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Patients with clinical T4 gastric cancers have high recurrence rates and low 5-year overall survival (OS) despite radical gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy. The invisible peritoneal metastasis may result in local recurrence due to the tumor invading the serosa and nearby organs. Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested as an adjuvant treatment strategy in these patients. We evaluated the efficacy of prophylactic HIPEC post-gastrectomy for patients with clinical T4 gastric cancer.We retrospectively reviewed data from 132 patients with clinical T4 gastric cancer who underwent gastrectomy + D2 lymphadenectomy between 2014 and 2020. Thirty-five of these patients also underwent prophylactic HIPEC perioperatively. We used propensity score matching (PSM) to reduce selection bias. We evaluated the risk factors for recurrence and compared the OS and disease-free survival (DFS) between the gastrectomy and prophylactic HIPEC groups.A total of 132 eligible patients were included in the study. Seventy preoperative patient characteristics were homogeneous post-PSM. Prophylactic HIPEC seemed to reduce the risk of postoperative peritoneal recurrence but did not influence the risk of distant metastasis. The risk factors for recurrence included advanced N stage, ascites, and lymphovascular invasion. OS (adjusted hazard ratio, 0.37; 95% CI, 0.17 to 0.81; p = 0.035) and DFS (adjusted hazard ratio, 0.33; 95% CI, 0.15 to 0.72; p = 0.017) were better in the prophylactic HIPEC group than in the gastrectomy alone group.Prophylactic HIPEC plus radical gastrectomy can reduce peritoneal recurrence and improve OS and DFS in patients with clinical T4 gastric cancer.

Colorectal cancer (CRC) is a major public health issue, and there are limited studies on the association between 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) polymorphism and CRC. We used two national databases from Taiwan to examine whether HSD17B4 rs721673, rs721675, and alcohol intake were independently and interactively correlated with CRC development. We linked the Taiwan Biobank (TWB) participants’ health and lifestyle information and genotypic data from 2012 to 2018 to the National Health Insurance Database (NHIRD) to confirm their medical records. We performed a genome-wide association study (GWAS) using data from 145 new incident CRC cases and matched 1316 healthy, non-CRC individuals. We calculated the odds ratios (OR) and 95% confidence intervals (CI) for CRC based on multiple logistic regression analyses. HSD17B4 rs721673 and rs721675 on chromosome 5 were significantly and positively correlated with CRC (rs721673 A > G, aOR = 2.62, p = 2.90 × 10−8; rs721675 A > T, aOR = 2.61, p = 1.01 × 10−6). Within the high-risk genotypes, significantly higher ORs were observed among the alcohol intake group. Our results demonstrated that the rs721673 and rs721675 risk genotypes of HSD17B4 might increase the risk of CRC development in Taiwanese adults, especially those with alcohol consumption habits.

BACKGROUND Identifying novel colorectal cancer (CRC) prognostic biomarkers is crucial to helping clinicians make appropriate therapy decisions. Melatonin plays a major role in managing the circadian rhythm and exerts oncostatic effects on different kinds of tumours. AIM To explore the relationship between MTNR1B single-nucleotide polymorphism (SNPs) combined with gene hypermethylation and CRC prognosis. METHODS A total of 94 CRC tumour tissues were investigated. Genotyping for the four MTNR1B SNPs (rs1387153, rs2166706, rs10830963, and rs1447352) was performed using multiplex polymerase chain reaction. The relationships between the MTNR1B SNPs and CRC 5-year overall survival (OS) was assessed by calculating hazard ratios with 95%CIs. RESULTS All SNPs (rs1387153, rs2166706, rs10830963, and rs1447352) were correlated with decreased 5-year OS. In stratified analysis, rs1387153, rs10830963, and rs1447352 risk genotype combined with CDKN2A and MGMT methylation status were associated with 5-year OS. A strong cumulative effect of the four polymorphisms on CRC prognosis was observed. Four haplotypes of MTNR1B SNPs were also associated with the 5-year OS. MTNR1B SNPs combined with CDKN2A and MGMT gene methylation status could be used to predict shorter CRC survival. CONCLUSION The novel genetic biomarkers combined with epigenetic biomarkers may be predictive tool for CRC prognosis and thus could be used to individualise treatment for patients with CRC.

The status of DNA methylation in primary tumor tissue and adjacent tumor-free tissue is associated with the occurrence of aggressive colorectal cancer (CRC) and can aid personalized cancer treatments at early stages. Tumor tissue and matched adjacent nontumorous tissue were extracted from 208 patients with CRC, and the correlation between the methylation levels of PTGER4 and ZNF43 at certain CpG loci and the prognostic factors of CRC was determined using the MassARRAY System testing platform. The Wilcoxon signed-rank test, a Chi-square test, and McNemar’s test were used for group comparisons, and Kaplan–Meier curves and a log-rank test were used for prediction. The hypermethylation of PTGER4 at the CpG_4, CpG_5, CpG_15, and CpG_17 tumor tissue sites was strongly correlated with shorter recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) [hazard ratio (HR) = 3.26, 95% confidence interval (CI) = 1.38–7.73 for RFS, HR = 2.35 and 95% CI = 1.17–4.71 for PFS, HR = 4.32 and 95% CI = 1.8–10.5 for OS]. By contrast, RFS and PFS were significantly longer in the case of increased methylation of ZNF43 at the CpG_5 site of normal tissue [HR = 2.33, 95% CI = 1.07–5.08 for RFS, HR = 2.42 and 95% CI = 1.19–4.91 for PFS]. Aberrant methylation at specific CpG sites indicates tissue with aggressive behavior. Therefore, the differential methylation of PTGER4 and ZNF43 at specific loci can be employed for the prognosis of patients with CRC.

