The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Disease spectrum and pathogenic genes of inherited metabolic disorder in Gansu Province of China / 中国当代儿科杂志

OBJECTIVES@#To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China.@*METHODS@#A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.@*RESULTS@#A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance.@*CONCLUSIONS@#This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Detection of Phosphatidylethanol in Whole Blood by UPLC-MS/MS / 法医学杂志

OBJECTIVES@#To establish the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to detect ethanol metabolites phosphatidylethanol (PEth) in whole blood.@*METHODS@#An appropriate amount of aqueous solution including 1% formic acid was added to 100 μL whole blood, the protein was precipitated with acetone, centrifuged and the supernatant was purified and enriched by using Bond Elut Certify column. The eluent was redissolved with 1/1 isopropanol/acetonitrile (v/v) solution after nitrogen blowing and then tested by UPLC-MS/MS. Selective reaction monitoring scanning was carried out in negative ionization mode, and quantitative analysis was performed by external standard method.@*RESULTS@#PEth showed a linear relationship over the concentration range of 1-160 ng/mL in whole blood (r=0.999 9) with peak area. The detection limit was 0.2 ng/mL, the quantification limit was 1 ng/mL, the recovery rate was 97.43%-103.61%, the accuracy was 0.99%-1.77%, the intra-day precision was 0.4%-2.4%, and the inter-day precision was 1.1%-3.3%, and the matrix effect was 91.00%-99.55%. PEth was not detected in the in vitro blood samples supplemented with ethanol. PEth was detected positive in three drunk driving cases, and the concentration were 195.49, 83.67 and 876.12 ng/mL, respectively.@*CONCLUSIONS@#The established method has high sensitivity and specificity and the analysis results are accurate. It is suitable for the qualitative and quantitative analysis of PEth in whole blood.

A Report of Chigger Mites on the Striped Field Mouse, Apodemus agrarius, in Southwest China

Based on the field investigations in 91 investigation sites (counties) in southwest China between 2001 and 2019, the present paper reported the chigger mites on A. agrarius mice in southwest China for the first time by using a series of statistical methods. From 715 striped field mice captured in 28 of 91 investigated sites, only 255 chiggers were collected, and they were identified as 14 species, 6 genera in 3 subfamilies under 2 families. Of 715 A. agrarius mice, only 24 of them were infested with chigger mites with low overall prevalence (PM=3.4%), overall mean abundance (MA=0.36 mites/host) and overall mean intensity (MI=10.63 mites/host). The species diversity and infestation of chiggers on A. agrarius were much lower than those previously reported on some other rodents in southwest China. On a certain species of rodent, A. agrarius mouse in southwest China seems to have a very low susceptibility to chigger infestations than in other geographical regions. Of 14 chigger species, there were 3 dominant species, Leptotrombidium sialkotense, L. rupestre and Schoengastiella novoconfuciana, which were of aggregated distribution among different individuals of A. agrarius hosts. L. sialkotense, one of 6 main vectors of scrub typhus in China, was the first dominant on A. agrarius. The species similarity of chigger mites on male and female hosts was low with CSS=0.25, and this reflects the sex-bias of different genders of A. agrarius mice in harboring different chigger species.

Infestation and Related Ecology of Chigger Mites on the Asian House Rat (Rattus tanezumi) in Yunnan Province, Southwest China

This paper is to illustrate the infestation and related ecological characteristics of chigger mites on the Asian house rat (Rattus tanezumi). A total of 17,221 chigger mites were collected from 2,761 R. tanezumi rats, and then identified as 131 species and 19 genera in 2 families. Leptotrombidium deliense, the most powerful vector of scrub typhus in China, was the first major dominant species on R. tanezumi. All the dominant mite species were of an aggregated distribution among different individuals of R. tanezumi. The species composition and infestations of chiggers on R. tanezumi varied along different geographical regions, habitats and altitudes. The species-abundance distribution of the chigger mite community was successfully fitted and the theoretical curve equation was Ŝ (R)=37e–(0.28R)2. The total chigger species on R. tanezumi were estimated to be 199 species or 234 species, and this further suggested that R. tanezumi has a great potential to harbor abundant species of chigger mites. The results of the species-plot relationship indicated that the chigger mite community on R. tanezumi in Yunnan was an uneven community with very high heterogeneity. Wide geographical regions with large host samples are recommended in the investigations of chigger mites.

