Transcriptomic, epigenomic and physiological comparisons reveal key factors for different manganese tolerances in three Chenopodium ambrosioides L. populations.

Chenopodium ambrosioides is a manganese (Mn) hyperaccumulator that can be used for Mn-polluted soil phytoremediation. However, the mechanism of Mn tolerance of C. ambrosioides remains largely unknown. In this study, the key factors for Mn tolerance of C. ambrosioides was investigated from the aspects of DNA methylation pattern, gene expression regulation and physiological function. We found that the two genotypes of C. ambrosioides populations have differentiated tolerance to Mn stress (Mn-tolerant: CS and XC, Mn-sensitive: WH). Although there was no difference in Mn accumulation between two types under excess Mn, the biomass and photosynthetic systems were more severely inhibited in Mn-sensitive type, as well as suffering more serious oxidative damage. More differentially expressed genes (DEGs) were downregulated in the Mn-tolerant type, indicating that the Mn-tolerant type tends to inhibit gene expression to cope with Mn stress. DEGs related to metal transport, antioxidant system, phytohormone and transcription factors contribute to the tolerance of C. ambrosioides to Mn, and account for difference in Mn stress sensitivities between the Mn-sensitive and tolerant types. We also found that DNA methylation variation may help to cope with Mn stress. The global DNA methylation level in C. ambrosioides increased under Mn stress, especially in the Mn-sensitive type. Dozens of methylated loci were significantly associated with the Mn accumulation trait of C. ambrosioides, and some critical DEGs were regulated by DNA methylation. Our study comprehensively demonstrated the Mn tolerance mechanism of C. ambrosioides for the first time, and highlighted the roles of epigenetic modification in C. ambrosioides response to Mn stress. Our findings may contribute to elucidating the adaptation mechanism of hyperaccumulator to the heavy metal toxicity.

Effect of transcranial direct current stimulation over the left dorsolateral prefrontal cortex on the aggressive behavior in methamphetamine addicts.

Aggressive behavior of drug addicts threatens human security and social stability, and Methamphetamine (MA) addicts show especially aggressive behavior. Researches showed that the decreased activity of dorsolateral prefrontal cortex (DLPFC) is closely related to violence and aggression, and continuous transcranial direct current stimulation (tDCS) on DLPFC can increase the activity of this position. So, the purpose of this study was to investigate the effect of tDCS on DLPFC for the aggressive behavior of MA addicts. Ninety MA addicts were recruited and randomly divided into anodal tDCS group, cathode tDCS group and sham tDCS group (current intensity was set as 2 mA, 2 mA and 0 mA, respectively). The tDCS intervention was conducted twice a day for five consecutive days. Taylor Aggression Paradigm (TAP) was used to measure the proactive aggressiveness and reactive aggressiveness of MA addicts at different time points (Pretest, Day 1, and Day 5). At the same time, we also recruited 30 healthy adult males as healthy controls, and measured their aggressiveness through TAP for comparative analysis. The results showed that the aggressiveness of MA addicts was significantly higher than that of healthy controls. The aggressiveness of MA addicts was effectively reduced by the anode intervention of tDCS on the left DLPFC, especially when they were subjected to high-intensity provocation, the 2-way interaction between time and tDCS group was statistically significant (F4,164 = 2.939, P = 0.022, ηp2 = 0.067). This study can provide a reference for how to correct the aggressive behavior of MA addicts.

Ciltacabtagene Autoleucel, an Anti-B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up.

PURPOSE: CARTITUDE-1, a phase Ib/II study evaluating the safety and efficacy of ciltacabtagene autoleucel (cilta-cel) in heavily pretreated patients with relapsed/refractory multiple myeloma, yielded early, deep, and durable responses at 12 months. Here, we present updated results 2 years after last patient in (median follow-up [MFU] approximately 28 months), including analyses of high-risk patient subgroups. METHODS: Eligible patients had relapsed/refractory multiple myeloma, had received ≥ 3 prior lines of therapy or were double refractory to a proteasome inhibitor and immunomodulatory drug and had received prior proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapy. Patients received a single cilta-cel infusion 5-7 days after lymphodepletion. Responses were assessed by an independent review committee. RESULTS: At a MFU of 27.7 months (N = 97), the overall response rate was 97.9% (95% CI, 92.7 to 99.7); 82.5% (95% CI, 73.4 to 89.4) of patients achieved a stringent complete response. Median duration of response was not estimable. Median progression-free survival (PFS) and overall survival (OS) were not reached; 27-month PFS and OS rates were 54.9% (95% CI, 44.0 to 64.6) and 70.4% (95% CI, 60.1 to 78.6), respectively. Overall response rates were high across all subgroups (95.1%-100%). Duration of response, PFS, and/or OS were shorter in patients with high-risk cytogenetics, International Staging System stage III, high tumor burden, or plasmacytomas. The safety profile was manageable with no new cilta-cel-related cytokine release syndrome and one new case of parkinsonism (day 914 after cilta-cel) since the last report. CONCLUSION: At approximately 28 months MFU, patients treated with cilta-cel maintained deep and durable responses, observed in both standard and high-risk subgroups. The risk/benefit profile of cilta-cel remained favorable with longer follow-up.

