The role of high-sensitivity C-reactive protein serum levels in the prognosis for patients with stroke: a meta-analysis.

Background: The impact of high-sensitivity C-reactive protein (hs-CRP) as a biomarker of inflammation on the prognosis of stroke patients remains controversial, this study was conducted to evaluate the prognostic value of hs-CRP levels for patients with stroke. Methods: PubMed, Web of Science, Embase, and Cochrane Library databases were searched from inception to October 28, 2022. Outcome measures were all-cause mortality, recurrent stroke, and poor prognosis. The relationship between the highest versus lowest levels of hs-CRP or per unit increment and outcomes as measured by risk ratio (RR) and corresponding 95% confidence intervals (CI). Results: A total of 39 articles were eligible for meta-analysis. High hs-CRP levels at admission were associated with mortality among patients with acute ischemic stroke (AIS) [RR = 3.84, 95% CI (2.41 ~ 6.111); p < 0.001], risk of recurrent stroke [RR = 1.88, 95%CI (1.41 ~ 2.52); p < 0.001], and poor prognosis [RR = 1.77, 95% CI (1.59 ~ 1.97); p < 0.001]. The risk ratios for the association of per unit increase in hs-CRP levels with mortality, risk of recurrent stroke, and poor prognosis were as follows, respectively: 1.42 [95% CI (1.19-1.69); p < 0.001], 1.03 [95% CI (1.01-1.04); p = 0.003], and 1.27 [95% CI (1.10-1.47); p = 0.001]. For hemorrhagic stroke (HS), the risk ratios (RR) for the highest versus the lowest (reference) category of hsCRP or per unit increment to all-cause mortality were 4.36 [95% CI (1.38-13.73); p = 0.012] and 1.03 [95% CI (0.98-1.08); p = 0.238]. Conclusion: Hs-CRP levels are strongly associated with mortality, risk of stroke recurrence and poor prognosis in stroke patients. Therefore, hs-CRP levels may contribute to the prognosis prediction of these patients.

Predictive value of neutrophil to lymphocyte ratio for ischemic stroke in patients with atrial fibrillation: A meta-analysis.

Objective: Atrial fibrillation (AF) is an important risk factor for stroke, but the currently used CHA2DS2-VASc score has significant limitations in predicting the risk of stroke. It is important to find new biomarkers to predict stroke risk in patients with AF or as a complement to the CHA2DS2-VASc score. Neutrophil-to-lymphocyte ratio (NLR) may be of potential value. This systematic review and meta-analysis evaluated the association between NLR and stroke risk. Methods: We searched in electronic databases such as PubMed and EMBASE. The final included studies were analyzed by Stata 12.0 software. Subgroup analyses were used to explore sources of heterogeneity. Publication bias was assessed by Egger's test and Begg's test. Sensitivity analyses assessed the stability of outcomes. Results: A total of 11 studies with a total of 35,221 patients were included. NLR levels are associated with stroke risk in patients with atrial fibrillation (WMD = 0.72, 95%CI = 0.43-1.01). There was a correlation between the occurrence of stroke and NLR level in AF patients (WMD = 1.96, 95%CI = 1.38-2.53). The incidence of stroke was significantly higher in patients with atrial fibrillation with NLR ≥3 than in those with NLR <3 (RR = 1.4, 95%CI = 1.24-1.58). Conclusion: This study shows that high NLR values are associated with a higher risk of stroke in AF patients. The incidence of stroke in AF patients with NLR ≥3 was 1.4 times higher than that with NLR <3 (p < 0.001). NLR may be considered as a complementary risk assessment for CHA2DS2-VASc score, especially for AF patients with CHA2DS2-VASc score <2. NLR may be a potential biomarker for predicting stroke risk in patients with AF.

Curcumin Regulates Gut Microbiota and Exerts a Neuroprotective Effect in the MPTP Model of Parkinson's Disease.

