Fine particulate matter (PM2.5) induces the stem cell-like properties of hepatocellular carcinoma by activating ROS/Nrf2/Keap1-mediated autophagy.

Exposure to fine particulate matter (PM2.5) has been linked to an increased incidence and mortality of hepatocellular carcinoma (HCC). However, the impact of PM2.5 exposure on HCC progression and the underlying mechanisms remain largely unknown. This study aimed to investigate the effects of PM2.5 exposure on the stem cell-like properties of HCC cells. Our findings indicate that PM2.5 exposure significantly enhances the stemness of HCC cells (p < 0.01). Subsequently, male nude mice were divided into two groups (n = 8/group for tumor-bearing assay, n = 5/group for metastasis assay) for control and PM2.5 exposure. In vivo assays revealed that exposure to PM2.5 promoted the growth, metastasis, and epithelial-mesenchymal transition (EMT) of HCC cells (p < 0.01). Further exploration demonstrated that PM2.5 enhances the stemness of HCC cells by inducing cellular reactive oxygen species (ROS) generation (p < 0.05). Mechanistic investigation indicated that elevated intracellular ROS inhibited kelch-like ECH-associated protein 1 (Keap1) levels, promoting the upregulation and nucleus translocation of NFE2-like bZIP transcription factor 2 (Nrf2). This, in turn, induced autophagy activation, thereby promoting the stemness of HCC cells (p < 0.01). Our present study demonstrates the adverse effects of PM2.5 exposure on HCC development and highlights the mechanism of ROS/Nrf2/Keap1-mediated autophagy. For the first time, we reveal the impact of PM2.5 exposure on the poor prognosis-associated cellular phenotype of HCC and its underlying mechanism, which is expected to provide new theoretical basis for the improvement of public health.

Healthy plant-based diet might be inversely associated with gastric precancerous lesions: new evidence from a case-control study based on dietary pattern and fecal metabolic profiling.

Preventing the progression of gastric precancerous lesions (GPLs) can reduce the morbidity and mortality of gastric cancer (GC). The preventive effect of a plant-based diet on cancers has been widely recognised. In this case-control study, 1,130 subjects were included using 1:1 propensity score matching for age and sex. Dietary habits, anthropometry and sample collection were conducted using standard and effective methods. Plant-based diet indices (PDIs) were calculated using a previously reported method. Faecal samples were analysed by untargeted metabolomics. Our study found that adherence to a healthy plant-based diet was inversely associated with the occurrence of GPLs. Metabolomic analysis identified six different metabolites correlated with GPLs, among which luteolin-related metabolites may be used as biomarkers of the association between PDIs and GPLs. In addition, the difference in N-acyl amides found in PDIs needs further verification. Our findings suggest that a healthy plant-based diet may have a protective effect against GPLs.

Adequate Intake of Dietary Fiber May Relieve the Detrimental Impact of Blood Lead on Dyslipidemia among US Adults: A Study of Data from the National Health and Nutrition Examination Survey Database.

Lead (Pb) exposure is a well-established risk factor for dyslipidemia, and people are exposed to it in multiple ways daily. Dietary fiber is presumed to improve lipid metabolism disorders, but it is still unknown whether it can relieve the detrimental impact of Pb on dyslipidemia. We used publicly accessible data from the 2011-2016 cycles of the National Health and Nutrition Examination Survey (NHANES). A total of 2128 US adults were enrolled for the subsequent analysis. Heavy metal concentrations in blood were measured using inductively coupled plasma mass spectrometry (ICP-MS). A weighted logistic regression was conducted to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The dose-response relationship between blood heavy metals and dyslipidemia was explored using a weighted restricted cubic spline (RCS) analysis. After fully adjusting for potential confounding factors (age, gender, race, education level, ratio of family income to poverty, marital status, body mass index, physical activity, waist circumference, smoke, alcohol drinking and history of metabolic syndrome, hypertension, and diabetes), a positive association between blood Pb levels and dyslipidemia risk was revealed (OR = 1.20, 95% CI: 1.03-1.40). Dietary fiber intake may significantly modify the association between blood Pb levels and dyslipidemia (p-interaction = 0.049), with a stronger association (OR = 1.26, 95% CI: 1.05-1.52) being revealed in individuals with an inadequate intake of dietary fiber (<14 g/1000 kcal/day), but a null association (OR = 1.01, 95% CI: 0.72-1.42) being observed in those with an adequate intake of dietary fiber (≥14 g/1000 kcal/day). Moreover, the weighted RCS analysis showed that compared with the average blood Pb exposure level (4.24 µg/dL), a lower blood Pb exposure level (3.08 µg/dL) may contribute to the risk of dyslipidemia in the group with an inadequate dietary fiber intake. Our findings suggest that Pb exposure in blood may be a risk factor for dyslipidemia. However, an adequate dietary fiber intake may offset the risk of dyslipidemia caused by blood Pb exposure. Since avoiding Pb exposure in daily life is difficult, increasing dietary fiber intake in the future might be a promising approach to alleviate dyslipidemia caused by Pb exposure.

