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The interferon (IFN)-mediated activation of the Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT1) signaling is crucial for cell sensitivity to ionizing radiation. Several preclinical studies have reported that the IFN/STAT1 pathway mediates radioresistance in the tumor microenvironment by shielding the immune responses and activating survival signaling pathways. This review focuses on the oncogenic function of the IFN/STAT1 pathway, emphasizing the major signaling pathway in radiation sensitization. Furthermore, it highlights the possibility of mediatory roles of the IFN/STAT1 pathway as a prognostic therapeutic target in the modulation of resistance to radiotherapy and chemotherapy. MicroRNA involved in the regulation of the IFN/STAT1 pathway is also discussed. A better understanding of radiation-induced IFN/STAT1 signaling will open new opportunities for the development of novel therapeutic strategies, as well as define new approaches to enhance radio-immunotherapy efficacy in the treatment of various types of cancers.

Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by inflammation of the articular tissue. This study aims to evaluate the expression of microRNA (miR)-146a-5p, miR-24-3p, and miR-125a-5p in the plasma of RA patients and compare them with those of healthy controls to obtain a specific expression profile for earlier diagnosis and assistance in treating patients. This study was performed on 50 RA patients and 50 healthy controls. Five microliters of blood were taken from each patient/control. Plasma RNA was extracted using the Trisol solution. cDNAs were synthesized; using moloney murine leukemia virus (MMLV) and deoxynucleoside triphosphate (dNTP). Real-time PCR was performed using SYBR green kit. The mean expression of miR-146a-5p, miR-24-3p, and miR-125a-5p in the RA group were 8.1±1.9, 6.5±1.2, and 6.8±2.2 and in the healthy group were 4.8±1.6, 3.6±2.2, and 3.4±1.7, respectively. Significant differences were also observed in the mean expression of these three miRNAs in four subgroups of RA patients with different disease activity based on disease activity score 28 (DAS28) (p

The new coronavirus, known as “SARS-CoV-2”; is the cause of one of the most prevalent infectious viral diseases that was recently announced pandemic by the world health organization. Ongoing research in the fields of prevention, management, and therapy establishes a functional scaffold for clinics during the time of crisis. To obtain this goal, it is necessary that all pathophysiologic aspects of COVID-19 from infection to predisposing backgrounds of infection be identified, so that all the ambiguities of researchers regarding transmission mechanisms, variable clinical manifestation, and therapeutic response can be solved. Here, we firstly discuss about the homology screening between nCoV-2019 and beta-coronavirus family using phylogenetic analyses. Secondly, we analyzed the viral motifs to show that viral entry into the host cells requires a primary activation step performed by FURIN and FURIN-like-mediated enzymatic cleavage on the structural glycoprotein. The cleavage increases viral performance by 1000 folds. We then present a comprehensive view on host cells and the significance of gene variants affecting activation enzymes, supportive entry, and spread mechanisms in humans including renin-angiotensin-aldosterone system (RAAS) a pathway results in certain phenotypes or exacerbate infection-related phenotypes in different organs, hence causes variable clinical manifestations. This is followed by discussing about the importance of personalized medicine in nCoV-2019 exposure. Moreover, chemical drugs prescribed for individuals affected with COVID-19, as well as genes involved in drug transport and metabolisms are reviewed as a prelude to drug response. Finally, we suggest some therapeutic approaches developed based on new methods and technology such as anti-sense therapy and antibodies.

