Emerging healthy lifestyle factors and all-cause mortality among people with metabolic syndrome and metabolic syndrome-like characteristics in NHANES.

BACKGROUND: The impact of integrated lifestyles on health has attracted a lot of attention. It remains unclear whether adherence to low-risk healthy lifestyle factors is protective in individuals with metabolic syndrome and metabolic syndrome-like characteristics. We aimed to explore whether and to what extent overall lifestyle scores mitigate the risk of all-cause mortality in individuals with metabolic syndrome and metabolic syndrome-like characteristics. METHODS: In total, 6934 participants from the 2007 to 2014 National Health and Nutrition Examination Survey (NHANES) were included. The weighted healthy lifestyle score was constructed based on smoking, alcohol consumption, physical activity, diet, sleep duration, and sedentary behavior information. Generalized linear regression models and restricted cubic splines were used to analyze the association between healthy lifestyle scores and all-cause mortality. ​ RESULTS: Compared to participants with relatively low healthy lifestyle scores, the risk ratio (RR) in the middle healthy lifestyle score group was 0.51 (RR = 0.51, 95% CI 0.30-0.88), and the high score group was 0.26 (RR = 0.26, 95% CI 0.15-0.48) in the population with metabolic syndrome. The difference in gender persists. In females, the RRs of the middle and high score groups were 0.47 (RR = 0.47, 95% CI 0.23-0.96) and 0.21 (RR = 0.21, 95% CI 0.09-0.46), respectively. In males, by contrast, the protective effect of a healthy lifestyle was more pronounced in the high score group (RR = 0.33, 95% CI 0.13-0.83) and in females, the protective effects were found to be more likely. The protective effect of a healthy lifestyle on mortality was more pronounced in those aged < 65 years. Higher lifestyle scores were associated with more prominent protective effects, regardless of the presence of one metabolic syndrome factor or a combination of several factors in 15 groups. What's more, the protective effect of an emerging healthy lifestyle was more pronounced than that of a conventional lifestyle. CONCLUSIONS: Adherence to an emerging healthy lifestyle can reduce the risk of all-cause mortality in people with metabolic syndrome and metabolic syndrome-like characteristics; the higher the score, the more obvious the protective effect. Our study highlights lifestyle modification as a highly effective nonpharmacological approach that deserves further generalization.

Activity-to-sedentary ratio provides novel insight into mortality reduction among male survivors of cardiovascular disease in the United States: national health and nutrition examination survey, 2007-2014.

BACKGROUND: Lower physical activity and sedentary behavior have been identified as modifiable risk factors for cardiovascular disease (CVD). However, the quantitative, dose-response association between activity-to-sedentary ratio (ASR) and mortality is unknown. METHODS: Prospective cohort studies with participants 50 to 80 years that reported the association between recreational physical activity, sedentary behavior, and all-cause mortality were included from the 2007 to 2014 United States National Health and Nutrition Examination Survey (NHANES) and followed through December 31, 2015. Cox or Weibull regression models and restricted cubic splines were used to determine the association between ASR and all-cause mortality. RESULTS: Sixty deaths occurred among 498 CVD survivors, with a median of 56 months of follow-up. After accounting for all covariates, CVD survivors with an ASR between 0.21 and 0.57 (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.25-0.87) and those with an ASR more than 0.57 (HR, 0.40; 95% CI, 0.20-0.81) were at significantly lower risk for mortality than participants with an ASR <  0.21. Moreover, a nonlinear negative association and an L-shaped association were observed for the level of ASR with risk of mortality among CVD survivors (P for nonlinearity = 0.004). What's more, adjusting for covariates, a statistically significant interaction (P for interaction = 0.016) between sex and ASR, an increase of ASR more than and equal to 0.18 was associated with a lower risk of mortality among males (HR, 0.23; 95% CI, 0.12-0.46). CONCLUSIONS: An negative correlation between ASR and mortality in CVD survivors, especially in males when ASR is more than 0.18. Our novel findings provide further insights into easing the global burden of deaths.

