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This paper explores applications of the coordinated multi-point (CoMP) architecture operation of enhanced node B (eNB) in wireless communication networks featuring device-to-device (D2D) signaling. This is applied to cellular phone coverage for rapid mass transit systems, such as the Taiwan high speed rail transport system, and indoor public environments. The paper is based on formulas pertaining to the link between budget design and guidelines, as well as principles and theories of engineering practice, allowing designers to analyze and fully control the uplink and downlink signals and output power of fiber repeaters linking cellular phones to base stations. Finally, we employ easily installed cellular-over-fiber optic solutions for a small cell enhancement (SCE) system with novel architecture based on a leakage coaxial cable system using LTE-A technology. As a result, we successfully applied enhanced coverage designs for distributed antenna systems. These can be used to create self-organizing networks (SoN) for an Internet of Things.

Background Chronic kidney disease has been identified as a risk factor affecting stroke prognosis. High-grade carotid artery stenosis (CAS) is associated with distal hemodynamic compromise. The association between the estimated glomerular filtration rate (eGFR) and ischemic stroke (IS) outcome in patients with high-grade CAS remains unclear. We aimed to investigate the association between eGFR and outcomes of acute IS patients with high-grade CAS. Methods From January 1, 2007 to April 30, 2012, we enrolled 372 acute IS patients with high-grade CAS and prospectively observed them for 5 years. The eGFR on admission was assessed using the Modification of Diet in Renal Disease Study equation. Demographic features, vascular risk factors, comorbidities, and outcomes were compared between different eGFR levels. Results Among 372 individuals, 76 (20.4%) had an eGFR 2. Compared to other groups, in the eGFR 2 group, the prevalence rates of hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, valvular heart disease, and gout were significantly higher (P = 0.013, P = 0.030, P = 0.001, P P = 0.043, and P 2 demonstrated lower hemoglobin and total cholesterol levels compared with other groups (P P = 0.048). The blood potassium and uric acid levels were significantly higher in patients with eGFR 2 (P P 2 was a significant risk factor for 5-year all-cause mortality in IS patients with high-grade CAS after adjusting for these variables (hazard ratio = 2.05; 95% CI = 1.31–3.21; P = 0.002). Conclusions eGFR 2 was associated with an increased risk of 5-year all-cause mortality in acute IS patients with high-grade CAS. Whether aggressive treatment of chronic kidney disease in IS patients with high-grade CAS can improve stroke outcomes should be confirmed in future studies.

Background: The coincidence of coronary artery disease (CAD) and carotid artery stenosis (CAS) was observed. However, the association between pre-existing CAD and ischemic stroke (IS) outcome in patients with high-grade CAS remains unclear. We aimed to investigate the association between pre-existing CAD and outcomes of acute IS patients with high-grade CAS. Methods: From January 1, 2007, to April 30, 2012, we enrolled 372 acute IS patients with high-grade CAS and prospectively observed them for 5 years. Demographic features, vascular risk factors, comorbidities, and outcomes were compared between patients with and without pre-existing CAD. Results: Among 372 individuals, 75 (20.2%) patients had pre-existing CAD and 297 (79.8%) patients did not have pre-existing CAD. The prevalence rates of hypertension, congestive heart failure, chronic kidney disease, and gout in patients with pre-existing CAD were significantly higher than in those without pre-existing CAD (p = 0.017, p < 0.001, p = 0.002, and p < 0.001, respectively). The multivariate Cox proportional hazards model revealed that pre-existing CAD was a significant risk factor for a 5-year all-cause mortality in acute IS patients with high-grade CAS (hazard ratio = 2.26; 95% confidence interval = 1.35–3.79; p = 0.002). Conclusion: Pre-existing CAD was associated with an increased risk of 5-year mortality in acute IS patients with high-grade CAS. Intensive treatment for the pre-existing CAD may reduce long-term mortality in acute IS patients with high-grade CAS.

Seven new cucurbitane-type triterpenoids, kuguaovins A–G (1–7), and five known ones were isolated from the rattans of wild Momordica charantia. Their structures were established by spectroscopic da...

