1,336 results
Search Results
102. EBV and Lymphomagenesis.
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Sausen, Daniel G., Basith, Ayeman, and Muqeemuddin, Syed
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HODGKIN'S disease , *CARCINOGENESIS , *B cell lymphoma , *KILLER cells , *TREATMENT effectiveness , *EPSTEIN-Barr virus , *T cells , *DISEASE risk factors - Abstract
Simple Summary: Epstein–Barr virus is a highly prevalent virus associated with a multitude of diseases, including autoimmune conditions such as multiple sclerosis and many types of cancer. As such, it is imperative to have a foundational understanding of this virus. This review discusses the contribution of the Epstein–Barr virus to key hematologic malignancies with a focus on the roles of latent proteins, including diffuse large B-cell lymphoma, Hodgkin lymphoma, Burkitt lymphoma, NK/T-cell lymphoma, and primary CNS lymphoma. It then provides a brief overview of treatment for each of these diseases. The clinical significance of Epstein–Barr virus (EBV) cannot be understated. Not only does it infect approximately 90% of the world's population, but it is also associated with numerous pathologies. Diseases linked to this virus include hematologic malignancies such as diffuse large B-cell lymphoma, Hodgkin lymphoma, Burkitt lymphoma, primary CNS lymphoma, and NK/T-cell lymphoma, epithelial malignancies such as nasopharyngeal carcinoma and gastric cancer, autoimmune diseases such as multiple sclerosis, Graves' disease, and lupus. While treatment for these disease states is ever evolving, much work remains to more fully elucidate the relationship between EBV, its associated disease states, and their treatments. This paper begins with an overview of EBV latency and latency-associated proteins. It will then review EBV's contributions to select hematologic malignancies with a focus on the contribution of latent proteins as well as their associated management. [ABSTRACT FROM AUTHOR]
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- 2023
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103. The immunoregulatory role of IL‐35 in patients with interstitial lung disease.
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Osuna‐Gómez, Rubén, Barril, Silvia, Mulet, Maria, Zamora Atenza, Carlos, Millan‐Billi, Paloma, Pardessus, Ana, Brough, Douglas E., Sabzevari, Helen, Semnani, Roshanak T., Castillo, Diego, and Vidal, Silvia
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INTERSTITIAL lung diseases , *PULMONARY fibrosis , *T cells , *CD4 antigen , *INTERLEUKIN-17 - Abstract
Pulmonary fibrosis involves various types of immune cells and soluble mediators, including TGF‐β and IL‐35, a recently identified heterodimeric cytokine that belongs to the IL‐12 cytokine family. However, the effect of regulatory IL‐35 may play an important role in fibrotic diseases. The aim of this paper is to explore the immunoregulatory role of IL‐35 in the development of fibrosis in interstitial lung disease (ILD). To gain a better understanding of this issue, the concentrations of IL‐35 and different profibrotic cytokines in fibrotic (F‐ILD) and non‐fibrotic (NF‐ILD) patients by ELISA were compared to that of intracellular IL‐35 and IL‐17 on CD4+ T cells stimulated in the presence of BAL or with different ratios of recombinant IL‐35 (rIL‐35) and TGF‐β (rTGF‐β), which were evaluated by flow cytometry. We observed that BAL concentration of IL‐35 was lower in F patients (p < 0.001) and was negatively correlated with concentrations of TGF‐β (p < 0.001) and IL‐17 (p < 0.001). In supplemented cell cultures, BAL from NF but not F patients enhanced the percentage of IL‐35 + CD4+ T (p < 0.001) cells and decreased the percentage of IL‐17 + CD4+ T cells (p < 0.001). The percentage of IL‐35 + CD4+ T cells correlated positively with BAL concentration of IL‐35 (p = 0.02), but correlated negatively with BAL concentrations of IL‐17 (p = 0.007) and TGF‐β (p = 0.01). After adjusting the concentrations of recombinant cytokines to establish a TGF‐β: IL‐35 ratio of 1:4, an enhanced percentage of IL‐35 + CD4+ T cells (p < 0.001) but a decreased percentage of IL‐17 + CD4+ T cells (p < 0.001) was observed. After adding recombinant IL‐35 to the BAL from F patients until a 1:4 ratio of TGF‐β: IL‐35 was reached, a significantly increased percentage of IL‐35 + CD4+ T cells (p < 0.001) and a decreased percentage of IL‐17 + CD4+ T cells (p = 0.003) was found. These results suggest that IL‐35 may induce an anti‐fibrotic response, regulating the effect of TGF‐β and the inflammatory response on CD4+ T cells. In addition, the TGF‐β: IL‐35 ratio in BAL has been shown to be a potential biomarker to predict the outcome of F patients with ILD. [ABSTRACT FROM AUTHOR]
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- 2023
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104. Global Dynamics of a Diffusive Within-Host HTLV/HIV Co-Infection Model with Latency.
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AlShamrani, Noura H., Elaiw, Ahmed, Raezah, Aeshah A., and Hattaf, Khalid
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HTLV , *HIV , *MIXED infections , *PARTIAL differential equations , *HIV infections , *LYAPUNOV functions , *T cells - Abstract
In several publications, the dynamical system of HIV and HTLV mono-infections taking into account diffusion, as well as latently infected cells in cellular transmission has been mathematically analyzed. However, no work has been conducted on HTLV/HIV co-infection dynamics taking both factors into consideration. In this paper, a partial differential equations (PDEs) model of HTLV/HIV dual infection was developed and analyzed, considering the cells' and viruses' spatial mobility. CD 4 + T cells are the primary target of both HTLV and HIV. For HIV, there are three routes of transmission: free-to-cell (FTC), latent infected-to-cell (ITC), and active ITC. In contrast, HTLV transmits horizontally through ITC contact and vertically through the mitosis of active HTLV-infected cells. In the beginning, the well-posedness of the model was investigated by proving the existence of global solutions and the boundedness. Eight threshold parameters that determine the existence and stability of the eight equilibria of the model were obtained. Lyapunov functions together with the Lyapunov–LaSalle asymptotic stability theorem were used to investigate the global stability of all equilibria. Finally, the theoretical results were verified utilizing numerical simulations. [ABSTRACT FROM AUTHOR]
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- 2023
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105. Therapeutic Implications of UVB Irradiation in Cancer by Enhancing Anti‐Tumor Immunity†.
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Hafeez, Bilal Bin, Alvarado, Ed W., and Kim, Dae Joon
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PROGRAMMED cell death 1 receptors , *DENDRITIC cells , *TRANSCRIPTION factors , *SKIN cancer , *COLORECTAL cancer , *T cells , *DOSE-response relationship (Radiation) , *IRRADIATION - Abstract
The UVB irradiation is well known for its impact on the development of skin cancer. However, low UVB irradiation plays a protective role against various human diseases including cancer through its effect on tumor suppression. This article summarizes the key findings of the paper by Park et al., which describes a novel molecular mechanism of moderate UVB irradiation in suppressing the growth of melanoma and colorectal cancer. Key observations in this article are that moderate UVB irradiation can enhance tumor immunity by (1) increased infiltration of CD4+ and CD8+ T cells; (2) increased infiltration of CD103+ conventional type 1 dendritic cells (cDC1); and (3) a significant decrease of M2 tumor associate macrophages (TAMs) into the tumor. The authors further identified the role of Batf3 transcription factor in moderate UVB irradiation‐mediated anti‐tumor immune response. Deletion of Batf3 transcription factor reversed the tumor suppressive effect with decreased CD103+ cDC1 cell infiltration. This pre‐clinical study provides a very novel mechanistic insight into the utilization of moderate UVB irradiation for the management of melanoma and colorectal cancer. This study further provides the direction of new future research to explore moderate UVB irradiation in combination with checkpoint blockade antibodies to enhance immunotherapeutic response against various solid tumors. [ABSTRACT FROM AUTHOR]
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- 2023
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106. A Comprehensive View of the Cancer-Immunity Cycle (CIC) in HPV-Mediated Cervical Cancer and Prospects for Emerging Therapeutic Opportunities.
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Avila, Jonathan Peña, Carvalho, Bruno Melo, and Coimbra, Eliane Campos
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MOLECULAR diagnosis , *MOLECULAR biology , *CELLULAR signal transduction , *GENE expression , *PAPILLOMAVIRUS diseases , *IMMUNITY , *TUMOR antigens , *T cells , *IMMUNOTHERAPY , *DRUG resistance in cancer cells , *DISEASE complications ,CERVIX uteri tumors - Abstract
Simple Summary: Every year, cervical cancer affects more than 500,000 women worldwide. The persistent infection caused by the human papillomavirus (HPV) is the main risk factor for the development of this type of cancer. Conventional treatments for cervical cancer are often associated with resistance and side effects. Therefore, it is necessary to find new targets for the development of more effective therapeutic approaches. In recent years, an increasing number of studies have been concerned with developing immunotherapeutic strategies for treating cancer. Thus, it is important to investigate new targets, such as the various molecules and cells that are involved in the cancer-immunity cycle (CIC). This process consists of the release of cancer antigens and their destruction by cytotoxic T-cells. Hence, in this review, we discuss the molecular changes that occur at each stage of the CIC for cervical cancer, including the impact of variables such as histological subtype and HPV infection. Moreover, we explore the latest immunotherapeutic approaches that have been adopted, together with their benefits and limitations. In this scenario, current studies are opening up new horizons in clinical practice for a personalized treatment of cervical cancer. Cervical cancer (CC) is the fourth most common cancer in women worldwide, with more than 500,000 new cases each year and a mortality rate of around 55%. Over 80% of these deaths occur in developing countries. The most important risk factor for CC is persistent infection by a sexually transmitted virus, the human papillomavirus (HPV). Conventional treatments to eradicate this type of cancer are accompanied by high rates of resistance and a large number of side effects. Hence, it is crucial to devise novel effective therapeutic strategies. In recent years, an increasing number of studies have aimed to develop immunotherapeutic methods for treating cancer. However, these strategies have not proven to be effective enough to combat CC. This means there is a need to investigate immune molecular targets. An adaptive immune response against cancer has been described in seven key stages or steps defined as the cancer-immunity cycle (CIC). The CIC begins with the release of antigens by tumor cells and ends with their destruction by cytotoxic T-cells. In this paper, we discuss several molecular alterations found in each stage of the CIC of CC. In addition, we analyze the evidence discovered, the molecular mechanisms and their relationship with variables such as histological subtype and HPV infection, as well as their potential impact for adopting novel immunotherapeutic approaches. [ABSTRACT FROM AUTHOR]
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- 2023
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107. Macroscopic limit of a kinetic model describing the switch in T cell migration modes via binary interactions.
