[Effects and mechanisms of negative air ions on blood pressure, oxidative stress and inflammation levels in SHR rats].

OBJECTIVE: To investigate the effects and possible mechanisms of negative air ions(NAIs) on blood pressure, oxidative stress, and inflammatory status in spontaneous hypertension rats(SHR). METHODS: A total of 60 SHR(half male and half female) were randomly divided into one-month and three-month groups, 30 rats per groups, based on the duration of the intervention. Each group was further randomized into three groups based on the daily intervention time: SHR control group, 2 h NAIs-SHR group, and 6 h NAIs-SHR group, 10 rats per groups. In addition, 20 Wistar Kyoto(WKY)(half male and half female), were randomized into one-month WKY group and three-month WKY group, 10 rats per groups, based on the intervention time. The 2 h NAIs-SHR group and 6 h NAIs-SHR group were exposed to an environment with NAIs concentrations of 4.5×10~4-5×10~4 cm~3 per day for 2 h and 6 h. The WKY group and SHR group were exposed to normal air on a daily basis. Blood pressure of rats in each group was measured every three days, while weight was measured once a week. After sacrificing the rats in the first month and the third month of rearing, wet weight of the organs was weighed. The enzyme linked immunosorbent assay(ELISA) was used to detect 8-hydroxylated deoxyguanosine(8-OHdG), interleukin-6(IL-6), interleukin-8(IL-8), tumor necrosis factor-α(TNF-α), nitric oxide(NO) and endothelin-1(ET-1) levels. Reactive oxygen species(ROS) detection kit was used to detect ROS level. Malondialdehyde(MDA) and superoxide dismutase(SOD), glutathione(GSH) and glutathione disulfide(GSSG) were measured by colorimetric analysis. HE staining was conducted to observe the histopathological morphological changes of the thoracic aorta in each group, and Western blot was conducted to detect the thoracic aortap38 mitogen-activated protein kinase(p38 MAPK), extracellular signal-regulated kinases(ERK), c-Jun n-terminal kinase(JNK), c-fos proteins, c-jun proteins and their phosphorylated proteins level. RESULTS: The weight of WKY male mice in the same week age group was higher than that of SHR control group, and there was no significant difference in the weight between the other groups. The coefficient of heart in SHR control group(4.66±0.48) was higher than that in WKY group(3.73±0.15)(P<0.05), while there were no significant differences in the coefficients of brain, kidney, liver and spleen among the groups. Blood pressure in WKY group at the same age was lower than that in SHR group, and blood pressure in SHR control group at 2-5 and 8-11 weeks was higher than that in 2 h NAIs-SHR and 6 h NAIs-SHR groups(P<0.05). HE staining showed that the internal, middle and external membranes of thoracic aorta in 2 h NAIs-SHR group and 6 h NAIs-SHR group were improved to varying degrees compared with those in SHR control group, including disordered internal membrane structure, thickened middle membrane and broken external membrane. In terms of oxidative stress levels, compared with the SHR control group, the ROS(0.66%±0.17%, 0.49%±0.32%) and 8-OHdG((48.29±8.00) ng/mL, (33.13±14.67)ng/mL) levels were lower in the 6 h NAIs-SHR group(P<0.05), while the GSH/GSSG ratio was higher in the one-month 6 h NAIs-SHR group(10.08±4.93). Compared with the 2 h NAIs-SHR group, the ROS level(0.99%±0.19%) was lower in the 6 h NAIs-SHR group(P<0.05). In terms of inflammatory factor levels, compared with the SHR control group, the IL-8 levels((160.44±56.54) ng/L, (145.77±38.39) ng/L) were lower in the 6 h NAIs-SHR group(P<0.05), while the ET-1 level((249.55±16.98) ng/L) was higher in the one-month WKY group. There was no significant difference in NO levels among the groups. The relative expression of p-p38 protein in the thoracic aorta of rats in the one-month SHR control group was lower than that in the WKY group(P<0.05). The relative expression of p-p38 and p-c-fos proteins in the thoracic aorta of rats at three-months was higher in the SHR control group than in the 2 h NAIs-SHR and 6 h NAIs-SHR groups(P<0.05). CONCLUSION: The intervention of NAIs at a concentration of 4.5×10~4-5×10~4/cm~3 may regulate the partial oxidation and inflammatory state of SHR rats through the ROS/MAPK/AP1 signaling pathway, thereby reducing their blood pressure level.

