scholarly journals How Do Inflammatory Mediators, Immune Response and Air Pollution Contribute to COVID-19 Disease Severity? A Lesson to Learn

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 182
Author(s):  
Cinzia Signorini ◽  
Patrizia Pignatti ◽  
Teresa Coccini
Keyword(s):  
Immune Response ◽  
Air Pollution ◽  
Poor Prognosis ◽  
Immune Mediators ◽  
Health Risk Factor ◽  
New Challenges ◽  
Defensive Mechanisms ◽  
Underlying Mechanisms ◽  
Inflammatory Syndrome

Inflammatory and immune processes are defensive mechanisms that aim to remove harmful agents. As a response to infections, inflammation and immune response contribute to the pathophysiological mechanisms of diseases. Coronavirus disease 2019 (COVID-19), whose underlying mechanisms remain not fully elucidated, has posed new challenges for the knowledge of pathophysiology. Chiefly, the inflammatory process and immune response appear to be unique features of COVID-19 that result in developing a hyper-inflammatory syndrome, and air pollution, the world’s largest health risk factor, may partly explain the behaviour and fate of COVID-19. Understanding the mechanisms involved in the progression of COVID-19 is of fundamental importance in order to avoid the late stage of the disease, associated with a poor prognosis. Here, the role of the inflammatory and immune mediators in COVID-19 pathophysiology is discussed.

scholarly journals MITF induces escape from innate immunity in melanoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Luis Sánchez-del-Campo ◽  
Román Martí-Díaz ◽  
María F. Montenegro ◽  
Rebeca González-Guerrero ◽  
Trinidad Hernández-Caselles ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Nk Cells ◽  
Nk Cell ◽  
Luciferase Reporter ◽  
Damage Repair ◽  
Reporter Assays ◽  
Underlying Mechanisms ◽  
Nk Cytotoxicity

Abstract Background The application of immune-based therapies has revolutionized cancer treatment. Yet how the immune system responds to phenotypically heterogeneous populations within tumors is poorly understood. In melanoma, one of the major determinants of phenotypic identity is the lineage survival oncogene MITF that integrates diverse microenvironmental cues to coordinate melanoma survival, senescence bypass, differentiation, proliferation, invasion, metabolism and DNA damage repair. Whether MITF also controls the immune response is unknown. Methods By using several mouse melanoma models, we examine the potential role of MITF to modulate the anti-melanoma immune response. ChIP-seq data analysis, ChIP-qPCR, CRISPR-Cas9 genome editing, and luciferase reporter assays were utilized to identify ADAM10 as a direct MITF target gene. Western blotting, confocal microscopy, flow cytometry, and natural killer (NK) cytotoxicity assays were used to determine the underlying mechanisms by which MITF-driven phenotypic plasticity modulates melanoma NK cell-mediated killing. Results Here we show that MITF regulates expression of ADAM10, a key sheddase that cleaves the MICA/B family of ligands for NK cells. By controlling melanoma recognition by NK-cells MITF thereby controls the melanoma response to the innate immune system. Consequently, while melanoma MITFLow cells can be effectively suppressed by NK-mediated killing, MITF-expressing cells escape NK cell surveillance. Conclusion Our results reveal how modulation of MITF activity can impact the anti-melanoma immune response with implications for the application of anti-melanoma immunotherapies.

scholarly journals Early Defensive Mechanisms against Human Papillomavirus Infection

2015 ◽  
Vol 22 (8) ◽  
pp. 850-857 ◽  
Author(s):  
Andrea Moerman-Herzog ◽  
Mayumi Nakagawa
Keyword(s):  
Human Papillomavirus ◽  
Immune Responses ◽  
Precancerous Lesion ◽  
Hpv Infection ◽  
Immune Mediators ◽  
Common Cancer ◽  
Papillomavirus Infection ◽  
Abnormal Cells ◽  
Defensive Mechanisms

ABSTRACTCervical cancer is the fourth most common cancer in women and is almost exclusively caused by human papillomavirus (HPV) infection. HPV is also frequently associated with other cancers arising from mucosal epithelium, including anal and oropharyngeal cancers, which are becoming more common in both men and women. Viral persistence and progression through precancerous lesion stages are prerequisites for HPV-associated cancer and reflect the inability of cell-mediated immune mechanisms to clear infections and eliminate abnormal cells in some individuals. Cell-mediated immune responses are initiated by innate pathogen sensing and subsequent secretion of soluble immune mediators and amplified by the recruitment and activation of effector T lymphocytes. This review discusses early defensive mechanisms of innate responders to natural HPV infection, their influence on response polarization, and the underappreciated role of keratinocytes in this process.

scholarly journals UPF1 Promotes Chemoresistance to Oxaliplatin Through Maintenance of Stemness by Increasing Phosphorylated TOP2A in Colorectal Cancer.

