Brain-derived neurotrophic factor as a biomarker for obsessive-compulsive disorder: A meta-analysis.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a growth factor that plays many critical functions in the central nervous system (CNS) and may be involved in the development of a range of psychopathologies, including depression, dementia, and neurodegenerative disorders. METHODS: In the present study, we performed the first systematic review with a meta-analysis to quantitatively compare the peripheral blood BDNF levels between patients with obsessive-compulsive disorder (OCD) and healthy controls (HCs). A systematic search was conducted using PubMed and Web of Science databases to identify the relevant articles. RESULTS: Nine studies encompassing 474 adults with OCD and 436 HCs were included in this meta-analysis. A random-effects meta-analysis showed that patients with OCD had significantly decreased peripheral blood levels of Brain-derived neurotrophic factor (BDNF) when compared with the HCs (Hedges' g = -0.722, 95% confidence interval [CI] = -1.152 to -0.292, P = 0.001). Subgroup analyses revealed decreased BDNF levels in plasma of patients (Hedges' g = -1.137, 95% CI = -1.463 to -0.810, P = 0.000) and drug-free patients (Hedges' g = -1.269, 95% CI = -1.974 to -0.564, P = 0.000) as compared to patients on active drug therapy and HCs. Meta-regression analyses showed that age, sex, sample size, Y-BOS total score, and publication year had no moderating effects on the outcome. CONCLUSION: Although the relationship between our findings and the pathophysiology of OCD and the role BDNF plays in the development of the disease remains to be determined, the outcomes suggest that BDNF may serve as a potential biomarker of OCD.

Traditional Chinese Medicine Decoction Combined With Antipsychotic for Chronic Schizophrenia Treatment: A Systematic Review and Meta-analysis.

Despite several studies suggesting the effectiveness of traditional Chinese medicine (TCM) in schizophrenia, there is still a lack of systematic summary and analysis on the role of TCM as adjuvant therapy in chronic schizophrenia. For this purpose, we conducted a meta-analysis to study the efficacy of TCM as an adjuvant combined with antipsychotics in the treatment of chronic schizophrenia. Until April 2020, based on the review of six electronic databases, eight articles were selected. The articles compared TCM decoction assisted antipsychotic therapies with an antipsychotic alone in the treatment of chronic schizophrenia by analyzing a total of 810 cases. The results showed that TCM combined with antipsychotics have beneficial effects on the Positive and Negative Syndrome Scale (PANSS), including the changes in total score, negative score, and the clinical effects evaluated by the PANSS scale. Subgroup analysis showed that the effects of auxiliary TCM with different efficacy on the positive and psychopathological scores were significantly different. It was found that adjuvant treatment with TCM can reduce some side effects and improve the patient's living conditions in the evaluation of the Schizophrenia Quality Of Life Scale (SQLS). Many studies have proved that TCM is safe and well-tolerated. Although the difficulties of using limited TCM remains to be generalized, it still has great potential in the adjuvant treatment of chronic schizophrenia.

Cerebrospinal fluid and blood Aß levels in Down syndrome patients with and without dementia: a meta-analysis study.

Abnormal ß-amyloid (Aß) levels were found in patients with Down syndrome (DS). However, Aß levels in patients with DS and DS with dementia (DSD) vary considerably across studies. Therefore, we performed a systematic literature review and quantitatively summarized the clinical Aß data on the cerebrospinal fluid (CSF) and blood of patients with DS and those with DSD using a meta-analytical technique. We performed a systematic search of the PubMed and Web of Science and identified 27 studies for inclusion in the meta-analysis. Random-effects meta-analysis indicated that the levels of blood Aß1-40 and Aß1-42 were significantly elevated in patients with DS compared with those in healthy control (HC) subjects. In contrast, there were no significant differences between patients with DS and those with DSD in the blood Aß1-40 and Aß1-42 levels. The CSF Aß1-42 levels were significantly decreased in patients with DS compared to those in HC subjects. Further, CSF Aß1-42 levels were significantly decreased in patients with DSD compared to those with DS, with a large effect size. Taken together, our results demonstrated that blood Aß1-40 and Aß1-42 levels were significantly increased in patients with DS while CSF Aß1-42, but not Aß1-40 levels were significantly decreased in patients with DS.

