Mechanistic and functional extrapolation of SET and MYND domain-containing protein 2 to pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal neoplasms worldwide and represents the vast majority of pancreatic cancer cases. Understanding the molecular pathogenesis and the underlying mechanisms involved in the initiation, maintenance, and progression of PDAC is an urgent need, which may lead to the development of novel therapeutic strategies against this deadly cancer. Here, we review the role of SET and MYND domain-containing protein 2 (SMYD2) in initiating and maintaining PDAC development through methylating multiple tumor suppressors and oncogenic proteins. Given the broad substrate specificity of SMYD2 and its involvement in diverse oncogenic signaling pathways in many other cancers, the mechanistic extrapolation of SMYD2 from these cancers to PDAC may allow for developing new hypotheses about the mechanisms driving PDAC tumor growth and metastasis, supporting a proposition that targeting SMYD2 could be a powerful strategy for the prevention and treatment of PDAC.

Anti-inflammatory effects of astaxanthin against fungal keratitis.

AIM: To characterize effect of astaxanthin (ASX) in Aspergillus fumigatus (A. fumigatus) induced keratitis in mouse model. METHODS: In vivo, fungal keratitis mouse model was established in C57BL/6 mice using A. fumigatus, followed by ASX or dimethyl sulfoxide (DMSO) treatment. Clinical responses were evaluated by clinical score and myeloperoxidase (MPO) assay. Inflammatory cytokines were assessed by reverse-transcription polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, and enzyme-linked immuno sorbent assay (ELISA). RESULTS: In animal model, ASX improved corneal transparency and clinical response, suppressed the expression of inflammatory cytokine like IL-1ß, TNF-α, and HMGB-1. Neutrophil levels have been shown to decrease in ASX-treated cornea by immunofluorescence and MPO. TLR2 and TLR4 levels were lower in ASX-treated group than DMSO-treated. CONCLUSION: ASX can suppress inflammatory response and reduce inflammatory cytokine production in mice model with A. fumigatus keratitis.

The characteristics of the frequent exacerbator with chronic bronchitis phenotype and non-exacerbator phenotype in patients with chronic obstructive pulmonary disease: a meta-analysis and system review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients with different phenotypes show different clinical characteristics. Therefore, we conducted a meta-analysis to explore the clinical characteristics between the non-exacerbator (NE) phenotype and the frequent exacerbator with chronic bronchitis (FE-CB) phenotype among patients with COPD. METHODS: CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases were searched from the times of their inception to April 30, 2019. All studies that reported the clinical characteristics of the COPD phenotypes and which met the inclusion criteria were included. The quality assessment was analyzed by Cross-Sectional/Prevalence Study Quality recommendations. The meta-analysis was carried out using RevMan5.3. RESULTS: Ten cross-sectional observation studies (n = 8848) were included. Compared with the NE phenotype, patients with the FE-CB phenotype showed significantly lower forced expiratory volume in 1 s percent predicted (FEV1%pred) (mean difference (MD) -8.50, 95% CI -11.36--5.65, P < 0.001, I2 = 91%), forced vital capacity percent predicted (FVC%pred) [MD - 6.69, 95% confidence interval (CI) -7.73--5.65, P < 0.001, I2 = 5%], and forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) (MD -3.76, 95% CI -4.58--2.95,P < 0.001, I2 = 0%); in contrast, Charlson comorbidity index (MD 0.47, 95% CI 0.37-0.58, P < 0.001, I2 = 0], COPD assessment test (CAT) score (MD 5.61, 95% CI 4.62-6.60, P < 0.001, I2 = 80%), the quantity of cigarettes smoked (pack-years) (MD 3.09, 95% CI 1.60-4.58, P < 0.001, I2 = 41%), exacerbations in previous year (2.65, 95% CI 2.32-2.97, P < 0.001, I2 = 91%), modified Medical British Research Council (mMRC) score (MD 0.72, 95% CI 0.63-0.82, P < 0.001, I2 = 57%), and body mass index (BMI), obstruction, dyspnea, exacerbations (BODEx) (MD 1.78, 95% CI 1.28-2.28, P < 0.001, I2 = 91%), I2 = 34%) were significantly higher in patients with FE-CB phenotype. No significant between-group difference was observed with respect to BMI (MD-0.14, 95% CI -0.70-0.42, P = 0.62, I2 = 75%). CONCLUSION: COPD patients with the FE-CB phenotype had worse pulmonary function and higher CAT score, mMRC scores, frequency of acute exacerbations, and the quantity of cigarettes smoked (pack-years) than those with the NE phenotype.

