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INTRODUCTION: Gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD) are prevalent in Taiwan. Few studies have investigated the associations between obesity indices with GERD and PUD simultaneously. This study aimed to investigate the correlations among obesity indices with GERD and PUD in a large cohort of participants, around 120,000, in the Taiwan Biobank (TWB). METHODS: A total of 121,583 participants (male: 43,698; female: 77,885; mean age 49.9 ± 11.0 years) were included to analyze the associations among obesity indices, including body mass index (BMI), waist-hip ratio (WHR), waist-to-height ratio (WHtR), body roundness index (BRI), abdominal volume index (AVI), lipid accumulation product (LAP), visceral adiposity index (VAI), and triglyceride-glucose index (TyG index), with GERD and PUD. Self-reported GERD and PUD were obtained by questionnaires. Multivariate logistic regression analysis was employed to analyze the relationship between obesity indices with GERD and PUD. RESULTS: The prevalence of GERD and PUD was 13.7% and 14.6%, respectively. After multivariable analysis, high WHR (odds ratio [OR] = 1.009, p < 0.001), WHtR (OR = 1.005, p = 0.003), BRI (OR = 1.022, p = 0.005), AVI (OR = 1.013, p < 0.001), LAP (OR = 1.001, p < 0.001), TyG index (OR = 1.068, p < 0.001), and VAI (OR = 1.013, p = 0.002) were significantly associated with GERD, except BMI (p = 0.384). On the other hand, low BMI (OR = 0.984; p < 0.001) and AVI (OR = 0.994; p = 0.036) were significantly associated with PUD. However, the values of WHR (p = 0.151), WHtR (p = 0.304), BRI (p = 0.452), LAP (p = 0.799), VAI (p = 0.347), and TyG index (p = 0.642) were not. CONCLUSION: This study found that high obesity indices are associated with GERD, but low obesity indices are associated with PUD in a large Taiwanese population study. Our findings may alert physicians to notice that different obesity index may be associated with different gastrointestinal disorder.
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Background: Hyperuricemia may play a role in various systemic diseases. However, few studies have investigated the relationship between hyperuricemia and the risk of peptic ulcer disease (PUD). Therefore, in this population-based study, we enrolled over 120,000 participants from the Taiwan Biobank (TWB) and examined the risk factors for self-reported PUD. In addition, we investigated sex differences in the association between hyperuricemia and self-reported PUD. Methods: Data of 121,583 participants were obtained from the TWB. Male participants with a serum uric acid level >7 mg/dl and female participants with a serum uric acid level >6 mg/dl were classified as having hyperuricemia. Details of self-reported PUD were obtained by questionnaire. The association between hyperuricemia and self-reported PUD in the male and female participants was examined using multivariable logistic regression analysis. Results: The overall prevalence of self-reported PUD was 14.6%, with a higher incidence in males (16.5%) compared to females (13.5%). After multivariable adjustment, male sex [vs. female sex; odds ratio (OR) = 1.139; 95% confidence interval (CI) = 1.084-1.198; p < 0.001], and hyperuricemia (OR = 0.919; 95% CI = 0.879-0.961; p < 0.001) were significantly associated with self-reported PUD. Further, a significant interaction was found between sex and hyperuricemia on self-reported PUD (p = 0.004). Hyperuricemia was associated with a low risk of self-reported PUD in males (OR = 0.890; 95% CI = 0.837-0.947; p < 0.001) but not in females (p = 0.139). Conclusion: The prevalence of self-reported PUD was higher in the male participants than in the female participants. Hyperuricemia was associated with low prevalence of self-reported PUD in males, but not in females. Further studies are needed to clarify the mechanisms behind these observations and verify the potential protective role of hyperuricemia on the development of self-reported PUD.
