Current Molecular Medicine - Volume 22, Issue 9, 2022

Skeletal muscles must generate and distribute energy properly in order to function perfectly. Mitochondria in skeletal muscle cells form vast networks to meet this need, and their functions may improve as a result of exercise. In the present review, we discussed exercise-induced mitochondrial adaptations, age-related mitochondrial decline, and a biomarker as a mitochondrial function indicator and exercise interference.

Currently, the world is facing the emergence of a virus that causes pneumonia in humans, which has a higher probability of causing complications, including respiratory distress syndrome and death. The new coronavirus 2019 (2019-nCoV), which is currently known as SARS-CoV-2, is the cause of the Coronavirus disease 2019 (COVID-19). This virus was first detected in Wuhan, Hubei Province of China, and appears to have been a zoonotic infection that has now adapted to humans. On March 11, 2020, COVID-19 was announced as a pandemic by the World Health Organisation (WHO), causing widespread panic worldwide. SARS-CoV-2 is genetically similar to the 2003 Severe Acute Respiratory Syndrome-related (SARS) and shares many similarities with the disease features of influenza virus infection. Scientists around the world are racing towards the development of vaccines and antivirals for COVID-19. This review will provide an update of COVID-19, a brief review of the symptoms and route of transmission of the SARS-CoV-2 virus, the reason why it is highly infectious, as well as the currently available treatments and comorbidities.

Although there are currently several factors that allow measuring the risk of having breast cancer or predicting its progression, the underlying causes of this malignancy have remained unknown. Several molecular studies have described some mechanisms involved in the progress of breast cancer. These have helped in identifying new targets with therapeutic potential. However, despite the therapeutic strategies implemented from the advances achieved in breast cancer research, a large percentage of patients with breast cancer die due to the spread of malignant cells to other tissues or organs, such as bones and lungs. Therefore, determining the processes that promote the migration of malignant cells remains one of the greatest challenges for oncological research. Several research groups have reported evidence on how the dedifferentiation of tumor cells leads to the acquisition of stemness characteristics, such as invasion, metastasis, the capability to evade the immunological response, and resistance to several cytotoxic drugs. These phenotypic changes have been associated with a complex reprogramming of gene expression in tumor cells during the Epithelial- Mesenchymal Transition (EMT). Considering the determining role that the transcriptional regulation plays in the expression of the specific characteristics and attributes of breast cancer during ETM, in the present work, we reviewed and analyzed several transcriptional mechanisms that support the mesenchymal phenotype. In the same way, we established the importance of transcription factors with a therapeutic perspective in the progress of breast cancer.

Background: MicroRNAs (miRNAs) are about 22-nucleotide, small, noncoding RNAs that control gene expression post-transcriptionally. Helminth parasites usually express a unique repertoire of genes, including miRNAs, across different developmental stages with subtle regulatory mechanisms. Objective: There is a necessity to investigate the involvement of miRNAs in the development of parasites, host-parasite interaction, immune evasion and their abilities to govern infection in hosts. MiRNAs present in helminth parasites have been summarized in the current systematic review (SR). Methods: Electronic databases, including PubMed, Scopus, ProQuest, Embase, and Google Scholar search engine, were searched to identify helminth miRNA studies published from February 1993 till December 2019. Only the published articles in English were included in the study. Results: A total of 1769 articles were preliminarily recorded. Following the strict inclusion and exclusion criteria, 105 studies were included in this SR. Most of these studies focused on the identification of miRNAs in helminth parasites and/or probing of differentially expressed host miRNA profiles in specific relevant tissues, while 12 studies aimed to detect parasite-derived miRNAs in host circulating system and 15 studies characterized extracellular vesicles (EV)-derived miRNAs secreted by parasites. Conclusion: In the current SR, information regarding all miRNAs expressed in helminth parasites has been comprehensively provided and the utility of helminth parasitesderived miRNAs in diagnosis and control of parasitic infections has been discussed. Furthermore, functional studies on helminth-derived miRNAs have also been presented.

Background: The immunohistochemical analysis of autophagy-related proteins (ATGs) has been recently applied in human pathology to study differentiation and cancer progression. The aim of the present study is to analyze a cohort of gastric carcinomas (GC) by five ATG antisera (Beclin-1, LC3A/B, p62, ULK-1 and AMBRA-1), also evaluating their possible relationship with clinicopathological parameters, HER2 status and final outcome of patients. Methods: A cohort of 123 GCs has been studied by ATG antisera utilizing Masuda's criteria that define positive cases in which at least two out of five protein expressions were documented. Results: The immunohistochemical signature for autophagy (A-IHC) was 49.59% as a whole. The percentage of A-IHC ranged from 31% for poorly cohesive carcinomas to 56% for adenocarcinomas. The performance of each ATG immunomarker documented high values for sensitivity, specificity and efficiency for LC3A/B, Beclin-1 and p62. In univariate analysis of GC, grade, stage, Ki67 expression, HER2 status as well as A-IHC appeared as emerged as relevant parameters with a high p-value (p < 0.001). Finally, in multivariate analysis, HER2 status, stage and A-IHC emerged as independent prognostic variables. In the comparison of survival curves, GC cases immunoreactive for A-IHC exhibited a shorter survival with a worse outcome. Conclusions: We have hypothesized that A-IHC could represent an additional morphological tool to provide prognostic elements in order to identify patients affected by aggressive with shorter survival and worse outcome.

Background: Collagen and calcium-binding EGF domain-1 (CCBE1) is essential for the development of the lymphatic vasculature and colorectal cancer (CRC) lymphangiogenesis as it enhances the proteolytic process of vascular endothelial growth factor C (VEGFC) activating VEGFR3. The fully processed mature VEGFC could also activate VEGFR2, the important endothelial-specific receptor tyrosine kinase, involved in blood vascular development and tumor angiogenesis. However, the role of CCBE1 in cancer angiogenesis remains undefined. Methods: In this paper, we find that the protein expression of CCBE1 is higher in the primary CRC tissue with distant metastasis and positively correlated with blood vessel density. Results: The mRNA expression of CCBE1 is closely positively correlated with the vascular endothelial marker CD31 and VEGFR2 in CRC from TCGA datasets. The supernatant of the colorectal cancer cell line HCT116 with CCBE1 overexpression significantly promotes the tube formation ability of the human umbilical vein endothelial cells (HUVECs) in vitro and enhances angiogenesis and tumor growth in vivo. Knockdown of CCBE1 decreases the angiogenic ability of CRC. Conclusion: Our results demonstrate the angiogenic role of CCBE1 in CRC.

Aim: To investigate the effects of PAXT mutations on tumor immunity. Background: Loss of function of PAX5 plays a key role in the PAX5 mutation tumor. Objective: PAX5 haploinsufficiency promoting tumorigenesis is related to immune escape, but there was no report about mechanisms of PAX5 mutation inducing tumor immunological escape. Methods: We constructed the PAX5 haplodeletion A20 cell lines using gene-editing technology, built allografted A20 tumor models and evaluated the effect of PAX5 haplodeletion on T cells and chemokines in the tumor microenvironment (TME). Results: Our results from different methods indicated percentages of CD3+ CD4+ T cells and CD3+ CD8+ T cells in TME of PAX5 haplodeletion clones decreased significantly compared with that of PAX5 wild type control. Several chemokines, such as Ccl2, Ccl4, Cxcl9 and Cxcl10, in TME of PAX5. Conclusion: Our study showed that PAX5 haploinsufficiency induced low T cell infiltration in TME using decreased chemokines.