Hepatocellular carcinoma (HCC) patients always have a background of cirrhosis. Aberrant epigenetic changes in cirrhosis provide a conductive environment for HCC tumorigenesis. Active enhancers (AEs) are essential for epigenetic regulation and play an important role in cell development and the progression of many diseases. However, the role of AEs in the progression from cirrhosis to HCC remains unclear. We systemically constructed a landscape of AEs that developed de novo in cirrhosis and were conserved in HCC, referred to as CL-HCC AEs. We observed significant upregulation of these CL-HCC AE-associated genes in cirrhosis and HCC, with no other epigenetic changes. Enrichment analysis of these CL-HCC AE-associated genes revealed enrichment in both hepatocyte-intrinsic tumorigenesis and tumor immune response, which might contribute to HCC tumorigenesis. Analysis of the diagnostic ability of these CL-HCC AE-associated genes provided a five-gene (THBS4, OLFML2B, CDKN3, GABRE, and HDAC11) diagnostic biomarker for HCC. Molecular subtype (MS) identification based on the CL-HCC AE-associated genes identified 3 MSs. Samples representing the 3 MSs showed differences in CL-HCC AE-associated gene expression levels, prognosis, copy number variation (CNV)/mutation frequencies, functional pathways, tumor microenvironment (TME) cell subtypes, immunotherapy responses and putative drug responses. We also found that the BET bromodomain inhibitor JQ1 downregulated the expression of CL-HCC AE-associated genes. Collectively, our results suggest that CL-HCC AEs and their associated genes contribute to HCC tumorigenesis and evolution, and could be used to distinguish the different landscapes of HCC and help explore the mechanism, classification, prediction, and precision therapy of HCC.

Qian Yang,1,* Laichao Ni,1,* Saber Imani,1,* Zhangqiang Xiang,1 Rui Hai,1 Ruilin Ding,1 Shaozhi Fu,1 Jing bo Wu,1,2 Qinglian Wen1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China; 2Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinglian WenDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, 3-319 Zhongshan Road, Luzhou, Sichuan 646000, People’s Republic of ChinaTel/ Fax +86-830-3160283Email wql73115@hotmail.comBackground: Anlotinib is a highly potent multi-target tyrosine kinase inhibitor, with very good anti-tumor activity against a variety of solid tumors. However, its effect on colorectal cancer (CRC) is not yet clearly understood. The objective of this study was to investigate the anti-tumor effect and underlying mechanism of anlotinib in the pathogenesis of CRC.Materials and Methods: Effects of anlotinib on CT26 cells proliferation and microvessel formation in endothelial cells were determined by MTT assay and tube formation assay. Cell migration and invasion were analyzed by using the wound healing assay and transwell assay. Cell cycle and apoptosis were detected by flow cytometry. A CRC xenograft mouse model was used for conducting in-vivo studies to verify the effect of anlotinib. The expression of Ki-67 and CD31 in the tumor tissue was detected by immunohistochemistry and protein expression was measured by Western blot.Results: In-vitro studies revealed that anlotinib inhibited the proliferation, migration, and invasion of CT26 cells and the tube formation of HUVECs in a dose-dependent manner. Anlotinib also significantly induced cell apoptosis and G2/M arrest. It effectively inhibited tumor growth and prolonged survival time in the CRC xenograft mouse model. Immunohistochemical analysis of the tumor tissue revealed that anlotinib downregulated CD31 and Ki-67 which are the biomarkers of microvessel density and proliferation. Furthermore, anlotinib was able to inhibit the activation of VEGFR-2/AKT and FGFR, PDGFRβ and their downstream signaling ERK.Conclusion: The findings of the present study suggested that anlotinib suppressed cell proliferation and angiogenesis via inhibition of AKT/ERK signaling pathway in colorectal cancer and could be a novel therapeutic strategy for treatment of CRC.Keywords: anlotinib, colorectal cancer, angiogenesis, proliferation, tyrosine kinase inhibitor

Coronaviruses are a group of enveloped viruses with single-stranded non-segmented positive-sense RNA genomes. In December 2019, SARS-CoV-2 appeared in China for the first time and quickly spread throughout the world. Although certain medications suggested for other afflictions tend to be potentially effective for curing the infection, there is no approved vaccination or drug available for this virus yet. Comprehension of the disease molecular pathogenesis could provide useful tools for COVID-19 patients in surveillance, prognosis, treatment, vaccine development and therapeutic targeting. The present research aims to summarize the association in COVID-19 patients between molecular dimensions of comorbidities with clinical and preclinical information. Developing an ACE2 inhibitor could be a possible therapeutic target. Plasmin is another possible candidate both in diagnosis and treatment areas. All predicted biomarkers must be validated either through randomized clinical trials or experimental assays before clinical application in patients.