Spectral Analysis of Interaction between Human Telomeric G-Quadruplex and Liliflorin A, the First Lignan Derivative Interacted with G-Quadruplex DNA.

Human telomeric G-quadruplex is a four-stranded structure folded by guanines (G) via Hoogsteen hydrogen bonding. The ligands which stabilize the G-quadruplex are often telomerase inhibitors and may become antitumor agents. Here, the interaction between a lignan derivative liliflorin A and human telomeric sequence dGGG (TTAGGG)3G-quadruplex HTG21 were examined by CD, FRET, and NMR spectroscopic methods. In addition, Molecular Docking was used to study the binding of liliflorin A to dTAGGG (TTAGGG)3 G-quadruplex HTG23. The CD data showed that liliflorin A enhanced HTG21 T(m). The T(m) value of G-quadruplex was enhanced 3.2 degrees C by 4.0 µmol x L(-1) liliflorin A in FRET. The NMR spectra of HTG21 showed vivid alteration after reacting with liliflorin A in 3 hours. Molecular Docking suggested liliflorin A bound to the wide groove of HTG23 at G9, G10, G16 and G17. Liliflorin A was the first lignan derivative that could stabilize HTG21 selectively and provided a new candidate for antitumor drug design targeting on human telomeric G-quadruplex.

Effect of Sodium Fluoride on the Proliferation and Gene Differential Expression in Human RPMI8226 Cells.

Although fluoride is known to reduce the incidence of caries, chronic excessive fluoride exposure can impair human health, even resulting in fluorosis. Now the underlying mechanisms of fluoride-induced toxicity are not fully understood. So, we conducted this study with the purpose of investigating the effect of sodium fluoride (NaF) in human RPMI8226 cells. In this experiment, human RPMI8226 cells were cultured with varied doses of fluoride (10, 20, 40, 80, 160, 320 µM). After 48 h exposure, the change of cell viability was examined by CCK-8 assay, and also the messenger RNA (mRNA) expression of relevant genes was assessed by QRT-PCR. Compared to the control group, fluoride exposure increased the human RPMI8226 cells viability at relatively lower levels (10-160 µM); however, when the concentration reached to 320 µM, the cell proliferation was significantly inhibited (p < 0.05). In addition, the genes mRNA expression, including ANKRD1, CRSP6, KLF2, SBNO2, ZNF649, FANCM, PDGFA, RNF152, CDK10, and CETN2 changed in a concentration-dependent manner and increased with fluoride exposure concentration. The results suggest that overexposure to fluoride (160-320 µM) can induce cytotoxicity and regulate relevant genes expression. Our findings provide novel insights into the mechanisms of action of fluoride-induced toxicity.

[Eudesmane sesquiterpenes from twigs of Manglietia hookeri].

Chemical constituents from the acetone extract of twigs of Manglietia hookeri were isolated and purified by various column chromatographic methods over silica gel and sephadex LH-20, and preparative TLC. The structures of these compounds were identified on the basis of physicochemical properties and spectral analysis, including NMR and MS spectra. Six eudesmane sesquiterpenes were obtained and their structures were identified as trans-eudesmane-4, 11-diol(1), ß-eudesmol(2), (-) -10-epi-5ß-hydroxy-ß-eudesmol (3), epi-carrisone (4), 6-hydroxy-eudesm-4(14) -ene(5) and gynurenol(6). All the compounds were isolated from this plant for the first time. Furthermore, the 13C-NMR data of compound 3 were reported for the first time.

A new illicinolide from leaves of Illicium micranthum Dunn.

The ethyl acetate extract from leaves of Illicium micranthum Dunn exhibited radical scavenging ability on DPPH radical-scavenging assay. Further phytochemical investigation led to the isolation of a new sesquiterpenoid, illicinolide C (1), and eight known compounds (2-9). The structural elucidations of the compounds were based on spectroscopic methods and by comparison of their spectroscopic data with those reported in the references. Except compound 9, all the other compounds were isolated from I. micranthum Dunn for the first time, while compounds 1 and 2 were new to the Illiciaceae family.