Research Advances of Leptotrombidium scutellare in China

Leptotrombidium scutellare is one of the 6 main vectors of scrub typhus in China. It has been found in more than 15 provinces of China. Especially in Yunnan, it was found to be mainly distributed in some mountainous areas with high altitude, low temperature and low precipitation. Rodents and some other small mammals were the most common hosts of L. scutellare. To date, more than 40 host species of L. scutellare have been recorded with very low host specificity, and the main hosts varied in different geographical regions. L. scutellare had a strong resistance against the cold environment, and the temperature and humidity were 2 important factors affecting its growth and development. Among different individuals of their rodent hosts, L. scutellare mites often showed an aggregated distribution pattern, which reflected the interspecific cooperation of the mites. The chromosome karyotype of L. scutellare was 2n=16 and all the 8 pairs of chromosomes were short rod-shaped with metacentric or sub-metacentric types. The isozyme spectrum supported that L. scutellare, L. deliense and L. rubellum were in the same species group. Based on the natural infection, experimental transmission and epidemiological evidence, L. scutellare has been eventually confirmed as the second major vector of scrub typhus in China, which is second only to L. deliense.

Infestation and Related Ecology of Chigger Mites on the Asian House Rat (Rattus tanezumi) in Yunnan Province, Southwest China

This paper is to illustrate the infestation and related ecological characteristics of chigger mites on the Asian house rat (Rattus tanezumi). A total of 17,221 chigger mites were collected from 2,761 R. tanezumi rats, and then identified as 131 species and 19 genera in 2 families. Leptotrombidium deliense, the most powerful vector of scrub typhus in China, was the first major dominant species on R. tanezumi. All the dominant mite species were of an aggregated distribution among different individuals of R. tanezumi. The species composition and infestations of chiggers on R. tanezumi varied along different geographical regions, habitats and altitudes. The species-abundance distribution of the chigger mite community was successfully fitted and the theoretical curve equation was Ŝ (R)=37e–(0.28R)2. The total chigger species on R. tanezumi were estimated to be 199 species or 234 species, and this further suggested that R. tanezumi has a great potential to harbor abundant species of chigger mites. The results of the species-plot relationship indicated that the chigger mite community on R. tanezumi in Yunnan was an uneven community with very high heterogeneity. Wide geographical regions with large host samples are recommended in the investigations of chigger mites.

Lignans with inhibitory effect on 5α-reductase from Urtica cannabina / 中国中药杂志

The lignans in Urtica cannabina were isolated by preparative HPLC, silica, and ODS column chromatographies, and identified by NMR and HR-MS. The inhibitory activities on 5α-reductase were evaluated in vitro. As a result, ten secolignans,(2R,4S)-2,4-bis(3-methoxyl-4-hydroxyphenyl)-3-butoxypropanol(1), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone(2), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(3), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(trans urticol, 4), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone-3-O-β-D-glucopyranoside(5), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-β-D-glucopyranoside(6), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-β-D-glucopyranoside(trans-urticol-7-O-β-D-glucopyranoside, 7), cycloolivil-4-O-β-D-glucopyranoside(8), isolariciresinol-4'-O-β-D-glucopyranoside(9), and olivil-4'-O-β-D-glucopyranoside(10), together with a polyphenol [α-viniferin(11)], were isolated from U. cannabina for the first time. Compound 1 was a new lignan. Compound 7 was potent in inhibiting 5α-reductase.