Long non-coding RNA DLGAP1-AS1 modulates the development of non-small-cell lung cancer via the microRNA-193a-5p/DTL axis.

Non-small cell lung cancer (NSCLC) is one of the most malignant cancers worldwide. A growing number of studies have suggested that long noncoding RNAs (lncRNAs) play a key role in the progression of non-small cell lung cancer (NSCLC). Here, we report a novel lncRNA DLGAP1 antisense RNA 1 (DLGAP1-AS1) that exhibits oncogenic properties in NSCLC. The lncRNA DLGAP1-AS1 and denticleless protein homolog (DTL) presented upregulated expression, but microRNA-193a-5p (miR-193a-5p) showed downregulated expression in cancerous tissues of human lung samples from 48 patients with NSCLC. Partial loss of lncRNA DLGAP1-AS1 reduced malignant cell viability, migration, and invasion but induced apoptosis. Dual-luciferase reporter gene, RNA pull-down and RNA binding protein immunoprecipitation assays demonstrated enrichment of lncRNA DLGAP1-AS1 in miR-193a-5p and Argonaute 2, suggesting that lncRNA DLGAP1-AS1 modulated DTL, a putative target of miR-193a-5p. We also found that restoration of miR-193a-5p rescued NSCLC cell biological functions affected by overexpression of lncRNA DLGAP1-AS1. Silencing lncRNA DLGAP1-AS1 was found to reduce the tumorigenesis of NSCLC cells xenografted into nude mice, which was rescued by DTL overexpression. In conclusion, our study highlights a novel regulatory network of the lncRNA DLGAP1-AS1/miR-193a-5p/DTL axis in NSCLC, providing a potential therapeutic strategy for NSCLC.

Plasma chromogranin A levels are associated with acute ischemic stroke with anterior circulation large vessel occlusion.

BACKGROUND AND AIMS: To investigate the relationship between chromogranin A (CgA) levels and acute ischemic stroke (AIS), especially anterior circulation large vessel occlusion (LVO). METHODS AND RESULTS: 587 subjects were included in this study, including 205 AIS patients with anterior circulation LVO and 205 nonocclusive patients, as well as 177 healthy controls. On admission, plasma CgA levels were measured and neurological deficits were assessed by the NIH Stroke Scale. Outcomes were assessed by the modified Rankin Scale at 3 months. The predictive properties of CgA were evaluated by receiver operating characteristic (ROC) curve analysis. Binary logistic analysis assessed the association of CgA levels and AIS or anterior circulation LVO. AIS patients had lower CgA levels than health controls (p < 0.001). Anterior circulation LVO patients had lower CgA levels than nonocclusive patients (p < 0.001). The area under the ROC curve of plasma CgA levels in predicting anterior circulation LVO from AIS was 0.744 and the optimal cutoff value was 15.49 ng/mL with a Youden value of 0.332. Logistic analysis showed that CgA ≤15.49 ng/mL remained an independent risk factor for anterior circulation LVO after adjusting for related factors (OR = 6.519, 95% CI: 3.790-11.214, p < 0.001). CgA was an independent protective factor for mild stroke and good prognosis (p = 0.009, p = 0.005); however, the association disappeared after adjusting for occlusion (p = 0.768, p = 0.335). CONCLUSION: CgA levels were lower in AIS patients, especially in anterior circulation LVO patients. Lower CgA levels are potential biomarker for anterior circulation LVO, and they may indicate good prognosis at 3 months in AIS.

Blood Neutrophil-to-Lymphocyte Ratio as a Predictor of Cerebral Small-Vessel Disease.