Objectives: The experiment aimed to explore the effects of curcumin on motor impairment, dopamine neurons, and gut microbiota in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model. Methods: Mice were randomly assigned to six groups: normal control group, solvent control group, MPTP group, curcumin-low-dose group (40 mg/kg), curcumin-medium-dose group (80 mg/kg), and curcumin-high-dose group (160 mg/kg). After 14 days, each group of mice was subjected to the pole text, the hanging test, and the open-field test. Tyrosine hydroxylase (TH) immunohistochemistry was used to observe the survival of nigrostriatal dopamine neurons. Moreover, ultrastructural changes were observed with a transmission electron microscope in mice striatal tissue cells. Then, 16S rRNA was used to assess changes in the gut microbiota. Results: (1) Each dose of curcumin reduced pole climbing time and increased suspension score and total distance moved dose-dependently. (2) All curcumin groups improved cell wrinkling and vacuolar degeneration, increased the number of TH positives, improved cell survival, and the higher the dose of curcumin, the better the effect. (3) There were differences in microbiota composition and a relative abundance among the groups. The relative abundance of Patescibacteria, Proteobacteria, and Verrucomicrobia was higher in the MPTP group. The relative abundance of Patescibacteria, Enterobacteriaceae, Enterococcaceae all decreased in all curcumin groups. In addition, the Kyoto Encyclopedia of Genes and Genomes pathways showed a reduction in the superpathway of N-acetylneuraminate degradation after medium- and high-dose curcumin administration. Conclusions: Curcumin regulates gut microbiota and exerts a neuroprotective effect in the MPTP mice model. This preliminary study demonstrates the therapeutic potential of curcumin for Parkinson's disease, providing clues for microbially targeted therapies for Parkinson's disease.

Cornuside ameliorated experimental autoimmune encephalomyelitis by limiting the recruitment of CD4+ T lymphocytes in the spinal cord

We conducted this study to determine whether cornuside could improve the neurological deficit symptoms of experimental autoimmune encephalomyelitis (EAE) rats, as well as determine the potential involvement of CD4+ T lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-α (TNF-α). Altogether, 32 Lewis rats were randomly divided into control, EAE, EAE/prednisolone, and EAE/cornuside, wherein their neurological function was assessed every day. CD4+ T lymphocyte recruitment into the spinal cord (SC) was evaluated using immunohistochemistry. The VCAM-1, ICAM-1 and TNF-α mRNA expressions in the SC were determined by real-time quantitative PCR, and the VCAM-1 and ICAM-1 proteins were determined by western blotting. Compared to the control group, the EAE group rats with neurological deficits had enhanced CD4+ T lymphocyte infiltration and higher expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Meanwhile, compared with the EAE group, the EAE/cornuside and EAE/prednisolone groups had lower neurological scores, less CD4+ T lymphocyte infiltrations, and lower expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Thus, cornuside ameliorated EAE, which could be owed to the inhibition of CD4+ T lymphocyte recruitment and VCAM-1, ICAM-1, and TNF-α expressions in the SC

Astragaloside IV Reduces Cerebral Ischemia/Reperfusion-Induced Blood-Brain Barrier Permeability in Rats by Inhibiting ER Stress-Mediated Apoptosis.

BACKGROUND: Previous studies proved that AS-IV could prevent blood-brain barrier (BBB) against an increase in permeability. However, its underlying molecular mechanism has not been enlightened yet. The aim of the study is to reveal the potential protective mechanism of astragaloside IV (AS-IV) on the blood-brain barrier after ischemia-reperfusion. METHODS: In vivo, AS-IV neurological protection was measured by Long's five-point scale and 2,3,5-triphenyltetrazolium chloride staining. AS-IV protection for BBB was observed by Evans blue extravasation technique. Endoplasmic reticulum stress and apoptosis-related protein levels were measured by western blot with AS-IV intervention. In vitro, cell apoptosis was analyzed by western blot and flow cytometry.Endoplasmic reticulum stress-related protein levels were quantified through western blot. RESULTS: AS-IV treatment could decrease the infarct size in rats' brain and protect the BBB against Evans blue permeating through brain, after ischemia/reperfusion, significantly. Further, ischemia/reperfusion or oxygen-glucose deprivation/reperfusion was found to have an increase in endothelial cell apoptosis proteins, such as Bax, Bcl-2, and caspase-3, and endoplasmic reticulum stress-associated proteins, such as phosphorylated PERK and eIF2α, Bip, and CHOP, which were attenuated by AS-IV treatment. CONCLUSIONS: AS-IV can effectively protect the blood-brain barrier and reduce the area of cerebral infarction via inhibiting endoplasmic reticulum stress-mediated apoptosis in endothelial cells.

