Ischemic stroke as an initial performance of polycythemia vera in young adults: A case report and literature review.

INTRODUCTION: As the second leading cause of death and disability worldwide, stroke is mainly caused by atherosclerosis and cardiac embolism, particularly in older individuals. Nevertheless, in young and otherwise healthy individuals, the causes of stroke can be more diverse and may include conditions such as patent foramen ovale, vasculitis, coagulopathies, genetic factors, or other undetermined causes. Although these other causes of stroke account for a relatively small proportion compared to ischemic stroke, they are becoming increasingly common in clinical practice and deserve attention. Here, we present a rare female patient with polycythemia vera (PV) who was admitted to the hospital as a stroke patient without any previous medical history. PATIENT CONCERNS: A 40-year-old young woman felt sudden dizziness and slow response. After 4 days of being admitted, she developed blurry vision on the right. DIAGNOSES: Cranial magnetic resonance imaging revealed aberrant signals in the left temporal and parietal lobe, as well as multiple small focal signal abnormalities were observed in the left frontal lobe. Magnetic resonance angiography revealed partial stenosis of the left internal carotid artery. The patient's blood routine examination revealed a significant elevation in complete blood counts, particularly the increase in red blood cells, as well as prolonged clotting time. An abdominal ultrasound and abdomen computed tomography showed splenomegaly. The outcome of the genetic testing was positive for the Janus kinase JAK2 exon V617F mutation (JAK2/V617F). The patient was diagnosed with PV-related stroke. INTERVENTIONS: The patient was treated with phlebotomy, cytoreductive therapy, and low-dose aspirin antiplatelet therapy and was regularly followed up in hematology and neurology clinics after discharge. OUTCOMES: The patient's red blood cell, leukocyte, and thrombocyte counts had fully normalized, with her hemoglobin level measuring at 146 g/L and hematocrit value at 43%. Furthermore, there had been a significant improvement in neurological symptoms. LESSONS: PV, a rare hematological disorder, can present with ischemic stroke as the initial performance, and the diagnosis mainly relies on routine blood tests, bone marrow biopsies, and genetic test. Therefore, clinicians should pay attention to PV, a low-prevalence disease, when encountering stroke in youth.

Thrombolysis Versus Nonthrombolyzed in Patients With Mild Strokes and Large Vessel Occlusions: Results of a Multicenter Stroke Registration.

BACKGROUND: The safety and efficacy of intravenous thrombolysis (IVT) in acute ischemic stroke patients with large vessel occlusions and mild neurological deficits are controversial. METHODS: Data of stroke patients presenting with mild initial stroke, which was defined as the National Institutes of Health Stroke Scale score (NIHSS) ≤5 and large vessel occlusion, were extracted from a large provincewide stroke registry. RESULTS: A total of 619 IVT and 2170 non-IVT patients were identified in this study. IVT patients had higher rates of favorable functional outcome Modified Rankin Scale(mRS) ≤1 (74.6% vs. 70.6%; P =0.047), lower mRS scores (1 vs. 1, P =0.001), and higher NIHSS score decreased (1 vs. 0, P <0.001) at discharge compared with the non-IVT patients. The rates were similar in symptomatic intracranial hemorrhage (2.1% vs. 2.0%, P =0.853), severe systemic bleeding (0.8% vs. 0.6%, P =0.474), and mortality at discharge (0.2% vs. 0.2%, P =0.906) between the 2 groups. A multiple Logistic regression model found that age above 80 years [adjusted OR (aOR) 2.056 (95% CI, 1.125 to 3.756)], history of stroke [aOR 1.577 (95% CI, 1.303 to 1.910)], hyperlipidemia [aOR 2.156 (95% CI, 1.059 to 4.388)], high admission NIHSS score [aOR 1.564 (95% CI, 1.473 to 1.611)], and non-IVT [aOR 1.667 (95% CI, 1.337 to 2.077)] were independent risk factors for mRS >1. CONCLUSIONS: IVT administration is safe and effective in eligible acute ischemic stroke patients. Age above 80 years, with a history of stroke and hyperlipidemia, high admission NIHSS score, and non-IVT were independent risk factors for mRS >1 at discharge in these patients.

