MCM2 promotes the proliferation, migration and invasion of cholangiocarcinoma cells by reducing the p53 signaling pathway.

The abnormal expressions of minichromosome maintenance protein 2 (MCM2) are closely related to the development of various kinds of cancers. We aimed to explore the functions and potential molecular mechanisms of MCM2 gene in cholangiocarcinoma (CCA) cell lines (Huh28 and RBE). First, the cell counting kit-8 (CCK-8), plate clone formation, transwell and invasion assays showed that MCM2 promotes the proliferation, migration and invasion of CCA cells. Flow cytometry assays showed that MCM2 significantly promotes the cell cycle, and inhibits the apoptosis of CCA cells. Further, by analyzing the RNA sequencing data of cholangiocarcinoma, we found that MCM2 gene is significantly negatively correlated with p53 signaling pathway. Quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting (WB) assays confirmed that MCM2 in CCA cells significantly down-regulated the mRNA and protein expression levels of p53 and BAX, and up-regulated the mRNA and protein expression levels of BCL2 and CCND1. Flow cytometry, qRT-PCR and WB assays confirmed that MCM2 promotes CCA through p53 pathway. Finally, we found that MCM2 is up-regulated in CCA tissues compared to the matched non-tumor cholangiocarcinoma tissues, and the high expressions of MCM2 are significantly associated with the poor clinical outcomes of CCA patients. In conclusion, this study revealed that MCM2 promotes the development of CCA by reducing the p53 pathway, and its high expression levels predict poor prognosis in CCA patients. These results provide a theoretical basis for the development of new clinical diagnosis and treatment of cholangiocarcinoma in the future.

Levamisole suppresses adipogenesis of aplastic anaemia-derived bone marrow mesenchymal stem cells through ZFP36L1-PPARGC1B axis.

Aplastic anaemia (AA) is a life-threatening hematopoietic disorder characterized by hypoplasia and pancytopenia with increasing fat cells in the bone marrow (BM). The BM-derived mesenchymal stem cells (MSCs) from AA are more susceptible to be induced into adipogenic differentiation compared with that from control, which may be causatively associated with the fatty BM and defective hematopoiesis of AA. Here in this study, we first demonstrated that levamisole displayed a significant suppressive effect on the in vitro adipogenic differentiation of AA BM-MSCs. Mechanistic investigation revealed that levamisole could increase the expression of ZFP36L1 which was subsequently demonstrated to function as a negative regulator of adipogenic differentiation of AA BM-MSCs through lentivirus-mediated ZFP36L1 knock-down and overexpression assay. Peroxisome proliferator-activated receptor gamma coactivator 1 beta (PPARGC1B) whose 3'-untranslated region bears adenine-uridine-rich elements was verified as a direct downstream target of ZFP36L1, and knock-down of PPARGC1B impaired the adipogenesis of AA BM-MSCs. Collectively, our work demonstrated that ZFP36L1-mediated post-transcriptional control of PPARGC1B expression underlies the suppressive effect of levamisole on the adipogenic differentiation of AA BM-MSCs, which not only provides novel therapeutic targets for alleviating the BM fatty phenomenon of AA patients, but also lays the theoretical and experimental foundation for the clinical application of levamisole in AA therapy.

Tryptanthrin Protects Mice against Dextran Sulfate Sodium-Induced Colitis through Inhibition of TNF-α/NF-κB and IL-6/STAT3 Pathways.

Inflammatory bowel disease (IBD) is a notable health problem and may considerably affect the quality of human life. Previously, the protective roles of tryptanthrin (TRYP) against dextran sulfate sodium (DSS) induced colitis has been proved, but the concrete mechanism remained elusive. It has been suggested that TRYP could diminish the weight loss and improve the health conditions of mice with DSS induced colitis. Hematoxylin and eosin staining revealed that TRYP could improve the histopathological structure of the colon tissue. Two signaling pathways (TNF-α/NF-κBp65 and IL-6/STAT3) were investigated using immunochemistry and western blot. The detected concentrations of the two cytokines TNF-α and IL-6 showed that their levels decreased after TRYP treatment of the colitis. The protein expression level of NF-κBp65 in cytoplasm increased after TRYP treatment of the induced colitis. However, the protein level of NF-κBp65 in the nucleus decreased after administration of TRYP. The expression level of IκBα, the inhibitory protein of NF-κBp65, was tested and the results suggested that TRYP could inhibit the degradation of IκBα. The phosphorylation level of STAT3 was inhibited by TRYP and the expression level of STAT3 and p-STAT3 decreased after administration of TRYP. We conclude that TRYP improves the health condition of mice with DSS induced colitis by regulating the TNF-α/NF-κBp65 and IL-6/STAT3 signaling pathways via inhibiting the degradation of IκBα and the phosphorylation of STAT3.