[Pathological voice detection based on gammatone short time spectral self-similarity].

The acoustic detection method based on machine learning and signal processing is an important method of pathological voice detection and the extraction of voice features is one of the most important. Currently, the features widely used have disadvantage of dependence on the fundamental frequency extraction, being easily affected by noise and high computational complexity. In view of these shortcomings, a new method of pathological voice detection based on multi-band analysis and chaotic analysis is proposed. The gammatone filter bank was used to simulate the human ear auditory characteristics to analyze different frequency bands and obtain the signals in different frequency bands. According to the characteristics that turbulence noise caused by chaos in voice will worsen the spectrum convergence, we applied short time Fourier transform to each frequency band of the voice signal, then the feature gammatone short time spectral self-similarity (GSTS) was extracted, and the chaos degree of each band signal was analyzed to distinguish normal and pathological voice. The experimental results showed that combined with traditional machine learning methods, GSTS reached the accuracy of 99.50% in the pathological voice database of Massachusetts Eye and Ear Infirmary (MEEI) and had an improvement of 3.46% compared with the best existing features. Also, the time of the extraction of GSTS was far less than that of traditional nonlinear features. These results show that GSTS has higher extraction efficiency and better recognition effect than the existing features.

The Counterproductive Effect of Right Anodal/Left Cathodal Transcranial Direct Current Stimulation Over the Dorsolateral Prefrontal Cortex on Impulsivity in Methamphetamine Addicts.

The current study aimed to evaluate the effect of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) on behavioral impulsivity in methamphetamine addicts. Forty-five methamphetamine addicts were recruited and randomly divided into active tDCS and sham tDCS groups to receive a daily tDCS intervention for 5 days, with the intensity set to 2 mA for the active group and 0 mA for the sham group. Anodal and cathodal electrodes were, respectively, placed over the right and left DLPFC. Behavioral impulsivity in methamphetamine addicts was examined by the 2-choice oddball task at 3-time points: before tDCS intervention (baseline), after the first intervention (day 1), and after 5 repeated interventions (day 5). Besides, twenty-four healthy male participants were recruited as the healthy controls who completed a 2-choice oddball task. Analysis of accuracy for the 2-choice oddball task showed that behavioral impulsivity was counterproductively increased in the active group, which was shown by the decreased accuracy for the deviant stimulus. The results suggested that the present protocol may not be optimal and other protocols should be considered for the intervention of methamphetamine addicts in the future.

Meta-analysis of ciltacabtagene autoleucel versus physician's choice therapy for the treatment of patients with relapsed or refractory multiple myeloma.

Objective: In the absence of head-to-head trials, indirect treatment comparisons (ITCs) between ciltacabtagene autoleucel (cilta-cel; in CARTITUDE-1) and treatments used in real-world clinical practice (physician's choice of treatment [PCT]), were previously conducted. We conducted multiple meta-analyses using available ITC data to consolidate the effectiveness of cilta-cel versus PCT for patients with triple-class exposed relapsed or refractory multiple myeloma (RRMM).Methods: Five ITCs were assessed for similarity to ensure robust comparisons using meta-analysis. Effectiveness outcomes were overall survival (OS), progression-free survival (PFS), time to next treatment (TTNT), and overall response rate (ORR). A robust variance estimator was used to account for the use of CARTITUDE-1 in each pairwise ITC. Analyses were conducted in both treated and enrolled populations of CARTITUDE-1.Results: Four ITCs were combined for evaluation of OS. Results were statistically significantly in favor of cilta-cel versus PCT in treated patients (hazard ratio [HR]: 0.24, 95% confidence interval [CI]: 0.22-0.26). Three ITCs were combined for evaluation of PFS and TTNT. Cilta-cel reduced the risk of progression and receiving a subsequent treatment by 80% (HR: 0.20 [95% CI: 0.06, 0.70]) and 83% (HR: 0.17 [95% CI: 0.12, 0.26]), respectively. Three ITCs were combined for evaluation of ORR. Cilta-cel increased the odds of achieving an overall response by 86-times versus PCT in treated patients. Findings were consistent in the enrolled populations and across sensitivity analyses.Conclusions: Evaluating multiple indirect comparisons, cilta-cel demonstrated a significantly superior advantage over PCT, highlighting its effectiveness as a therapy in patients with triple-class exposed RRMM.