A Chinese female patient with LGI1 and mGluR5 antibodies: A case report.

RATIONALE: Anti-LGI1 antibody encephalitis and anti-mGluR5 are both uncommon encephalitis, and we report the first case of autoimmune encephalitis (AE) with dual seropositive antibodies of leucine-rich glioma-inactivated 1 (LGI1) and mGluR5. PATIENT CONCERNS: We present a case of AE with dual seropositive antibodies of LGI1 and mGluR5 in a 65-year-old woman who presented with sudden onset left faciobrachial dystonic seizures and unresponsive for 5 hours. DIAGNOSIS: The patient was diagnosed with anti-LGI1 AE and anti-mGluR5 AE mainly based on the clinical symptoms and further test of the antibody in serum and cerebral spinal fluid (CSF). INTERVENTIONS AND OUTCOMES: The patient was treated with glucocorticoid intravenous drip. We also gave her the therapy of immunoglobulin (25 g q.d) for 5 days and anti-epileptic therapy. She had no more convulsions on the left side of the face and limbs. She did not complain of any uncomfort until July 18. LESSONS: Early recognition of AE is crucial. Specific autoantibodies are associated with corresponding syndromes. Our patient was initially diagnosed with acute ischemic stroke. Therefore, we should conduct further study on the related symptoms of AE.

Comparative study on treatment of acute cerebral infarction between mechanical thrombectomy by micro catheter and thrombectomy by Solitaire AB stent.

BACKGROUND: Acute cerebral artery occlusion is a common disease with high morbidity and mortality. At present, the commonly used mechanical thrombectomy schemes are mechanical thrombectomy and stent thrombectomy. However, the clinical differences between the two methods is not fully understood. The present study aimed to evaluate the clinical effectiveness of Solitaire AB stent thrombectomy for acute cerebral infarction (ACI). METHODS: A retrospective study was carried out in 96 ACI patients admitted to our department from January 2017 to January 2020. According to the treatment they received, they were divided into group A (conventional microcatheter mechanical thrombectomy, n = 48) and group B (Solitaire AB stent thrombectomy, n = 48). All patients were followed up for 3 months. Their pre- and post-operative nerve function indices were compared between the 2 groups. The therapeutic effects were evaluated by thrombolysis in cerebral infarction scale system, Glasgow coma scale (GCS), National Institutes of Health Stroke Scale (NIHSS), and modified Rankin scale statistics. RESULTS: Two groups of patients with NIHSS scores postoperative 3 and 30 days decreased significantly compared with preoperation. NIHSS score of group A 3 and 30 days postoperation was significantly higher than group B (P < .05). Two groups of patients with GCS scores postoperative 3 and 30 days increased significantly compared with preoperation. GCS score of group A 3 and 30 days postoperation was significantly lower than group B (P < .05). Group B with vascular recanalization ratio postoperative 30 days was higher than group A, however with no significant differences (P > .05). Moreover, group B with outcomes (modified Rankin scale score ≤2 points) postoperative 3 months was better than group A, however with no significant differences (P > .05). CONCLUSION: Solitaire AB stent embolectomy shows similar efficacy as mechanical thrombectomy in the treatment of ACI patients.

Klebsiella pneumoniae-related brain abscess and meningitis in adults: Case report.

