Associations of obesity indices change with cardiovascular outcomes: a dose-response meta-analysis.

BACKGROUND: Little is known about the degrees and shapes of associations of changes in obesity indices with cardiovascular disease (CVD) and mortality risks. We aimed to conduct a dose-response meta-analysis for the associations of changes in weight, body mass index (BMI), waist circumference (WC), waist-to-hip ratio, and waist-to-height ratio with CVD events, CVD-specific deaths, and all-cause mortality. METHODS: We searched MEDLINE via OvidSP, Embase via OvidSP, Web of Science, CINAHL, and Scopus for articles published before January 8th, 2023. Dose-response relationships were modeled using the one-stage mixed-effects meta-analysis. Random-effects models were used to pool the relative risk (RR) and 95% confidence interval (CI). RESULTS: We included 122 articles. Weight change was negatively associated with deaths from CVD and any cause, while WC change elevated CVD-specific mortality. Non-linear relationships also confirmed the adverse effects of increased WC on CVD-specific mortality. Additionally, gains of 5 kg in weight and 1 kg/m2 in BMI or more were associated with elevated CVD events, especially among young adults and individuals without CVD. Conversely, reductions of 5 kg in weight and 1 kg/m2 in BMI or more were associated with higher CVD-specific and all-cause deaths than increased counterparts, particularly among old adults and individuals with CVD. Similar non-linear relationships between relative changes in weight and BMI and deaths from CVD and any cause were observed. CONCLUSIONS: The effects of changes in weight and BMI on CVD outcomes were affected by age and cardiovascular health. Tailored weight management and avoidance of increased WC should be recommended.

Associations of dietary patterns and perceived stress with memory deficits in patients with heart failure.

This study aimed to examine the relationships between dietary patterns and perceived stress with memory deficits in 291 patients with heart failure aged 45-85 years. A total of 142 (48.8%) patients reported memory deficit. Three dietary patterns were identified by K-means clustering: nut-fruit-dairy, meat-processed, and traditional (high intake of cereals) diets. Compared to the traditional diet, the nut-fruit-dairy diet and meat-processed diet were associated with lower levels of deficits in short-term memory, delayed memory, and overall memory. What's more, perceived stress was positively associated with deficits in short-term memory and overall memory, but the association was only found in patients adhering to the traditional diet using stratified analyses. Our findings suggest that adhering to a healthy diet may be conducive to improving deficits in short-term memory, delayed memory, and overall memory, while also buffering the adverse association between perceived stress and deficits in short-term memory and overall memory.

Psychosocial factors associated with career success among nurses: A latent profile analysis.

AIM: In this study, a person-centred approach was used to analyse career success profiles and explore the associated psychosocial factors among nurses. DESIGN: A cross-sectional study was conducted from 15 April to 15 October 2019. METHODS: A total of 1155 registered Chinese nurses were recruited from two general hospitals using convenience sampling. Participants completed a printed questionnaire, including the Maslach Burnout Inventory, Stress of Conscience Questionnaire, Practice Environment Scale, and Career Success Scale. Latent profile analysis and multinomial logistic regression were performed. The data were analysed with Mplus 8.3 and SPSS version 26.0. RESULTS: Three latent profiles of career success were identified: high, moderate and low. Nurses with lower educational levels, more years of work experience, lower emotional exhaustion, higher personal achievement, lower stress of conscience and higher participation in hospital affairs were more likely to have higher career success than the other profiles. CONCLUSIONS: Burnout, stress of conscience, practice environment, educational level and years of work experience were associated with career success among nurses. Targeting interventions may help enhance nurses' career success. Future research should combine subjective and objective indicators (salary, title and so on) to assess career success and explore other determinants for formulating interventions to enhance nurses' career success. IMPACT: The heterogeneity and psychosocial factors associated with nurses' career success provide valuable evidence for the formulation of individualized interventions. Nursing managers should understand the importance of career success, develop interventions to reduce nurses' burnout and stress of conscience, and improve the practice environment to enhance their career success. NO PATIENT OR PUBLIC CONTRIBUTIONS: This study was designed to examine the psychosocial factors associated with nurses' career success. The study was not conducted using suggestions from the patient groups or the public.

Relationships between job burnout, ethical climate and organizational citizenship behaviour among registered nurses: A cross-sectional study.