Patients with colorectal cancer (CRC) undergo surgery, as well as perioperative chemoradiation or adjuvant chemotherapy primarily based on the tumor-node- metastasis (TNM) cancer staging system. However, treatment responses and prognostic outcomes of patients within the same stage vary markedly. The potential use of novel biomarkers can improve prognostication and shared decision making before implementation into certain therapies.To investigate whetherWe conducted a Taiwanese cohort study involving 208 patients with CRC recruited from Tri-Service General Hospital and applied the candidate gene approach to identify three genes involved in oncogenesis pathways. A methylation-specific polymerase chain reaction (MS-PCR) and EpiTYPER DNA methylation analysis were employed to detect methylation status and to quantify the methylation level of candidate genes in tumor tissue and adjacent normal tissue from participants. We evaluatedWe revealed various outcomes related to methylation and prognosis. Significantly shorter PFS and OS were associated with the CpG_3+CpG_7 hypermethylation ofOur study found that CpG_3+CpG_7 hypermethylation of

BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis. Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer (CRC). AIM To estimate whether a methylation gene panel in different clinical stages can reflect a different prognosis. METHODS We enrolled 120 CRC patients from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select six genes involved in carcinogenesis pathways. Patients were divided into two groups based on the methylation status of the six evaluated genes, namely, the < 3 aberrancy group and ≥ 3 aberrancy group. Various tumor stages were divided into two subgroups (local and advanced stages) on the basis of the pathological type of the following tissues: Tumor and adjacent normal tissues (matched normal). We assessed DNA methylation in tumors and adjacent normal tissues from CRC patients and analyzed the association between DNA methylation with different cancer stages and the prognostic outcome including time to progression (TTP) and overall survival. RESULTS We observed a significantly increasing trend of hazard ratio as the number of hypermethylated genes increased both in normal tissue and tumor tissue. The 5-year TTP survival curves showed a significant difference between the ≥ 3 aberrancy group and the < 3 aberrancy group. Compared with the < 3 aberrancy group, a significantly shorter TTP was observed in the ≥ 3 aberrancy group. We further analyzed the interaction between CRC prognosis and different cancer stages (local and advanced) according to the methylation status of the selected genes in both types of tissues. There was a significantly shorter 5-year TTP for tumors at advanced stages with the promoter methylation status of selected genes than for those with local stages. We found an interaction between cancer stages and the promoter methylation status of selected genes in both types of tissues. CONCLUSION Our data provide a significant association between the methylation markers in normal tissues with advanced stage and prognosis of CRC. We recommend using these novel markers to assist in clinical decision-making.

Background The role of Helicobacter pylori (H. pylori) infection in the development of colorectal neoplasia has been a matter of scientific debate with controversial findings. Aims This study examined the association between H. pylori infection and colorectal cancer (CRC) in a nationwide population-based Chinese cohort study. Methods A total of approximately 3936 individuals with newly diagnosed H. pylori infection (the H. pylori-infected cohort) and 15 744 age- and sex-matched patients with diagnoses absence of H. pylori infection (the comparison cohort) from 2000 to 2005 were identified from Taiwan’s National Health Insurance Research Database. The Kaplan–Meier method was used for measuring the cumulative incidence of CRC in each cohort. Cox proportional hazards models were used to compute hazard ratios (HRs) and accompanying 95% confidence intervals (CIs) for the estimation of the association between H. pylori infection and CRC. Results The cumulative incidence of CRC was higher in H. pylori-infected cohort than that in the comparison cohort (log-rank test, P Conclusions Our study demonstrated that H. pylori infection was associated with an increased risk of CRC, which warrants confirmation and exploration of the underlying biologic mechanisms by future studies.

Introduction: Sleep disorders, depression, and cancer have become increasingly prevalent worldwide. However, it is unknown whether coexistence of sleep disorders and depression influences the risk of cancer development. Therefore, we conducted a nationwide population-based study to examine this association among patients in Taiwan. Materials and Methods: A total of 105,071 individuals diagnosed with cancer and 420,284 age- and sex-matched patients without a diagnosis of cancer between 2000 and 2015 were identified from Taiwan’s National Health Insurance Research Database. The underlying chronic diseases of patients that may developed cancer were gathered and studied as the predictor. A multivariate Cox proportional odds model was used to estimate the crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) to estimate the interaction effect between sleep disorders and depression on the risk of cancer. Results: After adjusting for age, sex, comorbidities, and other covariates, the cancer group was associated with increased exposure to sleep disorders than the non-cancer group (aOR = 1.440, 95% CI = 1.392–1.489, p < 0.001). In addition, patients with both sleep disorders and depression were at an even higher risk for cancer than the general population (aOR = 6.857, p < 0.001). Conclusions: This retrospective cohort study shows that patients with both sleep disorders and depression are at a higher risk of cancer. Clinically, a meticulous cancer risk evaluation is recommended for patients with both sleep disorders and depression.

Several studies have investigated the association between gastroesophageal reflux disease (GERD) and colorectal cancer (CRC) risk, but the presented scientific results are highly debatable. This study examined the longitudinal association between GERD and CRC in an Asian population. A retrospective cohort study was performed using the National Health Insurance Research Database of Taiwan. The study cohort comprised 45,828 individuals with newly diagnosed GERD (the GERD cohort) and 229,140 age, sex, and date of enrollment-matched patients without GERD (the comparison cohort) from 2000 to 2006. The primary outcome was the incidence of CRC. To estimate the effect of GERD on the risk of CRC, the Cox proportional hazards model was fitted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). There were 785 newly diagnosed CRC patients in the 45,828 patients with GERD. Relatively, there were 2375 incident CRC cases in 229,140 patients without GERD. The incidence rate of CRC for the GERD cohort (17.60 per 10,000 person-years) was significantly higher than the corresponding incidence rate for the comparison cohort (10.22 per 10,000 person-years). After adjustment for confounders, GERD was associated with a significantly increased risk of CRC (adjusted HR,1.76; 95% CI, 1.62–2.90). Of note, a significant association between GERD and CRC risk was evident in both genders. In conclusion, this nationwide population-based cohort study supports the hypothesis that GERD was associated with a significantly increased risk of CRC. Our findings warrant still further investigation of the underlying mechanisms related to carcinogenic effect of GERD on colorectal carcinoma.