INTRODUCTION: Klebsiella pneumoniae is once thought to be a less common cause of brain abscess in adults and is mainly hospital-acquired. Community-acquired CNS infection (brain abscess and meningitis) caused by K pneumoniae without other metastatic septic abscesses is exceedingly rare. Therefore, we present a rare adult patient with invasive cerebral abscess and meningitis without other invasive abscesses related to K pneumoniae. PATIENT CONCERNS: A 64-year-old woman experienced a sudden onset of severe continuous headache accompanied by intermittent nausea, vomiting, and fever. Meanwhile, she experienced tinnitus and had a feeling of swelling in the right ear. DIAGNOSIS: Cranial magnetic resonance imaging revealed abnormal hyperintensity signals in the left head of the caudate nucleus. The next generation sequencing of cerebral spinal fluid showed infection with K pneumoniae. The patient was diagnosed with K pneumoniae-related brain abscesses and meningitis. INTERVENTIONS: Antibacterial treatment was carried out for 2 months. OUTCOMES: The patient recovered well. CONCLUSION: Despite the progress of modern neurosurgical techniques, new antibiotics, and modern imaging techniques, brain abscesses are still a potentially fatal infection. Streptococci are common organisms that result in brain abscesses. Nevertheless, Klebsiella species, once thought to be a less common cause of brain abscess in adults, has become an increasingly important cause of brain abscess, especially in Asia.

Past Exposure to Cigarette Smoke Aggravates Cognitive Impairment in a Rat Model of Vascular Dementia via Neuroinflammation.

Smoking is a risk factor for dementia. Cognitive function can be partially restored after quitting smoking, but still lower than never smoked group. The underlying mechanisms still remain unclear. The effects of smoking cessation combined with cerebral chronic hypoperfusion (CCH) on cognitive function have never been described. Here, we established a cigarette smoking cessation model, a CCH model, and a cigarette smoking cessation plus CCH model. We investigated cognitive function in these models and the mechanisms of the neuroinflammation, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)/cysteine aspartate-specific proteinase (caspase-1)/interleukin- 1ß (IL-1ß) pathway, and eucaryotic initiation factor 2α (eIF2α) /autophagy pathway. We used morris water maze (MWM) and novel object recognition (NOR) test to evaluate cognitive function in rats. Nissl staining was performed to observe cell morphology in the hippocampal CA1 area. A neuroinflammatory marker (glial fibrillary acidic protein, GFAP) was assessed by Western blot analysis and immunohistochemistry staining. IL-1ß levels were detected by ELISA. The protein levels of NLRP3/caspase-1/ IL-1ß and eIF2α/autophagy pathway were evaluated by Western blot analysis. LC3 was assessed by immunofluorescence staining. CCH can affect cognitive function by influencing neuroinflammation, NLRP3/caspase-1/IL-1ß pathway, and eIF2α/autophagy pathway. Past exposure to cigarette smoke can also affect cognitive function by influencing neuroinflammation and NLRP3/caspase-1/IL-1ß pathway, which may be induced by smoking and may not be alleviated after smoking cessation. Past exposure to cigarette smoke does not influence autophagy, which may be increased by smoking and then decrease to normal levels after smoking cessation. Past exposure to smoking can further aggravate cognitive impairment and neuroinflammation in VaD animals: cognitive impairment induced by CCH via neuroinflammation, NLRP3/caspase-1/IL-1ß, and eIF2α/autophagy pathway and cognitive impairment induced by past exposure to cigarette smoke via neuroinflammation and NLRP3/caspase-1/IL-1ß pathway. The combined group had the worst cognitive impairment because of harmful reasons.

O-GlcNAc Transferase (OGT) Protects Cerebral Neurons from Death During Ischemia/Reperfusion (I/R) Injury by Modulating Drp1 in Mice.