AIM: This study aimed to investigate the levels of nurses' organizational citizenship behaviour and the associations between job burnout and ethical climate with organizational citizenship behaviour. BACKGROUND: Organizational citizenship behaviour improves adverse outcomes led by nursing shortage. However, the associations between three dimensions of job burnout and organizational citizenship behaviour are inconsistent, and little is known about whether ethical climate is related to organizational citizenship behaviour in nurses. METHODS: In this cross-sectional study, 1157 nurses were selected using convenience sampling from April to October 2019. Self-report surveys assessed nurses' organizational citizenship behaviour, emotional exhaustion, depersonalization, personal accomplishment and perceptions of ethical climate. RESULTS: Mean organizational citizenship behaviour was high among nurses. The regression model showed that job burnout and ethical climate explained an additional 38.6% of the variance in organizational citizenship behaviour over and above sociodemographic factors, with 44.9% of the total variance. CONCLUSION: Nurses' organizational citizenship behaviour was at a relatively high level. Depersonalization was negatively associated with organizational citizenship behaviour while personal accomplishment and ethical climate were positively related to organizational citizenship behaviour. Therefore, nurse leaders are encouraged to take measures to help nurses reduce job burnout and create a favourable ethical climate for increasing nurses' organizational citizenship behaviour.

Associations between potential causal factors and colorectal cancer risk: A systematic review and meta-analysis of Mendelian randomization studies.

OBJECTIVE: To summarize the associations between potential causal factors and colorectal cancer (CRC) risk based on existing Mendelian randomization studies. METHODS: This systematic review and meta-analysis involved a literature search in Embase and Medline. All published articles using Mendelian randomization to explore potential causal factors of CRC were included. Studies that reported Mendelian randomization estimates of standard deviation changes in exposures were included in the meta-analysis. Subgroup analyses based on sex and anatomical sites were performed. RESULTS: One hundred and ninety studies presented in 51 articles were included in systematic review, and 114 studies conducted in 32 articles were included in the meta-analysis. Adult body mass index, waist circumference, waist hip ratio, body height, body fat percentage, arm fat ratio, childhood obesity, lifetime cigarette consumption, short sleep, coffee consumption, and blood levels of vitamin B12 , arachidonic acid, stearic acid, and insulin-like growth factor binding protein 3 were positively associated with CRC risk. Conversely, acceleration-vector-magnitude physical activity, milk consumption, and blood levels of adiponectin, linoleic acid, α-linolenic acid, oleic acid, palmitoleic acid, interleukin-6 receptor subunit-α, and tumor necrosis factor were inversely associated with CRC risk. CONCLUSIONS: Most obesity-related anthropometric characteristics, several unhealthy lifestyles, and blood levels of some micronutrients, fatty acids, and diabetes-related biomarkers were positively associated with CRC risk. In contrast, some lifestyles and blood levels of some fatty acids and inflammatory biomarkers were inversely associated with CRC risk. Future studies with more valid genetic variants are needed for factors with discrepancies between Mendelian randomization and epidemiological studies.

The Relationship Between Uncertainty in Illness and Quality of Life in Patients With Heart Failure: Multiple Mediating Effects of Perceived Stress and Coping Strategies.

BACKGROUND: Previous investigators have demonstrated that uncertainty in illness is associated with quality of life (QoL) in patients with chronic illness. However, little is known about the mechanism underlying the relationship in patients with heart failure. OBJECTIVE: The aim of this study was to examine the multiple mediating effects of perceived stress and coping strategies on the relationship between uncertainty in illness and QoL in patients with heart failure. METHODS: We conducted a cross-sectional study in 302 patients with heart failure recruited at a general hospital in China from October 2016 to September 2017. Uncertainty in illness, perceived stress, coping strategies, and QoL were assessed using self-reported questionnaires. The multiple mediation model was tested using the PROCESS macro for SPSS. RESULTS: Of the 302 patients, 51.7% had poor physical QoL and 45.7% had poor mental QoL (physical component summary or mental component summary score of <50 points). Uncertainty in illness had a significantly negative indirect effect on mental QoL through perceived stress and acceptance-resignation (indirect effect, -0.02; 95% confidence interval, -0.04 to -0.01). Uncertainty in illness also had a significantly negative indirect effect on mental QoL via perceived stress only (indirect effect, -0.18; 95% confidence interval, -0.26 to -0.09). CONCLUSIONS: Poor QoL is prevalent in patients with heart failure. Perceived stress and acceptance-resignation are important mediating factors between uncertainty in illness and mental QoL in patients with heart failure. Interventions aimed at reducing perceived stress and acceptance-resignation coping may be beneficial for improving mental QoL in patients with heart failure.