Does Childhood Adversity Lead to Drug Addiction in Adulthood? A Study of Serial Mediators Based on Resilience and Depression.

Drug addiction is a common problem worldwide. Research has shown adverse childhood experiences (ACEs) to be an important factor related to drug addiction. However, there are few studies on how ACEs lead to drug addiction and the role of resilience and depression in this process. Thus, the main purposes of the study were to determine the proportion of those with adverse childhood experiences who take drugs in adulthood and how resilience and depression affect this relationship. The results showed that (1) greater severity of ACEs made individuals more likely to take drugs; (2) ACEs were positively correlated with depression, and resilience was negatively correlated with ACEs and depression; and (3) ACEs not only affected drug addiction through resilience or depression alone but also through the combined action of resilience and depression, indicating that depression led to drug addiction while resilience weakened the effect of ACEs on depression and drug addiction. Furthermore, in the serial mediation model, abuse, neglect, and family dysfunction were significant predictors of drug addiction. Our results are encouraging in that they provide guidance in understanding the complex relationships among ACEs, resilience, depression, and drug addiction.

Mutation breeding of Aspergillus niger by atmospheric room temperature plasma to enhance phosphorus solubilization ability.

Background: Phosphorus (P) is abundant in soils, including organic and inorganic forms. Nevertheless, most of P compounds cannot be absorbed and used by plants. Aspergillus niger v. Tiegh is a strain that can efficiently degrade P compounds in soils. Methods: In this study, A. niger xj strain was mutated using Atmospheric Room Temperature Plasma (ARTP) technology and the strains were screened by Mo-Sb Colorimetry with strong P-solubilizing abilities. Results: Compared with the A. niger xj strain, setting the treatment time of mutagenesis to 120 s, four positive mutant strains marked as xj 90-32, xj120-12, xj120-31, and xj180-22 had higher P-solubilizing rates by 50.3%, 57.5%, 55.9%, and 61.4%, respectively. Among them, the xj120-12 is a highly efficient P solubilizing and growth-promoting strain with good application prospects. The growth characteristics such as plant height, root length, and dry and fresh biomass of peanut (Arachis hypogaea L.) increased by 33.5%, 43.8%, 43.4%, and 33.6%, respectively. Besides available P, the chlorophyll and soluble protein contents also vary degrees of increase in the P-solubilizing mutant strains. Conclusions: The results showed that the ARTP mutagenesis technology can improve the P solubilization abilities of the A. niger mutant strains and make the biomass of peanut plants was enhanced of mutant strains.

Effects of Sulcus Vocalis Depth on Phonation in Three-Dimensional Fluid-Structure Interaction Laryngeal Models.

Sulcus vocalis is an indentation parallel to the edge of vocal fold, which may extend into the cover and ligament layer of the vocal fold or deeper. The effects of sulcus vocalis depth d on phonation and the vocal cord vibrations are investigated in this study. The three-dimensional laryngeal models were established for healthy vocal folds (0 mm) and different types of sulcus vocalis with the typical depth of 1 mm, 2 mm, and 3 mm. These models with fluid-structure interaction (FSI) are computed numerically by sequential coupling method, which includes an immersed boundary method (IBM) for modelling the glottal airflow, a finite-element method (FEM) for modelling vocal fold tissue. The results show that a deeper sulcus vocalis in the cover layer decreases the vibrating frequency of vocal folds and expands the prephonatory glottal half-width which increases the phonation threshold pressure. The larger sulcus vocalis depth makes vocal folds difficult to vibrate and phonate. The effects of sulcus vocalis depth suggest that the feature such as phonation threshold pressure could assist in the detection of healthy vocal folds and different types of sulcus vocalis.