Plasma metabolome identifies potential biomarkers of gastric precancerous lesions and gastric cancer risk.

OBJECTIVES: Currently, metabolic biomarkers with great practicability of gastric cancer (GC) and gastric precancerous lesions (GPL) are scarce. Thus, we are devoted to determining the plasma metabolic profiles of patients with GPL or GC and validate candidate biomarkers for disease diagnosis. METHODS: In this hospital-based case-control study, 68 plasma samples from 27 non-atrophic gastritis (NAG, control), 31 GPL, and 10 GC patients were collected for targeted metabolomics analysis. Univariate and multivariate analyses were used for selecting the differential metabolites. A receiver operating characteristic curve combined with binary logistic regression analysis was performed to test the diagnostic performance of the differential metabolites. Dietary data were obtained using a semiquantitative food frequency questionnaire. RESULTS: Distinct metabolomic profiles were noted for NAG, GPL, and GC. Compared to the NAG patients, the levels of 5 metabolites in the GPL group and 4 metabolites in the GC group were found to significantly elevate. Compared with the model involving 9 traditional risk factors (AUC: 0.89, 95%CI: 0.78-1.00), Trimethylamine N-oxide, the most significant metabolite (P = 2.00 × 10-5, FDR = 0.003, FC > 2, VIP > 2), showed a good diagnostic performance for the patients with GC (AUC: 0.90, 95%CI: 0.78-1.00), and its diagnostic performance has been further improved with the integration of Rhamnose (AUC: 0.96, 95%CI: 0.89-1.00). CONCLUSION: In our study, 9 defined metabolites might serve as meaningful biomarkers for identifying the high-risk population of GPL and GC, possibly enhancing the prevention and control of GPL and GC.

Synergistic effects of low-dose arsenic and N-methyl-N'-nitro-N-nitrosoguanidine co-exposure by altering gut microbiota and intestinal metabolic profile in rats.

Biological organisms are exposed to low-dose arsenic or N-nitro compounds (NOCs) alone or in combination worldwide, especially in areas with high cancer prevalence through drinking water or food exposure; however, information on their combined exposure effects is limited. Here, we conducted an in-depth study of the effects on the gut microbiota, metabolomics, and signaling pathways using rat models exposed to arsenic or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), one of the most active carcinogenic NOCs, separately or in combination with metabolomics and high-throughput sequencing. Compared to exposure alone, combined exposure to arsenic and MNNG exacerbated damage to gastric tissue morphology, interfered with intestinal microflora and substance metabolism, and exerted a stronger carcinogenic effect. This may be related to intestinal microbiota disorders, including Dyella, Oscillibacter, Myroides, and metabolic pathways such as glycine, serine, and threonine metabolism, arginine biosynthesis, central carbon metabolism in cancer, and purine and pyrimidine metabolism, thereby enhancing the cancer-causing effects of gonadotrophin-releasing hormone (GnRH), P53, and Wnt signaling pathways.

Co-exposure to iron, copper, zinc, selenium and titanium is associated with the prevention of gastric precancerous lesions.

