Regulatory mechanism of HIF-1α and its role in liver diseases: a narrative review Qingfei Chu, Xinyu Gu, Qiuxian Zheng, Haihong Zhu

Background: The COVID-19 pandemic continues to pose an international public health threat. Prevention is of paramount importance to protect the high-risk group of older adults until specific treatments for COVID-19 become available; however, little work has been done to explore factors that promote preventive behaviors among this population. Objective: This study aims to investigate the knowledge, perceived beliefs, and preventive behaviors towards COVID-19 of older adults in China and determine the factors that influence their practice of preventive behaviors. Methods: From February 19 to March 19, 2020, a cross-sectional, web-based survey was administered to Chinese older adults in all 31 provinces of mainland China using a convenience sampling method to assess the respondents’ knowledge, perceived beliefs, and preventive behaviors towards COVID-19. Standard descriptive statistics and hierarchical linear regression analyses were conducted to analyze the data. Results: A total of 1501 participants responded to the survey, and 1263 valid responses (84.1%) were obtained for further analysis. The overall correct rate on the knowledge questionnaire was 87%, overall positive beliefs regarding COVID-19 were found, and the mean behavior score was 13.73/15 (SD 1.62, range 5-15). The hierarchical linear regression showed that respondents who were married or cohabitating and who lived in areas with community-level control measures were more likely to practice preventive behaviors (P<.01). Knowledge (β=0.198, P<.001), perceived susceptibility (β=0.263, P=.03), perceived benefits (β=0.643, P<.001), and self-efficacy in preventing COVID-19 (β=0.468, P<.001) were also found to be significantly associated with preventive behaviors. Conclusions: Most older residents had adequate knowledge and positive beliefs regarding COVID-19 and engaged in proactive behaviors to prevent the disease. Knowledge and beliefs were confirmed to be significantly associated with behavior responses. Our findings have significant implications in enhancing the effectiveness of COVID-19 prevention programs targeting the older population; these programs must be continued and strengthened as the epidemic continues.

In addition to playing a pivotal role in cellular energetics and biosynthesis, mitochondrial components are key operators in the regulation of cell death. In addition to apoptosis, necrosis is a highly relevant form of programmed liver cell death. Differential activation of specific forms of programmed cell death may not only affect the outcome of liver disease but may also provide new opportunities for therapeutic intervention. This review describes the role of mitochondria in cell death and the mechanism that leads to chronic liver hepatitis and liver cirrhosis. We focus on mitochondrial-driven apoptosis and current knowledge of necroptosis and discuss therapeutic strategies for targeting mitochondrial-mediated cell death in liver diseases.

RNA modification plays an important role in epigenetics at the posttranscriptional level, and 5-methylcytosine (m⁵C) has attracted increasing attention in recent years due to the improvement in RNA m⁵C site detection methods. By influencing transcription, transportation and translation, m⁵C modification of mRNA, tRNA, rRNA, lncRNA and other RNAs has been proven to affect gene expression and metabolism and is associated with a wide range of diseases, including malignant cancers. RNA m⁵C modifications also substantially impact the tumor microenvironment (TME) by targeting different groups of immune cells, including B cells, T cells, macrophages, granulocytes, NK cells, dendritic cells and mast cells. Alterations in immune cell expression, infiltration and activation are highly linked to tumor malignancy and patient prognosis. This review provides a novel and holistic examination of m⁵C-mediated cancer development by examining the exact mechanisms underlying the oncogenicity of m⁵C RNA modification and summarizing the biological effects of m⁵C RNA modification on tumor cells as well as immune cells. Understanding methylation-related tumorigenesis can provide useful insights for the diagnosis as well as the treatment of cancer.

Natural killer T cells (NKTs) are an important part of the immune system. Since their discovery in the 1990s, researchers have gained deeper insights into the physiology and functions of these cells in many liver diseases. NKT cells are divided into two subsets, type I and type II. Type I NKT cells are also named iNKT cells as they express a semi-invariant T cell-receptor (TCR) α chain. As part of the innate immune system, hepatic iNKT cells interact with hepatocytes, macrophages (Kupffer cells), T cells, and dendritic cells through direct cell-to-cell contact and cytokine secretion, bridging the innate and adaptive immune systems. A better understanding of hepatic iNKT cells is necessary for finding new methods of treating liver disease including autoimmune liver diseases, alcoholic liver diseases (ALDs), non-alcoholic fatty liver diseases (NAFLDs), and liver tumors. Here we summarize how iNKT cells are activated, how they interact with other cells, and how they function in the presence of liver disease.

Recently, long noncoding RNAs (lncRNAs) have attracted great attention from researchers. LncRNAs are non-protein-coding RNAs of more than 200 nucleotides in length. Multiple studies have been published on the relationship between lncRNA expression and the progression of human diseases. LncRNA small nucleolar RNA host gene 4 (SNHG4), a member of the lncRNA SNHG family, is abnormally expressed in a variety of human diseases, including gastric cancer, renal cell carcinoma, glioblastoma, neuroblastoma, prostate cancer, colorectal cancer, osteosarcoma, cervical cancer, liver cancer, lung cancer, non-small-cell lung cancer, neonatal pneumonia, diabetic retinopathy, neuropathic pain, acute cerebral infarction, acute myeloid leukaemia, and endometriosis. In this paper, the structure of SNHG4 is first introduced, and then studies in humans, animal models and cells are summarized to highlight the expression and function of SNHG4 in the above diseases. In addition, the specific mechanism of SNHG4 as a competing endogenous RNA (ceRNA) is discussed. The findings indicate that SNHG4 can be used as a biomarker for disease prognosis evaluation and as a potential target for disease diagnosis and treatment.