Previous studies have demonstrated that increased O-linked N-acetylglucosamine (O-GlcNAc) level could promote cell survival following environmental stresses. This study aimed to explore the role of O-GlcNAc transferase (OGT) during cerebral ischemia/reperfusion (I/R) injury. The mouse model with cerebral I/R injury was induced by middle cerebral artery occlusion/reperfusion (MCAO/R). The expression of ogt in brain tissues was detected by qRT-PCR, Western blot, and immunohistochemistry (IHC) staining assay. Neurological deficit was evaluated using a modified scoring system. The infarct volume was assessed by TTC staining assay. Neuronal apoptosis in brain tissues was evaluated by TUNEL staining assay. The level of cleaved caspase-3 in brain tissues was detected by Western blot and IHC staining assay. The expression of critical proteins involved in mitochondrial fission, including OPA1, Mfn1, and Mfn2, as well as Mff and Drp1 was detected by Western blot and IHC, respectively. The expression of ogt during cerebral I/R injury was significantly upregulated. Ogt knockdown significantly increased neurological score and infarct volume in I/R-induced mice. Meanwhile, ogt knockdown significantly enhanced neuronal apoptosis and cleaved caspase-3 level in brain tissues of I/R-induced mice. In addition, ogt knockdown markedly decreased serine 637 phosphorylation level of mitochondrial fission protein dynamin-related protein 1 (Drp1) and promoted Drp1 translocation from the cytosol to the mitochondria. Moreover, the specific Drp1 inhibitor mdivi-1 effectively attenuated ogt knockdown-induced brain injury of I/R-stimulated mice in vivo. Our study revealed that OGT protects against cerebral I/R injury by inhibiting the function of Drp1 in mice, suggesting that ogt may be a potential therapeutic target for cerebral I/R injury.

Sacubitril/valsartan inhibits ox­LDL­induced MALAT1 expression, inflammation and apoptosis by suppressing the TLR4/NF­κB signaling pathway in HUVECs.

The therapeutic effect of sacubitril/valsartan (S/V) on heart failure has been confirmed, while its role in atherosclerosis remains largely unexplored. The present study aimed to investigate the effects of S/V on the expression of metastasis­associated lung adenocarcinoma transcript 1 (MALAT1), inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs) induced by oxidized low­density lipoprotein (ox­LDL) and to elucidate its possible mechanism. Cell Counting Kit­8 assay was used to detect cell viability. Reverse transcription­quantitative PCR was performed to detect the MALAT1 expression. ELISA was performed to detect the levels of IL­1ß, IL­6 and TNF­α. Flow cytometry was conducted to detect the apoptotic rate of cells. A nitric oxide (NO) detection kit was used to determine the concentration of NO. Western blotting analysis was performed to determine the levels of intercellular cell adhesion molecule (ICAM)­1, vascular cell adhesion molecule (VCAM)­1, endothelin­1, caspase­3, Bax, Bcl­2, Toll­like receptor 4 (TLR4), p65 and p­p65. Compared with the ox­LDL group, S/V treatment significantly increased the cell viability, NO concentration and Bcl­2 expression, decreased the levels of IL­1ß, IL­6 and TNF­α and reduced the expressions of MALAT1, ICAM­1, VCAM­1, cleaved­caspase­3, Bax, TLR4 and p­p65. Overall, the findings suggested that S/V could downregulate the expression of MALAT1, inhibit inflammation and apoptosis and improve endothelial function in ox­LDL­induced HUVECs via inactivating the TLR4/NF­κB signaling pathway. Therefore, S/V might be utilized as a promising therapeutic strategy for the prevention and treatment of atherosclerosis.

Corrigendum: MicroRNA Let-7i Is a Promising Serum Biomarker for Post-stroke Cognitive Impairment and Alleviated OGD-Induced Cell Damage in vitro by Regulating Bcl-2.

[This corrects the article DOI: 10.3389/fnins.2020.00215.].

Effects of CircRNA-ITCH on proliferation and apoptosis of hepatocellular carcinoma cells through inhibiting Wnt/ß-catenin signaling pathway.