Gastric cancer is the third leading cause of cancer death, and gastric precancerous lesions (GPLs) are an important stage in the transformation of normal gastric mucosa to gastric cancer. Matched for age and sex, a total of 316 subjects were eventually included from our prospective observation population (including 1007 patients with GPLs and 762 normal controls), and a questionnaire survey was conducted. In total, 10 plasma elements (iron, copper, zinc, selenium, rubidium, strontium, titanium, aluminum, vanadium and arsenic) were measured by applying inductively coupled plasma‒mass spectrometry (ICP‒MS). A multivariate conditional logistic regression model and Bayesian kernel logistic regression model (BKMR) were used to analyze the association between plasma element concentrations and GPLs. In the multimetal model, plasma titanium concentrations were significantly and positively associated with the prevalence of GPLs, with a fourth-quartile OR of 11.56 ([95% CI]: [2.78-48.13]). Plasma selenium and copper were negatively correlated with GPLs, with the highest quartiles of selenium and copper having an OR of 0.03 ([95% CI]: [0.01-0.15]; P < 0.001) and 0.24 ([95% CI]: [0.07-0.82]), respectively. In the BKMR model, there was a significant negative combined correlation of five metals on GPLs: iron, copper, zinc, selenium, and titanium. The results of this study showed that plasma concentrations of selenium and copper were negatively correlated with GPLs, while plasma concentrations of titanium were positively correlated with GPLs, and the combined action of the five elements was negatively correlated with GPLs.

[Effects of whole grains on insulin resistance in overweight and obese adults: a Meta-analysis].

OBJECTIVE: To conduct a Meta-analysis of the effects of whole grains on insulin resistance in overweight and obese adults in randomize controlled trials. METHODS: Data were retrieved from PubMed, EMBASE, MEDLINE, Cochrane Library, CBM, CNKI and other databases from the database establishment to August 9, 2021. Randomize controlled trials of the effects of whole grains on insulin resistance in overweight and obese adults were screened out. Data extraction and quality evaluation were conducted for the literatures meeting the inclusion criteria. The Meta-analysis was conducted using R4.1.2 software. RESULTS: A total of 10 randomized controlled trials were included. Among the overweight and obese adults, the whole grains intake decreased their fasting plasma glucose(FPG)(MD=-0.08, 95%CI-0.12, -0.04), homeostasis model assessment of insulin resistance(HOMA-IR)(MD=-0.37, 95%CI-0.60, -0.14) and quantitative insulin sensitivity index(QUICKI)(MD=0.006, 95%CI 0.005, 0.007). However, there were no statistically significant among fasting insulin(FINS), postprandial blood glucose(PG), postprandial insulin(PI), and triglycerides(TG) in overweight and obese adults. In subgroup analysis, FPG was statistically significant in German, quality score 4, 150-200 g intake of whole grain, and health subgroups of each population. There was no statistical significance of the QUICKI group. In sensitivity analysis and publication bias, FINS, PG, PI and TG became significant after one article was removed. However, HOMA-IR result were not statistically significant after the removal of one article. Meanwhile, the publication bias of each index was analyzed by Egger regression. Based on the results of subgroup analysis, a further dose-response analysis was conducted on the whole grains intake. The result showed that the FPG effects scale was better when the daily intake of whole grains was between 140 g and 160 g. CONCLUSION: Daily intake of 140 g to 160 g of whole grains improves FPG levels in overweight and obese adults.

A Healthful Plant-Based Diet Is Associated with Lower Odds of Nonalcoholic Fatty Liver Disease.

There is little evidence for the associations of the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI) with the odds of nonalcoholic fatty liver disease (NAFLD). We present a nationwide cross-sectional study among US adults aged 18 years or older. Diet was assessed by 24-h recalls. Overall PDI, hPDI, and uPDI were constructed based on 18 food groups. NAFLD was defined based on controlled attenuation parameter derived via transient elastography (TE) in the absence of other causes of chronic liver disease. Among 3900 participants with eligible TE examination, 1686 were diagnosed with NAFLD. The overall PDI was not associated with NAFLD prevalence (comparing extreme tertiles of PDI score OR = 1.03, 95% CI 0.76, 1.38, ptrend = 0.609). However, hPDI was inversely (OR = 0.50, 95% CI 0.35, 0.72, ptrend < 0.001), while uPDI was positively associated with odds of NAFLD (OR = 1.37, 95% CI 0.93, 2.02, ptrend = 0.009) in the multivariable-adjusted models without body mass index (BMI). After further adjustment for BMI, only the association of hPDI with NAFLD remained statistically significant (OR = 0.64, 95% CI 0.46, 0.87, ptrend = 0.006). Such inverse association appeared stronger in non-Hispanic whites, but not in other racial/ethnic groups (pinteraction = 0.009). Our findings suggest that a plant-based diet rich in healthy plant foods might be associated with lower odds of NAFLD, particularly among US non-Hispanic whites. Clinical trials and cohort studies to validate our findings are needed.

A prospective study of carbohydrate intake and risk of all-cause and specific-cause mortality.

