The methylenetetrahydrofolate reductase (MTHFR) rs1801131 A/C variant results in a decrease in MTHFR enzymatic activity, which may play an important role in folate metabolism and is also an important ...source of DNA methylation and DNA synthesis. Several case-control studies have been conducted to assess the association of MTHFR rs1801131 polymorphism with the risk of urinary cancers, yet with conflicting conclusions. To derive a more precise estimation of above relationship, the association between the MTHFR rs1801131 A/C polymorphism and the risk of urinary cancer was performed.
A total of 28 case-control studies was identified. The odds ratios (OR) with 95% confidence intervals (CI) was calculated to assess.
On one hand, we found that the MTHFR rs1801131 A/C polymorphism was associated with increased whole urinary cancers' risk (for example CA vs. AA: OR = 1.12. 95%CI = 1.01-1.24). On the other hand, we found that the MTHFR rs1801131 A/C polymorphism might increase bladder cancer risk both in Asian (C-allele vs. A-allele: OR = 1.35. 95%CI = 1.15-1.60) and African populations (CA vs. AA: OR = 1.63. 95%CI = 1.17-2.25).
Our current analysis suggested that MTHFR rs1801131 A/C is associated with urinary cancers, especially bladder cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The causality between plasma branched-chain amino acids (BCAAs) levels and stroke remains uncertain and the stratified research on the association between BCAAs levels and subtypes of stroke is not ...well studied. Therefore, the association of genetically proxied circulating BCAA levels with the risks of stroke and its subtypes was explored by Mendelian randomization (MR) in this study.
Summary-level data derived from the published genome-wide association studies (GWAS) were employed for analyses. Data for plasma BCAA levels (
= 16,596) were obtained from a meta-analysis of GWAS. The MEGASTROKE consortium provided data for ischemic stroke (
= 440,328) and its subtypes and data for hemorrhagic stroke were available from 2 meta-analyses of GWAS of European-ancestry groups (intracerebral hemorrhage,
= 3,026; subarachnoid hemorrhage,
= 77,074). The inverse variance weighted (IVW) method was selected as the primary MR analysis. Supplementary analysis used included the weighted median, MR-Egger regression, Cochran's Q statistic, MR Pleiotropy Residual Sum and Outlier global test, and leave-one-out analysis method.
According to IVW analysis, 1-SD increment in genetically determined circulating isoleucine was associated with increased risks of cardioembolic stroke (CES) (OR: 1.56, 95% CI: 1.21-2.20,
= 0.0007), but not with risks of other stroke subtypes. We could not discover any proof that leucine and valine levels could increase risk of any stroke subtype. All heterogeneity tests produced stable findings, and there was no concrete evidence to indicate the perturbation of horizontal multiplicity.
Increasing plasma isoleucine level had a causal effect on the risk of CES but not on the risk of other stroke subtypes. Further research is needed to identify the mechanisms of the causal associations between BCAAs and stroke subtypes.
Based on these encouraging results of these studies, a randomized clinical trial is ongoing to further assess the efficacy of the RIC plus MT for AIS patients with large-vessel occlusion ...(ClinicalTrials.gov number: The neuroprotective benefits of RCI have been well established in preclinical models, and clinical trials have recently demonstrated to safety and feasibility of RCI in an ischemic stroke patient. ...RCI holds significant promise for future stroke treatment and rehabilitation. ...the technical skills and equipment required for the procedure are no different from that of a thrombectomy; cost and training are not hurdles to clinical implementation.
Rapid and selective therapeutic hypothermia is a promising neuroprotective method for acute ischemic stroke. A recent study developed a simple but efficient technique of transnasal cooling, in which ...air at ambient temperature was passed through standard nasal cannula to induce evaporative cooling of the brain. Selective brain temperature decrease was achieved within 25 minutes in piglets. It is a major step forward to initiate early brain cooling. However, it is still necessary to devise a more comprehensive strategy to enhance the benefits of selective brain cooling in the era of effective reperfusion.
Selective brain cooling is a promising technique for improving outcomes in ischemic stroke in the area of reperfusion. A recent study described the efficacy of a new method of selective brain cooling ...via active conductive head cooling. This is a major step forward in the administration of hypothermic treatment during pre-hospital transfer. However, to enhance the benefits of selective therapeutic cooling, a more comprehensive strategy preventing delay in hypothermic induction and increasing the accuracy of selectivity in the brain should be considered to mitigate the side effects related to therapeutic hypothermia.
Acute ischemic stroke is a leading cause of death and disability worldwide. Therapeutic hypothermia has long been considered as one of the most robust neuroprotective strategies. Although the ...neuroprotective effects of hypothermia have only been confirmed in patients with global cerebral ischemia after cardiac arrest and in neonatal hypoxic ischemic encephalopathy, establishing standardized protocols and strictly controlling the key parameters may extend its application in other brain injuries, such as acute ischemic stroke. In this review, we discuss the potential neuroprotective effects of hypothermia, its drawbacks evidenced in previous studies, and its potential clinical application for acute ischemic stroke especially in the era of reperfusion. Based on the different conditions between bench and bedside settings, we demonstrate the importance of vascular recanalization for neuroprotection of hypothermia by analyzing numerous literatures regarding hypothermia in focal cerebral ischemia. Then, we make a thorough analysis of key parameters of hypothermia and introduce novel hypothermic therapies. We advocate in favor of the process of clinical translation of intra-arterial selective cooling infusion in the era of reperfusion and provide insights into the prospects of hypothermia in acute ischemic stroke.