Study on changes of clinical indicators and key proteins from fluoride exposure.

Few studies have evaluated the biomarker changes of fluoride exposure. In order to explore early and sensitive indicators, animal experiment was designed. Ninety-six healthy SD rats (48 males and 48 females) weighing approximately 60 g were randomly divided into six groups of 16 animals each by gender average. Control animals were supplied with distilled water only as group 1. Exposure groups' animals were treated with 2, 4, 8, 16, and 32 mg NaF/kg bw, respectively, as groups 2, 3, 4, 5, and 6. Our study found that contents of white blood cell (WBC), lymphocyte percentage (LYMPH%), lymphocyte (LYM), mean platelet volume (MPV), and platelet distribution width (PDW) increased significantly in high-fluoride-exposure groups (p < 0.05), which revealed that immune system may be interfered by high fluoride. Meanwhile, levels of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), and ALT/AST in groups 5 and 6 decreased significantly compared to those in control group (p < 0.05), as well as the concentration of uric acid (UA) in groups 3, 4, 5, and 6 exhibited the same trends (p < 0.05). On the contrary, the level of blood B2 microglobulin (BB2MG) increased significantly (p < 0.05) in groups 4, 5, and 6. Changes of ALT, AST, UA, and BB2MG suggested the functions of the liver and kidney be altered by fluoride exposure. At the same time, the ATF4 content decreased gradually with the increase of fluoride concentration; furthermore, a highly significant (r = -0.586, p < 0.01) negative relationship between ATF4 content and fluoride exposure level was found. Results meant that clinical indicators cannot act as indicators of high fluoride exposure, and it also suggested that protein ATF4 might be the early and sensitive indicator in epidemiologic study of high fluoride exposure.

Photochemical Reaction of 7,12-Dimethylbenz[a]anthracene (DMBA) and Formation of DNA Covalent Adducts.

DMBA, 7,12-dimethylbenz[a]anthracene, is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a probable human carcinogen. It has been found that DMBA is phototoxic in bacteria as well as in animal or human cells and photomutagenic in Salmonella typhimurium strain TA102. This article tempts to explain the photochemistry and photomutagenicity mechanism. Light irradiation converts DMBA into several photoproducts including benz[a]anthracene-7,12-dione, 7-hydroxy-12-keto-7-methylbenz[a]anthracene, 7,12-epidioxy-7,12-dihydro-DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene and 12-hydroxymethyl-7-methylbenz[a]anthracene. Structures of these photoproducts have been identified by either comparison with authentic samples or by NMR/MS. At least four other photoproducts need to be assigned. Photo-irradiation of DMBA in the presence of calf thymus DNA was similarly conducted and light-induced DMBA-DNA adducts were analyzed by 32P-postlabeling/TLC, which indicates that multiple DNA adducts were formed. This indicates that formation of DNA adducts might be the source of photomutagenicity of DMBA. Metabolites obtained from the metabolism of DMBA by rat liver microsomes were reacted with calf thymus DNA and the resulting DNA adducts were analyzed by 32P-postlabeling/TLC under identical conditions. Comparison of the DNA adduct profiles indicates that the DNA adducts formed from photo-irradiation are different from the DNA adducts formed due to the reaction of DMBA metabolites with DNA. These results suggest that photo-irradiation of DMBA can lead to genotoxicity through activation pathways different from those by microsomal metabolism of DMBA.

Photochemical reaction of 7,12-dimethylbenz[a]anthracene (DMBA) and formation of DNA covalent adducts.