PURPOSE: To investigate the associations between carbohydrate intake and the risk of overall and specific-cause mortality in a prospective cohort study. METHODS: Diet was measured using 24 h dietary recalls. Underlying cause of death was identified through linkage to the National Death Index. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. RESULTS: During a median follow-up of 7.1 years among 35,692 participants who aged 20-85 years, a total of 3854 deaths [783 cardiovascular disease (CVD)-specific and 884 cancer-specific death] were identified. Carbohydrate intake was not associated with risk of overall mortality (multivariable-adjusted HR comparing extreme quartiles 1.03, 95% CI 0.94, 1.13, ptrend = 0.799), while higher fiber intake was associated with lower mortality risk (HR 0.86, 95% CI 0.77, 0.95, ptrend = 0.004). Replacing 5% of energy from carbohydrate with both plant fat and plant protein was associated with 13% (95% CI 8%, 17%) and 13% (95% CI 3%, 22%) lower risk of total and CVD mortality, respectively. Whereas a positive or null association was found when replacing carbohydrate with both animal fat and animal protein. Higher carbohydrate-to-fiber ratio was associated with increased risk of overall (HR 1.20, 95% CI 1.09, 1.33, ptrend < 0.001) and cancer-specific (HR 1.17, 95% CI 0.95, 1.44, ptrend = 0.031) mortality. CONCLUSIONS: Our findings suggested that high fiber diet or diet with low carbohydrate-to-fiber ratio was associated with lower long-term death risk, and provided evidence for the health benefit from dietary substitution of both plant fat and plant protein for carbohydrate.

All-Trans Retinoic Acid Prevents the Progression of Gastric Precancerous Lesions by Regulating Disordered Retinoic Acid Metabolism.

Retinoic acid (RA) is the most biologically active metabolite of vitamin A and is important for stomach physiological function. However, little is known about the metabolic status of RA in human gastric lesions. From 2015 to 2018, 1,392 local residents in Lujiang County were recruited into a cross-sectional survey program, which included a questionnaire interview and blood collection. We detected the mRNA and protein expression of RA metabolism-relevant factors in gastric tissues from 68 local patients with gastric lesions. The effects of all-trans retinoic acid (ATRA) supplementation were investigated in a gastric precancerous lesions (GPLs) rat model. In the cross-sectional survey, no significant differences in the level of RA precursor (P > 0.05) between the H. pylori seronegative and seropositive residents were observed. However, the mRNA and protein expression of RA synthesizing enzymes (RDH10 and ALDH1A1) were significantly decreased and catabolic enzyme (CYP26B1) was significantly increased in the patients (P < 0.05). Consistently, in the GPL rat model, we observed a similar disorder; however, ATRA supplementation significantly not only corrected the disorder by increasing Rdh10, Aldh1a1 and decreasing Cyp26b1, but also reduced claudin-18 (P < 0.05). Our study suggested that RA metabolism is disrupted in individuals with gastric lesions, while ATRA supplementation can prevent GPL from progressing to gastric cancer.

Protective effects of all-trans retinoic acid against gastric premalignant lesions by repressing exosomal LncHOXA10-pyruvate carboxylase axis.

PURPOSE: Long noncoding RNAs (LncRNAs) play a pivotal role in gastric tumorigenesis, while exosomes facilitate the LncRNAs transferring to recipient cells. However, the roles of exosomal LncRNAs in gastric premalignant lesions (GPL) remain unclear. METHODS: We analyzed the expression of LncHOXA10 and its role in GPL progression. The protective effect of all-trans retinoic acid (ATRA) on GPL was explored in vitro and in vivo. RESULTS: Here, we found that LncHOXA10 expression was obviously increased in serum exosomes and gastric tissues from individuals with GPL, and exosomal LncHOXA10 from patients with GPL markedly promoted the malignant progression of human gastric epithelial cell line GES-1. Furthermore, RNA-pulldown assay revealed that LncHOXA10 mainly interacted with pyruvate carboxylase (PC), an essential enzyme in various cellular metabolic pathways. In gastric tissues from patients with GPL and gastric cancer (GC), PC was also upregulated and positively correlated with LncHOXA10 expression, which predicted a poor prognosis as well. Moreover, PC silencing attenuated the malignant effects of exosomal LncHOXA10 on GES-1 cells. ATRA also ameliorated the deterioration of GPL and prevented the malignant progression of GPL by reducing exosomal LncHOXA10 and PC expression. CONCLUSIONS: Collectively, the LncHOXA10-PC axis participated in the early stage of GC tumorigenesis, and ATRA might be useful to prevent GPL from developing into GC because it targets this axis.

