Promoter profiles in plasma CfDNA exhibits a potential utility of predicting the efficacy of neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer. METHOD: First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy. RESULTS: The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978-0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response. CONCLUSION: These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.

Trends in prevalence of multimorbidity for chronic diseases in China: serial cross-sectional surveys from 2009 to 2018.

BACKGROUND: Multimorbidity, individuals suffering from two or more chronic diseases, has become a major health challenge worldwide, especially in populous and prosperous cities, where studies of this phenomenon in China are limited. We examined the prevalence, trends, patterns, and associated factors of multimorbidity from 2009 to 2018 among community-dwelling adults in Guangzhou, China. METHODS: We conducted serial cross-sectional surveys for chronic diseases in Guangzhou, China, in 2009, 2013, and 2018. General and stratified prevalence were standardized using demographic data. Multivariable logistic regression and hierarchical cluster analysis were applied to identify associated factors and to assess the correlations and patterns of multimorbidity, respectively. RESULTS: This study included 23,284 adults aged 18 and over in 2009, 18,551 in 2013, and 15,727 in 2018. The standardized prevalence of multimorbidity increased substantially, with 12.69% (95% CI: 10.45-15.33) in 2009, 25.44% (95% CI: 23.47-27.52) in 2013, and 35.13% (95% CI:32.64-37.70) in 2018 (P for trend <0.001). The highest bi- and triple-conditions of multimorbidity were dyslipidemia (DP) and overweight or obesity (OO) (12.54%, 95% CI: 11.68-13.46), and DP, OO, and Hypertension (HT) (3.99%, 95% CI: 3.47-4.58) in 2018. From 2009 to 2018, (1) The majority of multimorbidity patterns showed a high prevalence; (2) The percentage of participants with only one chronic condition was found lower, while the percentage with multiple conditions was higher. CONCLUSIONS: The prevalence of chronic disease multimorbidity in Guangzhou China, has increased substantially among adults. Effective policies targeting multimorbidity are urgently needed, especially for the health management of primary medical institutions.

The Association of Malnutrition and Health-Related Factors among 474,467 Older Community-Dwellers: A Population-Based Data Mining Study in Guangzhou, China.

BACKGROUND: This study aimed to examine the prevalence and associated factors of malnutrition in older community-dwellers and explore the interaction between associated factors. METHODS: A total of 474,467 older community-dwellers aged 65 or above were selected in Guangzhou, China. We used a two-step methodology to detect the associated factors of malnutrition and constructed logistic regression models to explore the influencing factors and interactive effects on three patterns of malnutrition. RESULTS: The prevalence of malnutrition was 22.28%. Older adults with both hypertension and diabetes (RERI = 0.13), both meat or fish diet and hypertension (RERI = 0.79), and both meat or fish diet and diabetes (RERI = 0.81) had positive additive interaction effects on the risk of obesity, whereas those on a vegetarian diet with hypertension (RERI = -0.25) or diabetes (RERI = -0.19) had negative additive interaction effects. Moreover, the interactions of physical activity with a meat or fish diet (RERI = -0.84) or dyslipidemia (RERI = -0.09) could lower the risk of obesity. CONCLUSIONS: Malnutrition was influenced by different health factors, and there were interactions between these influencing factors. Pertinent dietary instruction should be given according to different nutritional status indexes and the prevalence of metabolic diseases to avoid the occurrences of malnutrition among older adults.

Association of healthy lifestyle score with control of hypertension among treated and untreated hypertensive patients: a large cross-sectional study.

