Post-stroke depression (PSD) is a serious and common complication of stroke, which seriously affects the rehabilitation of stroke patients. To date, the pathogenesis of PSD is unclear and effective treatments remain unavailable. Here, we established a mouse model of PSD through photothrombosis-induced focal ischemia. By using a combination of brain imaging, transcriptome sequencing, and bioinformatics analysis, we found that the hippocampus of PSD mice had a significantly lower metabolic level than other brain regions. RNA sequencing revealed a significant reduction of miR34b-3p, which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E (eIF4E). Furthermore, silencing eIF4E inactivated microglia, inhibited neuroinflammation, and abolished the depression-like behaviors in PSD mice. Together, our data demonstrated that insufficient miR34b-3p after stroke cannot inhibit eIF4E translation, which causes PSD by the activation of microglia in the hippocampus. Therefore, miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.
Animals ; Mice ; Depression ; Eukaryotic Initiation Factor-4E/metabolism* ; MicroRNAs/metabolism* ; Neurons/metabolism* ; Stroke/metabolism*

Ischemic stroke is one of the main causes of death and long-term disability worldwide, which seriously affects the quality of life of patients and brings a heavy economic burden to families and society. Epidemiological studies have shown that stroke has become the second leading cause of death and major disabling disease in the world, with the characteristics of high morbidity, high recurrence, and high mortality. Epigenetic mechanism is the molecular process where gene expression and function in each cell are dynamically regulated and interconnected and a biological mechanism that changes genetic performance without changing the DNA sequence, including DNA methylation, histone modifications, and non-coding RNA. However, the research on epigenetics is currently focused on other diseases such as tumors. Recent studies have found that epigenetics has received extensive attention in the past few decades as a key factor involved in the pathophysiological process of ischemic stroke. The present study introduced the mediation of epigenetics in the induction of stroke, summarized the potential drug targets for these mechanisms in the treatment of stroke, and further explored the significance of traditional Chinese medicine(TCM) against cerebral ischemia injury based on TCM classification of stroke.
DNA Methylation ; Epigenesis, Genetic ; Humans ; Ischemic Stroke/genetics* ; Quality of Life ; RNA, Untranslated/metabolism* ; Stroke/genetics*

The ischemic penumbra is defined as functionally impaired but salvageable ischemic brain tissue surrounding an irreversibly damaged core. Therefore, rapid and precise identification of the penumbra is of considerable interest for decision-making in acute stroke treatment. The region with perfusion abnormality but no diffusion lesion (the so-called diffusion-perfusion mismatch) identifies tissue that is hypoperfused but that not yet experienced advanced bioenergetic failure and represents the penumbra. Thus, diffusion-perfusion mismatch are predicted to have the most lesion growth and may benefit most from any perfusion-altering therapies. The time window available for salvage of the penumbra in selected patients may be much longer than the traditional, presumed 3- to 6-hour window and that diffusion-perfusion MRI has the ability to identify these patients. Multimodal MRI allows therapeutic decisions to be based on individual patient pathophysiological information, allowing the time window to be extended in appropriate patients.
Brain ; Diffusion ; Energy Metabolism ; Humans ; Magnetic Resonance Imaging* ; Perfusion ; Stroke*

Objective To explore the expression profiles of circulating microRNA(miRNA)and potential markers for the diagnosis of adult fulminant myocarditis(FM). Methods The expression profiles of circulating miRNA were determined by microarray analysis and verified by real-time quantitative PCR.The key role of circulating miRNA in FM was determined via KEGG pathway enrichment.The correlations between miRNA and cardiac function parameters in patients with FM were analyzed.The receiver operating characteristic(ROC)curve was established to evaluate the sensitivity and specificity of circulating miRNA in the diagnosis of FM. Results Compared with healthy controls,the FM patients had up-regulated expression levels of miR-29b(t=18.925,P<0.001)and miR-125b(t=5.981,P=0.029)in the plasma.After treatment,the expression levels of miR-29b(t=12.943,P<0.001)and miR-125b(t=14.016,P<0.001)were significantly down-regulated.KEGG pathway enrichment showed that the targets of miR-29b were involved in inflammatory response and apoptosis pathways.The results of cell proliferation and apoptosis assay demonstrated the transfection of miR-29b mimic had a more significant inducing effect on cardiomyocyte apoptosis than that of miR-125b mimic(χ ²=6.168,P=0.047),whereas there was no significant difference in the inhibition of cell proliferation between the two groups(χ²=1.452,P=0.417).The expression levels of miR-29b and miR-125b were negatively correlated with left ventricular ejection fraction(r=-0.67,P=0.071;r=-0.49,P=0.003).They were positively correlated with cardiac troponin I level(r=0.61,P=0.019;r=0.52,P=0.016),interferon β level(r=0.42,P=0.014;r=0.36,P=0.021),and myocardial edema area(r=0.86,P=0.005;r=0.73,P=0.013).The ROC curve analysis demonstrated that miR-29b had higher sensitivity for the diagnosis of FM(93.6% vs.89.2%;t=0.896,P=0.795)and specificity(72.4% vs.59.6%;t=9.478,P=0.002)than miR-125b. Conclusion The circulating miR-29b may be a potential biomarker for the diagnosis of FM.
Adult ; Biomarkers/metabolism* ; Circulating MicroRNA/metabolism* ; Humans ; MicroRNAs/metabolism* ; Myocarditis/diagnosis* ; Stroke Volume ; Ventricular Function, Left