PURPOSE: To explore the effects of circular ribonucleic acid (circRNA)-E3 ubiquitin protein ligase (ITCH) on the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells and its possible molecular mechanism. METHODS: To study the role of circRNA-ITCH in the occurrence and development of HCC. The relative expression level of circRNA-ITCH was detected via quantitative polymerase chain reaction (qPCR) in four kinds of HCC Huh-7, U251, HB611 and SMMC-7721 cell lines, and human normal liver L-02 cell line. Moreover, the effect of overexpression of circRNA-ITCH on the TCF luciferase activity was detected using ß-catenin/TCF-responsive luciferase reporter assay. Finally, the influences of overexpression of circRNA-ITCH on the protein levels of ß-catenin and Wnt3α and the mRNA levels of c-myc and cyclinD1 were determined using Western blotting and qPCR, respectively. RESULTS: Compared with that in human normal liver L-02 cell line, the expression of circRNA-ITCH was significantly down-regulated in HCC Huh-7, U251, HB611 and SMMC-7721 cell lines (p<0.05). According to the results of CCK-8 assay, colony formation assay and flow cytometry, the overexpression of circRNA-ITCH could obviously inhibit cell proliferation, suppress colony formation ability and induce apoptosis (p<0.05). The results of dual-luciferase reporter assay revealed that there was a significant interaction between circRNA-ITCH and miR-7 or miR-214 (p<0.05). CircRNA-ITCH was involved in the regulating of Wnt/ß-catenin signal transduction pathway and inhibited the expressions of c-myc and cyclinD1. CONCLUSIONS: CircRNA-ITCH affects the proliferation and apoptosis of HCC cells through inhibiting the Wnt/ß-catenin signal transduction pathway, thereby exerting a carcinogenic effect in the occurrence and development of HCC. The research results provide a new therapeutic target for HCC.

MicroRNA Let-7i Is a Promising Serum Biomarker for Post-stroke Cognitive Impairment and Alleviated OGD-Induced Cell Damage in vitro by Regulating Bcl-2.

Background: The mechanism of post-stroke cognitive impairment (PSCI) has not been explained. We aimed to investigate whether miR-let-7i participates in the PSCI and illuminates its underlying role in oxygen-glucose deprivation (OGD)-induced cell apoptosis. Methods: Blood samples from 36 subjects with PSCI and 38 with post-stroke cognitive normality (Non-PSCI) were collected to evaluate the differential expression of miR-let-7 family members, using qRT-PCT analysis. Spearman correlation was performed to estimate the correlation between the miR-1et-7i level and Montreal Cognitive Assessment (MoCA) score. Treatment of SH-SY5Y cells with OGD was used to induce cell apoptosis in vitro. Effects of miR-let-7i on OGD-induced cell apoptosis was estimated after transfection. The target gene of miR-let-7i was analyzed by dual luciferase reporter gene assay. Results: The expression of miR-let-7i was up-regulated in PSCI patients compared with Non-PSCI (p < 0.001) and negatively correlated with MoCA score (r = -0.643, p < 0.001). When exposed to OGD, SH-SY5Y cells showed significant apoptosis accompanied by miR-let-7i up-regulation. In OGD-treated cells, miR-let-7i up-regulation was accompanied by cell apoptosis, while down-regulation showed the opposite effect. Luciferase reporter assay showed that Bcl-2 was a target gene of miR-let-7i. Western blot showed that miR-let-7i up-regulation promoted Bcl-2 expression, while qRT-PCR showed that miR-let-7i had no effect on Bcl-2 expression. Conclusion: miR-let-7i was overexpressed in PSCI patients and it could be used as a diagnostic biomarker for PSCI. We illuminated the potential mechanism that miR-let-7i alleviated OGD-induced cell damage by targeting Bcl-2 at the post-transcriptional level.

Iron dysregulation in vascular dementia: Focused on the AMPK/autophagy pathway.