The association between gender and stroke outcome in patients with high-grade internal carotid artery (ICA) stenosis remains unclear. We investigate gender differences in clinical characteristics and outcomes in ischemic stroke patients with high-grade ICA stenosis. Three-hundred and seventy-two acute ischemic stroke patients with high-grade ICA stenosis were enrolled and followed up for 5 years. Demographic features, vascular risk factors, co-morbidities, and outcomes were compared between male and female genders. Two-hundred and seventy-three (73.4%) patients were males and 99 (26.6%) patients were females. The prevalence of diabetes mellitus and atrial fibrillation was higher in females (P = 0.031 and P = 0.043), whereas the prevalence of smoking was higher in males (P 0.001). The 5-year mortality rate was not different between males and females (P = 0.437), whereas the 5-year recurrent stroke rate was significantly higher in males (OR, 2.14; 95% CI, 1.22-3.75; P = 0.004). After adjusting for the established clinical predictors of adverse outcomes, the multivariate Cox regression revealed that male gender is a significant predictor of recurrent ischemic stroke (HR, 1.95; 95% CI, 1.19-3.20; P = 0.008). In conclusion, male gender is associated with increased risk of recurrent ischemic stroke in patients with high-grade ICA stenosis during 5-year follow-up. Further prospective trial to assess whether male gender may benefit from more aggressive vascular risk factors control and treatment strategies for stroke prevention is warranted.

Simple Summary Chemoresistance of bladder cancer has become a major obstacle to clinical treatment, especially in first-line treatments involving gemcitabine (GCB). Epithelial-mesenchymal transition (EMT) is highly correlated with GCB resistance but less correlated with GCB metabolism and less reported as a novel therapeutic strategy. Our findings indicated that EMT-related GCB resistance occurs through the TGF-β/Smad signaling pathways and involves repressed expression of the GCB transporters hCNT1 and hENT1. Ellagic acid (EA) combined with GCB intensified the chemosensitivity of GCB in resistant cells by repressing Smad2, Smad3, and Smad4 expression and rescuing hCNT1 and hENT transcription. These data suggest that EA is a good adjuvant agent for blocking TGF-β/Smad signaling-related GCB resistance in bladder cancer. Abstract Gemcitabine (GCB) resistance is a major issue in bladder cancer chemoresistance, but its underlying mechanism has not been determined. Epithelial-mesenchymal transition (EMT) has been shown to be comprehensively involved in GCB resistance in several other cancer types, but the direct connection between EMT and GCB remains unclear. This study was designed to elucidate the mechanism of EMT-related GCB resistance in bladder cancer and identify a potential phytochemical to modulate drug sensitivity. The biological effects of ellagic acid (EA) or its combined effects with GCB were compared in GCB-resistant cells and the GCB-sensitive line in terms of cell viability, apoptosis, motility, and in vivo tumorigenicity. The molecular regulation of EMT-related GCB resistance was evaluated at both the mRNA and protein expression levels. Our results indicated that TGF-β/Smad induced the overactivation of EMT in GCB-resistant cells and reduced the expression of GCB influx transporters (hCNT1 and hENT1). Moreover, ellagic acid (EA) inhibited the TGF-β signaling pathway both in vitro and in vivo by reducing Smad2, Smad3, and Smad4 expression and thereby resensitized GCB sensitivity. In conclusion, our results demonstrate that TGF-β/Smad-induced EMT contributes to GCB resistance in bladder cancer by reducing GCB influx and also elucidate the novel mechanisms of EA-mediated inhibition of TGF-β/Smad-induced EMT to overcome GCB resistance. Our study warrants further investigation of EA as an effective therapeutic adjuvant agent for overcoming GCB resistance in bladder cancer.

Seven new cucurbitane-type triterpenoids, kuguaovins A–G (1–7), and five known ones were isolated from the rattans of wild Momordica charantia. Their structures were established by spectroscopic data analyses, including 1D and 2D NMR, IR, and MS techniques. The absolute configurations of the cucurbitanes were determined from NOESY data and partially by X-ray crystallographic analysis. In pharmacological studies, compounds 1–7 and 9–12 exhibited weak anti-inflammatory effects (IC(50) = 15–35 μM), based on an anti-NO production assay.