Background: Hypertension stands as the leading single contributor to the worldwide burden of mortality and disability. Limited evidence exists regarding the association between the combined healthy lifestyle score (HLS) and hypertension control in both treated and untreated hypertensive individuals. Therefore, we aimed to investigate the association between HLS and hypertension control among adults with treated and untreated hypertension. Methods: This cross-sectional study, including 311,994 hypertension patients, was conducted in Guangzhou using data from the National Basic Public Health Services Projects in China. The HLS was defined based on five low-risk lifestyle factors: healthy dietary habits, active physical activity, normal body mass index, never smoking, and no alcohol consumption. Controlled blood pressure was defined as systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg. A multivariable logistic regression model was used to assess the association between HLS and hypertension control after adjusting for various confounders. Results: The HLS demonstrated an inverse association with hypertension control among hypertensive patients. In comparison to the low HLS group (scored 0-2), the adjusted odds ratios (95% confidence intervals) for hypertension were 0.76 (0.74, 0.78), 0.59 (0.57, 0.60), and 0.48 (0.46, 0.49) for the HLS groups scoring 3, 4, and 5, respectively (Ptrend < 0.001). Notably, an interaction was observed between HLS and antihypertensive medication in relation to hypertension control (Pinteraction < 0.001). When comparing the highest HLS (scored 5) with the lowest HLS (scored 0-2), adjusted odds ratios (95% confidence intervals) were 0.50 (0.48, 0.52, Ptrend < 0.001) among individuals who self-reported using antihypertensive medication and 0.41 (0.38, 0.44, Ptrend < 0.001) among those not using such medication. Hypertensive patients adhering to a healthy lifestyle without medication exhibited better blood pressure management than those using medication while following a healthy lifestyle. Conclusion: HLS was associated with a reduced risk of uncontrolled blood pressure.

Prevalence of falls, injury from falls and associations with chronic diseases among community-dwelling older adults in Guangzhou, China: a cross-sectional study.

Introduction: As a developing country with the largest older adult population in the world, strengthening the research on falls among the older adults is undoubtedly an urgent item in China. This study aimed to explore the prevalence and risk factors associated with falls and injury from falls among community-dwelling older adults in Guangzhou, China, particularly focusing on their associations with chronic diseases. Methods: A total of 1,629 participants aged 65 years and above were selected from 11 counties in Guangzhou by the multi-stage stratified random sampling method in 2021. Socio-demographic characteristics, health and lifestyle factors, the status of falls, and injury from falls were measured by structured questionnaires through face-to-face interviews. Chi-square tests and logistic regression analysis were used to identify factors associated with falls and injury from falls. Chord diagrams were used to explore their associations with chronic diseases. Results: A total of 251 participants (15.41%, 95% CI: 13.98%-17.25%) reported falls, and 162 participants (9.46%, 95% CI:7.72%-11.55%) indicated an injury from falls. Logistic regression analysis showed the results as follows: female patients (adjusted OR = 1.721, 95% CI: 1.681-1.761) aged ≥80 years (1.910, 1.847-1.975), unemployed (1.226, 1.171-1.284), uninsured (1.555, 1.448-1.671), average monthly household income of 2,001-4,000 CNY (1.878, 1.827-1.930), number of services provided by the community health center ≥13 times per year (1.428, 1.383-1.475), illness within 2 weeks (1.633, 1.595-1.672), high-intensity physical activity (2.254, 2.191-2.32), sedentary (1.094, 1.070-1.117), and number of chronic disease illnesses ≥3 (1.930, 1.870-1.993). Meanwhile, those risk factors were also associated with injury from falls. The older adults with medium-intensity physical activity were at lower risk (0.721, 0.705-0.737) of falls and higher risk (1.086, 1.057-1.117) of being injured from falls. Chord diagrams showed the correlations between chronic diseases and falls and injury from falls among community-dwelling older adults in Guangzhou, China. Conclusion: The high prevalence of falls is found among community-dwelling older adults in Guangzhou, China, which is related to multiple factors such as demographic variables, lifestyle, and health status, especially for chronic diseases. Therefore, targeted interventions should be developed and implemented urgently.

Healthy Lifestyle Score and Glycemic Control in Type 2 Diabetes Mellitus Patients: A City-Wide Survey in China.

BACKGROUND: Few studies have investigated the combined impact of healthy lifestyle factors on glycemic control. Our study aimed to examine the associations of a healthy lifestyle score (HLS) with glycemic control and to explore the interactive effects of lifestyle factors among patients with type 2 diabetes mellitus (T2DM) in China. METHODS: This cross-sectional study was conducted among T2DM patients based on the health management of residents from Guangzhou, China. Good glycemic control was defined as fasting plasma glucose < 7.0 mmol/L. HbA1c < 7.0% was also defined as good glycemic control in sensitivity analysis. The HLS was defined as including physical activity, waist circumference, body mass index, dietary habit, smoking, and alcohol consumption. Logistic regression models were used to examine the associations and interactions between the lifestyle factors and glycemic control. RESULTS: Compared with participants with an HLS ≤ 2, the odds ratios (95% confidence intervals) for an HLS of 3, 4, 5, and 6 were 0.82 (0.77-0.87), 0.74 (0.70-0.79), 0.61 (0.57-0.65), and 0.56 (0.53-0.60), respectively. Significant interactions of healthy lifestyle factors in relation to glycemic control were shown (Pinteraction < 0.05). CONCLUSIONS: A healthier lifestyle was significantly associated with good glycemic control in patients with T2DM, and combined healthy lifestyle factors had a better effect than considering them individually.

