HDAC2 Induces DNA Methyltransferase DNMT3B Expression to Regulate the Wnt Signaling Pathway and Thus Promotes Glioma Development and Progression.

Purpose: To investigate the role and molecular mechanism of HDAC2 in glioma. Methods: GSE16011, GSE31262, and GSE90598 datasets were used to identify co-expressed genes, GO analysis, and KEGG analysis to identify gene enrichment pathways, and PPI networks were constructed to identify gene interrelationships. HDAC2 enrichment on DNMT3B promoter and DNMT3B enrichment on Bcl2 CpG island was detected by a ChIP assay. The expression, prognosis, and hierarchical distribution of HDAC2, DNMT3B, and Bcl2 were examined in the CGGA database, and the correlation between HDAC2 and DNMT3B, Bcl2, and DNMT3B and Bcl2 was assessed. Results: The HDAC2-DNMT3B-Bcl2 axis is differentially expressed and interacts in gliomas. HDAC2 activates the transcriptional activity of DNMT3B, and DNMT3B inhibits the expression of Bcl2. HDAC2 and DNMT3B are highly expressed in gliomas and have a poor prognosis, while Bcl2 is lowly expressed in gliomas and has a good prognosis. Conclusion: HDAC2 promotes DNMT3B transcriptional repression of Bcl2 expression and Wnt pathway activity, thereby activating glioma cell activity in vitro and in vivo.

First report of Corynespora cassicola causing black spot on Sarcandra glabra in China.

Sarcandra glabra is an important Chinese medicinal plant, which was widely cultivated under forest in south China. Guangxi province is the main producing areas of this herb. In June 2019, a serious leaf disease was found causing severe defoliation in the S. glabra plantation under bamboo forest in Rongan country, Guangxi province (109°13'N''E). About 70% of the plants in the plantation (300 ha) showed the similar symptoms. Initially, circular lesions appeared on young leaves as black spots (about 1 to 2 mm). Then, the spots gradually enlarged usually with an obvious yellowish margin (6 to 8 mm). Finally, the lesions coalesced and formed irregular, black, and large necrotic areas, resulting in the leaf abscission. For pathogen isolation, small pieces of tissue (5×5 mm) taken from 25 diseased leaves were sterilized with 75% ethanol for 30 s, subsequently, soaked in 0.1% HgCl2 for 2 min, rinsed three times in sterile distilled water, dried, and then placed aseptically onto the potato dextrose agar (PDA) plates, and incubated at 28 °C (12 h/12 h light/dark). Three days later, the isolates were placed on a new PDA plate for subsequent purification and sporulation. 20 pure fungal isolates were obtained from single spores. Of which, 15 isolates showed similar morphological characteristics.The colonies on PDA were round, dense, gray edge and dark gray in center area. Conidia in culture were appeared light brown, cylindrical in shape, with 0 to 8 septa, and 55 to 165 µm × 5.2 to 13.5 µm in size (mean = 106.2 µm × 8.6 µm, n = 30). These morphological characteristics resemble those of Corynespora sp. (Berk. & M.A. Curtis) C.T. Wei (Ellis et al. 1971). A single-spore isolate (ZD5) was selected from the 15 fungal isolates for a subsequent molecular identification. The genes of internal transcribed spacer (ITS) of ribosomal DNA, ß-tublin, and actin were amplified with the primer pairs ITS-1/ITS-4 (White et al. 1990), ß-tubulin 2-Bt2a/Bt2b (Glass and Donaldson 1995), ACT-512F/ACT-783R (Carbone and Kohn 1999), respectively. And the ITS, ß-tublin, and actin sequences were deposited in the GenBank database with the accession numbers MW362446, MW367029, and MW533122. Blast analysis and neighbor-joining analysis based on ITS, ß-tublin, and actin sequences using MEGA 6 revealed that the isolate was placed in the same clade as C. cassicola with 100% bootstrap support. Pathogenicity test was performed on the two-year-old potted S. glabra. Six-mm-diameter mycelial plugs were attached to the healthy leaves of S. glabra for co-culture, while the control group was attached with PDA. All plants were covered with plastic bags for 2 days in order to maintain high humidity and cultured in a greenhouse at 28 °C with a 12-h/12-h light/dark cycle. The symptoms appeared 2 days after co-culture were identical to those observed in the field. The same fungus was re-isolated from the lesions, and further morphological characterization and molecular assays, as described above.The control leaves remained symptomless during the pathogenicity tests. According to the previous literatures, C. cassicola is a plant pathogenic fungus with a broad host range, which can damage diverse tropical plants including Salvia miltiorrhiza (Lu et al. 2019), Solanum americanum (Wagner and Louise 2019), Vitex rotundifolia (Yeh and Kirschner 2017), Cucumis sativus, Lycopersicon esculentum (Hsu et al. 2002), Carica papaya (Tsai et al. 2015),and so on. To our knowledge, this is the first report of C. cassicola causing leaf spot on S. glabra in China.

