BACKGROUND Anthocyanins have been shown to improve endothelial function in animal models. However, whether these compounds have similar beneficial effects in humans is largely unknown. METHODS In a short-term crossover study, 12 hypercholesterolemic individuals were given oral anthocyanins (320 mg) isolated from berries or placebo. Brachial artery flow-mediated dilation (FMD) was assessed before and after the intervention. In a long-term intervention trial (12 weeks), 150 hypercholesterolemic individuals were given anthocyanins (320 mg/day, n = 75) or placebo (n = 75), after which we measured FMD, plasma cGMP, and other serum biomarkers. Another short-term intervention was conducted in the presence of NO-cGMP inhibitors in 6 people and in a rat aortic ring model (n = 8). RESULTS Significant increases of FMD from 8.3% (0.6%) at baseline to 11.0% (0.8%) at 1 h and 10.1% (0.9%) at 2 h were observed after short-term anthocyanin consumption, concomitantly with increases of plasma anthocyanin concentrations (P < 0.05). In the study participants who received long-term anthocyanin intervention, compared with the control group, we observed significant increases in the FMD (28.4% vs 2.2%), cGMP (12.6% vs −1.2%), and HDL-cholesterol concentrations, but decreases in the serum soluble vascular adhesion molecule-1 and LDL cholesterol concentrations (P < 0.05). The changes in the cGMP and HDL cholesterol concentrations positively correlated with FMD in the anthocyanin group (P < 0.05). In the presence of NO-cGMP inhibitors, the effects of anthocyanin on endothelial function were abolished in human participants and in a rat aortic ring model. CONCLUSIONS Anthocyanin supplementation improves endothelium-dependent vasodilation in hypercholesterolemic individuals. This effect involves activation of the NO-cGMP signaling pathway, improvements in the serum lipid profile, and decreased inflammation.
The miRNA cluster miR-17-92 is known to act as an oncogene in various cancers. Members of this cluster were also found to be involved in some other pathological process, such as steatosis, which is a pivotal event in the initiation and progression of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether miR-17, one of the most functional miRNAs in the miR-17-92 family, participates in the process of steatosis in hepatoma cells.We developed both a miR-17-expressing transgenic mouse model and a miR-17-expressing HepG2 cell model, the latter was established via stable transfection. Real-time PCR and western blot were applied to measure the expression levels of miR-17 and the potential target gene CYP7A1. The luciferase assay was used to confirm direct binding of miR-17 and CYP7A1. The oleic acid induction assay and Oil-Red-O staining were performed to support the determination of steatotic changes in HepG2 cell.Extensive steatotic changes were observed in the livers of transgenic mice. Fewer were seen in the wild-type animals. CYP7A1 was confirmed as a target gene of miR-17, and the expression of CYP7A1 was found to be negatively regulated in both the transgenic mice liver cells and the miR-17-expressing HepG2 cells. CYP7A1 was found to participate in miR-17-induced steatosis, as its repressed expression in miR-17 HepG2 cells exacerbated steatotic change. Re-introduction of CYP7A1 into miR-17 HepG2 cell partially alleviated steatosis.miR-17 is a novel regulator of CYP7A1 signaling in hepatic lipid metabolism, suggesting a potential therapeutic approach for fatty liver.
To explore the relationship between the fatty acid lipophilic index (LI) of the erythrocyte membrane and oral cancer risk, as well as to evaluate the possibility of LI acting as a mediator of the association between body mass index (BMI) and oral cancer.Twenty-three fatty acids (FAs) of the erythrocyte membrane were measured using gas chromatography in 380 patients with oral cancer and 387 control subjects. The LI was calculated based on the FA proportion and FA melting points. The association of BMI and erythrocyte LI with oral cancer risk was analysed using logistic regression. The mediation effect of LI on the association between BMI and oral cancer risk was evaluated using mediation analysis.Among the control group, 46.0% were overweight or obese, which was significantly higher than that of oral cancer patients (29.5%). Significant differences in erythrocyte membrane saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were observed between the patient and control groups. The proportion of C18:1 n-9 from the MUFA family increased in oral cancer patients (12.67%) compared with controls (12.21%). While the total proportion of n-3 PUFAs decreased in oral cancer patients compared with controls, with C20:5 n-3 decreasing from 0.66 to 0.47%, and C22:6 n-3 decreasing from 5.82 to 4.86%. The LI was lower in the control participants (M = 27.6, IQR: 27.3-27.9) than in the oral cancer patients (M = 28.2, IQR: 27.9-28.5). BMI was inversely associated with oral cancer risk with a fully adjusted OR of 0.59 (95% CI: 0.43-0.83), while LI was positively associated with oral cancer risk with a fully adjusted OR of 1.99 (95% CI:1.36-2.94). LI explained 7% of the variance in the relationship between BMI and oral cancer risk.The distribution of the FA profile in erythrocyte membranes differed between the oral cancer patients and the control group. The LI derived from the profile of FAs was positively associated with the risk of oral cancer, and the associations between BMI and oral cancer risk can be explained, at least in part, by LI.