Comparative analysis of serum biochemical indexes of Uygur and Kazak adults of different ages and genders in Xinjiang / 解剖学报

Objective To analyze the changes of serum biochemical indexes with age and gender in Xinjiang Uygur and Kazak populations, and to compare the differences of serum biochemical indexes between Xinjiang Uygur and Kazak populations in gender and age. Methods Totally 511 Xinjiang Uygur and Kazak healthy adults were randomly selected from a hospital in Xinjiang Uygur autonomous region for normal physical examination, including 252 and 259 Xinjiang Uygur and Kazak healthy adults. Serum biochemical indexes were detected by CX-7 automatic biochemical analyzer produced by Beckman, USA, and statistical analysis was conducted by variance analysis, t test, correlation analysis and chi-square test. Results Xinjiang Uygur nationality and Kazak serum biochemical indexes for the male and the female, including glutamic-pyruvic transaminase (GPT), direct bilirubin (DBil), uric acid (UA), creatinine (Cre) and urea (Ure), glucose (Glu), total bilirubin(TBil), cystatin C(Cys-C) increased with the growth of the age, and sex between different age groups were statistically significant (P 0. 05). There were statistically significant differences in Glu, TG, TC, LDL and HDL between Xinjiang Uygur and Kazak people of the same gender and age group (P < 0. 05). Conclusion The serum biochemical indexes of Uygur and Kazak in Xinjiang are different in different ages and genders. The Glu and lipid levels of Uygur nationality in Xinjiang are different from those of Kazak nationality.

The expression and prognostic significance of Aurora Kinase A in hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To explore the expression of Aurora Kinase A (AURKA) in hepatocellular carcinoma (HCC) and its prognostic value.Methods:mRNA expression profiles and clinical data of HCC patients were downloaded from the Cancer Genome Atlas (TCGA) database. Expression of AURKA mRNA in HCC patients of TCGA database from normal liver tissue and all tumor tissues, normal tissues adjacent to cancer and matched tumor tissues were analyzed, and then expression of AURKA to was investigated in HCC tissues and normal liver tissues in the Human Protein Atlas (HPA) database. According to the TNM stage information of HCC patients in TCGA database, expression of AURKA in different stages was analyzed. Kaplan-Meier method was used to analyze whether the high and low expression of AURKA in HCC patients of TCGA database (with the median as the cut-off value) was significantly related to the length of survival. The RNA-seq expression profile data of HCC patients in the public resource platform of the Kaplan-Meier Plotter website was used for external verification. Cox univariate and multivariate analysis were performed on the age, sex, degree of differentiation, TNM stage, and AURKA mRNA expression of TCGA database patients.Results:374 cases of HCC tumor tissues and 50 cases of adjacent normal liver tissues in the TCGA database were included. All HCC tumor tissues in the TCGA database compared with the paired adjacent tissues mRNA level of AURKA was significantly increased, and the protein level was also increased, the difference was statistically significant ( P<0.05); With the tumor TNM stage increase of AURKA mRNA expression showed a gradual upward trend, and the difference was statistically significant ( P<0.05); in the TCGA database HCC cohort, high expression of AURKA mRNA was associated with poor HCC prognosis, and was obtained in Kaplan Meier Plotter database. The difference was statistically significant ( P<0.05); Cox multivariate regression analysis showed that TNM stage ( HR=1.69, 95% CI: 1.37-2.10) and AURKA mRNA expression level ( HR=1.03, 95% CI: 1.01-1.10) are the independent prognostic factors of HCC patients. Conclusions:AURKA is highly expressed in HCC, which is associated with the poor prognosis of HCC. AURKA is an independent prognostic factor of HCC.

Relative Abundance of a Vector of Scrub Typhus, Leptotrombidium sialkotense, in Southern Yunnan Province, China

The chigger mite Leptotrombidium sialkotense is one of the 6 main vectors of scrub typhus in China. Before present study, L. sialkotense was found in some parts of Hunan province, China with a narrow geographical distribution. During field investigation 2016-2017, we found L. sialkotense in Jingha, southern Yunnan, China. Of 15 small mammal host species, L. sialkotense were collected from 6 species of the hosts. Rattus brunneusculus was a dominant host of L. sialkotense, from which 98.3% of the mites were collected. The chigger mite showed a relatively high infestation prevalence (PM=11.7%) and mean abundance (MA=0.5) in comparison with the rest 5 host species. These results reveal a certain host specificity of L. sialkotense to a rat R. brunneusculus. The mite L. sialkotense showed an aggregated distribution on the host (P<0.05). A positive correlation observed between L. sialkotense and the body length of hosts. There was a positive interspecific association between L. sialkotense and 2 other dominant vectors, L. deliense and L. scutellare.