[Sunshine environment in different forms of communities in Guiyang, China.] / è´µé˜³å¸‚ä¸åŒå½¢æ€ä½åŒºçš„æ—¥ç §çŽ¯å¢ƒ.

In this study, six different types of residential areas in Guiyang were selected as the research objects, including high-rise high-density, high-rise low-density, middle-rise high-density, middle-rise low-density, low-rise high-density and low-rise low-density. The indices of sunshine compliance rate and the building's sunshine hour ratio were constructed to compare and analyze sunshine environment across those six different residential areas. The factors influencing sunshine environment in different residential areas were studied. The results showed that the average sunshine compliance rates of the six types of residential areas were 36.9%, 61.9%, 20.6%, 69.6%, 26.5% and 45.0%, respectively. The average sunshine compliance rate of low-density residential areas was 2.25 times higher than that of high-density residential areas within the same type, among which the sunshine environment of low-density residential areas was better. The sunshine environment of different types of low-density residential areas was different. The sunshine hours for high-rise low-density and middle-rise low-density forms were concentrated in 5-6 hours, while the building's sunshine hour ratio was 0.24 and 0.32, respectively. The sunshine hours for low-rise low-density forms were mainly 6-7 hours, with a building's sunshine hour ratio of 0.28. Compared with other types of residential areas, the low-rise low-density type of sunlight environment was the best. The plot ratio was significantly positively correlated with the building's sunlight ratio of 0-1 h sunlight hours in the residential area.

Minocycline protects neurons against glial cells-mediated bilirubin neurotoxicity.

Unconjugated bilirubin, the end product of heme catabolism and antioxidant, induced brain damage in human neonates is a well-recognized clinical syndrome. However, the cellular and molecular mechanisms underlying bilirubin neurotoxicity remain unclear. To characterize the sequence of events leading to bilirubin-induced neurotoxicity, we investigated whether bilirubin-induced glial activation was involved in bilirubin neurotoxicity by exposing co-cultured rat glial cells and cerebellar granule neurons (CGN) to bilirubin. We found that bilirubin could markedly induce the expression of TNF-α and iNOS in glial cells, and even at low concentrations, the co-culture of glial cells with neurons significantly enhances neurotoxicity of bilirubin. Pretreatment of the co-cultured cells with minocycline protected CGN from glia-mediated bilirubin neurotoxicity and inhibited overexpression of TNF-α and iNOS in glia. Furthermore, we found that high doses of bilirubin were able to induce glial injury, and minocycline attenuated bilirubin-induced glial cell death. Our data suggest that glial cells play an important role in brain damage caused by bilirubin, and minocycline blocks bilirubin-induced encephalopathy possibly by directly and indirectly inhibiting neuronal death pathways.

Tenuivirus utilizes its glycoprotein as a helper component to overcome insect midgut barriers for its circulative and propagative transmission.

Many persistent transmitted plant viruses, including rice stripe virus (RSV), cause serious damage to crop production worldwide. Although many reports have indicated that a successful insect-mediated virus transmission depends on a proper interaction between the virus and its insect vector, the mechanism(s) controlling this interaction remained poorly understood. In this study, we used RSV and its small brown planthopper (SBPH) vector as a working model to elucidate the molecular mechanisms underlying the entrance of RSV virions into SBPH midgut cells for virus circulative and propagative transmission. We have determined that this non-enveloped tenuivirus uses its non-structural glycoprotein NSvc2 as a helper component to overcome the midgut barrier(s) for RSV replication and transmission. In the absence of this glycoprotein, purified RSV virions were unable to enter SBPH midgut cells. In the RSV-infected cells, this glycoprotein was processed into two mature proteins: an amino-terminal protein (NSvc2-N) and a carboxyl-terminal protein (NSvc2-C). Both NSvc2-N and NSvc2-C interact with RSV virions. Our results showed that the NSvc2-N could bind directly to the surface of midgut lumen via its N-glycosylation sites. Upon recognition, the midgut cells underwent endocytosis followed by compartmentalization of RSV virions and NSvc2 into early and then late endosomes. The NSvc2-C triggered cell membrane fusion via its highly conserved fusion loop motifs under the acidic condition inside the late endosomes, leading to the release of RSV virions from endosomes into cytosol. In summary, our results showed for the first time that a rice tenuivirus utilized its glycoprotein NSvc2 as a helper component to ensure a proper interaction between its virions and SBPH midgut cells for its circulative and propagative transmission.