The Syntheses and Spectroscopic Properties of the Styryl Quinoline Derivatives.

The simple method of the syntheses of the styryl quinoline derivatives was developed. The intermediate of 2-methylquinoline was synthesized from 10 mmol aniline and 20 mmol (E)-2-Butenal dissolved in 8 mL methylbenzene refluxing at 100 ℃ for 3 hours with 10 mL 6 M hydrochloric acid as catalyst. Eight derivatives were obtained in 15 mL glacial acetic acid using 2-methylquinoline (10 mmol) and aromatic aldehyde (12 mmol) as materials refluxing for 8 hours with a yield of 71%～88%. The method is simple, high yield, easy purification and environment friendly. The structures of all derivatives were confirmed with MS, 1HNMR and IR. The vicinal coupling constant of olefinic carbon hydrogen in 1HNMR is 12～18 Hz, and moderate strength absorption peaks appeared at 960～980 cm-1 in IR indicate that carbon-carbon double bond is transconfiguration. Maximum absorption wavelengths of eight products in CH3OH, DMSO, THF and DMF were measured, and emission wavelengths were measured using maximum absorption wavelengths as excitation wavelengths. It turned out that maximum absorption wavelengths among different solvents were 325～376 nm, and emission wavelengths were 367～477 nm. The molar extinction coefficients were within the range of 1.738×104～4.578×104 L·mol-1·cm-1. The maximum absorption wavelengths and emission wavelengths of styryl quinoline derivatives with methoxyl, hydroxyl and benzyl group are greater than others. Among four solvents, the maximum absorption wavelengths almost unchanged, however, the emission wavelengths varies significantly in the following order DMSO>DMF>CH3OH>THF, which indicates the Stokes shift of one product at aprotic solvent is greater than protic solvent. 2-(3,4,5-trimethoxyphenyl)styryl quinolone (Product Ⅱ) which shows the best fluorescence property and the highest Stokes shift value worth further studying.

Synthesis of new 4-anilinoquinazoline analogues and evaluation of their EGFR inhibitor activity.

Thirteen of 4-anilinoquinazoline derivatives with imine groups at position 6 of quinazoline ring were synthesized and their antitumor activities were evaluated by MTT assay and Western blotting analysis. Among these compounds, 13a-131 were reported first time. The MTT assay was carried out on three human cancer cell lines (A549, HepG2 and SMMC7721) with EGFR highly expressed. Among the tested compounds, 13i and 13j exhibited notable inhibition potency and their IC50 values on three cell lines were equivalent to or less than those of gefitinib. Compound 14, without imine group substituted, displayed excellent inhibitor potency only on A549 cell line. Compounds 14 and 13j were chosen to perform Western blotting analysis on A549. The results showed that both of the compounds could inhibit the expression level of phosphorylated EGFR remarkably. It was concluded that the inhibitor potency of compound 14 was almost equivalent to that of gefitinib and the inhibitor potency of 13j was better than that of gefitinib.

The effect of chronoradiotherapy on cervical cancer patients: A multicenter randomized controlled study.

