Association of plasma sphingosine-1-phosphate levels with disease severity and prognosis after intracerebral hemorrhage.

Purpose: Sphingosine-1-phosphate (S1P) is a signaling lipid involved in many biological processes, including inflammatory and immune regulatory responses. The study aimed to determine whether admission S1P levels are associated with disease severity and prognosis after spontaneous intracerebral hemorrhage (ICH). Methods: Data of 134 patients with spontaneous ICH and 120 healthy controls were obtained from Biological Resource Sample Database of Intracerebral Hemorrhage at the First Affiliated Hospital of Zhengzhou University. Plasma S1P levels were measured. Regression analyses were used to analyze the association between S1P levels and admission and 90-day modified Rankin scale (mRS) scores. Receiver operating characteristic (ROC) curves assessed the predictive value of S1P levels for ICH severity and prognosis. Results: Patients with ICH exhibited elevated plasma S1P levels compared to the control group (median 286.95 vs. 239.80 ng/mL, p < 0.001). When divided patients into mild-to-moderate and severe groups according to their mRS scores both at admission and discharge, S1P levels were significantly elevated in the severe group compared to the mild-to-moderate group (admission 259.30 vs. 300.54, p < 0.001; 90-day 275.24 vs. 303.25, p < 0.001). The patients were divided into three groups with different concentration gradients, which showed significant statistical differences in admission mRS scores (3 vs. 4 vs. 5, p < 0.001), 90-day mRS scores (2.5 vs. 3 vs. 4, p < 0.001), consciousness disorders (45.5% vs. 68.2% vs. 69.6%, p = 0.033), ICU admission (29.5% vs. 59.1% vs. 89.1%, p < 0.001), surgery (15.9% vs. 47.7% vs. 82.6%, p < 0.001), intraventricular hemorrhages (27.3% vs. 61.4% vs. 65.2%, p < 0.001) and pulmonary infection (25% vs. 47.7% vs. 84.8%, p < 0.001). Multivariate analysis displayed that S1P level was an independent risk factor for disease severity (OR = 1.037, 95% CI = 1.020-1.054, p < 0.001) and prognosis (OR = 1.018, 95% CI = 1.006-1.030, p = 0.003). ROC curves revealed a predictive value of S1P levels with an area under the curve of 0.7952 (95% CI = 0.7144-0.8759, p < 0.001) for disease severity and 0.7105 (95% CI = 0.6227-0.7983, p < 0.001) for prognosis. Conclusion: Higher admission S1P is associated with worse initial disease severity and 90-day functional outcomes in intracerebral hemorrhage.

Repetitive transcranial magnetic stimulation combined with cognitive behavioral therapy treatment in alcohol-dependent patients: A randomized, double-blind sham-controlled multicenter clinical trial.

Background: Alcohol dependence (AD) is a complex addictive disorder with a high relapse rate. Previous studies have shown that both repetitive transcranial magnetic stimulation (rTMS) and cognitive behavioral therapy (CBT) may be effective for AD, and we aim to explore more effective treatment options to reduce relapse rates for AD. Materials and methods: A total of 263 AD patients were recruited. They were divided into six groups according to the location and the type of rTMS: left dorsolateral prefrontal cortex (DLPFC), right DLPFC, sham stimulation, and whether they received CBT treatment: with a fixed schedule (C1) and without a fixed plan (C0). There were included in sham rTMS + C0 group (n = 50), sham rTMS + C1 group (n = 37), right rTMS + C0 group (n = 45), right rTMS + C1 group (n = 42), left rTMS + C0 group (n = 49), left rTMS + C1 group (n = 40). We used obsessive compulsive drinking scale (OCDS), visual analogue scale (VAS), alcohol dependence scale (ADS), montreal cognitive assessment (MoCA), generalized anxiety disorder-7 (GAD-7), patient health questionnaire-9 items (PHQ-9), and Pittsburgh sleep quality index (PSQI) to assess alcohol cravings, alcohol dependence, cognition, anxiety, depression, and sleep quality. They were followed up and evaluated for relapse. Results: The sham rTMS + C0 group relapse rate was significantly higher than the right rTMS + C1 group (P = 0.006), the left rTMS + C0 group (P = 0.031), the left rTMS + C1 group (P = 0.043). The right rTMS + C0 group showed significantly higher relapse rate compared to the right rTMS + C1 group (P = 0.046). There was no significant difference in relapse rates between other groups. The repeated-measures ANOVA showed an interaction effect between group and time was significant in the rate of patient health questionnaire-9 items (PHQ-9) scale reduction (P = 0.020). Logistic analysis indicated that smoking and alcohol consumption were independent determinants of relapse (P < 0.05). At 24 weeks of follow-up, Kaplan-Meier survival analysis reveal that there is statistically significant relapse rate between six groups (P = 0.025), left rTMS + C1 group has the best treatment effect for alcohol dependent patients. Cox regression analysis confirmed that current smoking, total cholesterol, and total bilirubin (TBIL) level were risk factors of relapse (P < 0.05). Conclusion: This study is the first to suggest that the combination of rTMS and CBT may be a potentially effective treatment for reducing relapse.

