Non-traditional lipid profiles and the risk of stroke: A systematic review and meta-analysis.

AIMS: An increasing number of studies on non-traditional lipid profiles have been investigated in recent years. However, the associations between non-traditional lipid profiles and the risk of stroke remained inconsistent. Therefore, this meta-analysis aimed to evaluate the associations between non-traditional lipid profiles and the risk of stroke and clarify the dose-response relations. DATA SYNTHESIS: We performed a systematic literature search in PubMed, Embase, and Web of Science databases until 1 November 2022 for relevant studies. Relative risks and 95% confidence intervals were pooled by random-effects or fixed-effects models. A total of 26 full-text studies with 676678 participants and 18057 stroke cases were eligible for the final study. We found a positive association between the risk of stroke and total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio (RR = 1.19,95%CI = 1.00-1.40, I2 = 74.6%), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio (RR = 1.24,95%CI = 1.10-1.41, I2 = 62.8%) or low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio (RR = 1.24, 95%CI = 1.11-1.39, I2 = 49.4%). When focusing on the stroke subtype, a more significant association was observed between the risk of ischemic stroke and four non-traditional lipid profiles. In dose-response analysis, we found a linear association between TC/HDL-C ratio and the risk of stroke (RR = 1.16,95%CI = 1.07-1.26). CONCLUSIONS: Elevated non-traditional lipid profiles were associated with an increased risk of ischemic stroke. The linear association showed the risk of stroke increased by 16% when the pooled RR of TC/HDL-C ratio per 1-unit increased. REGISTRATION NUMBER IN PROSPERO: CRD42022321251.

PVT1 regulates the malignant behaviors of human glioma cells by targeting miR-190a-5p and miR-488-3p.

The long non-coding RNA (lncRNA) PVT1 is reported to be involved in tumorigenesis and the progression of many malignancies. However, the function of PVT1 in gliomas remains unclarified. The present study demonstrated the expression level of PVT1 using qRT-PCR. The role of PVT1 in the regulation of biological behaviors of glioma cells was investigated using CCK-8 assay, Transwell assay and flow cytometry. The possible molecular mechanisms were also elucidated. In our results, PVT1 was up-regulated in glioma specimens and cell lines. Knockdown of PVT1 impaired the malignant behaviors of glioma cells via the suppression of proliferation, migration and invasion, as well as through promotion of apoptosis. Furthermore, PVT1 was identified to affect the glioma cells via binding to miR-190a-5p and miR-488-3p, which were down-regulated and played tumor suppressor roles in glioma cells. Up-regulated miR-190a-5p or miR-488-3p partially rescued the suppressive effect induced by PVT1 knockdown. Myocyte enhancer factor 2C (MEF2C) was a direct downstream target of miR-190a-5p and miR-488-3p, which was proved to be an oncogene and involved in the PVT1 knockdown induced regulation of biological behaviors of glioma cells. Over-expression of MEF2C up-regulated JAGGED1 by increasing the promoter activity of JAGGED1. PVT1 knockdown combined with miR-190a-5p and miR-488-3p over-expression contributed to the smallest tumor volume and the longest survivals in nude mice. In conclusion, PVT1-miR-190a-5p/miR-488-3p-MEF2C-JAGGED1 axis is involved in proliferation and progression of glioma. Thus, PVT1 may become a novel target in glioma therapy.

Ursolic Acid Ameliorated Neuronal Damage by Restoring Microglia-Activated MMP/TIMP Imbalance in vitro.