Objectives: To investigate the short-term efficacy and radiotoxicity 3.543of chronoradiotherapy in patients with cervical cancer. We also examined the overall symptom score and quality of life (QOL) of patients who underwent morning radiotherapy and evening radiotherapy. Methods: We conducted a multicenter randomized controlled trial to compare the effects of morning radiotherapy (9:00-11:00 AM) with evening radiotherapy (7:00-9:00 PM) in cervical cancer patients receiving radiotherapy. From November 2021 to June 2022, 114 cervical cancer patients admitted to eight cancer center hospitals in Tianjin, Chongqing, Hubei, Shanxi, Shandong, Shaanxi, Hebei, and Cangzhou were randomly divided into the morning radiotherapy group (MG; N = 61) and the evening radiotherapy group (EG; N = 53). The short-term efficacy of radiotherapy on cervical cancer patients at different time points and the occurrence of radiotoxicity were explored after patients had undergone radiotherapy. Results: The total effective response (partial remission [PR] + complete remission [CR]) rate was similar across the two groups (93.5% vs. 96.3%, p > 0.05). However, the incidence of bone marrow suppression and intestinal reaction in the two groups were significantly different (p < 0.05). The patients in the MG had significantly higher Anderson symptom scores than patients in the EG (21.64 ± 7.916 vs. 18.53 ± 4.098, p < 0.05). In terms of physical activity, functional status, and overall QOL, the MG had significantly lower scores than the EG (p < 0.05). No other measures showed a significant difference between the groups. Conclusion: The radiotherapy effect of the MG was consistent with that of the EG. The incidence of radiation enteritis and radiation diarrhea in the MG was significantly higher than that in the EG; however, bone marrow suppression and blood toxicity in the EG were more serious than in the MG. Because of the small sample size of the study, we only examined the short-term efficacy of radiotherapy. Therefore, further clinical trials are needed to verify the efficacy and side effects of chronoradiotherapy. Clinical Trial Registration: http://www.chictr.org.cn/searchproj.aspx, Registration Number: ChiCTR2100047140.

Food group intake among adolescents in Guangzhou city compared with the Chinese dietary guidelines.

UNLABELLED: Food group intake in adolescents has many health implications. However, no study has been conducted to assess food group intake among Chinese adolescents. OBJECTIVE: The purpose of this study was to evaluate food group intakes among Chinese adolescents living in Guangzhou city and the proportion of adolescents surveyed meeting the Chinese dietary guidelines, and the Chinese food pagoda for a balanced diet 2007. METHODS: A school-based cross-sectional survey was conducted in Guangzhou city between October 2006 and April 2007. A random sample of 2977 adolescents, aged 12 to 17 years, was interviewed. A self-administered semi-quantitative food frequency questionnaire was used to estimate food group intakes of adolescents. RESULTS: A high percentage of adolescents consumed too little plant foods including vegetables, fruit, and soybean products. Only 9%, 14% and 6% of adolescents surveyed reached the minimum daily recommended intake levels for vegetables, fruit, and soybean products and nuts. Nearly 70% of the studied adolescents consumed dairy less than the recommended daily intake and more than 20% adolescents reached the recommended amounts for cereals and eggs. More than one-third (35.6%) of adolescents did not meet any food group recommendations. And no adolescents reached all eight food group recommendations. An inadequate consumption of calcium and iron among adolescents was also found. CONCLUSIONS: The results of this study indicate that most adolescents living in Guangzhou city are not meeting the current recommendations for intakes of the various food groups.

[Leaf photosynthetic potential in canopy layers of un-thinned and thinned apple orchards].

Through the comparison of leaf photosynthetic potential and of photosynthetically active radiation (PAR), leaf nitrogen concentration (Nl), and mass per unit leaf area (Ml) in different canopy layers of un-thinned orchard (UOD) and thinned orchard (TOD), this paper studied the effects of UOD rebuilding on the use efficiencies of PAR and nitrogen, and their relationships to the fruit yield and quality. Thinning obviously improved the radiation environment in canopy. The radiation distribution in TOD canopy was more uniformly than that in UOD canopy, and the invalid space with relative PAR (PARr) less than 30% in TOD approached to zero, while the minimum mean PARr in UOD was 17%, and the space under 0. 3 of relative canopy height was invalid. The leaf photosynthetic efficiency in TOD was notably improved. Comparing with that in UOD, the photsynthetic rate (Pn) at the middle and bottom of the canopy in TOD was increased by 7.8% and 10.2%, respectively. Meanwhile, the photosynthetic potential parameters such as maximum carboxylation rate (Vmax) and maximum electron transfer rate (Jmax) also increased remarkably in TOD. The leaf photosynthetic potential had significant correlation with Nl, and the Nl was strongly correlated with PARr. As a result, leaf photosynthetic potential and PARr could be estimated according to the spatial distribution of relative leaf nitrogen concentration (Nlr).

Coffee consumption and risk of coronary heart diseases: a meta-analysis of 21 prospective cohort studies.