The altered functional connectivity density related to cognitive impairment in alcoholics.

Alcohol use disorder (AUD) is one of the most common substance use disorders contributing to both behavioral and cognitive impairments in patients with AUD. Recent neuroimaging studies point out that AUD is a typical disorder featured by altered functional connectivity. However, the details about how voxel-wise functional coordination remain unknown. Here, we adopted a newly proposed method named functional connectivity density (FCD) to depict altered voxel-wise functional coordination in AUD. The novel functional imaging technique, FCD, provides a comprehensive analytical method for brain's "scale-free" networks. We applied resting-state functional MRI (rs-fMRI) toward subjects to obtain their FCD, including global FCD (gFCD), local FCD (lFCD), and long-range FCD (lrFCD). Sixty-one patients with AUD and 29 healthy controls (HC) were recruited, and patients with AUD were further divided into alcohol-related cognitive impairment group (ARCI, n = 11) and non-cognitive impairment group (AUD-NCI, n = 50). All subjects were asked to stay stationary during the scan in order to calculate the resting-state gFCD, lFCD, and lrFCD values, and further investigate the abnormal connectivity alterations among AUD-NCI, ARCI, and HC. Compared to HC, both AUD groups exhibited significantly altered gFCD in the left inferior occipital lobe, left calcarine, altered lFCD in right lingual, and altered lrFCD in ventromedial frontal gyrus (VMPFC). It is notable that gFCD of the ARCI group was found to be significantly deviated from AUD-NCI and HC in left medial frontal gyrus, which changes probably contributed by the impairment in cognition. In addition, no significant differences in gFCD were found between ARCI and HC in left parahippocampal, while ARCI and HC were profoundly deviated from AUD-NCI, possibly reflecting a compensation of cognition impairment. Further analysis showed that within patients with AUD, gFCD values in left medial frontal gyrus are negatively correlated with MMSE scores, while lFCD values in left inferior occipital lobe are positively related to ADS scores. In conclusion, patients with AUD exhibited significantly altered functional connectivity patterns mainly in several left hemisphere brain regions, while patients with AUD with or without cognitive impairment also demonstrated intergroup FCD differences which correlated with symptom severity, and patients with AUD cognitive impairment would suffer less severe alcohol dependence. This difference in symptom severity probably served as a compensation for cognitive impairment, suggesting a difference in pathological pathways. These findings assisted future AUD studies by providing insight into possible pathological mechanisms.

TNF-α (G-308A) Polymorphism, Circulating Levels of TNF-α and IGF-1: Risk Factors for Ischemic Stroke-An Updated Meta-Analysis.

Objective: Accumulated studies have explored gene polymorphisms and circulating levels of tumor necrosis factor (TNF)-α and insulin-like growth factor (IGF)-1 in the etiology of ischemic stroke (IS). Of the numerous etiopathological factors for IS, a single-nucleotide polymorphism (SNP) rs1800629 located in the TNF-α gene promoter region and increased levels of TNF-α were found to be associated with IS in different ethnic backgrounds. However, the published results are inconsistent and inconclusive. The primary objective of this meta-analysis was to investigate the concordance between rs1800629 polymorphism and IS. A secondary aim was to explore circulating levels of TNF-α and IGF-1 with IS in different ethnic backgrounds and different sourced specimens. Methods: In this study, we examined whether rs1800629 genetic variant and levels of TNF-α and IGF-1 were related to the etiology of IS by performing a meta-analysis. Relevant case-control studies were retrieved by database searching and systematically selected according to established inclusion criteria. Results: A total of 47 articles were identified that explored the relationship between the rs1800629 polymorphism and levels of TNF-α and IGF-1 with IS risk susceptibility. Statistical analyses revealed a significant association between the rs1800629 polymorphism and levels of TNF-α and IGF-1 with IS pathogenesis. Conclusion: Our findings demonstrated that the TNF-α rs1800629 polymorphism, the increased levels of TNF-α, and decreased levels of IGF-1 were involved in the etiology of IS.

