BACKGROUND: Oxidative injury due to increased intracellular peroxides leads to more frequent onset of epileptic seizure, and the consumption of peroxides through oxidation-reduction played an important role in protection of the central nervous system neurons.OBJECTIVE: To analyze the changes of antioxidants in plasma and erythrocyte of patients with epilepsy.DESIGN: Nonrandomized, paralleled, concurrent controlled study.SETTING: Department of laboratory, psychology, and pharmacy in a university hospital.PARTICIPANTS: Totally 32 epileptic patients were diagnosed in the Department of Neurology, Xiangya Second Hospital, Central South University between March and December 2000 according to the diagnostic and classification criteria of International League Against Epilepsy. The patients consisted of 17 male and 15 female subjects aged from 27 to 59 years, all of whom denied previous anti-epileptic drug exposure(epileptic group) . Another 26concurrent epileptic patients, including 16 male and 10 female subjects aged from 24 to 58 years, confirmed according to the same criteria and treated at the Department of Neurology were also recruited in this study, who reported a history of anti-epileptic therapy with phenobarbiturals for more than one year without acute onset of epileptic seizures during this period(treatment group) .Totally 39 normal controls including 23 male and 16 female subjects were enrolled from those receiving routine health examinations with normal physical indexes. Informed consent was obtained from all these participants.METHODS: Fasting venous blood(2 mL) were collected from each subject at 8:00 - 9:00 am. Enzyme-coupled continuous monitoring was employed to determine the activity of erythrocyte glutathione reductase (EGR), glutathione peroxidase ( GSH-Px ), and catalase (CAT). Pyrogallol autoxidation colorimetry was used to determine the activity of erythrocyte superoxide dismutase(SOD) .The level of erythrocyte malonaldehyde(MDA) was examined with improved TBA colorimetry. Meanwhile hemoglobin(HB) concentration and osmotic fragility of incubated erythrocytes(expressed as the hemolytic percentage)were examined. Plasma vitamin A, C, and E were also determined with high-performance liquid chromatography. Plasna ceruloplasmin(CER) was examined with immunodiffusion assay.MAIN OUTCOME MEASURES: The activity of EGR, GSH-Px, SOD,CAT, content of MDA, erythrocyte hemolytic percentage and the levels of CER and vitamin A, C, E.RESULTS: Only one patient failed to complete the treatment. Erythrocyte MDA content, hemolytic percentage, activity of GSH-Px, and CAT, and CER in epileptic group [ ( 176. 5 ± 12.0) μmol/L, (3.32 ± 0.95 )%, ( 1 503.6±130.0) nkat/g, (75.3±14.6) K/g, (487.0±25.4) mg/L] and treatment group[(129.5±7.4) μmol/L, (1.52±0.20)%, (1 323.6± 95.0) nkat/g, (64.2 ± 10. 1) K/g, (345.0 ± 15.2) mg/L] were significantly higher than those in the control group( t = 2.46 -3.89, P ＜ 0.05 ], but the activity of erythrocyte GR and SOD and the content of plasma vitamin A, E,C[(101.7 ± 13.3) nkat/g, (20.2 ±0. 8) μkat/g, (1. 18 ±0. 83) μmol/L,(20.7 ±4. 5) μmol/L, (20. 6 ±3.6) μmol/L, and(213.4 ±45.0) nkat/g,(28.5 ±0. 9) μkat/g, (3. 14 ±0. 30) μmol/L, (40. 5 ±6.6) μmol/L,(38. 1 ±5.1) μmol/L] were significantly lower than those in the control group ( t = 2.46 - 2.97, P ＜ 0. 05). The activity of GR and SOD and plasma vitamin A, C content of normal control group were significantly higher than those in the epileptic group [(161.7±25.0) nkat/g, (26.7±0.9) μkat/g, (2.09±0. 35) μmol/L, (26.2 ±4. 1) μmol/L, t =2.46 -2.66, P ＜0.05].CONCLUSION: The decrement of intracellular GSH-Px and SOD, and plasma levels of vitamin A, C, E, and CER in epileptic patients can be indicative of the activity of the free radicals during the onset of epileptic seizures.

Objective To explore the potential genetic variants related with late-onset Alzheimer's disease(LOAD),and to broaden the AD genetic susceptibility factor profile.Methods We targetedly sequenced four lipids metabolism related genes including apolipoprotein E(APOE),sortilin-related receptor gene (SORL 1),apolipoprotein C-I (APOC1) and clusterin (CLU),validated these candidate variants in patients with LOAD and mild cognitive impairment (MCI)and the controls with normal cognitive function,and made a bioinformatic analysis.Results The mutation in the allele of CLU rs117389184,a low-frequency single nucleotide polymorphism,would increase the risk of LOAD and MCI[OR (95 ％ CI):3.56 (1.08-4.84),P =0.026;OR (95 ％ CI):3.06 (0.98-4.03),P =0.026],suggesting CLU rs117389184 gene variant was associated with cognitive impairment.This variation could affect CLU gene expression by interfering with the binding of transcription factors.Conclusions CLU rs117389184 is a new genetic risk variant for LOAD and MCI.

