Antiproliferation Effects of Curcumin on the STAT5 Signaling Parthway in K562 Cells

OBJECTIVE Curcumin is the major component of the spice turmeric and the yellow pigment in curry powder. Many studies have shown that curcumin （diferuloylmethane） has significant antiproliferative and apoptotic effects in cancer cells by several mechanisms. Signal transducers and activators of transcription （STAT） proteins are critical in mediating a response in hematopoietic cells. This study was designed to investigate whether curcumin is associated with proteins involved in signal transduction and activation of transcription （STAT） and to investigate the expression of signal transducers and activators of transcription and the significance of the STAT5 signaling pathway of by treating k562 cells and cells from CML patients with curcumin. METHODS The study was divided into the following groups： normal control cells （human bone marrow cells）, untreated K562 cells, curcumin treated K562 cells, IFN-γ treated K562 cells, curcumin plus IFN-γ treated K562 cells, and CML patient cells with and without curcumin treatment. Cell proliferation was measured by the MTT assay. The expression of STAT5 mRNA was determined by RT-PCR. The expression of the STAT5 protein was assayed by Western-blotting and the expression of STAT5 in K562 cells was examined under confocal laser-scanning microscopy. The expression of STAT5 mRNA of K562 cells was determined with in situ hybridization. EMSA was used to assess the change in binding of STAT5 with DNA in CML patient cells. RESULTS The proliferation of the K562 cells and CML primary cells was decreased in the curcumin-treated group and/or IFN-γ group. The expression of STAT5 mRNA and protein were decreased the curcumin-treated group as compared with the K562 untreated group （P〈0.01）. STAT5 mRNA and protein expression was decreased in the IFN-γ group compared to the untreated K562 group （P〈0.01）. Combined use of curcumin with IFN-γ inhibited the proliferation of K562 cells and decreased the expression of STAT5 mRNA and protein of the K562 cells. For the CML patient cells, the OD value of STAT5-DNA binding in the curcumin treated cells was less than that compared to untreated cells. CONCLUSION The antiproliferation effects of curcumin may partly be mediated through signal transduction and activation of transcription and may involve the STAT5 signaling pathway.

Associations of short-term ambient temperature exposure with lung function in middle-aged and elderly people:A longitudinal study in China

The short-term associations of ambient temperature exposure with lung function in middle-aged and elderly Chinese remain obscure.The study included 19,128 participants from the Dongfeng-Tongji cohort's first(2013)and second(2018)follow-ups.The lung function for each subject was determined between April and December 2013 and re-assessed in 2018,with three parameters(forced vital capacity[FVC],forced expiratory volume in 1 s[FEV1],and peak expiratory flow[PEF])selected.The China Meteorological Data Sharing Service Center provided temperature data during the study period.In the two follow-ups,a total of 25,511 records(average age:first,64.57;second,65.80)were evaluated,including 10,604 males(41.57%).The inversely J-shaped associations between moving average temperatures(lag01–lag07)and FVC,FEV1,and PEF were observed,and the optimum temperatures at lag04 were 16.5C,18.7C,and 16.2C,respectively.At lag04,every 1C increase in temperature was associated with 14.07 mL,9.78 mL,and 62.72 mL/s increase in FVC,FEV1,and PEF in the lowtemperature zone(<the optimum temperatures),whereas 5.72 mL,2.01 mL,and 11.64 mL/s decrease in the high-temperature zone(the optimum temperatures),respectively(all P<0.05).We observed significant effect modifications of gender,age,body mass index,body surface area,smoking status,drinking status,and physical activity on the associations(all Pmodification<0.05).Non-optimal temperatures may cause lung function decline.Several individual characters and lifestyles have effect modification on the temperature effects.

Expert consensus on One Health for establishing an enhanced and integrated surveillance system for key infectious diseases

China has been continuously improving its monitoring methods and strategies to address key infectious diseases(KIDs).After the severe acute respiratory syndrome epidemic in 2003,China established a comprehensive report-ing system for infectious diseases(IDs)and public health emergencies.The relatively lagging warning thresholds,limited warning information,and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs.Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority,with increasing demand for early warning thresholds,information,and tech-niques,thanks to constant innovation and development in molecular biology,bioinformatics,artificial intelligence,and other identification and analysis technologies.A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs(41 notifiable diseases and emerging IDs).The aim of this surveil-lance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans,animals,and vectors,along with associated environmental pathogens.By integrating factors influencing epidemic spread and risk assessment,the surveillance system can serve to detect,predict,and provide early warnings for the occurrence,development,variation,and spread of known or novel KIDs.Moreover,we recommend comprehensive ID monitoring based on the fourth-generation surveillance system,along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system.This series of considerations is based on systematic and comprehensive monitoring across multiple sectors,dimensions,factors,and pathogens that is sup-ported by data integration and connectivity.This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring,prediction,and early warning capabilities for the next generation of ID surveillance.This expert consensus will serve as a reference for ID prevention and control as well as other related activities.