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ESTRADA-RODRIGUEZ, G. and LORENZI, T.
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CELL migration , *CYTOTOXIC T cells , *LEVY processes , *T cells , *POISSON distribution , *BROWNIAN motion , *DISTRIBUTION (Probability theory) - Abstract
Experimental results on the immune response to cancer indicate that activation of cytotoxic T lymphocytes (CTLs) through interactions with dendritic cells (DCs) can trigger a change in CTL migration patterns. In particular, while CTLs in the pre-activation state move in a non-local search pattern, the search pattern of activated CTLs is more localised. In this paper, we develop a kinetic model for such a switch in CTL migration modes. The model is formulated as a coupled system of balance equations for the one-particle distribution functions of CTLs in the pre-activation state, activated CTLs and DCs. CTL activation is modelled via binary interactions between CTLs in the pre-activation state and DCs. Moreover, cell motion is represented as a velocity-jump process, with the running time of CTLs in the pre-activation state following a long-tailed distribution, which is consistent with a Lévy walk, and the running time of activated CTLs following a Poisson distribution, which corresponds to Brownian motion. We formally show that the macroscopic limit of the model comprises a coupled system of balance equations for the cell densities, whereby activated CTL movement is described via a classical diffusion term, whilst a fractional diffusion term describes the movement of CTLs in the pre-activation state. The modelling approach presented here and its possible generalisations are expected to find applications in the study of the immune response to cancer and in other biological contexts in which switch from non-local to localised migration patterns occurs. [ABSTRACT FROM AUTHOR]
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- 2023
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108. Exploring the Interactions of Oncolytic Viral Therapy and Immunotherapy of Anti-CTLA-4 for Malignant Melanoma Mice Model.
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Yu, Jui-Ling, Jang, Sophia R.-J., and Liu, Kwei-Yan
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ONCOLYTIC virotherapy , *MELANOMA , *T cells , *ANIMAL disease models , *IMMUNE checkpoint inhibitors , *IMMUNOTHERAPY - Abstract
Oncolytic ability to direct target and lyse tumor cells makes oncolytic virus therapy (OVT) a promising approach to treating cancer. Despite its therapeutic potential to stimulate anti-tumor immune responses, it also has immunosuppressive effects. The efficacy of OVTs as monotherapies can be enhanced by appropriate adjuvant therapy such as anti-CTLA-4. In this paper, we propose a mathematical model to explore the interactions of combined therapy of oncolytic viruses and a checkpoint inhibitor, anti-CTLA-4. The model incorporates both the susceptible and infected tumor populations, natural killer cell population, virus population, tumor-specific immune populations, virus-specific immune populations, tumor suppressive cytokine IFN-g, and the effect of immune checkpoint inhibitor CTLA-4. In particular, we distinguish the tumor-specific immune abilities of CD8+ T, NK cells, and CD4+ T cells and describe the destructive ability of cytokine on tumor cells as well as the inhibitory capacity of CTLA-4 on various components. Our model is validated through the experimental results. We also investigate various dosing strategies to improve treatment outcomes. Our study reveals that tumor killing rate by cytokines, cytokine decay rate, and tumor growth rate play important roles on both the OVT monotherapy and the combination therapy. Moreover, parameters related to CD8+ T cell killing have a large impact on treatment outcomes with OVT alone, whereas parameters associated with IFN-g strongly influence treatment responses for the combined therapy. We also found that virus killing by NK cells may halt the desired spread of OVs and enhance the probability of tumor escape during the treatment. Our study reveals that it is the activation of host anti-tumor immune system responses rather than its direct destruction of the tumor cells plays a major biological function of the combined therapy. [ABSTRACT FROM AUTHOR]
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- 2023
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109. Circuit-level design of radiation tolerant memory cell.
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Pandey, Monalisa and Islam, Aminul
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STATIC random access memory , *SINGLE event effects , *ASTROPHYSICAL radiation , *PARTICLE tracks (Nuclear physics) , *T cells , *SPACE environment , *ELECTROSTATIC discharges - Abstract
As transistors shrink in size, the integration density of memory circuits like Static Random Access Memory (SRAM) cells rises, making them increasingly susceptible to Single Event Effects (SEE). In the space environment, memory circuits face stability and reliability challenges due to the presence of various charged particles such as α-particles, neutrons, electrons, heavy ions, and photons. These high-energy particles create ion tracks when they strike the memory device, leading to upsets in the storage bits. Conventional 6 T SRAM cells are susceptible to these upsets. As a solution this paper proposes a new Radiation Tolerable (RT 13 T) SRAM cell that is better suited for deep-space applications compared to other memory cell. RT13T has been validated to withstand radiation hazards through Critical Charge (Q Crit) analysis, which shows that it exhibits 1.17×, 1.1×, 1.94× and 1.06× highest Q Crit than QUCCE 10 T/12 T,traditional 6 T and LIOR 13 T memory cells, respectively. As the comparison made, our Proposed RT 13 T saved by5.1 %,9.9 %, 20.1 % and 7 % of the power consumption compared to QUCCE10T/12 T/LIOR 13 T/SERSC-16 T SRAM cells at a nominal supply voltage of 0.7 V. It also exhibits shorter read delay (T RA) 10.6 %, 1.34 %, 9.6 %, 22.16 %compared to QUCCE 10 T/12 T,6T, SERSC-16Tmemory cells, respectively. In terms of stability,our proposed RT13T SRAM cell exhibits 2.32×/2.05×/2.9×/1.05×/1.01 × higher read stability as compared with QUCCE10T/12 T/6T/LIOR 13 T/SERSC-16 T memory cells during the read operation. The our proposed RT13T shows improvements in design metrics are at the expense of a longer write delay. To characterize the performances of the proposed RT13T, 16-nm CMOS predictive technology model and validated through extensive simulation with licensed PrimeSim HSPICE of Synopsys. The results of our proposed RT13T cell are compared with some other previously proposed memory cells such as 6 T, QUCCE 10 T, QUCCE 12 T, LIOR 13 T and SERSC-16 T memory cells. The obtained results are tabulated and plotted for graphical analysis. In terms of area consumption our proposed 13 T consumes 0.9×/0.6 × lesser area than QUCCE 12 T/SERSC-16 T memory cells but our proposed circuit consumes 3.1×/1.08×/1.05 × more area than QUCCE10T/conventional 6 T/LIOR 13 T because QUCCE10T and 6 T consist of less number of transistors in memory cells.The cell proposed in this paper demonstrates strong radiation-hardened capabilities and excellent overall performance, making it well-suited for aerospace electronic devices and ensuring stable operation in space radiation environments. [ABSTRACT FROM AUTHOR]
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- 2024
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110. Mathematical analysis of Hepatitis C Virus infection model in the framework of non-local and non-singular kernel fractional derivative.
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Slimane, Ibrahim, Nazir, Ghazala, Nieto, Juan J., and Yaqoob, Faheem
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HEPATITIS C , *CYTOTOXIC T cells , *MATHEMATICAL analysis , *HEPATITIS C virus , *T cells , *DENDRITIC cells - Abstract
In this paper, we study a mathematical model of Hepatitis C Virus (HCV) infection. We present a compartmental mathematical model involving healthy hepatocytes, infected hepatocytes, non-activated dendritic cells, activated dendritic cells and cytotoxic T lymphocytes. The derivative used is of non-local fractional order and with non-singular kernel. The existence and uniqueness of the system is proven and its stability is analyzed. Then, by applying the Laplace Adomian decomposition method for the fractional derivative, we present the semi-analytical solution of the model. Finally, some numerical simulations are performed for concrete values of the parameters and several graphs are plotted to reveal the qualitative properties of the solutions. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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111. Bile acids regulate MAdCAM-1 expression to link the gut microbiota to cancer immunosurveillance.
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Fidelle, Marine, Tian, Ai-Ling, Zitvogel, Laurence, and Kroemer, Guido
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BILE acids , *GUT microbiome , *LYMPHOID tissue , *IMMUNE checkpoint proteins , *T cells - Abstract
In a recent paper in Science, Fidelle et al. unravel a gut immune checkpoint that is subverted by antibiotic treatment. Post-antibiotic dysbiosis of the ileum causes an increase in bile acids that downregulate MAdCAM−1, thereby triggering the exodus of immunosuppressive T cells from gut-associated lymphoid tissues toward tumors. [ABSTRACT FROM AUTHOR]
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- 2023
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112. Ephedrae Herba polysaccharides inhibit the inflammation of ovalbumin induced asthma by regulating Th1/Th2 and Th17/Treg cell immune imbalance.
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Zhang, Beibei, Zeng, Mengnan, Zhang, Qinqin, Wang, Ru, Jia, Jufang, Cao, Bing, Liu, Meng, Guo, Pengli, Zhang, Yuhan, Zheng, Xiaoke, and Feng, Weisheng
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KILLER cells , *IMMUNOGLOBULIN E , *TUMOR necrosis factors , *TRANSFORMING growth factors , *POLYSACCHARIDES , *T helper cells , *T cells , *NEUTROPHILS - Abstract
This study aimed to investigate the anti-asthma effects of Ephedrae Herba polysaccharides (PE) and possible mechanisms related to immune inflammatory response. An asthma model was established in rats using ovalbumin (OVA). Seventy rats were randomly assigned to five groups: control, model, dexamethasone (DEX, 0.075 mg/kg), low dose polysaccharides (LPE, 137.71 mg/kg) and high dose polysaccharides (HPE, 275.42 mg/kg). The cough and asthma were used to evaluate the basic state of asthmatic rats. Histological studies were evaluated by hematoxylin and eosin (H&E), Masson, and periodic acid-schiff (PAS) staining. The levels of interferon-γ (IFN-γ), interleukin (IL)-4, immunoglobulin E (IgE), tumor necrosis factor α (TNF-α), and IL-17A in bronchoalveolar lavage fluid (BALF), and the levels of transforming growth factor β1 (TGF-β1), IL-6, and IL-10 in serum were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of Ifn-γ , Il-4 , Tgf-β1 , Il-6 , Il-10 , Tnf-α , Il-13 , and Il-17a were evaluated by quantitative real-time reverse transcription (qRT)-PCR. The dendritic cell (DCs), T helper cell (Th), natural killer cell (NK), regulatory T cell (Treg), and Th17 cells in blood, the lymphocytes, macrophages and neutrophils in spleen, and cell apoptosis and reactive oxygen species (ROS) in lung were analysed by flow cytometry (FCM). Immunohistochemistry (IHC) was used to stain DCs (CD11c+, CD86+, and CD80+), macrophages (CD68+), and neutrophils (MPO+) in the spleen and lung. The protein levels of IL-17A, CD11c, CD86, and CD80 in lung were measured by western blot. Our study demonstrated that PE could effectively improve the symptoms of asthmatic rats, ameliorate the lung pathological injury, inhibit inflammation, apoptosis and oxidative stress, regulate the levels of macrophages, neutrophils, DCs, NK, Thc, Treg and Th17 cells. PE could collectively inhibit the inflammation, apoptosis and ROS in asthma rats induced by OVA via regulating Th1/Th2 and Th17/Treg cell immune imbalance. [Display omitted] • This paper is the first to explore the intervention effect and mechanism of polysaccharides in Ephedrae Herba on OVA-induced allergic asthma. • Ephedrae Herba polysaccharides may treat OVA-induced allergic asthma by modulating inflammation and immunity. [ABSTRACT FROM AUTHOR]
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- 2022
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113. Modelling health impacts of hepatitis – model selection and treatment plans.