Modified Trizol Method for Extracting RNA from Mouse Skin / 中山大学学报(医学科学版)

@#【Objective】Due to the tough nature of skin tissue and a high presence of RNases，the isolation of skin RNA by the classical Trizol method presents a challenge. Therefore，we adapted and tested different sample treatment protocols to improve the Trizol method for high- quality extraction of skin RNA.【Methods】In this study，normal skin of mice processed by different treatments（Tri：submersion Trizol；Pro：RNA sample protector；Cry：cryopreservation in liquid nitrogen frozen and then - 80 ℃ refrigerator；LNG：liquid nitrogen grinding；Cut：scissor cutting）were used as the experimental groups. Spinal cord tissue（Sp）was used as the reference group，and skin tissue of mouse psoriasis model induced by imiquimod（IMQ）was used as the validation group. We compared skin RNA concentration，purity and integrity， as well as IL- 1β mRNA expression extracted by conventional Trizol methods（1-Tri，Nor）and modified Trizol methods（2-Tri，LNG-Tri，Tri-Cut，Pro），which were determined by UV spectrophotometry，agar gel electrophoresis and quantitative reverse transcription PCR（qRT- PCR）.【Results】① Compared with spinal cord（Sp），the total RNA of normal skin tissue extracted with the same classical Trizol method（1-Tri）was with lower yields，more obvious DNA contamination and 5S RNA bands，and higher IL-1β mRNA relative expression，suggesting that skin tissue was relatively special and the classical Trizol methods of skin RNA extraction should be improved. ② Among the different treatment methods of skin tissue，2-Tri and LNG-Tri methods resulted in higher RNA concentrations，lower RNA degradation and lower DNA contamination，and the expression of IL-1β mRNA was closer to normal levels. More importantly，the skin RNA samples extracted by the 2-Tri method can reflect more realistically the variation of IL-1β mRNA expression between normal and psoriasiform groups.【Conclusion】Improved 2-Tri or LNG-Tri method has the advantage of high quality of total RNA，and 2-Tri can more reliably reflect the mRNA expression pattern under physiological and pathological conditions.

New furo3,2-hisochroman from the mangrove endophytic fungus Aspergillus sp. 085242 / 中国天然药物

Four new compounds, asperisocoumarin G (1), asperisocoumarin H (2), (±)-asperisocoumarin I [(±)-3], along with the known pergillin (4) and penicisochroman L (5) were isolated from a mangrove endophytic fungus Aspergillus sp. 085242 by further chemical investigation. The structures of the new compounds, including their absolute configurations, were established by analysis of HR-ESI-MS and NMR spectroscopic data, and ECD calculation. Asperisocoumarins G-I (1-3) were new isocoumarins belonging to the class of furo[3, 2-h]isocoumarins which are rarely found in natural sources. All of the isolated compounds were evaluated for their α-glucosidase inhibitory effects, and compounds 1 and 4 showed moderate α-glucosidase inhibitory activity, respectively. In an antimicrobial test, the racemate of 3 showed antibacterial activity against Salmonella.