【Objective】 To analyze the clinical efficacy of 450 nm blue laser vaporization in the treatment of benign prostatic hyperplasia (BPH) and to summarize the preliminary experience. 【Methods】 Clinical data of 30 BPH patients who underwent transurethral 450 nm blue laser vaporization at our hospital during Jun. and Sep. 2023 were selected. The operation time, hemoglobin decrease value, bladder irrigation time, catheterization time, and incidence of complications were recorded. The changes in the international prostate symptom score (IPSS), quality of life score (QoL), postvoid residual (PVR) volume, and maximum urinary flow rate (Qmax) were compared before and 3 months after surgery. 【Results】 All operations were successfully completed without conversion to transurethral resection of the prostate (TURP) or open surgery. The operation time was (38.2±7.5) minutes, the hemoglobin decrease value was (10.4±3.5) g/L 24 hours after surgery, the bladder irrigation time was (15.1±3.3) hours, and the catheterization time was (4.5±0.5) days. Compared to preoperative, 3 months after surgery, the IPSS \[(26.28±2.22) vs. (6.29±2.10)\], QoL \[(5.25±0.85) vs. (2.33±0.95)\], and PVR were decreased \[(397.89±8.47) mL vs. (15.62±2.17) mL\], while the Qmax was increased \[(8.15±2.09) mL/s vs. (19.50±2.51) mL/s\], with statistical significance (P<0.05). Mild bladder mucosal injury occurred in 2 cases (6.6%) during surgery, a second indwelling catheter was placed in 1 case (3.3%) after surgery, and gross hematuria occurred in 1 case (3.3%) after surgery. No serious complications occurred. 【Conclusion】 The use of 450 nm blue laser vaporization for the treatment of BPH has advantages of fast, efficient and reliable hemostasis, and low incidence of complications, which can effectively improve urination and is worthy of clinical promotion and application.

Fungal genomes carry many gene clusters seemingly capable of natural products biosynthesis, yet most clusters remain cryptic or down-regulated. Genome mining revealed an unconventional paraherquonin-like meroterpenoid biosynthetic gene cluster in the chromosome of . The cryptic or down-regulated pathway was activated by constitutive expression of pathway-specific regulator gene encoded within biosynthetic gene cluster. Chemical analysis of mutant -OE: extracts enabled the isolation of four berkeleyacetal congeners, in which two of them are new. On the basis of careful bioinformatic analysis of the coding enzymes in the gene cluster, the biosynthetic pathway of berkeleyacetals was proposed. These results indicate that this approach would be valuable for discovery of novel natural products and will accelerate the exploitation of prodigious natural products in filamentous fungi.

Epigenetic modifications have been proved to be a powerful way to activate silent gene clusters and lead to diverse secondary metabolites in fungi. Previously, inactivation of a histone H3 deacetylase in had led to pleiotropic activation and overexpression of more than 75% of the biosynthetic genes and isolation of ten compounds. Further investigation of the crude extract of strain resulted in the isolation of twelve new diterpenoids including three cassanes (-), one cleistanthane (), six pimaranes (-), and two isopimaranes ( and ) along with two know cleistanthane analogues. Their structures were elucidated by extensive NMR spectroscopic data analysis. Compounds and showed potent inhibitory effects on the expression of MMP1 and MMP2 (matrix metalloproteinases family) in human breast cancer (MCF-7) cells.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic cardiac muscle disease that accounts for approximately 30% sudden cardiac death in young adults. The Ser358Leu mutation of transmembrane protein 43 (TMEM43) was commonly identified in the patients of highly lethal and fully penetrant ARVD subtype, ARVD5. Here, we generated TMEM43 S358L mouse to explore the underlying mechanism. This mouse strain showed the classic pathologies of ARVD patients, including structural abnormalities and cardiac fibrofatty. TMEM43 S358L mutation led to hyper-activated nuclear factor κB (NF-κB) activation in heart tissues and primary cardiomyocyte cells. Importantly, this hyper activation of NF-κB directly drove the expression of pro-fibrotic gene, transforming growth factor beta (TGFβ1), and enhanced downstream signal, indicating that TMEM43 S358L mutation up-regulates NF-κB-TGFβ signal cascade during ARVD cardiac fibrosis. Our study partially reveals the regulatory mechanism of ARVD development.

Endophytic fungi are promising producers of bioactive small molecules. Bioinformatic analysis of the genome of an endophytic fungus

Investigation on how nature produces natural compounds with chemical and biological diversity at the genetic level offers inspiration for the discovery of new natural products and even their biological targets. The polyketide rumbrin ( 1) is a lipid peroxide production and calcium accumulation inhibitor, which contains a chlorinated pyrrole moiety that is a rare chemical feature in fungal natural products. Here, we identify the biosynthetic gene cluster (BGC) rum of 1 and its isomer 12E-rumbrin ( 2) from Auxarthron umbrinum DSM3193, and elucidate their biosynthetic pathway based on heterologous expression, chemical complementation, and isotopic labeling. We show that rumbrins are assembled by a highly reducing polyketide synthase (HRPKS) that uniquely incorporates a proline-derived pyrrolyl-CoA starer unit, and followed by methylation and chlorination. Sequent precursor-directed biosynthesis was able to yield a group of rumbrin analogues. Remarkably, inspired by the presence of a human immunodeficiency virus (HIV)-Nef-associated gene in the rum cluster, we predicted and pharmacologically demonstrated rumbrins as potent inhibitors of HIV at the nanomolar level. This work enriches the recognition of unconventional starter units of fungal PKSs and provides a new strategy for genome mining-guided drug discovery.