BACKGROUND In recent studies, neutrophil-to-lymphocyte ratio (NLR) was reported to be a good predictor of acute ischemic stroke (AIS), but its role in cerebral small-vessel disease (CSVD) is still controversial. We aimed to explore the value of NLR to identify CSVD. MATERIAL AND METHODS We enrolled 466 CSVD patients and 413 controls. The total burden score of CSVD was calculated according to MRI results, and imaging subgroups were divided according to MRI. The 90-day outcome was evaluated using the modified Rankin scale (mRS). NIHSS score, mRS, clinical information, biochemical parameters, and NLR were recorded, and we analyzed the relationship between NLR and CSVD. RESULTS NLR was a risk factor for CSVD (OR 1.58, 95%CI 1.015~1.322; P=0.029). NLR was positively correlated with CSVD (r=0.259; P=0.001). The AUC was 0.774, with a cut-off value of 1.89 (95% CI 0.742~0.806), P=0.000. NLR was significantly different among the different total burden score groups of CSVD (P=0.009). NLRs were significant different among enlarged perivascular space (EPVS) groups (P=0.017), periventricular white matter high signal (PWMHS) groups (P=0.028), and deep white matter high signal (DWMHS) groups (P=0.004), but no significant difference was found among cerebral microbleeds (CMBs) groups (P=0.118). NLR was correlated with short-term outcome of CSVD (P=0.000). The AUC was 0.732 (95% CI 0.684~0.779), with a cut-off value of 2.413 for predicting a poor CSVD prognosis. CONCLUSIONS NLR has potential diagnostic value for CSVD, and it can predict the short-term outcome of CSVD. Therefore, NLR may be a useful biomarker to predict CSVD and its outcome.

The metabolic analysis in human aortic tissues of aortic dissection.

BACKGROUND: The metabolic profile of human aortic tissues is of great importance. Among the analytical platforms utilized in metabolomics, LC-MS provides broad metabolome coverage. The non-targeted metabolomics can comprehensively detect the entire metabolome of an organism and find the metabolic characteristics that have significant changes in the experimental group and the control group and elucidate the metabolic pathway concerning the recognized metabolites. Employing non-targeted metabolomics is helpful to develop biomarkers for disease diagnosis and disease pathology research; for instance, Aortic aneurysm (AA) and Aortic dissection (AD). AIM: This study sought to describe the non-targeted analysis of 18 aortic tissue samples, comparing between AA and AD. MATERIAL & METHODS: Our experimental flow included dividing the samples into (AA, nine samples) and (AD, nine samples), SCIEX quadrupole timeofflight tandem mass spectrometer (TripleTOF) 6600+ mass spectrometer data refinement, MetDNA database analysis, and pathway analysis. We performed an initial validation by setting quality control parameters to evaluate the stability of the analysis system during the computer operation. We then used the repeatability of the control samples to examine the stability of the instrument during the entire analysis process to ensure the reliability of the results. RESULTS: Our study found 138 novel metabolites involved in galactose metabolism. DISCUSSION: 138 novel metabolites found in this study will be further studied in the future. CONCLUSION: Our study found 138 novel metabolites between AA and AD, which will provide viable clinical data for future studies aimed to implement galactose markers in aortic tissue analysis.

Sex-specific relationship between serum uric acid levels and the prevalence of large vessel occlusion in acute ischemic stroke.

PURPOSE: Previous studies have found that uric acid (UA) plays a neuroprotective role in ischemic stroke patients. However, the relationship between serum UA of acute ischemic stroke (AIS) and large vessel occlusion (LVO) strokes is unclear. METHODS: In this retrospective study, 1318 AIS patients were enrolled. All patients underwent imaging examinations to assess the intracranial and carotid vessels. Multivariate logistic regression analysis was conducted to evaluate the relationship between UA levels and the prevalence of LVO. RESULTS: The 1318 enrolled AIS patients were comprised of 287 LVO and 1031 non-LVO patients. UA levels in males were higher than females (321.04 ± 91.28 vs. 274.43 ± 82.11, p < .001). The association between serum UA levels and LVO was modified by sex (p = .007). When serum UA levels were continuous, after adjusting for related risk factors, higher serum UA levels were still associated with a lower prevalence of LVO in males (odds ratio (OR) 0.997, 95% confidence interval (CI) 0.994-0.999), but not in female subjects (OR 0.998, 95% CI 0.995-1.001). When serum UA levels were divided into tertiles, higher UA levels had a lower risk of LVO than the moderate (p = .006) and lower tertiles of UA levels (p = .010) in males, but not in females (p = .402 and p = .206 for moderate and low tertiles, respectively). CONCLUSIONS: AIS patients with higher serum UA levels tend to be associated with a lower risk of LVO in males, but not in females.

