Association between advanced lung cancer inflammation index and all-cause and cardiovascular mortality among stroke patients: NHANES, 1999-2018.

Background: Stroke was a major global public health challenge, and its prognosis was remarkably associated with inflammation levels and nutritional status. The advanced lung cancer inflammation index (ALI) was a comprehensive indicator that combined inflammation and nutritional status. Currently, the relationship between ALI and the prognosis of stroke patients was not yet known. The purpose of the current study was to estimate their relationship. Methods: Cohort data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were collected. The association between ALI and all-cause and cardiovascular disease (CVD) mortality in stroke patients was estimated using a multivariable adjusted Cox model. Their non-linear relationship was analyzed by restricted cubic spline analysis. Sensitivity analysis was constructed through stratified analysis and interaction analysis. Results: 1,440 stroke patients were included in this study. An elevated ALI was significantly related to a reduced risk of all-cause mortality in stroke patients but not related to CVD mortality. A reverse J-shaped non-linear association between ALI and all-cause mortality in stroke patients, with an inflection point at 83.76 (the lowest of the mortality risk). On the left side of the inflection point, for each 10 U increase in ALI, there was a 16% reduction in the risk of all-cause mortality. However, on the right side, the risk increased by 6%. There was no remarkable interaction between stratified variables and ALI. Conclusion: This was the first study on the relationship between ALI and all-cause and CVD mortality in stroke patients. Elevated ALI was closely associated with a reduced risk of all-cause mortality. A reverse J-shaped non-linear relationship existed between the two, with an inflection point at 83.76. These findings implied that controlling the ALI of stroke patients within an appropriate range was crucial for their prognosis (such as weight management, albumin supplementation, anti-inflammatory treatment). The dynamic variation in ALI was also advantageous for clinicians in establishing personalized ALI criteria to maximize the long-term survival of stroke patients.

PCSK9 induces endothelial cell autophagy by regulating the PI3K/ATK pathway in atherosclerotic coronary heart disease.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease of the arteries, and its pathogenesis is related to endothelial dysfunction. It has been found that the protein convertase subtilin/kexin9 type (PCSK9) plays an important role in AS, but its specific mechanism is still unclear. METHODS: In this study, we first cultured human umbilical vein endothelial cells (HUVECs) with 50 or 100µg/ml oxidized low-density lipoprotein (ox-LDL) for 24 hours to establish a coronary atherosclerosis cell model. RESULTS: The results showed that ox-LDL induced HUVEC injury and autophagy and upregulated PCSK9 protein expression in HUVECs in a concentration-dependent manner. Silencing PCSK9 expression with siRNA inhibited ox-LDL-induced HUVEC endothelial dysfunction, inhibited the release of inflammatory factors, promoted HUVEC proliferation and inhibited apoptosis. In addition, ox-LDL increased the expression of LC3B-I and LC3B-II and decreased the expression of p62. However, these processes are reversed by sh-PCSK9. In addition, sh-PCSK9 can inhibit PI3K, AKT and mTOR phosphorylation and promote autophagy. CONCLUSION: Taken together, our research shows that silencing PCSK9 inhibits the PI3K/ATK/mTOR pathway to activate ox-LDL-induced autophagy in vascular endothelial cells, alleviating endothelial cell injury and inflammation.

Casein Reactivates Dopaminergic Nerve Injury and Intestinal Inflammation with Disturbing Intestinal Microflora and Fecal Metabolites in a Convalescent Parkinson's Disease Mouse Model.