The aim of the study is to investigate the ability of phytochemicals to overcome the multiple drug resistance (MDR) of bladder cancer. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay was used to evaluate the cytotoxic sensitivity of T24‐GCB cells, a GCB resistant cell line, to different phytochemicals, including capsaicin, quercetin, curcumin, and resveratrol, and their combination with gemcitabine. Western blot analysis was used to detect the expression of membranous ABCC2 and metabolic proteins, DCK, TK1, and TK2 in tumor cells. Animal models were used to confirm the treatment efficacy of phytochemicals in combination with gemcitabine to bladder cancer. The observed/expected ratio of cytotoxicity analysis revealed that capsaicin has synergistic effect with gemcitabine to T24‐GCB cells in a dose‐dependent pattern. Quercetin, curcumin, and resveratrol have additive effect with gemcitabine to T24‐GCB cells. Capsaicin and quercetin alone and combination with gemcitabine decreased the expression of ABCC2 and DCK and TKs, in T24‐GCB cells. On the contrary, resveratrol and curcumin alone and combination with gemcitabine increased the expression of ABCC2 but decreased cytoplasmic kinases simultaneously. In xenografted subcutaneous tumor model on nude mice, combination treatment of capsaicin and gemcitabine demonstrated the highest tumor suppression effect when compared to capsaicin or gemcitabine treatment alone. The MDR of bladder cancer is closely related to membranous ABCC2, cytoplasmic DCK, and TKs expression. Capsaicin owns the strongest synergistic cytotoxic effect of gemcitabine to T24‐GCB cells. This combination regimen may provide as an adjunctive treatment for overcoming MDR in bladder cancer.

Guillain-Barré syndrome concomitant with spinal cord involvement, which is defined as Guillain-Barré syndrome and acute transverse myelitis overlap syndrome, is rarely seen in the elders. Here we present a 68-year-old female patient who developed Guillain-Barré syndrome, as well as acute transverse myelitis at the same episode.This patient developed acute weakness of lower limbs, which then rapidly became tetraplegia and hyporeflexia within 5 days. She also had impaired pinprick and vibration sensations below T4, as well as urinary and defecation incontinence. The nerve conduction studies revealed a motorsensory axonal neuropathy. Cerebrospinal fluid analysis showed albuminocytological dissociation and elevated IgG index. The spinal magnetic resonance imaging study revealed heterogeneously contrastenhanced, long-segmental intramedullary lesion from C2 to T3. Other laboratory findings, including blood anti-aquaporin 4 antibody, were not remarkable. The patient's tetraplegia was gradually improved by plasmapheresis and methylprednisolone pulse therapy.Although Guillain-Barré syndrome and acute transverse myelitis overlap syndrome is occasionally seen in young adults, it could still occur in the elderly patients. Plasmapheresis and steroid pulse therapy could be beneficial to improve functional outcome of patients with this immunemediated neurological disease.

Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons. While extracellular Pgk1 (ePgk1) is reported to promote neurite outgrowth, it remains unclear if it can affect the survival of dopaminergic cells. To address this, we employed cerebroventricular microinjection (CVMI) to deliver Pgk1 into the brain of larvae and adult zebrafish treated with methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a PD-like model. The number of dopamine-producing cells in ventral diencephalon clusters of Pgk1-injected, MPTP-treated embryos increased over that of MPTP-treated embryos. Swimming distances of Pgk1-injected, MPTP-treated larvae and adult zebrafish were much longer compared to MPTP-treated samples. The effect of injected Pgk1 on both dopamine-producing cells and locomotion was time- and dose-dependent. Indeed, injected Pgk1 could be detected, located on dopamine neurons. When the glycolytic mutant Pgk1, Pgk1-T378P, was injected into the brain of MPTP-treated zebrafish groups, the protective ability of dopaminergic neurons did not differ from that of normal Pgk1. Therefore, ePgk1 is functionally independent from intracellular Pgk1 serving as an energy supplier. Furthermore, when Pgk1 was added to the culture medium for culturing dopamine-like SH-SY5Y cells, it could reduce the ROS pathway and apoptosis caused by the neurotoxin MPP+. These results show that ePgk1 benefits the survival of dopamine-producing cells and decreases neurotoxin damage.

Phytochemical investigation of the ethanol extract from wild Momordica charantia vines has resulted in isolation of seven cucurbitane-type triterpenoids, including six undescribed compounds, kuguaovins H‒M, and the known compound, momordicoside K. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses, including 1D and 2D NMR, and MS experiments. The chemical structure of momordicoside K was determined for the first time by X-ray crystallographic analysis and its absolute configuration assigned. The cytotoxicity against four human tumor cell lines and anti-inflammatory activities on LPS-stimulated RAW264.7 macrophages were evaluated. Of the isolates, kaguaovin L exhibited potential cytotoxicity against MCF-7, HEp-2, Hep-G2, and WiDr cancer cell lines and showed moderate anti-NO production activity. In addition, kuguaovins H and J also showed the stimulatory effect of GLP-1 secretion on the murine intestinal secretin tumor cell line (STC-1).