Impact of signs and symptoms on the prognosis of patients with HFmrEF.

BACKGROUND: Worsening of heart failure (HF) symptoms is the leading cause of medical contact and hospitalization of patients with mildly reduced ejection fraction (HFmrEF). The prognostic value of signs and symptoms for patients with HFmrEF is currently unclear. This study investigated the prognostic impact of signs and symptoms in HFmrEF patients. METHODS: A Cox proportional risk regression model analyzed the relationship between the number of signs/symptoms and outcomes in 1691 hospitalized HFmrEF patients. Ten significant signs and symptoms were included. Patients were divided into three groups (A: ≤2, B: 3-5, C: ≥6 signs/symptoms). Stratified analysis on male and female patients was performed. The primary endpoint was all-cause mortality, and the secondary outcome was a composite of cardiovascular death and heart failure readmission (CV events) post-discharge. RESULTS: After a median follow-up of 33 months, all-cause mortality occurred in 457 patients and CV events occurred in 977 patients. Incidence of all-cause mortality was 20.7%, 32.3%* and 49.4%*† in group A, B and C of male patients, (*P < 0.05 vs. A, †P < 0.05 vs. B) and 18.8%, 33.6% and 55.8%* in group A, B and C of female patients. Incidence of CV events was 64.8%, 70.1%* and 87.5%* in group A, B and C of male patients, 61.9%, 75.3%, and 86.1%* in group A, B and C of female patients. Multivariate Cox regression showed older age, renal insufficiency, higher number of signs and symptoms (≥ 3, hazard ratio [HR] 1.317, 95% confidence interval [CI] 1.070-1.621, P = 0.009; ≥6, HR 1.982, 95% CI 1.402-2.801, P < 0.001), myocardial infarction, stroke, faster heart rate on admission, and diabetes were independently associated with all-cause mortality(all P < 0.05). Similarly, higher number of signs and symptoms (≥ 3, HR 1.271, 95% CI 1.119-1.443, P < 0.001; ≥6, HR 1.955, 95% CI 1.524-2.508, P < 0.001), older age, renal insufficiency, atrial fibrillation, and diabetes were independently associated with cardiovascular events (all P < 0.05). CONCLUSIONS: Higher number of symptoms and signs is associated with increased risk of all-cause mortality and CV events in HFmrEF patients. Our results highlight the prognostic importance of careful inquiry on HF symptoms and related physical examination in HFmrEF patients.

LcERF2 modulates cell wall metabolism by directly targeting a UDP-glucose-4-epimerase gene to regulate pedicel development and fruit abscission of litchi.

Elucidating the biochemical and molecular basis of premature abscission in fruit crops should help develop strategies to enhance fruit set and yield. Here, we report that LcERF2 contributes to differential abscission rates and responses to ethylene in Litchi chinensis (litchi). Reduced LcERF2 expression in litchi was observed to reduce fruit abscission, concurrent with enhanced pedicel growth and increased levels of hexoses, particularly galactose, as well as pectin abundance in the cell wall. Ecoptic expression of LcERF2 in Arabidopsis thaliana caused enhanced petal abscission, together with retarded plant growth and reduced pedicel galactose and pectin contents. Transcriptome analysis indicated that LcERF2 modulates the expression of genes involved in cell wall modification. Yeast one-hybrid, dual-luciferase reporter and electrophoretic mobility shift assays all demonstrated that a UDP-glucose-4-epimerase gene (LcUGE) was the direct downstream target of LcERF2. This result was further supported by a significant reduction in the expression of the A. thaliana homolog AtUGE2-4 in response to LcERF2 overexpression. Significantly reduced pedicel diameter and enhanced litchi fruit abscission were observed in response to LcUGE silencing. We conclude that LcERF2 mediates fruit abscission by orchestrating cell wall metabolism, and thus pedicel growth, in part by repressing the expression of LcUGE.