Olfactory co-receptor Orco stimulated by Rice stripe virus is essential for host seeking behavior in small brown planthopper.

BACKGROUND: Laodelphax striatellus, the small brown planthopper (SBPH), is an economically important pest, besides sucking damage, which transmits rice viruses to cause severe damages to rice. In the process of virus transmission, the host orientation behavior of insect is mainly driven by olfaction. In this context, the molecular basis of olfaction in SBPH is of particular interest. RESULTS: Here, we identified the gene that encodes olfactory receptor co-receptor (Orco) and analyzed its expression profiles in Rice stripe virus (RSV)-infected and RSV-free SBPH. It was found that LstrOrco shared high identity with other Orcos from different order insects. LstrOrco was mainly expressed in the head of SBPH, and its expression was significantly stimulated by RSV-infection. The behavioral bioassay revealed that viruliferous SBPH might have a stronger olfactory and seeking ability for rice than RSV-free insect. After silencing of LstrOrco expression, the olfaction and seeking behavior of nymphs for rice seedlings was significantly inhibited, mainly in the increase of the 'no response' percent and the prolongation of the response time. CONCLUSION: These results suggested that Orco played an important role in olfactory signaling and seeking behavior of SBPH, which provided a basic for future development of olfactory-based agriculture pest management strategies. © 2018 Society of Chemical Industry.

A simple method for obtaining rice black-streaked dwarf virus-infected small brown planthopper nymphs.

Rice black-streaked dwarf virus (RBSDV), an important rice virus, is transmitted by vector small brown planthopper (SBPH) in a persistent manner, but not transovarial transmission. In order to obtain viruliferous SBPH nymphs for relevant research, a simple and reliable method was developed, through allowing SBPH adults laying eggs on RBSDV-infected rice plants. The results showed the hatching nymphs on diseased plants could early acquire virus, and the virus was detected in 2nd-instar nymphs from the spawning method, which was earlier than insect feed on diseased plant. The average viruliferous rate of SBPH from the spawning method was 32.9%, which was not lower than the feeding diseased plant method. The novel method was very easy to operate and time-saving, facilitating the study on the interaction between RBSDV and SBPH nymphs (especially young 2nd-4th instar nymphs), such as, the effect of RBSDV on nymph development, host plant orientation preference of viruliferous nymph, identification of viral interacting protein in nymph, etc.

Bacterial microbiota in small brown planthopper populations with different rice viruses.

The small brown planthopper (SBPH) is an important virus vector, transmitting Rice stripe virus (RSV), and Rice black-streaked dwarf virus (RBSDV). Insect symbionts play an essential role in the insect fitness, however, it is still unclear about their contributions to viral transmission by SBPH. Here, we investigated endosymbiont communities in non-viruliferous, RSV-infected, and RBSDV-infected SBPH populations using Illumina 16S rRNA gene MiSeq sequencing. In total, 281,803 effective sequences of the 16S rRNA gene were generated from different samples. Sequence analysis revealed the percentages of these bacterial groups in different SBPH populations on several taxonomic levels ranging from phyla to genera. The extremely consistent bacterial diversity and abundance indicated that RSV or RBSDV infection did not affect the composition and abundance of symbionts in SBPH. It was notable that Wolbachia was dominant in all populations. The symbiosis between Wolbachia and SBPH might be potentially studied and utilized to control pest SBPH in the future.

Oxaloacetate and adipose stromal cells-conditional medium synergistically protected potassium/serum deprivation-induced neuronal apoptosis.

Adipose stromal cells conditioned media (ASC-CM) protect neurons in a variety of neuronal death models including potassium/serum deprivation-induced neuronal apoptosis. In this study, we found that ASC-CM contained glutamate oxaloacetate transaminase and its substrate, oxaloacetate (OAA) directly protected cerebellar granule neurons (CGN) from apoptosis induced by serum and potassium deprivation. Additionally, OAA inhibited serum and potassium deprivation-induced caspase 3 activation. ASC-CM and OAA in combination had a synergistic neuroprotective effect. Clearly, different from ASC-CM-induced neuroprotection, OAA-induced neuroprotection was Akt- independent but JNK-dependent. These data establish a mechanistic basis supporting that the application of ASC-CM for neuroprotective treatments could be significantly enhanced by addition of OAA.