The protein level of muscle-specific human NogoA is abnormally upregulated in amyotrophic lateral sclerosis (ALS) mice and patients. On the other hand, while the presence of miR-206 in muscle cells delays onset and death in ALS, the relationship between these two phenomena remains unclear. Mammalian NogoA protein, also known as Reticulon 4a (Rtn4a), plays an important role in inhibiting the outgrowth of motor neurons. Our group previously identified zebrafish rtn4al as the target gene of miR-206 and found that knockdown of miR-206 increases rtn4al mRNA and Rtn4al protein in zebrafish embryos. It can be concluded from these results that neurite outgrowth of motor neurons is inhibited by Rtn4a1, which is entirely consistent with overexpression of either human NogoA or zebrafish homolog Rtn4al. Since an animal model able to express NogoA/rtn4al at the mature stage is unavailable, we generated a zebrafish transgenic line, Tg(Zα:TetON-Rtn4al), which conditionally and specifically overexpresses Rtn4al in the muscle tissue. After doxycycline induction, adult zebrafish displayed denervation at neuromuscular junction during the first week, then muscle disintegration and split myofibers during the third week, and, finally, significant weight loss in the sixth week. These results suggest that this zebrafish transgenic line, representing the inducible overexpression of Rtn4a1 in muscle, may provide an alternative animal model with which to study ALS because it exhibits ALS-like phenotype.

Background Folate receptor (FR) has been recognized as having the capacity to become a biological marker for early diagnosis or prognostication of bladder cancer in previous studies. The aim of this study was to evaluate the expression of FR in bladder cancer, and its potential relevance to clinicopathological characteristics and patient survival. Materials and methods Surgical specimens of cancer tissue were obtained from 78 patients with bladder cancer. The relative expression levels of FR in the bladder cancer tissue were measured by immunohistochemistry stain and graded according to stain intensity. Thereafter, the correlation with clinicopathological parameters and patient survival was analyzed. Results The staining intensity and positivity rate of FR were significantly higher in low grade tumor tissues than in high grade tissues (P = 0.0035 and 0.003). Nevertheless, in the univariate Cox proportional hval. There was no correlation of FR expression or intensity with patient survival was seen (P > 0.01). Conclusion In addition to tumor grade and stage, the expression of FR in bladder cancer is related to cellular differentiation. However, no correlation with patient survival was seen in this limited study.

Additional file 2: Supplementary 4. CARE checklist

Additional file 1: Supplementary 1. Cytokines tested in the cytokine array. Supplementary 2. Serial cytokine arrays of the patient’s plasma. Supplementary 3. Cytokine concentration determined by Luminex Assay

Diabetes mellitus (DM) is a risk factor for atrial fibrillation (AF) and is known to be an important risk factor for death from stroke. The influence of AF on long-term outcomes in patients with ischemic stroke remains controversial. To clarify the exact influence of AF on stroke outcome and exclude the effect from DM, we investigated the influence of AF on the 3-year outcomes of nondiabetic patients with acute first-ever ischemic stroke.Five-hundred seventy-four nondiabetic patients with acute first-ever ischemic stroke were enrolled and had been followed for 3 years. Patients were divided into 2 groups according to whether AF was diagnosed or not. Clinical presentations, risk factors for stroke, laboratory data, comorbidities, and outcomes were recorded.A total of 107 patients (18.6%) had AF. The age was significantly older in patients with AF. Total anterior circulation syndrome occurred more frequently among patients with AF (P .001). The mean length of stay in the acute ward was significantly higher in patients with AF (P .001). Furthermore, dependent functional status following discharge was higher in patients with AF (P .001). Multivariate Cox regression revealed that AF is a significant predictor of 3-year all-cause mortality (hazard ratio = 1.98, 95% confidence interval = 1.07-3.67, P = .022).AF is associated with increased risk of 3-year mortality in nondiabetic patients with acute first-ever ischemic stroke. Careful cardiac evaluation and treatment are essential in patients with AF and stroke.