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BACKGROUND: Gastroesophageal reflux disease (GERD) is a common global health issue. Previous studies have revealed a higher prevalence of GERD in females than in males, however few studies have investigated sex differences in the risk factors associated with GERD. Therefore, the aim of this population-based study was to examine sex differences in the risk factors for GERD in a large cohort of over 120,000 Taiwanese participants. METHODS: We enrolled 121,583 participants (male: 43,698; female: 77,885; mean age 49.9 ± 11.0 years) from the Taiwan Biobank. The presence of GERD was ascertained using self-reported questionnaires. Sex differences in the risk factors associated with GERD were examined using multivariable logistic regression analysis. RESULTS: The overall prevalence of GERD was 13.7%, including 13.0% in the male participants and 14.1% in the female participants (p < 0.001). Multivariable analysis showed that older age, hypertension, smoking history, alcohol history, low fasting glucose, and low uric acid were significantly associated with GERD in the male participants. In the female participants, older age, diabetes, hypertension, smoking history, alcohol history, low systolic blood pressure, low fasting glucose, high hemoglobin, high total cholesterol, low high-density lipoprotein cholesterol (HDL-C), low low-density lipoprotein cholesterol, and low uric acid were significantly associated with GERD. Significant interactions were found between sex and age (p < 0.001), diabetes (p < 0.001), smoking history (p < 0.001), fasting glucose (p = 0.002), triglycerides (p = 0.001), HDL-C (p = 0.001), and estimated glomerular filtration rate (p = 0.002) on GERD. CONCLUSIONS: Our results showed a higher prevalence of GERD among females compared to males. Furthermore, sex differences were identified in the risk factors associated with GERD, and older age, diabetes, smoking history, and low HDL-C were more closely related to GERD in females than in males.
Subject(s)
Gastroesophageal Reflux , Smoking , Humans , Gastroesophageal Reflux/epidemiology , Male , Female , Middle Aged , Taiwan/epidemiology , Risk Factors , Sex Factors , Adult , Prevalence , Smoking/epidemiology , Age Factors , Hypertension/epidemiology , Alcohol Drinking/epidemiology , Diabetes Mellitus/epidemiology , Uric Acid/blood , Blood Glucose/analysis , AgedABSTRACT
BACKGROUND: Trimethylamine N-oxide (TMAO), a metabolite produced by intestinal microbiota through metabolizing phosphatidylcholine, choline, l-carnitine and betaine in the diet, has been implicated in the pathogenesis of atherosclerosis (AS). Concurrently, dietary polyphenols have garnered attention for their potential to ameliorate obesity, diabetes and atherosclerosis primarily by modulating the intestinal microbial structure. Hickory (Carya cathayensis) nut, a polyphenol-rich food product favored for its palatability, emerges as a candidate for exploration. HYPOTHESIS/PURPOSE: The relationship between polyphenol of hickory nut and atherosclerosis prevention will be firstly clarified, providing theoretical basis for the discovery of natural products counteracting TMAO-induced AS process in hickory nut. STUDY DESIGN AND METHODS: Employing Enzyme-linked Immunosorbent Assay (ELISA) and histological examination of aortic samples, the effects of total polyphenol extract on obesity index, inflammatory index and pathological changes of atherosclerosis in C57BL/6 J mice fed with high-fat and high choline diet were evaluated. Further, the composition, abundance, and function of mouse gut microbiota were analyzed through 16srDNA sequencing. Concurrently, the levels of TMAO and the expression of key enzymes (CutC and FMO3) involved in its synthesis are quantified using ELISA, Western Blot and Real-Time Quantitative PCR (RT-qPCR). Additionally, targeted metabolomic profiling of the hickory nut polyphenol extract was conducted, accompanied by molecular docking simulations to predict interactions between candidate polyphenols and the CutC/FMO3 using Autodock Vina. Finally, the docking prediction were verified by microscale thermophoresis (MST) . RESULTS: Polyphenol extracts of hickory nut improved the index of obesity and inflammation, and alleviated the pathological changes of atherosclerosis in C57BL/6 J mice fed with high-fat and high-choline diet. Meanwhile, these polyphenol extracts also changed the composition and function of intestinal microbiota, and increased the abundance of microorganisms in mice. Notably, the abundance of intestinal microbiota endowed with CutC gene was significantly reduced, coherent with expression of CutC catalyzing TMA production. Moreover, polyphenol extracts also decreased the expression of FMO3 in the liver, contributing to the reduction of TMAO levels in serum. Furthermore, metabonomic profile analysis of these polyphenol extracts identified 647 kinds of polyphenols. Molecular docking predication further demonstrated that Casuariin and Cinnamtannin B2 had the most potential inhibition on the enzymatic activities of CutC or FMO3, respectively. Notably, MST analysis corroborated the potential for direct interaction between CutC enzyme and available polyphenols such as Corilagin, (-)-Gallocatechin gallate and Epigallocatechin gallate. CONCLUSION: Hickory polyphenol extract can mitigate HFD-induced AS by regulating intestinal microflora in murine models. In addition, TMA-FMO3-TMAO pathway may play a key role in this process. This research unveils, for the inaugural time, the complex interaction between hickory nut-derived polyphenols and gut microbial, providing novel insights into the role of dietary polyphenols in AS prevention.