Building better lithium-sulfur batteries: from LiNO3 to solid oxide catalyst.

Lithium nitrate (LiNO3) is known as an important electrolyte additive in lithium-sulfur (Li-S) batteries. The prevailing understanding is that LiNO3 reacts with metallic lithium anode to form a passivation layer which suppresses redox shuttles of lithium polysulfides, enabling good rechargeability of Li-S batteries. However, this view is seeing more challenges in the recent studies, and above all, the inability of inhibiting polysulfide reduction on Li anode. A closely related issue is the progressive reduction of LiNO3 on Li anode which elevates internal resistance of the cell and compromises its cycling stability. Herein, we systematically investigated the function of LiNO3 in redox-shuttle suppression, and propose the suppression as a result of catalyzed oxidation of polysulfides to sulfur by nitrate anions on or in the proximity of the electrode surface upon cell charging. This hypothesis is supported by both density functional theory calculations and the nitrate anions-suppressed self-discharge rate in Li-S cells. The catalytic mechanism is further validated by the use of ruthenium oxide (RuO2, a good oxygen evolution catalyst) on cathode, which equips the LiNO3-free cell with higher capacity and improved capacity retention over 400 cycles.

Hypoxia-inducible factor-1α mediates the toll-like receptor 4 signaling pathway leading to anti-tumor effects in human hepatocellular carcinoma cells under hypoxic conditions.

Hypoxia-inducible factor-1α (HIF-1α) and toll-like receptor 4 (TLR4) are involved in numerous mechanisms of cancer biology, including cell proliferation and survival; however the interaction of the two factors under hypoxic conditions remains unclear. The present study investigated the in vitro mechanism that results in the suppression of tumor cell growth and cellular functions when HIF-1α is silenced. In the present study, the human hepatocellular carcinoma HepG2 cell line was transfected with short hairpin RNA (shRNA) against HIF-1α and cultured under hypoxic conditions (1% O2 for 24 h). The expression of HIF-1α and various growth factors, including epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2), were examined using quantitative polymerase chain reaction and immunoblotting. Tumor growth was measured using a Cell Counting Kit-8 assay and tumor activity was measured using tumor cell invasion and migration assays. Lipopolysaccharide and TAK-242 were used to activate and inhibit TLR4, respectively, to observe the role of TLR4 in the HIF-1α silenced tumor cells. The expression of TLR4 signaling pathway associates, including myeloid differentiation primary response gene 88 (MyD88), apoptosis signal-regulating kinase 1 (ASK1), p38 mitogen-activated protein kinases and HIF-1α, were analyzed by western blot assay. Under hypoxic conditions, silencing of HIF-1α expression suppressed tumor cell growth and regulated the expression of tumor growth-associated genes, including EGF, HGF, VEGF and FG2. Suppression of tumor cell invasion and migration was also observed in the HIF-1α silenced HepG2 cell line. In addition, TLR4 was identified to be involved in HIF-1α and MyD88 accumulation, and activation of ASK1 and p38 were demonstrated to be critical for TLR4-mediated HIF-1α pathway. In conclusion, silencing of HIF-1α expression may induce anti-tumor effects under hypoxic conditions in HepG2 cells via the TLR4 mediated pathway, suggesting that the HIF-1α/TLR4 signaling cohort may act as a novel therapeutic target for the treatment of hepatocellular cancer.

Metformin prevents cerebellar granule neurons against glutamate-induced neurotoxicity.

Metformin, a wildly used drug for type 2 diabetes, has recently been proven to protect a variety of cells from stress including stroke. Glutamate is an excitatory neurotransmitter that contributes to excitatory neuronal damage involved in stroke and neurodegenerative disorders. In this study, we demonstrated that pretreatment of rat cerebellar granule neurons (CGN) with metformin greatly enhanced cell viability against glutamate-induced neurotoxicity. Metformin significantly attenuated neuronal apoptosis in glutamate-treated CGN by reducing cytochrome c releasing, caspase-3 activation and phosphorylation of MAP kinases. Our results suggested that metformin was able to directly inhibit glutamate induced excitotoxicity in neurons and might be beneficial to patients suffered from stroke and neurodegenerative disorders.