2020 ◽  
Author(s):  
Congcong Zhu ◽  
Long Zhang ◽  
Senlin Zhao ◽  
Weixing Dai ◽  
Yun Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cell Lines ◽  
Clinical Relevance ◽  
Poor Prognosis ◽  
Therapy Strategy ◽  
Underlying Mechanisms

Abstract Background: UPF1 is proved to dysregulate in multiple tumors and influence carcinogenesis. However, the role of UPF1 on oxaliplatin resistance in colorectal cancer (CRC) remains unknown.Methods: Firstly, we investigated the clinical relevance of UPF1 in CRC patients. Then, we explored the influence of UPF1 on chemoresistance to oxaliplatin in vitro and in vivo. Finally, we disclosed the underlying mechanisms of oxaliplatin resistance induced by UPF1.Results: UPF1 is upregulated in CRC and overexpression of UPF1 more likely results in recurrence in CRC patients and predicts a poorer overall survival (OS). UPF1 maintains stemness in CRC cell lines and promotes chemoresistance to oxaliplatin in CRC. UPF1-induced oxaliplatin resistance can be associated with interaction with TOP2A and increasing phosphorylated TOP2A.Conclusions: UPF1 was overexpressed and predicted a poor prognosis in CRC. UPF1 enhanced the stemness and chemoresistance to oxaliplatin by interaction with TOP2A and increase of phosphorylated TOP2A in CRC, which may provide a new therapy strategy for chemoresistance to oxaliplatin in CRC patients.

scholarly journals Systematic Analysis of the Oncogenic Role of WDR62 in Human Tumors

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Yulan Bu ◽  
Lihua Zhang ◽  
Xiaolin Ma ◽  
Rui Wang ◽  
Xuecheng Zhang ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Immune Cell ◽  
Treg Cells ◽  
Human Tumors ◽  
Systematic Analysis ◽  
Kaplan Meier ◽  
Promoter Dna ◽  
Underlying Mechanisms ◽  
Pan Cancer

Background. Emerging studies support the oncogenic role of WD repeat domain 62 (WDR62) in few tumors, while no pan-cancer analysis is available. In this study, we analyzed systematically the oncogenic role of WDR62 across a series of human tumors based on bioinformatic data mining. Methods. The expression level of WDR62 was analyzed via GEPIA2, TIMER, UALCAN, and StarBase databases. The prognostic role was analyzed via GEPIA2, TIMER, UALCAN, StarBase, TISIDB, TCGA portal, Kaplan-Meier Plotter, and PrognoScan databases. Then, we explored the causes for WDR62 abnormal expression via TCGA portal and UALCAN databases. Subsequently, the STRING and GeneMANIA databases were used to find the interactive networks for WDR62. Furthermore, we analyzed the correlation between WDR62 expression and immune features via TIMER and TISIDB databases. Results. We found that WDR62 was significantly upregulated in most of the tumors and correlated with poor prognosis mainly in 6 candidate tumors—BLCA, BRCA, KIRC, KIRP, LIHC, and LUAD. Abnormal WDR62 expression may be probably attributed to TP53 mutation and promoter DNA methylation. Relative network analysis demonstrated that WDR62 was mainly involved in MAPK and toll-like receptor signaling pathway. WDR62 expression was associated with various immune cell infiltrations, especially cancer-associated fibroblasts (CAF) and T cell regulatory (Treg) cells, and was markedly correlated with poor prognosis. Moreover, WDR62 expression was closely associated with the expression of some immunomodulators such as PD-L1 and has a significant prognostic value. Conclusions. Our study revealed that WDR62 could serve as a diagnostic and prognostic biomarker for several cancers. Importantly, WDR62 was closely associated with various immune cell infiltration, and to a certain extent, it can predict the effect of immunotherapy in particular PD1/PD-L1 inhibitors. Our pan-cancer study provided useful information on the oncogenic role of WDR62, contributing to further exploring the underlying mechanisms.

scholarly journals Skin Microbiota in Atopic Dermatitis

2020 ◽  
Vol 13 (4) ◽  
pp. 374-382
Author(s):  
Jessica Herlianez Saiful ◽  
Satya Wydya Yenny
Keyword(s):  
Immune Response ◽  
Atopic Dermatitis ◽  
Microbial Community ◽  
Immune Responses ◽  
Skin Diseases ◽  
Major Influence ◽  
First Line ◽  
Skin Microbiota ◽  
Immune Mediators