Mitochondria play a key role in various cell processes including ATP production, Ca homeostasis, reactive oxygen species (ROS) generation, and apoptosis. The selective removal of impaired mitochondria by autophagosome is known as mitophagy. Cerebral ischemia is a common form of stroke caused by insufficient blood supply to the brain. Emerging evidence suggests that mitophagy plays important roles in the pathophysiological process of cerebral ischemia. This review focuses on the relationship between ischemic brain injury and mitophagy. Based on the latest research, it describes how the signaling pathways of mitophagy appear to be involved in cerebral ischemia.
Animals ; Brain Ischemia ; metabolism ; pathology ; Humans ; Mitochondrial Degradation ; Reactive Oxygen Species ; metabolism ; Stroke ; metabolism ; pathology

PICK1 (protein interacting with C kinase 1) contains a PDZ (PSD-95/Dlg/ZO1) domain and a BAR (Bin/amphiphysin/Rvs) domain. Via the PDZ domain, PICK1 interacts directly with more than 40 proteins. Among these interacting proteins, some are important for physiological and pathophysiological processes of central nervous system. In this review, recent findings about how PICK1 is associated with central nervous system diseases are summarize.
Animals ; Carrier Proteins ; chemistry ; metabolism ; physiology ; Epilepsy ; metabolism ; Humans ; Nuclear Proteins ; chemistry ; metabolism ; physiology ; Schizophrenia ; metabolism ; Stroke ; metabolism

As men grow older, circulating testosterone declines while the incidence of cardiovascular disease increases. Thus, the role of sex hormones as biomarkers, and possibly contributing factors to clinical manifestations of cardiovascular disease in the increasing demographic of aging men, has attracted considerable interest. This review focuses on observational studies of endogenous androgens, namely circulating testosterone and dihydrotestosterone, which have examined their associations with cardiovascular events such as myocardial infarction and stroke. Studies which have examined the associations of endogenous estrogens, namely circulating estradiol, with these outcomes are also discussed. In large prospective cohort studies of predominantly middle-aged and older men, lower circulating testosterone consistently predicts higher incidence of cardiovascular events. Of note, both lower circulating testosterone and lower dihydrotestosterone are associated with higher incidence of stroke. These associations are less apparent when myocardial infarction is considered as the outcome. Results for estradiol are inconsistent. Lower circulating testosterone has been shown to predict higher cardiovascular disease-related mortality, as has lower circulating dihydrotestosterone. It is possible that the relationship of circulating androgens to cardiovascular events or mortality outcomes may be U-shaped rather than linear, with an optimal range defining men at lowest risk. Epidemiological studies are observational in nature and do not prove causality. Associations observed in studies of endogenous androgens need not necessarily translate into similar effects of exogenous androgens. Rigorous randomized controlled trials are needed to clarify the effects of testosterone treatment on cardiovascular risk in men.
Cardiovascular Diseases/mortality* ; Dihydrotestosterone/metabolism* ; Estradiol/metabolism* ; Humans ; Incidence ; Male ; Mortality ; Myocardial Infarction/metabolism* ; Stroke/metabolism* ; Testosterone/metabolism*

The purpose of this study was to quantitatively analyze the relationship between three dimensional arterial spin labeling (3D-ASL) and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) in ischemic stroke patients. Thirty patients with ischemic stroke were included in this study. All subjects underwent routine magnetic resonance imaging scanning, diffusion weighted imaging (DWI), magnetic resonance angiography (MRA), 3D-ASL and DSC-PWI on a 3.0T MR scanner. Regions of interest (ROIs) were drawn on the cerebral blood flow (CBF) maps (derived from ASL) and multi-parametric DSC perfusion maps, and then, the absolute and relative values of ASL-CBF, DSC-derived CBF, and DSC-derived mean transit time (MTT) were calculated. The relationships between ASL and DSC parameters were analyzed using Pearson's correlation analysis. Receiver operative characteristic (ROC) curves were performed to define the thresholds of relative value of ASL-CBF (rASL) that could best predict DSC-CBF reduction and MTT prolongation. Relative ASL better correlated with CBF and MTT in the anterior circulation with the Pearson correlation coefficients (R) values being 0.611 (P<0.001) and-0.610 (P<0.001) respectively. ROC curves demonstrated that when rASL ≤0.585, the sensitivity, specificity and accuracy for predicting ROIs with rCBF<0.9 were 92.3%, 63.6% and 76.6% respectively. When rASL ≤0.952, the sensitivity, specificity and accuracy for predicting ROIs rMTT>1.0 were 75.7%, 89.2% and 87.8% respectively. ASL-CBF map has better linear correlations with DSC-derived parameters (DSC-CBF and MTT) in anterior circulation in ischemic stroke patients. Additionally, when rASL is lower than 0.585, it could predict DSC-CBF decrease with moderate accuracy. If rASL values range from 0.585 to 0.952, we just speculate the prolonged MTT.
Brain Ischemia ; metabolism ; Humans ; Magnetic Resonance Angiography ; Retrospective Studies ; Stroke ; metabolism