Circadian rhythm is a master process observed in nearly every type of cell throughout the body, and it macroscopically regulates daily physiology. Recent clinical trials have revealed the effects of ...circadian variation on the incidence, pathophysiological processes, and prognosis of acute ischemic stroke. Furthermore, core clock genes, the cell-autonomous pacemakers of the circadian rhythm, affect the neurovascular unit–composing cells in a nonparallel manner after the same pathophysiological processes of ischemia/reperfusion. In this review, we discuss the influence of circadian rhythms and clock genes on each type of neurovascular unit cell in the pathophysiological processes of acute ischemic stroke.
Reperfusion therapy inevitably leads to brain-blood barrier (BBB) disruption and promotes damage despite its benefits for acute ischaemic stroke (AIS). An effective brain cytoprotective treatment is ...still needed as an adjunct to reperfusion therapy. Here, we explore the potential benefits of therapeutic hypothermia (HT) in attenuating early BBB leakage and improving neurological outcomes. Mild HT was induced during the early and peri-recanalization stages in a mouse model of transient middle cerebral artery occlusion and reperfusion (tMCAO/R). The results showed that mild HT attenuated early BBB leakage in AIS, decreased the infarction volume, and improved functional outcomes. RNA sequencing data of the microvessels indicated that HT decreased the transcription of the actin polymerization-related pathway. We further discovered that HT attenuated the ROCK1/MLC pathway, leading to a decrease in the polymerization of G-actin to F-actin. Arachidonic acid (AA), a known structural ROCK agonist, partially counteracted the protective effects of HT in the tMCAO/R model. Our study highlights the importance of early vascular protection during reperfusion and provides a new strategy for attenuating early BBB leakage by HT treatment for ischaemic stroke.Reperfusion therapy inevitably leads to brain-blood barrier (BBB) disruption and promotes damage despite its benefits for acute ischaemic stroke (AIS). An effective brain cytoprotective treatment is still needed as an adjunct to reperfusion therapy. Here, we explore the potential benefits of therapeutic hypothermia (HT) in attenuating early BBB leakage and improving neurological outcomes. Mild HT was induced during the early and peri-recanalization stages in a mouse model of transient middle cerebral artery occlusion and reperfusion (tMCAO/R). The results showed that mild HT attenuated early BBB leakage in AIS, decreased the infarction volume, and improved functional outcomes. RNA sequencing data of the microvessels indicated that HT decreased the transcription of the actin polymerization-related pathway. We further discovered that HT attenuated the ROCK1/MLC pathway, leading to a decrease in the polymerization of G-actin to F-actin. Arachidonic acid (AA), a known structural ROCK agonist, partially counteracted the protective effects of HT in the tMCAO/R model. Our study highlights the importance of early vascular protection during reperfusion and provides a new strategy for attenuating early BBB leakage by HT treatment for ischaemic stroke.
The translational failure of neuroprotective therapies in stroke may be influenced by the mismatch of existing comorbidities between animal models and patients. Previous studies found that ...single-target neuroprotective agents reduced infarction in Sprague–Dawley but not in spontaneously hypertensive rats. It is of great interest to explore whether multi-target neuroprotectants and stroke models with comorbidities should be used in further translational researches. Ischemic stroke was induced in normotensive or hypertensive rats by 90- or 120-min middle cerebral artery occlusion (MCAO) and reperfusion. Intra-Arterial Selective Cooling Infusion (IA-SCI) was started at the onset of reperfusion for 30 minutes. Acute neurological deficits, infarct volumes, gene expression and markers of A1-like and A2-like astrocytes were evaluated. In further analysis, TNFα and IL-1α were administrated intracerebroventricularly, phenotype shifting of astrocytes and infarct volumes were assessed. Normobaric oxygen treatment, as a negative control, was also assessed in hypertensive rats. IA-SCI led to similar benefits in normotensive rats with 120-min MCAO and hypertensive rats with both 90-min and 120-min MCAO, including mitigated functional deficit and reduced infarct volumes. IA-SCI shifted astrocyte phenotypes partly by downregulating A1-like astrocytes and upregulating A2-like astrocytes in both RNA and protein levels. Upregulated A1-type astrocyte markers levels, induced by intracerebroventricular injection of TNFα and IL-1α, were closely related to increased infarct volumes in hypertensive rats, despite receiving IA-SCI treatment. In addition, infarct volumes and A1/A2-like genes were not affected by normobaric oxygen treatment. IA-SCI reduced infarction in both normotensive and hypertensive rats. Our results demonstrated the neuroprotective effects of IA-SCI in hypertensive rats may be related with phenotype shifting of astrocytes.
PDF