DMBA, 7,12-dimethylbenz[a]anthracene, is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a probable human carcinogen. It has been found that DMBA is phototoxic in bacteria as well as in animal or human cells and photomutagenic in Salmonella typhimurium strain TA102. This article tempts to explain the photochemistry and photomutagenicity mechanism. Light irradiation converts DMBA into several photoproducts including benz[a]anthracene-7,12-dione, 7-hydroxy-12-keto-7-methylbenz[a]anthracene, 7,12-epidioxy-7,12-dihydro-DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene and 12-hydroxymethyl-7-methylbenz[a]anthracene. Structures of these photoproducts have been identified by either comparison with authentic samples or by NMR/MS. At least four other photoproducts need to be assigned. Photo-irradiation of DMBA in the presence of calf thymus DNA was similarly conducted and light-induced DMBA-DNA adducts were analyzed by 32P-postlabeling/TLC, which indicates that multiple DNA adducts were formed. This indicates that formation of DNA adducts might be the source of photomutagenicity of DMBA. Metabolites obtained from the metabolism of DMBA by rat liver microsomes were reacted with calf thymus DNA and the resulting DNA adducts were analyzed by 32P-postlabeling/TLC under identical conditions. Comparison of the DNA adduct profiles indicates that the DNA adducts formed from photo-irradiation are different from the DNA adducts formed due to the reaction of DMBA metabolites with DNA. These results suggest that photo-irradiation of DMBA can lead to genotoxicity through activation pathways different from those by microsomal metabolism of DMBA.

Photochemical transformation and phototoxicity of 1-aminopyrene.

1-Aminopyrene (1-AP) is an environmental mutagen and a metabolite of 1-nitropyrene (1-NO2P). On light irradiation, 1-AP transforms into oxidation products with a half-life of 7.1 min in 10% methanolic buffer. The presence of DNA or free-radical/ singlet oxygen scavengers 1,4-dithiothreitol, histidine, or NaN3 slows down 1-AP photochemical reaction. The photoproducts identified include 1-hydroxyaminopyrene, 1-nitrosopyrene, 1-NO2P, 1-amino-x-hydroxypyrene, and three covalent dimers. Since it is known that 1-NO2P and 1-nitrosopyrene are genotoxic and 1-hydroxyaminopyrnene can react with DNA to form covalent adducts, we used the Mutatox test to assess the toxicity of 1-AP and its photoproducts. It was found that the lowest-observed-effect concentrations for 1-AP, 1-AP photoproducts, and 1-NO2P are 1.25 microM, 10 microM, and NA (no mutagenic response was seen at this concentration range) in direct medium (no S-9) and NA, 5 microM, and 0.625 microM in S-9 medium, respectively. Therefore, 1-AP photoproducts are more genotoxic than 1-AP itself in the S-9 medium and more mutagenic than 1-NO2P in the direct medium. Thus, 1-NO2P alone cannot account for all the mutagenicity of the photoproducts. Irradiation of 1-AP together with DNA leads to covalent DNA adduct formation possibly via the 1-hydroxyaminopyrene intermediate. In this study, ultraviolet-A (UVA) was used at approximately the same magnitude as the outdoor UVA irradiance. Considering the half-life of 1-AP in the test solutions in this study, the aquatic biota (including humans) near the surface layer of a static water body are most likely subjected to the photoinduced toxicity of the study compound. The biota at the lower depths will also be affected if turbulence becomes a significant factor in enhancing the exposure risk for aquatic organisms.

Direct separation and quantitative determination of clenbuterol enantiomers by high performance liquid chromatography using an amide type chiral stationary phase.

Enantiomers of clenbuterol were directly separated by a new high performance chromatographic method on Chirex 3005 column. Several parameters such as mobile phase composition, column temperature and flow rate were studied. Baseline enantioseparation was achieved, using the optimized mobile phase of n-hexane-1,2-dicholoethane-methanol (54:38:8, v/v/v) at 17 degrees C and 1.0 ml/min, with the separation factor (alpha) 1.43 and the resolution factor (R(S)) 1.81. The mechanism of separation was also discussed. Standard linear calibration cures were established for the R- and S-enantiomers, over the range of 26.1-1,045.8 and 5.7-229.6 nmol/ml, with the correlation coefficient of 0.9999 for both. The limits of detection were 0.47 and 1.04 nmol/ml for R- and S-enantiomers, respectively. Recovery and precision of the method were also evaluated, which had been successfully used to monitor and identify quantitatively the profile of the clenbuterol enantiomers in human serum.