MicroRNAs (miRNA) precursor (pre-miRNA) molecules can be processed to release a miRNA/miRNA* duplex. In the canonical model of miRNA biogenesis, one strand of the duplex is thought to be the biologically active miRNA, whereas the other strand is thought to be inactive and degraded as a carrier or passenger strand called miRNA* (miRNA star). However, recent studies have revealed that miRNA* strands frequently play roles in the regulatory networks of miRNA target molecules. Our recent study indicated that miR-17 transgenic mice could abundantly express both the mature miR-17-5p and the passenger strand miR-17-3p. Here, we showed that miR-17 enhanced prostate tumor growth and invasion by increasing tumor cell proliferation, colony formation, cell survival and invasion. miRNA target analysis showed that both miR-17-5p and miR-17-3p repressed TIMP metallopeptidase inhibitor 3 (TIMP3) expression. Silencing with small interfering RNA against TIMP3 promoted cell survival and invasion. Ectopic expression of TIMP3 decreased cell invasion and cell survival. Our results demonstrated that mature miRNA can function coordinately with its passenger strand, enhancing the repressive ability of a miRNA by binding the same target. Within an intricate regulatory network, this may be among the mechanisms by which miRNA can augment their regulatory capacity.
Objective: To investigate the effects between fish, seafood and pickled food intakes on oral squamous cell carcinoma (OSCC). Methods: A case-control study was carried out in Fujian area during September 2010 to December 2016, in which 604 newly diagnosed primary OSCC cases confirmed by pathological diagnosis were collected from hospital and 1 343 control subjects were enrolled from community and healthy hospital population. Demographic data, history of smoking drinking and tea drinking, oral hygiene status and dietary behaviors (fish, seafood and pickled food intakes) were collected by in-person interviews using a standard questionnaire.Using unconditional logistic regression to estimate adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to assess the effects of fish, seafood and pickled food intakes on OSCC. Analysis stratified by smoking, alcohol drinking and bad prosthesis to explore the possible difference in association between subgroups. Multiplicative interactions and additive interactions between fish and bad prosthesis, seafood and alcohol drinking, pickled food and bad prosthesis were assessed by unconditional logistic regression, relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). Results: The average age of case group and control group were separately (58.69±13.92) years