Subject(s)
Atherosclerosis , Gastrointestinal Microbiome , Methylamines , Mice, Inbred C57BL , Oxygenases , Polyphenols , Animals , Polyphenols/pharmacology , Gastrointestinal Microbiome/drug effects , Methylamines/metabolism , Atherosclerosis/prevention & control , Atherosclerosis/drug therapy , Male , Mice , Nuts/chemistry , Diet, High-Fat/adverse effects , Choline , Plant Extracts/pharmacology , Plant Extracts/chemistry , Obesity/prevention & control , Molecular Docking SimulationABSTRACT
The expression of metastasis tumor-associated protein 2 (MTA2) and protein tyrosine kinase 7 (PTK7) is associated with hepatocellular carcinoma (HCC) progression. However, the functional effect and mechanism through which MTA2 regulates PTK7-mediated HCC progression remains unclear. Here, we found that MTA2 knockdown significantly down-regulated PTK7 expression in HCC cells (SK-Hep-1 and PLC/PRF/5). Data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases show that the PTK7 expression level was higher in HCC tissues than in normal liver tissues. In HCC patients, the PTK7 expression level clearly correlated with tumor stage and grade, lower overall survival (OS) correlated positively with MTA2 level, and PTK7 expression acted as a downstream factor for MTA2 expression. In addition, matrix metalloproteinase 7 (MMP7) expression was closely regulated by PTK7, and the mRNA and protein expression levels of MTA2 and PTK7 correlated positively with lower OS. MMP7 downregulation by PTK7 knockdown clearly decreased the migration and invasion abilities of HCC cells. In HCC cells, recombinant human MMP7 reversed the PTK7 knockdown-induced suppression of migration and invasion. Furthermore, deactivation of FAK using siFAK or FAK inhibitor (PF-573228, PF) synergistically contributed to PTK7 knockdown-inhibited FAK activity, MMP7 expression, and the migration and invasion abilities of HCC cells. Collectively, our findings show that PTK7 mediates HCC progression by regulating the MTA2-FAK-MMP7 axis and may be a diagnostic value for HCC patients.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Repressor Proteins , Humans , Carcinoma, Hepatocellular/pathology , Matrix Metalloproteinase 7/genetics , Matrix Metalloproteinase 7/metabolism , Liver Neoplasms/pathology , Down-Regulation , Cell Movement/genetics , Neoplasm Proteins/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Neoplasm Invasiveness/genetics , Cell Adhesion Molecules/metabolism , Receptor Protein-Tyrosine Kinases/genetics , Histone Deacetylases/genetics , Histone Deacetylases/metabolismABSTRACT
The goal of this study was to develop a ferroptosis-based molecular signature that can predict recurrence-free survival (RFS) in patients with prostate cancer (PCa). In this study, we obtained ferroptosis-related genes (FRGs) in FerrDb database and clinical transcriptome data in TCGA database and GEO database. Consensus cluster analysis was used to identify three molecular markers of ferroptosis in PCa with differential expression of 40 FRGs, including PD-L1 expression levels. We conducted a new ferroptosis-related signature for PCa RFS using four FRGs identified through univariate and multivariate Cox regression analyses. The signature was validated in the training, testing, and validation cohorts, and it demonstrated remarkable results in the area under the time-dependent receiver operating characteristic (ROC) curve of 0.757, 0.715, and 0.732, respectively. Additionally, we observed that younger patients, those with stage T III and stage T IV, stage N0, cluster 1, and cluster 2 PCa were more accurately predicted by the signature as independent predictors of RFS. DU-145 and RWPE-1 cells were successfully analyzed by qRT-PCR and Western blot for ASNS, GPT2, RRM2, and NFE2L2. In summary, we developed a novel ferroptosis-based signature for RFS in PC, utilizing four FRGs identified through univariate and multivariate Cox regression analyses. This signature was rigorously validated across training, testing, and validation cohorts, demonstrating exceptional performance as evidenced by its ROC curves. Notably, our findings indicate that this signature is particularly effective as an independent predictor of RFS in younger patients or those with stage T III and T IV, stage N0, and in clusters 1 and 2. Finally, we confirmed the expression of these four FRGs in DU-145 and RWPE-1 cell lines.
