CREBB repression of protein synthesis in mushroom body gates long-term memory formation in Drosophila.

Learned experiences are not necessarily consolidated into long-term memory (LTM) unless they are periodic and meaningful. LTM depends on de novo protein synthesis mediated by cyclic AMP response element-binding protein (CREB) activity. In Drosophila, two creb genes (crebA, crebB) and multiple CREB isoforms have reported influences on aversive olfactory LTM in response to multiple cycles of spaced conditioning. How CREB isoforms regulate LTM effector genes in various neural elements of the memory circuit is unclear, especially in the mushroom body (MB), a prominent associative center in the fly brain that has been shown to participate in LTM formation. Here, we report that i) spaced training induces crebB expression in MB α-lobe neurons and ii) elevating specific CREBB isoform levels in the early α/ß subpopulation of MB neurons enhances LTM formation. By contrast, learning from weak training iii) induces 5-HT1A serotonin receptor synthesis, iv) activates 5-HT1A in early α/ß neurons, and v) inhibits LTM formation. vi) LTM is enhanced when this inhibitory effect is relieved by down-regulating 5-HT1A or overexpressing CREBB. Our findings show that spaced training-induced CREBB antagonizes learning-induced 5-HT1A in early α/ß MB neurons to modulate LTM consolidation.

Lipid parameters, adipose tissue distribution and prognosis prediction in chronic kidney Disease patients.

BACKGROUND: Lipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis. PURPOSE: Explore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3-5. METHODS: This is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3-5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness.. RESULTS: 255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis.. CONCLUSION: Comprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3-5.

Regulation of Autophagy Signaling Pathways by Ginseng Saponins: A Review.

Ginseng saponins ( ginsenosides), bioactive compounds derived from ginseng, are widely used natural products with potent therapeutic properties in the management of various ailments, particularly tumors, cardiovascular and cerebrovascular diseases, and immune system disorders. Autophagy, a highly regulated and multistep process involving the breakdown of impaired organelles and macromolecules by autophagolysosomes and autophagy-related genes (ATGs), has gained increasing attention as a potential target for ginsenoside-mediated disease treatment. This review aims to provide a comprehensive overview of recent research advances in the understanding of autophagy-related signaling pathways and the role of ginsenoside-mediated autophagy regulation. By delving into the intricate autophagy signaling pathways underpinning the pharmacological properties of ginsenosides, we highlight their therapeutic potential in addressing various conditions. Our findings serve as a comprehensive reference for further investigation into the medicinal properties of ginseng or ginseng-related products.

Ultra-processed food consumption and the risk of incident chronic kidney disease: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Recent individual studies have indicated that ultra-processed food (UPF) consumption may be associated with the incidence of chronic kidney disease (CKD). We conducted a systematic review and meta-analysis based on those longitudinal studies evaluating the relationship between UPF consumption and the risk of incident CKD, and synthesizing the results. METHOD: PubMed, Embase, The Cochrane Library, Web of Science, and Scopus were searched from inception through 22 March 2023. Any longitudinal studies evaluating the relationship between UPF consumption and the risk of incident CKD were included. Two researchers independently conducted the literature screening and data extraction. RR and its 95% CI were regarded as the effect size. The Newcastle-Ottawa Scale (NOS) was applied to assess the quality of the studies included, and the effect of UPF consumption on the risk of incident CKD was analyzed with STATA version 15.1. This study's protocol was registered in PROSPERO (CRD42023411951). RESULTS: Four cohort studies with a total of 219,132 participants were included after screening. The results of the meta-analysis suggested that the highest UPF intake was associated with an increased risk of incident CKD (RR = 1.25; 95% CI: 1.18-1.33). CONCLUSIONS: High-dose UPF intake was associated with an increased risk of incident CKD. However, the underlying mechanisms remain unknown. Thus, more standardized clinical studies and further exploration of the mechanisms are needed in the future.

Parents' willingness to vaccinate themselves and their children with the booster vaccine against SARS-CoV-2: A cross-sectional study in Puyang city, China.