Background The association between elevated serum uric acid (UA) levels and the risk of developing colonic diverticulosis has not yet been investigated. Thus, this cross-sectional study aimed to examine this correlation in individuals from Taiwan. Methods From Jan. 1, 2010, to Dec. 31, 2016., approximately 5,605 patients (aged >20 years) from Tri-Service General Hospital who met the inclusion criteria according to colonoscopy and laboratory test findings were included in this research. The correlation between serum UA levels and colonic diverticulosis was investigated via regression analyses. Results Participants with elevated serum UA levels were at a higher risk of colonic diverticulosis. The area under the curve for serum UA levels was significantly higher in women than in men (0.651 [95% confidence interval: 0.596–0.707] vs. 0.55 [0.507–0.593]). There were specific trends in female-specific indicators for colonic diverticulosis across increasing quartiles of serum UA levels. Conclusions Patients with elevated serum UA levels should be cautious regarding the development of colonic diverticulosis disorder in female. Moreover, prospective studies may provide additional information on the relationship between elevated serum UA levels and colonic diverticulosis.

Background: The association between Helicobacter pylori (H. pylori) infection and the risk of developing irritable bowel syndrome (IBS) has yet to be investigated, thus, we conducted this nationwide cohort study to examine the association in patients from Taiwan. Methods: A total of approximately 2669 individuals with newly diagnosed H. pylori infection and 10,676 age- and sex-matched patients without a diagnosis of H. pylori infection from 2000 to 2013 were identified from Taiwan&rsquo, s National Health Insurance Research Database. The Kaplan&ndash, Meier method was used to determine the cumulative incidence of H. pylori infection in each cohort. Whether the patient underwent H. pylori eradication therapy was also determined. Results: The cumulative incidence of IBS was higher in the H. pylori-infected cohort than in the comparison cohort (log-rank test, p &lt, 0.001). After adjustment for potential confounders, H. pylori infection was associated with a significantly increased risk of IBS (adjusted hazard ratio (aHR) 3.108, p &lt, 0.001). In addition, the H. pylori-infected cohort who did not receive eradication therapy had a higher risk of IBS than the non-H. pylori-infected cohort (adjusted HR 4.16, p &lt, 0.001). The H. pylori-infected cohort who received eradication therapy had a lower risk of IBS than the comparison cohort (adjusted HR 0.464, p = 0.037). Conclusions: Based on a retrospective follow-up, nationwide study in Taiwan, H. pylori infection was associated with an increased risk of IBS, however, aggressive H. pylori infection eradication therapy can also reduce the risk of IBS. Further underlying biological mechanistic research is needed.

This study provide an insight that the panel genes methylation status in different clinical stage tended to reflect a different prognosis even in matched normal tissues, to clinical recommendation. We enrolled 153 colorectal cancer patients from a medical center in Taiwan and used the candidate gene approach to select five genes involved in carcinogenesis pathways. We analyzed the relationship between DNA methylation with different cancer stages and the prognostic outcome. There were significant trends of increasing risk of 5-year time to progression and event-free survival of subjects with raising number of hypermethylation genes both in normal tissue and tumor tissue. The group with two or more genes with aberrant methylation in the advanced cancer stages (Me/advanced) had lower 5-year event-free survival among patients with colorectal cancer in either normal or tumor tissue. The adjusted hazard ratios in the group with two or more genes with aberrant methylation with advanced cancer stages (Me/advanced) were 8.04 (95% CI, 2.80-23.1; P for trend0.01) and 8.01 (95% CI, 1.92-33.4; P for trend0.01) in normal and tumor tissue, respectively. DNA methylation status was significantly associated with poor prognosis outcome. This finding in the matched normal tissues of colorectal cancer patients could be an alternative source of prognostic markers to assist clinical decision making.

Colorectal cancer (CRC) is a common malignancy worldwide. CRC patients in the same stage often present with dramatically different clinical scenarios. Thus, robust prognostic biomarkers are urgently needed to guide therapies and improve treatment outcomes. The NKX6.1 gene has been identified as a hypermethylation marker in cervical cancer, functioning as a metastasis suppressor by regulating epithelial-mesenchymal transition. Here, we investigated whether hypermethylation of NKX6.1 might be a prognostic biomarker for CRC. By analyzing the methylation and expression of NKX6.1 in CRC tissues and CRC cell lines. We quantitatively examined the NKX6.1 methylation levels in 151 pairs of CRC tissues by using methylation-specific polymerase chain reaction analysis and found that NKX6.1 was hypermethylated in 35 of 151 CRC tissues (23%). NKX6.1 gene expression was inversely correlated with the DNA methylation level in CRC cell lines in vitro. Then, we analyzed the association of NKX6.1 methylation with clinical characteristics of these CRC patients. Our data demonstrated that patients with NKX6.1 methylation presented poorer 5-year overall survival (P = 0.0167) and disease-free survival (P = 0.0083) than patients without NKX6.1 methylation after receiving adjuvant chemotherapy. Most importantly, these data revealed that stage II CRC patients with NKX6.1 methylation had poorer 5-year disease-free survival (P = 0.0322) than patients without NKX6.1 methylation after adjuvant chemotherapy. Our results demonstrate that methylation of NKX6.1 is a novel prognostic biomarker in CRC and that it may be used as a predictor of the response to chemotherapy.

