Oral squamous cell carcinoma (OSCC) is a common malignancy that has been causally associated with both hereditary and acquired factors. The high mobility group box 1 (HMGB1) gene plays an important ...role as a DNA chaperone to help maintain nuclear homeostasis. Altered expression of HMGB1 has been implicated in a wide range of pathological processes, including inflammation and cancer. The present study explores the impact of HMGB1 gene polymorphisms, combined with environmental risks regarding susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms (SNPs) of the HMGB1 gene, rs1412125, rs2249825, rs1045411, and rs1360485, were evaluated in 1,200 normal controls and 772 patients with OSCC. We found an association between the wild-type allele of rs1045411 and genotypes CT and CT/TT (AOR=0.754, 95% CI=0.582-0.978 and AOR=0.778, 95% CI=0.609-0.995, respectively). Additionally, bioinformatics analysis was used to characterize the functional relevance of these variants for the miRNA-505-5p binding site and transcriptional regulation by the HMGB1 3'-UTR and promoter regions. Moreover, in considering behavioral exposure to environmental carcinogens, the presence of the four HMGB1 SNPs, combined with/without betel quid chewing and smoking showed, profoundly synergistic effects on the risk of OSCC. In conclusion, we present a potential clinical relevance for HMGB1 variants in OSCC, as well as associations between HMGB1 polymorphisms, haplotypes and environmental risk factors. The finding may help in development of optimal therapeutic approaches for OSCC patients.
There are inconsistent data on the durability of hepatitis B e antigen (HBeAg) seroconversion after lamivudine is discontinued. The aim of this study was to examine the determinants for sustained ...HBeAg response to lamivudine therapy. Both host and viral factors as well as the drug factor were compared between 43 patients with sustained HBeAg response and 39 patients whose response was not sustained. All of them received a mean period of 16 months (range, 3–55 months) lamivudine therapy and had achieved complete response (HBeAg seroconversion plus HBV DNA seroclearance by hybrid capture assay and normal alanine aminotransferase ALT) and were followed-up for a mean period of 44 months (range, 12–88 months). Stepwise logistic regression model was used to estimate the sustained response on the presence of the following variables: age; gender; pretherapy ALT; total bilirubin and HBV DNA levels; time to HBeAg seroconversion; additional lamivudine treatment after HBeAg seroconversion; total duration of treatment; hepatitis activity index scores; periportal, intralobular, and portal inflammation and fibrosis scores; scores excluding fibrosis; status of precore mutation; basal core promoter mutation; and genotype. The results showed that genotype (OR, 5.922; 95% CI, 1.611–21.768;
P = .007), age (OR, 0.943; 95% CI, 0.891–0.997;
P = .040), and additional treatment (OR, 1.097; 95% CI, 1.028–1.171;
P = .005) were independent factors to sustained HBeAg response. Further categorical analysis disclosed that patients with genotype B, age ≤36 years, and additional lamivudine treatment over 8 months have higher sustained response. In conclusion, HBV genotype, age, and additional treatment are the major determinants for the sustained HBeAg response to lamivudine therapy.
An efficient steady-state compensation method and a conceptual design for sizing the three-phase three-wire shunt active power filter (APF) under nonsinusoidal source voltages are presented in this ...paper. Conventionally, the compensation currents injected by the APF are determined to eliminate harmonic currents of the nonlinear load as well as to compensate reactive power and maintain the sinusoidal source currents. However, the subject related to the optimal control of the APF to meet the IEEE-519 harmonic current limits and other constraints, such as minimum load power factor requirement after compensation with an optimal kilovolt-ampere rating, are rarely investigated. In this paper, an optimization-based solution algorithm is proposed to determine the three-phase three-wire APF current injections to meet different constraints with an optimal filter size, where the voltage compensation-based control strategy is formulated as a nonlinear programming problem and is solved to find the optimal compensator gains and APF current injections. Results obtained by simulations with Matlab/Simulink show that the proposed approach is very flexible and effective for compensating harmonic currents generated by the nonlinear load with an optimal size of the APF.
► Dioscorea nipponica Makino, a popular folk medicine, exerts anti-inflammation properties. ► DNE inhibited migration/invasion capacities of human oral cancer cells, HSC-3. ► DNE inhibited matrix ...metalloproteinase-2 enzyme activity, and RNA and protein expression. ► DNE inhibited nuclear translocation and DNA binding activity of CREBand AP-1 on the MMP-2 promoter. ► DNE may have potential use as a chemopreventive agent against oral cancer metastasis.