Effect of acupoint application on T lymphocyte subsets in patients with chronic obstructive pulmonary disease: A meta-analysis.

BACKGROUND: The development of chronic obstructive pulmonary disease (COPD) is related to the T lymphocyte mediated inflammatory immune response and immune imbalance. The purpose of this systematic review was to evaluate the clinical efficacy and safety of acupoint application on T lymphocyte subsets in patients with COPD. METHODS: We searched CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, the Cochrane Library, and EMBASE for studies published as of Oct. 31, 2019. All randomized controlled trials of acupoint application on COPD patients that met the inclusion criteria were included. The Cochrane bias risk assessment tool was used for literature evaluation. RevMan5.3 software was used for meta-analysis. RESULTS: Eight studies (combined n = 524) qualified based on the inclusion criteria. Compared with routine treatment alone, acupoint application combined with routine treatment can significantly increase the T lymphocyte CD4/CD8 ratio (MD 0.12, 95% CI 0.03-0.21, P < .01, I = 49%), reduce CD8 T-cells (MD-0.99, 95% CI-1.70-0.28, P < .001, I = 37%), reduce the times of acute exacerbations (MD-0.28, 95% CI-0.35-0.21, P < .001, I = 0), and improve the clinical efficacy (MD 1.30, 95% CI 1.14-1.48, P < .001, I = 39%). CONCLUSION: Acupoint application can improve the CD4/CD8 ratio and CD8 T-cells in patients with COPD and has an auxiliary effect in reducing the times of acute exacerbations and improving clinical efficacy.

The characteristics of the frequent exacerbators with chronic bronchitis phenotype and the asthma-chronic obstructive pulmonary disease overlap syndrome phenotype in chronic obstructive pulmonary disease patients: A meta-analysis and system review.

To investigate the difference of clinical characteristics between chronic obstructive pulmonary disease (COPD) patients with the frequent exacerbators with chronic bronchitis (FE-CB) phenotype and those with the asthma-COPD overlap syndrome (ACO) phenotype.We searched CNKI, Wan Fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases for studies published as of April 30, 2019. All studies that investigated COPD patients with the FE-CB and ACO phenotypes and which qualified the inclusion criteria were included. Cross-sectional/prevalence study quality recommendations were used to measure methodological quality. RevMan5.3 software was used for meta-analysis.Ten studies (combined n = 4568) qualified the inclusion criteria. The FE-CB phenotype of COPD was associated with significantly lower forced vital capacity percent predicted (mean difference [MD] -9.05, 95% confidence interval [CI] [-12.00, -6.10], P < .001, I = 66%), forced expiratory volume in 1 second (FEV1) (MD -407.18, 95% CI [-438.63, -375.72], P < .001, I = 33%), forced expiratory volume in 1 second percent predicted (MD -9.71, 95% CI [-12.79, -6.63], P < .001, I = 87%), FEV1/forced vital capacity (MD -5.4, 95% CI [-6.49, -4.30], P < .001, I = 0%), and body mass index (BMI) (MD -0.81, 95% CI [-1.18, -0.45], P < .001, I = 44%) as compared to the ACO phenotype. However, FE-CB phenotype was associated with higher quantity of cigarettes smoked (pack-years) (MD 6.45, 95% CI [1.82, 11.09], P < .001, I = 73%), COPD assessment test score (CAT) (MD 4.04, 95% CI [3.46, 4.61], P < .001, I = 0%), mMRC score (MD 0.54, 95% CI [0.46, 0.62], P < .001, I = 34%), exacerbations in previous year (1.34, 95% CI [0.98, 1.71], P < .001, I = 68%), and BMI, obstruction, dyspnea, exacerbations (BODEx) (MD 1.59, 95% CI [1.00, 2.18], P < .001, I = 86%) as compared to the ACO phenotype.Compared with the ACO phenotype, COPD patients with the FE-CB phenotype had poorer pulmonary function, lower BMI, and higher CAT score, quantity of cigarettes smoked (pack-years), exacerbations in previous year, mMRC score, and BODEx.This study is an analysis of published literature, which belongs to the second study. Therefore, this study does not require the approval of the ethics committee. The findings will be disseminated through a peer-reviewed journal publication or conference presentation.