Diets with higher insulinaemic potential are associated with increased risk of overall and cardiovascular disease-specific mortality.

Hyperinsulinaemia and insulin resistance have been proposed to be associated with mortality risk, and diet can modulate insulin response. However, whether dietary patterns with high insulinaemic potential are associated with mortality remains unknown. We prospectively examined the associations between hyperinsulinaemic diets and the risk of total and cause-specific mortality in a large nationally representative population. Dietary factors were assessed by 24-h recalls. Two empirical dietary indices for hyperinsulinaemia (EDIH) and insulin resistance (EDIR) were developed to identify food groups most predictive of biomarkers for hyperinsulinaemia (C-peptide and insulin) and insulin resistance (homoeostatic model assessment for insulin resistance), respectively. Deaths from date of the first dietary interview until 31 December 2015 were identified by the National Death Index. Multivariable hazard ratios (HR) and 95 % CI were calculated using Cox regression models. During a median follow-up of 7·8 years, 4904 deaths were documented among 40 074 participants. For EDIH, the multivariable-adjusted HR (comparing extreme quintiles) were 1·20 (95 % CI 1·09, 1·32, P-trend<0·001) for overall mortality and 1·41 (95 % CI 1·15, 1·74, P-trend = 0·002) for CVD mortality. Similar associations were observed for EDIR with HR of 1·18 (95 % CI 1·07, 1·29, P-trend < 0·001) for total and 1·35 (95 % CI 1·09, 1·67, P-trend = 0·005) for CVD mortality. After further adjustments for BMI and diabetes, these positive associations were somewhat attenuated. Our findings suggested that diets with higher insulinaemic potential are associated with increased risk of overall and CVD-specific mortality.

A prospective study of healthful and unhealthful plant-based diet and risk of overall and cause-specific mortality.

PURPOSE: Although emphasis has recently been placed on the importance of diet high in plant-based foods, the association between plant-based diet and long-term risk of overall and cause-specific mortality has been less studied. We aimed to investigate whether plant-based diet was associated with lower death risk. METHODS: This prospective cohort study used data from the US National Health and Nutrition Examination Survey. Diet was assessed using 24 h dietary recalls. We created three plant-based diet indices including an overall plant-based diet index (PDI), a healthful plant-based diet index (hPDI), and an unhealthful plant-based diet index (uPDI). Deaths from baseline until December 31, 2015, were identified. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. RESULTS: We documented 4904 deaths among 40,074 participants after a median follow-up of 7.8 years. Greater adherence to PDI was associated with lower risk of overall (HR comparing extreme quintiles 0.80, 95% CI 0.73, 0.89, ptrend < 0.001) and cancer-specific (HR = 0.68, 95% CI 0.55, 0.85, ptrend < 0.001) mortality. These inverse associations remained for hPDI and overall mortality with a HR of 0.86 (95% CI 0.77, 0.95, ptrend = 0.001), but not for cancer or CVD mortality. Conversely, uPDI was associated with higher risk of total (HR = 1.33, 95% CI 1.19, 1.48, ptrend < 0.001) and CVD-specific (HR = 1.42, 95% CI 1.12, 1.79, ptrend = 0.015) mortality. CONCLUSIONS: Increased intake of a plant-based diet rich in healthier plant foods is associated with lower mortality risk, whereas a plant-based diet that emphasizes less-healthy plant foods is associated with high mortality risk among US adults.

Association of dietary inflammatory potential with risk of overall and cause-specific mortality.

