The Preventive Role of Hydrogen-Rich Water in Thioacetamide-Induced Cholangiofibrosis in Rat Assessed by Automated Histological Classification.
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ABSTRACT:
SUBMITTER: Li C
PROVIDER: S-EPMC8417776 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Dehydration is one of the intrauterine abnormalities that could lead to fetal growth retardation and to increase the risk of a variety of adult diseases later in life. This study were to determine the impact of hydrogen-rich water (HRW) supplementation on placental angiotensin II type 1 receptor and placental oxidative stress induced by water restriction. Pregnant Wistar rat were randomly assigned to one of the three groups (n =12 per group). In control group, pure water and food were supplied ad libitum. Water restriction group and HRW group were respectively given pure water and HRW with free access to food, excepting only one hour was available for drinking from day 7 to day 17 of pregnancy. The placental damages and biomarkers of stress were detected by histopathology, immunohistochemistry and western blot, as well as serological test were performed. We demonstrated that maternal water restriction resulted in reduced urine volume and increased serum osmotic pressure, along with decreased fetus weight and crown-rump length. Although placental weight and the number of fetuses had no significant difference among groups, the placental efficiency significantly increased after the oral administration of HRW to the mothers. Meanwhile, the serological derivatives of reactive oxygen metabolites decreased, a significant improvement of placental microstructure with more developed junctional zone and denser labyrinth was manifested, the upregulated expression of angiotensin II type 1 receptor, nuclear facto?B, malondialdehyde, 8-hydroxydeoxyguanosine, p38, c-Jun N-terminal kinase and down-regulation of superoxide dismutase were revealed in the placenta. Collectively, HRW administration is able to effectively attenuate placental stress induced by water restriction.
| S-EPMC6178645 | biostudies-other
Project description:Various factors are considered to be mechanisms of the increase in the sizes of cysts in patients with polycystic kidney disease. Vasopressin is one of the causes, and drinking large volumes of water shows an effect of suppressing an increase in cysts. On the other hand, it is known that hydrogen-rich water reduces oxidative stress and has a good effect on kidney injury. We examined whether drinking large volumes of hydrogen-rich water affected the increase in the sizes of cysts. Forty 5-week-old PCK rats were randomly assigned to four groups: C(Control), purified water; W(Water), water with sugar; H(Hydrogen), hydrogen-rich water; WH(Water+Hydrogen), hydrogen-rich water with sugar. They consumed water from 5 to 15 weeks of age. The intake of water in the groups in which sugar was added to the water (W, WH) significantly increased in comparison to C, but there was no significant change in the serum Creatinine concentration. The kidney weight per body weight in W was significantly decreased in comparison to C. The kidney weights in H and WH were significantly increased in comparison to W. There were no significant differences in the ratio of the cross-sectional area of the cysts to the whole area among the groups. This experiment showed that the effect of drinking large volumes of hydrogen-rich water was not significantly different from that of normal water, in terms of preventing an increase in the size of cysts in PCK rats. However, some papers acknowledge the influence of hydrogen water. Significant differences might become obvious if we change aspects such as the administration method or administration period.
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Project description:An automated image analysis system, e-Pathologist, was developed to improve the quality of colorectal biopsy diagnostics in routine pathology practice.The aim of the study was to evaluate the classification accuracy of the e-Pathologist image analysis software in the setting of routine pathology practice in two institutions.In total, 1328 colorectal tissue specimens were consecutively obtained from two hospitals (1077 tissues from Tokyo hospital, and 251 tissues from East hospital) and the stained specimen slides were anonymized and digitized. At least two experienced gastrointestinal pathologists evaluated each slide for pathological diagnosis. We compared the 3-tier classification results (carcinoma or suspicion of carcinoma, adenoma, and lastly negative for a neoplastic lesion) between the human pathologists and that of e-Pathologist.For the Tokyo hospital specimens, all carcinoma tissues were correctly classified (n=112), and 9.9% (80/810) of the adenoma tissues were incorrectly classified as negative. For the East hospital specimens, 0 out of the 51 adenoma tissues were incorrectly classified as negative while 9.3% (11/118) of the carcinoma tissues were incorrectly classified as either adenoma, or negative. For the Tokyo and East hospital datasets, the undetected rate of carcinoma, undetected rate of adenoma, and over-detected proportion were 0% and 9.3%, 9.9% and 0%, and 36.1% and 27.1%, respectively.This image analysis system requires some improvements; however, it has the potential to assist pathologists in quality improvement of routine pathological practice in the not too distant future.
