According to recent data, several mechanisms of viral invasion of the central nervous system (CNS) have been proposed, one of which is both direct penetration of the virus through afferent nerve fibers and damage to the endothelium of cerebral vessels. It has been proven that the SARS-CoV-2 virus affects pathologically not only the human cardiorespiratory system but is also associated with a wide range of neurological diseases, cerebrovascular accidents, and neuromuscular pathologies. However, the observed post-COVID symptom complex in patients, manifested in the form of headache, “fog in the head,” high temperature, muscle weakness, lowering blood pressure, does it make us think about the pathophysiological mechanisms that contribute to the development of this clinical picture? One possible explanation is a disruption in the signaling of the acetylcholine system (AChS) in the body. Viral invasions, and in particular COVID-19, can negatively affect the work of the AChS, disrupting its coordination activities. Therefore, the main goal of this literature review is to analyze the information and substantiate the possible mechanisms for the occurrence of post-COVID syndrome in people who have had COVID-19 from the standpoint of AChS dysfunctions.

Aging with dysregulated metabolic and immune homeostasis stimulates pyroptosis, neuroinflammation, and cellular senescence, thus contributing to etiopathogenesis of Alzheimer's disease. GATA-binding protein 4 (GATA4) functions as a transcriptional factor in response to DNA damage, and is associated with neuroinflammation and cellular senescence. The role of GATA4 in Alzheimer's disease was investigated. GATA4 was elevated in hippocampus of Aβ_1–42 fibril-infused rats. Injection with shRNA targeting GATA4 reduced escape latency with increase of time in target quadrant and number of platform crossings in Aβ_1–42 fibril-infused rats. Moreover, knockdown of GATA4 ameliorated morphological changes of hippocampus and reduced amyloid plaque deposition in Aβ_1–42 fibril-infused rats. Silence of GATA4 repressed neuroinflammation and apoptosis in Aβ_1–42 fibril-infused rats. Loss of GATA4 in Aβ_1–42 fibril-infused rats reduced the expression of specificity protein 1 (Sp1) to downregulate long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) and upregulated miR-361-3p. Loss of SNHG1 ameliorated learning and memory impairments in Aβ_1–42 fibril-infused rats. Overexpression of Sp1 attenuated GATA4 silence-induced decrease of escape latency, increase of time in target quadrant, and number of platform crossings in Aβ_1–42 fibril-infused rats. In conclusion, silence of GATA4 ameliorated cognitive dysfunction and inhibited hippocampal inflammation and cell apoptosis through regulation of Sp1/SNHG1/miR-361-3p.

Free flap reconstruction has been the mainstay among reconstruction surgeries for head and neck cancer. Intraoperative and postoperative hemoglobin (Hb) levels were both possible risk factors of flap failure and had been discussed widely. However, few investigations of preoperative Hb were seen in the previous study with its effect to flap condition remain uncertain and no conclusions in the literature. Patients who underwent free flap reconstruction after head and neck surgery in our institution between May 2014 and May 2019 were enrolled. The postoperative flap condition was observed carefully, and re-exploration was performed if necessary. We then retrospectively collected patient data with several intraoperative and postoperative indices. A total of 598 patients were enrolled in our study. The total major flap complication rate was 10.6%, with an overall success rate of 89.4%. They were predominantly male (95%), and most of them underwent free flap reconstruction for the first time (91%). A total of 81 (13%) patients received radiotherapy before reconstruction. Among all factors, the preoperative Hb level and free flap type showed significance in univariate and multivariate analyses. A previous history of radiotherapy, body mass index, nutrition status, or poorly controlled diabetes mellitus showed no significant results in either univariate or multivariate analysis. Our study showed that a lower preoperative Hb level affects free flap survival. Meanwhile, preoperative radiotherapy history has no significant influence in either univariate or multivariate analysis.

