Browsing by Author "Prakash, Hridayesh"

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    Host sphingolipids: Perspective immune adjuvant for controlling SARS-CoV-2 infection for managing COVID-19 disease
    (Elsevier Inc., 2020-11-02T00:00:00) Prakash, Hridayesh; Upadhyay, Dilip; Bandapalli, Obul Reddy; Jain, Aklank; Kleuser, Burkhard
    Sphingolipids are potent bioactive agents involved in the pathogenesis of various respiratory bacterial infections. To date, several sphingolipid derivatives are known, but S1P (Sphingosine-1-phosphate) and Ceramide are the best-studied sphingolipid derivatives in the context of human diseases. These are membrane-bound lipids that influence host-pathogen interactions. Based on these features, we believe that sphingolipids might control SARS-CoV-2 infection in the host. SARS-CoV-2 utilizes the ACE-II receptor (Angiotensin-converting enzyme II receptor) on epithelial cells for its entry and replication. Activation of the ACE-II receptor is indirectly associated with the activation of S1P Receptor 1 signaling which is associated with IL-6 driven fibrosis. This is expected to promote pathological responses during SARS-CoV-2 infection in COVID-19 cases. Given this, mitigating S1P signaling by application of either S1P Lyase (SPL) or S1P analog (Fingolimod / FTY720) seems to be potential approach for controlling these pathological outcomes. However, due to the immunosuppressive nature of FTY720, it can modulate hyper-inflammatory responses and only provide symptomatic relief, which may not be sufficient for controlling the novel COVID-19 infection. Since Th1 effector immune responses are essential for the clearance of infection, we believe that other sphingolipid derivatives like Cermaide-1 Phosphate with antiviral potential and adjuvant immune potential can potentially control SARS-CoV-2 infection in the host by its ability in enhancing autophagy and antigen presentation by DC to promote T cell response which can be helpful in controlling SARS-CoV-2 infection in novel COVID-19 patients. � 2020
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    Impact of noncoding RNAs on cancer directed immune therapies: Now then and forever
    (John Wiley and Sons Inc, 2022-04-30T00:00:00) Roy, Roshan Kumar; Yadav, Rakhi; Sharma, Uttam; Wasson, Mishi Kaushal; Sharma, Ashok; Tanwar, Pranay; Jain, Aklank; Prakash, Hridayesh
    Accumulating evidence demonstrates that the host genome's epigenetic modifications are essential for living organisms to adapt to extreme conditions. DNA methylation, covalent modifications of histone and interassociation of noncoding RNAs facilitate the cellular manifestation of epigenetic changes in the genome. Out of various factors involved in the epigenetic programming of the host, noncoding RNAs (ncRNAs) such as microRNA (miRNA), long noncoding RNA (lncRNA), circular RNA, snoRNA and piRNA are new generation noncoding molecules that influence a variety of cellular processes like immunity, cellular differentiation and tumor development. During tumor development, temporal changes in miRNA/lncRNA rheostat influence sterile inflammatory responses accompanied by the changes in the carcinogenic signaling in the host. At the cellular level, this is manifested by the upregulation of inflammasome and inflammatory pathways, which promotes cancer-related inflammation. Given this, we discuss the potential of lncRNAs, miRNAs, circular RNA, snoRNA and piRNA in regulating inflammation and tumor development in the host. � 2022 UICC.