Altered Global Signal Topography in Alcohol Use Disorders.

The most common symptom of patients with alcohol use disorders (AUD) is cognitive impairment that negatively affects abstinence. Presently, there is a lack of indicators for early diagnosis of alcohol-related cognitive impairment (ARCI). We aimed to assess the cognitive deficits in AUD patients with the help of a specific imaging marker for ARCI. Data-driven dynamic and static global signal topography (GST) methods were applied to explore the cross-talks between local and global neuronal activities in the AUD brain. Twenty-six ARCI, 54 AUD without cognitive impairment (AUD-NCI), and gender/age-matched 40 healthy control (HC) subjects were recruited for this study. We found that there was no significant difference with respect to voxel-based morphometry (VBM) and static GST between AUD-NCI and ARCI groups. And in dynamic GST measurements, the AUD-NCI patients had the highest coefficient of variation (CV) at the right insula, followed by ARCI and the HC subjects. In precuneus, the order was reversed. There was no significant correlation between the dynamic GST and behavioral scores or alcohol consumption. These results suggested that dynamic GST might have potential implications in understanding AUD pathogenesis and disease management.

Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis.

Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 µL exosomes via the tail vein (200 µg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1ß release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.

Induced Pluripotent Stem Cells for Ischemic Stroke Treatment.

Ischemic stroke is one of the main central nervous system diseases and is associated with high disability and mortality rates. Recombinant tissue plasminogen activator (rt-PA) and mechanical thrombectomy are the optimal therapies available currently to restore blood flow in patients with stroke; however, their limitations are well recognized. Therefore, new treatments are urgently required to overcome these shortcomings. Recently, stem cell transplantation technology, involving the transplantation of induced pluripotent stem cells (iPSCs), has drawn the interest of neuroscientists and is considered to be a promising alternative for ischemic stroke treatment. iPSCs are a class of cells produced by introducing specific transcription factors into somatic cells, and are similar to embryonic stem cells in biological function. Here, we have reviewed the current applications of stem cells with a focus on iPSC therapy in ischemic stroke, including the neuroprotective mechanisms, development constraints, major challenges to overcome, and clinical prospects. Based on the current state of research, we believe that stem cells, especially iPSCs, will pave the way for future stroke treatment.

Clinical and Radiological Characteristics of Children and Adults With First-Attack Myelin Oligodendrocyte Glycoprotein Antibody Disease and Analysis of Risk Factors for Predicting the Severity at Disease Onset in Central China.

Objective: To analyze and compare different clinical, laboratory, and magnetic resonance imaging characteristics between pediatric and adult patients with first-attack myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and to explore predictive factors for severity at disease onset. Methods: Patients diagnosed with MOGAD at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2021 were enrolled in this retrospective study. Age at disease onset, sex, comorbidities, laboratory tests, magnetic resonance imaging (MRI) characteristics, and Expanded Disability Status Scale (EDSS) scores were collected and analyzed. The association between risk factors and initial EDSS scores at disease onset was analyzed using logistic regression models and Spearman correlation analyses. A receiver-operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of the uric acid and homocysteine (Hcy) levels for the severity of neurological dysfunction at the onset of MOGAD. Results: Sixty-seven patients (female, n=34; male, n=33) with first-attack MOGAD were included in this study. The mean age at onset was 26.43 ± 18.22 years (range: 3-79 years). Among patients <18 years of age, the most common presenting symptoms were loss of vision (36.0%), and nausea and vomiting (24.0%), and the most common disease spectrum was acute disseminated encephalomyelitis (ADEM) (40.0%). Among patients aged ≥18 years, the most common presenting symptoms were loss of vision (35.7%), paresthesia (33.3%), and paralysis (26.2%), and the most common disease spectrum was optic neuritis (35.7%). The most common lesions were cortical gray matter/paracortical white matter lesions in both pediatric and adult patients. Uric acid [odds ratio (OR)=1.014; 95% confidence interval (CI)=1.006-1.022; P=0.000] and serum Hcy (OR=1.125; 95% CI=1.017-1.246; P=0.023) levels were significantly associated with the severity of neurological dysfunction at disease onset. Uric acid levels (r=0.2583; P=0.035) and Hcy levels (r=0.3971; P=0.0009) were positively correlated with initial EDSS scores. The areas under the ROC curve were 0.7775 (95% CI= 0.6617‒0.8933; P<0.001) and 0.6767 (95% CI=0.5433‒0.8102, P=0.014) for uric acid and Hcy levels, respectively. Conclusion: The clinical phenotype of MOGAD varies in patients of different ages. The most common disease spectrum was ADEM in patients aged<18 years, while optic neuritis was commonly found in patients aged ≥18 years. The uric acid and Hcy levels are risk factors for the severity of neurological dysfunction at disease onset in patients with first-attack MOGAD.

