Case Report: Early-Onset Guillain-Barre Syndrome Mimicking Stroke.

Introduction: Guillain-Barre syndrome (GBS) is an acute immune-mediated inflammatory demyelinating polyneuropathy characterized by symmetrical limb weakness and areflexia. GBS can have different clinical manifestations; hence, the initial symptoms are also varied. Here, we describe a rare case of GBS presenting as hemiparesis and cranial nerve palsy, which mimic brainstem stroke. Case Presentation: A 53-year-old man was admitted to the hospital with a 3-h history of left-arm weakness, glossolalia, and right eyelid droop. After admission, his condition suddenly worsened, with quadriplegia, bilateral peripheral facial palsy, bilateral ophthalmoplegia, and other neurological symptoms. Based on the findings from a neurological examination, MRI, cerebrospinal fluid analysis, and nerve conduction study, a diagnosis of GBS was made. He received intravenous immunoglobulin (0.4 kg/day) for 5 days. After 20 days of systematic therapy, his dysphagia, dyspnea, facial paralysis, ocular movement disorder, and leg weakness recovered almost completely, but his arms were still moderately impaired, with a power of 4/5. Fortunately, the patient recovered well without any sequelae after 2 years of follow-up. Conclusions: In patients with an atypical presentation, the diagnosis of GBS is often delayed. With this case report, we intend to highlight the fact that some symptoms mimicking stroke may be a feature of GBS at onset; close observation and timely diagnosis are crucial for clinicians. Neuroimaging is a valuable diagnostic tool in differentiating stroke from GBS.

miR-9-5p attenuates ischemic stroke through targeting ERMP1-mediated endoplasmic reticulum stress.

Ischemic stroke (IS) is a cerebrovascular disease with serious neurological function impairment, which may activate endoplasmic reticulum (ER) stress. However, the underlying regulatory mechanism of ER stress under IS remains unclear. miR-9-5p is enriched in the brain tissues and plays a role in the pathological process of IS. Therefore, the purpose of this study is to explore the effect of miR-9 on ER stress and underlying mechanism in IS. Here, a middle cerebral artery occlusion (MCAO) rat model was utilized to examine the alteration of brain pathology, and the expressions of miR-9 and ER stress-related proteins. Then SH-SY5Y cells with oxygen-glucose deprivation (OGD) were performed to further evaluate the functional role of miR-9 and preliminary mechanism. The results showed that miR-9 levels were decreased in the ischemic region of rats after MCAO. MCAO significantly increased the brain infract volume, reduced Nissl bodies and cell apoptosis, and increased ER stress-related proteins (ERMP1, GRP78, p-PERK, p-eIF2α and CHOP). Furthermore, overexpression of miR-9 by miR-9 mimics increased cell viability, inhibited LDH activity and cell apoptosis, and inactivated ER stress in OGD-neurons. Luciferase activity results showed that miR-9 negatively regulated ERMP1 expression by directly targeting ERMP1 3' UTR. Subsequently, we found that ERMP1 overexpression reversed the inhibition of miR-9 on GRP78-PERK-CHOP pathway in OGD neurons. In summary, our results suggest that the attenuation of miR-9 on ischemic injury may be involved in targeting ERMP1-mediated ER stress, which provides an available target for IS treatment.

Identification of Differentially Expressed Genes and Long Noncoding RNAs Associated with Parkinson's Disease.

OBJECTIVES: This study aims to determine differentially expressed genes (DEGs) and long noncoding RNAs (lncRNAs) associated with Parkinson's disease (PD) using a microarray. METHODS: We downloaded the microarray data GSE6613 from the Gene Expression Omnibus, which included 105 samples. We selected 72 samples comprising 22 healthy control blood samples and 50 PD blood samples for further analysis. Later, we used Limma to screen DEGs and differentially expressed lncRNAs (DElncRNAs) and estimated their functions by the Gene Ontology (GO). Besides, the competing endogenous RNA (ceRNA) network, including microRNAs, lncRNAs, and mRNAs, was constructed to elucidate the regulatory mechanism. Furthermore, we performed the KEGG pathway enrichment with mRNAs in the ceRNA regulatory network and constructed a final network, including pathways, mRNAs, microRNAs, and lncRNAs. RESULTS: Overall, we obtained 394 DEGs, including 207 upregulated DEGs and 187 downregulated DEGs, and 7 DElncRNAs, including 2 upregulated DElncRNAs and 5 downregulated DElncRNAs. Insulin-like growth factor-1 receptor (IGF1R) was considerably enriched in the endocytosis pathway. In the ceRNA regulation network, IGF1R was the target of hsa-miR-133b and lncRNAs of XIST, and PART1 could also be the target of hsa-miR-133b. While the upregulated DEGs were enriched in the GO terms of the cytoskeleton, cytoskeletal part, and microtubule cytoskeleton, the downregulated DEGs were enriched in the immune response. PRKACA was markedly enriched in numerous pathways, including the MAPK and insulin signaling pathways. CONCLUSIONS: IGF1R, PRKACA, and lncRNA-XIST could be potentially involved in PD, and these diverse molecular mechanisms could support the development of the similar treatment for PD.