old and (59.27±11.37) years old (χ(2)=4.75, P=0.191). The people whose fish and seafood intakes ≥3 times/week had the lower risk of OSCC, the adjusted OR (95%CI) values were 0.63 (0.52-0.77) and 0.51 (0.41-0.64); The stratified analysis indicated that the people having bad prosthesis had the lower risk of OSCC if they eating fish ≥3 times/week, and the adjusted OR (95%CI) values was 0.53 (0.39-0.71); the people having bad prosthesis had the higher risk of OSCC if they eating pickled food ≥3 times/week, the adjusted OR (95%CI) values was 1.37 (1.02-1.88). Regularly eating seafood can decrease the risk of OSCC for non-smokers, smokers, non-drinkers, drinkers, people without bad prosthesis and had bad prosthesis, the adjusted OR (95%CI) values were 0.49 (0.36-0.68), 0.52 (0.37-0.73), 0.41 (0.31-0.55), 0.77 (0.51-0.96), 0.49 (0.36-0.67), 0.59 (0.42-0.83). Crossover analysis showed fish and bad prosthesis exist multiplication interaction relationship (adjusted OR=0.66, 95%CI: 0.44-0.97) and additional interaction relationship (RERI=-0.81, 95%CI:-1.43--0.19; AP=-0.76, 95%CI:-1.35--0.17; S=0.08, 95%CI: 0.01-0.98); pickled food and bad prosthesis exist multiplication interaction relationship (adjusted OR=1.63, 95%CI: 1.06-2.51) and addition interaction relationship (RERI=0.65, 95%CI:0.08-1.22; AP=0.36, 95%CI:0.10-0.62; S=5.19, 95%CI:1.32-54.49). Conclusion: Reducing the consumption of pickled food, quitting smoking and limiting alcohol consumption, and regularly eating fish and seafood can prevent the occurrence of OSCC.目的： 分析食用腌制食品、鱼肉、海鲜与口腔鳞状细胞癌（OSCC）的关系。 方法： 采用病例-对照研究方法，收集2010年9月至2016年12月在医院确诊的604例OSCC新发病例；同期收集来自社区和医院体检的健康人群为对照组，共1 343名。采用统一编制的问卷，调查人口学特征、吸烟史、饮酒史、饮茶史、口腔卫生情况、膳食情况（包括食用腌制食品、鱼肉和海鲜）等。采用多因素二分类非条件logistic回归模型分析鱼肉、海鲜、腌制食品与OSCC发病的关系；采用分层分析方法，对食用鱼肉、海鲜和腌制食品等因素按照吸烟、饮酒和不良修复体携带情况进行分层分析；采用非条件logistic回归模型并结合超额相对危险度、归因比和交互作用指数等指标，对鱼肉与不良修复体、海鲜与饮酒、腌制食品与不良修复体分别进行相乘、相加交互作用分析。 结果： 病例组对象的年龄为（58.69±13.92）岁，对照组对象的年龄为（59.27±11.37）岁（χ(2)=4.75，P=0.191）。食用鱼肉≥3次/周、食用海鲜≥3次/周者发生OSCC风险较低，调整OR(95%CI)值分别为0.63（0.52~0.77）和0.51（0.41~0.64）。分层分析发现，食用鱼肉≥3次/周的不良修复体携带者发生OSCC的风险较低，调整OR(95%CI)值为0.53(0.39~0.71)；食用腌制食品的不良修复体携带者发生OSCC的风险增加，调整OR(95%CI)值为1.37(1.02~1.88)；无论非吸烟和吸烟者、非饮酒和饮酒者、不携带不良修复体和携带者中，食用海鲜≥3次/周均与发生OSCC呈负相关，调整OR(95%CI)值分别为0.49(0.36~0.68)、0.52(0.37~0.73)、0.41(0.31~0.55)、0.77(0.51~0.96)、0.49(0.36~0.67)、0.59(0.42~0.83)。交互作用分析发现，鱼肉与不良修复体存在负相乘交互作用（调整OR=0.66，95%CI：0.44~0.97）和负相加交互作用（超额相对危险度为-0.81，95%CI：-1.43~-0.19；归因比为-0.76，95%CI：-1.35~-0.17；交互作用指数为=0.08，95%CI：0.01~0.98）；腌制食品与不良修复体存在正相乘交互作用（调整OR=1.63，95%CI：1.06~2.51）和相加交互作用（超额相对危险度为0.65，95%CI：0.08~1.22；归因比为0.36，95%CI：0.10~0.62；交互作用指数为5.19，95%CI：1.32~54.49）。 结论： 减少食用腌制食品，戒烟限酒，及时根治不良修复体，规律地食用鱼肉、海鲜可能降低OSCC风险。.