Spinal Cord Protection of Aorto-Iliac Bypass in Open Repair of Extent II and III Thoracoabdominal Aortic Aneurysm.

BACKGROUND: Spinal cord injury (SCI) is one of the serious complications of thoracoabdominal aortic aneurysm (TAAA) repair. Cardiopulmonary bypass (CPB) and left heart bypass (LHB) are well-established extracorporeal circulatory assistance methods to increase distal aortic perfusion and prevent spinal cord ischaemia in TAAA repair. Aorto-iliac bypass, a new surgical adjunct offering distal aortic perfusion without the need of complex perfusion skills, was developed as a substitute for CPB and LHB. However, its spinal cord protective effect is unknown. METHODS: The perioperative data of 183 patients who had elective open Crawford extent II and III TAAA repair at our aortic centre from July 2011 to May 2019 were retrospectively analysed. Spinal cord protection was compared between the aorto-iliac bypass group (n=106) and the extracorporeal circulatory assistance group (n=77 [65 CPB, 12 LHB]), and the risk factors for SCI in these patients were explored. RESULTS: Eleven (11) patients had postoperative SCI: five (6.5%) in the extracorporeal circulatory assistance group (four with CPB and one with LHB), and six (5.7%) in the aorto-iliac bypass group. The incidence of SCI was 6.0% (11/183 cases). There was no difference between the aorto-iliac bypass group and the extracorporeal circulatory assistance group (p=1.0), while operation time, proximal aortic clamp time, intercostal artery clamp time, and length of intensive care unit stay were all increased in the latter group. Multivariate logistic regression analysis showed that cerebrospinal fluid pressure (odds ratio [OR] 1.270; 95% confidence interval [CI] 1.092-1.478 [p=0.002]) and lowest haemoglobin on the first postoperative day (OR 0.610; 95% CI 0.416-0.895 [p=0.011]) were the independent predictors of SCI in TAAA repair. CONCLUSIONS: Spinal cord protection of aorto-iliac bypass is comparable to that of CPB and LHB in open TAAA repair.

Association between uric acid and the prognosis of acute ischemic stroke: A systematic review and meta-analysis.

AIMS: Meta-analysis was performed to assess the value of serum uric acid in the prognosis of ischemic stroke. DATA SYNTHESIS: We searched the databases of PubMed, Embase, and Web of Science. The literature we searched was published from the establishment of the database to January 2021. The references of the included literature were also collected. Two researchers sifted through the literature according to the inclusion and exclusion criteria and extracted the data. Stata 16.0 software was used for meta-analysis, and funnel plots were used to evaluate publication bias. Ten studies fulfilled the research criteria and were eventually included, and the analysis results showed that there was no significant association between serum uric acid and the functional outcome (OR = 0.99, 95% CI; 0.97-1.10), poor outcome (OR = 1.07, 95% CI; 0.99-1.15), vascular events (OR = 0.86, 95% CI; 0.52-1.41), and mortality (OR = 1.08, 95% CI; 0.93-1.24) related to ischemic stroke. CONCLUSIONS: There was no significant correlation between serum uric acid level and prognosis of ischemic stroke.

SIRT1 protects against aortic dissection by regulating AP-1/decorin signaling-mediated PDCD4 activation.