Prevalence, awareness, treatment, and risk factor control of high atherosclerotic cardiovascular disease risk in Guangzhou, China.

Background: Identifying individuals at high risk of atherosclerotic cardiovascular disease (ASCVD) and implementing targeted prevention strategies might be the key to reducing the heavy disease burden in China. This study aimed to evaluate the prevalence, awareness, treatment, and risk factor control among individuals with high 10-year ASCVD risk in Guangzhou, China. Methods: This study included 15,165 adults (aged 18 years and older) from 138 urban and rural communities in the 2018 survey of China Chronic Disease and Risk Factors Surveillance in Guangzhou. 10-year ASCVD risk was estimated using the risk assessment models recommended in the Chinese Guideline for the Prevention of Cardiovascular Disease 2017. The prevalence, awareness, treatment, and risk factor control of high ASCVD risk (defined as 10-year risk ≥10%) were examined. Results: Among the study population, the weighted proportion of men was 51.9%, and the mean age was 41.27 ± 0.52 years. The overall standardized prevalence of high 10-year ASCVD risk was 13.8% (95% CI, 12.4%-15.3%). The awareness rates for hypertension, diabetes, and hyperlipidemia were 48.0% (95% CI, 42.8%-53.4%), 48.3% (95% CI, 43.0%-53.7%), and 17.9% (95% CI, 14.4%-22.1%) among those with corresponding risk factors. The proportions of drug use in prevention were relatively low in primary prevention, with the rates of using BP-lowering, glucose-lowering, lipid-lowering, and aspirin being 37.7% (95% CI, 32.8%-42.8%), 41.4% (95% CI, 35.8%-47.3%), 6.7% (95% CI, 4.5%-10.0%), and 1.0% (95% CI, 0.6%-1.8%), respectively. As for risk factor control, only 29.3% (95% CI, 25.7%-33.2%), 16.8% (95% CI, 15.0%-18.6%), and 36.0% (95% CI, 31.1%-41.2%) of individuals with high ASCVD risk had ideal levels of blood pressure, LDL-C, and body weight. Conclusion: The estimated prevalence of 10-year high ASCVD risk was high in Guangzhou, while the rates of treatment and risk factor control in primary prevention were still far from optimal, especially for lipid management. These findings suggested that substantial improvement in ASCVD prevention is needed in this population.

Association between meteorological factors and elderly falls in injury surveillance from 2014 to 2018 in Guangzhou, China.

Introduction: With rapid increase in the aging population, falls injuries have become an important public health problem. However, limited data have been reported on the associations between meteorological factors and falls injuries in the elderly. This study assessed the epidemiology of falls injuries and explored this association in the elderly in Guangzhou, China. Methods: Data on elderly falls injury cases and meteorological variables from 2014 to 2018 in Guangzhou were collected from the Guangzhou Injury Monitoring System and Guangzhou Meteorological Bureau, respectively. The monthly average data on falls injuries and meteorological factors were applied to the data analysis. These correlations were conducted using Pearson correlation analysis. A multiple linear regression model was used to estimate the effects of meteorological factors on falls injuries in the elderly in Guangzhou, China. Results: Accounting for 49.41% of causes of elderly injury were falls in the Guangzhou Injury Monitoring System from 2014 to 2018, which occupied first place for five consecutive years. The monthly number of elderly falls injury cases was lowest in April and highest in December, and had a positive correlation with monthly mean wind speed (r = 0.187, P < 0.01) and a negative correlation with monthly atmospheric pressure (r = -0.142, P < 0.05). A multiple linear regression model was constructed (F = 10.176, P < 0.01), which explained 23.7% of the variances (R 2 = 0.237). Monthly mean wind speed (ß = 76.85, P < 0.01) and monthly mean atmospheric pressure (ß = -3.162, P < 0.01) were independent factors affecting monthly elderly falls injuries. Conclusions: Falls are the primary cause of injury among elderly people in Guangzhou, China. Meteorological factors are related to falls injuries in the elderly population. Decreasing activity during high wind and low atmospheric pressure weather may help reduce the number of elderly falls injury cases.

