Risk Factors and Clinical Characteristics of First-ever Ischemic Stroke Caused by ICAS with Leukoaraiosis.

Background: Previous studies have mostly investigated the risk factors affecting the occurrence of leukoaraiosis and the risk factors affecting the severity of leukoaraiosis in patients with ischemic stroke, but there are relatively few studies on the risk factors and clinical characteristics affecting the severity of leukoaraiosis in the population with the most common type of first-episode ischemic stroke caused by intracranial atherosclerotic stenosis in China. Methods: We retrospectively studied patients with first-ever ischemic stroke due to intracranial atherosclerotic stenosis. All patients underwent diffusion weight magnetic resonance imaging and adjunctive examinations such as magnetic resonance angiography and/or computed tomography angiography and/or digital subtraction angiography. The characteristics and clinical data were also statistically analyzed. Results: Of the 504 patients enrolled, 176 (34.92%), 202 (40.08%), and 126 (25.00%) patients were in the mild, moderate, and severe groups, respectively, and the patients were older in the severe group compared with the moderate and mild groups (p < 0.05). Hypertension was more severe in the severe group compared with the severe and mild groups (p < 0.05). The time to hospital admission was shorter in the severe group compared with the moderate and mild groups (p < 0.05). The admission National Institutes of Health stroke scale was higher in the severe group than in the moderate and mild groups (p < 0.05). homocysteine, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio, and ultrasensitive C-reactive protein to albumin ratio levels were significantly different between the three groups (p < 0.05). There was no significant correlation between the distribution of infarct foci in the anterior and posterior circulation in the three groups (p > 0.05). Conclusion: Age and homocysteine were independent risk factors for leukoaraiosis severity in patients with acute ischemic stroke, and all were positively associated with leukoaraiosis severity. Hypertension, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio and ultrasensitive C-reactive protein to albumin ratio levels were highly significant in evaluating the prognosis of patients.

First report of a p.Cys484Tyr Notch3 mutation in a CADASIL patient with acute bilateral multiple subcortical infarcts-case report and brief review.

BACKGROUND: CADASIL(Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)is an inherited small vessel disease caused by mutations in NOTCH3 gene. Although NOTCH3 has numerous hotspots of gene mutations, mutations in exons 9 are rare. The p.C484T gene mutation type associated with it has not been reported in any relevant cases yet. Furthermore, CADASIL patients rarely present with acute bilateral multiple subcortical infarcts. CASE PRESENTATION: We report the case of a Chinese female patient with CADASIL who experienced "an acute bilateral subcortical infarction" because of"hemodynamic changes and hypercoagulability". In genetic testing, we discovered a new Cys484Tyr mutation in exon 9, which has also been found in the patient's two daughters. CONCLUSIONS: It is important to note that this discovery not only expands the mutation spectrum of Notch3 mutations in CADASIL patients, but also examines the mechanism behind acute bilateral subcortical infarction in CADASIL patients via case reviews and literature reviews, in order to provide some clinical recommendations for early intervention, diagnosis, and treatment in similar cases in the future.

Clinical features of ischemic stroke in patients with nonvalvular atrial fibrillation combined with intracranial atherosclerotic stenosis.

BACKGROUND: Nonvalvular atrial fibrillation (NVAF) and intracranial atherosclerotic stenosis (ICAS) are major causes of ischemic stroke. Relatively few studies have focused on the risk factors and clinical features of ischemic stroke caused by NVAF combined with ICAS. METHOD: We retrospectively evaluated NVAF and/or ICAS in patients with acute ischemic stroke admitted within 72 h after stroke. All patients with acute ischemic stroke underwent diffusion-weighted magnetic resonance imaging (DWI), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and/or digital subtraction angiography (DSA). NVAF was detected by routine electrocardiogram or 24-h Holter examination, Doppler echocardiography, and contrast echocardiography of the right heart. RESULTS: Among the 635 enrolled patients, NVAF, ICAS, and NVAF+ICAS were diagnosed in 170 (26.77%), 255 (40.16%), and 210 (33.07%) patients, respectively. Patients in the NVAF+ICAS group were older (p < .001), specifically aged ≥75 years (p < .001). The admission time of the NVAF+ICAS group was shorter (p < .001) than that of the ICAS group. The admission NIHSS score of the NVAF group was higher than that of the NVAF+ICAS group (p < .001). HsCRP, NTpro-BNP, and LEVF levels were significantly different among the three groups (p < .001). NVAF+ICAS ischemic stroke occurred mainly in the right hemisphere (52.4%). CONCLUSION: NVAF with ICAS ischemic stroke is more likely to occur in older patients. Infarctions occurred mainly in the right cerebral hemisphere. Neurological deficits in NVAF are more severe than those in NVAF combined with ICAS and in simple ICAS ischemic strokes. HsCRP, LEVF, andNTpro-BNP seem to be closely associated with NVAF+ICAS ischemic stroke.

