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Morbidity and mortality of cardiovascular diseases (CVDs) are exceedingly high worldwide. Researchers have found that the occurrence and development of CVDs are closely related to intestinal microecology. Imbalances in intestinal microecology caused by changes in the composition of the intestinal microbiota will eventually alter intestinal metabolites, thus transforming the host physiological state from healthy mode to pathological mode. Trimethylamine N-oxide (TMAO) is produced from the metabolism of dietary choline and L-carnitine by intestinal microbiota, and many studies have shown that this important product inhibits cholesterol metabolism, induces platelet aggregation and thrombosis, and promotes atherosclerosis. TMAO is directly or indirectly involved in the pathogenesis of CVDs and is an important risk factor affecting the occurrence and even prognosis of CVDs. This review presents the biological and chemical characteristics of TMAO, and the process of TMAO produced by gut microbiota. In particular, the review focuses on summarizing how the increase of gut microbial metabolite TMAO affects CVDs including atherosclerosis, heart failure, hypertension, arrhythmia, coronary artery disease, and other CVD-related diseases. Understanding the mechanism of how increases in TMAO promotes CVDs will potentially facilitate the identification and development of targeted therapy for CVDs.

Genome size variation and evolutionary forces behind have been long pursued in flowering plants. The genus Oryza, consisting of approximately 25 wild species and two cultivated rice, harbors eleven extant genome types, six of which are diploid (AA, BB, CC, EE, FF, and GG) and five of which are tetraploid (BBCC, CCDD, HHJJ, HHKK, and KKLL). To obtain the most comprehensive knowledge of genome size variation in the genus Oryza, we performed flow cytometry experiments and estimated genome sizes of 166 accessions belonging to 16 non-AA genome Oryza species. k-mer analyses were followed to verify the experimental results of the two accessions for each species. Our results showed that genome sizes largely varied fourfold in the genus Oryza, ranging from 279 Mb in Oryza brachyantha (FF) to 1,203 Mb in Oryza ridleyi (HHJJ). There was a 2-fold variation (ranging from 570 to 1,203 Mb) in genome size among the tetraploid species, while the diploid species had 3-fold variation, ranging from 279 Mb in Oryza brachyantha (FF) to 905 Mb in Oryza australiensis (EE). The genome sizes of the tetraploid species were not always two times larger than those of the diploid species, and some diploid species even had larger genome sizes than those of tetraploids. Nevertheless, we found that genome sizes of newly formed allotetraploids (BBCC-) were almost equal to totaling genome sizes of their parental progenitors. Our results showed that the species belonging to the same genome types had similar genome sizes, while genome sizes exhibited a gradually decreased trend during the evolutionary process in the clade with AA, BB, CC, and EE genome types. Comparative genomic analyses further showed that the species with different rice genome types may had experienced dissimilar amplification histories of retrotransposons, resulting in remarkably different genome sizes. On the other hand, the closely related rice species may have experienced similar amplification history. We observed that the contents of transposable elements, long terminal repeats (LTR) retrotransposons, and particularly LTR/Gypsy retrotransposons varied largely but were significantly correlated with genome sizes. Therefore, this study demonstrated that LTR retrotransposons act as an active driver of genome size variation in the genus Oryza.

Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) is used to assess leptomeningeal collateral circulation, but clinical outcomes of patients with FVH can be very different. The aim of the present study was to assess a FVH score and explore its relationship with clinical outcomes. Patients with acute ischemic stroke due to middle cerebral artery M1 occlusion underwent magnetic resonance imaging and were followed up at 10 days (National Institutes of Health Stroke Scale) and 90 days (modified Rankin Scale) to determine short-term clinical outcomes. Effective collateral circulation indirectly improved recovery of neurological function and short-term clinical outcome by extending the size of the pial penumbra and reducing infarct lesions. FVH score showed no correlation with 90-day functional clinical outcome and was not sufficient as an independent predictor of short-term clinical outcome.

Purpose: Idiopathic normal pressure hydrocephalus (iNPH) is known as a treatable form of dementia. Network analysis is emerging as a useful method to study neurological disorder diseases. No study has examined changes of structural brain networks of iNPH patients. We aimed to investigate alterations in the gray matter (GM) structural network of iNPH patients compared with normal elderly volunteers.Materials and Methods: Structural networks were reconstructed using covariance between regional GM volumes extracted from three-dimensional T1-weighted images of 29 possible iNPH patients and 30 demographically similar normal-control (NC) participants and compared with each other.Results: Global network modularity was significantly larger in the iNPH network (P < 0.05). Global network measures were not significantly different between the two networks (P > 0.05). Regional network analysis demonstrated eight nodes with significantly decreased betweenness located in the bilateral frontal, right temporal, right insula and right posterior cingulate regions, whereas only the left anterior cingulate was detected with significantly larger betweenness. The hubs of the iNPH network were mostly located in temporal areas and the limbic lobe, those of the NC network were mainly located in frontal areas.Conclusions: Network analysis was a promising method to study iNPH. Increased network modularity of the iNPH group was detected here, and modularity analysis should be paid much attention to explore the biomarker to select shunting-responsive patients.