We aimed to investigate the hesitancy and willingness of parents to vaccinate themselves and their children with a booster dose against severe acute respiratory syndrome coronavirus 2 and related factors. We conducted a cross-sectional study in Puyang city, China. The information was collected, including demographic characteristics, willingness to receive a booster dose of coronavirus disease 2019 (COVID-19) vaccine, and attitudes and concerns toward COVID-19 and vaccines. Vaccine hesitancy was assessed in individuals completing the first two doses and booster eligible, while vaccine willingness was assessed in those completing the first two doses and not yet booster eligible. Among the participants completing two primary doses while not meeting the booster criteria, 95.4% (1465/1536) and 95.0% (1385/1458) had a willingness to a booster dose of COVID-19 vaccine for themselves and their children, respectively. Among the participants who met the booster criteria, 40.3% had vaccine hesitancy. Vaccine hesitancy and unwillingness tended to occur in people who were younger, less educated, less healthy, and with unsureness of vaccines' efficacy and adverse events (AE). The younger age of children, children in poorer health, and concern about the efficacy and AE of vaccines contributed to the participants' unwillingness to vaccinate their children. We observed a high willingness to the booster dose of COVID-19 vaccine both for the parents and their children, regardless of the eligibility to a booster dose. However, 40% of people had delayed vaccination behaviors. The promotion of scientific knowledge of vaccines' effectiveness and safety is needed, especially for people in poor health and parents with young children. Timely disclosure of AE caused by COVID-19 vaccines and proper aiding offered to people encountering AE are suggested.

Impact of influenza virus infection on lung microbiome in adults with severe pneumonia.

BACKGROUND: Bacterial and viral infections are commonly implicated in the development of pneumonia. We aimed to compare the diversity and composition of lung bacteria among severe pneumonia patients who were influenza virus positive (IFVP) and influenza virus negative (IFVN). METHODS: Bronchoalveolar lavage fluid specimens were procured from patients diagnosed with severe pneumonia to investigate the microbiome utilizing 16S-rDNA sequencing. The alpha diversity of the microbiome was evaluated employing Chao1, Shannon, and Simpson indexes, while the beta diversity was assessed using principal component analysis and principal coordinate analysis. Linear discriminant analysis effect size (LEfSe) was employed to determine the taxonomic differences between the IFVP and IFVN groups. RESULTS: A total of 84 patients with 42 in the IFVP group and 42 in the IFVN group were enrolled. Slightly higher indexes of Shannon and Simpson were observed in the IFVP group without statistically significant difference. The dominant bacterial genera were Streptococcus, Klebsiella, Escherichia-Shigella in the IFVN group and Acinetobacter, Streptococcus, Staphylococcus in the IFVP group. Streptococcus pneumoniae and Acinetobacter baumannii were the most abundant species in the IFVN and IFVP groups, respectively. LEfSe analysis indicated a greater abundance of Klebsiella in the IFVN group. CONCLUSIONS: Individuals with severe pneumonia infected with IFV exhibit heightened susceptibility to certain bacteria, especially Acinetobacter baumannii, and the underlying mechanism of the interaction between IFV and Acinetobacter baumannii in the progression of pneumonia needs further investigation.

PIP3 depletion rescues myoblast fusion defects in human rhabdomyosarcoma cells.

Myoblast fusion is required for myotube formation during myogenesis, and defects in myoblast differentiation and fusion have been implicated in a number of diseases, including human rhabdomyosarcoma. Although transcriptional regulation of the myogenic program has been studied extensively, the mechanisms controlling myoblast fusion remain largely unknown. This study identified and characterized the dynamics of a distinct class of blebs, termed bubbling blebs, which are smaller than those that participate in migration. The formation of these bubbling blebs occurred during differentiation and decreased alongside a decline in phosphatidylinositol-(3,4,5)-trisphosphate (PIP3) at the plasma membrane before myoblast fusion. In a human rhabdomyosarcoma-derived (RD) cell line that exhibits strong blebbing dynamics and myoblast fusion defects, PIP3 was constitutively abundant on the membrane during myogenesis. Targeting phosphatase and tensin homolog (PTEN) to the plasma membrane reduced PIP3 levels, inhibited bubbling blebs and rescued myoblast fusion defects in RD cells. These findings highlight the differential distribution and crucial role of PIP3 during myoblast fusion and reveal a novel mechanism underlying myogenesis defects in human rhabdomyosarcoma.

