Multiomics Analysis Reveals Aberrant Metabolism and Immunity Linked Gut Microbiota with Insomnia.

Studies have confirmed that insomnia is related to gut microbiota. Previous research suggests that immunity and metabolism are also associated with insomnia. However, to our knowledge, the integration of these factors has not been investigated in insomnia. Here, we explored the correlations across gut microbiota, serum metabolism, and inflammatory factors in insomnia. Our results showed that the composition and structure of gut microbiota and metabolism in insomnia patients were different from healthy controls. Compared to healthy controls, the relative abundances of Lactobacillus, Streptococcus, and Lactobacillus crispatus were significantly increased in insomniacs. There were five metabolic pathways in insomniacs (glycerophospholipid metabolism; glutathione metabolism; nitrogen metabolism; alanine, aspartate, and glutamate metabolism; aminoacyl-tRNA biosynthesis) significantly different between the two groups. Moreover, we found that IL-1ß levels were significantly higher in insomnia patients while TNF-α was significantly reduced. We further identified that the changes in the level of IL-1ß and TNF-α were associated with some specific bacteria and metabolites, such as Prevotella amnii, Prevotella buccalis, Prevotella timonensis, and Prevotella colorans. Mediation analysis further determined that the immune factors and metabolites could mediate the relationship between gut microbes and insomnia. IMPORTANCE Our study indicated that systematic inflammation and metabolites might be a pathway linking the gut microbiome with insomnia. These findings provide new insights and a better understanding of gut microbiota's role in insomnia as well as potential novel microbiome-related etiologies for insomnia.

Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA.

BACKGROUND: Comparisons between ticagrelor and clopidogrel for the secondary prevention of stroke in CYP2C19 loss-of-function carriers have not been extensively performed. METHODS: We conducted a randomized, double-blind, placebo-controlled trial at 202 centers in China involving patients with a minor ischemic stroke or transient ischemic attack (TIA) who carried CYP2C19 loss-of-function alleles. Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive ticagrelor (180 mg on day 1 followed by 90 mg twice daily on days 2 through 90) and placebo clopidogrel or to receive clopidogrel (300 mg on day 1 followed by 75 mg once daily on days 2 through 90) and placebo ticagrelor; both groups received aspirin for 21 days. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days. RESULTS: A total of 11,255 patients were screened and 6412 patients were enrolled, with 3205 assigned to the ticagrelor group and 3207 to the clopidogrel group. The median age of the patients was 64.8 years, and 33.8% were women; 98.0% belonged to the Han Chinese ethnic group. Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008). Secondary outcomes were generally in the same direction as the primary outcome. Severe or moderate bleeding occurred in 9 patients (0.3%) in the ticagrelor group and in 11 patients (0.3%) in the clopidogrel group; any bleeding occurred in 170 patients (5.3%) and 80 patients (2.5%), respectively. CONCLUSIONS: Among Chinese patients with minor ischemic stroke or TIA who were carriers of CYP2C19 loss-of-function alleles, the risk of stroke at 90 days was modestly lower with ticagrelor than with clopidogrel. The risk of severe or moderate bleeding did not differ between the two treatment groups, but ticagrelor was associated with more total bleeding events than clopidogrel. (Funded by the Ministry of Science and Technology of the People's Republic of China and others; CHANCE-2 ClinicalTrials.gov number, NCT04078737.).

Upregulation of miR-874-3p decreases cerebral ischemia/reperfusion injury by directly targeting BMF and BCL2L13.

Ischemic stroke represents a major cause of adult physical disability, which is triggered by cerebral artery occlusion induced blood flow blockage. MiR-874-3p has been reported to be down-regulated in the brain injury induced by ischemia-reperfusion (I/R), but the direct evidence associated with injury of I/R remains unknown. In this study, we found that miR-874-3p levels significantly decreased in rat I/R brain induced by middle cerebral artery occlusion/reperfusion (MCAO/R) and SH-SY5Y cells following oxygen-glucose deprivation and reperfusion (OGD/R) treatment. Upregulation of miR-874-3p reduced infarct volumes and cell apoptosis in the in vivo I/R stroke model using TTC and TUNEL staining, as well as increased proliferation and inhibited apoptosis in OGD/R induced SH-SY5Y cells by CCK-8, Edu staining and flow cytometry analysis. Mechanistically, bioinformatics analysis and luciferase reporter assay confirmed BCL-2-modifying factor (BMF) and Bcl-2 family protein Bcl-rambo (BCL2L13) were the direct targets of miR-874-3p. Furthermore, BMF or BCL2L13 knockdown also provided significant protection against OGD/R induced injury, while their overexpression reversed the protective effects of miR-874-3p on SH-SY5Y cells following OGD/R. In summary, our results suggest that miR-874-3p attenuated ischemic injury by negatively regulating BMF and BCL2L13, highlighting a novel therapeutic target for ischemic stroke.

The coexistence of a patent foramen ovale and obstructive sleep apnea may increase the risk of wake-up stroke in young adults.