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Reisch, Cordula
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HEPATITIS B , *HEPATITIS , *GRAVES' disease , *HEPATITIS C , *LIVER cells , *T cells - Abstract
Hepatitis B and C are viruses causing liver infections and resulting in grave secondary diseases. While there are different treatments for chronic liver infections, the process of evolving chronic diseases is still not fully understood. This paper presents an economic-inspired model for the overall health of an infected organism. The health model is based on the results of a reaction diffusion model for describing the space-dependent dynamics of virus and T cells during a liver infection. The different treatments affect the parameters of the reaction diffusion model and influence therefore the well-being of the infected person during an infection. The health model is selected in a detailed process out of a class of possible models. The presented work provides a foundation for an optimal control problem for finding the best treatment strategy. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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114. Analysis of HIV latent infection model with multiple infection stages and different drug classes.
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Alshorman, Areej, Al-hosainat, Nidal, and Jackson, Trachette
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LATENT infection , *HIV infections , *HIGHLY active antiretroviral therapy , *HIV , *HIV infection transmission , *T cells - Abstract
Latently infected CD 4 + T cells represent one of the major obstacles to HIV eradication even after receiving prolonged highly active anti-retroviral therapy (HAART). Long-term use of HAART causes the emergence of drug-resistant virus which is then involved in HIV transmission. In this paper, we develop mathematical HIV models with staged disease progression by incorporating entry inhibitor and latently infected cells. We find that entry inhibitor has the same effect as protease inhibitor on the model dynamics and therefore would benefit HIV patients who developed resistance to many of current anti-HIV medications. Numerical simulations illustrate the theoretical results and show that the virus and latently infected cells reach an infected steady state in the absence of treatment and are eliminated under treatment whereas the model including homeostatic proliferation of latently infected cells maintains the virus at low level during suppressive treatment. Therefore, complete cure of HIV needs complete eradication of latent reservoirs. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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115. TMPRSS4 is a novel biomarker and correlated with immune infiltration in thyroid carcinoma.
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Xu, Xiaoqin, Sun, Ting, and Jing, Jiexian
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BIOMARKERS , *THYROID gland tumors , *PROTEOLYTIC enzymes , *LYMPH nodes , *CELL receptors , *TREATMENT effectiveness , *TUMOR classification , *KAPLAN-Meier estimator , *GENETIC markers , *HISTOLOGY , *T cells , *CHEMOKINES - Abstract
Transmembrane protease serine 4 (TMPRSS4) is a cancer-associated protease associated with prognosis in various types of cancer. Mechanistically, TMPRSS4 mainly regulates malignant phenotypes, such as tumor invasion and metastasis, by either the epithelial to mesenchymal transition (EMT) program or promoting the proliferation of cancer cells. To date, TMPRSS4 and immune infiltration in thyroid carcinoma (TC) are largely unknown. Thus, this paper evaluated the expression of TMPRSS4 in tumor tissue through the Tumor Immune Estimation Resource (TIMER) database, and Oncomine, and its correlation with clinical parameters by UALCAN databases. Furthermore, we analyzed its prognostic value from Kaplan-Meier Plotter database, and the relationship between TMPRSS4 and the abundance of tumor-infiltrating lymphocytes (TILs) in TC in TISIDB, screening potential immune targets to explore novel mechanisms for the clinical management of TC. Finally, we assessed the correlation between TMPRSS4 and some immune markers to uncover a potential immune-related biomarker in TC patients by TIMER2.0. The results revealed that TMPRSS4 was highly expressed in TC and was also associated with lymphatic metastasis, advanced stage, histological subtype, and favorable clinical outcome. The stratified analysis based on immune cell content showed that decreased TMPRSS4 had worse prognosis in CD8+ T cell-enriched TC patients. TMPRSS4 was positively correlated with tumor immune infiltration and the expression of gene markers of immune cells. Notably, its expression was lower in the lymphocyte-depleted subtype than in other immunosubtypes in TC. Moreover, TMPRSS4 was closely related to chemokines as well as their receptors and the immunosuppressive checkpoints CTLA-4, PD-1, and HLA-G. In conclusion, TMPRSS4 may act as a novel biomarker predicting prognosis and immune infiltration in TC. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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116. Cytomegalovirus-Specific T Cells from Third-Party Donors Successfully Treated Refractory Cytomegalovirus Retinitis after Unrelated Umbilical Cord Blood Transplantation.
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Li, Na, Sun, Guangyu, Zhu, Lihua, Ding, Kang, Liu, Huilan, Zhu, Xiaoyu, Tang, Baolin, Yao, Wen, Wan, Xiang, Geng, Liangquan, Qiang, Ping, Song, Kaidi, Zheng, Changcheng, Sun, Zimin, and Tong, Juan
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CORD blood transplantation , *T cells , *CORD blood , *HEMATOPOIETIC stem cell transplantation , *TREATMENT effectiveness , *CYTOMEGALOVIRUS retinitis treatment , *CYTOMEGALOVIRUS retinitis , *CYTOMEGALOVIRUSES - Abstract
Umbilical cord blood (UCB) transplants (UCBTs) are becoming increasingly common in the treatment of a variety of hematologic and nonhematologic conditions. The T cells from UCB are naïve T cells, which have not yet been exposed to antigens and therefore do not contain T cells with specific immune functions against viruses. Cytomegalovirus (CMV) infections occur in more than 80% of patients after UCBT compared to other types of transplantation. Anti-CMV medications are currently restricted, with ganciclovir, foscarnet, and valganciclovir being the most common in China; however, with limited efficacy and considerable side effects, all these drugs are susceptible to viral resistance. In recent years, cytomegalovirus-specific T cells (CMVST) have advanced the treatment of viral infections in immunodeficient patients. CMVST usually uses the same donor as hematopoietic stem cell transplantation. CMVST should be administered to UCBT patients because of the absence of donors after UCBT. In China, there is no report on the use of CMVST to treat CMV infection after UCBT, and foreign reports are also limited. This paper reported a 20-year-old male patient with acute myeloid leukemia who developed cytomegalovirus retinitis (CMVR) after umbilical cord blood transplantation. After ineffective viral treatment, he was treated with a third-party donor CMVST and was successfully transformed into CMV nucleic acid negative. [ABSTRACT FROM AUTHOR]
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- 2022
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117. Clinical Study of the Relationship between Sjögren Syndrome and T-Cell Large Granular Lymphocytic Leukemia: Single-Center Experience.
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Gorodetskiy, Vadim, Vasilyev, Vladimir, Sidorova, Yulia, Biderman, Bella, Kupryshina, Natalia, Vagida, Murad, Ryzhikova, Natalya, and Sudarikov, Andrey
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LYMPHOCYTIC leukemia , *SJOGREN'S syndrome , *T cells , *ANTINUCLEAR factors , *RHEUMATISM - Abstract
The relationship between Sjögren syndrome (SS) and T-cell large granular lymphocytic (T-LGL) leukemia remains unclear. In this paper, we report for the first time a large case series of 21 patients with primary and secondary SS associated with T-LGL leukemia. Our results suggest the importance of considering T-LGL leukemia in the diagnostic evaluation of SS patients, particularly when neutropenia occurs. We also postulate that elevated antinuclear antibody titers in patients with T-LGL leukemia indicate the need for the clinical assessment of SS. To assess whether SS affects the frequency of the signal transducer and activator of transcription 3 (STAT3) gene mutations in T-LGL leukemia, we examined STAT3 mutations by next-generation sequencing in two cohorts of patients: with SS-associated T-LGL leukemia and T-LGL leukemia in the setting of rheumatic diseases but without SS. While our results suggest that SS, per se, is not associated with an increased frequency of STAT3 mutations in T-LGL leukemia, further studies are needed to better assess the role of the STAT pathway in the development of concomitant SS and T-LGL leukemia. [ABSTRACT FROM AUTHOR]
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- 2022
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118. Attention-aware contrastive learning for predicting T cell receptor–antigen binding specificity.
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Fang, Yiming, Liu, Xuejun, and Liu, Hui
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SUPERVISED learning , *T cells , *T cell receptors , *MAJOR histocompatibility complex , *KILLER cells , *TASK performance , *AMINO acids - Abstract
Motivation It has been proven that only a small fraction of the neoantigens presented by major histocompatibility complex (MHC) class I molecules on the cell surface can elicit T cells. This restriction can be attributed to the binding specificity of T cell receptor (TCR) and peptide-MHC complex (pMHC). Computational prediction of T cells binding to neoantigens is a challenging and unresolved task. Results In this paper, we proposed an attention-aware contrastive learning model, ATMTCR, to infer the TCR–pMHC binding specificity. For each TCR sequence, we used a transformer encoder to transform it to latent representation, and then masked a percentage of amino acids guided by attention weights to generate its contrastive view. Compared to fully-supervised baseline model, we verified that contrastive learning-based pretraining on large-scale TCR sequences significantly improved the prediction performance of downstream tasks. Interestingly, masking a percentage of amino acids with low attention weights yielded best performance compared to other masking strategies. Comparison experiments on two independent datasets demonstrated our method achieved better performance than other existing algorithms. Moreover, we identified important amino acids and their positional preference through attention weights, which indicated the potential interpretability of our proposed model. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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119. Treatment horizon in multiple myeloma.