Parkinson's disease (PD) is the fastest-growing neurodegenerative disease, with pathogenic causes elusive and short of effective treatment options. Investigations have found that dairy products positively correlate with the onset of PD, but the mechanisms remain unexplored. As casein is an antigenic component in dairy products, this study assessed if casein could exacerbate PD-related symptoms by stimulating intestinal inflammation and unbalanced intestinal flora and be a risk factor for PD. Using a convalescent PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the results showed casein reduced motor coordination, caused gastrointestinal dysfunction, reduced dopamine content, and induced intestinal inflammation. Meanwhile, casein disturbed gut microbiota homeostasis by increasing the Firmicutes/Bacteroidetes ratio, decreasing α-diversity, and caused abnormal alterations in fecal metabolites. However, these adverse effects of casein attenuated much when it had hydrolyzed by acid or when antibiotics inhibited the intestinal microbiota of the mice. Therefore, our results suggested that casein could reactivate dopaminergic nerve injury and intestinal inflammation and exacerbate intestinal flora disorder and its metabolites in convalescent PD mice. These damaging effects might be related to disordered protein digestion and gut microbiota in these mice. These findings will provide new insights into the impact of milk/dairy products on PD progression and supply information on dietary options for PD patients.

Combined analysis of single-cell and bulk RNA sequencing reveals the expression patterns of circadian rhythm disruption in the immune microenvironment of Alzheimer's disease.

Background: Circadian rhythm disruption (CRD) represents a critical contributor to the pathogenesis of Alzheimer's disease (AD). Nonetheless, how CRD functions within the AD immune microenvironment remains to be illustrated. Methods: Circadian rhythm score (CRscore) was utilized to quantify the microenvironment status of circadian disruption in a single-cell RNA sequencing dataset derived from AD. Bulk transcriptome datasets from public repository were employed to validate the effectiveness and robustness of CRscore. A machine learning-based integrative model was applied for constructing a characteristic CRD signature, and RT-PCR analysis was employed to validate their expression levels. Results: We depicted the heterogeneity in B cells, CD4+ T cells, and CD8+ T cells based on the CRscore. Furthermore, we discovered that CRD might be strongly linked to the immunological and biological features of AD, as well as the pseudotime trajectories of major immune cell subtypes. Additionally, cell-cell interactions revealed that CRD was critical in the alternation of ligand-receptor pairs. Bulk sequencing analysis indicated that the CRscore was found to be a reliable predictive biomarker in AD patients. The characteristic CRD signature, which included 9 circadian-related genes (CRGs), was an independent risk factor that accurately predicted the onset of AD. Meanwhile, abnormal expression of several characteristic CRGs, including GLRX, MEF2C, PSMA5, NR4A1, SEC61G, RGS1, and CEBPB, was detected in neurons treated with Aß1-42 oligomer. Conclusion: Our study revealed CRD-based cell subtypes in the AD microenvironment at single-cell level and proposed a robust and promising CRD signature for AD diagnosis. A deeper knowledge of these mechanisms may provide novel possibilities for incorporating "circadian rhythm-based anti-dementia therapies" into the treatment protocols of individualized medicine.

Exercise training has a protective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model with improved neural and intestinal pathology and modified intestinal flora.

Parkinson's disease (PD) is a common neurodegenerative disease with the exact etiology still unclear, but gut microbial disorders are thought to be related to the initiation and progression of it. Exercise training has a significant effect on the intestinal flora, so to investigate the promotion effect of exercise training on Parkinson's disease, we performed a rotarod walking training (5 times a week at 25 rpm for 20 min for 8 weeks) on a chronic mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and observed the locomotor function of mice, function of dopaminergic neurons, intestinal mucosal barrier condition, intestinal inflammation and the structure and composition of intestinal flora. The results showed in these PD mice, exercise training improved their motility, increased the dopamine (DA) content in the striatum, along with promoted the gene expression of tyrosine hydroxylase and brain-derived neurotrophic factor in the striatum, which suggests this exercise training might protect striatal dopaminergic neurons from MPTP damage; the results also showed exercise training promoted recovery from ileal pathology, reduced the gene expression of intestinal inflammatory factors, and significantly altered the composition and structure of the intestinal flora in these mice.

Bibliometric and visualization analysis of research trend in mental health problems of children and adolescents during the COVID-19 pandemic.