Inflammation is a central mechanism in metabolic disorders associated with morbidity and mortality and dietary factors can modulate inflammation. We aimed to prospectively investigate the association between an empirically developed, food-based dietary inflammatory pattern (EDIP) score and the risk of overall and cause-specific mortality, using data from the US National Health and Nutrition Examination Survey from 1999 to 2014. EDIP score was derived by entering thirty-nine predefined commonly consumed food groups into the reduced rank regression models followed by stepwise linear regression, which was most predictive of two plasma inflammation biomarkers including C-reactive protein and leucocyte count among 25 500 US adults. This score was further validated in a testing set of 9466 adults. Deaths from baseline until 31 December 2015 were identified through record linkage to the National Death Index. During a median follow-up of 7·8 years among 40 074 participants, we documented 4904 deaths. Compared with participants in the lowest quintile of EDIP score, those in the highest quintile had a higher risk of overall death (hazard ratio (HR) = 1·19, 95 % CI 1·08, 1·32, Ptrend = 0·002), and deaths from cancer (HR = 1·41, 95 % CI 1·14, 1·74, Ptrend = 0·017) and CVD (HR = 1·22, 95 % CI 0·98, 1·53, Ptrend = 0·211). When stratified by age, the association of EDIP with overall mortality was stronger among individuals under 65 years of age (Pinteraction = 0·001). Diets with a higher inflammatory potential were associated with increased risk of overall and cancer-specific mortality. Interventions to reduce the adverse effect of pro-inflammatory diets may potentially promote health and longevity.

Higher dietary insulinaemic potential is associated with increased risk of liver steatosis and fibrosis.

BACKGROUND AND AIMS: Hyperinsulinaemia and insulin resistance play a central role in the progression of hepatic steatosis and fibrosis, and diet can modulate insulin response. We thus hypothesised that diet with higher insulinaemic potential is associated with an increased risk of these conditions. METHODS: Two empirically dietary indices for hyperinsulinaemia (EDIH) and insulin resistance (EDIR) were derived to identify food groups most predictive of fasting concentrations of C-peptide and insulin and homeostatic model assessment for insulin resistance respectively. Hepatic steatosis and fibrosis were defined by controlled attenuation parameter and liver stiffness measurement using transient elastography (TE). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. RESULTS: Of the 4171 participants with TE examination, 1436 (age-standardised prevalence, 33.8%) were diagnosed with steatosis, 255 (5.6%) with advanced fibrosis and 101 (2.2%) with cirrhosis. The multivariable-adjusted ORs for participants comparing the highest to the lowest EDIH tertile were 1.17 (95% CI: 0.99-1.39, Ptrend  = .005) for steatosis, 1.74 (95% CI: 1.24-2.44, Ptrend  = .001) for advanced fibrosis and 2.05 (95% CI: 1.21-3.46, Ptrend  = .004) for cirrhosis. Similar associations were observed for EDIR with ORs of 1.32 (95% CI: 1.11-1.55, Ptrend  < .001) for steatosis and 1.43 (95% CI: 1.03-1.99, Ptrend  = .006) for advance fibrosis. These positive associations remained among never drinkers and individuals who were free of hepatitis B and/or C. CONCLUSIONS: Our findings suggest that hyperinsulinaemia and insulin resistance may partially underlie the influence of diet on hepatic steatosis and fibrosis, and highlight the importance of reducing or avoiding insulinaemic dietary pattern.

Dairy Consumption and Liver Cancer Risk: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies.

The relationship of dairy consumption and liver cancer risk is still controversial. We conducted a meta-analysis of published cohort and case-control studies to summarize the epidemiologic evidence on the relationship between dairy products consumption and the risk of liver cancer. The literatures were screened from PubMed, EMBASE, and Cochrane Library before May 2020. A total of seven cohort studies and eight case-control studies (5,121 cases) were included. The summary relative risks (RRs) were 1.17 (95% CI: 0.87‒1.57) and 1.08 (95% CI: 0.78‒1.51) for milk and total dairy, respectively. 0.50 (95% CI: 0.27-0.91) and 1.16 (95% CI: 0.83-1.52) were yogurt, cheese, and curd. Subgroup analysis revealed that study duration, alcohol, and design were associated the RRs. Dose-response analysis showed that the liver cancer risk was decreased by 5.4% (P for linear trend = 0.002) with a 40 g/day increment of yogurt intake. These results suggested that total dairy, milk, cheese, and curd were positive associations with the liver cancer risk although they were not statistically significant, however higher yogurt intake would reduce the risk. Further studies are necessary to verify the relationship of dairy foods with cancer.

Aqueous extract of Polygonatum sibiricum ameliorates ethanol-induced mice liver injury via regulation of the Nrf2/ARE pathway.