Subject(s)
Ferroptosis , Prostatic Neoplasms , Male , Humans , Ferroptosis/genetics , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , Biomarkers , Blotting, Western , Cell LineABSTRACT
Adulteration of meat and meat products causes a concerning threat for consumers. It is necessary to develop novel robust and sensitive methods which can authenticate the origin of meat species to compensate for the drawbacks of existing methods. In the present study, the sarcoplasmic proteins of six meat species, namely, pork, beef, mutton, chicken, duck and turkey, were analyzed by one-dimensional gel electrophoresis. It was found that enolase could be used as a potential biomarker protein to distinguish between livestock and poultry meats. The glycosylation sites and glycans of enolase were analyzed by UPLC-QTOF-MS and a total of 41 glycopeptides were identified, indicating that the enolase N-glycopeptide profiles of different meats were species-specific. The identification models of livestock meat, poultry and mixed animal were established based on the glycopeptide contents, and the explanation degree of the three models was higher than 90%. The model prediction performance and feasibility results showed that the average prediction accuracy of the three models was 75.43%, with the animal-derived meat identification model showing superiority in identifying more closely related species. The obtained results indicated that the developed strategy was promising for application in animal-derived meat species monitoring and the quality supervision of animal-derived food.
Subject(s)
Glycopeptides , Red Meat , Cattle , Animals , Meat/analysis , Poultry , Red Meat/analysis , Chickens , Phosphopyruvate HydrataseABSTRACT
Gastric cancer (GC) organoids are frequently used to examine cell proliferation and death as well as cancer development. Invasion/migration assay, xenotransplantation, and reactive oxygen species (ROS) production were used to examine the effects of antioxidant drugs, including perillaldehyde (PEA), cinnamaldehyde (CA), and sulforaphane (SFN), on GC. PEA and CA repressed the proliferation of human GC organoids, whereas SFN enhanced it. Caspase 3 activities were also repressed on treatment with PEA and CA. Furthermore, the tumor formation and invasive activities were repressed on treatment with PEA and CA, whereas they were enhanced on treatment with SFN. These results in three-dimensional (3D)-GC organoids showed the different cancer development of phase II enzyme ligands in 2D-GC cells. ROS production and the expression of TP53, nuclear factor erythroid 2-related factor (NRF2), and Jun dimerization protein 2 were also downregulated on treatment with PEA and CA, but not SFN. NRF2 knockdown reversed the effects of these antioxidant drugs on the invasive activities of the 3D-GC organoids. Moreover, ROS production was also inhibited by treatment with PEA and CA, but not SFN. Thus, NRF2 plays a key role in the differential effects of these antioxidant drugs on cancer progression in 3D-GC organoids. PEA and CA can potentially be new antitumorigenic therapeutics for GC.
Subject(s)
Antioxidants , Stomach Neoplasms , Humans , Antioxidants/pharmacology , Apoptosis , Cell- and Tissue-Based Therapy , Isothiocyanates/pharmacology , Isothiocyanates/metabolism , NF-E2-Related Factor 2/metabolism , Organoids/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , Sulfoxides/pharmacologyABSTRACT
BACKGROUND: Gastrectomy remains the curative option in gastric cancer. However, the growing concern that preoperative waiting jeopardizes survival has not been fully addressed. The present population-based cohort study aimed to clarify the impact of preoperative waiting time (PreWT). METHODS: We included patients with clinical Stage II-III gastric cancer who received curative surgery from 2008 to 2017 of Taiwan Cancer Registry. PreWT was defined as the time from endoscopic diagnosis to surgery. The prognostic impact on overall survival (OS) was evaluated with Cox and restricted cubic spline regressions. RESULTS: A total of 3059 patients with a median age of 68 years were evaluated. The median PreWT was 16 days (interquartile range, 11-24 days), and patients with a shorter PreWT were younger, had a more advanced disease and received adjuvant therapies. Despite a shorter OS occurring with prolonged PreWT (median OS by PreWT [days]: 7-13, 2.7 years; 14-20, 3.1 years; 21-27, 3.0 years; 28-34, 4.7 years; 35-31, 3.7 years; 42-48, 3.4 years; 49-118, 2.8 years; p = 0.029), the differences were not significant after adjustment. The Cox and restricted cubic spline regressions showed that prolonged PreWT was not a significant prognostic factor for OS (p = 0.719). CONCLUSIONS: The population-based study suggests that a PreWT of 49-118 days does not independently correlate with a poor prognosis in Stage II-III gastric cancer. The study provides rationale for a window period for preoperative therapies and patient optimization.