Purpose: The oxygen and glucose deprivation-reoxygenation (OGDR) model is widely used to evaluate ischemic stroke and cerebral ischemia-reperfusion (I/R) injury in vitro. Excessively activated microglia produce pro-inflammatory mediators such as matrix metalloproteinases [MMPs] and their specific inhibitors, tissue inhibitors of metalloproteinases [TIMPs], causing neuronal damage. Ursolic acid (UA) acts as a neuroprotective agent in the rat middle cerebral artery occlusion/reperfusion (MCAO/R) model keeping the MMP/TIMP balance with underlying mechanisms unclear. Our study used OGDR model to determine whether and how UA reduces neuronal damage by reversing MMP/TIMP imbalance caused by microglia in I/R injury in vitro. Methods: SH-SY5Y cells were first cultured with 95% N2 and 5% CO2 and then cultivated regularly for OGDR model. Cell viability was tested for a proper UA dose. We established a co-culture system with SH-SY5Y cells and microglia-conditioned medium (MCM) stimulated by lipopolysaccharide (LPS) and interferon-gamma (IFNγ). MMP9 and TIMP1 levels were measured with ELISA assay to confirm the UA effect. We added recombinant MMP9 (rMMP9) and TIMP1 neutralizing antibody (anti-TIMP1) for reconfirmation. Transmission electron microscopy was used to observe cell morphology, and flow cytometry and Annexin V-FITC and PI labeling for apoptotic conditions. We further measured the calcium fluorescence intensity in SH-SY5Y cells. Results: The MCM significantly reduced cell viability of SH-SY5Y cells after OGDR (p<0.01), which was restored by UA (0.25 µM) (p<0.05), whereas lactate dehydrogenase activity, intraneuronal Ca2+ concentration, and apoptosis-related indexes were showed significant improvement after UA treatment (p<0.01). UA corrected the MMP/TIMP imbalance by decreasing MMP9 expression and increasing TIMP1 expression in the co-culture system (p<0.01) and the effects of UA on SH-SY5Y cells were mitigated by the administration of rMMP9 and anti-TIMP1 (p<0.01). Conclusion: We demonstrated that UA inhibited microglia-induced neuronal cell death in an OGDR model of ischemic reperfusion injury by stabilizing the MMP9/TIMP1 imbalance.

Sex-specific prediction value of common carotid artery diameter for stroke risk in a hypertensive population: a cross-sectional study.

BACKGROUND: The importance of sex as a risk factor for stroke has been established. This study aimed to assess sex-related disparities in carotid artery diameter and stroke in a hypertensive population. METHODS: The cross-sectional survey was conducted in rural areas of northeast China. A multistage cluster sampling method was employed to select a representative population. The study comprised 3,245 individuals with hypertension. The common carotid artery (CCA) interadventitial diameter was measured by ultrasound. A linear model of restricted cubic spline function was used to characterize the concentration-response (C-R) relationship between CCA diameter and stroke. RESULTS: The overall prevalence of stroke was 8.9% among hypertensive individuals, with a higher rate in men than in women (10.8% vs. 7.6%). When the women's CCA diameters were divided into quartiles, the top quartile (>8.10 mm) had a 2.49 (95% CI: 1.36-4.56) times greater risk of stroke compared to the bottom quartile (≤6.80 mm) after adjustment was made for other variables. The C-R relationship further confirmed a positive association between CCA diameter and stroke prevalence in women. Moreover, a category-free net reclassification index (0.325; 95% CI: 0.173-0.476; P<0.001) and an integrated discrimination index (0.008; 95% CI: 0.004-0.012, P<0.001) showed improvement in predicting the probability of stroke from CCA diameter. However, no significant relationship between CCA diameter and prevalence of stroke was found in men. CONCLUSIONS: The risk of stroke increased proportionally with the enlargement of the CCA diameter in women, supporting the sex-specific value of CCA diameter in optimizing the risk stratification of stroke.

Sex difference in the correlation between carotid artery diameter and prevalence of stroke: Insights from a Chinese population.