Lin28B regulates the fate of grafted mesenchymal stem cells and enhances their protective effects against Alzheimer's disease by upregulating IGF-2.

Mesenchymal stem cells (MSCs) transplantation has emerged as a potential therapeutic approach for Alzheimer's disease (AD). However, the poor proliferation capacity and low survival rate of engrafted MSCs in the hostile microenvironment of AD limit their therapeutic efficiency. Lin28B is a conserved RNA-binding protein associated with cell self-renewal and survival. The purpose of the present study was to explore whether lin28B might influence the functions of implanted MSCs and strengthen their neuroprotective potential in AD. A gain-of-function assay was used to upregulate lin28B expression in MSCs by lentiviral transfection. Our in vitro results indicated that lin28B promoted MSCs proliferation and migration, and protected MSCs against Aß1-42-induced cell death by upregulating insulin-like growth factor-2 (IGF-2). Blockage of IGF-2 partially abrogated the above effects of lin28B. After intracerebroventricular injection into amyloid precursor protein/presenilin 1 mice, implanted MSCs were monitored using bioluminescence imaging. We observed that administration of MSCs transfected with lin28B significantly stimulated their proliferation and prolonged cell retention after delivery. Moreover, administration of the transfected MSCs markedly mitigated cognitive deficits, promoted amyloid plaque clearance, decreased the activation of microglia, and reduced neuronal cell death. The data above confirmed our hypothesis that lin28B is a crucial modulator determining the fate of transplanted MSCs by regulating IGF-2-associated pathways and thereby enhancing their protective effects against AD.

Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier.

Mesenchymal stem cell (MSC) transplantation has been shown to represent a potential treatment for traumatic spinal cord injury (SCI). However, there are several obstacles that need to be overcome before MSCs can be considered for clinical application, such as failure of MSCs to reach the spinal cord lesion core and possible tumor formation. Recent studies have suggested that MSC treatment is beneficial owing to paracrine-secreted factors. Extracellular vesicles are considered to be some of the most valuable paracrine molecules. However, the therapeutic mechanism of extracellular vesicles on spinal cord injury has not been studied clearly. Therefore, our study investigated the effect of systemic administration of extracellular vesicles on the loss of motor function after SCI and examined the potential mechanisms underlying their effects. Disruption of the blood-spinal cord barrier (BSCB) is a crucial factor that can be detrimental to motor function recovery. Pericytes are an important component of the neurovascular unit, and play a pivotal role in maintaining the structural integrity of the BSCB. Our study demonstrated that administration of bone mesenchymal stem cell-derived extracellular vesicles (BMSC-EV) reduced brain cell death, enhanced neuronal survival and regeneration, and improved motor function compared with the administration of BMSC-EV free culture media (EV-free CM). Besides, the BSCB was attenuated and pericyte coverage was significantly decreased in vivo. Furthermore, we found that exosomes reduced pericyte migration via downregulation of NF-κB p65 signaling, with a consequent decrease in the permeability of the BSCB. In summary, we identified that extracellular vesicles treatment suppressed the migration of pericytes and further improved the integrity of the BSCB via NF-κB p65 signaling in pericytes. Our data suggest that extracellular vesicles may serve as a promising treatment strategy for SCI.