Cross-cultural differences in nurse burnout and the relationship with patient safety: An East-West comparative study.

AIMS: To compare levels of nurse burnout across eastern and western cultures, as well as examine the influence of burnout on patient safety cross-culturally. DESIGN: Comparative cross-sectional study. METHODS: Survey data were collected from nurses between August and October 2017 in Australia (n = 730) and between April and October 2019 in China (n = 1107). Variables included burnout (emotional exhaustion, depersonalization, personal accomplishment), nurse leadership and support, staffing and resource adequacy, and perceived patient safety. Data were analysed separately for each jurisdiction using bootstrapped hierarchical regressions, which tested the relationships between burnout indicators and patient safety, controlling for support resources. RESULTS: Emotional exhaustion and depersonalization scores were significantly higher in the Australian sample compared with the Chinese sample. Australian participants reported significantly lower patient safety grades than Chinese participants and were less likely to agree that support resources were present in their current job. Separate regressions indicated that patient safety was significantly associated with staffing and resource adequacy, nurse leadership and support, and depersonalization among Australian participants (30% of variance explained in the final regression model), while staffing and resource adequacy, nurse leadership and support, personal accomplishment and emotional exhaustion predicted patient safety for Chinese participants (22% of variance explained in the final model). CONCLUSION: Australian nurses are at greater risk of burnout than Chinese nurses. Burnout dimensions are differentially associated with patient safety across cultures. Culturally relevant interventions may be more optimal than universal approaches for improving burnout and patient safety in nursing. IMPACT: This study increased understanding of cross-cultural differences in nurse burnout and the relationship with patient safety. Australian nurses were at greater risk of burnout than Chinese nurses. Emotional exhaustion, depersonalization and personal accomplishment influenced patient safety distinctively across the countries. These findings inform interventions designed to reduce nurse burnout and improve patient safety internationally.

The multiple mediating effects of social connectedness and self-care confidence on the relationship between subjective social status and emotional well-being in patients with heart failure: a cross-sectional study.

BACKGROUND: Previous studies have shown that subjective social status (SSS) was positively associated with well-being in various populations. However, little is known about the relationship considering the underlying mechanism in patients with heart failure (HF). AIMS: The aim was to study the effects of social connectedness and self-care confidence on the relationship between SSS and well-being in patients with HF according to the Reserve Capacity Model. METHODS AND RESULTS: We recruited 296 patients from a general hospital using convenience sampling. SSS, social connectedness, self-care confidence, and well-being were assessed using self-reported questionnaires. A multiple mediation model was examined using the PROCESS macro in SPSS.Higher levels of SSS (r = 0.18, P < 0.01), social connectedness (r = 0.21, P < 0.01), and self-care confidence (r = 0.20, P < 0.01) were positively correlated with better emotional well-being, but not with physical well-being. The multiple mediation analysis revealed that the relationship between SSS and emotional well-being was mediated by social connectedness (effect: 0.061, 95% CI [0.014, 0.148]) and self-care confidence (effect: 0.110, 95% CI [0.006, 0.249]) separately, and together in serial (effect: 0.008, 95% CI [0.001, 0.028]). CONCLUSIONS: Social connectedness and self-care confidence are multiple mediators of the relationship between SSS and emotional well-being. Interventions targeting to strengthening social connectedness and self-care confidence may improve emotional well-being directly. In addition, emotional well-being may be improved by enhancing SSS indirectly in patients with HF.

[Analysis of volatile oil components of different species of Curcumae Rhizoma based on GC-MS and chemometrics].