Subject(s)
Esophageal Neoplasms , Stomach Neoplasms , Humans , Aged , Stomach Neoplasms/pathology , Cohort Studies , Waiting Lists , Prognosis , Esophagogastric Junction/surgery , Esophagogastric Junction/pathology , Gastrectomy , Esophageal Neoplasms/pathology , Retrospective Studies , Neoplasm StagingABSTRACT
Aims: To investigate the safety profile, dose-limiting toxicity and antitumor activity of PEP503 (NBTXR3) nanoparticles with radiotherapy and concurrent chemotherapy in patients with locally advanced or unresectable rectal cancer. Methods: Patients will receive a single intratumoral injection of the nanoparticles, followed by radiotherapy and intravenous infusion of fluorouracil or oral capecitabine concurrently. In phase Ib (escalation phase, 3 + 3 design), volume escalation is based on the tumor volume of 5, 10, 15 and 22% of total baseline tumor volume. In phase II (expansion phase), 18 additional patients will be enrolled. Discussion: This study will be the first prospective, open-label, single-arm, nonrandomized study to investigate the efficacy and safety profile of PEP503 (NBTXR3) nanoparticles with radiotherapy and chemotherapy in these patients. Trial registration number: NCT02465593 (ClinicalTrials.gov).
Preoperative concurrent chemoradiotherapy is the standard treatment for patients with locally advanced rectal cancer. PEP503 (NBTXR3) has radioenhancement properties. Therefore, the dose per fraction during radiotherapy could be reduced, and the same therapeutic efficacy could be retained when PEP503 (NBTXR3) nanoparticles are used during radiotherapy. This study reveals the protocol of a phase Ib/II study to investigate the safety profile, dose-limiting toxicity and antitumor activity of PEP503 (NBTXR3) nanoparticles with radiotherapy combined with concurrent chemotherapy in patients with locally advanced or unresectable rectal cancer.
Subject(s)
Antineoplastic Agents , Rectal Neoplasms , Humans , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols , Capecitabine/therapeutic use , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Fluorouracil/therapeutic use , Prospective Studies , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapyABSTRACT
The lotus seed pod is one of the main organs of the lotus plant and is commonly used in traditional medicine. It is believed to have dehumidifying and anti-rheumatic effects. This study, utilized the non-targeted approach of identification via UPLC-QTOF-MS/MS to identify the main chemical components in the lotus seed pod extracts and found a total of 118 compounds. Among them, 25 components were identified for the first time in the lotus seed pod. Next, using the molecular docking technique, common gout receptors (PDB ID: 1N5X, 1FIQ, 2EIQ) were docked to the compounds in the extracts, and their activities were screened using the LibDock and CDOCKER modules. In order to screen compounds with anti-gout activity in the lotus seed pod, acid precipitation (AP) fractions were prepared by an established extraction method of flavonoids, which were then analyzed qualitatively and quantitatively. Finally, a rodent model bearing acute gout and hyperuricemia was established by ankle injection of sodium urate and intraperitoneal injection of xanthine and potassium oxonate. The results of this study showed that AP could not only significantly alleviate joint swelling and pro-inflammatory cytokine levels, but also reduce synovial and renal pathological damage. This indicated the efficacy of AP in the treatment of gouty arthritis.