MicroRNA-21 attenuates doxorubicin-induced cardiotoxicity by activating silent information regulator 1 signaling pathway / 第二军医大学学报

Objective To explore whether microR-21 (miR-21) can alleviate doxorubicin (DOX)-induced cardiotoxicity and whether silent information regulator 1 (SIRT1) signaling pathway mediates the roles. Methods Neonatal rat cardiac myocytes were treated with DOX (1 µmol/L) to induce DOX myocardial toxicity model. The cardiomyocytes were randomized into 8 groups: control group, miR-21 group, miR-21 inhibitor group, DOX group, miR-21+DOX group, miR-21 inhibitor+DOX group, Sirtinol+miR-21+DOX group and Sirtinol+DOX group. The miR-21 mimics, miR-21 inhibitors and Sirtinol (SIRT1 inhibitor) were given at 24 h before DOX treatment. After treatment with DOX for 24 h, the cell viability, apoptosis rate, and the expression levels of apoptosis-related proteins and SIRT1 signaling pathway were detected. Results Compared with the control group, the cell viability, and the expression levels of Bcl-2 and SIRT1 were significantly decreased in the cardiomyocytes after treatment with DOX for 24 h, while the expression levels of Bax and cleaved Caspase-3, and apoptotic rate were significantly increased (P<0.05). Compared with the DOX group, miR-21 significantly increased cell viability and the expression levels of Bcl-2 and SIRT1, and significantly decreased the expression levels of Bax and cleaved Caspase-3 and apoptotic rate (P<0.05). Inhibiting SIRT1 signaling pathway could significantly weaken the protective effect of miR-21 on cardiomyocytes (P<0.05). Conclusion miR-21 can inhibit cardiomyocyte apoptosis, increase cell viability and alleviate DOX-induced cardiotoxicity by activating SIRT1 signaling pathway.

MicroRNA expression profile in chronic nonbacterial prostatitis revealed by next-generation small RNA sequencing / 亚洲男科学杂志(英文版)

MicroRNAs (miRNAs) are considered to be involved in the pathogenic initiation and progression of chronic nonbacterial prostatitis (CNP); however, the comprehensive expression profile of dysregulated miRNAs, relevant signaling pathways, and core machineries in CNP have not been fully elucidated. In the current research, CNP rat models were established through the intraprostatic injection of carrageenan into the prostate. Then, next-generation sequencing was performed to explore the miRNA expression profile in CNP. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) bioinformatical analyses were conducted to reveal the enriched biological processes, molecular functions, and cellular components and signaling pathways. As a result, 1224, 1039, and 1029 known miRNAs were annotated in prostate tissues from the blank control (BC), normal saline injection (NS), and carrageenan injection (CAR) groups (n = 3 for each group), respectively. Among them, 84 miRNAs (CAR vs BC) and 70 miRNAs (CAR vs NS) with significantly different expression levels were identified. Compared with previously reported miRNAs with altered expression in various inflammatory diseases, the majority of deregulated miRNAs in CNP, such as miR-146b-5p, miR-155-5p, miR-150-5p, and miR-139-5p, showed similar expression patterns. Moreover, bioinformatics analyses have enriched mitogen-activated protein kinase (MAPK), cyclic adenosine monophosphate (cAMP), endocytosis, mammalian target of rapamycin (mTOR), and forkhead box O (FoxO) signaling pathways. These pathways were all involved in immune response, which indicates the critical regulatory role of the immune system in CNP initiation and progression. Our investigation has presented a global view of the differentially expressed miRNAs and potential regulatory networks containing their target genes, which may be helpful for identifying the novel mechanisms of miRNAs in immune regulation and effective target-specific theragnosis for CNP.

Anemia prevalence and its influencing factors for the infants aged 6-23 months in poor areas in Gansu Province / 中华疾病控制杂志