The volatile oil of Curcumae Rhizoma has many active components,which are the key to the quality of Curcumae Rhizoma. Exploring the difference between volatile oil of different kinds of Curcumae Rhizoma facilitates the quality control and rational application of resources. In this study,GC-MS was applied to realize online qualitative and semi-quantitative analysis of the chemical composition spectrum of volatile oil from Curcuma wenyujin( CW),C. phaeocaulis( CP),and C. kwangsiensis( CK). Forty components were identified and their fingerprints were compared and evaluated. Hierarchical cluster analysis( HCA),principal component analysis( PCA),and orthogonal partial least squares discrimination analysis( OPLS-DA) were adopted to analyze the overall and outlier data. The results showed that the whole data could be divided into three kinds according to each analysis mode,and the volatile components of Curcumae Rhizoma vary greatly among species. PCA explored the difference between outliers and the mean value of the group and found that some volatile oils from CW may be greatly affected by the origin. By OPLS-DA,the samples from Zhejiang were able to gather,but those from Guizhou remained isolated,indicating the influence of growing environment on Curcumae Rhizoma metabolites. Based on VIP results combined with the heat map,characteristic volatile oil components of Curcumae Rhizoma from different varieties were screened out: curdione and linalool for CW; 2-undecanone for CP; humulene,γ-selinene,and zederone for CK. The GCMS method established in this study describes Curcumae Rhizoma samples comprehensively and accurately,and the characteristic components screened based on chemometrics can be used to distinguish Curcumae Rhizoma from different varieties and give them unique pharmacodynamic significance,which is fast,convenient,stable,and reliable and supports the rational application of Curcu-mae Rhizoma resources. It is found that the region of origin has great influence on CW,which is worthy of further study.

Identification of factors associated with social dysfunction in patients with heart failure.

AIMS: Social dysfunction is adversely associated with individuals' physical and mental quality of life. However, little is known about the status of social dysfunction and its associated factors in patients with heart failure. Our study aimed to reveal the prevalence of social dysfunction, and the associations between fatigue, dyspnoea, anxiety, depression, social connectedness, and social dysfunction in patients with heart failure. METHODS AND RESULTS: We assessed the social dysfunction, fatigue, dyspnoea, anxiety, depression, and social connectedness using self-report questionnaires among 291 patients (64.13 ± 11.84 years, 53.3% male) with heart failure. Two stepwise forward logistic regression models were employed to identify the factors associated with social dysfunction, and the area under receiver operating characteristic curve was used to calculate the variance of the associated factors accounting for social dysfunction. Of the 291 patients, 76.6% reported social dysfunction. The logistic regression model after adjusting co-variables showed that fatigue [odds ratio (OR) 4.233, 95% confidence interval (CI) 1.778-10.081], dyspnoea (OR 0.866, 95% CI 0.756-0.991), depression (OR 1.173, 95% CI 1.037-1.328) were positively associated with social dysfunction, whereas social connectedness (OR 0.394, 95% CI 0.203-0.764) was negatively associated with social dysfunction. Four factors explained 84.5% of the variance of social dysfunction in patients with heart failure. CONCLUSIONS: Social dysfunction is prevalent in patients with heart failure, and fatigue, dyspnoea, depression, and social connectedness are the associated factors. The findings indicate that the key to helping heart failure patients return to social life may be to attenuate fatigue, dyspnoea, and depression and to improve social connectedness.

The multiple mediating effects of illness perceptions and coping strategies on the relationship between physical symptoms and depressive symptoms in patients with heart failure.

BACKGROUND: Depressive symptoms are prevalent and cause poor health outcomes in patients with heart failure. Studies show that the physical symptoms of heart failure are associated with depressive symptoms. However, little is known about the underlying mechanisms of this relationship. AIMS: The purpose of our study was to examine the associations between physical symptoms, illness perceptions, coping strategies and depressive symptoms and to test the multiple mediation effects of illness perceptions and coping strategies on the relationship between physical symptoms and depressive symptoms in patients with heart failure. METHODS: Physical symptoms, illness perceptions, coping strategies and depressive symptoms were assessed using self-reported questionnaires among 302 patients (64.2±11.9 years, 54% male) with heart failure in a tertiary general hospital. A serial multiple mediation model was tested using the PROCESS macro for SPSS. RESULTS: Depressive symptoms were positively correlated with physical symptoms (r=0.487, p<0.01), illness perceptions (r=0.499, p<0.01) and acceptance-resignation coping (r=0.580, p<0.01). The relationship between physical symptoms and depressive symptoms was mediated by illness perceptions (indirect effect: 0.036, confidence interval (0.014, 0.059)) and by acceptance-resignation (indirect effect: 0.034, confidence interval (0.019, 0.053)), respectively, and by these two in serial (indirect effect: 0.021, confidence interval (0.013, 0.033)). CONCLUSION: Patients with heart failure who have more physical symptoms are vulnerable to the development of depression. Healthcare providers should implement interventions focused on changing illness perceptions and reducing acceptance-resignation coping to relieve depressive symptoms.