Background and Purpose: It is still not clear whether Notch1 signaling inhibition can promote functional outcomes after stroke, given that it plays time-dependent roles in the sequential process of endogenous neurogenesis. The purpose of this study was to identify the appropriate time frame for Notch1 signaling inhibition according to the temporal evolution of Notch1 signaling activation and the responses of neural stem cells (NSCs), in order to target it for therapeutic intervention and stimulate neurorestorative strategies after stroke.Methods: Sprague-Dawley (SD) rats were subjected to 90-min of middle cerebral artery occlusion (MCAO). Rats were sacrificed before, and at day 1, day 2, day 3, day 4, and day 7 after ischemia for immunohistochemical analysis of the Notch intracellular domain (NICD), Nestin and doublecortin (Dcx). Next, MCAO rats were treated with the γ-secretase inhibitor N-[N-(3,5-di uorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT) or with saline at day 4 after ischemia, and subsequently evaluated with behavioral test analysis and magnetic resonance imaging (MRI). The rat brains were then harvested for immunohistochemical analysis of Dcx, NeuN and myelin basic protein (MBP) at 2, 3, 4, and 8 weeks.Results: Notch1 signaling was maximally activated at day 3 after ischemia in parallel with the temporal evolution of NSCs. Inhibiting Notch1 signaling at day 4 after reperfusion with DAPT further promoted recovery of MRI parameters of the corticospinal tract (CST) and the functional outcomes, concomitantly with an increase in neuroblasts, their migration to the ischemic boundary, and potential differentiation to mature neurons, as well as the amelioration of axonal bundle integrity.Conclusion: Inhibition of Notch1 signaling at the subacute stage of stroke could maximally promote endogenous neurogenesis and axonal reorganization.

Objective. The Notch signaling pathway is involved in angiogenesis induced by brain ischemia and can be efficiently inhibited by the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT). The aim of the present study was to noninvasively investigate the effect of DAPT treatment on angiogenesis in brain repair after stroke using magnetic resonance imaging (MRI). Methods. Sprague-Dawley rats (n=40) were subjected to 90 minutes of transient middle cerebral artery (MCA) occlusion and treated with PBS (n=20) or DAPT (n=20) at 72 hours after the onset of ischemia. MRI measurements including T2-weighted imaging (T2WI), susceptibility-weighted imaging (SWI), and cerebral blood flow (CBF) were performed at 24 hours after reperfusion and weekly up to 4 weeks using a 3-Tesla system. Histological measurements were obtained at each time point after MRI scans. Results. SWI showed that DAPT treatment significantly enhanced angiogenesis in the ischemic boundary zone (IBZ) with respect to the control group, with local CBF in the angiogenic area elevated, along with increases in vascular density confirmed by histology. Conclusion. Treatment of ischemic stroke with DAPT significantly augments angiogenesis, which promotes poststroke brain remodeling by elevating CBF level, and these processes can be dynamically monitored and evaluated by MRI.

Notch homolog 1 (Notch 1) signaling is regarded as a potential therapeutic target for modulating the inflammatory response and exhibiting neuroprotective effects in cerebral injury following stroke. N‑[N‑(3,5‑difluorophenacetyl)‑1‑alanyl]‑S‑phenylglycine tbutylester (DAPT) efficiently inhibits activation of the Notch 1 signaling pathway in microglia and may protect brain tissue from ischemic damage. However, the temporal proliferation and morphological alterations of microglia/macrophages throughout progression of the disease, as well as the comprehensive alterations of the whole brain following DAPT treatment, remain to be elucidated. The present study evaluated the temporal proliferation and the morphological alterations of microglia/macrophages over the period of the subacute and chronic stages, in addition to dynamic alterations of brain tissue, using the magnetic resonance imaging (MRI) method, following DAPT treatment. Sprague‑Dawley rats (n=40) were subjected to 90 min of middle cerebral artery occlusion and were treated with DAPT (n=20) or acted as controls with no treatment (n=20). The two groups of rats underwent MRI scans prior to the induction of stroke symptoms and at 24 h, 7, 14, 21 and 28 days following the stroke. A total of five rats from each group were sacrificed at 7, 14, 21 and 28 days following induction of stroke. Compared with control rats, the MRI data of the ipsilateral striatum in treated rats revealed ameliorated brain edema at the subacute stage and recovered brain tissue at the chronic stage. In addition to this, treatment attenuated the round‑shape and promoted a ramified‑shape of microglia/macrophages. The present study confirmed the protective effect of DAPT treatment by dynamically monitoring the cerebral alterations and indicated the possibility of DAPT treatment to alter microglial characteristics to induce a protective effect, via inhibition of the Notch signaling pathway. [ABSTRACT FROM AUTHOR]