Honeycomb (Nidus vespae) is traditional Chinese medicine and can treat rheumatoid arthritis (RA), and protocatechuic acid (PCA) is a bioactive component of honeycomb. This study aimed to investigate whether PCA could reduce the H₂O₂-induced migration and oxidative stress of RA fibroblast-like synoviocytes (RA-FLSs). H₂O₂-induced RA-FLSs were used to simulate the in vitro model of RA. The viability, apoptosis, migration, invasion, and oxidative stress of RA-FLSs were detected by Cell Counting Kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, wound healing, transwell assays, DCFDA staining, and malonaldehyde and superoxide dismutase enzyme-linked immunosorbent assay kits. The expression of migration and invasion-related proteins and Nrf2/Keap1 signaling pathway-related proteins was analyzed by western blotting. As a result, PCA suppressed the viability, migration, invasion, and oxidative and promoted apoptosis of H₂O₂-induced RA-FLSs by activating the Nrf2/Keap1 signaling pathway. ML-385, an Nrf2 inhibitor, could enhance the viability, migration, invasion, and oxidative and inhibited apoptosis of H₂O₂-induced RA-FLSs. In conclusion, PCA reduced H₂O₂-induced migration and oxidative stress of RA-FLSs by activating the Nrf2-Keap1 signaling pathway.

Anesthetics exposure induces neurocognitive deficits during brain development and impairs self-renewal and differentiation of neural stem cells (NSCs). Tripartite motif 72 (TRIM72, also known as mitsugumin 53, MG53) is involved in tissue repair and plasma membrane damage repair. The neuroprotective effect of TRIM72 against sevoflurane-induced neurotoxicity of NSCs was investigated in this study. First, human NSCs were exposed to different concentrations of sevoflurane. Results showed that TRIM72 was downregulated in sevoflurane-treated NSCs. Exposure to sevoflurane reduced cell viability in NSCs. Second, sevoflurane-treated NSCs were stimulated with recombinant human TRIM72 (rhTRIM72). Treatment with rhTRIM72 enhanced the cell viability in sevoflurane-treated NSCs. Moreover, treatment with a rhTRIM72-attenuated sevoflurane-induced increase in caspase-3 activity in NSCs. Third, JC-1 aggregates were deceased and JC-1 monomer was increased in sevoflurane-treated NSCs, which were reversed by rhTRIM72. Furthermore, rhTRIM72 also weakened sevoflurane-induced decrease in superoxide dismutase and glutathione peroxidase and increase in malondialdehyde and reactive oxygen species in NSCs. Finally, reduced phosphorylation levels of protein kinase B (AKT) and phosphatidylinositol 3-kinase (PI3K) in sevoflurane-treated NSCs were upregulated by rhTRIM72. In conclusion, TRIM72 inhibited cell apoptosis and reduced the mitochondria membrane potential of sevoflurane-treated NSCs through activation of the PI3K/AKT pathway.

Prostate cancer (PCa) is one of the leading causes of cancer-related death in males worldwide and exploring more reliable biomarkers for PCa is essential for the diagnosis and therapeutics for the disease. Although the functions of miR-141-3p and AlkB homolog 5 (ALKBH5) were identified in some cancers, whether they were involved in the development of PCa remains unclear. In this study, reverse transcription-quantitative polymerase chain reaction unveiled that the expression of ALKBH5 was reduced in PCa tissues and was negatively correlated with miR-141-3p. ALKBH5 attenuated the malignant development of PCa through suppressing the growth, migration, invasion, and sphere formation abilities of PCa cells. In addition, the luciferase activity assay identified that ALKBH5 was corroborated as a downstream target of miR-141-3p. Moreover, miR-141-3p expression was boosted in PCa tissues and cells and inhibition of miR-141-3p suppressed the tumor growth of PCa in vivo. Moreover, ALKBH5 was confirmed to suppress protein arginine methyltransferase 6 (PRMT6) expression through N6-methyladenosine (m⁶A) modification. We further identified that miR-141-3p-modulated PRMT6 level through mediating ALKBH5. Furthermore, PRMT6 level was positively correlated with miR-141-3p level and negatively associated with ALKBH5 level. Finally, rescue assays also uncovered that miR-141-3p aggravated PCa development by regulating PRMT6. In conclusion, miR-141-3p accelerated the malignant progression of PCa through ALKBH5-mediated m6A modification of PRMT6, which might offer a novel insight into the role of miR-141-3p and ALKBH5 in the treatments of PCa patients.