Epidemiological characteristics of hand, foot, and mouth disease clusters during 2016-2020 in Beijing, China.

Hand, foot, and mouth disease (HFMD) is an infectious disease that usually occurs in children under 5 years and is caused by a group of enteroviruses. This study aimed to investigate the epidemiological characteristics of HFMD clusters from 2016 to 2020 in Tongzhou, Beijing, and explored the genetic evolution of CV-A6. The HFMD case information came from the Information System of China Center for Disease Control and Prevention (CDC), as well as the clusters information verification and on-site investigation by Tongzhou CDC. ARIMA model was applied to forecast HFMD clusters in 2020. Totally 440 HFMD clusters were reported during 2016-2020. The large peak of the clusters occurred in April-July, followed by a smaller peak in October-November during 2016-2019. However, in 2020, the two peaks disappeared. The main site of HFMD clusters was childcare facilities (65.0%) and mostly occurred in urban areas (46.1%). The detection rate of CV-A6 was the highest (36.1%), and cases with CV-A6 infection had the highest proportion of fever. The phylogenetic analysis based on CV-A6 VP1 gene showed that the predominant strains mainly located in Group F during 2016-2017, while changed into Group A during 2018-2020. HFMD clusters presented seasonality, mainly located in childcare facilities and urban areas, and CV-A6 was the major causative agent. Targeted prevention and control measures should be taken to reduce HFMD clusters.

Change in willingness to COVID-19 vaccination in China: Two online surveys during the pandemic.

OBJECTIVE: As the variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, periodic vaccine booster immunization may become a normal policy. This study investigated the changes and factors associated with vaccination intentions in various epidemic situations, which can provide suggestions for the construction and modification of routine vaccination program strategies. METHODS: Two cross-sectional online surveys were conducted in January and June of 2021. The willingness and confidence of the coronavirus disease 2019 (COVID-19) vaccination were measured following propensity score matching (PSM) treatment. The difference in the willingness for COVID-19 Vaccination in the two surveys was analyzed by single or multi-factor analyses. RESULTS: The willingness to accept the SARS-CoV-2 vaccine was higher in the second survey than that in the first survey (90.5% vs. 66.6%, p < 0.001). Concerns about the vaccine's safety declined (71.0% vs. 47.6%, p < 0.001), but concerns about the efficacy increased (22.4% vs. 30.9%, p < 0.001). Confidence in the SARS-CoV-2 vaccine had an important impact on the increased uptake willingness (odds ratio = 3.19, 95% confidence interval: 2.23-4.58, p < 0.001). CONCLUSIONS: There has been a significant increase in attitudes towards the SARS-CoV-2 vaccine which was associated with higher vaccine confidence. Vaccine effectiveness received more concerns from respondents rather than safety after nearly 6 months' utilization of the SARS-CoV-2 vaccine. It indicates that aggressive communication and timely disclosure of vaccine data can build vaccine confidence.

Ketamine promotes breast tumor growth in a mouse breast tumor model involving with high expression of miR-27b-3p and EGFR.

Non-medical use of ketamine as an adulterant to ecstasy is more prevalent than amphetamine in Taiwan. Ketamine's effect on immunosuppression might play some functional role in tumor growth, while it is still controversial whether ketamine abuse could increase tumor growth or not. This study aimed to investigate the influence of ketamine addiction in breast tumors and related gene expressions. The effect of ketamine treatment on proliferation, colony formation, migration, and invasion of triple-negative breast cancer cell line EO771 was examined. In addition, a ketamine addiction mice model was established by intraperitoneal injection (IP) of ketamine in mice and used to investigate the effects of ketamine addiction on tumor growth and the possible mechanisms. In the in vitro studies, ketamine treatment at different concentrations did not affect EO771 cell proliferation and colony formation. But ketamine did enhance migration and invasion of EO771 cells. The in vivo experiments showed significantly increased breast tumor volume and weight in ketamine-addicted mice than in normal saline groups. miR-27b-3p level, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR) significantly increased in tumors of ketamine addiction mice compared to control mice. In vivo evidence showed that Ketamine might increase tumor growth on the tumor microenvironment, and miR-27b-3p, HER2, and EGFR might play a role in the process.

