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Drug Repurposing and Novel Antiviral Drugs for COVID-19 Management
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Shailendra Dwivedi, Aakanksha Rawat, Amit Ranjan, Ruchika Agrawal, Radhieka Misra, Sunil Kumar Gupta, Surekha Kishore, Sanjeev Misra
Recently researchers from China (Beijing, Shanghai, and Hubei) completed a study in which they successfully transplanted human MSCs [57] (Table 7.2). The study noted improvement in the outcome of seven treated patients with COVID-19 pneumonia in Beijing Youan Hospital, China, from January 23, 2020 to February 16, 2020. After MSC injection, the alterations in inflammatory, immune function levels as well as adverse effects of the patients were evaluated for 14 days. All seven patients showed significant improvements in pulmonary function and reduction in symptoms within two days of MSC transplantation without any adverse effects. After transplantation, peripheral lymphocyte counts increased, with a decrease in the C-reactive protein (infection and inflammatory marker). Moreover, it triggered cytokine secreting immune cells CXCR3 + CD4 + T cells, CXCR3 + CD8 + T cells, and CXCR3 + NK cells disappeared in 3–6 days. Increase in a group of CD14 + CD11c + CD11bmid regulatory DC population was also noticed. Additionally, the level of pro-inflammatory TNF-α was reduced, and anti-inflammatory IL-10 levels were increased remarkably in the MSC treated group compared to the control placebo group. Thus the very first study of safe and effective intravenous transplantation of MSCs has opened new horizons for the treatment of patients with COVID-19 pneumonia [58].
Targeted Therapy for Cancer Stem Cells
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Rama Krishna Nimmakayala, Saswati Karmakar, Garima Kaushik, Sanchita Rauth, Srikanth Barkeer, Saravanakumar Marimuthu, Moorthy P. Ponnusamy
Another kind of unconventional T cells, Gamma delta T cells, are innate effector immune cells. These cells have been shown to express a higher amount of CCR5 and CXCR3 receptors and enhance CSC specific immune response. These cells have also been reported to proliferate and secrete TNF-α and IFN-γ, and produce apoptotic and cytotoxic granzymes, and target CSCs when administered with zoledronate in colon cancer [37, 38].
Chemokines and Chemokine Receptor Interactions and Functions
Published in Thomas R. O’Brien, Chemokine Receptors and AIDS, 2019
Philip L. Shields, David H. Adams
Early studies showed high levels of some chemokines in particular situations. For example, in acute bacterial pneumonia there is a huge influx of neutrophils into the lung associated with high levels of the neutrophil chemoattractant IL-8 in bronchoalveolar fluid (91). In rheumatoid arthritis high levels of MIP-1α and MIP-1β were found in synovial fluid associated with a mononuclear cell infiltrate (92). In chronic hepatitis C virus infection, characterised by T cell infiltration of the liver, there is increased expression of the chemokines IP-10 and Mig. T cells infiltrating the liver express high levels of CXCR3 and CCR5 compared with autologous circulating T cells, suggesting that the ligands of these two receptors play a role in the selective recruitment of T cells to the inflamed liver. Moreover, the anatomical distribution of the chemokines and receptor-bearing infiltrating cells suggests that different chemokine receptor/chemokine interactions may determine the extent and severity of the infiltration (58). Similar observations have been made in multiple sclerosis where CCR5 and CXCR3 appear to be particularly important (93). The role played by chemokines and chemokine receptors in the pathogenesis of a range of disease states will now be described in more detail.