Medial degeneration of aorta wall is the principal feature of aortic dissection (AD). Sirtuin 1 (SIRT1) plays essential protective effect on many aortic-associated disease. However, it is still unclear whether SIRT1participates in the process of medial degeneration-mediated AD. The purpose of this study is to explore the association between SIRT1 and AD process. qRT-PCR was used to evaluate the transcriptional level of genes involved in study. Protein levels and acetylation detection were measured by Western blotting. The regulatory relations between AP-1 and decorin was assessed by luciferase reporter gene assay. Acute aortic dissection (AAD) mice model was constructed by feeding with ß-aminopropionitrile monofumarate (BAPN). Haematoxylin and eosin (HE) and Mallory staining were performed for pathological analysis. In clinical aorta tissue of thoracic aortic dissection (TAD), the expression of SIRT1, activator protein 1 (AP-1) and decorin were in accordant trend. AP-1 expression which acts on Decorin promoter region is possibly regulated in a SIRT1-mediated deacetylation dependent manner. Resveratrol or SRT1720-initiated SIRT1 activation ameliorated BAPN-induced AAD symptoms accompanied by the activation of AP-1/decorin signaling and decorin-mediated programmed cell death 4 (PDCD4) expression by inhibiting miR-21 and miR-181b. These data suggest that SIRT1/AP-1/decorin signal cascades possibly play a part role in the process of AD. Our research demonstrate that activation of SIRT1 protects against AAD symptoms by enhancing AP-1-mediated decorin expression and downstream PDCD4 signaling pathway. Possibly, SIRT1 is served as a protective factor of AD and targeting SIRT1 therapy might be an attractive therapeutic approaches for AD treatment.

The onset of acute type A aortic dissection following recovery of type B intramural haematoma: a case report.

BACKGROUND: Aortic intramural hematoma is a life-threatening condition reported with increasing frequency. It can be classified into Stanford type A or B depending on whether the ascending or descending aorta are involved, respectively. However, the onset of acute type A aortic dissection following recovery of type B intramural haematoma is rarely reported. CASE PRESENTATION: We present an uncommon case of acute Stanford type A aortic dissection developing 3 months after recovery of type B IMH in a 47-year-old female. She complained acute chest pain. The operation was successfully done. She was in good condition and asymptomatic at a 3-month follow-up. CONCLUSIONS: Type B intramural haematoma can lead to type A aortic dissection even after totally absorbed and the primary entry has the potential to be located in the ascending aorta. Unsatisfied blood pressure control may be the underlying cause.

Serum miR-133 as a Potential Biomarker in Acute Cerebral Infarction Patients.

BACKGROUND: The study explores the expression and significance of miR-133 expression in peripheral blood of patients with acute cerebral infarction (ACI), so as to provide new evidence for the diagnosis and treatment of ACI. METHODS: Serum levels of miR-133, interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) were examined using RT-PCR and ELISA, respectively. Pearson's correlation assay was used to analyze the relationship between the level of serum miR-133 and inflammatory factors. Kaplan-Meier method was used to analyze the 10-year survival rate of ACI patients with different levels of miR-133 expression. RESULTS: The level of serum miR-133 in the ACI group was significantly higher than that in healthy group. Mean-while, the level of serum miR-133 in the large infarction group, middle infarction group, small infarction group, and lacunar infarction group was higher than in the healthy group. Moreover, the serum levels of miR-133 in patients with atherosclerotic thrombotic cerebral infarction (AT) and cardioembolic stroke (CE) were significantly higher than those in healthy subjects and small artery occlusive cerebral infarction (SAD) subjects. Serum levels of IL-6, IL-8, CRP and TNF-α in ACI group were significantly higher than those in healthy group. The correlation analysis showed that serum miR-133 was positively correlated with IL-6, IL-8, CRP, and TNF-α in ACI patients. The 10-year survival rate of the low-expression group was significantly higher than that of the high-expression group. CONCLUSIONS: Serum level of miR-133 may indicate the onset and progression of cerebral infarction and may be a potential biomarker for the diagnosis of ACI.

MicroRNA-181a regulates the activation of the NLRP3 inflammatory pathway by targeting MEK1 in THP-1 macrophages stimulated by ox-LDL.