In human body, the skin is the largest organ that has the function of mediating contact with the outside world and providing our body first line of defense against all kinds of pathogens, poisons and dangerous environments. The role of skin which are physical and immunological, supported by the microbial community that inhabits the skin. Skin microbiota contributes to barrier function by competing with pathogens and dealing with immune cells in the skin, to modulate local and systemic immune responses. Skin microbiota and immune mediators, for example complement system, have two-way interactions, and this shows that commensal microbes must be considered an important part of healthy skin. Many evidence shows that the composition of microbiota, especially in the intestines and also on the skin, can have a major influence on an individual's health. The influence of gut microbiota and its influence on the immune response has been widely studied, but the link of skin microbiota, immune response and certain skin diseases has not been widely discussed in the literature. Skin microbiota is expected to be affected in certain dermatological conditions, such as in psoriasis and in atopic dermatitis, which further shows the importance of the skin microbial community for human health. Understanding of skin microbiota role in pathogenesis of atopic dermatitis is still needed.

scholarly journals Attenuated Chromosome Oscillation as a Cause of Chromosomal Instability in Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4531
Author(s):  
Kenji Iemura ◽  
Yujiro Yoshizaki ◽  
Kinue Kuniyasu ◽  
Kozo Tanaka
Keyword(s):  
Cancer Therapy ◽  
Error Correction ◽  
Cancer Cells ◽  
Chromosomal Instability ◽  
Poor Prognosis ◽  
Mutual Relationship ◽  
Aurora Kinases ◽  
Chromosome Dynamics ◽  
Underlying Mechanisms

Chromosomal instability (CIN) is commonly seen in cancer cells, and related to tumor progression and poor prognosis. Among the causes of CIN, insufficient correction of erroneous kinetochore (KT)-microtubule (MT) attachments plays pivotal roles in various situations. In this review, we focused on the previously unappreciated role of chromosome oscillation in the correction of erroneous KT-MT attachments, and its relevance to the etiology of CIN. First, we provided an overview of the error correction mechanisms for KT-MT attachments, especially the role of Aurora kinases in error correction by phosphorylating Hec1, which connects MT to KT. Next, we explained chromosome oscillation and its underlying mechanisms. Then we introduced how chromosome oscillation is involved in the error correction of KT-MT attachments, based on recent findings. Chromosome oscillation has been shown to promote Hec1 phosphorylation by Aurora A which localizes to the spindle. Finally, we discussed the link between attenuated chromosome oscillation and CIN in cancer cells. This link underscores the role of chromosome dynamics in mitotic fidelity, and the mutual relationship between defective chromosome dynamics and CIN in cancer cells that can be a target for cancer therapy.

scholarly journals The Role of Extracellular Vesicles in the Progression of Human Neuroblastoma

2021 ◽  
Vol 22 (8) ◽  
pp. 3964
Author(s):  
Danilo Marimpietri ◽  
Irma Airoldi ◽  
Angelo Corso Faini ◽  
Fabio Malavasi ◽  
Fabio Morandi
Keyword(s):  
Immune Response ◽  
Drug Resistance ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Human Neuroblastoma ◽  
Response To Chemotherapy ◽  
Underlying Mechanisms ◽  
Tumor In Childhood ◽  
Molecular Components

The long-underestimated role of extracellular vesicles in cancer is now reconsidered worldwide by basic and clinical scientists, who recently highlighted novel and crucial activities of these moieties. Extracellular vesicles are now considered as king transporters of specific cargoes, including molecular components of parent cells, thus mediating a wide variety of cellular activities both in normal and neoplastic tissues. Here, we discuss the multifunctional activities and underlying mechanisms of extracellular vesicles in neuroblastoma, the most frequent common extra-cranial tumor in childhood. The ability of extracellular vesicles to cross-talk with different cells in the tumor microenvironment and to modulate an anti-tumor immune response, tumorigenesis, tumor growth, metastasis and drug resistance will be pinpointed in detail. The results obtained on the role of extracellular vesicles may represent a panel of suggestions potentially useful in practice, due to their involvement in the response to chemotherapy, and, moreover, their ability to predict resistance to standard therapies—all issues of clinical relevance.

scholarly journals Role of Nutritional Status in the Treatment Outcome for Esophageal Squamous Cell Carcinoma

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2997
Author(s):  
Miao-Fen Chen ◽  
Ching-Chuan Hsieh ◽  
Ping-Tsung Chen ◽  
Ming-Shian Lu
Keyword(s):  
Immune Response ◽  
Squamous Cell Carcinoma ◽  
Nutritional Status ◽  
Cell Carcinoma ◽  
Cancer Patients ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Neoadjuvant Treatment ◽  
Tumor Model