Sleep Factors in Relation to Metabolic Dysfunction-Associated Fatty Liver Disease in Middle-Aged and Elderly Chinese.

CONTEXT: Accumulating evidence implies that sleep disturbance is involved in metabolic disorders. OBJECTIVE: We comprehensively evaluated the association between various dimensions of sleep behaviors and the risk for metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: In this cross-sectional study of 5011 participants with self-reported sleep behaviors and radiologically diagnosed MAFLD, a comprehensive healthy sleep score was generated to evaluate the associations between sleep behaviors and MAFLD risk using multivariate logistic regression adjusting for demographics, lifestyles, medication, and metabolic comorbidities. Furthermore, mediation analysis was utilized to assess the extent to which obesity explains the effect of sleep quality on MAFLD risk. RESULTS: Late bedtime, snoring, and daytime napping for over 30 minutes significantly associated with an increased risk of MAFLD, with odds ratios (OR) of 1.37 (95% CI 1.10, 1.70), 1.59 (95% CI 1.33, 1.91), and 1.17 (95% CI 1.02, 1.35), respectively, after full adjustments including obesity. Participants with disturbance in nighttime sleep and prolonged daytime napping showed the highest risk for MAFLD (OR 2.38, 95% CI 1.73, 3.27). Each additional increase of healthy sleep score was associated with a 16% reduction in MAFLD risk. Further stratified analysis revealed that people with a sedentary lifestyle and central obesity experienced more prominent adverse effects from poor sleep quality than others. Moreover, obesity accounted for only 20.77% of the total effect of sleep quality on MAFLD risk. CONCLUSIONS: Sleep behaviors, both cumulatively and individually, are associated with MAFLD risk. Public health awareness and strategies should be encouraged to curb MAFLD.

Prevalence and patterns of multimorbidity in chronic diseases in Guangzhou, China: a data mining study in the residents' health records system among 31 708 community-dwelling elderly people.

OBJECTIVES: Examination of the prevalence, influence factors and patterns of multimorbidity among the elderly people in Guangzhou, China. DESIGN: Cross-sectional study. PARTICIPANTS: 31 708 community-dwelling elderly people aged 65 and over. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence, influence factors and patterns of multimorbidity in seven chronic conditions among the participants. A multistage, stratified random sampling was adopted for selection of health records in the residents' health records system of Guangzhou. Data mining by association rule mining analysis was used to explore the correlations and multimorbidity patterns between seven chronic diseases. RESULTS: The prevalence of morbidity was 55.0% (95% CI 40.1% to 60.1%) and the multimorbidity was 15.2% (95% CI 12.4% to 18.4%) among the participants. Elderly, women, higher education level, being single, living in urban areas and having medical insurance were more likely to have chronic diseases and multimorbidity. Data mining by association rule mining analysis reveals patterns of multimorbidity among the participants, including coexistence of hypertension and diabetes (support: 12.5%, confidence: 17.6%), hypertension and coronary heart disease (support: 4.4%, confidence: 5.7%), diabetes and coronary heart disease (support: 1.6%, confidence: 5.7%), diabetes, coronary heart disease and hypertension (support: 1.4%, confidence: 4.4%). CONCLUSIONS: A high prevalence of morbidity (especially on hypertension and diabetes) and a relatively low multimorbidity of chronic diseases exist in elderly people. Data mining of residents' health records will help for strengthening the management of residents' health records in community health service centres of Guangzhou, China.

Targeted Next-Generation Sequencing of Circulating Tumor DNA Mutations among Metastatic Breast Cancer Patients.