Background: The early dysfunction and subsequent recovery after stroke, characterized by the destruction and remodeling of connective pathways between cortex and subcortical regions, is associated with neuroinflammation. As major components of the inflammatory process, reactive astrocytes have double-edged effects on pathological progression. The temporal patterns of astrocyte and neuronal pathway activity can be revealed by systemic and stereotactic manganese-enhanced magnetic resonance imaging (MEMRI), respectively. In the present study, we aimed to detect an association between astrocyte activity and recovery of neuronal connective pathways by combining systemic with stereotactic MEMRI.Methods: Fifty adult rats, divided into two groups, underwent a 60-min occlusion of the middle cerebral artery. The groups were given either a systemic administration or stereotactic injection of MnCl2 at 1, 3, 7, and 14 days after stroke and underwent MRI 4 and 2 days later, respectively. Immunofluorescence (IF) of group 1 was conducted to corroborate the results. Repetitive behavioral testing was also performed with all rats at 1, 3, 7, and 14 days to obtain a functional score.Results: Ring- or crescent-shaped enhancements formed in the striatal peri-infarct regions (STR) at 11 and 18 days. This was concurrent with the activity of glial fibrillary acidic protein (GFAP)-positive astrocytes, which mainly localized at the peri-infarct region and significantly increased in number at 11 and 18 days after stroke. Microglia/macrophages, detected by IF, mainly localized in the lesion core, rather than in the region of enhancement. The ipsilateral substantia nigra (SN) revealed Mn-related signal enhancement reduction and subsequent signs of the recovery process at 3 to 5 days and 9 to 16 days, respectively. Behavioral testing showed that sensorimotor functions were initially disturbed, but subsequently recovered at 7 and 14 days.Conclusions: We found a positive temporal correlation between astrogliosis and the recovery of neuronal connective pathways at the chronic stage by using the in vivo method of MEMRI. Our results highlighted the potential contribution of astrocytes to the neuronal recovery of these connective pathways. [ABSTRACT FROM AUTHOR]

Objective: To assess fluid-attenuated inversion recovery (FLAIR) vascular hyper-intensity (FVH) and explore its relationship with CT perfusion (CTP) penumbral/infarct core mismatch ratio and diffusion weighted imaging (DWI) final infarct volume in acute ischemic stroke (AIS) patients with middle cerebral artery occlusion (MCAO). Methods: The CTP and MRI images of 38 AIS patients with MCAO were reviewed. The FVH score (longitudinal direction) [FVH score (L)] and FVH score (transverse direction) [FVH score (T)] were quantified on the FLAIR images. The FVH score (L) (range, 0-16) was based on a rostrocaudal extension of FVH and the FVH score (T) (range, 0-3) was based on FVH supply of the occluded MCA territory. The mismatch ratio was calculated from the ratio of the [mean transit time - cerebral blood volume (CBV)] lesion/CBV lesion on the CTP images. The DWI infarct volume was measured on the DWI images. Results: The mismatch ratio was larger for the group of FVH score (L)=7~8 than those of FVH score (L)=5~6 and FVH score (L)=3~4 (p=0.03), whereas the DWI infarct volume was smaller (p=0.04). Similarly, the mismatch ratio of FVH score (T)=2~3 group was larger than FVH score (T)=1 group (p=0.01), whereas the DWI infarct volume was smaller (p=0.02). Both FVH score (L) and FVH score (T) correlated positively with mismatch ratio (P=0.02, P=0.001, respectively), but negatively with DWI infarct volume (P=0.03, P=0.004, respectively). Conclusions: Higher FVH score is associated with larger mismatch ratio and smaller DWI infarct volume in AIS patients with MCAO. FLAIR vascular hyperintensity may represent collateral arterial circulation, and may play a role in protecting the ischemic penumbra. [ABSTRACT FROM AUTHOR]