Atrial fibrillation (AF) and subsequent stroke and death have become major public health problems in China. Oral anticoagulant (OAC) forms the backbone of prevention of AF-related stroke. However, the quality of OAC use in AF patients in China is not clear. The focus of this narrative review is to summarize the current status of OAC therapy in China and compare it with the studies conducted internationally. In general, most data of OAC use in China were reported around 10-50%, with an increasing proportion of high-risk patients receiving OACs, however, still much lower than those in other countries and regions. Moreover, the phenomenon of inappropriate OAC prescribing and poor long-term persistence and adherence with OAC therapy in AF patients in China have also been noted. The 1-year adherence and persistence of OACs are as low as 50%. Multiple factors from the physicians, patients, and OAC drugs contribute to these phenomena. The management of OACs in AF patients in China needs to be further improved by the joint efforts of healthcare administration (policy makers) and health systems including medical associations, hospitals, and physicians.
Phase separation refers to a phenomenon in which different components of a cell collide and fuse with each other to form droplets such that some components are encapsulated within the droplet and some are blocked outside. It is prevalent in eukaryotic cells and is closely related to genome assembly and transcriptional regulation, enabling multiple biological functions. With the development of high-throughput sequencing technologies, several non-coding RNAs (ncRNAs) have been shown to play an important role in epigenetic regulation of gene expression in addition to their roles at the transcriptional and post-transcriptional levels. In addition, some ncRNAs are involved in the formation of membraneless organelles (MLOs), the regulation of genomic stability and stress response through phase separation. Notably, phase separation can also affect the biogenesis, processing and maturation of ncRNAs. This review summarizes recent discoveries related to the relationship between ncRNAs and phase separation, providing new perspectives to guide future interventions.
Female reproductive senescence is heralded by hypothalamus region-specific changes in the transcription of genes such as Kiss1 under estradiol (E2) positive feedback, associated with luteinizing hormone (LH) surge dysfunction and reproductive decline. The current study explored whether the anteroventral periventricular nucleus (AVPV) displayed epigenetic changes mediated by age-related dysregulation of gene expression and whether an epigenetic-based intervention could alleviate an aging-related neuroendocrine disorder. Chromatin immunoprecipitation sequencing (ChIP-seq) and ChIP-qPCR were used to assess the differential acetylation of histone H3 in the AVPV and the expression of genes in hormone-primed middle-aged rats. The association between acetylated histone H3 and Kiss1 expression and the underlying mechanisms of dysregulation were determined using pharmacological inhibitors and molecular experiments in vitro and in vivo. An AVPV gene expression program failed to initiate in middle-aged females displaying typical genome-wide hypoacetylation of histone H3, and this coincided with decreased LH. Hypoacetylation of histone H3 at the 3' intergenic region of Kiss1 in particular was associated with enhanced chromatin looping between the promoter and enhancer. Restoration of physiological histone H3 acetylation by intracerebroventricular injection of trichostatin A (TSA) restored the expression of Kiss1 by modifying chromatin looping and led to the restoration of Kiss1 neuronal activation and Kiss1 synthesis as well as circulating LH. These findings have revealed novel epigenetic-associated changes in gene expression in female reproductive aging. These results also suggest that HDAC enzyme-based treatment is a potential therapeutic approach for insufficient preovulatory LH release in aging females.
Mounting evidence has suggested that phase separation, and especially liquid-liquid phase separation (LLPS), underlies the formation of membraneless organelles, which are supramolecular assemblies of proteins and RNA molecules in cells. These membraneless organelles are also called biomolecular condensates. Evidence is now growing that condensates, such as stress granules, P bodies, Cajal bodies, and nucleoli, play vital roles in biological processes, like RNA storage and processing, signaling regulation, transcription regulation, gene regulation, and transport. Conversely, condensates may cause diseases, such as neurodegenerative diseases and tumors, when they go wrong. Condensates initially have liquid-like properties, but accumulating biological and chemical mutations with age render them into a more solid-like state, like amyloids in Alzheimer's disease, Huntington's disease, and Parkinson's disease. Research into phase separation is still in its infancy, but this field is a promising avenue for treatment of aging-related diseases.