Subject(s)
Arthritis, Gouty , Gout , Hyperuricemia , Molecular Docking Simulation , Tandem Mass Spectrometry , Plant Extracts/chemistry , Molecular Structure , Hyperuricemia/drug therapy , Hyperuricemia/pathology , Seeds/chemistryABSTRACT
We prepared three-dimensional (3-D) organoids of human stomach cancers and examined the correlation between the tumorigenicity and cytotoxicity of Helicobacter pylori (H. pylori). In addition, the effects of hepatoma-derived growth factor (HDGF) and tumor necrosis factor (TNFα) on the growth and invasion activity of H. pylori-infected gastric cancer organoids were examined. Cytotoxin-associated gene A (CagA)-green fluorescence protein (GFP)-labeled H. pylori was used to trace the infection in gastric organoids. The cytotoxicity of Cag encoded toxins from different species of H. pylori did not affect the proliferation of each H. pylori-infected cancer organoid. To clarify the role of HDGF and TNFα secreted from H. pylori-infected cancer organoids, we prepared recombinant HDGF and TNFα and measured the cytotoxicity and invasion of gastric cancer organoids. HDGF controlled the growth of each organoid in a species-specific manner of H. pylori, but TNFα decreased the cell viability in H. pylori-infected cancer organoids. Furthermore, HDGF controlled the invasion activity of H. pylori-infected cancer organoid in a species-dependent manner. However, TNFα decreased the invasion activities of most organoids. We found different signaling of cytotoxicity and invasion of human gastric organoids in response to HDGF and TNFα during infection by H. pylori. Recombinant HDGF and TNFα inhibited the development and invasion of H. pylori-infected gastric cancer differently. Thus, we propose that HDGF and TNFα are independent signals for development of H. pylori-infected gastric cancer. The signaling of growth factors in 3-D organoid culture systems is different from those in two-dimensional cancer cells.
Subject(s)
Carcinoma, Hepatocellular , Helicobacter Infections , Helicobacter pylori , Liver Neoplasms , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Tumor Necrosis Factor-alpha/metabolism , Helicobacter pylori/metabolism , Antigens, Bacterial/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Organoids/metabolism , Helicobacter Infections/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/pharmacology , Bacterial Proteins/metabolismABSTRACT
BACKGROUND: This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed. METHODS: Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry. RESULTS: Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn's disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non-reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively. CONCLUSIONS: The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.
Subject(s)
Colitis, Ulcerative , Crohn Disease , Hepatitis B , Inflammatory Bowel Diseases , Humans , Taiwan , Remission Induction , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Recurrence , Treatment Outcome , Retrospective StudiesABSTRACT
Objective:To prepare a recombinant hemagglutinin trimer (HA-Tri) vaccine against influenza viruses and to study its immunogenicity in a mouse model.Methods:A stable CHO cell line that could express HA-Tri was constructed. Western blot, single radial immunodiffusion, protein particle size detection and N-glycosylation site analysis were performed for qualitative and quantitative analysis of the recombinant protein. According to the different treatment conditions such as dosage and adjuvant, BALB/c mice were divided into 11 groups and subjected to consistent immunization procedures. Serum neutralizing antibody titers were measured on 56 d after the first immunization to evaluate the immunogenicity of HA-Tri.Results:The constructed CHO cells could secret and express HA-Tri proteins. The HA-Tri proteins were biologically active and capable of forming precipitation rings in the single radial immunodiffusion. The particle size of HA-Tri was approximately 18.79 nm and 10 N-glycosylation sites were detected, including high mannose, complex glycoforms and heterozygous glycoforms. After prime-boost immunization, there was no statistically significant difference in the titers of neutralizing antibodies induced in mice by 3.75 μg of HA-Tri in combination with RFH01 adjuvant and 15 μg of monovalent vaccine stock solution ( P=0.431 2, U=36). Serum antibody titers in the HA-Tri+ RFH01 groups were higher than those in the corresponding HA-Tri groups without RFH01 adjuvant, and the highest titer was induced in the 15 μg HA-Tri+ RFH01 group, which was 1 280. Conclusions:The recombinant HA-Tri protein was successfully prepared. HA-Tri in combination with RFH01 adjuvant could induce humoral immune responses against influenza viruses in BALB/c mice, which would provide reference for the development of influenza virus recombinant subunit vaccines.
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BACKGROUND: Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients. METHODS: We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively. RESULTS: For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor. CONCLUSIONS: An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).