Atherosclerosis (AS) is a chronic inflammatory disease that is characterized by the deposition of lipids in the vascular wall and the formation of foam cells. Macrophages play a critical role in the development of this chronic inflammation. An increasing amount of research shows that microRNAs affect many steps of inflammation. The goal of our study was to investigate the regulatory effect of miR-181a on the NLRP3 inflammasome pathway and explore its possible mechanism. Compared with the control group, the expression of miR-181a was downregulated in the carotid tissue of AS group mice, while the expression of MEK1 and NLRP3-related proteins was upregulated significantly. In vitro, when THP-1 macrophages were stimulated with oxidized low-density lipoprotein (ox-LDL), the expression of miR-181a was decreased, the MEK/ERK/NF-κB inflammatory pathways were activated and the expression of NLRP3 inflammasome-related proteins was upregulated. Exogenous overexpression of miR-181a downregulated the activation of the MEK/ERK/NF-κB pathway and decreased the expression of NLRP3 inflammasome-related proteins (such as NLRP3, caspase-1, interleukin-18 [IL-18], IL-1ß, etc). Exogenous miR-181a knockdown showed the opposite results to those of overexpression group. A luciferase reporter assay proved that miR-181a inhibited the expression of MEK1 by binding to its 3'-untranslated region. When we knocked down miR-181a and then treated cells with U0126 before ox-LDL stimulation, we found that U0126 reversed the increased activation of the MEK/ERK/NF-κB pathway and upregulation of NLRP3 inflammasome-related proteins (NLRP3, caspase-1, IL-18, IL-1ß) that resulted from miR-181a knockdown. Our study suggests that miR-181a regulates the activation of the NLRP3 inflammatory pathway by altering the activity of the MEK/ERK/NF-κB pathway via targeting of MEK1.

LncRNA MALAT1 promotes oxidized low-density lipoprotein-induced autophagy in HUVECs by inhibiting the PI3K/AKT pathway.

Emerging evidence suggests that long noncoding RNAs (lncRNAs) are involved in many biological processes, such as cell growth, differentiation, apoptosis, and autophagy. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), highly expressed in endothelial cells, is well conserved and implicated in endothelial cell migration and proliferation. However, whether MALAT1 participates in oxidized low-density lipoprotein (ox-LDL)-induced autophagy regulation in human umbilical vein endothelial cells (HUVECs) remains unknown. In this study, we observed that autophagy was upregulated and MALAT1 expression was markedly increased in HUVECs treated with ox-LDL. The ox-LDL-induced autophagy of HUVECs is significantly associated with the PI3K/AKT pathway. Furthermore, we found that MALAT1 overexpression inhibited PI3K, Akt and p70S6K phosphorylation and downregulated RHEB expression, simultaneously increasing ox-LDL-induced autophagy. MALAT1 silencing caused higher phosphorylated PI3K, Akt and p70S6K levels, upregulated RHEB expression and markedly suppressed autophagy. These results indicated that lncRNA MALAT1 promotes ox-LDL-induced autophagy in HUVECs partly through the PI3K/AKT signaling pathway.

Potential therapeutic drugs for ischemic stroke based on bioinformatics analysis.

Ischemic stroke (IS) is a complex disease affected by various environmental factors, genetic factors and their interactions. Because genetic factors occupy an irreplaceable place in the pathogenesis of IS, the identification of genetic factors has become one of the hot spots in the current research. In the present study, we aimed to identify possible gene targets and relevant drug molecules in the pathogenesis of IS. Microarray dataset of GSE16561 was downloaded from Gene Expression Omnibus database. The differentially expressed genes (DEGs) between IS group and control group were obtained using limma package in R. Ground-Operation Simulation package in R language was used to cluster DEGs according to their biological process, cellular components and molecular functions with respect to the GO annotation. The DEGs were analyzed by Search Tool for the Retrieval of Interacting Genes online database and Cytoscape software to predict their interaction relationship. Finally, the DEGs were submitted to DGIdb dataset and related drug molecules were retrieved. 20 DEGs were identified from IS group including 1 downregulated and 19 upregulated genes. The function enrichment analysis revealed that the DEGs were enriched in three GO terms, mainly including inflammatory response, positive regulation of protein kinase activity and innate immune response. Finally, 10 drug molecules were identified from the DEGs. Our study identified some potential biological targets and drug molecules for the treatment of IS.