Pd/TiO2-Photocatalyzed Self-Condensation of Primary Amines To Afford Secondary Amines at Ambient Temperature.

Symmetric secondary amines were synthesized by the self-condensation of primary amines over a palladium-loaded titanium dioxide (Pd/TiO2) photocatalyst. The reactions afforded a series of secondary amines in moderate to excellent isolated yields at ambient temperature (30 °C, in cyclopentyl methyl ether). Applicability for one-pot pharmaceutical synthesis was demonstrated by a photocatalytic reaction sequence of self-condensation of an amine followed by N-alkylation of the resulting secondary amine with an alcohol.

Crystal structures of HpSoj-DNA complexes and the nucleoid-adaptor complex formation in chromosome segregation.

ParABS, an important DNA partitioning process in chromosome segregation, includes ParA (an ATPase), ParB (a parS binding protein) and parS (a centromere-like DNA). The homologous proteins of ParA and ParB in Helicobacter pylori are HpSoj and HpSpo0J, respectively. We analyzed the ATPase activity of HpSoj and found that it is enhanced by both DNA and HpSpo0J. Crystal structures of HpSoj and its DNA complexes revealed a typical ATPase fold and that it is dimeric. DNA binding by HpSoj is promoted by ATP. The HpSoj-ATP-DNA complex non-specifically binds DNA through a continuous basic binding patch formed by lysine residues, with a single DNA-binding site. This complex exhibits a DNA-binding adept state with an active ATP-bound conformation, whereas the HpSoj-ADP-DNA complex may represent a transient DNA-bound state. Based on structural comparisons, HpSoj exhibits a similar DNA binding surface to the bacterial ParA superfamily, but the archaeal ParA superfamily exhibits distinct non-specific DNA-binding via two DNA-binding sites. We detected the HpSpo0J-HpSoj-DNA complex by electron microscopy and show that this nucleoid-adaptor complex (NAC) is formed through HpSoj and HpSpo0J interaction and parS DNA binding. NAC formation is promoted by HpSoj participation and specific parS DNA facilitation.

Author Correction: N-Alkylation of functionalized amines with alcohols using a copper-gold mixed photocatalytic system.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Effect of Rhubarb on Gastrointestinal Dysfunction in Critically Ill Patients: A Retrospective Study Based on Propensity Score Matching.

BACKGROUND: Gastrointestinal dysfunction plays a critical role in the prognosis of critically ill patients. Previous studies showed rhubarb, a traditional Chinese herb, can protect the intestinal barrier function, prevent intestinal bacterial translocation, and promote gastrointestinal peristalsis, but the clinical studies are less. The aim of this study was to evaluate the effects of rhubarb on gastrointestinal dysfunction in critically ill patients. METHODS: From June 2015 to May 2017, a total of 368 critically ill patients with Grade I-III acute gastrointestinal injury (AGI) were enrolled in this study. Patients were divided into two groups according to the exposure factors (whether the patients received rhubarb treatment): the rhubarb group and the usual treatment group. Clinical data were collected within the first 24 h of the Intensive Care Unit (ICU) admission and 7 days after treatment. Survival data on day 28 after ICU admission and the durations of ICU and total hospitalization were also collected. Propensity score matching (PSM) was conducted to reduce confounding bias between the groups. The logistic regression was conducted to screen the influence factors. RESULTS: The eligible patients were divided into rhubarb group (n = 219, 59.5%) and usual treatment group (n = 149, 40.5%). Before PSM, the remission rate of feeding intolerance in rhubarb group and usual treatment group were 59.8% and 39.6%, respectively. After PSM, the remission rate of feeding intolerance in rhubarb group and usual treatment group was 77.9% and 30.9%, respectively. The remission rates of feeding intolerance in rhubarb group were significantly higher than those in the usual treatment group (all P < 0.05). Compared with the usual treatment group, the rhubarb group had a higher rate of AGI improvement, lower level of C-reactive protein, shorter stay in ICU before and after PSM (P < 0.05). There was no significant difference in 28-day mortality between rhubarb and usual treatment groups before and after PSM (48 vs. 33, P = 0.959; and 16 vs. 21, P = 0.335). The logistic regression analysis showed that the single factor, whether receiving rhubarb therapy, affected the proportion of patients whose enteral nutrition needs ≥83.7 kJ·kg-1·d-1 after 7 days of treatment (odds ratio: 7.908, 95% confidence interval: 3.661-17.083, P < 0.001). No serious adverse effects were found in two groups. CONCLUSIONS: The rhubarb might significantly improve feeding tolerance and relieve gastrointestinal dysfunction in critically ill patients, without serious adverse reactions. It provided proof for the treatment of gastrointestinal dysfunction with rhubarb during clinical practice.