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Project description:Molecular hydrogen is a hopeful agent for oxidative stress-related and/or inflammatory disorders. However, the molecular mechanism for these therapeutic effects of hydrogen still remains to be fully elucidated. We examined whether molecular hydrogen alters gene expression levels in normal mouse livers by DNA microarray analysis. We identified 140 mouse genes that were upregulated (31 genes) or downregulated (109 genes) after three weeks of the inhalation of 2% hydrogen-containing air with oral intake of hydrogen-rich water. Ingenuity Pathway Analysis revealed that hydrogen influenced expression of NF-kB- and NFAT-regulated genes. Western blot analysis showed that hydrogen attenuated Erk, p38 MAPK, and NF-kB signaling in mouse livers.
2014-08-01 | GSE48826 | GEO
Project description:The hepatotoxicity of thioacetamide (TA) has been known since 1948. In rats, single doses cause centrolobular necrosis accompanied by increases in plasma transaminases and bilirubin. To elicit these effects, TA requires oxidative bioactivation, leading first to its S-oxide (TASO) and then to its chemically reactive S,S-dioxide (TASO(2)), which ultimately modifies amine-lipids and proteins. To generate a suite of liver proteins adducted by TA metabolites for proteomic analysis and to reduce the need for both animals and labeled compounds, we treated isolated hepatocytes directly with TA. Surprisingly, TA was not toxic at concentrations up to 50 mM for 40 h. On the other hand, TASO was highly toxic to isolated hepatocytes as indicated by LDH release, cellular morphology, and vital staining with Hoechst 33342/propidium iodide. TASO toxicity was partially blocked by the CYP2E1 inhibitors diallyl sulfide and 4-methylpyrazole and was strongly inhibited by TA. Significantly, we found that hepatocytes produce TA from TASO relatively efficiently by back-reduction. The covalent binding of [(14)C]-TASO is inhibited by unlabeled TA, which acts as a "cold-trap" for [(14)C]-TA and prevents its reoxidation to [(14)C]-TASO. This in turn increases the net consumption of [(14)C]-TASO despite the fact that its oxidation to TASO(2) is inhibited. The potent inhibition of TASO oxidation by TA, coupled with the back-reduction of TASO and its futile redox cycling with TA, may help explain phenomena previously interpreted as "saturation toxicokinetics" in the in vivo metabolism and toxicity of TA and TASO. The improved understanding of the metabolism and covalent binding of TA and TASO facilitates the use of hepatocytes to prepare protein adducts for target protein identification.
| S-EPMC3444651 | biostudies-literature
Project description:The effects of the administration of molecular hydrogen-saturated drinking water (hydrogen water) on hepatic gene expression were investigated in rats. Using DNA microarrays, 548 upregulated and 695 downregulated genes were detected in the liver after a 4-week administration of hydrogen water. Gene Ontology analysis revealed that genes for oxidoreduction-related proteins, including hydroxymethylglutaryl CoA reductase, were significantly enriched in the upregulated genes.