The influence of pneumonia in acute stroke stage on the clinical presentation and long-term outcomes of patients with acute ischemic stroke is still controversial. We investigate the influence of pneumonia in acute stroke stage on the 3-year outcomes of patients with acute first-ever ischemic stroke. Nine-hundred and thirty-four patients with acute first-ever ischemic stroke were enrolled and had been followed for 3years. Patients were divided into two groups according to whether pneumonia occurred during acute stroke stage or not. Clinical presentations, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded. The result showed that a total of 100 patients (10.7%) had pneumonia in acute stroke stage. The prevalence of older age, atrial fibrillation was significantly higher in patients with pneumonia in acute stroke stage. Total anterior circulation syndrome and posterior circulation syndrome occurred more frequently among patients with pneumonia in acute stroke stage (P

Epithelial-mesenchymal transition (EMT) accompanying loss of E-cadherin is important for invasiveness and metastasis of bladder cancer. MicroRNAs (miRs) had been associated with cancer progression and differentiation in several cancers. Our goal is to find out the specific miR which modulates EMT in bladder cancer. Real-time quantitative polymerase chain reaction was used to measure the miRs expression in urothelial cell carcinoma (UCC) cell lines. MiR or siRNA mimics was used to regulate miR and mRNA level respectively. Migration and scratch assays were used to determine the migratory ability. Zymography assay was used to confirm the metalloproteinase activity. Western blotting was used to elucidate the mechanism which regulated by specific miR. MiR-429 was highly expressed in low grade UCC cell lines. Exogenous mimic of miR-429 treatment dramatically inhibited the migratory ability of T24 cells. MiR-429 downstream target ZEB1 was decreased, E-cadherin was restored, and β-catenin was contrarily decreased by exogenous mimic of miR-429 treatment in T24 cells. Cell invasive ability was also inhibited by exogenous mimic of miR-429 treatment through inactivating the MMP-2 activity in T24 cells. E-cadherin protein expression level was inhibited by E-cadherin siRNA accompanied with increasing cell migratory ability when compared with control group in low grade TSGH8301 cells. MiR-429 decreased the cell migratory and invasive abilities through reducing ZEB1 and β-catenin, restoring the E-cadherin expression and inactivation of MMP-2 of UCC cells. MiR-429 might be used as a progression marker of bladder cancer.

Gemcitabine (GCB), which functions via the inhibition of DNA synthesis, is commonly used in the treatment of bladder cancer; however, its response rate is not satisfactory due to the development of drug resistance. The potential for phytochemicals to reverse drug resistance in bladder cancer tumor cells was evaluated. A human bladder cancer cell line, T24, was cultured, and GCB-resistant cells (T24-GCB) were also established. The acquired resistance of T24-GCB to GCB was measured using an MTT assay. The gene expression of ATP-binding cassette (ABC) transporter protein family members was analyzed using reverse transcription-quantitative PCR analysis, and western blotting was performed to verify ABC family protein, cytoplasmic thymidine kinase (TK) and poly (ADP-ribose) polymerase (PARP) expression on whole cell lysates. Subsequently, resveratrol and curcumin were used to evaluate their modulation potential in decreasing the drug resistance of T24-GCB cells to GCB using MTT and migration assays. T24-GCB cells have increased drug resistance ability, with an 18.75-fold higher ID(50) value compared with native T24 cells (105 vs. 5.6 nM). T24-GCB cells also exhibit increased cross resistance to mitomycin C and paclitaxel. The mRNA expression of ABCC2 in T24-GCB cells increased compared with that in native T24 cells. Via western blot analysis, it was determined that the expression of ABCC2 protein was also increased in T24-GCB cells. Conversely, the expression of ABCB1, ABCG2, deoxycytidine kinase (DCK), TK1 and TK2 decreased. Following curcumin and resveratrol treatment alone or combined with GCB, additive cytotoxic enhancement was observed, and the migratory abilities of T24-GCB cells were significantly decreased. Western blot analysis revealed that ABCC2 protein expression increased, and DCK, TK1 and TK2 expression decreased following co-treatment of T24-GCB cells with GCB + curcumin or resveratrol compared with GCB alone. Of note, there was a marked increase in cleaved-PARP expression in T24-GCB cells treated with a combination of GCB + curcumin or resveratrol. Both curcumin and resveratrol could reverse the drug resistance of T24-GCB cells in an additive pattern though PARP enhancement without changes in ABCC2 and DCK, TK1 and TK2 expression.