Plasma miR-126 and miR-143 as Potential Novel Biomarkers for Cerebral Atherosclerosis.

BACKGROUND: Cerebral atherosclerosis is the most important mechanism for ischemic stroke. However, specific plasma biomarkers to assess atherosclerosis susceptibility are still lacking. Circulating miRNAs have been shown to be promising biomarkers for various pathologic conditions. We investigated whether plasma miR-126 and miR-143 could be used as biomarkers for identifying and evaluating cerebral atherosclerosis. Results showed that miR-143 and miR-126 might participate in the process of atherosclerosis and were minimally affected by cerebral infarction. Using Pearson correlation analysis, we showed that miR-126 and miR-143 were correlated with the presence and severity of cerebral atherosclerosis. The ability of miR-126 and miR-143 to differentiate atherosclerosis patients from healthy controls was demonstrated via a receiving operating characteristic curve with high specificity and sensitivity. Our data thus indicate that miR-126 and miR-143 may be potential specific biomarkers for atherosclerosis.

Associations of miR-146a, miR-149, miR-196a2, and miR-499 Polymorphisms with Ischemic Stroke in the Northern Chinese Han Population.

BACKGROUND Recently, miR-146a C>G, miR- 149 T>C, miR-196a2 T>C and miR-499 A>G polymorphisms have been associated with susceptibility to many diseases, including ischemic stroke (IS). However, results have been reported inconsistency in IS, especially in the Chinese population. This study aimed to investigate the polymorphisms of the 4 miRNAs and IS risk in the Chinese population. MATERIAL AND METHODS We used a case-control study to explore these associations in 396 patients with IS and 378 healthy controls. According to TOAST standards, the selected patients were divided into subgroups: the large artery atherosclerosis (LAA) subgroup and the small artery occlusion (SAO) subgroup. The method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotypes. RESULTS The miR-146a C>G polymorphism was remarkably different (CC vs. CG+GG: P=0.027; CC+CG vs. GG: P=0.020; C vs. G: P=0.006). The miR-149 T>C polymorphism was also remarkably different (TT vs. TC+CC: P=0.017; TT+TC vs. CC: P=0.020; T vs. C: P=0.004). The miR-146a and miR-149 polymorphisms were also remarkably different in the LAA subgroup (P<0.05). However, we did not find an association of miR-196a2 T>C or miR-499 A>G polymorphisms with IS (P>0.05); we did not find any association in the LAA subgroup or the SAO subgroup (P>0.05). CONCLUSIONS Our study suggested that miR-146a C>G and miR-149 T>C polymorphisms might remarkably increase the risk of IS, which might be mainly associated with an increased risk in LAA stroke; however, the miR-196a2 T>C and miR-499 A>G polymorphisms might not be associated with IS risk in the northern Chinese Han population.

Coping with drought: stress and adaptive mechanisms, and management through cultural and molecular alternatives in cotton as vital constituents for plant stress resilience and fitness.

Increased levels of greenhouse gases in the atmosphere and associated climatic variability is primarily responsible for inducing heat waves, flooding and drought stress. Among these, water scarcity is a major limitation to crop productivity. Water stress can severely reduce crop yield and both the severity and duration of the stress are critical. Water availability is a key driver for sustainable cotton production and its limitations can adversely affect physiological and biochemical processes of plants, leading towards lint yield reduction. Adaptation of crop husbandry techniques suitable for cotton crop requires a sound understanding of environmental factors, influencing cotton lint yield and fiber quality. Various defense mechanisms e.g. maintenance of membrane stability, carbon fixation rate, hormone regulation, generation of antioxidants and induction of stress proteins have been found play a vital role in plant survival under moisture stress. Plant molecular breeding plays a functional role to ascertain superior genes for important traits and can offer breeder ready markers for developing ideotypes. This review highlights drought-induced damage to cotton plants at structural, physiological and molecular levels. It also discusses the opportunities for increasing drought tolerance in cotton either through modern gene editing technology like clustered regularly interspaced short palindromic repeat (CRISPR/Cas9), zinc finger nuclease, molecular breeding as well as through crop management, such as use of appropriate fertilization, growth regulator application and soil amendments.