Genetic variations of NF-κB and its inhibitor IκB genes and their biological mechanism in oral cancer were not well recognized. The purpose of this study was to evaluate the associations of polymorphisms in NFKB1 and NFKBIA with oral cancer susceptibility, and further explore their potential mechanism in vitro. First, the polymorphisms of NFKB1 and NFKBIA were genotyped through iPLEX Sequenom MassARRAY platform in a case-control study with 425 oral cancer patients and 485 healthy controls. Then, the function was explored by a luciferase reporter assay and an electrophoretic mobility shift assay (EMSA) in human tongue squamous cell carcinoma cell lines. The results indicated that NFKB1 rs28362491 Del/Del and rs72696119 G/G genotypes were associated with the risk of oral cancer, with a strong linkage disequilibrium (D' = 0.991, r
Objective To investigate the association between dietary fatty acid (FA) patterns and the risk of oral cancer. Method A case-control study which included 446 patients with oral cancer and 448 controls subjects was conducted in Southeast China. A structured food frequency questionnaire was used to assess the dietary FA consumption before cancer diagnosis. FA patterns were identified using the principal component analysis, and the relationship between the dietary FA patterns and oral cancer was analyzed by logistic regression. Results General differences in FA intake were observed between the patient and control groups. The intakes of saturated FAs (SFAs) C14:0, C16:0, C18:0, and monounsaturated FA C18:1 were higher in the patient group than the control group ( p < 0.001). Four FA patterns were derived by principal component analysis. The “SFA” pattern, “Polyunsaturated FA” pattern, “Monounsaturated FA” pattern, and “Medium- and long-chain FA” pattern, which could explain 75.7% of the variance of the dietary FA intake, were submitted to logistic regression analysis. A positive association was observed between the “SFA” pattern and oral cancer risk. Compared with the lowest quartile score, the OR of the highest quartile score was 3.71 (95% CI : 2.31, 5.94, P trend < 0.001) in the multivariate logistic regression model. No significant association was found among the other three patterns and oral cancer risk. Conclusions General differences in dietary FA intake were observed between patients with oral cancer and controls. A positive association between the “SFA” pattern and risk of oral cancer was observed after adjusting for potential confounders.
Evidence about ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and oral cancer risk were limited. We aimed to evaluate the association of erythrocyte ω-3 PUFAs with the risk of oral cancer in a population from China.Erythrocyte ω-3 PUFAs of 236 oral cancer patients and 300 controls were determined by gas chromatography. Restricted cubic spline and logistic regression were used to analyze the association between erythrocyte ω-3 PUFAs and oral cancer risk. The crude and adjusted OR with 95% CI was calculated. Stratification analysis was performed to explore the potential interaction between ω-3 PUFAs and other traditional risk factors such as smoking and drinking.Eicosapentaenoic acids (EPA), docosahexaenoic acids (DHA) and ω-3 index were negatively but non-linearly related to risk of oral cancer as observed by restricted cubic spline. The adjusted OR of EPA, DHA, and ω-3 index were 0.52 (95% CI: 0.35-0.76), 0.19 (95% CI: 0.08-0.44), 0.20 (95% CI: 0.09-0.44), respectively. Stratification analysis showed that the adverse correlation between EPA and oral cancer was only significant in the non-smoking group, while the adverse correlation of ɑ-linolenic acid (ALA), EPA, and DHA were only significant in the non-drinking group. General multiplicative interactions were observed between ω-3 PUFAs and smoking or drinking.Adverse but non-linear associations were observed between erythrocyte EPA, DHA, ω-3 index, and oral cancer risk. Additionally, there were multiplicative interactions between ω-3 PUFAs and other behavior factors such as smoking and drinking. The protective effect of ω-3 PUFAs maybe more significant in the non-smoking or non-drinking population.
Abstract Background To explore the effect of smoking and drinking on survival of patients with oral cancer by comparing the characteristics and survival of nonsmoking and nondrinking (NSND) patients in contrast to smoking and/or drinking (SD) patients. Methods This prospective study including 1165 patients with oral cancer was conducted in Fujian, China from January 2005 to January 2019. The patients were categorized to two groups, the NSND group and SD group. We compared overall survival and disease‐specific survival between the two groups using the Kaplan‐Meier method and Cox proportional hazards regression before and after propensity score matching (PSM) to explore the effect of smoking and drinking on the prognosis of patients with oral cancer. Results NSND patients accounted for 55.45% (646 patients) of all the patients with oral cancer. SD patients with oral cancer tended to be older and mainly are male (98.46%) and with more advanced disease status. There are trends toward both higher risk of all‐cause death (HR = 1.678; 95% CI: 1.086‐2.594) and oral cancer specific death (HR = 1.632; 95% CI: 1.044‐2.552) in SD patients with oral cancer before PSM. After PSM, the association is still significant, with adjusted HR of 1.897 (95% CI: 1.138‐3.165) for all‐cause death and adjusted HR of 1.764 (95% CI: 1.043‐2.983) for oral cancer‐specific death. Additionally, PSM can improve the HR value and result in a stronger association. Conclusions Social and clinical characteristics of NSND patients differed from SD patients with oral cancer. SD patients with oral cancer have higher all‐cause mortality and oral cancer‐specific mortality than NSND patients.
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