Periodontal disease (PD) and colorectal cancer (CRC) were associated with chronic inflammation. This retrospective cohort study examined the association between PD severity and CRC in a large-scale, population-based Chinese cohort.A total of approximately 106,487 individuals with newly diagnosed PD and 106,487 age-matched and sex-matched patients without PD from 2000 to 2002 were identified from Taiwan's National Health Insurance Research Database (NHIRD).The Kaplan-Meier analysis revealed that the cumulative incidence of CRC was significantly higher in patients with PD than in those without PD (log-rank test, P 0.001). After adjustment for age, sex, and comorbidities, patients with PD were associated with a significantly higher risk of CRC compared with those without PD (adjusted HR = 1.64, 95% CI = 1.50-1.80). Further, the risk of CRC appeared to increase with increasing frequency of PD medical visits [adjusted HR (95% CI) was 1.78 (1.58-2.02) and 1.53 (1.35-1.74) for annual visits 10 and 4, respectively].Based on our study, PD severity was associated with an increase in the risk of CRC. Further mechanistic research is needed.

This study aimed to determine the antiobesity effects of raspberry ketone (RK), one of the major aromatic compounds contained in raspberry, and its underlying mechanisms. During adipogenesis of 3T3-L1 cells, RK (300 μM) significantly reduced lipid accumulation and downregulated the expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferation-activated receptor γ (PPARγ), fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS). RK also reduced the expression of light chain 3B (LC3B), autophagy-related protein 12 (Atg12), sirtuin 1 (SIRT1), and phosphorylated-tuberous sclerosis complex 2 (TSC2), whereas it increased the level of p62 and phosphorylated-mammalian target of rapamycin (mTOR). Daily administration of RK decreased the body weight (ovariectomy [Ovx] + RK, 352.6 ± 5 vs Ovx, 386 ± 5.8 g; P < 0.05), fat mass (Ovx + RK, 3.2 ± 0.05 vs Ovx, 5.0 ± 0.4 g; P < 0.05), and fat cell size (Ovx + RK, 6.4 ± 0.6 vs Ovx, 11.1 ± 0.7 × 103 μm2; P < 0.05) in Ovx-induced obesity in rat...

This study provide an insight that the panel genes methylation status in different clinical stage tended to reflect a different prognosis even in matched normal tissues, to clinical recommendation. We enrolled 153 colorectal cancer patients from a medical center in Taiwan and used the candidate gene approach to select five genes involved in carcinogenesis pathways. We analyzed the relationship between DNA methylation with different cancer stages and the prognostic outcome. There were significant trends of increasing risk of 5-year time to progression and event-free survival of subjects with raising number of hypermethylation genes both in normal tissue and tumor tissue. The group with two or more genes with aberrant methylation in the advanced cancer stages (Me/advanced) had lower 5-year event-free survival among patients with colorectal cancer in either normal or tumor tissue. The adjusted hazard ratios in the group with two or more genes with aberrant methylation with advanced cancer stages (Me/advanced) were 8.04 (95% CI, 2.80–23.1; P for trend

Colorectal cancer (CRC) is one of the most common cancers and the second leading cause of cancer-related deaths. Discrepancies in clinical outcomes are observed even among patients with same-stage CRC due to molecular heterogeneity. Thus, biomarkers for predicting prognosis in CRC patients are urgently needed. We previously demonstrated that stage II CRC patients with NKX6.1 methylation had poor 5-year overall survival. However, the methylation frequency of NKX6.1 was only 23% in 151 pairs of CRC tissues. Thus, we aimed to develop a more robust prognostic panel for CRC using NKX6.1 in combination with three genes: LIM homeobox transcription factor 1α (LMX1A), sex-determining region Y-box 1 (SOX1), and zinc finger protein 177 (ZNF177). Through quantitative methylation analysis, we found that LMX1A, SOX1, and ZNF177 were hypermethylated in CRC tissues. LMX1A methylation was significantly associated with poor 5-year overall, and disease-free survivals in stage I and II CRC patients. Sensitivity and specificity analyses of the four-gene combination revealed the best sensitivity and optimal specificity. Moreover, patients with the four-gene methylation profile exhibited poorer disease-free survival than those without methylation. A significant effect of the four-gene methylation status on overall survival and disease-free survival was observed in early stage I and II CRC patients (p = 0.0016 and p = 0.0230, respectively). Taken together, these results demonstrate that the combination of the methylation statuses of NKX6.1, LMX1A, SOX1, and ZNF177 creates a novel prognostic panel that could be considered a molecular marker for outcomes in CRC patients.

Aberrant DNA methylation plays a crucial role in cancer development; however, prospective evidence of an interaction between molecular biomarkers and cancer staging for predicting the prognosis of colorectal cancer (CRC) is still limited. We examined DNA methylation in tumors and adjacent normal tissues from patients who underwent CRC surgical resection, and evaluated the interaction between cancer staging (advanced vs local) and DNA methylation to predict the prognosis of CRC. We recruited 132 patients with CRC from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select 3 tumor suppressor genes involved in carcinogenesis pathways. ORs and 95% CIs were computed using logistic regression analyses while adjusting for potential covariates. Advanced cancer stage was correlated with cancer recurrence (OR 7.22, 95% CI 2.82 to 18.45; p