NLRP3 inflammasome contributes to neurovascular unit damage in stroke.

Recently, a wealth of information has emerged connecting the activation of the NLRP3 (NOD-like receptor family pyrin domain-containing 3) inflammasome to stroke pathogenesis, although the exact influence of the NLRP3 inflammasome on stroke is still in the stage of preliminary study and is awaiting further confirmation. In this paper, we will review the structure, assembly and activation of the NLRP3 inflammasome and its expression in the neurovascular units and will speculate on its possible roles in neurovascular injury post-stroke. Evidence on this topic suggests that targeting NLRP3-mediated inflammation at multiple levels may provide a new therapeutic strategy to prevent the deterioration of neurovascular units after stroke. However, many aspects of the biological link between the NLRP3 inflammasome and stroke remain ill-defined or even completely unknown. As fresh insights come to light regarding the NLRP3 inflammasome, the opportunities to develop new therapeutic strategies for stroke patients are expected to improve accordingly.

Tail Vein Infusion of Adipose-Derived Mesenchymal Stem Cell Alleviated Inflammatory Response and Improved Blood Brain Barrier Condition by Suppressing Endoplasmic Reticulum Stress in a Middle Cerebral Artery Occlusion Rat Model.

BACKGROUND The current study was designed to explore the pathway through which adipose-derived mesenchymal stem cells (ADMSCs) affect brain ischemic injury. MATERIAL AND METHODS The improving effect of ADMSCs on the brain function and structure was evaluated in a middle cerebral artery occlusion (MCAO) rat model. The permeability of the brain-blood barrier (BBB), inflammatory response, and endoplasmic reticulum (ER) stress-related signaling induced by ischemia were determined. RESULTS The administration of ADMSCs decreased neurological severity score when compared with that in the MCAO group and also restricted the brain infarction area as well as cell apoptosis. ADMSCs suppressed the inflammation in brains by decreasing the expressions of IL-1ß, IL-6, and TNF-α, contributing to the decreased permeability of the BBB. The expressions of pro-apoptosis factors in ER stress were inhibited while that of anti-apoptosis factors were induced. CONCLUSIONS ADMSCs affected brain injury in multiple ways, not only by suppressing inflammation in the brain infarction area, but also by blocking ER stress-induced apoptosis.

A case report of neuromyelitis optica spectrum disorder with peripheral neuropathy as the first episode.

RATIONALE: Neuromyelitis optica spectrum disorders (NMOSDs) represent recurrent autoimmune diseases, generally beginning with optic nerve neuritis or acute transverse myelitis. PATIENT CONCERNS: A 57-year-old male with long-term alcohol intake was hospitalized because of limb numbness. EMG examination showed the peripheral sensory nerve was in demyelination and an axonal injury was found. His symptoms could not be improved by vitamin B injection but were later significantly attenuated by dexamethasone treatment. Four months later, symptoms of optic neuritis in the left eye appeared, and 6 months later he exhibited peripheral neuropathy with acute myelitis. DIAGNOSES: He was diagnosed NMOSD. OUTCOMES: Immunotherapy improved his peripheral neuropathy and myelitis symptoms. LESSONS: NMOSD patients could represent peripheral neuropathy as the first episode.

Rapid improvement of angiostenosis due to isolated middle cerebral artery dissection: A case report.