Aggressive lipid-lowering treatment reduces the risk of cardiovascular events, but remains controversial in stroke patients. We investigate the influence of total cholesterol level on 5-year outcomes of ischemic stroke patients with high-grade internal carotid artery (ICA) stenosis and poststroke functional dependence.One-hundred and ninety-six acute ischemic stroke patients with high-grade ICA stenosis and modified Rankin Scale score ≥ 3 upon discharge were enrolled and prospectively observed for 5 years. Patients were divided into 2 groups according to total cholesterol level at admission: ≥200 mg/dL or200 mg/dL. Demographic features, vascular risk factors, co-morbidities, and outcomes were compared between the 2 groups.117 (59.7%) patients had higher and 79 (40.3%) patients had lower total cholesterol levels. The prevalence of older age and atrial fibrillation was significantly higher in patients with lower total cholesterol; the prevalence of diabetes mellitus was higher in patients with higher total cholesterol. After adjusting for the established clinical predictors of adverse outcomes, the multivariate Cox regression revealed that lower total cholesterol level is a significant predictor of 5-year mortality (HR (hazard ratio) = 1.88, 95% CI (confidence interval) = 1.09-3.23, P = .023).Lower total cholesterol level is associated with increased risk of 5-year mortality in ischemic stroke patients with high-grade ICA stenosis and post-stroke functional dependence. Aggressive treatment of hyperlipidemia should be carefully considered in these patients although it could reduce the risk of atherosclerotic cardiovascular diseases and stroke recurrence in some stroke patients.

The influence of renal dysfunction on the clinical presentation and outcomes of patients with acute ischemic stroke is still controversial. We investigate the influence of renal dysfunction on the outcomes of patients with acute first-ever ischemic stroke.Nine-hundred thirty-four patients with acute first-ever ischemic stroke were enrolled and followed for 3 years. Renal function was assessed using the equation of the Modification Diet for Renal Disease for estimated glomerular filtration rate (eGFR). Serum creatinine levels were obtained within 3 days of acute stroke onset. Reduced eGFR was defined as eGFR60ml/min/1.73m(2). Clinical presentation, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded.Total 264 patients (28.3%) had a reduced eGFR. The prevalence of older age, hypertension, and atrial fibrillation was significantly higher in patients with a reduced eGFR. Total anterior circulation syndrome occurred more frequently among patients with a reduced eGFR (P=0.010). Multivariate Cox regression revealed that a reduced eGFR is a significant predictor of 3-year mortality (HR=1.67, 95% CI=1.06-2.62, P=0.026).Reduced eGFR during the acute stroke stage is associated with increased risk of 3-year mortality. Furthermore, risk of acute complications and poor functional outcomes following discharge was significantly higher in patients with a reduced eGFR.

A series of tetracyclic heterocyclic azathioxanthones were synthesized and evaluated for cell proliferations, topoisomerase inhibitions, and NCI-60 cell panel assay, respectively. Compounds 5, 7, 8, 16, and 19 were selected for topoisomerase assay after MTT assay. 7 not only showed cytotoxic effect (IC50 = 2.84 ± 0.64 μM) in PC-3 cells but also revealed topoisomerases inhibition with IC50 (10-25 μM) and increased apoptotic cleavage of PARP and caspase 3 activity. The overall of novel azathioxanthones with different cytostatic and cytotoxic activities should be further developed as new potential candidates for anticancer drugs.

Multipotent adult neural precursor cells (NPCs) have tremendous intrinsic potential to repair the damaged spinal cord. However, evidence shows that the regenerative capabilities of endogenous and transplanted NPCs are limited in the microenvironment of spinal cord injury (SCI). We previously demonstrated that injury-induced upregulation of matrix chondroitin sulfate proteoglycans (CSPGs) restricts the survival, migration, integration, and differentiation of NPCs following SCI. CSPGs are long-lasting components of the astroglial scar that are formed around the lesion. Our recent in vivo studies demonstrated that removing CSPGs from the SCI environment enhances the potential of transplanted and endogenous adult NPCs for spinal cord repair; however, the mechanisms by which CSPGs regulate NPCs remain unclear. In this study, using in vitro models recapitulating the extracellular matrix of SCI, we investigated the direct role of CSPGs in modulating the properties of adult spinal cord NPCs. We show that CSPGs significantly decrease NPCs growth, attachment, survival, proliferation, and oligodendrocytes differentiation. Moreover, using genetic models, we show that CSPGs regulate NPCs by signaling on receptor protein tyrosine phosphate sigma (RPTPσ) and leukocyte common antigen-related phosphatase (LAR). Intracellularly, CSPGs inhibitory effects are mediated through Rho/ROCK pathway and inhibition of Akt and Erk1/2 phosphorylation. Downregulation of RPTPσ and LAR and blockade of ROCK in NPCs attenuates the inhibitory effects of CSPGS. Our work provide novel evidence uncovering how upregulation of CSPGs challenges the response of NPCs in their post-SCI niche and identifies new therapeutic targets for enhancing NPC-based therapies for SCI repair. Stem Cells 2015;33:2550–2563