Ginseng-Astragalus-oxymatrine injection ameliorates cyclophosphamide-induced immunosuppression in mice and enhances the immune activity of RAW264.7 cells.

ETHNOPHARMACOLOGICAL SIGNIFICANCE: Ginseng quinquefolium (L.), Astragalus membranaceus, and Sophora flavescens Aiton are popular folk medicines in many Asian countries and regions. These three traditional Chinese herbs and their extracts have been reported to considerably enhance the immune function. G. quinquefolium (L.) is considered the king of herbs in China. Traditionally, G. quinquefolium (L.) is believed to replenish vitality, which is considered as immune enhancement in modern Chinese pharmacy. One of the main uses of Astragalus is immunity enhancement; S. flavescens and oxymatrine obtained from its extract have been used to treat leukopenia. Considering the pharmacological properties of Ginseng, Astragalus, and oxymatrine, we evaluated the immunopotentiation effects of their combination, Ginseng-Astragalus-oxymatrine (GAO), in the present study. AIM OF THE STUDY: This study aimed to expand the clinical application of GAO and to preliminarily explore its mechanism of action by determining whether GAO injection can enhance immunity in vivo and in vitro. METHODS: Overall, 17 major chemical components in GAO were analysed using HPLC and LC-MS. The immunity-enhancing effect of GAO was studied in the cyclophosphamide (CTX)-induced immunosuppressive mouse model and RAW 264.7 cells. RESULTS: Quantitative analysis showed that the potential active components of GAO include at least ginsenosides, astragaloside IV, and oxymatrine. GAO could significantly improve the nonspecific immunity including the indices of the thymus and spleen, number of peripheral blood leukocytes, levels of TNF-α and IL-6, phagocytic function of macrophages, and cytotoxic activity of natural killer (NK) cells. Additionally, GAO enhanced the humoural immunity, characterised by the antibody production ability of B cells, and cellular immunity, characterised by the activity of T cells, in immunosuppressed mouse. Moreover, GAO could enhance the phagocytic and adhesion functions of RAW 264.7 cells, which may be related to the activation of reactive oxygen species and NF-κB signalling pathway. CONCLUSION: GAO could dramatically ameliorate CTX-induced immunosuppression in mouse and stimulate the immune activity in RAW 264.7 cells possibly by activating the NF-κB signalling pathway.

Ginsenoside Rc Ameliorates Endothelial Insulin Resistance via Upregulation of Angiotensin-Converting Enzyme 2.

Type 2 diabetes mellitus (T2DM) is a major health concern which may cause cardiovascular complications. Insulin resistance (IR), regarded as a hallmark of T2DM, is characterized by endothelial dysfunction. Ginsenoside Rc is one of the main protopanaxadiol-type saponins with relatively less research on it. Despite researches confirming the potent anti-inflammatory and antioxidant activities of ginsenoside Rc, the potential benefits of ginsenoside Rc against vascular complications have not been explored. In the present study, we investigated the effects of ginsenoside Rc on endothelial IR and endothelial dysfunction with its underlying mechanisms using high glucose- (HG-) cultured human umbilical vein endothelial cells (HUVECs) in vitro and a type 2 diabetic model of db/db mice in vivo. The results showed that ginsenoside Rc corrected the imbalance of vasomotor factors, reduced the production of Ang (angiotensin) II, and activated angiotensin-converting enzyme 2 (ACE2)/Ang-(1-7)/Mas axis in HG-treated HUVECs. Besides, ginsenoside Rc improved the impaired insulin signaling pathway and repressed oxidative stress and inflammatory pathways which constitute key factors leading to IR. Interestingly, the effects of ginsenoside Rc on HG-induced HUVECs were abolished by the selective ACE2 inhibitor MLN-4760. Furthermore, ginsenoside Rc exhibited anti-inflammatory as well as antioxidant properties and ameliorated endothelial dysfunction via upregulation of ACE2 in db/db mice, which were confirmed by the application of MLN-4760. In conclusion, our findings reveal a novel action of ginsenoside Rc and demonstrate that ginsenoside Rc ameliorated endothelial IR and endothelial dysfunction, at least in part, via upregulation of ACE2 and holds promise for the treatment of diabetic vascular complications.