Obesity is a strong risk factor for the development of cardiovascular diseases and is associated with a marked increase in circulating leptin concentration. Leptin is a peptide hormone mainly produced by adipose tissue and is regulated by energy level, hormones and various inflammatory mediators. Genistein is an isoflavone that exhibits diverse health‐promoting effects. Here, we investigated whether genistein suppressed the atherogenic effect induced by leptin. The A10 cells were treated with leptin and/or genistein, and then the cell proliferation and migration were analysed. The reactive oxygen species (ROS) and proteins levels were also measured, such as p44/42MAPK, cell cycle‐related protein (cyclin D1 and p21) and matrix metalloproteinase‐2 (MMP‐2). Immunohistochemistry and morphometric analysis were used for the neointima formation in a rat carotid artery injury model. Genistein (5 μM) significantly inhibited both the proliferation and migration of leptin (10 ng/ml)‐stimulated A10 cells. In accordance with these finding, genistein decreased the leptin‐stimulated ROS production and phosphorylation of the p44/42MAPK signal transduction pathway. Meanwhile, genistein reversed the leptin‐induced expression of cyclin D1, and cyclin‐dependent kinase inhibitor, p21. Genistein attenuated leptin‐induced A10 cell migration by inhibiting MMP‐2 activity. Furthermore, the leptin (0.25 mg/kg)‐augmented neointima formation in a rat carotid artery injury model was attenuated in the genistein (5 mg/kg body weight)‐treated group when compared with the balloon injury plus leptin group. Genistein was capable of suppressing the atherogenic effects of leptin in vitro and in vivo, and may be a promising candidate drug in the clinical setting.

Promoting white adipose tissue (WAT) to acquire brown-like characteristics is a promising approach for obesity treatment. Although raspberry ketone (RK) has been reported to possess antiobesity activity, its effects on the formation of brown-like adipocytes remain unclear. Therefore, we investigated the effects and underlying mechanism of RK on WAT browning in 3T3-L1 adipocytes and rats with ovariectomy (Ovx)-induced obesity. RK (100 μM) significantly induced browning of 3T3-L1 cells by increasing mitochondrial biogenesis and the expression of browning-specific proteins (PR domain containing 16, PRDM16; peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC-1α; uncoupling protein-1, UCP-1) and lipolytic enzymes (hormone-sensitive lipase and adipose triglyceride lipase). RK significantly reduced the expression of the autophagy-related protein Atg12 and increased the expression of p62 and heme oxygenase 1 (HO-1). Additionally, these effects of RK were reversed by the HO-1 inhibitor SnPP (20 μM). In addition, RK (160 mg/kg, gavage, for 8 weeks) significantly reduced body weight gain (Ovx+RK, 191.8 ± 4.6 g vs. Ovx, 223.6 ± 5.9; P < .05), food intake, the amount of inguinal adipose tissue (Ovx+RK, 9.05 ± 1.1 g vs Ovx, 12.9 ± 0.92 g; P < .05) and the size of white adipocytes in Ovx rats. Moreover, compared to expression in the Ovx group, the levels of browning-specific proteins were significantly higher and the levels of autophagy-related proteins were significantly lower in the Ovx+RK group. Therefore, this study elucidated the mechanism associated with RK-induced WAT browning and thus provides evidence to support the clinical use of RK for obesity treatment.

The role of atopic dermatitis (AD) in the development of colorectal cancer (CRC) has been a matter of scientific debate with mixed results. We conducted a nationwide cohort study to assess the association between AD and risk of CRC. Drawing on Taiwan's National Health Insurance Research Database, 46,703 patients with AD (the AD cohort) and 186,812 sex, age, and index year-matched patients without AD (the non-AD cohort) were identified in the period between 2000 and 2008. Follow-up time was calculated from the date of entry in the cohort until the occurrence of a first CRC diagnosis, death, or the end of the observation period (December 31, 2013), whichever occurred first. Hazards ratios (HRs) and accompanying 95% confidence intervals (CIs) derived from the Fine-Gray competing risk model were used to estimate the association between AD and CRC risk. After multivariable adjustment, AD was associated with an increased risk of CRC (adjusted HR, 1.26; 95% CI, 1.14–1.40). Of note, a significant positive association between AD and CRC risk was evident in both men and women and in all age groups. In summary, this population-based cohort study revealed that AD was associated with an increased risk of CRC in an Asian population. It will be of interest for cohort studies with prediagnostic specimens to evaluate the potential relationship between AD and CRC using biomarkers for allergy status.

An azetidine-2,4-dione was applied to synthesize dendrons with four carbons in the end ([G-0.5]-C4 and [G-1]-C4) via a selective ring-opening addition reaction, which was subsequently extended to obtain a dendritic surfactant ([G-1]-C4 surfactant) by acidification. The dendrons were characterized by Fourier transform infrared (FT-IR), 1 H nuclear magnetic resonance ( 1 H NMR), elemental analyzer (EA), and fast atom bombardment mass spectrometry (FAB MS). The dendritic surfactant, with a cationic head and branched hydrophobic C4 tails, was dissolved in 2 wt.% dimethyl sulfoxide (DMSO) aqueous solution for the determination of critical micelle concentration (CMC) by fluorescence and electrical conductivity measurements. The resulted CMC values were very close within measurements, ca. 0.013–0.05 mM. Transmission electron microscopy (TEM) and zeta potential measurement also provided an evidence of micelle formation and shape. Moreover, anionic dyes were adsorbed onto the micelles successfully to confirm the positive charge of [G-1]-C4 surfactant.