Liquid biopsy through the detection of circulating tumor DNA (ctDNA) has potential advantages in cancer monitoring and prediction. However, most previous studies in this area were performed with a few hotspot genes, single time point detection, or insufficient sequencing depth. In this study, we performed targeted next-generation sequencing (NGS) with a customized panel in metastatic breast cancer (MBC) patients. Fifty-four plasma samples were taken before chemotherapy and after the third course of treatment for detection and analysis. Paired lymphocytes were also included to eliminate clonal hematopoiesis (CH)-related alternatives. A total of 1182 nonsynonymous mutations in 419 genes were identified. More ctDNA mutations were detected in patients with tumors > 3 cm (p = 0.035) and HER2(-) patients (p = 0.029). For a single gene, the distribution of ctDNA mutations was also correlated with clinical characteristics. Multivariate regression analysis revealed that HER2 status was significantly associated with mutation burden (OR 0.02, 95% CI 0-0.62, p = 0.025). The profiles of ctDNA mutations exhibited marked discrepancies between two time points, and baseline ctDNA was more sensitive and specific than that after chemotherapy. Finally, elevated ctDNA mutation level was positively correlated with poor survival (p < 0.001). Mutations in ctDNA could serve as a potential biomarker for the evaluation, prediction, and clinical management guidance of MBC patients with chemotherapy.

Prevalence and related factors of depression and falls among the elderly living in rural communities of Guangzhou.

Few studies have concentrated on the prevalence and related factors of depression and falls among the elderly living in rural communities of Guangzhou. A total of 335 participants aged ≥60 years were recruited by simple random sampling method. A structural equation model was applied to determine interrelationships between depression, falls and other variables. As high as 27.5% and 23.3% participants had reported depressive symptoms and falls, respectively. The path analysis showed the total effect (ß = -0.58) of depression on quality of life (QOL) consisted of a direct effect (ß = -0.51) and an indirect effect (ß = -0.07), which was mediated by family function and number of falls, and the R2 was 0.36. The model fit indices were χ2/df = 1.096, P > 0.05, Root Mean Square Error of Approximation (RMSEA) = 0.017, Tucker-Lewis Index (TLI) = 0.998 and Comparative Fit Index (CFI) = 0.999. Depression and falls were prevalent among the elderly living in rural communities of Guangzhou city. Pay attention to strengthen family function and prevent falls may prevent depression and improve the QOL among the elderly.

Associations of Genetic Variants at Nongenic Susceptibility Loci with Breast Cancer Risk and Heterogeneity by Tumor Subtype in Southern Han Chinese Women.

Current understanding of cancer genomes is mainly "gene centric." However, GWAS have identified some nongenic breast cancer susceptibility loci. Validation studies showed inconsistent results among different populations. To further explore this inconsistency and to investigate associations by intrinsic subtype (Luminal-A, Luminal-B, ER-&PR-&HER2+, and triple negative) among Southern Han Chinese women, we genotyped five nongenic polymorphisms (2q35: rs13387042, 5p12: rs981782 and rs4415084, and 8q24: rs1562430 and rs13281615) using MassARRAY IPLEX platform in 609 patients and 882 controls. Significant associations with breast cancer were observed for rs13387042 and rs4415084 with OR (95% CI) per-allele 1.29 (1.00-1.66) and 0.83 (0.71-0.97), respectively. In subtype specific analysis, rs13387042 (per-allele adjusted OR = 1.36, 95% CI = 1.00-1.87) and rs4415084 (per-allele adjusted OR = 0.82, 95% CI = 0.66-1.00) showed slightly significant association with Luminal-A subtype; however, only rs13387042 was associated with ER-&PR-&HER2+ tumors (per-allele adjusted OR = 1.55, 95% CI = 1.00-2.40), and none of them were linked to Luminal-B and triple negative subtype. Collectively, nongenic SNPs were heterogeneous according to the intrinsic subtype. Further studies with larger datasets along with intrinsic subtype categorization should explore and confirm the role of these variants in increasing breast cancer risk.

Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women.