[Proton magnetic resonance spectroscopy study of prefrontal lobe and thalamus in schizophrenics on modified electroconvulsive therapy].

OBJECTIVE: To explore the potential effects of modified electroconvulsive therapy (MECT) in prefrontal lobe and thalamus in patients with schizophrenia by proton magnetic resonance spectroscopy ((1)H-MRS). METHODS: From November 2010 to June 2011, a total of 31 schizophrenics fulfilling the third edition of the Chinese Classification of Mental Disorders (CCMD-III) were recruited. And prefrontal lobe and thalamus were evaluated by multi-voxel (1)H-MRS before and after 8 sessions of MECT. The subjects were evaluated by the positive and negative syndrome scale (PANSS). And the N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine compounds (Cr) were measured and the ratios of NAA/Cr and Cho/Cr determined. RESULTS: (1) In left prefrontal lobe and bilateral thalamus, the NAA/Cr ratio at post-treatment demonstrated higher than that at pre-treatment (1.50 ± 0.31 vs 1.35 ± 0.30, t = 2.07, P < 0.05; 1.53 ± 0.31 vs 1.38 ± 0.27, t = 2.03, P < 0.05; 1.51 ± 0.29 vs 1.36 ± 0.26, t = 2.14, P < 0.05). (2) The major influencing factors of the changes of NAA/Cr in left prefrontal lobe were age of onset, decrease rate of PANSS, baseline PANSS total score and duration of illness. And the major influencing factors for left thalamus were age of onset and duration of illness while a major influencing factor for right thalamus was baseline PANSS total score. CONCLUSION: MECT may modify brain metabolism as measured by (1)H-MRS. The pattern of changes suggests possible neuroprotective effects in schizophrenics. And these effects are correlated with age of onset, duration and severity of illness.

[Hydrolysis technology optimization of phorbol esters by orthogonal experiment].

OBJECTIVE: To establish the best hydrolytic conditions from phorbol esters. METHOD: The orthogonal experiment was used to optimize 4 factors, which were reaction time, ratio of solid-to-liquid, hydrolytic times, and temperature. Diamonsil C18 column (4. 6 mm x 250 mm, 5 microm) was used and the mobile phase was consisted of acetonitrile and water for HPLC detection. The detection wavelength was set at 234 nm, the flow rate was 1 mL x min(-1), and the column temperature was 25 degrees C. RESULT: The optimum conditions were 10 h of reaction time, 1:6 of solid-to-liquid (BaOH/MeOH) ratio, 25 degrees C of temperature, and one time of hydrolysis. There was a good linear relationship of phorbol in the range of 4.28-107 mg x L(-1) (r = 0.999 9), and the average recovery was 97.89%, with RSD 0.78%. CONCLUSION: The method is steady, reliable and reproducible, and it provides a mean for future study.

[Proton magnetic resonance spectroscopy of prefrontal lobe and thalamus in schizophrenics: correlation with clinical characteristics].