1Division of Colorectal Surgery, Department of Surgery, and 7Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, No.325, Sec.2, Chenggong Rd., Neihu District, Taipei, Taiwan (Republic of China) 2Graduate Institute of Life Sciences, and 3School of Public Health, National Defense Medical Center, No.161 Sec. 6, Minquan E. Rd., Neihu Dist., Taipei, Taiwan (Republic of China) 4Department of Surgery, Landseed Hospital, Taiwan No.77, Kwang-Tai Rd., Pingjen City, Tao-Yuan, Taiwan (Republic of China) 5Department of Public Health, College of Medicine, Fu-Jen Catholic University, No. 510, Jhong-Jheng Rd., Sin-Jhuang, New Taipei, Taiwan (Republic of China) 6Department of Health Business Administration, Meiho University, No.23, Pingguang Rd., Neipu, Pingtung, Taiwan (Republic of China)

Al-doped ZnO (AZO) nanorod arrays thin film with hydrogen treatment is directly used as a photoelectrode for solar water splitting without an extra transparent conducting oxide (TCO) thin film because it possesses the functions of TCO thin film and photoactive 1-dimensional nanostructured semiconductor simultaneously. To enhance the absorption in the visible region, PbS nanoparticles decorated the AZO nanorods via successive ionic layer adsorption and reaction route. The PbS nanoparticles have a face-centered cubic structure and their decoration does not destroy the 1-dimensional morphology of AZO nanorod arrays. With increasing the cycle number of PbS nanoparticles decoration, the grain size and loading of PbS nanoparticles become larger gradually which leads to lower energy bandgap and stronger absorption. A maximum photocurrent density of 1.65 mW cm−2 is obtained when the cycle number is 20, which is much higher than those without PbS nanoparticles sensitization or hydrogen treatment. This demonstrates that the AZO nanorod array thin film with hydrogen treatment can be directly used as a photoelectrode without an extra TCO thin film. Because the use of expensive metals can be avoided and the pre-fabrication of TCO thin film substrate is necessary no more, the fabrication of such a composite photoelectrode becomes simple and low-cost. So, it has great potentials in solar water splitting after sensitization by quantum dots capable of visible light absorption.

ZnO nanorod array thin film with Al-doping and hydrogen treatment was developed as a photoelectrode combining the functions of transparent conducting oxide thin film and photoactive 1-dimensional nanostructured semiconductor into a single layer for photoelectrochemical water splitting. It was demonstrated that hydrogen treatment and Al-doping enhanced the dark currents, photocurrents, and hydrogen generation efficiencies largely and the enhancement by hydrogen treatment was more significant. The maximum photoinduced hydrogen generation efficiency was about 0.020%. Furthermore, hydrogen treatment also improved the photosensitivity and the stability under illumination significantly. The minimum decay time constant and rise time constant were 1.71 and 1.22 s, respectively. And after current–voltage scanning upon illumination for 50 cycles, the 1-dimensional morphology still remained unchanged but those without Al-doping and/or hydrogen treatment were altered seriously. The good photoresponse and stability made the Al-doped ZnO nanorod array thin film with hydrogen treatment have wide applications in the photoelectrochemical field.

Mouse Xin-alpha (mXin-alpha) encodes a Xin repeat-containing, actin-binding protein localized to the intercalated disc (ICD). Ablation of mXin-alpha progressively leads to disrupted ICD structure, cardiac hypertrophy and cardiomyopathy with conduction defects during adulthood. Such conduction defects could be due to ICD structural defects and/or cell electrophysiological property changes. Here, we showed that despite the normal ICD structure, juvenile mXina-null cardiomyocytes (from 3~4-week-old mice) exhibited a significant reduction in the transient outward K+ current (ITO), similar to adult mutant cells. Juvenile but not adult mutant cardiomyocytes also had a significant reduction in the delayed rectifier K+ current. In contrast, the mutant adult ventricular myocytes had a significant reduction in the inward rectifier K+ current (IK1) on hyperpolarization. These together could account for the prolongation of action potential duration (APD) and the ease of developing early afterdepolarization observed in juvenile mXin-alpha-null cells. Interestingly, juvenile mXin-alpha-null cardiomyocytes had a notable decrease in the amplitude of intracellular Ca2+ transient and no change in the L-type Ca2+ current, suggesting that the prolonged APD did not promote an increase in intracellular Ca2+ for cardiac hypertrophy. Juvenile mXin-alpha-null ventricles had reduced levels of membrane-associated Kv channel interacting protein 2, an auxiliary subunit of ITO, and filamin, an actin cross-linking protein. We further showed that mXin-alpha interacted with both proteins, providing a novel mechanism for ITO surface expression.

Background: Colorectal cancer (CRC) is a common malignancy worldwide. CRC patients in the same stage often present with dramatically different clinical scenarios. Thus, robust prognostic biomarkers are urgently needed to guide therapies and improve treatment outcomes. The NKX6.1 gene has been identified as a hypermethylation marker in cervical cancer and functions as a metastatic suppressor by regulating epithelial-mesenchymal transition (EMT). Here, we investigated whether hypermethylation of NKX6.1 might be a prognostic biomarker for CRC. Results: In this study, we analyzed the methylation and expression of NKX6.1 in CRC tissues and CRC cell lines. We quantitatively examined the NKX6.1 methylation levels in 151 pairs of CRC tissues by using methylation-specific polymerase chain reaction (MS-PCR) analysis and found that NKX6.1 was hypermethylated in 35 of 151 CRC tissues (23.18%). NKX6.1 gene expression was inversely correlated with the DNA methylation level in CRC cell lines in vitro. Then, we analyzed the association of NKX6.1 methylation with clinical characteristics of these CRC patients. NKX6.1 methylation was positively associated with tumor size [odds ratio (OR): 2.84; 95% confidence interval (CI): 1.24 to 6.52]. These data demonstrated that patients with NKX6.1 methylation presented poorer 5-year overall survival (p=0.0167) and disease-free survival (p=0.0083) than patients without NKX6.1 methylation after receiving adjuvant chemotherapy. Most importantly, our data revealed that stage II CRC patients with NKX6.1 methylation had poorer 5-year disease-free survival (p=0.0322) than patients without NKX6.1 methylation after adjuvant chemotherapy. Conclusions: Our results demonstrated that methylation of NKX6.1 is a novel prognostic biomarker in CRC and may be used as a predictor of the response to chemotherapy. Citation Format: Ya-Wen Lin, Sou-Yi Chang, Chih-Chi Kuo, Cheng-Wen Hsiao, Chih-Hsiung Hsu, Yu-Ching Chou, Yu-Lueng Shih. NKX6.1 hypermethylation predicts the outcome of stage II colorectal cancer patients undergoing chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2575.