N-Alkylation of functionalized amines with alcohols using a copper-gold mixed photocatalytic system.

Direct functionalization of amino groups in complex organic molecules is one of the most important key technologies in modern organic synthesis, especially in the synthesis of bio-active chemicals and pharmaceuticals. Whereas numerous chemical reactions of amines have been developed to date, a selective, practical method for functionalizing complex amines is still highly demanded. Here we report the first late-stage N-alkylation of pharmaceutically relevant amines with alcohols at ambient temperature. This reaction was achieved by devising a mixed heterogeneous photocatalyst in situ prepared from Cu/TiO2 and Au/TiO2. The mixed photocatalytic system enabled the rapid N-alkylation of pharmaceutically relevant molecules, the selective mono- and di-alkylation of primary amines, and the non-symmetrical dialkylation of primary amines to hetero-substituted tertiary amines.

Rhubarb Monomers Protect Intestinal Mucosal Barrier in Sepsis via Junction Proteins.

BACKGROUND: Leakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan failure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins. METHODS: Healthy male Sprague-Dawley rats (weighing 230-250 g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP). After surgical preparation, rats were randomly assigned to eight groups (n = 6 or 8 each group): sham group (Group A: normal saline gavage); sepsis group (Group B: normal saline gavage); Group C (intraperitoneally, dexamethasone 0.5 mg/kg) immediately after CLP surgery; and rhubarb monomer (100 mg/kg in normal saline)-treated groups (Group D: rhein; Group E: emodin; Group F: 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid; Group G: 1-O-caffeoyl-2-(4-hydroxy-O-cinnamoyl)-D-glucose; and Group H: daucosterol linoleate). Animals were sacrificed after 24 h. Intestinal histology, lactulose, mannitol concentrations were measured, and zonula occludens (ZO)-1, occludin and claudin-5 transcription (polymerase chain reaction), translation (by Western blot analysis), and expression (by immunohistochemistry) were also measured. RESULTS: Intestinal histology revealed injury to intestinal mucosal villi induced by sepsis in Group B, compared with Group A. Compared with Group A (0.17 ± 0.41), the pathological scores in Groups B (2.83 ± 0.41, P < 0.001), C (1.83 ± 0.41, P < 0.001), D (2.00 ± 0.63, P < 0.001), E (1.83 ± 0.41, P < 0.001), F (1.83 ± 0.75, P < 0.001), G (2.17 ± 0.41, P < 0.001),and H (1.83 ± 0.41, P < 0.001) were significantly increased. Lactulose/mannitol (L/M) ratio in Group B (0.046 ± 0.003) was significantly higher than in Group A (0.013 ± 0.001, P< 0.001) while L/M ratios in Groups C (0.028 ± 0.002, P< 0.001), D (0.029 ± 0.003, P< 0.001), E (0.026 ± 0.003, P< 0.001), F (0.027 ± 0.003, P< 0.001), G (0.030 ± 0.005, P< 0.001), and H (0.026 ± 0.002, P< 0.001) were significantly lower than that in Group B. ZO-1, occludin and claudin-5 transcription, translation, and expression in Group B were significantly lower than that in Group A (P < 0.001), but they were significantly higher in Groups C, D, E, F, G, and H than those in Group B (P < 0.05). CONCLUSION: Rhubarb monomer treatment ameliorated mucosal damage in sepsis via enhanced transcription, translation, and expression of junction proteins.