GWAS have identified variation in the FGFR2 locus as risk factors for breast cancer. Validation studies, however, have shown inconsistent results by ethnics and pathological characteristics. To further explore this inconsistency and investigate the associations of FGFR2 variants with breast cancer according to intrinsic subtype (Luminal-A, Luminal-B, ER-&PR-&HER2+, and triple negative) among Southern Han Chinese women, we genotyped rs1078806, rs1219648, rs2420946, rs2981579, and rs2981582 polymorphisms in 609 patients and 882 controls. Significant associations with breast cancer risk were observed for rs2420946, rs2981579, and rs2981582 with OR (95% CI) per risk allele of 1.19 (1.03-1.39), 1.24 (1.07-1.43), and 1.17 (1.01-1.36), respectively. In subtype specific analysis, above three SNPs were significantly associated with increased Luminal-A risk in a dose-dependent manner (P trend < 0.01); however, only rs2981579 was associated with Luminal-B, and none were linked to ER-&PR- subtypes (ER-&PR-&HER2+ and triple negative). Haplotype analyses also identified common haplotypes significantly associated with luminal-like subtypes (Luminal-A and Luminal-B), but not with ER-&PR- subtypes. Our results suggest that associations of FGFR2 SNPs with breast cancer were heterogeneous according to intrinsic subtype. Future studies stratifying patients by their intrinsic subtypes will provide new insights into the complex genetic mechanisms underlying breast cancer.

3'3-Diindolylmethane inhibits migration, invasion and metastasis of hepatocellular carcinoma by suppressing FAK signaling.

Late stage hepatocellular carcinoma (HCC) usually has a low survival rate because it has high potential of metastases and there is no effective cure. 3'3-Diindolylmethane (DIM) is the major product of the acid-catalyzed oligomerization of indole-3-carbinol present in cruciferous vegetables. DIM has been proved to exhibit anticancer properties. In this study, we explored the effects and molecular mechanisms of anti-metastasis of DIM on HCC cells both in vitro and in vivo. We chose two HCC cell lines SMMC-7721 and MHCC-97H that have high potential of invasion. The results showed that DIM inhibited the proliferation, migration and invasion of these two cell lines in vitro. In addition, in vivo study demonstrated that DIM significantly decreased the volumes of SMMC-7721 orthotopic liver tumor and suppressed lung metastasis in nude mice. Focal Adhesion Kinase (FAK) is found over activated in HCC cells. We found that DIM decreased the level of phospho-FAK (Tyr397) both in vitro and in vivo. DIM inhibition of phospho-FAK (Tyr397) led to down-regulation of MMP2/9 and decreased potential of metastasis. DIM also repressed the migration and invasion induced by vitronectin through inactivation of FAK pathway and down-regulation of MMP2/9 in vitro. We also found that pTEN plays a role in down-regulation of FAK by DIM. These results demonstrated that DIM blocks HCC cell metastasis by suppressing tumor cell migration and invasion. The anti-metastasis effect of DIM could be explained to be its down-regulated expression and activation of MMP2/9 partly induced by up-regulation of pTEN and inhibition of phospho-FAK (Tyr397).

Cadmium Induced Apoptosis in MG63 Cells by Increasing ROS, Activation of p38 MAPK and Inhibition of ERK 1/2 Pathways.

BACKGROUND/AIMS: Cadmium (Cd) induces apoptosis in different kinds of cells, including osteoblasts, both in vivo and in vitro. However, little is known about the mechanisms by which Cd induces apoptosis. METHODS: In the present study, we used the human osteosarcoma cell line MG63, which has characteristics similar to human osteoblasts, as an in vitro model to determine the cellular mechanisms by which Cd induces apoptosis. RESULTS: We found that short-term exposure to CdCl2 induced apoptosis in MG63 cells. Furthermore, the incubation of cells with CdCl2 significantly increased the level of phosphorylated p38MAPK and significantly decreased the phosphorylation of ERK1/2 in a concentration-dependent manner. Additionally, the inhibition of the phosphorylation of p38 MAPK by SB202190 protected MG63 cells from Cd-induced apoptosis. The incubation of MG63 cells with the ERK1/2 inhibitor PD98059 significantly increased apoptosis in MG63 cells. CdCl2 also significantly increased the intracellular levels of ROS. N-acetylcysteine (NAC) significantly reduced ROS levels and reversed the effects of CdCl2 on MAPK signaling. CONCLUSION: Our results suggested that Cd induced apoptosis in MG63 cells by increasing ROS, activation of p38 MAPK and inhibition of ERK1/2 pathways.

Genetic polymorphisms in estrogen-related genes and the risk of breast cancer among Han Chinese women.