Subject(s)
Esomeprazole , Peptic Ulcer , Humans , Esomeprazole/therapeutic use , Proton Pump Inhibitors/therapeutic use , Ulcer/complications , Peptic Ulcer Hemorrhage/drug therapy , Peptic Ulcer/complications , Peptic Ulcer/drug therapy , RecurrenceABSTRACT
Doxorubicin (DOX) is a potent chemotherapeutic agent used for cancer treatment, however, DOX-induced cardiotoxicity is a serious clinical problem because it causes acute and chronic heart dysfunction. Many studies have indicated that the α1-adrenergic receptor protects the heart from pathologic stress through activation survival signaling, however, the mechanism remains largely unknown. Previous studies have detected that the phenylephrine-induced complex-1 (PEX1) transcription factor, also known as zinc-finger protein 260 (Zfp260), is an effector of α1-adrenergic signaling in cardiac hypertrophy. Our present study aimed to investigate the role and underlying mechanism of PEX1 in cardiomyocyte survival during DOX-induced cardiotoxicity. Mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg) to generate DOX-induced cardiotoxicity. We found that PEX1 expression was downregulated in DOX-treated murine hearts. PEX1 deficiency resulted in increased apoptosis, and conversely, PEX1 overexpression alleviated apoptosis induced by DOX in primary cardiomyocytes, as well as upregulated antiapoptotic genes such as BCL-2 and BCL-XL. Mechanistically, we identified that PEX1 might exert its antiapoptosis effect by playing a pivotal role in the action of α1-adrenergic signaling activation, which depends on the presence of GATA-4. Based on these findings, we supposed that PEX1 may be a novel transcription factor involved in cardiac cell survival and a promising candidate target for DOX-induced cardiotoxicity.
Subject(s)
Adrenergic Agents , Cardiotoxicity , Mice , Animals , Cardiotoxicity/metabolism , Adrenergic Agents/metabolism , Adrenergic Agents/pharmacology , Doxorubicin/toxicity , Myocytes, Cardiac/metabolism , Apoptosis , Transcription Factors/metabolism , Oxidative Stress , ATPases Associated with Diverse Cellular Activities/metabolism , ATPases Associated with Diverse Cellular Activities/pharmacologyABSTRACT
Objective: This study aims to investigate the expression of neuronal transcription factor SOX11 in small-cell lung cancer (SCLC) and compare it with the expression of CD56 (nerve cell adhesion molecule), synaptophysin (Syn), chromogranin A (CgA), and thyroid transcription factor-1 (TTF-1) to explore the application value of SOX11 in the pathological diagnosis of SCLC. Methods: Immunohistochemical methods were used to detect the expression of SOX11, TTF-1, CD56, Syn, and CgA in 120 lung tumor tissues, and experimental results were analyzed using SPSS23.0 statistical software. Results: Immunohistochemical results showed that in the 120 lung tumor samples, SOX11 was highly expressed in SCLC and localized to the nucleus, with low or no expression in control carcinoid/lung neuroendocrine tumors, lung adenocarcinomas, and lung squamous cell carcinomas. Statistical analysis results revealed the following points. First, the expression of SOX11 was closely related to the tumor histological type. The expression of SOX11 in SCLC (positive rate of 63.33%) was significantly higher than that in carcinoid/neuroendocrine tumors (positive rate of 12.50%), lung adenocarcinoma (positive rate of 0%), and lung squamous cell carcinoma (positive rate of 0%). Second, immunohistochemical investigation of 60 SCLC cases revealed that the highest positive rates of CD56, TTF-1, and Syn, respectively, were 93.33 percent, 95 percent, and 86.67 percent. SOX11 also exhibited high sensitivity (0.633) and specificity (0.875) in SCLC. The positive rates of SOX11 and CgA were 63.33% and 50.00%, respectively. Statistical results revealed that the positive rate of CgA had no significant difference (P > 0.05). Lastly, the combined use of antibodies SOX11, CgA, CD56, Syn, and TTF-1 was more beneficial to improving the diagnosis rate of SCLC than the single use of one or two antibodies. Conclusion: The expression of SOX11 in different histological types of lung tumors differs considerably. SOX11 is highly expressed in SCLC. SOX11 can be used as a beneficial supplement to the combination of classical neuroendocrine markers and in combination with CgA, CD56, Syn, and TTF-1 to assist in the diagnosis of SCLC.