Effect of genetic variation in microRNA binding site in WNT1-inducible signaling pathway protein 1 gene on oral squamous cell carcinoma susceptibility.

BACKGROUND: Oral squamous cell carcinoma (OSCC), which is the most common head and neck cancer, accounts for 1%-2% of all human malignancies and is characterized by poor prognosis and reduced survival rates. WNT1-inducible signaling pathway protein 1 (WISP1), a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and may be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms (SNPs) to elucidate OSCC susceptibility and clinicopathologic characteristics. METHODOLOGY/PRINCIPAL FINDINGS: Real-time polymerase chain reaction was used to analyze 6 SNPs of WISP1 in 900 OSCC patients and 1200 cancer-free controls. The results showed that WISP1 rs2929970 polymorphism carriers with at least one G allele were susceptible to OSCC. Moreover, compared with smokers, non-smoker patients with higher frequencies of WISP1 rs2929970 (AG + GG) variants had a late stage (stages III and IV) and a large tumor size. In addition, OSCC patients who were betel quid chewers and carried WISP1 rs16893344 (CT + TT) variants had a low risk of lymph node metastasis. CONCLUSION: Our results demonstrate that a joint effect of WISP1 rs2929970 with smoking as well as WISP1 rs16893344 with betel nut chewing causally contributes to the occurrence of OSCC. WISP1 polymorphism may serve as a marker or a therapeutic target in OSCC.

Hepatitis B virus PreS2-mutant large surface antigen activates store-operated calcium entry and promotes chromosome instability.

Hepatitis B virus (HBV) is a driver of hepatocellular carcinoma, and two viral products, X and large surface antigen (LHBS), are viral oncoproteins. During chronic viral infection, immune-escape mutants on the preS2 region of LHBS (preS2-LHBS) are gain-of-function mutations that are linked to preneoplastic ground glass hepatocytes (GGHs) and early disease onset of hepatocellular carcinoma. Here, we show that preS2-LHBS provoked calcium release from the endoplasmic reticulum (ER) and triggered stored-operated calcium entry (SOCE). The activation of SOCE increased ER and plasma membrane (PM) connections, which was linked by ER- resident stromal interaction molecule-1 (STIM1) protein and PM-resident calcium release- activated calcium modulator 1 (Orai1). Persistent activation of SOCE induced centrosome overduplication, aberrant multipolar division, chromosome aneuploidy, anchorage-independent growth, and xenograft tumorigenesis in hepatocytes expressing preS2- LHBS. Chemical inhibitions of SOCE machinery and silencing of STIM1 significantly reduced centrosome numbers, multipolar division, and xenograft tumorigenesis induced by preS2-LHBS. These results provide the first mechanistic link between calcium homeostasis and chromosome instability in hepatocytes carrying preS2-LHBS. Therefore, persistent activation of SOCE represents a novel pathological mechanism in HBV-mediated hepatocarcinogenesis.

Sgo1 is a potential therapeutic target for hepatocellular carcinoma.

Shugoshin-like protein 1 (Sgo1) is an essential protein in mitosis; it protects sister chromatid cohesion and thereby ensures the fidelity of chromosome separation. We found that the expression of Sgo1 mRNA was relatively low in normal tissues, but was upregulated in 82% of hepatocellular carcinoma (HCC), and correlated with elevated alpha-fetoprotein and early disease onset of HCC. The depletion of Sgo1 reduced cell viability of hepatoma cell lines including HuH7, HepG2, Hep3B, and HepaRG. Using time-lapse microscopy, we showed that hepatoma cells were delayed and ultimately die in mitosis in the absence of Sgo1. In contrast, cell viability and mitotic progression of immortalized cells were not significantly affected. Notably, mitotic cell death induced upon Sgo1 depletion was suppressed upon inhibitions of cyclin-dependent kinase-1 and Aurora kinase-B, or the depletion of mitotic arrest deficient-2. Thus, mitotic cell death induced upon Sgo1 depletion in hepatoma cells is mediated by persistent activation of the spindle assembly checkpoint. Together, these results highlight the essential role of Sgo1 in the maintenance of a proper mitotic progression in hepatoma cells and suggest that Sgo1 is a promising oncotarget for HCC.