A review and meta-analysis of the epidemiology and clinical presentation of coxsackievirus A6 causing hand-foot-mouth disease in China and global implications.

Coxsackievirus A6 (CV-A6) has been associated with increasingly occurred sporadic hand-foot-mouth disease (HFMD) cases and outbreak events in many countries. In order to understand epidemiological characteristics of CV-A6, we collected the information describing HFMD caused by CV-A6 to describe the detection rate, severe rate and onychomadesis rate, which is defined as one or more nails defluvium, caused by CV-A6 from 2007 to 2017. The results showed that there was an outbreak of CV-A6 every other year, and overall trend of the epidemic of CA6-associated HFMD was increasing in China. The detection rate of CV-A6 in other countries was 32.0% (95% CI: 25.0%~40.0%) before 2013 and 28.0% (95% CI: 20.0%~36.0%) after 2013, respectively. Although the severe rate of HFMD caused by CV-A6 was low (0.10%, 95% CI: 0.01%~0.20%), CV-A6 can cause a high incidence of onychomadesis (28.0%, 95%CI: 21.9%-34.3%). Thus, it would be worthwhile to research and develop an effective multivalent vaccine for CV-A6 to achieve a more powerful prevention of HMFD.

Differential inhibitory effects of resveratrol on excitotoxicity and synaptic plasticity: involvement of NMDA receptor subtypes.

Objectives: The neuroprotective effects of resveratrol against excitatory neurotoxicity have been associated with N-methyl-D-aspartate receptor (NMDAR) inhibition. This study examined the differential inhibitory effects of resveratrol on NMDAR-mediated responses in neuronal cells with different NMDAR subtype composition.Methods: The effects of resveratrol on NMDA-induced cell death and calcium influx in immature and mature rat primary cortical neurons were determined and compared. Moreover, the potencies and efficacies of resveratrol to inhibit NR1/NR2A, NR1/NR2B, NR1/NR2C, and NR1/NR2D NMDAR expressed in HEK 293 cells were evaluated.Results: Resveratrol significantly attenuated NMDA-induced cell death in mature neurons, but not in immature neurons. Resveratrol also concentration-dependently reduced NMDA-induced calcium influx among all NMDAR subtypes, but displayed NR2 subunit selectivity, with a potency rank order of NR2B = NR2D > NR2A = NR2C and an efficacy rank order of NR2B = NR2C > NR2A = NR2D. Data show the stronger inhibitory effects of resveratrol on NR1/NR2B than other subtypes. Moreover, resveratrol did not affect hippocampal long-term potentiation (LTP), but impaired long-term depression (LTD).Discussion: These findings reveal the specific NMDAR modulating profile of resveratrol, providing further insight into potential mechanisms underlying the protective effects of resveratrol on neurological disorders.

Sonogenetic Modulation of Cellular Activities Using an Engineered Auditory-Sensing Protein.

Biomolecules that respond to different external stimuli enable the remote control of genetically modified cells. We report herein a sonogenetic approach that can manipulate target cell activities by focused ultrasound stimulation. This system requires an ultrasound-responsive protein derived from an engineered auditory-sensing protein prestin. Heterologous expression of mouse prestin containing two parallel amino acid substitutions, N7T and N308S, that frequently exist in prestins from echolocating species endowed transfected mammalian cells with the ability to sense ultrasound. An ultrasound pulse of low frequency and low pressure efficiently evoked cellular calcium responses after transfecting with prestin(N7T, N308S). Moreover, pulsed ultrasound can also noninvasively stimulate target neurons expressing prestin(N7T, N308S) in deep regions of mouse brains. Our study delineates how an engineered auditory-sensing protein can cause mammalian cells to sense ultrasound stimulation. Moreover, our sonogenetic tools will serve as new strategies for noninvasive therapy in deep tissues.

Tylophorine-based compounds are therapeutic in rheumatoid arthritis by targeting the caprin-1 ribonucleoprotein complex and inhibiting expression of associated c-Myc and HIF-1α.