Objectives: To analyze the evolution of research on children and adolescents mental health issues during COVID-19 pandemic and discuss research hotspots and cutting-edge developments. Methods: The literature obtained from the web of science core collection as of June 28, 2022, was analyzed using Citespace, VOSviewer bibliometric visualization mapping software. Results: A total of 6,039 relevant papers were found, of which 5,594 were included in the study. The number of literatures is growing since 2020; and the country, institution, and journal publications were analyzed. The co-citation analysis shows that there are more research articles among the highly cited articles and a lack of systematic reviews that use critical thinking for review. In the cluster analysis, mental health and life change were the most representative. The timeline view of the keywords shows that Online learning (#0), Public health (#1), and Mental health (#2) are the three largest clusters and shows the change over time. Conclusion: This study helped analyze the mental health of children and adolescents during the COVID-19 pandemic and identified hot trends and shortcomings, which are important references for the theoretical basis of future research and decision making and technical guidance for systematic reviews.

Phoenixin-20 Prevents ox-LDL-Induced Attachment of Monocytes to Human Aortic Endothelial Cells (HAECs): A Protective Implication in Atherosclerosis.

The exact cause of atherosclerosis is not known, and therefore, the current treatment options are limited. The activation of endothelial cells by oxidized low-density lipoprotein (ox-LDL) plays a key role in the initiation and progression of atherosclerosis. Phoenixin-20 is one of the newly identified neuropeptides with pleiotropic effects in the regulation of reproduction and other biological functions. G-protein receptor-coupled 173 (GPR173) is the putative receptor of Phoenixin-20. In the present study, we show that endothelial GPR173 is repressed upon ox-LDL stimulation in human aortic endothelial cells (HAECs). We further elaborate on the hypothesis that GPR173 could be involved in the pathogenesis of atherosclerosis through a series of experiments. Our results indicate that ox-LDL remarkably triggers the increase of ROS, NOX-4, pro-inflammatory cytokines IL-1ß, IL-8, and MCP-1 expression, as well as adhesion molecules ICAM-1 and VCAM-1 release. However, the agonism of GPR173 using Phoenixin-20 significantly ameliorates all of these harmful effects from ox-LDL by suppressing the NF-κB pathway. Furthermore, we show that agonism of GPR173 by Phoenixin-20 prevents the attachment of monocytes THP-1 to endothelial cells, which is an important therapeutic approach to preventing atherogenesis. In conclusion, our study demonstrates that GPR173 agonism by Phoenixin-20 plays a protective role against ox-LDL-induced endothelial dysfunction, implying that Phoenixin-20 may have therapeutic implications in atherosclerosis.

Taxifolin inhibits the scar cell carcinoma growth by inducing apoptosis, cell cycle arrest and suppression of PI3K/AKT/mTOR pathway.

PURPOSE: Plant metabolites have gained considerable attention as the anticancer agents over the last few decades. Previous studies have indicated the potential of taxifolin as an anticancer agent. However, the information on the anticancer activity of taxifolin against skin scar cell carcinoma as well as several other types of cancers is scantly. Against this background, the present study was designed to investigate the anticancer activity of taxifolin against a panel of skin scar cell carcinoma cell lines. MATERIALS AND METHODS: Proliferation rate of the cells was monitored by MTT assay. DAPI and annexin V/PI assay was used to investigate the induction of apoptosis. Flow cytometery was employed to carry out the cell cycle analysis. Transwell assay was used to check the invasion of the cancerous cells. RESULTS: The results indicated that taxifolin inhibits the growth of the skin scar cell carcinoma cell lines. However the anticancer effects were more profound on the SSCC cancer cells (IC50, 20 µM). In contrast the anticancer effects of taxifolin on the non-cancerous skin cells were minimal. Further investigation revealed that the anticancer effects of taxifolin on the SSCC cells is due to the induction of apoptosis and cell cycle arrest. Moreover, taxifolin could also inhibit the invasion of SSCC cells which was associated with downregulation of the MMP-2 and MMP-9 expression indicative of the potential of taxifolin in the treatment of scar cell carcinoma Conclusion: It is was found that taxifolin inhibited the growth of skin scar cell carcinoma growth by triggering apoptosis and cell cycle arrest and also inhibited cell invasion capacity and therefore this study warrants further investigation on the anticancerous potential of taxifolin.