Objectives We aimed to investigate the effect of hypercholesterolemia on recovery after acute ischemic stroke. Methods Data of 3048 patients admitted for acute ischemic stroke from January to December 2009 were collected from the Stroke Registry in the Chang Gung Healthcare System. Baseline characteristics of patients with and without hypercholesterolemia were compared. The association of hypercholesterolemia with neurological severity and recovery was analyzed using multivariate logistic regression. The patients were then divided on the basis of age for subgroup analysis. Results The number of patients with and without a history of hypercholesterolemia was 474 (15.6%) and 2574 (84.4%), respectively. Univariate analysis showed that patients with hypercholesterolemia had a lower National Institutes of Health Stroke Scale (NIHSS) score on admission ( p =0.004). However, during hospitalization, these patients displayed less improvement in their NIHSS score ( p =0.002). These results remained significant in multivariate logistic regression analysis ( p p =0.002, respectively). Subgroup analysis showed a similar association for hypercholesterolemia in both younger (age Conclusions Acute ischemic stroke in patients with hypercholesterolemia was correlated with reduced severity on admission and less favorable recovery during hospitalization, regardless of age.

Recognizing the cause is essential for the management of meralgia paresthetica (MP), also known as lateral femoral cutaneous neuropathy. The aim of this study was to investigate the etiologies of MP and their influence on each other. This retrospective study enrolled referral patients with electromyographic studies who fulfilled the clinical and electrodiagnostic criteria of MP from January 2003 to December 2013. Data including age, gender, body weight, body height, occupation, and relevant medical history were collected. The etiological analysis was based on age and gender. A total of 50 patients (30 males and 20 females) were enrolled. The average age (±standard deviation) at diagnosis was 49.8±12.8years. Risk factors were identified in 29 cases (58.0%). More patients younger than 50years of age were male (73.1%, p=0.049). Peaks of age occurred between 41-50years in men and 51-60years in women. More males had a body mass index≥24kg/m2 (69.2% vs. 31.6%, p=0.012) and ≥27kg/m2 (34.6% vs. 0.0%, p=0.006). Overweight and obese patients were more vulnerable to occupational factors (50.0% vs. 19.0%, p=0.030). Only one case had diabetes mellitus (2%). Male middle-aged patients with a higher body mass index and certain occupations had an increased risk of MP. In contrast to the peak age distribution of the male patients, the frequency of developing MP was relatively even among the women at all ages. The cause was often obscure.

J. Neurochem. (2012) 122, 147–161. Abstract The mechanisms that regulate synapse formation and maintenance are incompletely understood. In particular, relatively few inhibitors of synapse formation have been identified. Receptor protein tyrosine phosphatase σ (RPTPσ), a transmembrane tyrosine phosphatase, is widely expressed by neurons in developing and mature mammalian brain, and functions as a receptor for chondroitin sulfate proteoglycans that inhibits axon regeneration following injury. In this study, we address RPTPσ function in the mature brain. We demonstrate increased axon collateral branching in the hippocampus of RPTPσ null mice during normal aging or following chemically induced seizure, indicating that RPTPσ maintains neural circuitry by inhibiting axonal branching. Previous studies demonstrated a role for pre-synaptic RPTPσ promoting synaptic differentiation during development; however, subcellular fractionation revealed enrichment of RPTPσ in post-synaptic densities. We report that neurons lacking RPTPσ have an increased density of pre-synaptic varicosities in vitro and increased dendritic spine density and length in vivo. RPTPσ knockouts exhibit an increased frequency of miniature excitatory post-synaptic currents, and greater paired-pulse facilitation, consistent with increased synapse density but reduced synaptic efficiency. Furthermore, RPTPσ nulls exhibit reduced long-term potentiation and enhanced novel object recognition memory. We conclude that RPTPσ limits synapse number and regulates synapse structure and function in the mature CNS.