Undernourishment is reported to impair treatment response, further leading to poor prognosis for cancer patients. We aimed to investigate the role of nutritional status on the prognosis of squamous cell carcinoma (SCC) of the esophagus, and its correlation with anticancer immune responsiveness. We retrospectively reviewed 340 esophageal-SCC patients who completed curative treatment and received a nutrition evaluation by the Patient-Generated Subjective Global Assessment (PGSGA) score at the beginning and completion of neoadjuvant treatment at our hospital. The correlation between the nutritional status and various clinicopathological parameters and prognosis were examined. In addition, the role of nutritional status in the regulation of the anticancer immune response was also assessed in cancer patients and in a 4-nitroquinoline 1-oxide (4NQO)-induced esophageal tumor model. Our data revealed that malnutrition (patients with a high PGSGA score) was associated with advanced stage and reduced survival rate. Patients in the group with a high PGSGA score were correlated with the higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived-suppressor cells (MDSC) and increased IL-6 level. Furthermore, surgical resection brought the survival benefit to patients in the low PGSGA group, but not for the malnourished patients after neoadjuvant treatment. Using a 4NQO-induced tumor model, we found that nutrition supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. In conclusion, malnutrition was associated with poor prognosis in esophageal-SCC patients. Nutritional status evaluated by PGSGA may be useful to guide treatment decisions in clinical practice. Nutritional supplementation is suggested to improve prognosis, and it might be related to augmented anticancer immune response.

scholarly journals The Conceptual Framework for SARS-CoV-2 Related Lymphopenia

2020 ◽  
Author(s):  
Ilnaz Rahimmanesh ◽  
Shirin Kouhpayeh ◽  
Hossein Khanahmad
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Viral Infections ◽  
Innate Immune ◽  
Atp Depletion ◽  
High Morbidity ◽  
Adaptive Immune ◽  
Underlying Mechanisms ◽  
Nad Depletion

The emerging of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is associated with high morbidity and mortality rates globally. One of the most prominent characteristics of coronavirus disease-19 (COVID-19) is lymphopenia which is in contrast to other viral infections. This controversy might be explained by the evaluation of impaired innate and adaptive immune responses during the SARS-CoV-2 infection. During the innate immune response, poly-ADP-ribose polymerase (PARP) hyperactivated due to virus entry and extensive DNA damage sequentially leading to NAD+ depletion, ATP depletion and finally cell death. In contrast to the immune response against viral infections, cytotoxic T lymphocytes decline sharply in SARS-CoV-2 infection which might be due to infiltration and trapping in the lower respiratory tract. In addition, there are more factors proposed to involve in lymphopenia in COVID-19 infection like the role of CD38 which functions as NADase and intensifies NAD depletion which in turn affects NAD+ dependent Sirtuin proteins, as the regulators of cell death and viability. Lung tissue sequestration following cytokine storm supposed to be another reason for lymphopenia in COVID-19 patients. Protein 7a as one of the virus-encoded proteins induces apoptosis in various organ-derived cell lines. These mechanisms proposed to induce lymphopenia, although there are still more studies needed to clarify the underlying mechanisms for lymphopenia in COVID-19 patients.

Response Interference as a Mechanism Underlying Implicit Measures

2008 ◽  
Vol 24 (4) ◽  
pp. 218-225 ◽  
Author(s):  
Bertram Gawronski ◽  
Roland Deutsch ◽  
Etienne P. LeBel ◽  
Kurt R. Peters
Keyword(s):  
Task Performance ◽  
Psychological Research ◽  
Implicit Measures ◽  
Mediation Model ◽  
Response Interference ◽  
Relevant Evidence ◽  
Moderated Mediation Model ◽  
Stimulus Features ◽  
Underlying Mechanisms

Over the last decade, implicit measures of mental associations (e.g., Implicit Association Test, sequential priming) have become increasingly popular in many areas of psychological research. Even though successful applications provide preliminary support for the validity of these measures, their underlying mechanisms are still controversial. The present article addresses the role of a particular mechanism that is hypothesized to mediate the influence of activated associations on task performance in many implicit measures: response interference (RI). Based on a review of relevant evidence, we argue that RI effects in implicit measures depend on participants’ attention to association-relevant stimulus features, which in turn can influence the reliability and the construct validity of these measures. Drawing on a moderated-mediation model (MMM) of task performance in RI paradigms, we provide several suggestions on how to address these problems in research using implicit measures.

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