Long non-coding RNA XIST regulates miR-106b-5p/P21 axis to suppress tumor progression in renal cell carcinoma.

Long non-coding RNAs (lncRNAs) have been demonstrated to exert important roles in cancer development and progression. The biological function of lncRNA X-inactive specific transcript (XIST) in the development of renal cell carcinoma (RCC) and the underlying mechanisms are still largely unknown. In this study, we found that XIST was down-regulated in RCC tissues and cells. Overexpression of XIST significantly suppressed cell proliferation and induced cell G0/G1 arrest in vitro and inhibited tumor growth in vivo. We further found that XIST could directly interact with miR-106b-5p and increase the expression of P21. Thus, XIST positively regulated the expression of P21 through sponging miR-106b-5p, and played a tumor suppressor role in RCC. Moreover, we found that curcumin could regulate XIST/miR-106b-5p/P21 axis in RCC cells. Our study exhibits the role of XIST as a miRNA sponge in RCC and supports the potential application of XIST in RCC therapy.

Mesenchymal Stem Cell-Derived Exosomes Reduce A1 Astrocytes via Downregulation of Phosphorylated NFκB P65 Subunit in Spinal Cord Injury.

BACKGROUND/AIMS: Neurotoxic A1 astrocytes are induced by inflammation after spinal cord injury (SCI), and the inflammation-related Nuclear Factor Kappa B (NFκB) pathway may be related to A1-astrocyte activation. Mesenchymal stem cell (MSC) transplantation is a promising therapy for SCI, where transplanted MSCs exhibit anti-inflammatory effects by downregulating proinflammatory factors, such as Tumor Necrosis Factor (TNF)-α and NFκB. MSC-exosomes (MSC-exo) reportedly mimic the beneficial effects of MSCs. Therefore, in this study, we investigated whether MSCs and MSC-exo exert inhibitory effects on A1 astrocytes and are beneficial for recovery after SCI. METHODS: The effects of MSC and MSC-exo on SCIinduced A1 astrocytes, and the potential mechanisms were investigated in vitro and in vivo using immunofluorescence and western blot. In addition, we assessed the histopathology, levels of proinflammatory cytokines and locomotor function to verify the effects of MSC and MSC-exo on SCI rats. RESULTS: MSC or MSC-exo co-culture reduced the proportion of SCIinduced A1 astrocytes. Intravenously-injected MSC or MSC-exo after SCI significantly reduced the proportion of A1 astrocytes, the percentage of p65 positive nuclei in astrocytes, and the percentage of TUNEL-positive cells in the ventral horn. Additionally, we observed decreased lesion area and expression of TNFα, Interleukin (IL)-1α and IL-1ß, elevated expression of Myelin Basic Protein (MBP), Synaptophysin (Syn) and Neuronal Nuclei (NeuN), and improved Basso, Beattie & Bresnahan (BBB) scores and inclined-plane-test angle. In vitro assay showed that MSC and MSC-exo reduced SCI-induced A1 astrocytes, probably via inhibiting the nuclear translocation of the NFκB p65. CONCLUSION: MSC and MSC-exo reduce SCI-induced A1 astrocytes, probably via inhibiting nuclear translocation of NFκB p65, and exert antiinflammatory and neuroprotective effects following SCI, with the therapeutic effect of MSCexo comparable with that of MSCs when applied intravenously.

MicroRNA Let-7f-5p Promotes Bone Marrow Mesenchymal Stem Cells Survival by Targeting Caspase-3 in Alzheimer Disease Model.

Widespread death of transplanted mesenchymal stem cells (MSCs) hampers the development of stem cell therapy for Alzheimer disease (AD). Cell pre-conditioning might help cope with this challenge. We tested whether let-7f-5p-modified MSCs could prolong the survival of MSCs after transplantation. When exposed to Aß25-35in vitro, MSCs showed significant early apoptosis with decrease in the let-7f-5p levels and increased caspase-3 expression. Upregulating microRNA let-7f-5p in MSCs alleviated Aß25-35-induced apoptosis by decreasing the caspase-3 levels. After computerized analysis and the luciferase reporter assay, we identified that caspases-3 was the target gene of let-7f-5p. In vivo, hematoxylin and eosin staining confirmed the success of MSCs transplantation into the lateral ventricles, and the let-7f-5p upregulation group showed the lowest apoptotic rate of MSCs detected by TUNEL immunohistochemistry analysis and immunofluorescence. Similarly, bioluminescent imaging showed that let-7f-5p upregulation moderately prolonged the retention of MSCs in brain. In summary, we identified the anti-apoptotic role of let-7f-5p in Aß25-35-induced cytotoxicity, as well as the protective effect of let-7f-5p on survival of grafted MSCs by targeting caspase-3 in AD models. These findings show a promising approach of microRNA-modified MSCs transplantation as a therapy for neurodegenerative diseases.