[Research Progress of Adaptive Intervention].

Adaptive intervention(AI)is a methodology which dynamically evaluates adaptive variables at decision points and timely adjusts and develops tailored strategies to meet individual needs.The study reviewed the origin and development and elaborated the core elements(including intervention outcomes,intervention options,decision points,tailoring variables,and decision rules)and the classification of AI.Based on the literature,the key points of the design and implementation of AI were prospected,which can provide evidence for the research and development of health behavior intervention.

Vitexin protects melanocytes from oxidative stress via activating MAPK-Nrf2/ARE pathway.

INTRODUCTION: Vitiligo is the most common type of depigmented skin disease. Cellular oxidative stress caused by reactive oxygen species (ROS) has been implicated in the pathogenesis of vitiligo. Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway plays an important role in melanocytes against hydrogen peroxide (H2O2) induced oxidative stress. In addition, vitexin may protect vitiligo by inhibiting oxidative stress and inflammation. OBJECTIVE: In the present study, we aimed to investigate the antioxidant effect of vitexin-activated mitogen-activated protein kinase (MAPK)-Nrf2/ARE axis in vitiligo. METHODS: MTT assay identified cell viability of human melanocyte PIG1. Cell apoptosis was evaluated by flow cytometry. Gene and protein expression levels were analyzed by quantitative real-time PCR (qPCR) and Western blotting. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of inflammatory factors and ROS production. RESULTS: Vitexin inhibited H2O2-induced melanocyte apoptosis and promoted cell proliferation. Moreover, vitexin decreased expression of interleukin-1ß (IL-1ß), IL-17A, and ROS in melanocytes induced by H2O2. Subsequently, activation of MAPK-Nrf2/ARE signaling was readily induced by vitexin treatment, as evidenced by the upregulation of antioxidant genes including heme oxygenase 1 (HO-1) and superoxide dismutase (SOD). Knockdown of Nrf2 reversed the protective effect of vitexin on H2O2-induced melanocytes. And, knockdown of Nrf2 increased the expression of IL-1ß, IL-17A and ROS, and reduced HO-1 and SOD expression. CONCLUSIONS: Vitexin protected melanocytes from oxidative stress by activating MAPK-Nrf2/ARE signaling pathway. Our results suggested that the role of the Nrf2/ARE axis in the antioxidant defense of melanocytes, and the potential therapeutic strategy for vitiligo.

Incorporation of nonstandard amino acids into proteins: principles and applications.

The cellular ribosome shows a naturally evolved strong preference for the synthesis of proteins with standard amino acids. An in-depth understanding of the translation process enables scientists to go beyond this natural limitation and engineer translating systems capable of synthesizing proteins with artificially designed and synthesized non-standard amino acids (nsAA) featuring more bulky sidechains. The sidechains can be functional groups, with chosen biophysical or chemical activities, that enable the direct application of these proteins. Alternatively, the sidechains can be designed to contain highly reactive groups: enabling the ready formation of conjugates via a covalent bond between the sidechain and other chemicals or biomolecules. This co-translational incorporation of nsAAs into proteins allows for a vast number of possible applications. In this paper, we first systematically summarized the advances in the engineering of the translation system. Subsequently, we reviewed the extensive applications of these nsAA-containing proteins (after chemical modification) by discussing representative reports on how they can be utilized for different purposes. Finally, we discussed the direction of further studies which could be undertaken to improve the current technology utilized in incorporating nsAAs in order to use them to their full potential and improve accessibility across disciplines.