BACKGROUND: A large amount of cohort studies addressed coffee consumption and risk of coronary heart disease (CHD) and yielded inconsistent results. We conducted a meta-analysis to estimate the pooling effects. METHODS: We searched for all published English articles indexed in MEDLINE or PubMed from January 1966 to January 2008. Twenty-one independent prospective cohort studies, which tested CHD risk by coffee consumption, were identified. A general variance-based method was used to pool the relative risks (RR). 15,599 cases from 407,806 participants were included in pooling the overall effects. RESULTS: As compared to the light coffee consumption (<1 cup/d in US or or=6 or >or=7 cups/d) categories of coffee consumption (all p>0.05); Moderate coffee consumption showed significantly lower CHD RR (95% CI) of 0.82 (0.73-0.92) (p<0.001) in women, and of 0.87 (0.80-0.86) (p=0.001) in men and women followed

[Study on food preference and dietary behavior to overweight/obesity in school children and adolescents in Guangzhou: a case-control study].

OBJECTIVE: This study assessed the effect of food preference and dietary behaviors on the risk of overweight or obesity in school children and adolescents aged 6 - 19 years. METHODS: All overweight or obese students, with age- and school-matched controls were recruited for this case-control study from 28 elementary and secondary schools in Guangzhou urban districts from October 2006 to April 2007. Weight and height were measured, and body mass index was calculated for the classification of obesity, overweight and underweight. Their food preference and behaviors were assessed using a structured questionnaire completed by their parents. Behavior and food preference were classified into four levels, and the relevant bottom levels were defined as control groups. Logistic regression was used to assess independent determinants of overweight and obesity. RESULTS: Among 7136 participants, 1947 cases and 2136 normal weight controls from 5755 students with valid questionnaire data were included in the study. Results from univariate analysis showed that odds ratios for overweight or obesity were 0.60-0.69 in those with most preference (top group) on vegetables, fruits, candy, evening snacks, 0.50 in the students of less food partiality, 1.84, 1.30 and 1.26 in those of most preference for pork, beef and deep-fried foods, and 5.14 in students with fastest speed during eating, respectively (all P < 0.05). Vegetable intake, evening snacks preference, speed during eating and food partiality remained with significant association with overweight and obesity in multivariate analysis after adjusted for age, sex, family socio-economical status and their parents' body build. The adjusted odds ratios (OR) and 95% confidence intervals (95%CI) of the above items became 0.55 (0.42 - 0.73), 0.48 (0.35 - 0.65), 0.50 (0.39 - 0.65), and 4.32 (3.23 - 5.80) as compared to the relevant lowest categories, respectively. CONCLUSION: Behaviors as eating more vegetables and slow-eating might be protective factors against overweight and obesity in school children.

[Current attitudes and knowledge about suicide in community members: a qualitative study].

OBJECTIVE: Understand the public's current attitudes and knowledge about suicide and, thus, provide essential information to the development of targeted public education programs-important components of the suicide prevention effort. METHODS: Seventeen mental health professionals who were extensively trained in the methods of conducting focus groups used a pre-tested focus group outline on attitudes and knowledge about suicide to conduct 101 focus groups and 18 individual in-depth interviews with a total of 842 community respondents from 6 regions in northern China. The focus groups and in-depth interviews were audio-taped, transcribed and analyzed using the QSR Nvivo text analysis software. RESULTS: Most respondents believed that suicide was a greater problem in rural areas and among women and identified physical illnesses, economic problems and interpersonal conflicts (particularly family conflicts) as the main causes of suicide. Rural residents and women were believed to exhibit impulsive suicidal behavior because of their personal limitations and over-sensitiveness. Most thought that suicide was understandable and a small proportion felt that it was acceptable behavior in certain circumstances. Almost all felt that suicide resulted in the stigmatization and a loss of 'face' for the family. Most believed that one should show concern for persons who have suicidal behavior and their family members and expressed a willingness to have superficial social relationships with them but were unwilling to establish close personal relations with them. The vast majority believed that suicide was either very difficult or impossible to prevent. CONCLUSIONS: In China the community is tolerant, sympathetic and, in some cases, accepting of suicide but there remains a substantial underlying stigmatization of suicide. Community members have some misunderstandings about suicide; the most obvious misunderstanding is the underestimation of the importance of mental illness as a cause of suicide. The content of public health messages used in suicide prevention programs should be developed by combining findings from both qualitative and quantitative research.