2010-12-31 | GSE26363 | GEO
Project description:Colonoscopy is an effective tool to detect colorectal lesions and needs the support of pathological diagnosis. This study aimed to develop and validate deep learning models that automatically classify digital pathology images of colon lesions obtained from colonoscopy-related specimen. Histopathological slides of colonoscopic biopsy or resection specimens were collected and grouped into six classes by disease category: adenocarcinoma, tubular adenoma (TA), traditional serrated adenoma (TSA), sessile serrated adenoma (SSA), hyperplastic polyp (HP), and non-specific lesions. Digital photographs were taken of each pathological slide to fine-tune two pre-trained convolutional neural networks, and the model performances were evaluated. A total of 1865 images were included from 703 patients, of which 10% were used as a test dataset. For six-class classification, the mean diagnostic accuracy was 97.3% (95% confidence interval [CI], 96.0-98.6%) by DenseNet-161 and 95.9% (95% CI 94.1-97.7%) by EfficientNet-B7. The per-class area under the receiver operating characteristic curve (AUC) was highest for adenocarcinoma (1.000; 95% CI 0.999-1.000) by DenseNet-161 and TSA (1.000; 95% CI 1.000-1.000) by EfficientNet-B7. The lowest per-class AUCs were still excellent: 0.991 (95% CI 0.983-0.999) for HP by DenseNet-161 and 0.995 for SSA (95% CI 0.992-0.998) by EfficientNet-B7. Deep learning models achieved excellent performances for discriminating adenocarcinoma from non-adenocarcinoma lesions with an AUC of 0.995 or 0.998. The pathognomonic area for each class was appropriately highlighted in digital images by saliency map, particularly focusing epithelial lesions. Deep learning models might be a useful tool to help the diagnosis for pathologic slides of colonoscopy-related specimens.
| S-EPMC9329279 | biostudies-literature
Project description:Molecular hydrogen is a hopeful agent for oxidative stress-related and/or inflammatory disorders. However, the molecular mechanism for these therapeutic effects of hydrogen still remains to be fully elucidated. We examined whether molecular hydrogen alters gene expression levels in normal mouse livers by DNA microarray analysis. We identified 140 mouse genes that were upregulated (31 genes) or downregulated (109 genes) after three weeks of the inhalation of 2% hydrogen-containing air with oral intake of hydrogen-rich water. Ingenuity Pathway Analysis revealed that hydrogen influenced expression of NF-kB- and NFAT-regulated genes. Western blot analysis showed that hydrogen attenuated Erk, p38 MAPK, and NF-kB signaling in mouse livers. We divided 10-week male BALB/c mice into two groups: 1) control group: fed with control water in air (n=4), 2) hydrogen-treated group: fed with hydrogen-rich water in 2% hydrogen/98% air (n=4). Hydrogen-rich water (0.7mM dissolved hydrogen) was generated from distilled water with 0.44 mM Na2SO4 using Aquela Blue, a water-electrolyzing device to produce electrolyzed hydrogen-saturated water near neutral pH (MiZ Co., Ltd, Fujisawa, Japan). The control water was prepared by gently stirring hydrogen-rich water in open air for 24 hours. Hydrogen-rich water or control water was administrated ad libitum to the mice with a 50-ml closed glass vessel equipped with an outlet line having a ball bearing. After 3-week rearing, the mice were sacrificed and their livers were removed for RNA extraction. We mixed equal amount of RNA from four mice in each group (control vs. hydrogen-treated) and compared gene expression profile by microarray.
2014-08-01 | E-GEOD-48826 | biostudies-arrayexpress
Project description:Characterization of the molecular attributes and spatial arrangements of cells and features within complex human tissues provides a critical basis for understanding processes involved in development and disease. Moreover, the ability to automate steps in the analysis and interpretation of histological images that currently require manual inspection by pathologists could revolutionize medical diagnostics. Toward this end, we developed a new imaging approach called multidimensional microscopic molecular profiling (MMMP) that can measure several independent molecular properties in situ at subcellular resolution for the same tissue specimen. MMMP involves repeated cycles of antibody or histochemical staining, imaging, and signal removal, which ultimately can generate information analogous to a multidimensional flow cytometry analysis on intact tissue sections. We performed a MMMP analysis on a tissue microarray containing a diverse set of 102 human tissues using a panel of 15 informative antibody and 5 histochemical stains plus DAPI. Large-scale unsupervised analysis of MMMP data, and visualization of the resulting classifications, identified molecular profiles that were associated with functional tissue features. We then directly annotated H&E images from this MMMP series such that canonical histological features of interest (e.g. blood vessels, epithelium, red blood cells) were individually labeled. By integrating image annotation data, we identified molecular signatures that were associated with specific histological annotations and we developed statistical models for automatically classifying these features. The classification accuracy for automated histology labeling was objectively evaluated using a cross-validation strategy, and significant accuracy (with a median per-pixel rate of 77% per feature from 15 annotated samples) for de novo feature prediction was obtained. These results suggest that high-dimensional profiling may advance the development of computer-based systems for automatically parsing relevant histological and cellular features from molecular imaging data of arbitrary human tissue samples, and can provide a framework and resource to spur the optimization of these technologies.