Atorvastatin Upregulates the Expression of miR-126 in Apolipoprotein E-knockout Mice with Carotid Atherosclerotic Plaque.

Carotid atherosclerosis (AS) is a chronic inflammatory disease of the carotid arterial wall, which is very important in terms of the occurrence of cerebral vascular accidents. Studies have demonstrated that microRNAs (miRNAs) and their target genes are involved in the formation of atherosclerosis and that atorvastatin might reduce atherosclerotic plaques by regulating the expression of miRNAs. However, the related mechanism is not yet known. In this study, we first investigated the effects of atorvastatin on miR-126 and its target gene, i.e., vascular cell adhesion molecule-1 (VCAM-1) in apolipoprotein E-knockout (ApoE-/-) mice with carotid atherosclerotic plaque in vivo. We compared the expressions of miR-126 and VCAM-1 between the control, atherosclerotic model and atorvastatin treatment groups of ApoE-/- mice using RT-PCR and Western blot. We found the miR-126 expression was significantly down-regulated, and the VCAM-1 expression was significantly up-regulated in the atherosclerotic model group, which accelerated the progression of atherosclerosis in the ApoE-/- mice. These results following atorvastatin treatment indicated that miR-126 expression was significantly up-regulated, VCAM-1 expression was significantly down-regulated and atherosclerotic lesions were reduced. The present results might explain the mechanism by which miR-126 is involved in the formation of atherosclerosis in vivo. Our study first indicated that atorvastatin might exert its anti-inflammatory effects in atherosclerosis by regulating the expressions of miR-126 and VCAM-1 in vivo.

Plasma levels of miR-137 and miR-124 are associated with Parkinson's disease but not with Parkinson's disease with depression.

MicroRNAs (miRNAs) are a class of small, non-coding RNAs that regulate gene expression at the post-transcriptional level. Recently, it was reported that miR-137, miR-124, and miR-184 were widely expressed in the central nervous system and were vital to neuronal regulation. In this study, we detected the circulating levels of miR-137, miR-124, and miR-184 in PD patients, and explored the potential role of miR-124, miR-137, and miR-184 in the diagnosis of PD. We further described the relationship between these miRNAs and PD with depression (PD-Dep). The study recruited 60 controls and 60 PD patients, which were further divided into two subgroups, PD with depression (PD-Dep, n = 24) and non-depressed group (PD-NDep, n = 36) according to Hamilton Rating Scale for Depression. Plasma levels of miR-137, miR-124, and miR-184 were detected by qRT-PCR. Receiver-operating characteristic (ROC) curve was used to evaluate miR-124 and miR-137 levels as potential diagnostic biomarkers for PD. The results demonstrated that there were no significant differences in levels of miR-184 between PD patients and controls (p > 0.05). However, miR-137 levels were increased significantly for PD patients compared to controls (p < 0.05), while miR-124 levels were down-regulated (p < 0.05). The areas under the ROC curve (AUC) of miR-137 and miR-124 were 0.707 (95% CI 0.615-0.789, p < 0.05) and 0.709 (95% CI 0.618-0.633, p < 0.05), respectively. Correlation analysis revealed that there was no relationship between these two miRNAs levels and UPDRS scores or H&Y stage. There were no significant differences in miR-137 and miR-124 levels between PD-Dep and PD-NDep (p > 0.05). Thus, plasma levels of miR-137 and miR-124 are associated with Parkinson's disease and might be potential biomarkers of the diagnosis of PD. There were no associations of plasma miR-137 and miR-124 with the severity of PD motor symptoms or PD-Dep.