Oxymatrine Inhibition of Hepatitis B Virus Replication Through ERK1/2 Pathway and HNF1α and HNF4α Block in vitro.

OBJECTIVE: To explore the molecular mechanism of oxymatrine (OM) by increasing the phosphorylation of ERK1/2 signal factor and blocking the transcription factors HNF1α and HNF4α expression against hepatitis B virus (HBV) antigen secretion and HBV DNA replication in HepG2.2.15 cells. STUDY DESIGN: An experimental study. Place and Duration of the Study: Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Jiangxi, China, between May 2020 and December 2022. METHODOLOGY: HepG2.2.15 cells, known for stably expressing HBV particles, were utilised as a cell-based model to explore potential pathways pertaining to the OM inhibition of HBV replication. An MTT assay was utilised to measure cytotoxicity. HBsAg or HBeAg content was measured using an enzyme-linked immunosorbent assay kit. HBV DNA in cell-free culture media was examined using a fluorescent quantitative PCR kit. Real-time PCR was utilised to analyse HNF1α and HNF4α mRNA expression, whereas Western blotting was performed to evaluate HNF1α, HNF4α, and ERK1/2 protein expression. RESULTS: OM inhibited HBV DNA copy number in the cell supernatant, 3.5-kb RNA gene expression in cells, and HBsAg and HBeAg secretion. OM upregulated p-ERK1/2 protein and significantly downregulated HNF1α and HNF4α gene transcription and protein translation. CONCLUSION: OM may inhibit the replication of HBV by inducing the phosphorylation of ERK1/2 and blocking the transcription factors HNF1α and HNF4α expression that are essential for viral replication. KEY WORDS: Oxymatrine, ERK1/2, Hepatocyte nuclear factor, Anti-HBV.

Research progress on ferroptosis in the pathogenesis and treatment of neurodegenerative diseases.

Globally, millions of individuals are impacted by neurodegenerative disorders including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Although a great deal of energy and financial resources have been invested in disease-related research, breakthroughs in therapeutic approaches remain elusive. The breakdown of cells usually happens together with the onset of neurodegenerative diseases. However, the mechanism that triggers neuronal loss is unknown. Lipid peroxidation, which is iron-dependent, causes a specific type of cell death called ferroptosis, and there is evidence its involvement in the pathogenic cascade of neurodegenerative diseases. However, the specific mechanisms are still not well known. The present article highlights the basic processes that underlie ferroptosis and the corresponding signaling networks. Furthermore, it provides an overview and discussion of current research on the role of ferroptosis across a variety of neurodegenerative conditions.

The emerging role of extracellular vesicles in fungi: a double-edged sword.

Fungi are eukaryotic microorganisms found in nature, which can invade the human body and cause tissue damage, inflammatory reactions, organ dysfunctions, and diseases. These diseases can severely damage the patient's body systems and functions, leading to a range of clinical symptoms that can be life-threatening. As the incidence of invasive fungal infections has progressively increased in the recent years, a wealth of evidence has confirmed the "double-edged sword" role of fungal extracellular vesicles (EVs) in intercellular communication and pathogen-host interactions. Fungal EVs act as mediators of cellular communication, affecting fungal-host cell interactions, delivering virulence factors, and promoting infection. Fungal EVs can also have an induced protective effect, affecting fungal growth and stimulating adaptive immune responses. By integrating recent studies, we discuss the role of EVs in fungi, providing strong theoretical support for the early prevention and treatment of invasive fungal infections. Finally, we highlight the feasibility of using fungal EVs as drug carriers and in vaccine development.

LncRNA SNHG15 modulates gastric cancer tumorigenesis by impairing miR-506-5p expression.

The gastric cancer (GC) patients commonly have a poor prognosis due to its invasiveness and distant metastasis. Growing evidence proved that aberrant long non-coding RNAs (lncRNAs) expression contributes to tumor development and progression. LncRNA SNHG15 has been reported to be involved in many different kinds of cancer, while its role in GC remains unclear. In the present study, we found that SNHG15 was up-regulated in GC tissues and cell lines. Silencing SNHG15 suppressed proliferation migration, invasion and promoted apoptosis of AGS cells. More importantly, microRNA-506-5p (miR-506-5p) was predicted as a direct target of SNHG15 by binding its 3'-UTR and further verified using luciferase reporter assay. Meanwhile, the results of rescue experiments revealed that knockdown of miR-506-5p expression reversed the functional effects of SNHG15 silenced cell proliferation, migration, invasion and apoptosis. In conclusion, our findings revealed that SNHG15 executed oncogenic properties in GC progression through targeting miR-506-5p, which might provide a novel target for the GC treatment.

MicroRNA­129 inhibits colorectal cancer cell proliferation, invasion and epithelial­to­mesenchymal transition by targeting SOX4.

Colorectal cancer (CRC) is one of the most common digestive tract cancers and ~90% of CRC­related deaths are caused by metastasis. MicroRNA (miR)­129 has been reported to be involved in the metastasis of various malignant tumors. However, the role of miR­129 in CRC metastasis remains unclear. The purpose of the present study was to identify the potential functions and mechanisms of action of miR­129 in CRC progression. The expression of miR­129 and sex­determining region Y­related high­mobility group­box 4 (SOX4) was determined in CRC tissues or cell lines by reverse transcription­quantitative PCR, western blot or immunofluorescence assays. The mechanism underlying the role of miR­129 in CRC progression was assessed by MTT, wound healing, Transwell, western blot and dual­luciferase report assays. The results revealed that miR­129 was significantly decreased, whereas SOX4 was increased, in CRC tissues and cell lines. SW620 and SW480 cells exhibited a higher proliferation, migration and invasion capacity compared with NCM460 cells. miR­129 overexpression significantly inhibited cell proliferation, migration, invasion and epithelial­to­mesenchymal transition (EMT), and it activated the nuclear factor (NF)­κB signaling pathway in CRC cells, while the inhibition of miR­129 exerted opposite effects. Additionally, SOX4 was identified as a direct target gene of miR­129. Taken together, the findings of the present study suggested that miR­129 may act as a tumor suppressor in CRC by inhibiting CRC cell proliferation, migration, invasion and EMT, in part through targeting the 3'­untranslated region of SOX4 mRNA, and the mechanism may involve activation of the NF­κB signaling pathway.