Exposure to high levels of estrogen is considered an important risk factor for susceptibility to breast cancer. Common polymorphisms in genes that affect estrogen levels may be associated with breast cancer risk, but no comprehensive study has been performed among Han Chinese women. In the present study, 32 single-nucleotide polymorphisms (SNPs) in estrogen-related genes were genotyped using the MassARRAY IPLEX platform in 1076 Han Chinese women. Genotypic and allelic frequencies were compared between case and control groups. Unconditional logistic regression was used to assess the effects of SNPs on breast cancer risk. Associations were also evaluated for breast cancer subtypes stratified by estrogen receptor (ER) and progesterone receptor (PR) status. Case-control analysis showed a significant relation between heterozygous genotypes of rs700519 and rs2069522 and breast cancer risk (OR = 0.723, 95% CI = 0.541-0.965, p = 0.028 and OR = 1.500, 95% CI = 1.078-2.087, p = 0.016, respectively). Subgroup comparisons revealed that rs2446405 and rs17268974 were related to ER status, and rs130021 was associated with PR status. Our findings suggest that rs700519 and rs2069522 are associated with susceptibility to breast cancer among the Han Chinese population and have a cumulative effect with three other identified SNPs. Further genetic and functional studies are needed to identify additional SNPs, and to elucidate the underlying molecular mechanisms.

Selection of reference genes for quantitative real-time PCR normalization in Panax ginseng at different stages of growth and in different organs.

Quantitative real-time reverse transcription PCR (qRT-PCR) has become a widely used method for gene expression analysis; however, its data interpretation largely depends on the stability of reference genes. The transcriptomics of Panax ginseng, one of the most popular and traditional ingredients used in Chinese medicines, is increasingly being studied. Furthermore, it is vital to establish a series of reliable reference genes when qRT-PCR is used to assess the gene expression profile of ginseng. In this study, we screened out candidate reference genes for ginseng using gene expression data generated by a high-throughput sequencing platform. Based on the statistical tests, 20 reference genes (10 traditional housekeeping genes and 10 novel genes) were selected. These genes were tested for the normalization of expression levels in five growth stages and three distinct plant organs of ginseng by qPCR. These genes were subsequently ranked and compared according to the stability of their expressions using geNorm, NormFinder, and BestKeeper computational programs. Although the best reference genes were found to vary across different samples, CYP and EF-1α were the most stable genes amongst all samples. GAPDH/30S RPS20, CYP/60S RPL13 and CYP/QCR were the optimum pair of reference genes in the roots, stems, and leaves. CYP/60S RPL13, CYP/eIF-5A, aTUB/V-ATP, eIF-5A/SAR1, and aTUB/pol IIa were the most stably expressed combinations in each of the five developmental stages. Our study serves as a foundation for developing an accurate method of qRT-PCR and will benefit future studies on gene expression profiles of Panax Ginseng.

Risk-association of CYP11A1 polymorphisms and breast cancer among Han Chinese women in Southern China.

Exposure to endogenous sex hormones has been reported as a risk factor for breast cancer. The CYP11A1 gene encodes the key enzyme that catalyzes the initial and rate-limiting step in steroid hormone synthesis. In this study, the associations between single nucleotide polymorphisms (SNPs) in CYP11A1 and breast cancer susceptibility were examined. Six SNPs in CYP11A1 were genotyped using the MassARRAY IPLEX platform in 530 breast cancer patients and 546 healthy controls. Association analyses based on a χ(2) test and binary logistic regression were performed to determine the odds ratio (OR) and 95% confidence interval (95% CI) for each SNP. Two loci (rs2959008 and rs2279357) showed evidence of associations with breast cancer risk. The variant genotype C/T-C/C of rs2959008 was significantly associated with a decreased risk (age-adjusted OR, 0.75; 95% CI, 0.58-0.96; P = 0.023) compared with the wild-type TT. However, the homozygous TT variant of rs2279357 exhibited increased susceptibility to breast cancer (age-adjusted OR, 1.44; 95% CI, 1.05-1.98; P = 0.022). The locus rs2959003 also showed an appreciable effect, but no associations were observed for three other SNPs. Our results suggest that polymorphisms of CYP11A1 are related to breast cancer susceptibility in Han Chinese women of South China.