Heart failure with preserved ejection fraction (HFpEF) is a syndrome with highly heterogeneous clinical symptoms, and its incidence has been increasing in recent years. Compared with heart failure with reduced ejection fraction (HFrEF), HFpEF has a worse prognosis. Traditional therapies targeting the internal mechanisms of the heart show limited or inefficacy on HFpEF, and new therapeutic targets for HFpEF are expected to be found by focusing on the extracardiac mechanisms. Recent studies have shown that cardiopulmonary pathophysiological interaction exacerbates the progression of HFpEF. Hypertension, systemic vascular injury, and inflammatory response lead to coronary microvascular dysfunction, myocardial hypertrophy, and coronary microvascular remodeling. Acute kidney injury affects myocardial energy production, induces oxidative stress and catabolism of myocardial protein, which leads to myocardial dysfunction. Liver fibrosis mediates heart injury by abnormal protein deposition and inflammatory factors production. Skeletal muscle interacts with the sympathetic nervous system by metabolic signals. It also produces muscle factors, jointly affecting cardiac function. Metabolic syndrome, gut microbiota dysbiosis, immune system diseases, and iron deficiency promote the occurrence and development of HFpEF through metabolic changes, oxidative stress, and inflammatory responses. Therefore, the research on the extracardiac mechanisms of HFpEF has certain implications for model construction, mechanism research, and treatment strategy formulation.
Humans ; Heart Failure/diagnosis* ; Stroke Volume/physiology* ; Myocardium/metabolism* ; Cardiomyopathies/metabolism* ; Hypertension ; Ventricular Function, Left

OBJECTIVETo study the relationship between the expressions of thrombin-antithrombin (TAT) complex and excess syndrome of stroke (ESS) and depletion syndrome of stroke (DSS) by dynamically observing the expressions of TAT complex in the plasma and hematoma fluid of intracerebral hemorrhage (ICH) patients.

METHODSSixty patients were assigned to three groups according to syndrome typing, i.e., as yang excess group (18 cases), yin excess group (22 cases), and depletion syndrome group (20 cases). The hemorrhage volume was assessed. NIHSS and GCS were scored. Besides, 30 healthy volunteers at the Physical Examination Center, Second People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine were recruited as the normal control group. Another 10 patients in need of lumbal anesthesia were recruited as the cerebrospinal fluid control group, who suffered from surgical, gynecologic pelvic diseases, or diseases from lower limbs, but unaccompanied with cardio-/cerebrovascular diseases. The expressions of TAT complex were detected in the venous blood and hematoma fluid of the patient groups and in the venous blood or the cerebrospinal fluid of the control group using ELISA.

RESULTSThe syndromes were sequenced as the depletion syndrome > the yin excess syndrome > the yang excess syndrome according to the hemorrhage volume and NIHSS score. They were sequenced as the yang excess syndrome > the yin excess syndrome >the depletion syndrome according to the GCS score. The plasma TAT complex content on the 4th day in the ICH group was lower than that at the rest time points, showing statistical significance (P<0.01). Compared with the normal control group, the plasma TAT complex on the 1st, 2nd, and 4th day all increased with statistical difference (P<0.01). Statistical significance of the TAT complex in the hematoma fluid of the ICH group existed when compared it on the 1st, 2nd, and 4th day (P<0.01). Compared with the cerebrospinal fluid control group, the contents of the TAT complex in the hematoma fluid of the ICH group increased with statistical difference (P<0.01). The hemorrhage volume of ICH patients was positively correlated with NIHSS (r=0.809, P<0.01) and negatively correlated with GCS (r=-0.833, P<0.01). The TAT complex was obviously higher in the ICH group than in the two control groups in a dynamic way (P<0.01). There was obvious difference in the expressions of TAT among yang excess group, yin excess group, and depletion syndrome group (P<0.01). The expressions of TAT in the plasma and the hematoma fluid of the ICH group were negatively correlated with GCS score and positively correlated with NIHSS score (both P<0.01).

CONCLUSIONSTAT complex participated in secondary neuron injury after ICH, which could be taken as an objective index for clinical observation. It also could provide evidence for syndrome quantification of excess syndrome and depletion syndrome.

Antithrombin III ; metabolism ; Case-Control Studies ; Cerebral Hemorrhage ; blood ; diagnosis ; metabolism ; Hematoma ; blood ; diagnosis ; metabolism ; Humans ; Medicine, Chinese Traditional ; Peptide Hydrolases ; metabolism ; Stroke ; blood ; diagnosis ; metabolism ; Thrombin ; metabolism