In Madagascan waters, both Tetraclita rufotincta Pilsbry 1916 and T. africana Ren 1989 have been reported. Tetraclita rufotincta is more widely distributed than T. africana, extending to the western Indian Ocean and east Africa. Tetraclita africana is reported from Madagascar and no further distribution record has been made apart from its type locality. Both species have pink parietes and are similar in size, which could lead to identification confusion. In this study, we revealed that T. africana differed from T. rufotincta in having multicuspidate setae on cirrus III, a feature that can be observed with both light microscopy and SEM. Additionally, the tergum of T. africana has a rounded spur and a larger basi-scutal angle than that of T. rufotincta. However, since the name Tetraclita africana has been pre-occupied under the name Tesseropora (Tetraclita) wireni africana Nilsson-Cantell, 1932, we, therefore, propose herein a replacement name, Tetraclita reni nom. nov. Based on museum specimens examined, Tetraclita reni nom. nov. is present in northeastern and southern Madagascar and Mauritius but absent from Yemen, Kenya, South Africa, Aldabra and northwestern Madagascar, suggesting the distribution of T. reni nom. nov. could be confined to the south and northeast of Madagascar and adjacent waters.

Amorphous TiO2-coated ZnO nanoparticles were prepared by the solvothermal synthesis of ZnO nanoparticles in ethanol and the followed by sol–gel coating of TiO2 nanolayer. The analyses of X-ray diffraction (XRD) and transmission electron microscopy (TEM) revealed that the resultant ZnO nanoparticles were hexagonal with a wurtzite structure and a mean diameter of about 60 nm. Also, after TiO2 coating, the TEM images clearly indicated the darker ZnO nanoparticles being surrounded by the lighter amorphous TiO2 layers. The zeta potential analysis revealed the pH dependence of zeta potentials for ZnO nanoparticles shifted completely to that for TiO2 nanoparticles after TiO2 coating, confirming the formation of core-shell structure and suggesting the coating of TiO2 was achieved via the adhesion of the hydrolyzed species Ti–O− to the positively charged surface of ZnO nanoparticles. Furthermore, the analyses of Fourier transform infrared (FTIR) and Raman spectra were also conducted to confirm that amorphous TiO2 were indeed coated on the surface of ZnO nanoparticles. In addition, the analyses of ultraviolet–visible (UV–VIS) and photoluminescence (PL) spectra revealed that the absorbance of amorphous TiO2-coated ZnO nanoparticles at 375 nm gradually decreased with an increase in the Ti/Zn molar ratio and the time for TiO2 coating, and the emission intensity of ZnO cores could be significantly enhanced by the amorphous TiO2 shell.

ZnO nanorod arrays were synthesized by chemical bath deposition. After heat treatment in hydrogen or air, Ag nanoparticles were deposited on ZnO nanorod arrays by photo-reduction method. The size of Ag nanoparticles as well as the surface morphology, structure, composition, and optical property of ZnO nanorod arrays before and after the deposition of Ag nanoparticles were characterized by SEM, XRD, EDS, and UV/VIS/NIR spectrophotometer. As compared to the samples with heat treatment in air or without heat treatment, the ZnO nanorod arrays after heat treatment in hydrogen allowed Ag nanoparticles to be deposited more uniformly, densely, and numerously. Also, they exhibited higher efficiency for the visible light-driven photocatalytic degradation of Rhodamine 6G (R6G) dye. The effects of the amount of Ag nanoparticles, initial dye concentration, and temperature on the photocatalytic degradation efficiency were investigated. Furthermore, they also exhibited better surface-enhanced Raman scattering property for the detection of R6G dyes.

The electroluminescence of the light-emitting diodes with five-, ten and 30-fold p-type Ge quantum dots grown on n+ Si substrates is studied. The enhanced integral electroluminescence intensity and blueshift of the 30-fold one at high temperature (>200K) act contrary to those in five- and ten-fold ones. It is attributed to the emission in the higher-fold quantum dots enabled by the injected electrons diffusing the farther at the higher temperature. Transmission electron microscopy shows that the size of the Ge quantum dots and the Si component in them, both increase with increasing the fold number. Due to the strain-induced intermixing at the high-fold quantum dots, those dots hence have large band gap and result in the intensity increment and blueshift at the high temperature.

A new noninvasive screening tool for colorectal neoplasia detects epigenetic alterations exhibited by gastrointestinal tumor cells shed into stool. There is insufficient existing data to determine temporal associations between colorectal cancer (CRC) progression and aberrant DNA methylation. To evaluate the feasibility of using fecal DNA methylation status to determine CRC progression, we collected stool samples from 14 male SD rats aged six weeks, and administered subcutaneous injections of either 1,2-dimethylhydrazine or saline weekly. p16 DNA methylation statuses in tumorous and normal colon tissue, and from stool samples were determined using methylation-specific PCR. Additionally, p16 methylation was detected in stool DNA from 85.7% of the CRC rats. The earliest change in p16 methylation status in the DMH-treated group stool samples occurred during week nine; repeatabilities were 57.1% in week 19 (p = 0.070) and 85.7% in week 34 (p = 0.005). A temporal correlation was evidenced between progression of CRC and p16 methylation status, as evidenced by DMH-induced rat feces. Using fecal DNA methylation status to determine colorectal tissue methylation status can reveal CRC progression. Our data suggests that p16 promoter methylation is a feasible epigenetic marker for the detection and may be useful for CRC screening.