This study investigates the hepatoprotective effect of the aqueous extract of Polygonatum sibiricum (AEPS) against ethanol-induced oxidative stress and explores underlying mechanisms. AEPS was administered by gavage to ICR mice for 30 days. The experimental mice were fed a 5% (v/v) ethanol on last 10 days and followed by a single megadose of ethanol (5 g/kg) to induce ethanol-induced liver injury. Pretreatment with AEPS significantly suppressed the ethanol-induced elevation of aminotransferase activities, total bilirubin (TBIL) level, triglyceride level, and alleviated liver histopathological lesions. Meanwhile, AEPS reduced the level of oxidative stress in the liver and significantly suppressed the mRNA levels of NOX1, p67phox, gp91phox, and CYP2E1. Additionally, AEPS significantly increased the mRNA and protein levels of Nrf2 and its downstream antioxidant genes and promoted the nuclear translocation of Nrf2 in mice liver. Therefore, AEPS can effectively reduce ethanol-induced liver injury via regulation of the Nrf2/ARE pathway. PRACTICAL APPLICATIONS: Alcohol abuse and alcoholism have become a serious public health problem worldwide. Since liver is the major organ of alcohol metabolism, the most impactful damage of alcohol occurs in the liver. Polygonatum sibiricum is a traditional Chinese galenical and it also can be used as food ingredients. Most studies have reported that polysaccharide, flavonoids and saponins are the main bioactive compounds in Polygonatum sibiricum which play important roles in anti-oxidation. AEPS is the aqueous extract of Polygonatum sibiricum and AEPS can protect the mice liver against ethanol-induced oxidative damage. Thus it can be potential antioxidants to product hepatoprotective food and the study also provides a theoretical basis for the development and application of food about Polygonatum sibiricum.

All-trans retinoic acid suppressed GES-1 cell proliferation induced by exosomes from patients with precancerous lesions by arresting the cell cycle in S-phase.

We aimed to detect the expression of specific LncRNAs in exosomes isolated from the serum of patients with precancerous lesions and to study the effect of these serum exosomes on the activity of GES-1 cells in patients with precancerous lesions, as well as the activity of all-trans retinoic acid on GES-1 cells with or without the exosomes. Exosomes were extracted from the serum of patients with precancerous lesions and normal controls. Based on our previous sequencing results, quantitative real time-PCR was used to detect differentially expressed LncRNAs. Exosomes from the serum of patients with precancerous lesions were cocultured with GES-1 cells, and 5 µM all-trans retinoic acid was added as an intervention. Changes in cell viability and expression of LncHOXA10 were observed. Compared with the blank group, the proliferation activity of GES-1 cells cocultured with exosomes derived from the serum of patients with precancerous lesions was increased (P < 0.01), the proportion of cells in S phase was increased (P < 0.05). After adding 5 µM all-trans retinoic acid, the viability of cells decreased significantly (P < 0.01), the proportion of cells in S phase decreased significantly (P < 0.05). The expression of LncHOXA10 was decreased (P < 0.05). All-trans retinoic acid can conduct its chemopreventive effects by inhibiting the expression of LncHOXA10, thereby reducing the activity of LncHOXA10 in GES-1 cells cocultured with serum exosomes from patients with precancerous lesions.

All-Trans Retinoic Acid Rescues the Tumor Suppressive Role of RAR-ß by Inhibiting LncHOXA10 Expression in Gastric Tumorigenesis.

Numerous long noncoding RNAs (LncRNAs) were having recently been shown to be involved in cancer development, including gastric cancer (GC). However, the precise mechanism and treatments to target these molecules have rarely been studied. Thus, we aimed to investigate the function of LncHOXA10 in gastric tumorigenesis and targeted therapy. First, we measured the differences in LncHOXA10 and retinoic acid receptor ß (RAR-ß) levels in gastric cancer tissues and cell lines compared with those in noncancerous tissues and cell lines. We observed that LncHOXA10 was significantly upregulated in gastric cancer tissues and cell lines, whereas RAR-ß showed the opposite trend. Subsequently, loss and gain of LncHOXA10 cell lines were constructed to determine whether LncHOXA10 plays a role in gastric tumorigenesis. The results showed that LncHOXA10 promoted the proliferation, migration, and invasion of cells, whereas apoptosis was markedly inhibited. Subsequently, mechanistic investigations revealed that LncHOXA10 can repress RAR-ß expression and that all-trans retinoic acid (ATRA) can rescue the expression of RAR-ß. Finally, we showed that ATRA can reverse the pro-cancerous function of LncHOXA10. We showed that LncHOXA10 may be a prognostic and therapeutic factor of gastric cancer by negatively regulating RAR-ß. Furthermore, ATRA can inhibit the role of LncHOXA10 in gastric tumorigenesis.