BACKGROUND: Patent foramen ovale (PFO) and obstructive sleep apnea (OSA) are independent risk factors for young conscious stroke which may also be concomitant symptoms with it. But there is no sufficient attention on these phenomena. OBJECTIVE: To investigate the relationship between PFO, OSA and young stroke, and to look for proper treatment. METHODS: Three patients with young conscious stroke were reported, each of them was combined with PFO and OSA. All patients were diagnosed as wake-up stroke (WUS). Contrast-enhanced transcranial doppler ultrasound (c-TCD) and polysomnography (PSG) test were used for auxiliary diagnosis. RESULTS: Right-to-left shunts and moderate to severe sleep apnea were observed. Increased body mass index (BMI), hemoglobin (HGB) and hematocrit (HCT) index were also observed. After continuous positive airway pressure (CPAP) therapy, the number of microbubbles was reduced in one patient. CONCLUSIONS: These suggest that coexistence of PFO and OSA may associate with a greater risk of youth stroke. Decrease risk of stroke might occur if treating with CPAP in patients with OSA.

Relationship between carotid artery sclerosis and blood pressure variability in essential hypertension patients.

OBJECTIVES: This study aimed to investigate the relationship between the presence of carotid arteriosclerosis (CAS) and blood pressure variability (BPV) in patients with essential hypertension. METHODS: One hundred and forty four essential hypertension patients underwent ambulatory BP monitoring for 24h after hospitalization. Common BPV metrics were calculated. General clinical parameters, including age, gender, height, weight, history of coronary heart disease, stroke, diabetes, hypertension, smoking and drink, were recorded. Biochemical indices were obtained from a blood test. Carotid intima-media thickness (IMT) and carotid plaques were assessed to separate patients into a non-CAS group (IMT≤0.9mm; n=82) and a CAS group (IMT>0.9mm; n=62). BPV metrics and clinical parameters were analyzed and compared between the two groups. Multivariate logistic regression analysis was performed to determine the associated risk factors of CAS. RESULTS: Multivariate logistic regression analysis revealed that two BPV metrics, the standard deviation of daytime systolic blood pressure (SSD) (OR: 1.587, 95%CI: 1.242-2.028), the difference between average daytime SBP and nighttime SBP (OR: 0.914, 95%CI: 0.855-0.977), as well as three clinical parameters (age, OR: 1.098, 95%CI: 1.034-1.167; smoking, OR: 4.072, 95%CI: 1.466-11.310, and fasting blood glucose, OR: 2.029, 95%CI: 1.407-2.928), were significant factors of CAS in essential hypertension patients. CONCLUSION: SSD, in combination with the ageing, smoking and FBG, has been identified as risk factors for CAS in patients with essential hypertension.

Influence of acetylsalicylate on plasma lysophosphatidic acid level in patients with ischemic cerebral vascular diseases.

BACKGROUND AND PURPOSE: Lysophosphatidic acid (LPA) is released from activated platelets. Acetylsalicylate (aspirin) is the most commonly used antiplatelet drug. The purpose of this study is to observe whether treatment with acetylsalicylate decreases the LPA level in patients with ischemic cerebrovascular diseases. METHODS: We performed a study examining LPA level in fresh plasma in cases and controls enrolled in the LPA and Stroke Prevention Study. Level of LPA was assayed by measuring its inorganic phosphorus after separation by chromatography. RESULTS: An elevated LPA level was seen in cases (n = 254) with ischemic cerebrovascular disease (3.11+/- 1.55 micromol/l) compared with 136 healthy controls (1.77 +/- 1.04 micromol/l) (p < 0.001). Administration of aspirin (100 mg q.d.) for 1 month significantly lowered LPA level in patients (n = 142) (2.41 +/- 1.03 mu mol/l) compared with that before taking acetylsalicylate (4.06 +/- 1.03 micromol/l) (p < 0.001). However, the LPA level in patients (n = 36) who stopped acetylsalicylate after taking it for 1 month was re-elevated. Before and after taking acetylsalicylate for 1 month, their LPA levels were 4.23 +/- 1.15 and 1.93 +/- 0.85 micromol/l, respectively. After 1 month withdrawal, level was 3.90 +/- 1.09 micromol/l (p < 0.001 compared that before taking acetylsalicylate). CONCLUSION: Our findings support a close association between increased plasma LPA level and platelet activation. Acetylsalicylate could decrease plasma LPA levels, which may be used as a mechanism for acetylsalicylate in the prevention of ischemic stroke.

[Progress of studies on the mechanism of acupuncture treatment of acute ischemic cerebral stroke].

In the present paper, the authors review the current development of studies on mechanisms of acupuncture treatment of acute ischemic cerebral apoplexy from (1) blood rheology, (2) cerebral microcirculation, 3) metabolism of cerebral tissue, (4) cerebral electrical activity, (5) free radicals and lipid peroxidation reaction, (6) excitatory aminoacid, (7) calcium overload, (8) nitrogen monoxidum, and (9) cerebral apoptosis. Cerebral stroke includes ischemic stroke and hemorrhagic stroke. Ischemic cerebral stroke accounted for about 60%-70% of all the stroke cases. At present, the main remedies for treating acute ischemic cerebral stroke includes thrombolysis, anti-platelet aggregation, improving microcirculation and symptomatic therapy. In stroke, highlighting the efficacy of acupuncture therapy in the treatment of stroke.