母体外周血胎儿有核红细胞及其在无创产前诊断中的应用

母体外周血中存在来源于胎儿的具有完整细胞核的红细胞,即胎儿有核红细胞(fetal nucleated red blood cells,FNRBCs).FNRBCs在整个妊娠期内持续存在于母体血液循环之中,具有全套的胎儿遗传物质、细胞器、各类生物分子以及代谢物等,包含丰富的胎儿生理信息,同时还表达多种特异性蛋白,是用于无创式产前检测/诊断的理想分析靶标.然而,孕妇外周血中存在数量巨大的红细胞(~10~9个/mL)和白细胞(~10~6个/mL),FNRBCs则十分稀少(<10^(3)个/mL).在完成母体静脉采血后,如何高效率高纯度分离富集血样中的FNRBCs、确定其胎儿源性并开展面向临床的生化分析极具挑战.本文从实施无创产前检测/诊断的重要意义出发,对母体外周血FNRBCs这一潜力巨大的无创产前检测/诊断标志物进行综述,在介绍FNRBCs来源及特征的基础上,总结FNRBCs分离富集与鉴定分析技术的发展现状,并阐述FNRBCs的临床应用、当前面临的挑战以及今后的发展方向,旨在为相关研究和临床转化提供参考.

Depression and stress levels increase risk of liver cancer through epigenetic downregulation of hypocretin

Recent studies suggest that Hypocretin (HCRT, Orexin) are involved in stress regulation of depression through the hypothalamic-pituitary-adrenal (HPA) axis. However, the molecular mechanism by which Hypocretin regulate neurobiological responses is unknown. Herein, the effects of chronic stress on the epigenetic modification of HCRT and its association with depression were explored with regard to a potential role in cancer progression. In the study, Sprague Dawley (SD) rats were used to establish an animal model of cancer with depression by administrating n-nitrosodiethylamine (DEN) and chronic unpredictable mild stress (CUMS). RNA-sequencing was used to detect differentially expressed genes in the hippocampus of rats and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the results of RNA-sequencing. The status of HCRT promoter methylation was assessed by methylation specific polymerase chain reaction. Behavioral tests showed that rats exposed to CUMS had significant depressive-like behaviors. The number of liver tumors and tumor load in depressed rats exposed to CUMS was higher than in SD rats without CUMS. RNA-sequencing revealed that HCRT was one of the most siginificantly downregulated gene in the hippocampus of SD rats with CUMS compared to non-stressed group, which was validated by qRT-PCR. HCRT mRNA expression was downregulated and the promoter for HCRT was hyper-methylated in those with depression. These results identified a critical role for chronic psychological stressors in tumorigenesis and cancer progression, via epigenetic HCRT downregulation. Such epigenetic downregulation may be the molecular basis for the association of cancer with depression.

30-Year Trends in the Disease Burden, Incidence, and Prevention of Pneumoconiosis

The global incidence of pneumoconiosis,a lung disease caused by inhaling industrial dust,has increased by 61.5%from 1990 to 2019,according to a recent report.China had the highest number of cases in 2019,followed by India and the United States.The all-age standard incidence rate for pneumoconiosis was 2.39 per 100,000 population in 2019,with China also having the highest rate.However,there was a decrease in the incidence rate in Belgium and Italy during the same period.The report also highlights regional variations in the changing trend,with the largest increase in cases observed in North Africa and the Middle East.Improved dust prevention and control measures are urgently needed to reduce workplace dust exposure and combat the rising cases of pneumoconiosis globally.

Zinc-finger protein 382 antagonises CDC25A and ZEB1 signaling pathway in breast cancer

Our previous studies found that Zinc-finger protein 382(ZNF382)played as a tumor suppressor gene in esophageal and gastric cancers,and a positive correlation between the high expression of ZNF382 and better outcome in breast cancer patients.However,the biological roles and mechanisms of ZNF382 in breast cancer remains unclear.We detected ZNF382 expression by reverse-transcription PCR(RT-PCR)and real-time quantitative PCR(qRT-PCR)in breast cancer cells and tissues,and explored the impacts and mechanisms of ectopic ZNF382 expression in breast cancer cells in vitro and in vivo,respectively.Our results revealed that ZNF382 was significantly down-regulated in breast cancer tissues compared with adjacent non-cancer tissues.Restoration of ZNF382 expression in silenced breast cancer cells not only inhibited tumor cell colony formation,viability,migration and invasion,and epithelial-mesenchymal-transition(EMT),but also induced apoptosis and G0/G1 arrest.In conclusion,ZNF382 could induce G0/G1 cell cycle arrest through inhibiting CDC25A signaling,and,inhibit cell migration,invasion and EMT by antagonizing ZEB1 signaling in breast cancer cells.

Novel hepacivirus in Asian house shrew, China

Dear Editor,Hepatitis C virus (HCV) is a leading global cause of various liver diseases, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The genome of HCV is monopartite, single-stranded, positive RNA, about 10 kb in size.HCV is the prototype species of the Hepacivirus genus,which contains 14 species according to the update from the International Committee on Taxonomy of Viruses (Smith et al., 2016).

