Protein phosphatase 2A (PP2A) is a heterotrimeric protein phosphatase consisting of a 36-k_D catalytic C subunit (PP2Ac). This study aimed to explore the prognostic and biological significance of PP2Ac in human hepatocellular carcinoma (HCC). High PP2Ac expression was significantly (P < 0.01) associated with serum hepatitis B surface antigen positivity, serum hepatitis B e antigen positivity, liver cirrhosis, moderate to poor differentiation grade, advanced disease stage, intrahepatic metastasis, and early recurrence in HCC. Multivariate analysis revealed PP2Ac as an independent prognostic factor for overall survival. Enforced expression of hepatitis B virus X protein (HBx) and its carboxyl-terminal truncated isoform induced PP2Ac expression in HCC cells. Co-immunoprecipitation assay revealed a direct interaction between PP2Ac and HBx. Small interfering RNA-mediated knockdown of PP2Ac significantly inhibited in vitro cell proliferation, colony formation, migration, and invasion and reduced tumor growth in an xenograft mouse model. In contrast, overexpression of PP2Ac promoted HCC cell proliferation, colony formation, and tumorigenesis. Additionally, silencing of PP2Ac impaired the growth-promoting effects on HepG2 HCC cells elicited by overexpression of carboxyl-terminal truncated HBx. Gene expression profiling analysis showed that PP2Ac downregulation modulated the expression of numerous genes involved in cell cycle and apoptosis regulation. Collectively, PP2Ac upregulation has a poor prognostic impact on the overall survival of HCC patients and contributes to the aggressiveness of HCC. PP2Ac may represent a potential therapeutic target for HCC.

MicroRNAs (miRNAs) are emerging as important regulators of various physiological and pathological processes and may serve key roles in the maintenance of bone homeostasis via effects on osteoblast differentiation. The aim of the present study was to define the role of miR‑877‑3p in osteoblast differentiation using MC3T3‑E1 cells, an osteoblast precursor cell line. It was demonstrated using RT‑qPCR analysis that miR‑877‑3p was gradually increased in MC3T3‑E1 cells during the osteoblastic differentiation induced by transforming growth factor (TGF)‑β1. Gain‑of‑function and loss‑of‑function experiments revealed that the overexpression of miR‑877‑3p promoted the osteoblastic differentiation of MC3T3‑E1 cells, whereas depletion of miR‑877‑3p inhibited this process in vitro and in vivo. Bioinformatics analysis and validation experiments demonstrated that Smad7, which acts as a negative regulator of osteogenesis, was a target of miR‑877‑3p. Furthermore, the overexpression of Smad7 partially reversed the osteoblastic differentiation of MC3T3‑E1 cells induced by miR‑877‑3p. In conclusion, the results of the present study suggest that the miR‑877‑3p/Smad7 axis is associated with the osteoblastic differentiation of MC3T3‑E1 cells and may indicate a potential therapeutic approach for osteogenesis disorders.

The most essential and crucial step during the pathogenesis of transmissible spongiform encephalopathy is the conformational change of cellular prion

Background: Leading to a sustained epidemic spread with >2,000,000 confirmed human infections, including >100,000 deaths, COVID-19 was caused by SARS-CoV-2 and resulted in acute respiratory distress syndrome (ARDS) and sepsis, which brought more challenges to the patient’s treatment. The S-glycoprotein, which recognized as the key factor for the entry of SARS-CoV-2 into the cell, contains two functional domains: an ACE2 receptor binding domain and a second domain necessary for fusion of the coronavirus and cell membranes. FURIN activity, exposes the binding and fusion domains, is essential for the zoonotic transmission of SARS-CoV-2. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, FURIN enzyme and ACE2 receptor were expressed in airway epithelia, cardiac tissue, and enteric canals, which considered as the potential target organ of the virus. However, report about the expression of FURIN and ACE2 in oral tissues was limited. Methods: In order to investigate the potential infective channel of new coronavirus in oral cavity, we analyze the expression of ACE2 and FURIN that mediate the new coronavirus entry into host cells in oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemical staining experiment was performed to confirm the expression of ACE2 and FURIN in the protein level. Results: The bioinformatics results indicated the differential expression of ACE2 and FURIN on epithelial cells of different oral mucosal tissues and the proportion of FURIN-positive cells was obviously higher than that of ACE2-positive cells. IHC experiments revealed that both the ACE2-positive and FURIN-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, which further confirm the bioinformatics results. Conclusions: Based on these findings, we speculated that SARS-CoV-2 could effectively invade oral mucosal cells though two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by FURIN protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2, which provides valuable information for virus-prevention strategy in clinical care as well as daily life.

MicroRNAs (miRNAs) have emerged as pivotal regulators in various physiological and pathological processes at the post‑transcriptional level, and may serve important roles in osteogenic differentiation. However, their roles and functions are not fully understood. In the present study, miR‑223‑5p was identified as a modulator of osteoblastic differentiation in MC3T3‑E1 cells. Reverse transcription‑quantitative polymerase chain reaction and western blotting demonstrated that miR‑223‑5p was significantly upregulated in MC3T3‑E1 cells following the induction of osteoblast differentiation. Overexpression of miR‑223‑5p promoted osteogenic differentiation both in vitro and vivo. Expression of histone deacetylase 2 (HDAC2), which acts as a negative regulator of osteogenesis, was regulated by miR‑223‑5p. Collectively, the results of the present study revealed a novel miR‑223‑5p/HDAC2 axis that regulates osteoblast differentiation, and may serve as a potential target for enhancing bone formation in vivo.