BACKGROUND: The atherosclerotic process can cause compensatory enlargement of artery diameter. However, the association between common carotid artery (CCA) diameter and stroke remains unclear. METHODS: This cross-sectional study included 5668 participants ≥40 years of age residing in rural northeast China, in whom the inter-adventitial diameter of CCA was measured. The association between CCA diameter and stroke prevalence was explored using multivariate logistic regression and concentration-response relationship in females and males, respectively. RESULTS: CCA diameter (mm) was greater in stroke than in non-stroke populations in both males (7.73 versus [vs.] 7.49; P < 0.05) and females (7.69 vs. 7.13; P < 0.001). Among males, when dividing CCA diameters into quartiles, the second quartile (6.86-7.5 mm) had a 1.64 times higher risk for stroke than the bottom quartile (≤6.85 mm) (P < 0.05) in the adjusted model. In females, the top quartile (>7.95 mm) had a 2.08 (1.07-4.04) times higher risk than the bottom quartile (≤6.50 mm) (P < 0.01) (overall trend 1.19 [1.00-1.43]). Moreover, dose-response relationship confirmed correlations between CCA diameter and stroke in females (P < 0.05). The net reclassification index (NRI) and integrated discrimination index (IDI) confirmed the incremental value of CCA diameter in predicting probability of stroke in females (NRI 0.353 [95% confidence interval (CI) 0.198-0.497], P < 0.001; IDI 0.004 [95% CI 0.001-0.006], P < 0.01) and males (NRI 0.201 [95% CI 0.158-0.241], P < 0.001; IDI 0.005 [95% CI 0.001-0.009], P < 0.01). CONCLUSIONS: This study highlighted the incremental value of CCA diameter in optimizing risk classification and stroke prevention in a Chinese population.

Incremental significance and sex discrepancies of neck circumference on the odds of ischaemic stroke: a multistage, population-based, cross-sectional study from Northeast China.

OBJECTIVES: Accumulated evidence suggests that neck circumference (NC) is associated with cardiometabolic risk factors. However, limited studies are available regarding the association between NC or height normalised NC (neck-to-height ratio (NHR)) and risk of ischaemic stroke (IS) in the Chinese population. Therefore, we aimed at examining the associations between NC or NHR and odds of IS and exploring the discrepancies between men and women. DESIGN: A multistage cluster cross-sectional study. SETTING: A population-based study carried out in Northeast China. METHODS: A cross-sectional study was undertaken in Northeast China between September 2017 and March 2019, involving 7236 men and 11 352 women, respectively. The median age of participants was 60.30 years, ranging from 40 to 97 years. The associations between NC or NHR and odds of IS were calculated using multiple logistic regression models. Dose-response relationships were depicted using restricted cubic spline functions. Reclassification analyses were carried out to determine the incremental significance of NC or NHR on the odds of IS. RESULTS: In women, NC and NHR were significantly associated with the odds of IS, independent of traditional risk factors and other anthropometric parameters for obesity. The highest quartile of NC and NHR had a 1.60 (95% CI 1.16 to 2.22)-and 1.72 (95% CI 1.23 to 2.41) times higher odds of IS compared with the lowest quartile. Furthermore, the odds of IS increased by 1.10 (95% CI 1.01 to 1.20) and 1.12 (95% CI 1.02 to 1.22) times per 1 SD increase in NC and NHR, respectively. Reclassification analyses showed that the proportion of correct classification increased by 11.5% (95% CI 2.2% to 20.7%) and 22.8% (95% CI 13.5% to 32.0%) after the addition of NC or NHR into established models, respectively. However, the findings could not be replicated in men. CONCLUSION: NC and NHR might be promising independent indicators for women IS. Their incremental value in the risk stratification of IS enables the individualised prevention of IS in women.

Differential Expression of mRNAs in Peripheral Blood Related to Prodrome and Progression of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease that affects the quality of life of elderly individuals, while the pathogenesis of AD is still unclear. Based on the bioinformatics analysis of differentially expressed genes (DEGs) in peripheral blood samples, we investigated genes related to mild cognitive impairment (MCI), AD, and late-stage AD that might be used for predicting the conversions. Methods. We obtained the DEGs in MCI, AD, and advanced AD patients from the Gene Expression Omnibus (GEO) database. A Venn diagram was used to identify the intersecting genes. Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) were used to analyze the functions and pathways of the intersecting genes. Protein-protein interaction (PPI) networks were constructed to visualize the network of the proteins coded by the related genes. Hub genes were selected based on the PPI network. Results. Bioinformatics analysis indicated that there were 61 DEGs in both the MCI and AD groups and 27 the same DEGs among the three groups. Using GO and KEGG analyses, we found that these genes were related to the function of mitochondria and ribosome. Hub genes were determined by bioinformatics software based on the PPI network. Conclusions. Mitochondrial and ribosomal dysfunction in peripheral blood may be early signs in AD patients and related to the disease progression. The identified hub genes may provide the possibility for predicting AD progression or be the possible targets for treatments.