Job satisfaction of staff in agencies for disease prevention and control in Hainan Province, China.

This study done in Hainan from March 2017 to June aimed to assess job satisfaction status and influencing factors among the staff of agencies for disease prevention and control in Hainan Province. A questionnaire survey was administered to some staff members at 6 centers for disease control and prevention in Hainan Province, job satisfaction in the questionnaire was rated on a 5-points Likert scale (totally agree, agree, not sure, disagree, totally disagree). The average score of job satisfaction for the six centers was 3.35±0.77, which was relatively low. According to the Wilcoxon rank-sum test, job satisfaction showed significant differences among different job titles (P <0.05). Logistic regression showed that the factors influencing job satisfaction were personal development space, rulesand regulations in CDC, personal safety, public health system, and workload. The factors influencing the staff's satisfaction are personal development space, rules and regulations in CDC, personal safety, public health system and workload.

Morphological alterations of intrinsically photosensitive retinal ganglion cells after ablation of mouse photoreceptors with selective photocoagulation.

In this work, we investigated changes in the morphology of intrinsically photosensitive retinal ganglion cells (ipRGCs), M1 subtype, and pupillary light reflex following local and selective ablation of photoreceptors in mice. Laser photocoagulation was used to selectively destroy four patches of photoreceptors per eye at around 4 papillary diameters from the optic disc and at the 3, 6, 9, and 12 o'clock positions between the retinal vessels in the adult mouse retina, leaving cells in the inner retina intact. Morphological parameters of individual M1 cells specifically labeled by the antibody against melanopsin (PA1-780), including dendritic field size, total dendritic length, and dendritic branch number, were examined 1, 2, 4, and 8 weeks after photocoagulation with Neurolucida software. A considerable reduction in these parameters in M1 cells in the "lesioned areas" was found at all the four time points after photocoagulation, as compared with those in the "unlesioned areas". Although M1 cells in the lesioned areas showed significant changes as early as 1 week after laser treatment and the changes gradually increased, reaching a peak value at 2 weeks, morphological restoration was clearly seen in these cells over time. However, no difference in the morphological parameters of M1 cells was observed between the unlesioned areas of laser-treated mice and the corresponding areas of age-matched normal mice without laser lesions. Fluorescence intensity of the somata of melanopsin-positive M1 cells located inside the lesioned areas was significantly decreased at all the four time points after photocoagulation, whereas no changes in pupillary light reflex were detected at different light irradiations, indicating that photocoagulation-induced local photoreceptor loss and alterations of ipRGCs may be insufficient to cause abnormalities in non-image-forming (NIF) visual functions. The results suggest that intact photoreceptors could be crucial for maintaining the expression levels of melanopsin and normal morphology of M1 cells.

Multicenter surveillance study of surgical site infection and its risk factors in radical resection of colon or rectal carcinoma.

BACKGROUND: Colorectal surgery is associated with high rates of surgical site infection (SSI). We investigated SSI in radical resection of colon or rectal carcinoma and its epidemiological distribution in 26 hospitals in China. METHODS: We conducted prospective surveillance of patients who underwent radical resection of colon or rectal carcinoma in 26 selected hospitals from January 2015 to June 2016.An information system monitored all of the surgical inpatients. Infection control professionals observed the inpatients with suspected SSI who had been screened by the system at the bedside. The infection status of the incisions was followed up by telephone 1 month after the operation. RESULTS: In total, 5729 patients were enrolled for the two operations; SSIs occurred in 206 patients, and the infection rate was 3.60%. The incidence of SSI after radical resection of rectal carcinoma (5.12%; 119/2323) was 2.1 times higher than that after radical resection of colon carcinoma (2.55%; 87/3406) (P < 0.0001). Additionally, in the colon versus rectal groups, the rate of superficial incisional SSI was 0.94% versus 2.28% (P < 0.0001), the rate of deep incisional SSI was 0.56% versus 1.11% (P = 0.018), and the rate of organ space SSI was 1.06% versus 1.72% (P = 0.031), respectively. The most common pathogens causing SSIs after radical resection of colon carcinoma were Escherichia coli (21/38) and Pseudomonas aeruginosa (5/38). Escherichia coli (24/65) and Enterococcus spp. (14/65) were the two most common pathogens in the rectal group. The multivariate logistic regression analysis showed that only the operating time and number of hospital beds were common independent risk factors for SSIs after the two types of surgery. CONCLUSION: This multicenter study showed that there were significant differences in the incidence of SSIs, three types of SSIs, and some risk factors between radical resection of colon carcinoma and rectal carcinoma.