Effect of Qigong on self-rating depression and anxiety scale scores of COPD patients: A meta-analysis.

OBJECTIVE: To explore the clinical efficacy and safety of Qigong in reducing the self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores of patients with chronic obstructive pulmonary disease (COPD). METHODS: We searched CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE for studies published as of Dec 31, 2018. All randomized controlled trials of Qigong in COPD patients, which met the inclusion criteria were included. The Cochrane bias risk assessment tool was used for literature evaluation. RevMan 5.3 software was used for meta-analysis. RESULTS: Six studies (combined n = 415 patients) met the inclusion criteria. Compared with conventional therapy alone, Qigong in combination with conventional therapy significantly improved the following outcome measures: SDS score [mean difference (MD) -3.99, 95% CI (-6.17, -1.82), P < .001, I = 69%]; SAS score[MD -4.57, 95% CI (-5.67, -3.48), P < .001, I = 15%]; forced expiratory volume in one second/prediction (FEV1% pred) [MD 3.77, 95% CI (0.97,6.58), P < .01, I = 0]; forced expiratory volume in one second (FEV1) [MD 0.21, 95% CI (0.13, 0.30), P < .001, I = 0%]; forced vital capacity (FVC) [MD 0.28, 95% CI (0.16, 0.40), P < .001, I = 0]; 6-minute walk test (6MWT) distance [MD 39.31, 95% CI (18.27, 60.34), P < .001, I = 32%]; and St. George's Respiratory Questionnaire (SGRQ) total score [MD -11.42, 95% CI (-21.80, -1.03), P < .05, I = 72%]. CONCLUSION: Qigong can improve the SDS and SAS scores of COPD patients, and has auxiliary effects on improving lung function, 6MWT distance, and SGRQ score.

Proteomic Analysis Reveals Different Involvement of Embryo and Endosperm Proteins during Aging of Yliangyou 2 Hybrid Rice Seeds.

Seed aging is a process that results in a delayed germination, a decreased germination percentage, and finally a total loss of seed viability. However, the mechanism of seed aging is poorly understood. In the present study, Yliangyou 2 hybrid rice (Oryza sativa L.) seeds were artificially aged at 100% relative humidity and 40°C, and the effect of artificial aging on germination, germination time course and the change in protein profiles of embryo and endosperm was studied to understand the molecular mechanism behind seed aging. With an increasing duration of artificial aging, the germination percentage and germination rate of hybrid rice seeds decreased. By comparing the protein profiles from the seeds aged for 0, 10 and 25 days, a total of 91 and 100 protein spots were found to show a significant change of more than 2-fold (P < 0.05) in abundance, and 71 and 79 protein spots were identified, in embryos and endosperms, respectively. The great majority of these proteins increased in abundance in embryos (95%) and decreased in abundance in endosperms (99%). In embryos, most of the identified proteins were associated with energy (30%), with cell defense and rescue (28%), and with storage protein (18%). In endosperms, most of the identified proteins were involved in metabolism (37%), in energy (27%), and in protein synthesis and destination (11%). The most marked change was the increased abundance of many glycolytic enzymes together with the two fermentation enzymes pyruvate decarboxylase and alcohol dehydrogenase in the embryos during aging. We hypothesize that the decreased viability of hybrid rice seeds during artificial aging is caused by the development of hypoxic conditions in the embryos followed by ethanol accumulation.

A proteomic analysis of seeds from Bt-transgenic Brassica napus and hybrids with wild B. juncea.