| S-EPMC4503351 | biostudies-literature
Project description:AIM:To investigate the efficacy and safety of mineral water with a high content of hydrogen carbonate in patients with heartburn. METHODS:This open, single-center, single-arm clinical pilot study enrolled 50 patients, 18-64 years old, who had been suffering from heartburn at least twice a week for at least 3 mo before entering the study. Pharmacological treatment of heartburn was not permitted, and patients with severe organic diseases were excluded. After a run-in period of one week, the participants received 1.5 L of the test water for the following 6 wk; 300 mL with meals t.i.d., the remainder to be drunk throughout the day. During the trial, there were five visits at the study center (screening, baseline, two interim visits and the final visit). The efficacy endpoints included incidence and duration of heartburn episodes per week by patient's self-assessment (heartburn diary) as well as changes in symptom severity as per symptom specific questionnaires [Reflux Disease Questionnaire (RDQ); Quality of Life in Reflux and Dyspepsia (QOLRAD); Gastrointestinal Quality of Life Index] and overall health-related quality of life per SF-12 (12-question short form) at each visit. At the end of the study, patients and investigators independently rated the overall efficacy of the test water on a 4-point Likert scale. Safety was assessed by evaluation of adverse events (AEs), vital signs (heart rate, blood pressure) and laboratory parameters. Changes from initial to final examinations were assessed by the non-parametric Wilcoxon test; categorical variables were compared using the ?(2) test, and for more than 5 categories, by the U-test. RESULTS:Twenty-eight participants were men, 22 women. The mean age of the patients in the full analysis set/intention-to treat population (FAS/ITT) was 40.6 years. Forty-two participants completed the study according to the study protocol and formed the per-protocol set (PP population); 48 participants drank the water at least once as requested and were analyzed as ITT population. The occurrence of heartburn was statistically significantly reduced at wk 6 in both the ITT and the PP populations. At wk 6, the mean number of heartburn episodes/week decreased by 5.1 episodes (P < 0.001) and the mean duration of heartburn symptoms by 19 min (ITT) (P = 0.002). The frequency of heartburn symptoms was reduced in 89.6% of the patients (P < 0.001), and the duration of symptoms in 79.2% of patients (ITT) (P < 0.001). All dimensions of the RDQ (heartburn, regurgitation, gastro-esophageal reflux disease symptoms, dyspepsia) showed a significant improvement at 6 wk. Likewise, disease-specific quality of life improved significantly (QOLRAD, GIQLI). Overall, 89.4% of patients rated the efficacy of the test water as "good" or "very good", as did the investigators for 91.5% of the patients. There were no serious AEs. After 6 wk, systolic and diastolic blood pressure values decreased slightly but significantly [-3.5 and -3.0 mmHg, respectively (P = 0.008 and P = 0,002)]. Ninety-six percent of patients and investigators for the same percentage of patients rated the tolerability of the water as "good" or "very good". CONCLUSION:The data demonstrate effectiveness of a hydrogen carbonate-rich mineral water in alleviating heartburn frequency and severity, thereby improving quality of life. The water has excellent tolerability.
| S-EPMC4753184 | biostudies-literature