Oral cancer mortality has increased during the last decade due to the difficulties in treating related metastasis. Dioscorea nipponica Makino, a popular folk medicine, exerts anti-obesity and anti-inflammation properties. However, the effect of this folk medicine on metastasis of oral cancer has yet to be fully elucidated. The present study demonstrates that D. nipponica extracts (DNE), at a range of concentrations (0–50μg/mL), concentration-dependently inhibited migration/invasion capacities of human oral cancer cells, HSC-3, without cytotoxic effects. The anti-migration effect of DNE was also observed in two other OSCC cell lines, Ca9-22 and Cal-27. Zymography, real time PCR, and Western blotting analyses revealed that DNE inhibited matrix metalloproteinase-2 (MMP-2) enzyme activity, and RNA and protein expression. The inhibitory effects of DNE on MMP-2 proceeded by up-regulating tissue inhibitor of metalloproteinase-2 (TIMP-2), as well as suppressing nuclear translocation and DNA binding activity of cAMP response element-binding (CREB) and activating protein-1 (AP-1) on the MMP-2 promoter in HSC-3 cells. In conclusion, DNE inhibited the invasion of oral cancer cells and may have potential use as a chemopreventive agent against oral cancer metastasis.
The efficacy of hemoperfusion (HP) in patients with acute paraquat poisoning (PQ) remains controversial. We conducted a multi-center retrospective study to include acute PQ-poisoned patients admitted ...to two tertiary medical centers between 2005 and 2015. We used the Severity Index of Paraquat Poisoning (SIPP) to stratify the severity of PQ-poisoned patients. The indication to start HP was a positive result for the semiquantitative urine PQ test and presentation to the hospital was within 24 h. Early HP was defined as the first session of HP performed within five hours of PQ ingestion. A total of 213 patients (100 HP group, 113 non-HP group) were eligible for the study. The overall 60-day mortality of poisoned patients was 75.6% (161/213). Multivariate Cox regression analysis showed no statistically significant difference in 60-day survival between HP and non-HP groups (95% confidence interval (CI): 0.84–1.63, p = 0.363). Further subgroup analysis in the HP group showed early HP (95% CI: 0.54–1.69, p = 0.880), and multiple secessions of HP (95% CI: 0.56–1.07, p = 0.124) were not significantly related to better survival. Among acute PQ-poisoned patients, this study found that HP was not associated with increased 60-day survival. Furthermore, neither early HP nor multiple secessions of HP were associated with survival.
This investigation evaluated the efficacy by which resistance training enhances body composition, metabolic, and functional outcomes for obese patients undergoing a 12-week medically supervised ...hypocaloric treatment.
This was a single-blind, randomized, parallel-group prospective trial. Morbidly obese patients were prescribed a 12-week proprietary very low calorie diet (VLCD) treatment (Optifast®) with supplemental protein (1120 kcals/day) and were placed in one of two groups for 14 weeks: 1) Standard Treatment Control (CON) (n = 5) or 2) Resistance Training (RT) (n = 6). Both groups underwent a pedometer-based walking program; however only RT performed resistance training 3 days/week for 12 weeks. Body composition, resting energy expenditure (REE), neuromuscular function, and serum biomarkers were measured at weeks 0, 6, and 13.
Both groups exhibited a significant loss of total body mass (TBM) (CON: −19.4 ± 2.3 kg, p = 0.0009 vs. RT: −15.8 ± 1.5 kg, p = 0.0002) and fat mass (FM) (CON: −14.7 ± 1.8 kg, p = 0.0002 vs. RT: −15.1 ± 2.1 kg, p = 0.0002) with no group differences. CON lost 4.6 ± 0.8 kg (p = 0.004) of lean mass (LM) while RT demonstrated no changes. Group differences were found for the relative proportion of total weight-loss due to FM-loss (CON: 75.6 ± 3.4% vs. RT: 96.0 ± 6.0%, p = 0.03) and LM-loss (CON: 24.4 ± 3.2% vs. RT: 4.0 ± 6.5%, p = 0.03). CON demonstrated a 328.6 ± 72.7 kcal/day (−14.3 ± 2.4%) (p = 0.02) decrease in REE while RT exhibited a non-significant decrease of 4.6 ± 1.6% (p = 0.78). RT demonstrated greater improvements in all measures of contractile function and strength when compared to CON (p < 0.05). At post-treatment, RT exhibited greater serum free fatty acids (p = 0.01), glycerol (p = 0.003), and β-hydroxybutyrate (p = 0.005) than CON.