Short-term impacts of air pollution on the platelet-lymphocyte ratio and neutrophil-lymphocyte ratio among urban adults in China

The short-term impacts of urban air pollution on the platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) remain obscure.In this study,we included 3487 urban adults from the Wuhan-Zhuhai cohort.Individual inhalation exposure to air pollutants was estimated by combining participants’daily breath volume and ambient concentrations of six air pollutants (includingfine particulate matter (PM_(2.5)),inhalable particulate matter(PM_(10)),nitrogen dioxide (NO_(2)),sulfur dioxide (SO_(2)),carbon monoxide (CO) and ozone (O_(3))).The cumulative impacts were assessed by applying lag structures of up to 7 days before the survey date.Associations of air pollutants with PLR and NLR were assessed using a linear mixed model and Bayesian kernel machine regression (BKMR) model.We found that PLR was negatively related to PM_(2.5)(lag02-lag06),PM_(10)(lag02-lag07),NO_(2)(lag02-lag07),and SO_(2)(lag03-lag05) and NLR was negatively related to PM_(10)(lag05 and lag07).In the BKMR model,a negative joint association between the six-air-pollutant mixture and PLR and NLR was observed,whereas PM_(10)and NO_(2)appeared to be more important than the other pollutants in the mixture.The negative impact of air pollutants was stronger in males,participants with lower body mass index (<24 kg/m^(2)),those cooking meals at home,drinkers,and nonexercisers.In conclusion,short-term exposure to air pollutants is significantly related to PLR and NLR in peripheral blood.PLR and NLR may provide new insight into the molecular mechanism underlying the adverse health impact of air pollutants.

Multiple Center Research on Relationship Between Screening Quality and Detection of Cervical Cancer—Six Provinces,China,June–December 2021

The coverage and quality of screening are essential for reducing the incidence of cervical precancers and cervical cancer.This multicenter study aimed to investigate the relationship between screening quality and the detection of cervical precancers and cervical cancer.The study was conducted from June to December 2021 in six hospitals across six provinces.The 2,945 participants were non-pregnant women who underwent colposcopy examinations.The average age of participants was 40.9±11.5 years old.Only 6.9%of participants had received human papillomavirus(HPV)vaccination.A total of 92.6%of participants had abnormal cervical screening results.Of the participants,577 had high-grade squamous intraepithelial lesions(HSIL)or worse(≥HSIL),with a detection rate of 19.6%.Univariate analysis indicated that a lack of cervical cancer screening history in the past five years,as well as positive cervical screening and abnormal colposcopic impression,were independent associated factors of the≥HSIL detection rate.A multivariable logistic regression showed that positive cervical screening[odds ratio(OR)=1.75,95%confidence interval(CI):1.07–2.86]was a risk factor for detecting≥HSIL.Low-grade,high-grade,and cancer of colposcopic impression were associated with a higher risk for detecting≥HSIL(OR=2.94,95%CI:2.13–4.08;OR=36.64,95%CI:26.07–51.48).It is important to disseminate health knowledge to improve public awareness of cervical cancer prevention and to enhance the capacity building of professional staff to improve the quality of cervical cancer screening.

Prevalence of High-Risk Human Papillomavirus in Cervical Intraepithelial Neoplasia in the Pre-Vaccine Era—China,2017–2018

What is already known about this topic?Human papillomavirus(HPV)type-specific strategies play a key role in the prevention of cervical intraepithelial neoplasia(CIN),but evidence on the HPV type-specific prevalence in CIN is limited.What is added by this report?This multicentric study estimates the prevalence of high-risk HPV types in CIN cases and the associations of HPV infection patterns with high-grade CIN in China in 2017–2018.What are the implications for public health practice?Population-based prevention strategies should give preference to HPV-16 and 18,and strategies for non-16/18 high-risk HPV are essential for the elimination of cervical cancer.

Neutralization of interleukin-11 attenuates silica particles-induced pulmonary inflammation and fibrosis in vivo

Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is unclear, and the effective treatments are lacking to date. In this study, we aim to explore the molecular mechanism by which interleukin-11(IL-11) affects silica particles-induced lung inflammation and fibrosis. We observed that IL-11 expressions in mouse lungs were significantly increased after silica exposure, and maintained at high levels across both inflammation and fibrosis phase. Immunofluorescent dual staining further revealed that the overexpression of IL-11 mainly located in mouse lung epithelial cells and fibroblasts. Using neutralizing anti-IL-11 antibody could effectively alleviate the overexpression of pro-inflammatory cytokines(i.e., interleukin-6 and tumor necrosis factor-α) and fibrotic proteins(i.e., collagen type I and matrix metalloproteinase-2) induced by silica particles. Most importantly, the expressions of IL-11 receptor subunit α(IL-11Rα), Glycoprotein130(GP130), and phosphorylated extracellular signal-regulated kinase(p-ERK) were significantly increased in response to silica, whereas blocking of IL-11 markedly reduced their levels. All findings suggested that the overexpression of IL-11 was involved in the pathological of silicosis, while neutralizing IL-11 antibody could effectively alleviate the silica-induced lung inflammation and fibrosis by inhibiting the IL-11Rα/GP130/ERK signaling pathway. IL-11 might be a promising therapeutic target for lung inflammation and fibrosis caused by silica particles exposure.