Prophylactic Administration of Perampanel for Post-Stroke Epilepsy (PROPELLER Study): A Trial Protocol.

Background: Post-stroke epilepsy can reduce patients' abilities to carry out various activities of daily living. Despite their importance in preventing the onset of post-stroke epilepsy, the prophylactic administration of antiepileptic drugs is controversial due to a lack of high-level clinical research. In this study, we initiated a prospective interventional study of prophylactic antiepileptic drug administration in patients with a subcortical hemorrhage, who are at the highest risk of developing epilepsy after experiencing a stroke.

Laparoscopic Gastrectomy Using External Oblique Intercostal Block Versus Wound Infiltration: A Trial Protocol.

Objective: A novel external oblique intercostal block (EOIB) might have analgesic effects on T6-10 and be indicated for laparoscopic gastrectomy. However, EOIB effects on postoperative pain are unknown. We aim to generate evidence to support such EOIB application.

The clinical trial of alternative relugolix administration for uterine leiomyoma prior to surgically treatment: a study protocol for Non-Adverse Relugolix Administration (NARA) trial.

Background: Uterine leiomyomas are common for reproductive-aged women and affect women's quality of life due to heavy menstrual bleeding or dysmenorrhea. Leiomyomas grow according to estradiol exposure and decrease after post-menopause. In case serious symptoms are caused by leiomyomas, pharmacotherapy or surgical treatment is proposed.

Benefit of glucosyl Hesperidin in patients with primary biliary cholangitis: A multicenter, open-label, randomized control study.

Introduction: Globally, the number of patients with primary biliary cholangitis (PBC) is increasing. Growing evidence suggests that oxidative stress plays a significant role in the pathogenesis of chronic liver disease regardless of its etiology. Hesperidin, a natural antioxidative substance derived from citrus peel, has been shown to have an anti-inflammatory effect in a rat arthritis model and may be a potential substance to attenuate intrahepatic inflammation in patients with PBC.

Effect of combined farnesoid X receptor agonist and angiotensin II type 1 receptor blocker on ongoing hepatic fibrosis.

Objective: Nonalcoholic steatohepatitis (NASH) is difficult to diagnose in patients with no symptoms. We aimed to investigate the combined effect of farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), and angiotensin II type 1 receptor blocker (ARB: losartan) on an ongoing hepatic fibrosis in a NASH rat model.

Methods: Fischer 344 rats were fed with choline-deficient L-amino-acid-defined (CDAA) diet for 16 weeks.

Novel oral plasminogen activator inhibitor‑1 inhibitor TM5275 attenuates hepatic fibrosis under metabolic syndrome via suppression of activated hepatic stellate cells in rats.

An orally bioavailable small molecule inhibitor of plasminogen activator inhibitor‑1 (PAI‑1) is currently being clinically assessed as a novel antithrombotic agent. Although PAI‑1 is known to serve a key role in the pathogenesis of metabolic syndrome (MetS) including nonalcoholic steatohepatitis (NASH), the pharmacological action of an oral PAI‑1 inhibitor against the development of MetS‑related liver fibrosis remains unclear. The current study was designed to explicate the effect of TM5275, an oral PAI‑1 inhibitor, on MetS‑related hepatic fibrogenesis.

Hydralazine Sensitizes to the Antifibrotic Effect of 5-Aza-2'-deoxycytidine in Hepatic Stellate Cells.

Background: Hepatic stellate cell (HSC) activation is essential for the development of liver fibrosis. Epigenetic machinery, such as DNA methylation, is largely involved in the regulation of gene expression during HSC activation. Although the pharmacological DNA demethylation of HSC using 5-aza-2'-deoxycytidine (5-aza-dC) yielded an antifibrotic effect, this drug has been reported to induce excessive cytotoxicity at a high dose.

Combined effect of a farnesoid X receptor agonist and dipeptidyl peptidase-4 inhibitor on hepatic fibrosis.

Aim: Non-alcoholic steatohepatitis (NASH) has a broad clinicopathological spectrum (inflammation to severe fibrosis). The farnesoid X receptor agonist obeticholic acid (OCA) ameliorates the histological features of NASH; satisfactory antifibrotic effects have not yet been reported. Here, we investigated the combined effects of OCA + a dipeptidyl peptidase-4 inhibitor (sitagliptin) on hepatic fibrogenesis in a rat model of NASH.

Oral administration of fructose exacerbates liver fibrosis and hepatocarcinogenesis via increased intestinal permeability in a rat steatohepatitis model.

Recent reports have revealed the impact of a western diet containing large amounts of fructose on the pathogenesis of non-alcoholic steatohepatitis (NASH). Fructose exacerbates hepatic inflammation in NASH by inducing increasing intestinal permeability. However, it is not clear whether fructose contributes to the progression of liver fibrosis and hepatocarcinogenesis in NASH.

Effect of combined farnesoid X receptor agonist and angiotensin II type 1 receptor blocker on hepatic fibrosis.