Recent researches suggested that iron dysregulation play an important role in the pathogenesis of vascular dementia (VD). Iron deposition had been found in hippocampus in vascular dementia model in recent research. Nevertheless, the underlying mechanisms of iron deposition and its neurotoxicity in vascular dementia was still unclear. Thus, our research was aimed at whether the neurotoxicity of iron was associated with autophagy regulation. We established a chronic cerebral hypoperfusion model in the rat brain in order to mimic the vascular dementia using permanent bilateral common carotid artery occlusion (2VO). The preparation of iron overloaded rats model by intraperitoneal injection of iron dextran. Following, we tested the learning and memory function of each group using Morris Water Maze. Consequently, we analyzed the iron content and iron transport related molecules (TFR1, DMT1) in hippocampus. Furthermore, we examined the effect of iron deposition on autophagy-related molecules including AMPK, Beclin1 and LC3 and the number of autophagosomes in hippocampus. Last, we tested the apoptosis of neurons in hippocampus. We found that iron deposition in hippocampus in model groups which accompanied the decline of learning and memory function. And the expression of TFR1 and DMT1 were up-regulated in model groups. Moreover, iron deposition up-regulated the expression of AMPK, Beclin1 and LC3 and increase the number of autophagosomes in hippocampus. And the expression of Bax was up-regulated and Bcl-2 was down-regulated in iron deposition groups. To sum up, our data suggested that iron deposition increased AMPK/autophagy pathway associated molecules in the hippocampus and promoted neuronal apoptosis, which might be a new pathogenesis in vascular dementia.

SS31 ameliorates age-related activation of NF-κB signaling in senile mice model, SAMP8.

Aging has been attributed to oxidative stress and inflammatory response, in which NF-κB and Nrf2-ARE signaling pathways play significant roles. Senescence accelerated mouse prone 8 (SAMP8) is generally used an animal model for aging studies. Here, we investigated the NF-κB and Nrf2-ARE signaling pathways in SAMP8 brains at different ages and their responses to SS31 peptide treatment. Thirty six SAMP8 mice were separated into aging groups and SS31-treatment groups. The hippocampus from each mouse was dissected for RNA and protein extraction. Cytokines and ROS levels were measured using ELISA and standardised method. Gene expressions of NF-κB, Nrf2 and HO-1 were measured by RT-qPCR. Total protein amount of NF-κB and HO-1, as well as the concentrations of nuclear and cytoplasmic Nrf2 were measured using Western blots. Our data showed that aging could activate both NF-κB and Nrf2-ARE signaling pathways, which could be suppressed and activated by SS31 treatment respectively. Regression analysis revealed that NF-κB gene expression was the most important parameter predicting aging process and SS31 treatment effects in SAMP8. Our findings suggested that SS31 treatment may modulate the inflammatory and oxidative stress status of the aged brains and exert protective effects during brain aging.

SS31, a Small Molecule Antioxidant Peptide, Attenuates ß-Amyloid Elevation, Mitochondrial/Synaptic Deterioration and Cognitive Deficit in SAMP8 Mice.

Mitochondrial dysfunction, oxidative stress and ß -amyloid (Aß) formation are thought to cause neuronal and synaptic degeneration underlying cognitive decline in Alzheimer's disease (AD). The senescence-accelerated mouse-prone 8 (SAMP8) mice have been used as an animal model for mechanistic and translational research for AD. In the present study we characterized mitochondrial and synaptic alterations in SAMP8 mice relative to SAMR1control mice and explored a protective effect of the small molecule peptide SS31, a cell membrane penetrant antioxidant, on mitochondrial and synaptic protein integrity as well as cognitive performance. Electron microscopic analysis revealed mitochondrial/synaptic deterioration in 10 months-old SAMP8 relative to SAMR1 mice, with the changes in the former rescued following 8 weeks treatment with SS31 (5 mg/kg/day, i.p.). Elevation of Aß42, mitochondrial fission protein (DLP1, Fis1) and matrix protein cyclophilin D (CypD), and reductions of mitochondrial fusion protein (Mfn2) and synaptic (i.e., synaptophysin, postsynaptic density protein 95 and growth associated protein 43) proteins, were detected in hippocampal lysates in SAMP8 mice relative to SAMR1. The above altered protein expressions in the SAMP8 mouse brain were restored with the SS31 treatment. Moreover, the SS31 treatment rescued learning and memory deficits detected in 10 month-old SAMP8 mice. Together, the findings suggest that this mitochondria-targeting antioxidant peptide may be of potential utility for AD therapy, with its pharmacological efficacy involves lowering of central Aß levels and protection of mitochondrial homeostasis and synaptic integrity, which may help slow down cognitive decline.