A review of current biomarkers in chronic rhinosinusitis with or without nasal polyps
Published in Expert Review of Clinical Immunology, 2023
Tsuguhisa Nakayama, Shin-Ichi Haruna
On the other hand, CSF3 has been reported to be a useful marker for type 3 inflammation in CRSwNP and non-eCRSwNP at the mRNA level [14,64]. Type 1 inflammatory endotypes in CRSsNP can be identified using IFNG, a representative type 1 inflammatory cytokine that has been shown to be a useful biomarker at the mRNA level. Additionally, CXCL9 and CXCL10 exhibit increased mRNA levels compared to controls, non-type 1 CRSsNP, and even CRSwNP, indicating that they could be potential specific biomarkers for type 1 inflammation in CRSsNP [23]. However, since previous studies have reported high expression of CXCL9, CXCL10, and CXCL11 in non-eCRSwNP [64], their specific role in characterizing type 1 CRSsNP, even with the inclusion of CRSwNP, may be influenced by the regiotype of CRSwNP. Nevertheless, these CXCR3 mediated cytokines have the potential to serve as indicators of type 1 inflammation. IL17A, IL17F, CSF3, SAA, and IL1B have been reported as promising markers for type 3 inflammation in CRSsNP [23]. SAA is also elevated in non-eCRSwNP when compared to eCRSwNP and control groups [64].
CXCL10-armed oncolytic adenovirus promotes tumor-infiltrating T-cell chemotaxis to enhance anti-PD-1 therapy
Published in OncoImmunology, 2022
Xiaofei Li, Mingjie Lu, Manman Yuan, Jing Ye, Wei Zhang, Lingyan Xu, Xiaohan Wu, Bingqing Hui, Yuchen Yang, Bin Wei, Ciliang Guo, Min Wei, Jie Dong, Xingxin Wu, Yanhong Gu
Accumulating evidence has shown that CXCR3 and its ligands play a positive role in tumor prognosis and anti-PD-1 therapy.8–11 CXCR3 is a chemokine receptor expressed in cytotoxic lymphocytes (CTLs), natural killer cells (NKs), NKT cells, DCs and B cells that can be recruited to specific sites by its ligands CXCL9/10/11.10,12 Our previous work has shown that CXCR3 expression in peripheral T cells can be used as a biomarker to predict the efficacy of PD-1 antibodies, while exogenous supplementation with intratumoural CXCL9/10 can assist PD-1 antibodies in inhibiting tumor growth by increasing the proportion of CXCR3+ T cells in the TME in a mouse melanoma model.13 Furthermore, many other studies have suggested that intratumoural CXCL10 signaling is positively correlated with the efficacy of immune checkpoint blockade (ICB) treatment.11,14,15 Consistent with our former discovery, the reported mechanism of these articles is related to more CXCR3+ T cells infiltrating the TME, making ‘cold’ tumors ‘hot’ and helping PD-1 antibodies achieve better antitumour effects. The evidence mentioned above implies the crucial status of CXCR3-CXCL9/10/11 in ICB, and the key point of this hypothesis was the sustained intratumoural chemokine concentration.
Serum IFNγ–induced protein 10 (IP10/CXCL10): association with asthma exacerbations and severity in children
Published in Journal of Asthma, 2022
Hanan M. Osman, Noussa Ragab El Basha, Ahmed F. Mansour, Mariam Onsy F. Hanna
Chemokines and cytokines play a central role in asthma airway inflammation by recruiting and activating multiple inflammatory cells (4). Airway inflammation is associated with the secretion of the interferonγ–inducible protein 10 kDa (IP10, CXCL10) from various cells. Important cellular sources of CXCL10 expression in asthma include endothelial cells, smooth muscle cells, bronchial epithelial cells, neutrophils, eosinophils, T cells and monocytes (5). The receptor for CXCL10, CXCR3 mediates CXCL10 functions such as promoting the chemotactic activity of CXCR3 expressing cells, inducing apoptosis, regulating cell growth and proliferation, and regulating angiostasis. CXCR3 is predominantly expressed by activated T lymphocytes, innate lymphoid cells, natural killer cells and dendritic cells, in addition to mast cells and eosinophils (6). CXCR3 ligands, namely CXCL9, CXCL10, and CXCL11 have been considered to be part of the T helper (Th) 1 immune response because they are produced by cells in response to stimulation by interferon (IFN)γ, although CXCL10 is also induced by IFNs α/β and weakly by tumor necrosis factor (TNF)α (7,8). CXCL10 can also stimulate antigen-dependent IFNγ production from peripheral blood mononuclear cells up to 120-fold (9).