Objective To understand the prevalence of anemia and its influencing factors in infants aged 6 to 24 months in poor areas of Gansu Province, and to provide reference for improving the prevalence of anemia in local children. Methods A multi-stage sampling method was used to conduct a survey on infant and caregivers, in the 12 children nutrition improvement project counties in Gansu Province. T-test and analysis of variance were used to compare the hemoglobin content, the chi-square test was used to compare the prevalence of anemia, and the Logistic regression model was used to analyze the influencing factors. Results Among the 3 188 effective data, the detection rate of anemia was 25.69% (819). The detection rate of anemia among boys and girls was 24.54% and 26.90%, respectively. There was no significant difference in the detection rate of anemia among different sexes ( 2=2.326, P=0.127). The detection rate of anemia between different age groups were statistically significant ( 2=42.339, P<0.001); The results of multivariate analysis showed that children's age, children's ethnic groups, parents' awareness of feeding knowledge, the feeding method of 6 months after birth and the way of taking nutritional packs were associated with anemia (all P<0.05). Conclusions The prevalence of anemia in infants aged 6 to 24 months in poor areas in Gansu Province was relatively high. Strengthening the education of caretakers’ knowledge of guardian feeding and scientific child-rearing, and ensuring the nutrition packages intake can significantly reduce the prevalence of anemia prevalence in poor areas in Gansu Province.

Research Progress on Leptotrombidium deliense

This article reviews Leptotrombidium deliense, including its discovery and nomenclature, morphological features and identification, life cycle, ecology, relationship with diseases, chromosomes and artificial cultivation. The first record of L. deliense was early in 1922 by Walch. Under the genus Leptotrombidium, there are many sibling species similar to L. deliense, which makes it difficult to differentiate L. deliense from another sibling chigger mites, for example, L. rubellum. The life cycle of the mite (L. deliense) includes 7 stages: egg, deutovum (or prelarva), larva, nymphochrysalis, nymph, imagochrysalis and adult. The mite has a wide geographical distribution with low host specificity, and it often appears in different regions and habitats and on many species of hosts. As a vector species of chigger mite, L. deliense is of great importance in transmitting scrub typhus (tsutsugamushi disease) in many parts of the world, especially in tropical regions of Southeast Asia. The seasonal fluctuation of the mite population varies in different geographical regions. The mite has been successfully cultured in the laboratory, facilitating research on its chromosomes, biochemistry and molecular biology.

Effects of Silencing NSD2 Gene by shRNA on Proliferation, Apoptosis and Akt /mTOR Signal Pathway in OCI-Ly3 Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of silencing NSD2 gene by RNA interference on the proliferation, apoptosis and the alteration of Akt /mTOR signaling pathway in diffuse large B cell lymphoma OCI-Ly3 cells.</p><p><b>METHODS</b>The shRNA targeting NSD2 gene was transfected into OCI-Ly3 cells by lentivirus infection. The NSD2 mRNA and protein were detected by real time Q-PCR and Western blot, respectively. The cell proliferation was detected by CCK-8 and apoptosis was measured by flow cytometry. The expressions of BCL-2, BAX, caspase-3, Akt, p-Akt, p-mTOR, p-P70S6K, H3K36me2 were detected by Western blot.</p><p><b>RESULTS</b>After transfecting the OCI-Ly3 cells by NSD2-shRNA for 72 h, the expressions of NSD2 mRNA and protein both were down-regulated(P<0.05), the proliferation rate of cells in NSD2 shRNA group was significantly lower than that in control and Neg shRNA groups (P<0.05); the apoptosis rate of cells in NSD2 shRNA group was significantly higher than that in control and neg-shRNA group (30.37±4.22)% vs 1.36±0.52 % and 2.17±1.43)%(P<0.05); the expressions of BAX and caspase-3 were up-regulated, while the expression of BCL-2 was down-regulated; the H3K36me2 level significantly decreased as compared with control group, no obvious decrease of the total protein level of AKT was found, but the expressions of p-Akt, p-mTOR and p-70S6K were down-regulated.</p><p><b>CONCLUSION</b>The silencing NSD2 gene can inhibit the proliferation and induce the apoptosis of OCI-Ly3 cells, their mechanisms may relate with regulating the H3K36me2 level, specifically inhibiting the activivty of AKT/mTOR signal pathway.</p>

Regulatory effect of curcumin on renal apoptosis and its mechanism in overtraining rats / 中国应用生理学杂志