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Soekojo, Cinnie Yentia and Chng, Wee Joo
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MULTIPLE myeloma , *ANTIBODY-drug conjugates , *MONOCLONAL antibodies , *OVERALL survival , *T cells - Abstract
Objectives: This paper reviews current and emerging therapies for multiple myeloma (MM). Methods: Narrative review. Results: MM is a complex, heterogenous condition, and in recent years there has been an expansion in the number and range of treatments. Several new treatment approaches, including enhanced monoclonal antibodies, antibody‐drug conjugates, bispecific T‐cell engagers, and chimeric antigen‐T‐cell therapy are under development. Conclusions: The emergence of new treatments that aim to tackle MM‐associated immune dysfunction has led to improvements in overall survival. [ABSTRACT FROM AUTHOR]
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- 2022
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120. Implications and Emerging Therapeutic Avenues of Inflammatory Response in HPV+ Head and Neck Squamous Cell Carcinoma.
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Castellano, Lúcio Roberto Cançado, Cruz, Sara Brito Silva Costa, Hier, Michael, Bonan, Paulo Rogério Ferreti, Alaoui-Jamali, Moulay A., and da Silva, Sabrina Daniela
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HEAD & neck cancer treatment , *CANCER patient psychology , *GENETIC mutation , *CANCER chemotherapy , *HEAD & neck cancer , *CELL physiology , *TREATMENT effectiveness , *PAPILLOMAVIRUS diseases , *QUALITY of life , *T cells , *CELL lines , *SQUAMOUS cell carcinoma , *COMORBIDITY , *DRUG resistance in cancer cells , *IMMUNOTHERAPY - Abstract
Simple Summary: Cancer in the head and neck region (HNSCC) is exponentially increasing due to human papillomavirus (HPV) infections. This paper helps us to understand the complexity of the inflammatory networks and the mechanisms of immune evasion in HPV+ HNSCC to open up new avenues and drive the discovery of useful tools to be translated clinically in the screening and treatment of these cases, especially to overcome resistance and improve patients' quality of life. Head and neck squamous cell carcinomas (HNSCC) are a heterogeneous group of malignancies which have shown exponential incidence in the last two decades especially due to human papillomavirus (HPV) infection. The HPV family comprises more than 100 types of viruses with HPV16 and HPV18 being the most prevalent strains in HNSCC. Literature data reveal that the mutation profile as well as the response to chemotherapy and radiotherapy are distinct among HPV+ versus HPV-negative tumors. Furthermore, the presence of the virus induces activation of an immune response, in particular the recruitment of specific antiviral T lymphocytes to tumor sites. These T cells when activated produce soluble factors including cytokines and chemokines capable of modifying the local immune tumor microenvironment and impact on tumor response to the treatment. In this comprehensive review we investigated current knowledge on how the presence of an HPV can modify the inflammatory response systemically and within the tumor microenvironment's immunological responses, thereby impacting on disease prognosis and survival. We highlighted the research gaps and emerging approaches necessary to discover novel immunotherapeutic targets for HPV-associated HNSCC. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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121. The effect of noise in an HIV infection model with cytotoxic T-lymphocyte impairment.
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Majumder, Abhijit, Sardar, Shibani, and Bairagi, Nandadulal
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HIV infections , *CYTOTOXIC T cells , *HIV , *STOCHASTIC analysis , *T cells , *CELLULAR recognition - Abstract
The human immunodeficiency virus (HIV) interacts with the immune cells within the human body, where the environment is uncertain and noisy. Stochastic models can successfully encapsulate the effect of such a noisy environment compared to their deterministic counterparts. The human immune system is complex but well-coordinated with various immune cells like C D 4 + T cells, dendritic cells, and cytotoxic T-lymphocyte (CTL) cells, among many others. The CTL can kill the antigenic cells after its recognition. However, the efficacy of CTL in removing the infected C D 4 + T cells is progressively compromised in HIV-infected individuals. This paper considers a noise-induced HIV-immune cell interaction model with immune impairment. A multiplicative white noise is introduced in the infection rate parameter to represent the fluctuations around the average value of the rate parameter as a causative effect of the noise. We analyzed the deterministic and stochastic models and prescribed sufficient conditions for infection eradication and persistence. It is determined under what parametric restrictions the asymptotic solutions of the noise-induced system will be a limiting case of the deterministic solutions. Simulation results revealed that the solutions of the deterministic system either converge to a CTL-dominated interior equilibrium or a CTL-free immunodeficient equilibrium, depending on the initial values of the system. Stochastic analysis divulged that higher noise might be helpful in the infection removal process. The extinction time of infected C D 4 + T cells for some fixed immune impairment gradually decreases with increasing noise intensity and follows the power law. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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122. Abstracts of papers presented at the 32nd Annual Meeting of the American Society of Dermatopathology.
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SKIN diseases , *ANNUAL meetings , *GRANULOMA , *CUTANEOUS manifestations of general diseases , *ETIOLOGY of diseases , *T cells - Abstract
This article focuses on abstracts of papers presented at the 32nd annual meeting of the American Society of Dermatopathology at Intercontinental Hotel, New Orleans between February 1-3, 1995. The Kveim-Siltzbach Reactions (KSR) is an important model for investigating immunologic events in granuloma formation. It has been shown that T lymphocyte predominance with oligocionality of infiltrating cells in 4 week-old KSR. Verruciform xanthoma is a rare benign condition that commonly involves the oral mucosa. Cutaneous lesions are less often observed, predominantly occurring at anogenital sites. Despite anecdotal reports of its occurrence in a variety of disease states, the etiology of this condition remains unclear.
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- 1995
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123. Abstracts of papers presented at the 29th Annual meeting of the American Society of Dermatopathology.
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DERMATOLOGY , *ANNUAL meetings , *PATHOLOGY , *T cells - Abstract
The article presents information on abstracts of papers presented at the 29th Annual meeting of the American Society of Dermatopathology. Some of the titles are, "Histomorphometry of Dysplastic and Other Melanocytic Lesions: Correlation With Subjective grading and Flow Cytometry," by R.L. Barnhill, J.A. Bruijn, M. Berwick, M.C. Mihm, Jr., and D. Weinberg, " "Basaloid Follicular Hamartoma: Solitary and Multiple Types," by M.H. Brownstein, "CD30 Positive Plemorphic Large Cell Cutaneous T-Cells Lymphoma," by N.P. Burrows, S. Whittaker, R. Russell Jones, and others.
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- 1991
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124. Educational paper. The expanding clinical and immunological spectrum of severe combined immunodeficiency.
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van der Burg, Mirjam and Gennery, Andy R.
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IMMUNODEFICIENCY , *T cells , *LYMPHOCYTES , *PEDIATRIC emergencies , *IMMUNOPATHOLOGY - Abstract
Severe combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency characterized by absence of functional T lymphocytes. It is a paediatric emergency, which is life-threatening when recognized too late. The clinical presentation varies from the classical form of SCID through atypical SCID to Omenn syndrome. In addition, there is a considerable immunological variation, which can hamper the diagnosis. In this educational review, we describe the immunopathological background, clinical presentations and diagnostic process of SCID, as well as the therapeutic possibilities. [ABSTRACT FROM AUTHOR]
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- 2011
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125. CAR-T cells secreting immune checkpoint antibodies relieve immunosuppression.
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Lv, Keyi
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IMMUNE checkpoint proteins , *IMMUNOGLOBULINS , *IMMUNOSUPPRESSION , *PROGRAMMED death-ligand 1 , *IMMUNOLOGICAL tolerance , *T cells , *PROGRAMMED cell death 1 receptors , *CYTOTOXIC T cells - Abstract
Tumor microenvironment (TME) plays a key role in tumor immune escape. PD-1/PD-L1 signal transduction pathway can achieve tumor immune escape by enhancing tumor cell immune tolerance and inhibiting the activation of T lymphocytes. In recent years, immunosuppression, as one of the many mechanisms of tumor immune escape, has also become a research hotspo. The optimized CAR-T cells released immunosuppression by secreting antibodies against checkpoint inhibitors. Therefore, CAR-T therapy targeting tumor micro environment and PD-1/PD-L1 pathway are important methods for cancer treatment. This paper summarizes the role of PD-1/PD-L1 signaling pathway in mediating tumor escape in tumor microenvironment, and briefly introduces CAR-T immunotherapy and its TME-related targets. [ABSTRACT FROM AUTHOR]
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- 2022
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126. Regulatory T Cells in Bioactive Peptides-Induced Oral Tolerance; a Two-Edged Sword Related to the Risk of Chronic Diseases: A Systematic Review.
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Barati, Meisam, Jabbari, Masoumeh, Nickho, Hamid, Esparvarinha, Mojgan, Javadi Mamaghani, Amirreza, Majdi, Hasan, Fathollahi, Anwar, and Davoodi, Sayed Hossein
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DIETARY bioactive peptides , *CHRONIC disease risk factors , *TUMOR risk factors , *COLLAGEN , *ONLINE information services , *CARDIOVASCULAR diseases risk factors , *SYSTEMATIC reviews , *RISK assessment , *DIETARY supplements , *OSTEOARTHRITIS , *T cells , *MEDLINE - Abstract
This systematic review assesses the literature regarding beneficial and potential detrimental effects of bioactive peptides (BPs), focusing on evidence of regulatory T cells (T-regs) mediated oral tolerance (OT), collagen hydrolysate (CH) supplementation in osteoarthritis (OA) and the association of T-regs with chronic disease. The systematic search was done for articles published from inception to April 2019 using the PubMed and Scopus databases. About 3081 papers were identified by three different search strategies and screened against inclusion criteria which resulted in the inclusion of 22 articles. From the included articles, 12 papers were related to treatment of different disease in vivo by oral administration of BPs, six articles evaluated the effects of CH supplementation, as a rich source of BPs, on OA pain-relief and four observational studies assessed the association of circulating T-regs and risk of cancer and cardiovascular disease (CVD). The evidence obtained from first search strategy, indicated that oral administration of BPs improve clinical manifestations of animal models of allergy, arthritis, atherosclerosis, ulcerative colitis and allograft rejection by T-regs expansion; while, observational studies showed that although higher levels of circulating T-regs reduced risk of CVD and allergy, but, increased risk of solid cancers. [ABSTRACT FROM AUTHOR]
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- 2021
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127. Meet the authors: Dr. Clint Allen and Dr. Sandro Santagata.