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    Macrophage Activation Syndrome and COVID 19: Impact of MAPK Driven Immune-Epigenetic Programming by SARS-Cov-2
    (Frontiers Media S.A., 2021-10-01T00:00:00) Roy, Roshan Kumar; Sharma, Uttam; Wasson, Mishi Kaushal; Jain, Aklank; Hassan, Md. Imtaiyaz; Prakash, Hridayesh
    [No abstract available]
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    Micrornas and long noncoding rnas as novel therapeutic targets in estrogen receptor-positive breast and ovarian cancers
    (MDPI, 2021-04-15T00:00:00) Barwal, Tushar Singh; Sharma, Uttam; Bazala, Sonali; Singh, Ipsa; Jain, Manju; Prakash, Hridayesh; Shekhar, Shashank; Sandberg, Elise N.; Bishayee, Anupam; Jain, Aklank
    Aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane have shown to prevent metastasis and angiogenesis in estrogen receptor (ER)-positive breast and ovarian tumors. They function primarily by reducing estrogen production in ER-positive post-menopausal breast and ovarian cancer patients. Unfortunately, current AI-based therapies often have detrimental side-effects, along with acquired resistance, with increased cancer recurrence. Thus, there is an urgent need to identify novel AIs with fewer side effects and improved therapeutic efficacies. In this regard, we and others have recently suggested noncoding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), as potential molecular targets for utilization in modulating cancer hallmarks and overcoming drug resistance in several cancers, including ER-positive breast and ovarian cancer. Herein, we describe the disruptive functions of several miRNAs and lncRNAs seen in dysregulated cancer metabolism, with a focus on the gene encoding for aromatase (CYP19A1 gene) and estrogen synthesis as a novel therapeutic approach for treating ER-positive breast and ovarian cancers. Furthermore, we discuss the oncogenic and tumor-suppressive roles of several miRNAs (oncogenic miRNAs: MIR125b, MIR155, MIR221/222, MIR128, MIR2052HG, and MIR224; tumor-suppressive miRNAs: Lethal-7f, MIR27B, MIR378, and MIR98) and an oncogenic lncRNA (MIR2052HG) in aromatase-dependent cancers via transcriptional regulation of the CYP19A1 gene. Additionally, we discuss the potential effects of dysregulated miRNAs and lncRNAs on the regulation of critical oncogenic molecules, such as signal transducer, and activator of transcription 3, ?-catenin, and integrins. The overall goal of this review is to stimulate further research in this area and to facilitate the development of ncRNA-based approaches for more efficacious treatments of ER-positive breast and ovarian cancer patients, with a slight emphasis on associated treatment� delivery mechanisms. � 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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    A Pleiotropic Role of Long Non-Coding RNAs in the Modulation of Wnt/?-Catenin and PI3K/Akt/mTOR Signaling Pathways in Esophageal Squamous Cell Carcinoma: Implication in Chemotherapeutic Drug Response
    (MDPI, 2022-03-28T00:00:00) Sharma, Uttam; Murmu, Masang; Barwal, Tushar Singh; Tuli, Hardeep Singh; Jain, Manju; Prakash, Hridayesh; Kaceli, Tea; Jain, Aklank; Bishayee, Anupam
    Despite the availability of modern techniques for the treatment of esophageal squamous cell carcinoma (ESCC), tumor recurrence and metastasis are significant challenges in clinical management. Thus, ESCC possesses a poor prognosis and low five-year overall survival rate. Notably, the origin and recurrence of the cancer phenotype are under the control of complex cancer-related signaling pathways. In this review, we provide comprehensive knowledge about long non-coding RNAs (lncRNAs) related to Wnt/?-catenin and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in ESCC and its implications in hindering the efficacy of chemotherapeutic drugs. We observed that a pool of lncRNAs, such as HERES, TUG1, and UCA1, associated with ESCC, directly or indirectly targets various molecules of the Wnt/?-catenin pathway and facilitates the manifestation of multiple cancer phenotypes, including proliferation, metastasis, relapse, and resistance to anticancer treatment. Additionally, several lncRNAs, such as HCP5 and PTCSC1, modulate PI3K/Akt/mTOR pathways during the ESCC pathogenesis. Furthermore, a few lncRNAs, such as AFAP1-AS1 and LINC01014, block the efficiency of chemotherapeutic drugs, including cisplatin, 5-fluorouracil, paclitaxel, and gefitinib, used for ESCC treatment. Therefore, this review may help in designing a better therapeutic strategy for ESCC patients. � 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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    Rapid Arc-SBRT: Non-Invasive Immune Adjuvant for Advanced Stage Non-Small Cell Lung Carcinoma
    (Bentham Science Publishers, 2021-03-23T00:00:00) Chairmadurai, Arun; Jain, Sandeep K.; Jain, Aklank; Prakash, Hridayesh
    In conjunction with radio-chemotherapy, pulmonary resection is recommended for early-stage non-small-cell lung carcinoma but not for advanced-stage NSCLC patients having high-grade metastatic lesions. In these cases, the rapid Arc-Stereotactic body radiotherapy (Ra-SBRT) technique offers a therapeutic advantage by delivering focal irradiation to metastatic lung lesions and reduces the bystander toxicity to normal tissues. We have previously demonstrated that Ra-SBRT ablates metastatic lesions and induces tumor immune rejection of metastatic tumors by promoting in situ programming of M2 TAM towards M1-TAM and infiltration of Siglec-8+ Eosinophils. Most interestingly, Ra SBRT has very low abscopal impact and spares normal tissues, which are the significant limitations with conventional radiotherapy. In view of this and the immune adjuvant potential of Ra SBRT, it promotes normalization of aberrant vasculature and inhibits the metastatic potential of NSCLC lesions. In view of this, we here propose that Ra-SBRT indeed represents an immunogenic approach for the effective management of advanced-stage NSCLC. � 2022 Bentham Science Publishers.