Resistance training was advantageous for weight-loss composition by preservation of LM without compromising overall weight- or fat-loss in morbidly obese men and women undergoing a protein supplemented VLCD. These changes accompanied positive adaptations for resting metabolism and muscular function.
Immunotherapy is a highly promising approach for the treatment of gastric cancer, the third-leading cause of overall cancer death worldwide. In particular, tumor-infiltrating lymphocytes and ...peripheral blood mononuclear cells are believed to mediate host immune responses, although this activity may vary depending on the activation status and/ or their microenvironments. Here, we examined the expression of a specific zinc finger transcription factor, Helios (IKZF2), in gastric tumor-infiltrating lymphocytes by immunohistochemistry and the correlation with survival. Segregation of gastric cancer patients into high- vs. low-Helios-expressing tumor-infiltrating lymphocytes showed those with high expression to exhibit longer survival in gastric cancer patients, Helicobacter pylori-infected gastric cancer patients and advanced stage (III–IV) gastric cancer patients. In particular, Helios expression was an independent factor for survival in advanced gastric cancer patients. We performed immunofluorescence staining to detect Helios expression in tumor-infiltrating lymphocytes and peripheral blood mononuclear cells. We found that Helios is expressed more in CD4+ T cells and little in CD8+ T cells in infiltrated lymphocytes in gastric cancer. In summary, we believe that the study of specific characteristics of tumor-infiltrating lymphocytes can delineate the interactions of immune and tumor cells to improve upon immunotherapy strategies.
Purpose: Diabetes mellitus (DM) increases the risk of cardiovascular and all-cause mortality. The coexistence of depression and DM is associated with an increased risk of DM complications and ...functional morbidity. The independent effect of depression on mortality in patients with DM is unclear, and relevant Asian studies have provided inconsistent results. Accordingly, this study assessed the independent and additive effects of DM and depression on mortality in a nationally representative cohort of older adults in Taiwan over a 10-year observation period. Patients and Methods: A total of 5041 participants aged 50 years or older were observed between 1996 and 2007. We defined depression as a score of greater than or equal to8 on the 10-item Center for Epidemiologic Studies Depression (CES-D 10) scale. Additionally, we defined participants as having type 2 DM if they had received a diagnosis of type 2 DM from a health-care provider. Cox proportional hazard models were applied to analyze predictors of mortality in depression and DM comorbidity groups. Results: During the 10-year follow-up period, 1637 deaths were documented. After adjustment for potential confounders, the hazard ratios for mortality in participants with both depression and DM, DM only, and depression only were 2.47 (95% confidence interval CI: 2.02-3.03), 1.95 (95% CI: 1.63-2.32), and 1.23 (95% CI: 1.09-1.39), respectively. Conclusion: The co-occurrence of depression with DM in Asian adults increased overall mortality rates. Our results indicate that the increased mortality hazard in individuals with DM and depression was independent of sex. Keywords: diabetes mellitus, depression, mortality, cohort
Hepatocellular carcinoma (HCC) is a prevalent primary neoplasm of the liver, whose heterogeneous global incidence suggests the likely impact of genetic variations among individuals on the ...susceptibility to this disease. Increasing evidence indicates that melatonin exhibits oncostatic properties in many cancer types at least in part mediated by its membrane-bound receptors, melatonin receptor 1A (encoded by
) and 1B (
). In this study, the effect of melatonin receptor gene polymorphisms on the risk and progression of hepatic tumors was evaluated between 335 HCC patients and 1196 cancer-free subjects. We detected a significant association of MTNR1A single nucleotide polymorphism (SNP), rs6553010, with the elevated risk of HCC (AOR, 1.587; 95% CI, 1.053-2.389;
= 0.027) after being adjusted for two potential confounders, age and alcohol use. In addition, patients who carry at least one polymorphic allele (heterozygote or homozygote) of MTNR1A rs2119882 or rs2375801 were more prone to develop distant metastasis (OR, 5.202; 95% CI, 1.163-23.270;
= 0.031, and OR, 7.782; 95% CI, 1.015-59.663;
= 0.048, for rs2119882 and rs2375801, respectively). Further analyses revealed that rs2119882 is located on the consensus binding site of GATA2 transcription factor within the promoter region of
gene, and that a correlation between the levels of GATA2 and melatonin receptor 1A was observed in the TCGA (The Cancer Genome Atlas) dataset. Moreover, individuals bearing a specific haplotype of four
SNPs were more prone to develop HCC. In conclusion, our data suggest an association of melatonin receptor gene polymorphisms with the risk of HCC and hepatic cancer metastasis.
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