Oral Chinese Herbal Medicine as an Adjuvant Treatment for Chemotherapy, or Radiotherapy, Induced Myelosuppression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Myelosuppression is a common side effect in cancer patients receiving chemotherapy or radiotherapy. Chinese herbal medicine (CHM) has shown promise in alleviating myelosuppression. METHOD: We searched for randomized controlled trials (RCTs) from seven databases without language restriction. We included RCTs in adults, in which hematological toxicity was measured according to WHO criteria and control group underwent chemotherapy and/or radiotherapy and the treatment group was given oral CHM. RESULTS: We searched 1021 articles from the date of databases inception to October 7, 2016. We selected 14 articles for the final analysis. Pooled data showed that CHM significantly decreased the suppression rate of leukocytes, neutrophils, hemoglobin, and platelets compared with the control group, particularly in grade III-IV toxicity (leukocytes: RR = 0.43, 95% CI = 0.33-0.56; neutrophils: RR = 0.39, 95% CI = 0.27-0.58; hemoglobin: RR = 0.33, 95% CI = 0.18-0.61; platelets: RR = 0.61, 95% CI = 0.39-0.95). CONCLUSIONS: CHM as an adjuvant can alleviate myelosuppression induced by chemotherapy or radiotherapy, reduce grade III-IV toxicity, and maintain therapeutic dose and treatment cycle. However, due to heterogeneity and publication bias, the results should be interpreted with caution and validated by conducting strictly designed multicenter RCTs of high quality and large scale.

Ferulic acid attenuates brain microvascular endothelial cells damage caused by oxygen-glucose deprivation via punctate-mitochondria-dependent mitophagy.

Ferulic acid (FA) has an important effect on scavenging free radicals, which is related to the alleviation of various neurodegenerative diseases. However, there are few studies about its effects on vascular dementia. In this study, we demonstrated the effect of FA on oxidative damage of brain microvascular endothelial cells (BMECs) which underwent oxygen-glucose deprivation (OGD) for 2h. Our data showed that FA significantly reversed the oxidative stress state of OGD-treated BMECs and reduced mitochondrial dysfunction. In further study, we found that FA upregulated the expression of LC3-II, a marker of autophagy. Besides, mitophagy was observed by transmission electron microscopy. The mechanism of FA inducing autophagy was found to be related to mitochondrial fission, according to the effects of siRNA and inhibitor of dynamin-related protein 1, which was responsible for fission. All above suggested that FA mitigated OGD-induced mitochondrial oxidative damage by punctate-mitochondria-dependent autophagy.

Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System.

Sodium Tanshinone IIA sulfonate (STS) is a derivative of Tanshinone IIA (Tan IIA). Tan IIA has been reported to possess neuroprotective effects against Alzheimer's disease (AD). However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP-) induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg) and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE) and increased the activity of choline acetyltransferase (ChAT) in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD) and decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3). STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction.

Abstract Next Subvolume Method: a logical process-based approach for spatial stochastic simulation of chemical reactions.

The spatial stochastic simulation of biochemical systems requires significant calculation efforts. Parallel discrete-event simulation is a promising approach to accelerate the execution of simulation runs. However, achievable speedup depends on the parallelism inherent in the model. One of our goals is to explore this degree of parallelism in the Next Subvolume Method type simulations. Therefore we introduce the Abstract Next Subvolume Method, in which we decouple the model representation from the sequential simulation algorithms, and prove that state trajectories generated by its executions statistically accord with those generated by the Next Subvolume Method. The experimental performance analysis shows that optimistic synchronization algorithms, together with careful controls over the speculative execution, are necessary to achieve considerable speedup and scalability in parallel spatial stochastic simulation of chemical reactions. Our proposed method facilitates a flexible incorporation of different synchronization algorithms, and can be used to select the proper synchronization algorithm to achieve the efficient parallel simulation of chemical reactions.