Transgene insertions might have unintended side effects on the transgenic host, both crop and hybrids with wild relatives that harbor transgenes. We employed proteomic approaches to assess protein abundance changes in seeds from Bt-transgenic oilseed rape (Brassica napus) and its hybrids with wild mustard (B. juncea). A total of 24, 15 and 34 protein spots matching to 23, 13 and 31 unique genes were identified that changed at least 1.5 fold (p < 0.05, Student's t-test) in abundance between transgenic (tBN) and non-transgenic (BN) oilseed rape, between hybrids of B. juncea (BJ) × tBN (BJtBN) and BJ × BN (BJBN) and between BJBN and BJ, respectively. Eight proteins had higher abundance in tBN than in BN. None of these proteins was toxic or nutritionally harmful to human health, which is not surprising since the seeds are not known to produce toxic proteins. Protein spots varying in abundance between BJtBN and BJBN seeds were the same or homologous to those in the respective parents. None of the differentially-accumulated proteins between BJtBN and BJBN were identical to those between tBN and BN. Results indicated that unintended effects resulted from transgene flow fell within the range of natural variability of hybridization and those found in the native host proteomes.

[Linkage analysis of susceptibility loci in 2 target chromosomes in pedigrees with paranoid schizophrenia and undifferentiated schizophrenia].

OBJECTIVE: To investigate the relationship of susceptibility loci in chromosomes 1q21-25 and 6p21-25 and schizophrenia subtypes in Chinese population. METHODS: A genomic scan and parametric and non-parametric analyses were performed on 242 individuals from 36 schizophrenia pedigrees, including 19 paranoid schizophrenia and 17 undifferentiated schizophrenia pedigrees, from Henan province of China using 5 microsatellite markers in the chromosome region 1q21-25 and 8 microsatellite markers in the chromosome region 6p21-25, which were the candidates of previous studies. All affected subjects were diagnosed and typed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revised (DSM-IV-TR; American Psychiatric Association, 2000). All subjects signed informed consent. RESULTS: In chromosome 1, parametric analysis under the dominant inheritance mode of all 36 pedigrees showed that the maximum multi-point heterogeneity Log of odds score method (HLOD) score was 1.33 (α = 0.38). The non-parametric analysis and the single point and multi-point nonparametric linkage (NPL) scores suggested linkage at D1S484, D1S2878, and D1S196. In the 19 paranoid schizophrenias pedigrees, linkage was not observed for any of the 5 markers. In the 17 undifferentiated schizophrenia pedigrees, the multi-point NPL score was 1.60 (P= 0.0367) at D1S484. The single point NPL score was 1.95(P= 0.0145) and the multi-point NPL score was 2.39 (P= 0.0041) at D1S2878. Additionally, the multi-point NPL score was 1.74 (P= 0.0255) at D1S196. These same three loci showed suggestive linkage during the integrative analysis of all 36 pedigrees. In chromosome 6, parametric linkage analysis under the dominant and recessive inheritance and the non-parametric linkage analysis of all 36 pedigrees and the 17 undifferentiated schizophrenia pedigrees, linkage was not observed for any of the 8 markers. In the 19 paranoid schizophrenias pedigrees, parametric analysis showed that under recessive inheritance mode the maximum single-point HLOD score was 1.26 (α = 0.40) and the multi-point HLOD was 1.12 (α = 0.38) at D6S289 in the chromosome 6p23. In nonparametric analysis, the single-point NPL score was 1.52 (P= 0.0402) and the multi-point NPL score was 1.92 (P= 0.0206) at D6S289. CONCLUSION: Susceptibility genes correlated with undifferentiated schizophrenia pedigrees from D1S484, D1S2878, D1S196 loci, and those correlated with paranoid schizophrenia pedigrees from D6S289 locus are likely present in chromosome regions 1q23.3 and 1q24.2, and chromosome region 6p23, respectively.

Polycyclic N-heterocyclic compounds. Part 62: Reaction of N-(quinazolin-4-yl)amidine derivatives with hydroxylamine hydrochloride and anti-platelet aggregation activity of the products.

The reactions of N-(5,6,7,8-tetrahydroquinazolin-4-yl)amidines and their amide oximes with hydroxylamine hydrochloride gave abnormal cyclization products via a ring cleavage of pyrimidine component accompanied with a ring closure of 1,2,4-oxadiazole to give N-[2-([1,2,4]oxadiazol-5-yl)cyclohexen-1-yl]formamide oximes. Similarly, N-(quinazolin-4-yl)amidines reacted with hydroxylamine hydrochloride gave the same results. The evaluation of inhibitory activities against platelet aggregation in vitro is also described to show one derivative has potent activity.