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Allen, Clint and Santagata, Sandro
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HEAD & neck cancer , *PHENOTYPIC plasticity , *LUNGS , *CYTOTOXIC T cells , *T cells - Abstract
In this Q&A, Cell Press Community Review Scientific Editor Leia Judge talks to Dr. Clint Allen and Dr. Sandro Santagata about their new papers "Phenotypic plasticity and reduced tissue retention of exhausted tumor-infiltrating T cells following neoadjuvant immunotherapy in head and neck cancer" and "Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma" and their experiences with publishing through Cell Press Community Review. [ABSTRACT FROM AUTHOR]
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- 2023
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128. Hypoxia-Regulated Tumor-Derived Exosomes and Tumor Progression: A Focus on Immune Evasion.
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Shao, Xuejun, Hua, Shenghao, Feng, Tao, Ocansey, Dickson Kofi Wiredu, and Yin, Lei
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EXOSOMES , *CANCER invasiveness , *MYELOID-derived suppressor cells , *REGULATORY T cells , *T cells , *IMMUNOSUPPRESSION - Abstract
Tumor cells express a high quantity of exosomes packaged with unique cargos under hypoxia, an important characteristic feature in solid tumors. These hypoxic tumor-derived exosomes are, crucially, involved in the interaction of cancer cells with their microenvironment, facilitating not only immune evasion, but increased cell growth and survival, enhanced angiogenesis, epithelial–mesenchymal transition (EMT), therapeutic resistance, autophagy, pre-metastasis, and metastasis. This paper explores the tumor microenvironment (TME) remodeling effects of hypoxic tumor-derived exosome towards facilitating the tumor progression process, particularly, the modulatory role of these factors on tumor cell immune evasion through suppression of immune cells, expression of surface recognition molecules, and secretion of antitumor soluble factor. Tumor-expressed exosomes educate immune effector cells, including macrophages, monocytes, T cells, natural killer (NK) cells, dendritic cells (DCs), γδ T lymphocytes, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), mast cells, and B cells, within the hypoxic TME through the release of factors that regulate their recruitment, phenotype, and function. Thus, both hypoxia and tumor-derived exosomes modulate immune cells, growth factors, cytokines, receptor molecules, and other soluble factors, which, together, collaborate to form the immune-suppressive milieu of the tumor environment. Exploring the contribution of exosomal cargos, such as RNAs and proteins, as indispensable players in the cross-talk within the hypoxic tumor microenvironmental provides a potential target for antitumor immunity or subverting immune evasion and enhancing tumor therapies. [ABSTRACT FROM AUTHOR]
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- 2022
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129. T-cell receptor variable region usage in Chagas disease: A systematic review of experimental and human studies.
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de Souza-Silva, Thaiany Goulart, Gollob, Kenneth J., and Dutra, Walderez O.
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CHAGAS' disease , *NEGLECTED diseases , *T cells , *MAJOR histocompatibility complex , *SCIENCE databases , *BURULI ulcer - Abstract
T cells recognize their ligand, the peptide major histocompatibility complex (MHC), via the T-cell receptor (TCR), which is composed of covalently linked α and β or γ and δ chains. This recognition is critical for T-cell ontogeny and controls the selection, activation, and function of T lymphocytes. Specific TCR αβ variable regions have been associated with immunopathogenesis of Chagas disease. Here, we present a systematic review that compiles experimental in vivo and human data regarding the preferential expression of variable alpha (Vα) and variable beta (Vβ) chain regions in Trypanosoma cruzi infection. The original studies indexed in PubMed/Medline, Scopus, and Web of Science databases were screened according to the PRISMA strategy. The analysis showed that expression of TCR Vα subfamilies were evaluated in one human study, and, unlike TCR Vβ, TCR Vα presented a more restricted usage. Despite the great variability in the usage of TCR Vβ regions in human Chagas disease, a down-regulation of TCR Vβ5 expression by T cells from patients in the acute phase of the disease was shown. Opposingly, this TCR region was found overly expressed in CD4+ T cells from chronic Chagas patients. It was also demonstrated that murine Vβ9+ T cells derived from nonlymphoid organs of T. cruzi-infected animals had a modulatory profile, while splenic Vβ9+ T cells produced inflammatory cytokines, indicating that although they display the same TCR Vβ region usage, these cells are functionally distinct. Despite the limitations of few papers and year of publication of the studies, compiling the data derived from them reveals that further investigation of TCR usage will point to their potential role in protective or pathogenic responses, as biomarkers of disease progression, and in the search for dominant peptides potentially useful for the development of vaccines or therapies. Author summary: Chagas disease is a neglected tropical disease, caused by infection with Trypanosoma cruzi. Differential expression of certain T-cell receptor (TCR) variable regions has been associated with the immunopathogenesis of Chagas disease. Here, we present a systematic review that compiled experimental in vivo and human data regarding the preferential expression of TCR alpha and beta chain variable regions in Chagas disease. The original studies indexed in the PubMed/Medline, Scopus, and Web of Science databases were screened according to the PRISMA strategy. Despite the great variability in the use of TCR Vβ in T. cruzi infection, the outcomes indicate that there is a down-regulation of TCR Vβ5 expression in T cells from patients in the acute phase of Chagas disease. However, this region is preferentially expressed by CD4+ T cells from chronic Chagas patients. Additionally, it has been demonstrated that murine Vβ9+ T cells derived from nonlymphoid organs displayed a modulatory profile, while splenic Vβ9+ T cells produced inflammatory cytokines, indicating that although they express the same TCR Vβ region, these cells are functionally distinct. Information on TCR expression, specificity and function have critical impact on vaccine design. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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130. Pathological and Molecular Features of Nodal Peripheral T-Cell Lymphomas.
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Satou, Akira, Takahara, Taishi, and Tsuzuki, Toyonori
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ANAPLASTIC large-cell lymphoma , *T-cell lymphoma , *T helper cells , *LYMPHOMAS , *T cells , *CUTANEOUS T-cell lymphoma - Abstract
Peripheral T-cell lymphomas (PTCLs) are uncommon neoplasms derived from mature T cells or NK cells. PTCLs comprise numerous disease entities, with over 30 distinct entities listed in the latest WHO classification. They predominantly affect adults and elderly people and usually exhibit an aggressive clinical course with poor prognosis. According to their presentation, PTCLs can be divided into nodal, extranodal or cutaneous, and leukemic types. The most frequent primary sites of PTCLs are lymph nodes, with over half of cases showing nodal presentation. Nodal PTCLs include ALK-positive and ALK-negative anaplastic large cell lymphoma; nodal T-cell lymphoma with T follicular helper cell origin; and PTCL, not otherwise specified. Adult T-cell leukemia/lymphoma also frequently affects lymph nodes. Recent pathological and molecular findings in nodal PTCLs have profoundly advanced the identification of tumor signatures and the refinement of the classification. Therefore, the therapies and pathological diagnosis of nodal PTCLs are continually evolving. This paper aims to provide a summary and update of the pathological and molecular features of nodal PTCLs, which will be helpful for diagnostic practice. [ABSTRACT FROM AUTHOR]
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- 2022
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131. Fault self-healing: A biological immune heuristic reinforcement learning method with root cause reasoning in industrial manufacturing process.
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Tian, JiaYi, Yin, Ming, and Jiang, Jijiao
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REINFORCEMENT learning , *MANUFACTURING processes , *T helper cells , *T cells , *HEALING , *CONVOLUTIONAL neural networks , *INDUSTRIALISM - Abstract
Stable fault self-healing ensures the smooth operation of intelligent industrial manufacturing processes. However, current research, while capable of inferring fault propagation paths or individually controlling manufacturing processes, still faces some challenges and limitations in addressing issues within manufacturing processes. In particular, it is easy to overlook the impact of fault variables on normal causal relationships in the manufacturing process and how to achieve adaptive fault repair from the source of faults. The biological immune system possesses sensitive nodes and a neuro-endocrine-immune network with interconnected functionalities, bearing remarkable resemblance to the sensor arrays, information networks, and intelligent controller systems in modern self-healing control systems. These problem domains have significant practical implications in industrial manufacturing processes and urgently require new methods and technologies to address them. To address the issue of root cause fault self-healing in intelligent industrial manufacturing processes, this paper proposes an innovative method that utilizes root cause inference and bio-inspired heuristic reinforcement learning models to achieve fault self-healing in industrial processes. First, innovatively introduce the Variational Autoencoder (VAE) into the Time Convolutional Network (TCN) to construct the TCN-VAE network. By performing feature reconstruction, the network's feature extraction capability is enhanced, further exploring the relationships between latent variables, and consequently building a causal graph of faults. A multi-head attention mechanism is introduced into the network, and the inference process is quantitatively evaluated, thereby improving the generalization and accuracy of root cause inference. Root cause determination rules are established to identify the fundamental reasons for fault occurrence, ensuring self-healing from the source of faults. Next, we developed for the first time a fault self-healing model based on reinforcement learning, utilizing the immune repair process of effector T cells to characterize the fault self-healing process. It effectively adapts to eliminate various levels of faults based on the state transition process of antigens in T helper cells. Additionally, stability control analysis is performed on the proposed model. The average reward function curve and Sobol sensitivity index demonstrates the model's strong robustness in practical applications. The validation results from case studies on the Tennessee Eastman (TE) and Continuous Stirred Tank Reactor (CSTR) show that the average improvement in fault repair F1 score was 0.0941 and 0.105 respectively, and the fastest improvement in fault repair response time was 0.266s and 0.258s respectively. It was confirmed that the root cause inference and fault repair results align with the actual mechanisms of the manufacturing processes. The proposed method has been verified to achieve stable and accurate root cause fault repair in real-world intelligent industrial manufacturing systems, making a significant contribution to achieving stable and accurate root cause fault repair in intelligent industrial manufacturing systems. • TCN-VAE enables feature reconstruction and latent variable exploration for root cause reasoning. • Multi-head attention enhances generality and accuracy in root cause reasoning. • Effector T-cell immune-inspired RL adapts to eliminate faults effectively. • The fault self-healing model exhibits strong reliability and robustness. • Method validated on Tennessee Eastman and continuous stirred-tank reactor datasets. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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132. Immunotoxicity of microplastics in fish.