Interruption of the Warburg effect - the observation that un-stimulated macrophages reprogram their core metabolism from oxidative phosphorylation toward aerobic glycolysis to become pro-inflammatory M1 macrophages upon stimulation - is an emerging strategy for the treatment of cancer and anti-inflammatory diseases such as rheumatoid arthritis. We studied this process with view to the discovery of novel therapeutics, and found that tylophorine-based compounds targeted a ribonucleoprotein complex containing caprin-1 and mRNAs of c-Myc and HIF-1α in LPS/IFN-γ stimulated Raw264.7 cells, diminished the protein levels of c-Myc and HIF-1α, and consequently downregulated their targeted genes that are associated with the Warburg effect, as well as the pro-inflammatory iNOS and COX2. The tylophorine-based compound DBQ 33b significantly meliorated the severity and incidence of type II collagen-monoclonal antibody-induced rheumatoid arthritis and diminished gene expressions of c-Myc, HIF-1α, iNOS, COX2, TNFα, and IL-17A in vivo. Moreover, pharmacological inhibition of either c-Myc or HIF-1α exhibited similar effects as the tylophorine-based compound DBQ 33b, even though inhibition of c-Myc reversed the induction of iNOS and COX2 in LPS/IFN-γ stimulated Raw264.7 cells to a lesser degree. Therefore, simultaneous inhibition of both c-Myc and HIF-1α is efficacious for anti-inflammation in vitro and in vivo and merits further study.

Discovery of Isoplumbagin as a Novel NQO1 Substrate and Anti-Cancer Quinone.

Isoplumbagin (5-hydroxy-3-methyl-1,4-naphthoquinone), a naturally occurring quinone from Lawsonia inermis and Plumbago europaea, has been reported to have anti-inflammatory and antimicrobial activity. Inflammation has long been implicated in cancer progression. In this study, we examined the anticancer effect of chemically synthesized isoplumbagin. Our results revealed that isoplumbagin treatment suppressed cell viability and invasion of highly invasive oral squamous cell carcinoma (OSCC) OC3-IV2 cells, glioblastoma U87 cells, non-small cell lung carcinoma H1299 cells, prostate cancer PC3 cells, and cervical cancer HeLa cells by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Boyden chamber assays. In vivo studies demonstrate the inhibitory effect of 2 mg/kg isoplumbagin on the growth of orthotopic xenograft tumors derived from OSCC cells. Mechanistically, isoplumbagin exerts its cytotoxic effect through acting as a substrate of reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H] dehydrogenase quinone 1 (NQO1) to generate hydroquinone, which reverses mitochondrial fission phenotype, reduces mitochondrial complex IV activity, and thus compromises mitochondrial function. Collectively, this work reveals an anticancer activity of isoplumbagin mainly through modulating mitochondrial dynamics and function.

Epigenetic Regulation of WNT3A Enhancer during Regeneration of Injured Cortical Neurons.

Traumatic brain injury is known to reprogram the epigenome. Chromatin immunoprecipitation-sequencing of histone H3 lysine 27 acetylation (H3K27ac) and tri-methylation of histone H3 at lysine 4 (H3K4me3) marks was performed to address the transcriptional regulation of candidate regeneration-associated genes. In this study, we identify a novel enhancer region for induced WNT3A transcription during regeneration of injured cortical neurons. We further demonstrated an increased mono-methylation of histone H3 at lysine 4 (H3K4me1) modification at this enhancer concomitant with a topological interaction between sub-regions of this enhancer and with promoter of WNT3A gene. Together, this study reports a novel mechanism for WNT3A gene transcription and reveals a potential therapeutic intervention for neuronal regeneration.

WNT3A Promotes Neuronal Regeneration upon Traumatic Brain Injury.

The treatment of traumatic brain injury (TBI) remains a challenge due to limited knowledge about the mechanisms underlying neuronal regeneration. This current study compared the expression of WNT genes during regeneration of injured cortical neurons. Recombinant WNT3A showed positive effect in promoting neuronal regeneration via in vitro, ex vivo, and in vivo TBI models. Intranasal administration of WNT3A protein to TBI mice increased the number of NeuN+ neurons without affecting GFAP+ glial cells, compared to control mice, as well as retained motor function based on functional behavior analysis. Our findings demonstrated that WNT3A, 8A, 9B, and 10A promote regeneration of injured cortical neurons. Among these WNTs, WNT3A showed the most promising regenerative potential in vivo, ex vivo, and in vitro.