The farnesoid X receptor (FXR) agonist, a bile acid-activated nuclear receptor, has been shown to improve the histologic features of nonalcoholic steatohepatitis (NASH); however, a satisfactory effect on hepatic fibrosis has not been achieved. We aimed to investigate the combined effect of FXR agonist and angiotensin II type 1 receptor blocker on hepatic fibrogenesis in rat models of NASH. For 8 weeks, two rat models of NASH were developed.

Combined treatment with dipeptidyl peptidase-4 inhibitor (sitagliptin) and angiotensin-II type 1 receptor blocker (losartan) suppresses progression in a non-diabetic rat model of steatohepatitis.

Aim: Dipeptidyl peptidase-4 (DPP4) inhibitors (DPP4-I) are oral glucose-lowering drugs for type 2 diabetes mellitus. Previously, we reported that DPP4-I (sitagliptin) exerted suppressive effects on experimental liver fibrosis in rats. Blockade of the renin-angiotensin system by angiotensin-II type 1 receptor blocker (losartan), commonly used in the management of hypertension, has been shown to significantly alleviate hepatic fibrogenesis and carcinogenesis.

DNA methylation of angiotensin II receptor gene in nonalcoholic steatohepatitis-related liver fibrosis.

Aim: To clarify whether methylation is involved in the development of nonalcoholic steatohepatitis (NASH)-related liver fibrosis in adult rats.

Methods: A choline-deficient amino acid (CDAA) diet model was employed for methylation analysis of NASH-related liver fibrosis. methylation levels were measured in the livers of CDAA- and control choline-sufficient amino acid (CSAA)-fed rats for 8 and 12 wk using quantitative methylation-specific PCR.

Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, ameliorates the development of liver fibrosis in diabetic Otsuka Long-Evans Tokushima fatty rats.

Background: It is widely understood that insulin resistance (IR) critically correlates with the development of liver fibrosis in several types of chronic liver injuries. Several experiments have proved that anti-IR treatment can alleviate liver fibrosis. Sodium-glucose cotransporter 2 (SGLT2) inhibitors comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules, improving IR.

Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan.

Background: A previous multicenter prospective randomized study from Japan showed that Helicobacter pylori eradication reduced the development of metachronous gastric cancer (MGC) after endoscopic resection for early gastric cancer. MGC risk, however, is not eliminated; yet few studies have evaluated its long-term incidence and risk factors. In this study, we investigated the incidence of and risk factors for MGC in patients who underwent endoscopic resection for early gastric cancer with successful H.

Association of gastric cancer risk factors with DNA methylation levels in gastric mucosa of healthy Japanese: a cross-sectional study.

Helicobacter pylori infection induces aberrant DNA methylation, and methylation levels of several specific marker genes in gastric mucosa are associated with gastric cancer risk. However, it is unclear whether gastric cancer risk factors are associated with methylation levels of marker genes in healthy individuals. We conducted a cross-sectional study of 281 Japanese cancer screenees aged 40-69 years with no history of H.

Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study.

Background: Epigenetic alterations accumulate in normal-appearing tissues of patients with cancer, producing an epigenetic field defect. Cross-sectional studies show that the degree of the defect may be associated with risk in some types of cancer, especially cancers associated with chronic inflammation.

Objective: To demonstrate, by a multicentre prospective cohort study, that the risk of metachronous gastric cancer after endoscopic resection (ER) can be predicted by assessment of the epigenetic field defect using methylation levels.

Hereditary diffuse gastric cancer in a Japanese family with a large deletion involving CDH1.

Hereditary diffuse gastric cancer (HDGC), characterized by susceptibility to gastric signet ring cell carcinomas (SRCCs) and caused by CDH1 germline mutations, is rare in the Japanese. We present here a Japanese family with HDGC identified by comparative genomic hybridization (CGH) analysis. A 55-year-old woman was treated with completion gastrectomy for multiple SRCCs, and pathological examination revealed approximately 200 foci of SRCC with loss of E-cadherin expression.

Clinical application of the CpG island methylator phenotype to prognostic diagnosis in neuroblastomas.

Clinical applications of aberrant DNA methylation to cancer diagnostics and therapeutics are accelerating. Especially, the CpG island methylator phenotype (CIMP), simultaneous methylation of multiple genes, provides information that cannot be obtained by other diagnostic methods and therapeutic opportunities. CIMP is known to be associated with poor or good prognosis depending upon cancer types.

EGFR L2 domain mutation is not correlated with resistance to cetuximab in metastatic colorectal cancer patients.

Background: The KRAS mutation has been associated with resistance to cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in metastatic colorectal cancer (mCRC). However, the predictive biomarkers of cetuximab resistance in KRAS wild-type mCRC remain unknown except BRAF, NRAS, and PIK3CA exon 20. The objective of the study is to study the impact of EGFR L2 mutations on resistance to cetuximab in KRAS wild-type patients.

Stronger prognostic power of the CpG island methylator phenotype than methylation of individual genes in neuroblastomas.

Objective: The CpG island methylator phenotype is strongly associated with poor survival in neuroblastomas. Neuroblastomas with the CpG island methylator phenotype include almost all neuroblastomas with MYCN amplification, and, even among neuroblastomas without MYCN amplification, have worse prognosis. At the same time, methylation of individual tumor-suppressor genes is also reported to be associated with poor survival.