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Li, Huiqi, Liu, Huanpeng, Bi, Liuliu, Liu, Yinai, Jin, Libo, and Peng, Renyi
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IMMUNOTOXICOLOGY , *MICROPLASTICS , *POLLUTANTS , *T cells , *HOMEOSTASIS , *PLASTIC scrap , *WATER pollution - Abstract
Plastic waste degrades slowly in aquatic environments, transforming into microplastics (MPs) and nanoplastics (NPs), which are subsequently ingested by fish and other aquatic organisms, causing both physical blockages and chemical toxicity. The fish immune system serves as a crucial defense against viruses and pollutants present in water. It is imperative to comprehend the detrimental effects of MPs on the fish immune system and conduct further research on immunological assessments. In this paper, the immune response and immunotoxicity of MPs and its combination with environmental pollutants on fish were reviewed. MPs not only inflict physical harm on the natural defense barriers like fish gills and vital immune organs such as the liver and intestinal tract but also penetrate cells, disrupting intracellular signaling pathways, altering the levels of immune cytokines and gene expression, perturbing immune homeostasis, and ultimately compromising specific immunity. Initially, fish exposed to MPs recruit a significant number of macrophages and T cells while activating lysosomes. Over time, this exposure leads to apoptosis of immune cells, a decline in lysosomal degradation capacity, lysosomal activity, and complement levels. MPs possess a small specific surface area and can efficiently bind with heavy metals, organic pollutants, and viruses, enhancing immune responses. Hence, there is a need for comprehensive studies on the shape, size, additives released from MPs, along with their immunotoxic effects and mechanisms in conjunction with other pollutants and viruses. These studies aim to solidify existing knowledge and delineate future research directions concerning the immunotoxicity of MPs on fish, which has implications for human health. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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133. Optimization of polydimethylsiloxane (PDMS) surface chemical modification and formulation for improved T cell activation and expansion.
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Zeng, Qiongjiao, Xu, Bowen, Deng, Jiewen, Shang, Kun, Guo, Zhenhong, and Wu, Shuqing
- Subjects
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T cells , *MECHANICAL chemistry , *POLYDIMETHYLSILOXANE , *YOUNG'S modulus , *SURFACE chemistry , *T cell receptors , *BIOCHEMICAL substrates - Abstract
Adoptive T cell therapy has undergone remarkable advancements in recent decades; nevertheless, the rapid and effective ex vivo expansion of tumor-reactive T cells remains a formidable challenge, limiting their clinical application. Artificial antigen-presenting substrates represent a promising avenue for enhancing the efficiency of adoptive immunotherapy and fostering T cell expansion. These substrates offer significant potential by providing flexibility and modularity in the design of tailored stimulatory environments. Polydimethylsiloxane (PDMS) silicone elastomer stands as a widely utilized biomaterial for exploring the varying sensitivity of T cell activation to substrate properties. This paper explores the optimization of PDMS surface modification and formulation to create customized stimulatory surfaces with the goal of enhancing T cell expansion. By employing soft PDMS elastomer functionalized through silanization and activating agent, coupled with site-directed protein immobilization techniques, a novel T cell stimulatory platform is introduced, facilitating T cell activation and proliferation. Notably, our findings underscore that softer modified elastomers (Young' modulus E∼300 kPa) exhibit superior efficacy in stimulating and activating mouse CD4+ T cells compared to their stiffer counterparts (E∼3 MPa). Furthermore, softened modified PDMS substrates demonstrate enhanced capabilities in T cell expansion and Th1 differentiation, offering promising insights for the advancement of T cell-based immunotherapy. [Display omitted] • Chemically modified layers and Protein A enhance antibody density and stability. • Softer elastomers better stimulate CD4+ T cells compared to stiffer ones. • Softened PDMS substrates enhance T cell expansion and Th1 differentiation. • Study shows surface chemistry and mechanical cues influence T cell behavior. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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134. FOXP3 (in)stability and cancer immunotherapy.
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Mortezaee, Keywan
- Subjects
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FORKHEAD transcription factors , *T cells , *REGULATORY T cells , *DEUBIQUITINATING enzymes , *IMMUNOTHERAPY - Abstract
• FOXP3 controls Treg differentiation and activity. • FOXP3 induces metabolic versatility in intra-tumoral Tregs. • Treg subsets show different reliance on FOXP3. Dysregulation of regulatory T cells (Tregs) is described in the context of inflammatory and autoimmune diseases, and cancer. Forkhead box P3 (FOXP3) is a transcription factor that its activity is an indicator of Treg identity. FOXP3 induces metabolic versatility in intra-tumoral Tregs, so that its deficiency mediates Treg instability or even gives rise to the acquisition of effector T cell phenotype. FOXP3 dysregulation and defectiveness occurs upon ubiquitination, methylation and presumably acetylation. Stimulators of PTEN, mammalian target of rapamycin complex 2 (mTORC2), and nucleus accumbens–associated protein-1 (NAC1), and inhibitors of B lymphocyte-induced maturation protein-1 (Blimp-1), Deltex1 (DTX1) and ubiquitin-specific peptidase 22 (USP22) are suggested to hamper FOXP3 stability, and to promote its downregulation and further Treg depletion. A point is that Treg subsets reveal different reliance on FOXP3, which indicates that not all Tregs are strictly dependent on FOXP3, and presumably Tregs with different origin rely on diverse regulators of FOXP3 stability. The focus of this review is over the current understanding toward FOXP3, its activity in Tregs and influence from different regulators within tumor microenvironment (TME). Implication of FOXP3 targeting in cancer immunotherapy is another focus of this paper. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
135. The interaction between the costimulatory molecules CD80/86 and CD28 contributed to CD4+ T lymphocyte activation in flounder (Paralichthys olivaceus).
- Author
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Xing, Jing, Hu, Yujie, Liu, Wenjing, Tang, Xiaoqian, Sheng, Xiuzhen, Chi, Heng, and Zhan, Wenbin
- Subjects
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T cells , *CD28 antigen , *LYMPHOCYTE transformation , *PARALICHTHYS , *CD4 antigen , *RECOMBINANT proteins , *T cell receptors - Abstract
CD28 and CD80/86 are crucial co-stimulatory molecules for the T cell activation. Previous study illustrated that CD28 and CD80/86 present on T cells and antigen-presenting cells in flounder (Paralichthys olivaceus), respectively. The co-stimulatory molecules were closely associated with cell immunity. In this paper, recombinant protein of flounder CD80/86 (rCD80/86) and phytohemagglutinin (PHA) were added to peripheral blood leukocytes (PBLs) in vitro. Lymphocytes were significantly proliferated with CFSE staining, and the proportion of CD4+ and CD28+ lymphocytes significantly increased. In the meantime, genes related to the CD28-CD80/86 signaling pathway or T cell markers were significantly upregulated (p < 0.05). For further study, the interaction between CD80/86 and CD28 was confirmed. The plasmid of CD28 (pCD28-FLAG and pVN-CD28) or CD80/86 (pVC-CD80/86) was successfully constructed. In addition, pVN-ΔCD28 without the conserved motif "TFPPPF" was constructed. The results showed that bands of pCD28-FLAG bound to rCD80/86 were detected by both anti-FLAG and anti-CD80/86. pVN-CD28 complemented to pVC-CD80/86 showing positive fluorescent signals, and pVN-ΔCD28 failed to combine with pVC-CD80/86. The motif "TFPPPF" in CD28 played a crucial role in this linkage. These results indicate that CD28 and CD80/86 molecules interact with each other, and their binding may modulate T lymphocytes immune response in flounder. This study proved the existence of CD28-CD80/86 signaling pathway in flounder. • RCD80/86 and PHA induced lymphocyte proliferation and proportion of CD4+ cells in flounder. • RCD80/86 and PHA upregulated the expression of B7-CD28 signaling pathway genes, T cell markers, and cytokines. • PCD28-FLAG bound to rCD80/86, and pVN-CD28 complemented to pVC-CD80/86 in vitro. • Motif of "TFPPPF" in CD28 plays crucial role in the interaction between CD28 and CD80/86. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
136. Targeted delivery of mycophenolic acid to the mesenteric lymph node using a triglyceride mimetic prodrug approach enhances gut-specific immunomodulation in mice.
- Author
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Kochappan, Ruby, Cao, Enyuan, Han, Sifei, Hu, Luojuan, Quach, Tim, Senyschyn, Danielle, Ferreira, Vilena Ivanova, Lee, Given, Leong, Nathania, Sharma, Garima, Lim, Shea Fern, Nowell, Cameron J., Chen, Ziqi, von Andrian, Ulrich H., Bonner, Daniel, Mintern, Justine D., Simpson, Jamie S., Trevaskis, Natalie L., and Porter, Christopher J.H.
- Subjects
- *
MYCOPHENOLIC acid , *GRAFT versus host disease , *LYMPH nodes , *IMMUNOREGULATION , *T cells , *LYMPHOID tissue - Abstract
The mesenteric lymph nodes (MLN) are a key site for the generation of adaptive immune responses to gut-derived antigenic material and immune cells within the MLN contribute to the pathophysiology of a range of conditions including inflammatory and autoimmune diseases, viral infections, graft versus host disease and cancer. Targeting immunomodulating drugs to the MLN may thus be beneficial in a range of conditions. This paper investigates the potential benefit of targeting a model immunosuppressant drug, mycophenolic acid (MPA), to T cells in the MLN, using a triglyceride (TG) mimetic prodrug approach. We confirmed that administration of MPA in the TG prodrug form (MPA-TG), increased lymphatic transport of MPA-related species 83-fold and increased MLN concentrations of MPA >20 fold, when compared to MPA alone, for up to 4 h in mice. At the same time, the plasma exposure of MPA and MPA-TG was similar, limiting the opportunity for systemic side effects. Confocal microscopy and flow cytometry studies with a fluorescent model prodrug (Bodipy-TG) revealed that the prodrug accumulated in the MLN cortex and paracortex at 5 and 10 h following administration and was highly associated with B cells and T cells that are found in these regions of the MLN. Finally, we demonstrated that MPA-TG was significantly more effective than MPA at inhibiting CD4+ and CD8+ T cell proliferation in the MLN of mice in response to an oral ovalbumin antigen challenge. In contrast, MPA-TG was no more effective than MPA at inhibiting T cell proliferation in peripheral LN when mice were challenged via SC administration of ovalbumin. This paper provides the first evidence of an in vivo pharmacodynamic benefit of targeting the MLN using a TG mimetic prodrug approach. The TG mimetic prodrug technology has the potential to benefit the treatment of a range of conditions where aberrant immune responses are initiated in gut-associated lymphoid tissues. [Display omitted] • Targeting lymphocytes in the mesenteric lymph nodes (MLN) enhances immunomodulation. • An oral triglyceride based prodrug promoted lymphatic transport and MLN targeting. • The prodrug also enhanced drug exposure to MLN lymphocytes. • A prodrug of mycophenolic acid suppressed lymphocyte proliferation in antigen challenge studies. • Triglyceride-based prodrugs may provide a means to enhance intestinal immunomodulation. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
137. Tracking down tumor-specific T cells.
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Reading, James, Foster, Kane, Joshi, Kroopa, and Chain, Benny
- Subjects
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CANCER cells , *T cells - Abstract
Two papers published in this edition of Cancer Cell (Zheng et al., 2022 and Veatch et al., 2022) provide an elegant illustration of how single-cell sequencing can be used to define a molecular phenotype which identifies tumor-specific T cells. Two papers published in this edition of Cancer Cell (Zheng et al., 2022 and Veatch et al., 2022) provide an elegant illustration of how single-cell sequencing can be used to define a molecular phenotype which identifies tumor-specific T cells. [ABSTRACT FROM AUTHOR]
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- 2022
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138. Therapeutic opportunities for regulatory T-cell enhancing approaches.