RATIONALE: Intracranial arterial dissection is a rare cause of ischemic stroke, and isolated middle cerebral artery dissection (MCAD) is extremely rare, having been described only in sparse case reports. The etiology, clinicoradiological features, and treatment strategies are not yet well understood. PATIENT CONCERNS: A 49-year-old man presented with rapidly progressive aphasia and motor disturbance of the right limbs. DIAGNOSES: Neuroimaging evaluation confirmed a diagnosis of MCAD and cerebral infarction. INTERVENTIONS: The patient underwent oral anti-platelet therapy (100 mg aspirin daily). OUTCOMES: The patient recovered to normal status within 2 weeks following antiplatelet treatment. During a follow-up period of 2 years, he remained neurologically asymptomatic and led a virtually normal life. LESSONS: It is crucial for clinicians to be aware of this entity, as the diagnosis of MCAD is quite challenging. Antiplatelet therapy is effective for treating this condition, and the prognosis can be favorable.

Combining Telomerase Reverse Transcriptase Genetic Variant rs2736100 with Epidemiologic Factors in the Prediction of Lung Cancer Susceptibility.

Genetic variants from a considerable number of susceptibility loci have been identified in association with cancer risk, but their interaction with epidemiologic factors in lung cancer remains to be defined. We sought to establish a forecasting model for identifying individuals with high-risk of lung cancer by combing gene single-nucleotide polymorphisms with epidemiologic factors. Genotyping and clinical data from 500 lung cancer cases and 500 controls were used for developing the logistic regression model. We found that lung cancer was associated with telomerase reverse transcriptase (TERT) rs2736100 single-nucleotide polymorphism. The TERT rs2736100 model was still significantly associated with lung cancer risk when combined with environmental and lifestyle factors, including lower education, lower BMI, COPD history, heavy cigarettes smoking, heavy cooking emission, and dietary factors (over-consumption of meat and deficiency in fish/shrimp, vegetables, dairy products, and soybean products). These data suggest that combining TERT SNP and epidemiologic factors may be a useful approach to discriminate high and low-risk individuals for lung cancer.

In silico analyses for molecular genetic mechanism and candidate genes in patients with Alzheimer's disease.

This study aimed to identify candidate genes and explore the molecular pathogenesis of Alzheimer's disease (AD). Exon microarray data composed by of three human entorhinal cortex samples of AD patients and three non-demented controls (NDC) were analyzed, then expression profile data were preprocessed with the Oligo package and differentially expressed genes (DEGs) were identified by limma package in R/Bioconductor. In addition, protein-protein interaction (PPI) network was predicted and constructed using the STRING database. Finally, gene ontology (GO)-biological processes (BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched by DEGs were recognized. A total of 124 up-regulated and 218 down-regulated genes were identified. TGF-beta-activated kinase 1/MAP3K7 binding protein 2 (TAB 2) and chromogranin B (secretogranin 1) (CHGB) were the significantly up- and down-regulated genes, respectively. In addition, DEGs of DnaJ (Hsp40) homolog, subfamily B, member 1 (DNAJB1) and heat shock 70 kDa protein 1A (HSPA1A) were in the up-regulated network, while synaptophysin (SYP) and somatostatin (SST) were in the down-regulated network. Furthermore, the up-regulated genes were enriched in GO-BP terms of protein stimulus, unfolding and organic substance, etc., and pathways of ECM-receptor interaction, etc. The down-regulated genes were mainly associated with nerve-related transmission and neuroactive substances transportation. Protein folding abnormality and altered synaptic transmission could have a synergistic effect on the pathomechanism of AD. DEGs including DNAJB1 and HSPA1A may be involved in both the processes, while CHGB, SYP and SST may be important for the regulation of synaptic transmission to contribute to the progress and development of AD.

Proteolipid protein 1 gene sequencing of hereditary spastic paraplegia.

PCR amplification and sequencing of whole blood DNA from an individual with hereditary spastic paraplegia, as well as family members, revealed a fragment of proteolipid protein 1 (PLP1) gene exon 1, which excluded the possibility of isomer 1 expression for this family. The fragment sequence of exon 3 and exon 5 was consistent with the proteolipid protein 1 sequence at NCBI. In the proband samples, a PLP1 point mutation in exon 4 was detected at the basic group of position 844, T→C, phenylalanine→leucine. In proband samples from a male cousin, the basic group at position 844 was C, but gene sequencing signals revealed mixed signals of T and C, indicating possible mutation at this locus. Results demonstrated that changes in PLP1 exon 4 amino acids were associated with onset of hereditary spastic paraplegia.