miR-23a-3p/SIX1 regulates glucose uptake and proliferation through GLUT3 in head and neck squamous cell carcinomas.

SIX1 overexpression has been reported in several cancers. However, its involvement in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study we investigated the clinical significance and biological roles of SIX1 in HNSCC. SIX1 expression was upregulated in HNSCC and correlated with TNM stage and nodal metastasis. Analysis of TCGA dataset demonstrated that high SIX1 expression correlated with poor patient prognosis. Overexpression of SIX1 in the Fadu cell line upregulated cell proliferation, colony formation, glucose uptake and ATP production. In contrast, SIX1 depletion in the Detroit562 cell line downregulated cell proliferation, colony formation, glucose uptake and ATP production. We analyzed a series of genes involved in glucose metabolism and found that SIX1 overexpression upregulated GLUT3, an important glucose transporter, at both mRNA and protein levels. Using the TRANSFAC database, we found that SIX1 had potential binding sites on the GLUT3 promoter, which was validated by chromatin immunoprecipitation (ChIP) assays. Next, we focused on miR-23a-3p, which could target SIX1 in HNSCC cells. The miR-23a-3p mimic downregulated SIX1 expression while the miR-23a-3p inhibitor upregulated SIX1 expression. The binding of miR-23a-3p to the 3'-UTR of SIX1 was confirmed using the luciferase reporter assay. Analysis of TCGA dataset showed a negative correlation between the miR-23a-3p and SIX1. Furthermore, the miR-23a-3p mimic inhibited cell proliferation, ATP production and glucose uptake, which could be rescued by transfection with the SIX1 plasmid. In summary, our study demonstrated that SIX1 facilitated HNSCC cell growth through regulation of GLUT3 and glucose uptake. miR-23a-3p targeted the SIX1/GLUT3 axis and suppressed glucose uptake and proliferation in HNSCC.

25-Hydroxyvitamin D level, vitamin D intake, and risk of stroke: A dose-response meta-analysis.

BACKGROUND & AIMS: A growing number of studies have shown that vitamin D are related to the risk of stroke, however, the dose-response association between vitamin D and the risk of stroke is still unclear. Accordingly, we conducted a dose-response meta-analysis to evaluate the relationships between 25-hydroxyvitamin D [25(OH)D] level, vitamin D intake, and the risk of stroke by summarizing cohort studies. METHODS: PubMed, Embase, Cochrane and the Web of Science database were searched for related studies. Cohort studies examining the influence of 25(OH)D level and vitamin D intake on stroke risk were summarized. Dose-response relationships were determined using a random-effect model. RESULTS: Twenty cohort studies involving 217,235 participants were included. The pooled relative risk for the high-versus-low categories was 0.74 (95% CI: 0.66-0.83) for 25(OH)D level, and 0.75 (95% CI: 0.57-0.98) for vitamin D intake. In addition, there were non-linear relationships between 25(OH)D level, vitamin D intake, and stroke risk. The incidence of stroke was reduced to its lowest point, with a reduction of about 20%, when 25(OH)D level was about 50 nmol/L or vitamin D intake was about 12 µg/day. CONCLUSION: 25(OH)D level and vitamin D intake were both inversely related to stroke risk, with a non-linear dose-response relationship.

Association between skipping breakfast and risk of cardiovascular disease and all cause mortality: A meta-analysis.