Difference analysis in prevalence of incidental pancreatic cystic lesions between computed tomography and magnetic resonance imaging.

BACKGROUND: The purpose was to investigate the difference of detection rate of incidental pancreatic cystic lesions (PCLs) with computed tomography (CT) and magnetic resonance imaging (MRI) and to compare the difference between CT and MRI and to explore the effect of this difference on surgical resection. METHODS: We reviewed the diagnostic reports for incidental PCLs between 2013 and 2016. Images of PCLs would be re-evaluated. Clinical and imaging data were recorded. The chi-square and independent t-test were conducted for categorical and continuous variables. RESULTS: The prevalence of PCLs was 1.91% (1038/54210) and 3.36% (1282/38099) on CT and MRI respectively, and increased with increasing age (P < 0.001). No significant differences were found in the annual prevalence of PCLs on CT (P = 0.796) and MRI (P = 0.213) from 2013 to 2016 while the number of examinations was increasing every year. The annual detection rate of MRI for small PCLs (< 20 mm) was significantly higher than CT (P < 0.001), but was not significantly different for large PCLs (≥20 mm). The rate of surgical resection of PCLs (≥20 mm) in MRI group was higher than CT (55.2% vs. 37.0%, P < 0.001). CONCLUSIONS: The detection rate of PCLs on CT and MRI tended to be stable despite increasing scan volumes. Female had a slightly more frequency of PCLs than male. MRI detected more small PCLs(< 20 mm) and had higher impact on surgical resection of large PCL(≥20 mm) compared with CT.

Effect of a novel Ca-Si composite mineral on Cd bioavailability, transport and accumulation in paddy soil-rice system.

Ubiquitous cadmium (Cd) contamination in mine impacted paddy soil has been jeopardizing regional rice quality, which represents a dominant pathway of Cd exposure in populations depending on a rice diet. Two major aspects of mitigation, soil liming and Si fertilization, were integrated and investigated with a Ca-Si-rich composite mineral (CS) derived from feldspar and carbonate. With the CS amendment, bioavailable Cd in rice rhizosphere was reduced by 92-100% from tillering to maturation stage, paralleled by a marked increase in Cd bound to Fe/Mn oxides and carbonate. As indicated by XRD analysis, the much reduced labile pool of Cd in the CS-amended soil could be mainly attributed to Cd (co)precipitation (Cd(OH)2, Cd2(OH)3Cl, CH6Br3CdN) and surface complexation on more negatively charged oxides at elevated soil pH with CS addition. EDX line scan illustrated much more intensified Si deposition along root cross-section in the CS treatment, which resulted in 1.5-2.1-fold higher Cd sequestration in the CS-amended root than control. As a direct result, the root-to-shoots Cd translocation was reduced significantly by 42-51%, while a slightly less significant decrease in brown rice Cd was obtained with the CS treatment relative to control. The CS amendment showed differing effects on brown rice mineral accumulation, with 1.2-1.5-fold increase in brown rice Zn and simultaneously reduced Fe, Mn, Mg and Cu in brown rice. Our results call the readers' attention to the potential impact of soil ameliorator on grain mineral uptake, and we suggest that proper fortification with mineral fertilizers should be supplemented to assist sustainable rice production with improved mineral nutrition.