Naked-Eye 3D Display Based on Microlens Array Using Combined Micro-Nano Imprint and UV Offset Printing Methods.

An optical film integrating microlens array (MLAs) and 3D micro-graphics is an important way to achieve the naked-eye 3D display effect. The 3D micro-graphics is traditionally generated by the micro-nano imprint technology based on precision engraving mold, which leads to high production cost and low production efficiency, and thus restricts the rapid response to production tasks and large-scale popularization and application. In this study, a process scheme for large-scale printing of 3D micro-graphics using UV offset printing based on presensitized (PS) plate was proposed, matching with the MLAs fabricated by micro-nano imprint process to achieve naked-eye 3D display effect. We used the laser confocal microscope to systematically measure and analyze the geometric and optical performance of the fabricated MLAs in terms of height, curvature radius, center distance, spacing, focal length, and numerical aperture, and evaluated the influence of the publishing resolution of the PS plate on the display effect of 3D micro-graphics. The printing quality and display effect of 3D micro-graphics were further improved by adjusting process parameters such as printing speed and printing pressure. The results of the current study demonstrate that the combined application of micro-nano imprint technology based on precision mold and UV offset printing technology based on PS plate can achieve an excellent naked-eye 3D display effect in 360° all angles, which is efficient, cost-saving, and highly flexible.

Distinct effects of resveratrol on seizures and hyperexcitability induced by NMDA and 4-aminopyridine.

Objectives: The antiepileptic activity of resveratrol has been revealed in various experimental models of epilepsy. The present study evaluated the effects of resveratrol on the seizures and hyperexcitable neuronal activity associated with activation of N-methyl-d-aspartic acid (NMDA) receptor and inhibition of voltage-gated potassium channels.Methods: The effects of resveratrol on seizure thresholds, excitatory field potentials (EFPs) and action potentials induced by NMDA and 4-aminopyridine (4-AP) were monitored in mice, the mouse cortical slices and rat cortical neurons, respectively.Results: Resveratrol increased the NMDA-induced seizure thresholds and suppressed the frequency of NMDA/glycine-evoked EFPs and action potentials. However, resveratrol lowered the 4-AP-induced thresholds for myoclonic twitch and face and forelimb clonus, yet enhanced the thresholds for running and bouncing clonus and tonic hindlimb extension at the higher dose (50 mg/kg). A similar biphasic response of resveratrol was observed in the frequency of EFPs and action potential firings evoked by 4-AP, with enhancement at lower concentrations, but suppression at higher concentrations.Discussion: These findings suggest that resveratrol might be capable of protecting against the seizure types related to neuronal excitability and progression mediated by NMDA receptor activation, but not suitable for the seizures caused by disturbance of the voltage-dependent potassium channels.

Mitochondrial therapy promotes regeneration of injured hippocampal neurons.

Due to the inhibitory microenvironment and reduced intrinsic growth capacity of neurons, neuronal regeneration of central nervous system remains challenging. Neurons are highly energy demanding and require sufficient mitochondria to support cellular activities. In response to stimuli, mitochondria undergo fusion/fission cycles to adapt to environment. It is thus logical to hypothesize that the plasticity of mitochondrial dynamics is required for neuronal regeneration. In this study, we examined the role of mitochondrial dynamics during regeneration of rat hippocampal neurons. Quantitative analysis showed that injury induced mitochondrial fission. As mitochondrial dysfunction has been implicated in neurodegenerative diseases, we tested the possibility that the mitochondrial therapy may promote neuronal regeneration. Supplying freshly isolated mitochondria to the injured hippocampal neurons not only significantly increased neurite re-growth but also restored membrane potential of injured hippocampal neurons. Together, our findings support the importance of mitochondrial dynamics during regeneration of injured hippocampal neurons and highlight the therapeutic prospect of mitochondria to the injured central nervous system.