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Tough, David F and Lombardi, Giovanna
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REGULATORY T cells , *T cells , *IMMUNE response , *AUTOIMMUNE diseases , *IMMUNE system , *AUTOANTIGENS - Abstract
Summary: The immune system plays a critical role in protecting the host against infection but is subject to numerous levels of control that are necessary to prevent pathological, tissue-damaging responses. Inappropriate inflammatory immune responses to self-antigens, innocuous commensal microorganisms, or environmental antigens can lead to chronic, debilitating, and degenerative diseases. Regulatory T cells have an essential, non-redundant, and dominant function in preventing pathological immune responses, as shown by the development of systemic fatal autoimmunity in humans and animals with a genetic deficiency in regulatory T cells. In addition to controlling immune responses, there is a growing understanding that regulatory T cells also contribute directly to tissue homeostasis by promoting tissue regeneration and repair. For these reasons, the prospect of enhancing regulatory T-cell numbers and/or function in patients represents an appealing therapeutic opportunity with potential applications in many diseases, including some where the pathological role of the immune system has only recently been recognized. Approaches to enhance regulatory T cells are now starting to be explored in clinical studies in humans. This review series brings together papers highlighting the Treg-enhancing approaches that are most advanced clinically and examples of therapeutic opportunities based on our growing understanding of regulatory T-cell functions. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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139. Review on the Effect of Exercise Training on Immune Function.
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Du, Feijiao and Wu, Cuicui
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EXERCISE physiology , *EXERCISE , *IMMUNITY , *EXERCISE intensity , *BODY movement , *T cells - Abstract
Exercise training is not only a necessary means to improve the level of exercise, but also an important means to improve the body's immunity. Different time, intensity, items, and forms of exercise training have different effects on the body's immune function. As a double-edged sword to improve the body's immune function, exercise training is a different reaction mechanism of different immune cells after exercise training. This paper combined with foreign scholars' studies on the immune function of the body of literature from different exercise intensity, different time, different sports, different movement forms, and different external environment such as angle of view for athletes body's immune cells and humoral immunity summarized the various indexes such as combing, in order to help academia, medicine, and sports. It provides enlightenment to the contemporary public on how to participate in sports training more healthily. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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140. T-Cell Intracellular Antigen 1-Like Protein in Physiology and Pathology.
- Author
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Velasco, Beatriz Ramos and Izquierdo, José M.
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- *
PHYSIOLOGY , *T cells , *RNA-binding proteins , *ANTIGENS , *CELL death , *NUCLEOCYTOPLASMIC interactions , *CYTOTOXIC T cells , *NUCLEAR membranes - Abstract
T-cell intracellular antigen 1 (TIA1)-related/like (TIAR/TIAL1) protein is a multifunctional RNA-binding protein (RBP) involved in regulating many aspects of gene expression, independently or in combination with its paralog TIA1. TIAR was first described in 1992 by Paul Anderson's lab in relation to the development of a cell death phenotype in immune system cells, as it possesses nucleolytic activity against cytotoxic lymphocyte target cells. Similar to TIA1, it is characterized by a subcellular nucleo-cytoplasmic localization and ubiquitous expression in the cells of different tissues of higher organisms. In this paper, we review the relevant structural and functional information available about TIAR from a triple perspective (molecular, cellular and pathophysiological), paying special attention to its expression and regulation in cellular events and processes linked to human pathophysiology. [ABSTRACT FROM AUTHOR]
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- 2022
- Full Text
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141. Advances in CD247.
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Dexiu, Chen, Xianying, Lei, Yingchun, Hu, and Jiafu, Li
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T cells , *AUTOIMMUNE diseases , *PEPTIDES - Abstract
CD247, which is also known as CD3ζ, CD3H, CD3Q, CD3Z, IMD25, T3Z and TCRZ, encodes CD3ζ protein, which is expressed primarily in natural killer (NK) and T cells. Since the discovery of the ζ peptide in 1986, it has been continuously investigated. In this paper, we review the composition, molecular mechanisms and regulatory factors of CD247 expression in T cells; and review the autoimmune diseases, tumours and inflammatory diseases associated with CD247, providing a detailed and comprehensive reference for further research on the mechanism of CD247 and related diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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142. PECAM-1 Is Down-Regulated in γδT Cells during Remission, but Up-Regulated in Relapse of Multiple Sclerosis.
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Zarobkiewicz, Michał K., Morawska, Izabela, Kowalska, Wioleta, Halczuk, Paweł, Roliński, Jacek, and Bojarska-Junak, Agnieszka A.
- Subjects
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MULTIPLE sclerosis , *T cells , *FLOW cytometry , *CD3 antigen - Abstract
Introduction. PECAM-1 and NKRP1A are both involved in the vascular transmigration of T lymphocytes. Vascular transmigration is a crucial process in multiple sclerosis pathogenesis. Methods and aim. The current paper presents an analysis of PECAM-1 and NKRP1A expression on γδ T cells. Expression of PECAM-1 and NKRP1A on subsets of γδ T cells was performed with flow cytometry. Results. Based on the flow cytometry data, PECAM1 was slightly differentially modulated on γδ T cells—it was up-regulated during relapse, but down-regulated during remission. Moreover, a significant downregulation of CD3 expression was noted on γδ T cells from MS patients, most notably during relapse. Conclusions. This may be a sign of the overall activation of γδ T cells in the course of multiple sclerosis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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143. Emerging Therapies for Hepatocellular Carcinoma (HCC).
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Chakraborty, Eesha and Sarkar, Devanand
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THERAPEUTIC use of monoclonal antibodies , *DELAYED diagnosis , *CHEMORADIOTHERAPY , *PROTEIN-tyrosine kinase inhibitors , *GENE expression , *GENE therapy , *LIVER transplantation , *T cells , *HEPATOCELLULAR carcinoma , *NANOPARTICLES - Abstract
Simple Summary: Primary liver cancer, also known as Hepatocellular carcinoma (HCC), is considered to be a major global health challenge. Due to delays in diagnosis at early asymptomatic stages, HCC reaches a severe aggressive stage, thereby having a significant negative impact on patient survival. In addition, HCC shows marked resistance to conventional cancer treatments such as chemo- and radiotherapy. A variety of new and advanced therapies are continuously being evaluated to acquire a breakthrough in HCC treatment to enhance overall and recurrence-free survival. Appropriate identification and selection of target genes and utilization of safe and effective therapeutic approaches, such as gene therapy or immunotherapy, are key strategies for the effective treatment for HCC. This review paper intends to provide a perspective on emerging approaches as avenues towards more effective and safer therapies for HCC. Hepatocellular carcinoma (HCC) arises from hepatocytes and accounts for 90% of primary liver cancer. According to Global Cancer Incidence, Mortality and Prevalence (GLOBOCAN) 2020, globally HCC is the sixth most common cancer and the third most common cause of cancer-related deaths. Reasons for HCC prognosis remaining dismal are that HCC is asymptomatic in its early stages, leading to late diagnosis, and it is markedly resistant to conventional chemo- and radiotherapy. Liver transplantation is the treatment of choice in early stages, while surgical resection, radiofrequency ablation (RFA) and trans arterial chemoembolization (TACE) are Food and Drug Administration (FDA)-approved treatments for advanced HCC. Additional first line therapy for advanced HCC includes broad-spectrum tyrosine kinase inhibitors (TKIs), such as sorafenib and lenvatinib, as well as a combination of immunotherapy and anti-angiogenesis therapy, namely atezolizumab and bevacizumab. However, these strategies provide nominal extension in the survival curve, cause broad spectrum toxic side effects, and patients eventually develop therapy resistance. Some common mutations in HCC, such as in telomerase reverse transcriptase (TERT), catenin beta 1 (CTNNB1) and tumor protein p53 (TP53) genes, are still considered to be undruggable. In this context, identification of appropriate gene targets and specific gene delivery approaches create the potential of gene- and immune-based therapies for the safe and effective treatment of HCC. This review elaborates on the current status of HCC treatment by focusing on potential gene targets and advanced techniques, such as oncolytic viral vectors, nanoparticles, chimeric antigen receptor (CAR)-T cells, immunotherapy, and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9), and describes future prospects in HCC treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
144. Association of the tissue infiltrated and peripheral blood immune cell subsets with response to radiotherapy for rectal cancer.
- Author
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Zhu, Min, Li, Xingjie, Cheng, Xu, Yi, Xingxu, Ye, Fang, Li, Xiaolai, Hu, Zongtao, Zhang, Liwei, Nie, Jinfu, and Li, Xueling
- Subjects
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BLOOD cells , *RECTAL cancer , *GENE expression profiling , *CANCER radiotherapy , *BIOMARKERS , *T cells - Abstract
Background: Tumor microenvironment plays pivotal roles in carcinogenesis, cancer development and metastasis. Composition of cancer immune cell subsets can be inferred by deconvolution of gene expression profile accurately. Compositions of the cell types in cancer microenvironment including cancer infiltrating immune and stromal cells have been reported to be associated with the cancer outcomes markers for cancer prognosis. However, rare studies have been reported on their association with the response to preoperative radiotherapy for rectal cancer. Methods: In this paper, we deconvoluted the immune/stromal cell composition from the gene expression profiles. We compared the composition of immune/stromal cell types in the RT responsive versus nonresponsive for rectal cancer. We also compared the peripheral blood immune cell subset composition in the stable diseases versus progressive diseases of rectal cancer patients with fluorescence-activated cell sorting from our institution. Results: Compared with the non-responsive group, the responsive group showed higher proportions of CD4+ T cell (0.1378 ± 0.0368 vs. 0.1071 ± 0.0373, p = 0.0215), adipocytes, T cells CD4 memory resting, and lower proportions of CD8+ T cell (0.1798 ± 0.0217 vs. 0.2104 ± 0.0415, p = 0.0239), macrophages M2, and preadipocytes in their cancer tissue. The responsive patients showed a higher ratio of CD4+/CD8+ T cell proportions (mean 0.7869 vs. 0.5564, p = 0.0210). Consistently, the peripheral blood dataset showed higher proportion of CD4+ T cells and higher ratio of CD4+/CD8+ T cells, and lower proportion of CD8+ T cells for favorable prognosis. We validated these results with a pooled dataset of GSE3493 and GSE35452, and more peripheral blood data, respectively. Finally, we imported these eight cell features including eosinophils and macrophage M1 to Support Vector Machines and could predict the pre-radiotherapy responsive versus non-responsive with an accuracy of 76%, ROC AUC 0.77, 95% confidential interval of 0.632–0.857, better than the gene signatures. Conclusions: Our results showed that the proportions of tumor-infiltrating subsets and peripheral blood immune cell subsets can be important immune cell markers and treatment targets for outcomes of radiotherapy for rectal cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