The vestibule of the inner ear is susceptible to certain chemotherapeutic agents in clinical practice. Therefore, it is of great significance to discover molecular pathways and targets that can protect the vestibule from chemotherapeutic drugs. The Notch signaling pathway is closely related to hair cell regeneration in the inner ear. However, the role of Notch signaling in chemotherapeutic drug-induced vestibular injury still remains unclear. The aim of this study was first to evaluate the role of Notch signaling in chemotherapy-induced vestibular injury. Cisplatin-induced vestibular injury of mice was evaluated by the swimming test. Changes of vestibular hair cells and the expression levels of Notch1, Jagged1, and Hes1 in Notch signaling were observed by immunofluorescence. The results showed that Notch signaling was found activated in cisplatin-induced injured vestibular cells, while, DAPT (Notch signaling inhibitor) could reversed this effect. In conclusion, the Notch signaling pathway may play a critical role in chemotherapeutic drug-induced vestibular injury and, therefore, serves as a promising therapeutic target for vestibular injury.
Interleukin 11 (IL-11) was discovered in 1990 in fibrocyte-like stromal cells of the bone marrow, but there has recently been an increased interest in the cytokine. Understanding the physiological roles of cytokines will allow their use as pharmacological agents in clinical practice. Studies have indicated that IL-11 affects the mechanism for the development of a number of pathologies of the nervous system. IL-11 plays a significant role in the central nervous system. The local expression of this cytokine by nerve cells has been observed. The current work summarizes the results of studies which found that the cytokine affects the mechanism of development of pathologies of the central nervous system. In the near future, this cytokine may be used clinically to fix the mechanisms that are involved in the development of pathological conditions of the nervous system.
During a six-week period from July 20 to August 31, 2022, Japan experienced its highest level of COVID-19 infection ever, with an average of nearly 200,000 new infections per day nationwide. Cases requiring inpatient care peaked at 1,993,062. Twenty-seven prefectures (out of 47 prefectures) had an average hospital bed occupancy of 50% or higher, and bed occupancy in Kanagawa in particular reached 98% in mid-August. In Tokyo, bed occupancy by patients with severe COVID-19 reached 57% and peaked at 64% in mid-August. Although the number of new infections per day has decreased since September, hospital bed occupancy, the number of severe cases, and deaths remain high nationwide. Efforts including vaccination campaigns, domestic surveillance, and routine infection control measures based on the varied knowledge that the Japanese public already has should be thoroughly implemented to reduce the number of the infected in order to avoid an increase the number of serious cases and deaths.
COVID-19 has been a topic of interest since a pandemic struck in 2019. The morbidity of influenza tended to decrease due to the measures to prevent COVID-19. Indeed, influenza seems to be "ignored" in this era of COVID-19. However, influenza has not disappeared from the scene. Presented here are two examples of recent influenza epidemics in China and Australia. Possible interactions between COVID-19 and influenza are discussed. Measures against COVID-19 may reduce contact with influenza, subsequently reducing adaptive immunity against influenza in the general population. Influenza might not be center stage right now, but insufficient adaptive immunity in the population may potentially trigger a future influenza pandemic. Coinfection with COVID-19 and influenza might potentially be a thorny problem. Hence, influenza cannot be ignored. Governments around the world should take measures to prepare for a possible influenza pandemic in the future.
Hepatocellular carcinoma (HCC) remains a health challenge with increasing incidence worldwide. Radiofrequency ablation (RFA) is a potentially curative option for patients with early-stage HCC. However, the high rate of tumor recurrence limits long-term survival when the tumors are larger than 2 cm and undergoing insufficient RFA (iRFA). Notably, in situ tumor necrosis due to thermal ablation is assumed to be a source of antigens that induce antitumor immunity. Therefore, mounting studies and trials have attempted to provide a rational and effective therapeutic strategy combining RFA and immunotherapy to treat HCC. Nowadays, many controversies and challenges with this combined therapeutic strategy remain to be resolved, such as the indications for adjuvant immunotherapy along with RFA in early HCC, the sequence of the two treatments in advanced HCC, and the optimal timing of immunotherapy before or after RFA. In addition, individualized treatment strategies need to be perfected for patients with HCC.