Synthesis, crystal structures, photoluminescence properties and DNA binding of triazine-nickel(II) complexes for DNA detection.

We report here the synthesis of three new nickel(II) complexes: [Ni(PzTA)2CO3]·5H2O (PzTA=2,4-diamino-6-(2'-pyrazin)-1,3,5-triazine) in 1, [NiQ(PyTA)(H2O)2]Cl·H2O (HQ=8-hydroxyquinoline, PyTA=2,4-diamino-6-(2'-pyridyl)-1,3,5-triazine) in 2, [NiQ(PzTA)(H2O)2]Cl·H2O in 3, and they were characterized by UV spectroscopy, elemental analysis, molar conductivity and X-ray single crystal diffraction. Binding of the complexes to ct-DNA was investigated with electronic spectroscopy, ethidium bromide displacement from DNA, viscometry and cyclic voltammetry. The results depicted the DNA binding mode of the three complexes was intercalation, and complex 1 together with external static-electricity. Moreover, the three complexes also presented potential anti-oxidant activity. Interestingly, we found 1 was sensitive to oxygen and to the polarity of nonaqueous solvents in fluorescence spectroscopy. Fluorescence of 2 and 3 is weak in neutral aqueous solvents, but is greatly enhanced by addition of ct-DNA. Thus, 2 and 3 can be used to DNA detection as DNA fluorescence probes with a LOD of 1.61 ng mL(-1), 4.90 ng mL(-1) for the relative wide linear range of 0.01-20 µg mL(-1), 0.02-30 µg mL(-1), respectively. These findings indicate that 1 may be a potential optical probe for oxygen-free environments in nonaqueous form, while 2 and 3 were DNA-targeted probes.

Role of autophagy and mTOR signaling in neural differentiation of bone marrow mesenchymal stem cells.

Autophagy is involved in cell differentiation. We present evidence that autophagy is activated during ß-mercaptoethanol (ß-ME)-induced neuronal differentiation of bone marrow mesenchymal stem cells (MSCs), in which mammalian target of rapamycin (mTOR) signaling is important. mTOR activity declined after being transported from the nucleus to the cytoplasm. Using 3-methyladenine (3-MA) and rapamycin to regulate the activity of mTOR, it was found that the efficiency of neuronal differentiation was affected.

MicroRNA-9 regulates neural apoptosis in methylmalonic acidemia via targeting BCL2L11.

Methylmalonic acidemia (MMA) is an autosomal-recessive inborn metabolic disorder that results from a deficiency in methylmalonyl-coenzyme A mutase or its cofactor, adenosylcobalamin. Currently, neurological manifestations in MMA are thought to be associated with neural apoptosis. BCL2L11, which is a proapoptotic Bcl-2 family member, is resident in the outer mitochondrial membrane, where this protein acts as a central regulator of the intrinsic apoptotic cascade and mediates excitotoxic apoptosis. MicroRNAs (miRNAs) are a class of non-coding RNAs that function as endogenous triggers of the RNA interference pathway. Currently, little is known regarding the role of miRNA in MMA. In our previous study, we preliminarily found that the expression of miR-9 was significantly down-regulated in MMA patient plasma and sensitively changed after VitB12 treatment, which may act as a potential "competitor" of gas chromatography-mass spectrometry for the diagnosis of MMA. In the present study, we first confirmed that miR-9 inhibited BCL2L11 expression by directly targeting its 3'-untranslated region, and the up-regulation of miR-9 reduced neural apoptosis induced by methylmalonate via targeting BCL2L11. Taken together, our results suggested that miR-9 might act as a monitor of changes in MMA and might provide new insights into a therapeutic entry point for treating MMA.