Aluminum-doped zinc oxide (AZO) nanorod array thin film with hydrogen treatment possesses the functions of transparent conducting oxide thin film and 1-D nanostructured semiconductor simultaneously. To enhance the absorption in the visible light region, it is sensitized by cadmium sulfide (CdS) nanoparticles which efficiently increase the absorption around 460 nm. The CdS nanoparticles-sensitized AZO nanorod array thin film with hydrogen treatment exhibits significantly improved photoelectrochemical property. After further heat treatment, a maximum short current density of 5.03 mA cm−2 is obtained under illumination. They not only are much higher than those without CdS nanoparticles sensitization and those without Al-doping and/or hydrogen treatment, but also comparable and even slightly superior to some earlier works for the CdS-sensitized zinc oxide nanorod array thin films with indium tin oxide (ITO) or fluorine-doped tin oxide (FTO) as substrates. This demonstrated successfully that the AZO nanorod array thin film with hydrogen treatment is quite suitable as an ITO/FTO-free photoanode and has great potentials in solar water splitting after sensitization by quantum dots capable of visible light absorption.

Leptin is a peptide hormone, which has a central role in the regulation of body weight; it also exerts many potentially atherogenic effects. Ferulic acid ethyl ester (FAEE) has been approved for antioxidant properties. The aim of this study was to investigate whether FAEE can inhibit the atherogenic effects of leptin and the possible molecular mechanism of its action. Both of cell proliferation and migration were measured when the aortic smooth muscle cell (A10 cell) treated with leptin and/or FAEE. Phosphorylated p44/42MAPK, cell cycle-regulatory protein (for example, cyclin D1, p21, p27), β-catenin and matrix metalloproteinase-9 (MMP-9) proteins levels were also measured. Results demonstrated that leptin (10, 100 ng ml(-1)) significantly increased the proliferation of cells and the phosphorylation of p44/42MAPK in A10 cells. The proliferative effect of leptin was significantly reduced by the pretreatment of U0126 (0.5 μM), a MEK inhibitor, in A10 cells. Meanwhile, leptin significantly increased the protein expression of cyclin D1, p21, β-catenin and decreased the expression of p27 in A10 cells. In addition, leptin (10 ng ml(-1)) significantly increased the migration of A10 cells and the expression of MMP-9 protein. Above effects of leptin were significantly reduced by the pretreatment of FAEE (1 and 10 μM) in A10 cells. In conclusion, FAEE exerts multiple effects on leptin-induced cell proliferation and migration, including the inhibition of p44/42MAPK phosphorylation, cell cycle-regulatory proteins and MMP-9, thereby suggesting that FAEE may be a possible therapeutic approach to the inhibition of obese vascular disease.

Al-doped ZnO (AZO) nanorod array thin films with various Al/Zn molar ratios were synthesized by chemical bath deposition. The resultant AZO nanorods were well-aligned at the glass substrate, growing vertically along the c-axis [001] direction. In addition, they had an average diameter of 64.7 +/- 16.8 nm and an average length of about 1.0 microm with the structure of wurtzite-type ZnO. Analyses of energy dispersive x-ray spectra and x-ray photoelectron spectra indicated that Al atoms had been doped into the ZnO crystal lattice. The doping of Al atoms did not result in significant changes in the structure and crystal orientation, but the electrical resistivity was found to increase first and then decrease with increasing Al content owing to the increase of carrier concentration and the decrease of mobility. In addition, the transmission in the visible region increased but the increase was reduced at higher Al doping levels. After hydrogen treatment, the morphology of the AZO nanorod array thin films remained unchanged. However, the electrical resistivity decreased significantly due to the formation of oxygen vacancies and interstitial hydrogen atoms. When the real Al/Zn molar ratio was about 3.7%, the conductivity was enhanced about 1000 times and a minimum electrical resistivity of 6.4 x 10( - 4) Omega cm was obtained. In addition, the transmission of the ZnO nanorod array thin film in the visible region was significantly increased but the increase was less significant for the AZO nanorod array thin film, particularly at higher Al doping levels. In addition, the current-voltage curves of the thin film devices with ZnO or AZO nanorod arrays revealed that AZO had a higher current response than ZnO and hydrogen treatment led to a more significant enhancement of current responses (about 100-fold).

This study presents data for 27 nonpolar narcotic compounds regarding toxicity to Pseudokirchneriella subcapitata as evaluated using a closed-system algal toxicity test with an exposure time of 48 h. Two test endpoints, dissolved oxygen production and algal growth rate, were used to assess the toxicity of nonpolar narcotic chemicals on algae. Hydrophobicity (1-octanol-water partition coefficient [K(OW)]) provided satisfactory descriptions for the toxicity of nonpolar narcotic compounds, and quantitative structure-activity relationships based on log K(OW) were established. The relative sensitivity of various aquatic organisms to nonpolar chemicals was as follows: P. subcapitata > Vibriofischeri > or = Nitrosomonas sp. > fathead minnow > Daphnia magna > polytox > activated sludge. In addition, linear relationships were found between the toxicity observed in P. subcapitata and other aquatic organisms, except in the case of Nitrosomonas sp. Therefore, for nonpolar toxicants, the closed-system technique applied in the present study can be an ideal surrogate for other tests, such as fathead minnow and D. magna, that are either time-consuming or labor-intensive. However, because the current toxicity database is based primarily on the conventional batch tests, it cannot provide adequate assessment regarding the effects of various organic toxicants. Therefore, more extensive research is needed to revise the database for the toxicity of organic compounds on phytoplankton using the closed-system technique.