BACKGROUND & AIMS: Previous studies on the association between skipping breakfast and risk of cardiovascular disease and all cause mortality have drawn controversial conclusions. Therefore, we carried out a meta-analysis to illuminate this association. METHODS: Studies about the association between skipping breakfast and risk of cardiovascular disease and all cause mortality were identified by searching Pubmed, Embase, Cochrane, and Web of Science databases until June 2019. Then we screened articles for eligibility, extracted data, and pooled the results using a random-effects model. RESULTS: Seven cohort studies concerning a total of 221,732 participants were included in this meta-analysis. Skipping breakfast was associated with elevated risk of cardiovascular disease (relative risk 1.22 95% confidence interval 1.10-1.35) and all cause mortality (relative risk 1.25 95% confidence interval 1.11-1.40) compared with eating breakfast regularly. CONCLUSION: Skipping breakfast increases the risk of cardiovascular disease and all cause mortality. Eating breakfast regularly may promote cardiovascular health and decrease all cause mortality.

Activation of TLR4-mediated NFkappaB signaling in hemorrhagic brain in rats.

Inflammation and immunity play a crucial role in the pathogenesis of Intracerebral hemorrhage (ICH). Toll-like receptor 4- (TLR4-) mediated nuclear factor kappa-B (NFkappaB) signaling plays critical roles in the activation and regulation of inflammatory responses in injured brain. However, the involvement of TLR4-mediated NFkappaB signaling in the pathogenesis of ICH remains unknown. The present study was to evaluate the temporal profile of the expression of TLR4 and the activation of TLR4-mediated NFkappaB signaling in brain tissues of Wistar rats after ICH. TLR4 mRNA and protein, the phosphorylation of inhibitors of kappa B (p-IkappaBalpha), and the activity of NFkappaB were examined in hemorrhagic cerebral tissue by Rt-PCR, Western blots, immunohistochemistry staining, and EMSA. Compared with saline control, the TLR4 mRNA and protein significantly increased starting at 6 hours after ICH, peaked on the 3rd day after ICH, and then decreased but still maintained at a higher level on the 7th day after ICH (P < .05). The level of p-IkappaBalpha and the activity of NFkappaB also increased in the brain after ICH compared with saline control. The present study firstly suggests that TLR4-mediated NFkappaB signaling participates in the pathogenesis of ICH, which may become a therapeutic target for ICH-induced brain damage.

Anger, hostility and risk of stroke: a meta-analysis of cohort studies.

OBJECTIVE: A growing number of studies have been conducted on the relationship between anger and hostility and the risk of stroke, and their conclusions are not consistent. Accordingly, we performed a meta-analysis to evaluate the relationship between anger and hostility and the risk of stroke. METHODS: We searched the PubMed and Embase databases for cohort studies, focusing on the relationship between anger and hostility and risk of stroke. Then studies were selected according to the inclusion and exclusion criteria. Study results were pooled using a random effects model. RESULTS: Ten studies from seven articles involving 52,277 participants were included in this meta-analysis. No significant association was found between anger and hostility level and risk of stroke (hazard ratio 1.08; 95% confidence interval 0.79-1.47). However, a positive association was seen when people with high socioeconomic status were excluded (hazard ratio 1.30; 95% confidence interval 1.06-1.59). CONCLUSION: A higher level of anger and hostility is not associated with elevated risk of stroke. However, the association is positive among people with lower socioeconomic status.

Overexpression of TRIM24 Stimulates Proliferation and Glucose Metabolism of Head and Neck Squamous Cell Carcinoma.

