ABSTRACT
Colorectal cancer (CRC) accounts for one of the main cancer-related mortality and morbidity worldwide. The molecular mechanisms of CRC development have been broadly investigated and, over the last decade, it has become evident that aberrant transcription of microRNAs (miRNAs), a class of small, noncoding RNA molecules, has a significant role in the inception and promotion of CRC. In the involved tissues of CRC, the transcription profile of miRNAs is modulated, and their expression templates are related with prognosis, diagnosis, and treatment outcomes. Here, in the current review, we attempted to discuss the latest information regarding the aberrantly expressed miRNAs in CRC and the advantages of utilizing miRNAs as biomarkers for early diagnosis and prognosis of CRC as well as potential therapeutic application. The effect of miRNAs involved in various signaling pathways, primarily p53, EGFR, Wnt, and TGF-ß pathways, was clarified.
Subject(s)
Colorectal Neoplasms , MicroRNAs , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Gene Expression Regulation, Neoplastic , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/drug therapy , Prognosis , Signal Transduction/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolismABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic has affected the daily lives of millions of people worldwide and had caused significant mortality; hence, the assessment of therapeutic options is of great interest. The leading cause of death among COVID-19 patients is acute respiratory distress syndrome caused by hyperinflammation secondary to cytokine release syndrome (CRS). Cytokines, such as tumor necrosis factor-α, interleukin-6, interferon-γ and interleukin-10, are the main mediators of CRS. Based on recent evidence, the angiotensin-converting enzyme (ACE) II is known to be the target of the COVID-19 spike protein, which enables the virus to penetrate human cells. ACE II also possesses an anti-inflammatory role in many pathologies such as cardiovascular disease, hypertension, diabetes mellitus and other conditions, which are the main risk factors of poor prognosis in COVID-19 infection. Changes in tissue ACE II levels are associated with many diseases and hyperinflammatory states, and it is assumed that elevated levels of ACE II could aggravate the course of COVID-19 infection. Therefore, the use of renin-angiotensin-aldosterone system inhibitors (RASis) in COVID-19 patients could be hypothetically considered, though sufficient evidence is not presented by the scientific community. In this work, based on the most recent pieces of evidence, the roles of RAS and RASi in immunologic interactions are addressed. Furthermore, the molecular and immunologic aspects of RASi and their potential significance in COVID-19 are discussed.
Subject(s)
Angiotensin-Converting Enzyme 2/physiology , COVID-19 , SARS-CoV-2/physiology , Virus Internalization , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Humans , Immune System/metabolism , Immune System/pathology , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/physiology , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effectsABSTRACT
CD39 (nucleoside triphosphate diphosphohydrolase) and Ecto-5-nucleotidase (CD73) have been recognized as important factors mediating various pathological and physiological responses in the tumor microenvironment. Elevated expression of CD73 and CD39 is correlated with the over-production of adenosine in the tumor region. This increase is associated with an immunosuppressive state in the tumor site that enhances various tumor hallmarks such as metastasis, angiogenesis, and cell proliferation. Adenosine promotes these behaviors through interaction with four adenosine receptors, including A3R, A2BR, A2AR, and A1R. Signaling of these receptors reduces the function of immune effector cells and enhances the expansion and function of tumor-associated immune cells. Several studies have been shown the important role of adenosine/CD73/CD39/ARs axis in the immunopathogenesis of colorectal cancer. These findings imply that components of this axis can be considered as a worthy target for colorectal cancer immunotherapy. In this review, we summarized the role of CD73/CD39/adenosine/ARs in the immunopathogenesis of colorectal cancer.
Subject(s)
Adenosine/metabolism , Colorectal Neoplasms/metabolism , Receptors, Purinergic P1/metabolism , 5'-Nucleotidase/metabolism , Animals , Antigens, CD/metabolism , Apyrase/metabolism , HumansABSTRACT
The 1986 accident at the Chernobyl Nuclear Power Plant led to large-scale changes in the environmental situation. The purpose of our study was to conduct a comparative analysis of the morphological states of the dentition of individuals living in regions exposed to radiation to determine the groups at risk for the main classes of dental anomalies. We believe our results will support the development of a differentiated system for dental rehabilitation and follow-up of individuals exposed to radiation. The prevalence rate of dental anomalies was studied in 1,889 patients of both sexes divided by age in accordance with dentition formation stages and by regions of residence in accordance with the 137Cs soil-contamination level. A statistically significant decrease was observed in the number of patients with normal dentition for their age among those who had been exposed to prenatal radiation. A sharp increase in combined dental anomalies was revealed in patients who lived in regions with a137Cs soil-contamination level ranging from 555 to 1665 GBq/km2; concomitantly, multidirectional fluctuations were observed in the numbers of tooth and occlusion anomalies. Among the examined population, the most severe pathology of the oral organs was found in prenatally irradiated patients (born between April 26, 1986, and April 30, 1987). The prevalence of dental anomalies is interrelated not only with the level of radioactive contamination in the soil of the dwelling area, but also with the age of the surveyed individuals at the moment of the accident.