[The cognitive and neural bases of abstract concepts].

Words denoting abstract concepts constitute nearly half of human lexicon and serve as building blocks of the human culture. Since the advent of non-invasive neuroimaging techniques, great progress has been made in revealing the neurobiological foundation of concrete object and action concepts, yet it remains unclear how abstract concepts are stored and processed in the brain. Here we review recent development in this field, focusing on both theoretical perspectives and neuroimaging findings. We found that abstract concepts can be represented via linguistic and experiential information; the neural correlates of abstract concepts are partly in line with such a theoretical framework. Future studies are warranted to uncover the cognitive and neural mechanisms of language and experience in abstract word representation, which will help to deepen our understanding of general computational principles of the human conceptual system and to promote the development of the brain-like artificial intelligence.

[XP gene polymorphisms and haplotypes with genetic susceptibility to lung cancer].

OBJECTIVE: To investigate the association of DNA repair gene XPB, XPD and XPG gene polymorphisms and haplotypes with genetic susceptibility to lung cancer. METHODS: A case-control study was conducted, the case group was 100 lung cancer patients in Hainan Province, while the control group was 100 cases of respiratory diseases in Hainan Province. The polymorphism of XPB gene rs4150441 and rs4150434 loci, the polymorphism of the rs171140 and rs11878544 loci of the XPD gene, the XPG gene rs4771436, and the polymorphism of the rs2094258 and rs17655 loci were detected by mass spectrometry. Halopview software was used to investigate the association between XP gene polymorphism and haplotype and genetic susceptibility to lung cancer. RESULTS: The experimental result showed that the rs4150434 locus of XPB gene, the rs4771436 locus of XPG gene and the rs2094258 locus of XPG gene were associated with the genetic susceptibility of lung cancer(P < 0. 05). Among the rs4150434 loci of XPB gene, the susceptibility of individuals carrying heterozygous GA to lung cancer was 2. 071 times than wild type GG(OR = 2. 071, 95% CI = 1. 055-4. 067). The susceptibility of individuals with mutant AA to lung cancer was 2. 535 times than wild type GG(OR =2. 535, 95%CI = 1. 063-6. 044). In the rs4771436 locus of XPG gene, the susceptibility of individuals carrying mutant GG to lung cancer was 2. 494 times than wild type TT(OR = 2. 494, 95% CI = 1. 038-5. 992). In the rs2094258 locus of XPG gene, the susceptibility of individuals carrying mutant AA to lung cancer was 3. 020 times than wild type GG(OR = 3. 020, 95%CI = 1. 015-8. 980). As haplotype result show, compared with GG haplotypes of rs4150441-rs4150434 loci in XPB gene, the risk of lung cancer in GA haplotype was 3. 643 times than GG haplotype(OR = 3. 643, 95% CI = 1. 113-11. 921). Compared with GTC haplotypes of rs2094258-rs4771436-rs17655 loci in XPG gene, the risk of lung cancer in ATC haplotype was 3. 800 times than GTC haplotype(OR = 3. 800, 95%CI = 1. 073-13. 459). CONCLUSION: XPB rs4150434, XPG rs4771436, XPG rs2094258 locus polymorphism and haplotype are associated with the genetic susceptibility to lung cancer.

MiR-514 attenuates proliferation and increases chemoresistance by targeting ATP binding cassette subfamily in ovarian cancer.

Cisplatin is one of the most popular chemotherapeutic drugs in treating ovarian cancer. Resistance to cisplatin is a common clinical challenge that needs to be solved to increase its anti-tumor effects. The relation of miR-514 expression with prognosis in ovarian cancer patients was analyzed based on GSE73584 datasets. The regulation of miR-514 on proliferation and cisplatin chemosensitivity of ovarian cells was examined by MTT assay, colony-formation assay and soft-agar colony-formation assay. Dual luciferase assay was performed to detect the direct interaction of miR-514 with its downstream targets. Immunobloting and qRT-PCR were performed for target gene expression analysis. Low expression of miR-514 was related to poor prognosis in ovarian cancer patients. MiR-514 repressed proliferation and decreased cisplatin chemosensitivity in ovarian cancer cells by targeting ATP binding cassette subfamily. MiR-514 is of clinically significance in ovarian cancer by attenuating proliferation of ovarian cancer cells and decreasing chemoresistance of cisplatin by targeting ATP binding cassette subfamily.