TRIM24 (Tripartite Motif Containing 24) is a recently identified oncogene overexpressed in various cancers. However, the molecular mechanism of TRIM24 in the progression of head and neck squamous cell carcinoma (HNSCC) remains ambiguous. In the present study, we analyzed the expression pattern of TRIM24 in 100 HNSCC tissues and found that TRIM24 was overexpressed in 43/100 HNSCC cases. Significant association was found between TRIM24 overexpression and tumor-node-metastasis (TNM) stage (p = 0.0034) and T stage (p = 0.0048). Furthermore, we overexpressed and knocked down TRIM24 in Detroit 562 and FaDu cell lines, respectively. TRIM24 overexpression promoted proliferation, colony formation, and invasion, while TRIM24 depletion inhibited proliferation, colony formation, and invasion. Further studies showed that TRIM24 facilitated cell cycle transition and upregulated cyclin D1 and p-Rb. In addition, we found that GLUT3, a key protein involved in regulating glucose metabolism, was altered in HNSCC cells overexpressing TRIM24. We demonstrated that TRIM24 overexpression increased glucose uptake ATP production. Overexpression of TRIM24 increases cell sensitivity to glucose deprivation in Detroit cells. Depleting TRIM24 in FaDu cells demonstrated the opposite results. We also showed that TRIM24 could bind to the promoter region of cyclin D1. In conclusion, TRIM24 is upregulated in HNSCC and promotes HNSCC cell growth and invasion through modulation of cell cycle, glucose metabolism, and GLUT3, making TRIM24 a potential oncoprotein in HNSCC.

25-Hydroxyvitamin D Levels and the Risk of Dementia and Alzheimer's Disease: A Dose-Response Meta-Analysis.

Background and Purpose: Conclusions of previous cohort studies on the relationship between 25-hydroxyvitamin D level and the risk of dementia and Alzheimer's disease were not consistent. Thus, we performed a dose-response meta-analysis to evaluate this relationship by summarizing cohort studies. Methods: Pubmed, Embase, Cochrane, and Web of Science databases were searched for relevant studies. Cohort studies concerning the association between 25-hydroxyvitamin D level and dementia or Alzheimer's disease were included. Results of studies were pooled and the dose-response relationship was determined using a random-effect model. Results: Ten cohort studies, with 28,640 participants were included. A significant inverse relationship was found between 25-hydroxyvitamin D level and the risk of dementia and Alzheimer's disease. In addition, we found a linear dose-response relationship in that a 10 nmol/L increase in 25-hydroxyvitamin D level may lead to a 5% decrease in the risk of dementia (relative risk, 0.95; 95% confidence interval, 0.93-0.98) and 7% in the risk of Alzheimer's disease (relative risk, 0.93; 95% confidence interval, 0.89-0.97). Conclusion: Plasma or serum 25-hydroxyvitamin D concentration was inversely related to the risk of dementia and Alzheimer's disease, consistent with a linear dose-response relationship.

Epileptic seizures as the first symptom of Wernicke's encephalopathy with cerebral cortical lesions.

Wernicke's encephalopathy (WE) is acute metabolic disease of the central nervous system caused by deficiency of thiamine. Typical imaging findings are bilateral and symmetric signal in mammillary bodies, medial thalamus and periaqueductal gray. We present a 45-year-old man diagnosed for WE with two seizures and unconsciousness. The magnetic resonance imaging showed bilateral and symmetrical signal hyper-intensities in the frontal and parietal cortex, in addition to the classical MRI findings of WE. Cortical damage in WE is rare. The patient was improved significantly from unconsciousness to obeying commands and answering questions after 3days by thiamine supplementation. But the muscle strength and conscious state did not improve after 1year. This case report reminds us that we should take into account the possibility of WE when imaging shows cortical damage.

[Maxillary ameloblastic fibroma: a case report].

Ameloblastic fibroma (AF) is a benign tumor, it is a true mixed tumor composed of neoplastic epithelium and mesenchymal. This tumor is rare, and it almost arises in the mandible. A 22-years old female patient referred AF in the maxillary was present. The tumor was asymptomatic, except the right facial bulge. The radiograph showed a well-circumscribed neoplasm with several low density cysts involving the right maxillary and ethmoid. The lesion was enucleated and the material was sent for histopathologic examination. Microscopically, it was composed epithelium and mesenchymal with histopathological diagnosis of ameloblastic fibroma.