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    The regulatory roles of long non-coding RNAs in the development of chemoresistance in breast cancer
    (Impact Journals LLC, 2017) Malhotra, Akshay; Jain, Manju; Prakash, Hridayesh; Vasquez, Karen M.; Jain, Aklank; Malhotra, A.; Jain, M.; Prakash, H.; Vasquez, K.M.; Jain, A.
    Chemoresistance is one of the major hurdles in the treatment of breast cancer, which limits the effect of both targeted and conventional therapies in clinical settings. Therefore, understanding the mechanisms underpinning resistance is paramount for developing strategies to circumvent resistance in breast cancer patients. Several published reports have indicated that lncRNAs play a dynamic role in the regulation of both intrinsic and acquired chemoresistance through a variety of mechanisms that endow cells with a drug-resistant phenotype. Although a number of lncRNAs have been implicated in chemoresistance of breast cancer, their mechanistic roles have not been systematically reviewed. Thus, here we present a detailed review on the latest research findings and discoveries on the mechanisms of acquisition of chemoresistance in breast cancer related to lncRNAs, and how lncRNAs take part in various cancer signalling pathways involved in breast cancer cells. Knowledge obtained from this review could assist in the development of new strategies to avoid or reverse drug resistance in breast cancer chemotherapy. ? 2017 Malhotra et al.
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    Role of Hedgehog and Hippo signaling pathways in cancer: A special focus on non-coding RNAs
    (Academic Press, 2022-10-28T00:00:00) Sharma, Uttam; Tuli, Hardeep Singh; Uttam, Vivek; Choudhary, Renuka; Sharma, Bunty; Sharma, Ujjawal; Prakash, Hridayesh; Jain, Aklank
    Despite advanced clinical and translational oncology research, mortality rates are still increasing worldwide. Recently, a class of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been well investigated in regulating biological, molecular, and cellular signaling pathways. This review article provided the current research progress on how miRNAs, lncRNAs, and circRNAs regulate Hedgehog (Hh) and Hippo signaling pathways in various cancers. These ncRNAs target both pathways' key downstream molecules and may be used for targeted cancer treatment. Moreover, Hh and Hippo signaling pathways crosstalked with each other through Gli1 of Hh pathways and YAP1/TEAD molecules of Hippo pathways during cancer progression. Additionally, Hh and Hippo signaling pathways regulate resistance against the chemo, radio, and immune therapies for several types of cancer via inducing GLI and YAP/TAZ proteins level. Therefore, to improve the treatment regime, we presented the role of various prominent phytochemicals such as curcumin, resveratrol, genistein, quercetin, paclitaxel, and silibinin in regulating lncRNAs, miRNAs, circRNA through Hedgehog and Hippo signaling pathways� constituents in cancers. We believe that knowledge obtained from this review may help make new drugs for cancer treatment in the future. � 2022 Elsevier Ltd
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    Yin and yang of immunological memory in controlling infections: Overriding self defence mechanisms
    (Taylor and Francis Ltd., 2021-04-19T00:00:00) Roy, Roshan Kumar; Yadav, Rakhi; Jain, Aklank; Tripathi, Vishwas; Jain, Manju; Singh, Sandhya; Prakash, Hridayesh
    Immunological memory is critical for host immunity and decisive for individual to respond exponentially to previously encountered infection. Both T and B cell memory are known to orchestrate immunological memory with their central and effector memory arms contributing in prolonged immunity/defence mechanisms of host. While central memory helps in maintaining prolonged immunity for a particular infection, effector memory helps in keeping local/seasonal infection in control. In addition to this, generation of long-lived plasma cells is pivotal for generating neutralizing antibodies which can enhance recall and B cell memory to control re-infection. In view of this, scaling up memory response is one of the major objectives for the expected outcome of vaccination. In this line, this review deals with the significance of memory cells, molecular pathways of their development, maintenance, epigenetic regulation and negative regulation in various infections. We have also highlighted the significance of both T and B cell memory responses in the vaccination approaches against range of infections which is not fully explored so far. Highlights Pathogens induce IL-10R, PD-1, T-reg; and downregulate IL7R and IL15R for hijacking memory response IL-7, 15, Tcf-1 (Wnt5/7A), and CD28 signaling is decisive for TCM/TEM and TRM recall. Bach2 expression suppress Bim and Puma and promotes memory B cell activities VCAM1, IFN-?, and GM-CSF pathways are critical for local activation of memory cells Multi-epitope vaccines/adjuvants are potent for inducing specific memory response. � 2021 Taylor & Francis Group, LLC.