OBJECTIVE: To explore the characteristics of different subtypes of schizophrenics on prefrontal lobe and thalamus by proton magnetic resonance spectroscopy ((1)H-MRS) and its relationship. METHODS: From August 2007 to April 2010 at our center, a total of 159 schizophrenics fulfilling the third edition criteria of Chinese Classification of Mental Disorders (CCMD-III) were recruited. And prefrontal lobe and thalamus were evaluated by multi-voxel (1)H-MRS. There were 88 males and 71 females. There were first-episode (n = 54) and not-first-episode (n = 105), negative subtype (n = 125) and positive subtype (n = 34), medicated (n = 96) and non-medicated (n = 63) by different criteria. The levels of N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine compounds (Cr) were measured and the ratios of NAA/Cr and Cho/Cr determined. Positive and negative syndrome scale (PANSS) and Wisconsin card sorting test (WCST) were also assessed. Only 45 normal controls received (1)H-MRS. RESULTS: On left prefrontal lobe and left thalamus, the NAA/Cr ratios in different subtypes of patients were lower than those in normal controls (P < 0.05 or 0.01). The NAA/Cr ratios in patients of non-first-episode (1.48 ± 0.34), negative subtype (1.40 ± 0.35) and medicated (1.47 ± 0.36) on right thalamus were also lower than those in normal controls (1.62 ± 0.37, t = 2.25, 3.56, 2.28, P < 0.05 or P < 0.01). Compared with positive subtype schizophrenics, the NAA/Cr ratios in those of negative subtype on right thalamus were lower (1.40 ± 0.35 vs 1.60 ± 0.37, t = 2.92, P < 0.01). On right thalamus of non-medicated schizophrenics, there was a negative correlation between the duration of illness and the ratio of NAA/Cr (r = -0.38, P < 0.05) and a positive correlation between the duration of illness and the ratio of Cho/Cr (r = 0.43, P < 0.01). On right thalamus of negative subtype schizophrenics, the ratios of NAA/Cr were negatively correlated with the total score of PANSS and the score of negative factor respectively (r = -0.36, -0.40, P < 0.05). On left prefrontal lobe of different subtypes, the ratios of NAA/Cr were negatively correlated with the total score of PANSS, the score of negative factor, responses errors and persistent errors (P < 0.01) and positively correlated with completed categories and conceptual level responses (P < 0.05 or P < 0.01). CONCLUSION: Abnormalities in neuronal function and/or integrity are present on left prefrontal lobe and left thalamus in schizophrenics. And right thalamus is probably involved in non-first-episode subtype, negative subtype and non-medicated subtype. Different subtypes of schizophrenics may have different characteristics of (1)H-MRS due to the duration of illness and their clinical symptoms.

Inhibition of aldehyde dehydrogenase-2 suppresses cocaine seeking by generating THP, a cocaine use-dependent inhibitor of dopamine synthesis.

There is no effective treatment for cocaine addiction despite extensive knowledge of the neurobiology of drug addiction. Here we show that a selective aldehyde dehydrogenase-2 (ALDH-2) inhibitor, ALDH2i, suppresses cocaine self-administration in rats and prevents cocaine- or cue-induced reinstatement in a rat model of cocaine relapse-like behavior. We also identify a molecular mechanism by which ALDH-2 inhibition reduces cocaine-seeking behavior: increases in tetrahydropapaveroline (THP) formation due to inhibition of ALDH-2 decrease cocaine-stimulated dopamine production and release in vitro and in vivo. Cocaine increases extracellular dopamine concentration, which activates dopamine D2 autoreceptors to stimulate cAMP-dependent protein kinase A (PKA) and protein kinase C (PKC) in primary ventral tegmental area (VTA) neurons. PKA and PKC phosphorylate and activate tyrosine hydroxylase, further increasing dopamine synthesis in a positive-feedback loop. Monoamine oxidase converts dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL), a substrate for ALDH-2. Inhibition of ALDH-2 enables DOPAL to condense with dopamine to form THP in VTA neurons. THP selectively inhibits phosphorylated (activated) tyrosine hydroxylase to reduce dopamine production via negative-feedback signaling. Reducing cocaine- and craving-associated increases in dopamine release seems to account for the effectiveness of ALDH2i in suppressing cocaine-seeking behavior. Selective inhibition of ALDH-2 may have therapeutic potential for treating human cocaine addiction and preventing relapse.

[Pilot-scale study on riparian Scirpus yagara Ohw zone improving water quality of river].

In one year polluted water was treated with Scirpus yagara Ohw to investigate its impact on river water quality in pilot scale test, and COD, NH4(+) -N, TP, turbidity and water temperature were tested. The results show that the Scirpus yagara Ohw gives better water quality in summer and autumn than in winter and spring. In summer, the Scirpus yagara Ohw zone removes 44.10% of the COD, 78.66% of the ammonia, 69.44% of the phosphorous, and 99.53% of the turbidity. It also can improve water quality to some extent in winter. The Scirpus yagara Ohw can reduce effluent temperature and effluent temperature difference between evening and morning and then improve water microenvironment locally. Comparisons between the Scirpus yagara Ohw riparian zone and control zone showed that the Scirpus yagara Ohw affects importantly on removing pollutants, improving local microenvironment of water.