Subject(s)
Carcinoid Tumor , Carcinoma, Neuroendocrine , Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Neuroendocrine Tumors , Small Cell Lung Carcinoma , Biomarkers, Tumor/metabolism , Carcinoma, Neuroendocrine/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Chromogranin A , Humans , Lung Neoplasms/metabolism , Neuroendocrine Tumors/pathology , SOXC Transcription Factors/genetics , Small Cell Lung Carcinoma/diagnosis , Transcription FactorsABSTRACT
This study was aimed to investigate the structural and immunological properties of parvalbumin from mandarin fish during the Maillard reaction. The microwave-assisted the Maillard reaction was optimized by orthogonal designed experiments. The results showed that the type of sugar and heating time had a significant effect on the Maillard reaction (p < 0.05). The SDS-PAGE analysis displayed that the molecular weight of parvalbumin in mandarin fish changed after being glycated with the Maillard reaction. The glycated parvalbumin was analyzed by Nano-LC-MS/MS and eleven glycation sites as well as five glycation groups were identified. By using the indirect competitive ELISA method, it was found that microwave heating gave a higher desensitization ability of mandarin fish parvalbumin than induction cooker did. In vitro gastric digestion experiments showed that microwave-heated parvalbumin was proved to be digested more easily than that cooked by induction cookers. The microwave-assisted Maillard reaction modified the structure of parvalbumin and reduced the immunoreactivity of parvalbumin of mandarin fish.
ABSTRACT
PURPOSE: To assess the diagnostic performance of contrast-enhanced (CE) US Liver Imaging Reporting and Data System (LI-RADS) version 2017 and propose a diagnostic algorithm in diagnosing hepatocellular carcinoma (HCC) in patients with occult HBV infection (OBI). METHODS: 251 OBI patients with 251 newly diagnosed focal liver lesions were retrospectively enrolled. Each nodule was evaluated according to CEUS LI-RADS. The subgroup analyses were also performed in patients with alpha-fetoprotein (AFP) more than 20ug/L or not. Diagnostic performance of CEUS LI-RADS for diagnosing HCC was validated via sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV), respectively. RESULTS: There were 90 HCCs (90 of 251, 35.9%), of which 2 (2.0%), 53 (53.5%), and 35 (35.4%) were classified as LR-4, LR-5, and LR-M, respectively. The sensitivity, specificity, accuracy, PPV, and NPV of CEUS LR-5 for HCC diagnosis were 58.9%, 88.8%, 78.1%, 74.6%, and 79.4%, respectively. AFP increased in 50.6% (45/89) HCCs. Using a proposed diagnostic algorithm (for OBI patients with AFP more than 20 ug/L, LR-5 nodules were diagnosed as definitely HCC), the sensitivity, specificity, accuracy, PPV, and NPV were 62.2%, 71.4%, 63.5%, 93.3%, and 22.7%, respectively. Therefore, 12.2% (30 of 246) nodules could be confirmed as HCC by CEUS without biopsy. CONCLUSION: HCC diagnosis in patients with OBI is challenging. However, using LR-5 as a noninvasively diagnostic standard in OBI patients with AFP more than 20ug/L, HCC could be confirmed by CEUS without biopsy.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis B , Liver Neoplasms , Algorithms , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/diagnostic imaging , Contrast Media , Hepatitis B/complications , Hepatitis B/diagnostic imaging , Humans , Liver Neoplasms/complications , Liver Neoplasms/diagnostic imaging , Magnetic Resonance Imaging/methods , Retrospective Studies , Sensitivity and SpecificityABSTRACT
Chemotherapy is generally considered as the main treatment for metastatic gastric adenocarcinoma. The role of gastrectomy for metastatic gastric cancer without obvious symptoms is controversial. The objective of this study is to investigate survival outcomes of treatment modalities using a real-world data setting. A retrospective cohort study was designed using the Taiwan Cancer Registry database. We identified the treatment modalities and used Kaplan-Meier estimates and Cox regressions to compare patient survival outcomes. From 2008 to 2015, 5599 gastric adenocarcinoma patients were diagnosed with metastatic disease (M1). The median overall survival (OS) of patients with surgery plus chemotherapy had the longest survival of 14.2 months. The median OS of the patients who received chemotherapy alone or surgery alone was 7.0 and 3.9, respectively. Age at diagnosis, year of diagnosis, tumor grade, and treatment modalities are prognostic factors for survival. The hazard ratios for patients who received surgery plus chemotherapy, surgery alone, and supportive care were 0.47 (95% CI 0.44-0.51), 1.22 (95% CI 1.1-1.36), and 3.23 (95% CI 3.01-3.46), respectively, by multivariable Cox regression analysis when using chemotherapy alone as a referent. Chemotherapy plus surgery may have a survival benefit for some selected gastric adenocarcinoma patients with metastatic disease.