET/HGF in metabolic dysregulation, tumor-microenvironment and immune modulation in HNSCC have emerged. Several clinical trials have been established against c-MET/ hepatocyte growth factor (HGF) signaling network to bring up targeted and effective therapeutic strategies against HNSCC. In this review, we discuss the molecular mechanism(s) and current understanding of c-MET/HGF signaling and its effect on HNSCC. Graphical abstract: [Figure not available: see fulltext.] - Oxidative stress in cancer cell metabolism
A2 Katsausartikkeli tieteellisessä aikakauslehdessä(2021-05) Arfin, Saniya; Jha, Niraj Kumar; Jha, Saurabh Kumar; Kesari, Kavindra Kumar; Ruokolainen, Janne; Roychoudhury, Shubhadeep; Rathi, Brijesh; Kumar, DhruvReactive oxygen species (ROS) are important in regulating normal cellular processes whereas deregulated ROS leads to the development of a diseased state in humans including cancers. Several studies have been found to be marked with increased ROS production which activates pro-tumorigenic signaling, enhances cell survival and proliferation and drives DNA damage and genetic instability. However, higher ROS levels have been found to promote anti-tumorigenic signaling by initiating oxidative stress-induced tumor cell death. Tumor cells develop a mechanism where they adjust to the high ROS by expressing elevated levels of antioxidant proteins to detoxify them while maintaining pro-tumorigenic signaling and resistance to apoptosis. Therefore, ROS manipulation can be a potential target for cancer therapies as cancer cells present an altered redox balance in comparison to their normal counterparts. In this review, we aim to provide an overview of the generation and sources of ROS within tumor cells, ROS-associated signaling pathways, their regulation by antioxidant defense systems, as well as the effect of elevated ROS production in tumor progression. It will provide an insight into how pro-and anti-tumorigenic ROS signaling pathways could be manipulated during the treatment of cancer. - Re-establishing the comprehension of phytomedicine and nanomedicine in inflammation-mediated cancer signaling
A2 Katsausartikkeli tieteellisessä aikakauslehdessä(2022-11) Jha, Niraj Kumar; Arfin, Saniya; Jha, Saurabh Kumar; Kar, Rohan; Dey, Abhijit; Gundamaraju, Rohit; Ashraf, Ghulam Md; Gupta, Piyush Kumar; Dhanasekaran, Sugapriya; Abomughaid, Mosleh Mohammad; Das, Sabya Sachi; Singh, Sachin Kumar; Dua, Kamal; Roychoudhury, Shubhadeep; Kumar, Dhruv; Ruokolainen, Janne; Ojha, Shreesh; Kesari, Kavindra KumarRecent mounting evidence has revealed extensive genetic heterogeneity within tumors that drive phenotypic variation affecting key cancer pathways, making cancer treatment extremely challenging. Diverse cancer types display resistance to treatment and show patterns of relapse following therapy. Therefore, efforts are required to address tumor heterogeneity by developing a broad-spectrum therapeutic approach that combines targeted therapies. Inflammation has been progressively documented as a vital factor in tumor advancement and has consequences in epigenetic variations that support tumor instigation, encouraging all the tumorigenesis phases. Increased DNA damage, disrupted DNA repair mechanisms, cellular proliferation, apoptosis, angiogenesis, and its incursion are a few pro-cancerous outcomes of chronic inflammation. A clear understanding of the cellular and molecular signaling mechanisms of tumor-endorsing inflammation is necessary for further expansion of anti-cancer therapeutics targeting the crosstalk between tumor development and inflammatory processes. Multiple inflammatory signaling pathways, such as the NF-κB signaling pathway, JAK-STAT signaling pathway, MAPK signaling, PI3K/AKT/mTOR signaling, Wnt signaling cascade, and TGF-β/Smad signaling, have been found to regulate inflammation, which can be modulated using various factors such as small molecule inhibitors, phytochemicals, recombinant cytokines, and nanoparticles (NPs) in conjugation to phytochemicals to treat cancer. Researchers have identified multiple targets to specifically alter inflammation in cancer therapy to restrict malignant progression and improve the efficacy of cancer therapy. siRNA-and shRNA-loaded NPs have been observed to downregulate STAT3 signaling pathways and have been employed in studies to target tumor malignancies. This review highlights the pathways involved in the interaction between tumor advancement and inflammatory progression, along with the novel approaches of nanotechnology-based drug delivery systems currently used to target inflammatory signaling pathways to combat cancer. - Specific targeting cancer cells with nanoparticles and drug delivery in cancer therapy
A2 Katsausartikkeli tieteellisessä aikakauslehdessä(2021-02) Raj, Sibi; Khurana, Sartaj; Choudhari, Ramesh; Kesari, Kavindra; Kamal, Mohammad Amjad; Garg, Neha; Ruokolainen, Janne; Das, Bhudev; Kumar, DhruvNanotechnology has been the latest approach for diagnosis and treatment for cancer, which opens up a new alternative therapeutic drug delivery option to treat disease. Nanoparticles (NPs) display a broad role in cancer diagnosis and has various advantages over the other conventional chemotherapeutic drug delivery. NPs possess more specific and efficient drug delivery to the targeted tissue, cell, or organs and minimize the risk of side effects. NPs undergo passive and active mode of drug targets to tumor area with less elimination of the drug from the system. Size and surface characteristics of nanoparticles play a crucial role in modulating nanocarrier efficiency and the biodistribution of chemo drugs in the body. Several types of nanocarriers, such as polymers, dendrimers, liposome-based, and carbon-based, are studied widely in cancer therapy. Although FDA approved very few nanotechnology drugs for cancer therapy, a large number of studies are undergoing for the development of novel nanocarriers for potent cancer therapy. In this review, we discuss the details of the nano-based therapeutics and diagnostics strategies, and the potential use of nanomedicines in cancer therapy and cancer drug delivery. - Viral pathogenesis of SARS-CoV-2 infection and male reproductive health
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä(2021-01-20) Roychoudhury, Shubhadeep; Das, Anandan; Jha, Niraj Kumar; Kesari, Kavindra Kumar; Roychoudhury, Shatabhisha; Jha, Saurabh Kumar; Kosgi, Raghavender; Choudhury, Arun Paul; Lukac, Norbert; Madhu, Nithar Ranjan; Kumar, Dhruv; Slama, PetrCoronavirus disease 2019 (COVID-19) has emerged as a new public health crisis, threatening almost all aspects of human life. Originating in bats, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted to humans through unknown intermediate hosts, where it is primarily known to cause pneumonia-like complications in the respiratory system. Organ-to-organ transmission has not been ruled out, thereby raising the possibility of the impact of SARS-CoV-2 infection on multiple organ systems. The male reproductive system has been hypothesized to be a potential target of SARS-CoV-2 infection, which is supported by some preliminary evidence. This may pose a global threat to male fertility potential, as men are more prone to SARS-CoV-2 infection than women, especially those of reproductive age. Preliminary reports have also indicated the possibility of sexual transmission of SARS-CoV-2. It may cause severe complications in infected couples. This review focuses on the pathophysiology of potential SARS-CoV-2 infection in the reproductive organs of males along with their invasion mechanisms. The risks of COVID-19 on male fertility as well as the differences in vulnerability to SARS-CoV-2 infection compared with females have also been highlighted.