OBJECTIVE@#To study the effects and mechanisms of curcumin alleviating oxidative stress induced by overtraining and inhibiting renal apoptosis in rats.@*METHODS@#Male Wistar rats of 7 weeks old were divided into control group (C group, 12), overtraining group (OM group, 11), curcumin + overtraining group (COM group, 14). Group C did not undergo any exercise intervention. Rats in OM group and COM group underwent 8-week incremental load swimming training. During the training, the COM group was treated with curcumin at the dose of 200 mg/(kg·d) in the volume as 5 ml/kg by intragastric administration, and the other groups was treated with an equal volume of 0.5% carboxymethylcellulose. Twenty-four hours after the last training, renal histopathological changes were observed by light microscopy, related biochemical indicators in blood and renal tissue were detected.@*RESULTS@#The results showed that after 8 weeks of incremental load swimming training, the renal tissue structure of group C was normal under light microscope; histopathological changes were observed in OM group; COM group was significantly relieved compared with OM group. Compared with group C, serum levels of corticosterone (Cor), creatinine (Cr) and blood urea nitrogen (BUN) in OM group were increased (0.05), while the expression of heme oxygenase-1 (HO-1) was decreased (<0.05), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were decreased (<0.01), malondialdehyde (MDA) concentration was increased (<0.01); the renal apoptosis was increased (<0.01), the expression of anti-apoptotic B cell lymphoma-2 protein (Bcl-2) was decreased (<0.01), and the expression of proapoptotic Bcl-2 associated X protein (Bax) was increased (<0.01). Compared with the OM group, Cor level was decreased (<0.01) in the COM group, T level was increased (<0.01), Cr and BUN levels were lower (<0.05); the expression of Nrf2 and HO-1 were increased (<0.05), T-AOC and SOD activity were increased (<0.01), MDA concentration was decreased (<0.05); the renal apoptosis was decreased (<0.05), the expression of Bcl-2 was increased (<0.05), and the expression of Bax was decreased (<0.01). The trend of testosterone/corticosterone ratio between groups was consistent with testosterone change, and the change trend of Bcl-2/Bax ratio was consistent with the change of Bcl-2.@*CONCLUSIONS@#The 8-week incremental load swimming training triggered excessive training in rats, aggravated oxidative stress and accelerated renal apoptosis, leading to pathological changes and dysfunction of kidney. Curcumin can up-regulate expression of Nrf2 and HO-1, effectively alleviates oxidative stress induced by overtraining, thereby increasing Bcl-2 expression, decreasing Bax expression, inhibiting renal apoptosis and protecting renal tissue structure and function properly.

Migraine Susceptibility Genes in Han Chinese of Fujian Province

BACKGROUND AND PURPOSE: Five single-nucleotide polymorphisms (SNPs) (rs4379368, rs10504861, rs10915437, rs12134493 and rs13208321) were recently identified in a Western population with migraine. These migraine-associated SNPs have not been evaluated in a Han Chinese population. This study investigated the associations of specific SNPs with migraine in a Han population. METHODS: This was a case-control study of Han Chinese residing in Fujian Province. Polymerase chain reaction—restriction-fragment-length polymorphism analysis and direct sequencing were used to characterize the relationships of SNPs in a control group of 200 subjects and in a migraine group of 201 patients. RESULTS: The frequencies of the five SNPs did not differ between patients with migraine and healthy non migraine controls. However, subgroup analysis indicated certain SNPs were more strongly associated with migraine with aura or migraine without aura than with controls. The CT genotype of rs4379368 was more common in migraine patients with aura (75%) than in migraine patients without aura (47.9%) and controls (48.5%) (p<0.05), and the TT genotype of rs10504861 was more common in migraine patients with aura than in controls (8.3% vs. 0.5%) (p<0.05). Meanwhile, the CC genotype of rs12134493 was less common in migraine patients without aura than in controls (80.6% vs. 88%) (p<0.05). CONCLUSIONS: Our findings suggest that the rs4379368 and rs10504861 SNPs are markers for susceptibility to migraine with aura and that rs12134493 is a marker for the risk of migraine without aura in this Han population. Future studies should further explore if these associations vary by ethnicity.