20(S)-Protopanaxadiol inhibits epithelial-mesenchymal transition by promoting retinoid X receptor alpha in human colorectal carcinoma cells.

Colorectal carcinoma (CRC) recurrence is often accompanied by metastasis. Most metastasis undergo through epithelial-mesenchymal transition (EMT). Studies showed that retinol X receptor alpha (RXRα) and 20(S)-Protopanaxadiol (PPD) have anti-tumour effects. However, the anti-metastasis effect of 20(S)-PPD and the effect of RXRα on EMT-induced metastasis are few studies on. Therefore, the role of RXRα and 20(S)-PPD in CRC cell metastasis remains to be fully elucidated. RXRα with clinicopathological characteristics and EMT-related expression in clinical samples were examined. Then, RXRα and EMT level in SW480 and SW620 cells, overexpressed and silenced RXRα in SW620 cells and SW480 cells, respectively, were evaluated. Finally, 20(S)-PPD effect on SW620 and SW480 cells was evaluated. The results showed that a lower RXRα expression in cancer tissues, and a moderate negative correlation between RXRα and N stage, and tended to higher level of EMT. SW480 and SW620 cells had the highest and lowest RXRα expression among four CRC cell lines. SW480 had lower EMT level than SW620. Furthermore, 20(S)-PPD increased RXRα and inhibited EMT level in SW620 cell. Finally, 20(S)-PPD cannot restore SW480 cells EMT level to normal when RXRα silencing. These findings suggest that 20(S)-PPD may inhibit EMT process in CRC cells by regulating RXRα expression.

Panax quinquefolius L. Saponins Protect Myocardial Ischemia Reperfusion No-Reflow Through Inhibiting the Activation of NLRP3 Inflammasome via TLR4/MyD88/NF-κB Signaling Pathway.

At present, many patients who undergo reperfusion immediately after percutaneous coronary intervention will undergo microvascular obstruction and reduction in myocardial blood flow. This phenomenon is called "no-reflow (NR)," and there is still no effective therapy for NR. Studies showed Panax quinquefolius L. saponins (PQS) have effect on MI/R injury, while the effect and mechanism of PQS on MI/R induced NR are not clear. In this study, we established a MI/R model to investigate whether PQS decrease NR phenomenon via suppression of inflammation. We found that PQS significantly alleviated the symptoms of NR by reducing ischemia, infarction, and NR area; improving cardiac function; preventing pathological morphology changes of myocardium; depressing leukocytes' aggregation and adhesion; and suppressing the excessive inflammation. Further study demonstrated that PQS remarkably inhibited TLR4, MyD88, p-NF-κB, and NLRP3 inflammasome-associated protein, and these effects could be reversed by LPS. These results indicated that PQS may protect NR by inhibiting the activation of NLRP3 inflammasome via TLR4/MyD88/NF-κB signaling pathway in part, suggesting that PQS exist potential in preventing NR induced by MI/R.

Neuroprotective effects of pramipexole transdermal patch in the MPTP-induced mouse model of Parkinson's disease.

Parkinson's disease (PD) is characterized by the selective death of dopaminergic neurons. To avoid inconvenience of frequent administration caused by short half life and recurrence of symptoms such as tremor and bradykinesia incurred by drug elimination, a novel long-acting pramipexole transdermal patch has been made. In the present study, we evaluated the neuroprotective effects and underlying mechanisms of pramipexole patch (PPX patch) in a subacute PD mouse model induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results showed that PPX patch treatment improved dyskinesia. MPTP-induced reduction of DA as well as its metabolites DOPAC and HVA in the striatum were prevented by PPX patch in a dose-dependent manner. PPX patch also restored the activity of antioxidant enzymes including SOD, GSH-Px and CAT in the striatum while reduced the content of MDA. Furthermore, PPX patch upregulated Nrf2/HO-1 expression. The protective effects of PPX patch was also associated with downregulation of the Bax/Bcl-2 ratio and Apaf-1, inhibition of cytochrome c release and inactivation of caspase-9 and caspase-3. In conclusion, our studies demonstrated that the long-acting pramipexole patch exerts its neuroprotective effects, at least in part, by inhibiting oxidative stress and mitochondrial apoptosis pathway and holds promise as a candidate drug.