145. Targeting CD10 on B-Cell Leukemia Using the Universal CAR T-Cell Platform (UniCAR).
- Author
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Mitwasi, Nicola, Arndt, Claudia, Loureiro, Liliana R., Kegler, Alexandra, Fasslrinner, Frederick, Berndt, Nicole, Bergmann, Ralf, Hořejší, Vaclav, Rössig, Claudia, Bachmann, Michael, and Feldmann, Anja
- Subjects
- *
CD19 antigen , *T cells , *CHIMERIC antigen receptors , *B cells , *LEUKEMIA , *LYMPHOBLASTIC leukemia - Abstract
Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
146. Progressive Depletion of B and T Lymphocytes in Patients with Ataxia Telangiectasia: Results of the Italian Primary Immunodeficiency Network.
- Author
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Cirillo, Emilia, Polizzi, Agata, Soresina, Annarosa, Prencipe, Rosaria, Giardino, Giuliana, Cancrini, Caterina, Finocchi, Andrea, Rivalta, Beatrice, Dellepiane, Rosa M., Baselli, Lucia A., Montin, Davide, Trizzino, Antonino, Consolini, Rita, Azzari, Chiara, Ricci, Silvia, Lodi, Lorenzo, Quinti, Isabella, Milito, Cinzia, Leonardi, Lucia, and Duse, Marzia
- Subjects
- *
ATAXIA telangiectasia , *PRIMARY immunodeficiency diseases , *T cells , *B cells , *SPINOCEREBELLAR ataxia , *LYMPHOPENIA , *INTERSTITIAL lung diseases - Abstract
Ataxia telangiectasia (AT) is a rare neurodegenerative genetic disorder due to bi-allelic mutations in the Ataxia Telangiectasia Mutated (ATM) gene. The aim of this paper is to better define the immunological profile over time, the clinical immune-related manifestations at diagnosis and during follow-up, and to attempt a genotype–phenotype correlation of an Italian cohort of AT patients. Retrospective data of 69 AT patients diagnosed between December 1984 and November 2019 were collected from the database of the Italian Primary Immunodeficiency Network. Patients were classified at diagnosis as lymphopenic (Group A) or non-lymphopenic (Group B). Fifty eight out of 69 AT patients (84%) were genetically characterized and distinguished according to the type of mutations in truncating/truncating (TT; 27 patients), non-truncating (NT)/T (28 patients), and NT/NT (5 patients). In 3 patients, only one mutation was detected. Data on age at onset and at diagnosis, cellular and humoral compartment at diagnosis and follow-up, infectious diseases, signs of immune dysregulation, cancer, and survival were analyzed and compared to the genotype. Lymphopenia at diagnosis was related per se to earlier age at onset. Progressive reduction of cellular compartment occurred during the follow-up with a gradual reduction of T and B cell number. Most patients of Group A carried bi-allelic truncating mutations, had a more severe B cell lymphopenia, and a reduced life expectancy. A trend to higher frequency of interstitial lung disease, immune dysregulation, and malignancy was noted in Group B patients. Lymphopenia at the onset and the T/T genotype are associated with a worst clinical course. Several mechanisms may underlie the premature and progressive immune decline in AT subjects. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
147. A Study on Dynamics of CD4 + T-Cells under the Effect of HIV-1 Infection Based on a Mathematical Fractal-Fractional Model via the Adams-Bashforth Scheme and Newton Polynomials.
- Author
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Najafi, Hashem, Etemad, Sina, Patanarapeelert, Nichaphat, Asamoah, Joshua Kiddy K., Rezapour, Shahram, and Sitthiwirattham, Thanin
- Subjects
- *
MATHEMATICAL models , *HIV , *T cells , *MATHEMATICAL forms , *CD4 antigen - Abstract
In recent decades, AIDS has been one of the main challenges facing the medical community around the world. Due to the large human deaths of this disease, researchers have tried to study the dynamic behaviors of the infectious factor of this disease in the form of mathematical models in addition to clinical trials. In this paper, we study a new mathematical model in which the dynamics of CD 4 + T-cells under the effect of HIV-1 infection are investigated in the context of a generalized fractal-fractional structure for the first time. The kernel of these new fractal-fractional operators is of the generalized Mittag-Leffler type. From an analytical point of view, we first derive some results on the existence theory and then the uniqueness criterion. After that, the stability of the given fractal-fractional system is reviewed under four different cases. Next, from a numerical point of view, we obtain two numerical algorithms for approximating the solutions of the system via the Adams-Bashforth method and Newton polynomials method. We simulate our results via these two algorithms and compare both of them. The numerical results reveal some stability and a situation of lacking a visible order in the early days of the disease dynamics when one uses the Newton polynomial. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
148. ESTIMATES FOR APPROXIMATE SOLUTIONS TO A FUNCTIONAL DIFFERENTIAL EQUATION MODEL OF CELL DIVISION.
- Author
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TAYLOR, STEPHEN and YANG, XUESHAN
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CELL division , *CELL size , *FUNCTIONAL differential equations , *DEATH rate , *T cells , *ANALYTICAL solutions - Abstract
The functional partial differential equation (FPDE) for cell division, $$ \begin{align*} &\frac{\partial}{\partial t}n(x,t) +\frac{\partial}{\partial x}(g(x,t)n(x,t))\\ &\quad = -(b(x,t)+\mu(x,t))n(x,t)+b(\alpha x,t)\alpha n(\alpha x,t)+b(\beta x,t)\beta n(\beta x,t), \end{align*} $$ is not amenable to analytical solution techniques, despite being closely related to the first-order partial differential equation (PDE) $$ \begin{align*} \frac{\partial}{\partial t}n(x,t) +\frac{\partial}{\partial x}(g(x,t)n(x,t)) = -(b(x,t)+\mu(x,t))n(x,t)+F(x,t), \end{align*} $$ which, with known $F(x,t)$ , can be solved by the method of characteristics. The difficulty is due to the advanced functional terms $n(\alpha x,t)$ and $n(\beta x,t)$ , where $\beta \ge 2 \ge \alpha \ge 1$ , which arise because cells of size x are created when cells of size $\alpha x$ and $\beta x$ divide. The nonnegative function, $n(x,t)$ , denotes the density of cells at time t with respect to cell size x. The functions $g(x,t)$ , $b(x,t)$ and $\mu (x,t)$ are, respectively, the growth rate, splitting rate and death rate of cells of size x. The total number of cells, $\int _{0}^{\infty }n(x,t)\,dx$ , coincides with the $L^1$ norm of n. The goal of this paper is to find estimates in $L^1$ (and, with some restrictions, $L^p$ for $p>1$) for a sequence of approximate solutions to the FPDE that are generated by solving the first-order PDE. Our goal is to provide a framework for the analysis and computation of such FPDEs, and we give examples of such computations at the end of the paper. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
149. Optimizing antiviral therapy for COVID-19 with learned pathogenic model.
- Author
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Dutta, Abhishek
- Subjects
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COVID-19 treatment , *COVID-19 , *T cells , *HEALTH care industry , *REMDESIVIR , *PHARMACOLOGY - Abstract
COVID-19 together with variants have caused an unprecedented amount of mental and economic turmoil with ever increasing fatality and no proven therapies in sight. The healthcare industry is racing to find a cure with multitude of clinical trials underway to access the efficacy of repurposed antivirals, however the much needed insights into the dynamics of pathogenesis of SARS-CoV-2 and corresponding pharmacology of antivirals are lacking. This paper introduces systematic pathological model learning of COVID-19 dynamics followed by derivative free optimization based multi objective drug rescheduling. The pathological model learnt from clinical data of severe COVID-19 patients treated with remdesivir could additionally predict immune T cells response and resulted in a dramatic reduction in remdesivir dose and schedule leading to lower toxicities, however maintaining a high virological efficacy. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
150. What Is Currently Known about the Role of CXCL10 in SARS-CoV-2 Infection?
- Author
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Gudowska-Sawczuk, Monika and Mroczko, Barbara
- Subjects
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CHEMOKINES , *COVID-19 , *SARS-CoV-2 , *T cells , *KILLER cells , *CHEMOKINE receptors , *CYTOKINE release syndrome , *DENDRITIC cells - Abstract
Dysregulation of the immune response plays an important role in the progression of SARS-CoV-2 infection. A "cytokine storm", which is a phenomenon associated with uncontrolled production of large amounts of cytokines, very often affects patients with COVID-19. Elevated activity of chemotactic cytokines, called chemokines, can lead to serious consequences. CXCL10 has an ability to activate its receptor CXCR3, predominantly expressed on macrophages, T lymphocytes, dendritic cells, natural killer cells, and B cells. So, it has been suggested that the chemokine CXCL10, through CXCR3, is associated with inflammatory diseases and may be involved in the development of COVID-19. Therefore, in this review paper, we focus on the role of CXCL10 overactivity in the pathogenesis of COVID-19. We performed an extensive literature search for our investigation using the MEDLINE/PubMed database. Increased concentrations of CXCL10 were observed in COVID-19. Elevated levels of CXCL10 were reported to be associated with a severe course and disease progression. Published studies revealed that CXCL10 may be a very good predictive biomarker of patient outcome in COVID-19, and that markedly elevated CXCL10 levels are connected with ARDS and neurological complications. It has been observed that an effective treatment for SARS-CoV-2 leads to inhibition of "cytokine storm", as well as reduction of CXCL10 concentrations. It seems that modulation of the CXCL10–CXCR3 axis may be an effective therapeutic target of COVID-19. This review describes the potential role of CXCL10 in the pathogenesis of COVID-19, as well as its potential immune–therapeutic significance. However, future studies should aim to confirm the prognostic, clinical, and therapeutic role of CXCL10 in SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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