Exposure to beta-cypermethrin impairs the reproductive function of female mice.

This study aimed to investigate the effects of beta-cypermethrin (ß-CYP) on female reproductive function and examine the morphology of the uterine endometrium and follicular development. The results found that the rate of successful pregnancy in the ß-CYP-treated groups significantly decreased. The levels of serum E2 and FSH were significantly increased in the ß-CYP-treated groups. The concentrations of serum P and LH were significantly decreased in the ß-CYP-treated groups. The uterine endometrium was damaged and the endometrial pinopode was markedly inhibited. In addition, the total number of follicles of all types was significantly lower in the medium- and high-dose ß-CYP-treated groups. These results suggest that ß-CYP significantly affected the reproductive function of female mice. ß-CYP may have significantly decreased the fertility of female mice by disturbing the reproductive hormone concentrations and inhibiting the development of the endometrium and the endometrial pinopode.

Effects of chronic exposure to Formaldehyde on micronucleus rate of bone marrow cells in male mice.

Formaldehyde (FA) is the major volatile organic chemical (VOC) present in indoor air, and a constituent known to be associated with sick building syndrome. In the present study, mice were exposed to different concentrations of FA (0, 1, 10 mg/ m3) through static inhalation for 2 hours per day for 20 weeks. The polychromatic erythrocytes/ normochromatic erythrocyte (PCE/NCE) ratio and the micronucleus rates in bone marrow cells were detected. Data indicated that the PCE/NCE ratio in two FA exposure groups were statistically significant lower than the negative control group (P <0.05), and the micronucleus rate in two FA exposure groups were not significantly higher than the control group (P>0.05). These results suggest that chronic static inhalation of FA can reduce the ratio of PCE/NCE in the mice bone marrow, but the effects to the mice bone micronucleus rate are not sure.

Antitumor activity of 4-O-Methylhonokiol in human oral cancer cells is mediated via ROS generation, disruption of mitochondrial potential, cell cycle arrest and modulation of Bcl-2/Bax proteins.

PURPOSE: The plant-derived natural product 4-O-methylhonokiol (MH) has been reported to possess tremendous pharmacological potential ranging from neuroprotection to anticancer activity. However, the anticancer activity of MH in oral squamous cell carcinoma (OSCC) cells has not been evaluated. In the present study, MH was evaluated for its anticancer activity against OSSC PE/CA-PJ41 cells and the possible underlying mechanism was determined. METHODS: Cell cytotoxicity was evaluated by colorimetrybased MTT assay while the effects on cell cycle phase distribution were assessed by flow cytometry. Effects of MH on reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were evaluated by flow cytometry. Western blot assay was finally utilized to study the effects of MH on key cancer and apoptosis-linked proteins including Bax and Bcl-2. RESULTS: MH induced cytotoxicity in OSCC PE/CA-PJ41 cells with an observed IC50 of 1.25 µM. It also caused significant increase in the production of ROS and disrupted the MMP in a dose-dependent manner. The reduction in MMP favored mitochondrial apoptotic pathway which was further confirmed by determining the expression of Bax and Bcl-2. It was observed that MH downregulated the expression of Bax and upregulated the expression of MMP, ultimately leading to apoptosis of OSSC PE/CA-PJ41 cells. Additionally, MH also caused G2/M cell cycle arrest in a dose-dependent manner. CONCLUSION: Taken together, our results indicate that 4-Omethylhonokiol may prove a potential natural anticancer molecule against human oral carcinoma cells.

Prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection.

BACKGROUND: Hexokinase-2 (HK2) and Beta2-adrenergic receptor (Beta2AR) are overexpressed in hepatocellular carcinoma (HCC) tissues and associated with poor prognosis. However, the synergistic effect of HK2 and Beta2AR in HCC prognosis is not elucidated. The present study aims to investigate the association between HK2 and Beta2AR expressions in HCC tissues, and to evaluate the synergistic effect of HK2 and Beta2AR in HCC prognosis. METHODS: Immunohistochemistry of HK2 and Beta2AR was performed on 155 paraffin embedded HCC samples retrieved from the archives of pathology department. Corresponding clinical data and prognostic data were collected through searching medical record systems, death registration systems and interviews with patient families. Spearman correlation test was performed to evaluate the association between HK2 and Beta2AR expression. Kaplan-Meier survival curves and Cox regressions were employed to evaluate HK2 and Beta2AR expression in HCC prognosis, respectively and synergistically. RESULTS: 109 of 155 HCC patients reached the death point, the survival time of HCC patients was 46.23 ± 31.01 months after curative surgical resections of HCC. Kaplan-Meier survival analysis showed that large tumor size (more than 5 cm) (hazard ratio (HR) = 8.42, 95 % confidence interval (CI) = 3.81-18.59, P < 0.0001), advanced TNM stage (III and IV stages) (HR = 2.09, 95%CI = 1.21-3.62, P < 0.001) and AFP more than 20 µg/L (HR = 1.49, 95%CI = 1.02-2.18, P = 0.0302) were predictors for poor prognosis. HK2 and Beta2AR positive expression was detected in 66 (42.58) and 122 (78.71 %) HCC samples respectively. In univariate analysis, HK2(+) (HR = 2.70, 95%CI = 1.76-4.15, P < 0.0001) and Beta2AR(+) (HR = 4.61, 96%CI = 3.14-6.76, P < 0.0001) were associated with poor prognosis. In multivariate analysis, HK2(+) (P < 0.0001) and Beta2AR(+) (P < 0.0001) were also associated with poor prognosis. HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2(-)/Beta2AR(-) in both univariate analysis (HR = 4.69, 95%CI = 2.91-7.57, P < 0.0001) and multivariate analysis (P < 0.0001). HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2(-)/Beta2AR(+) in both univariate analysis (HR = 1.76, 95%CI = 1.17-2.64, P = 0.003) and multivariate analysis (P = 0.004). CONCLUSION: HK2 and Beta2AR play important roles in HCC progression. HK2 and Beta2AR expression in HCC is correlated positively. Beta2AR may increase HCC invasion and metastasis in collaboration with HK2. HK2 and Beta2AR can predict HCC prognosis both independently and synergistically.

[Study on the effect of deficient ERCC2/XPD gene on the repair of DNA damage induced by UVC in CHO cell line].

OBJECTIVE: To explore the function of ERCC2/XPD in the repair of DNA damage induced by UVC. METHODS: Chinese hamster ovary (CHO) cell line including AA8 (wild-type) and UV5 (mutant type, ERCC2/XPD defective), was selected as a cell control model. The cell inhibition rate of AA8 and UV5 after UVC treatment was estimated by MTT assay, and DNA repair capacity to difference irradiation intensity of UVC in cells after 1 h, 3 h, 6 h, 24 h incubation were measured by the Comet Assay and Rad51 immunofluorescence test. RESULTS: As compared to AA8, UV5 was more sensitive to UVC, and whose cell viability decreased. Comet assay and Rad51 immunofluorescence test results show, DNA damage level of UV5 was more serious than AA8. In addition, the DNA damage repair capacity reduced obviously compared with AA8. CONCLUSION: DNA damage repair capacity of UV5 cells reduced due to ERCC2/XPD defective, indicating us that ERCC2/XPD play a critical role in the repair process of DNA damage induced by UVC.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer.

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.