Ethanol Extract of Orostachys japonicus A. Berger (Crassulaceae) Protects Against Type 2 Diabetes by Reducing Insulin Resistance and Hepatic Inflammation in Mice.

Type 2 diabetes (T2D) is a threaten human health problem, and accompanied by hyperglycemia and disorder of insulin secretion, is a major cause of abnormalities in maintaining blood glucose homeostasis. Also, low-grade inflammation, as well as insulin resistance (IR), is a common feature in patients with T2D. Numerous causes of the outbreak of T2D have been suggested by researchers, who indicate that genetic background and epigenetic predisposition, such as overnutrition and deficient physical activity, hasten the promotion of T2D milieu. Orostachys japonicus A. Berger (O. japonicus) is a herbal and remedial plant whose various activities include hemostatic, antidotal, febrile, and anti-inflammatory. Hence, we designed to evaluate the antidiabetic efficacy of ethanol extracts of O. japonicus (OJE). Six-week-old C57BL/Ksj-db/db (db/db) mice were used. The results showed that mice given various concentrations of OJE (0, 50, 100, and 200 mg/kg per day) for 8 weeks showed significantly reduced hyperglycemia, IR, and liver injury, confirmed by measuring diabetic parameters, serum, and hepatic biochemicals. Furthermore, the treatment of OJE markedly decreased the mRNA levels of proinflammatory cytokines, lipid accumulation, and gluconeogenesis-related genes. Consistently, western blot analysis indicated that mice treated with OJE showed increased levels of phospho-c-Jun N-terminal kinase, phospho-Akt, glucose transporters 2 and 4 (GLUT2 and GLUT4) in T2D mice. Likewise, much the same results were obtained in in vitro experiments. Taken together, OJE had hopeful advantage in sustaining the glucose homeostasis and diminishing IR, and could be a safe alternative remedy for treating T2D.

Orostachys japonicus ameliorates acetaminophen-induced acute liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonicus A. Berger (O. japonicus), referred to as Wa-song in Korea is a traditional and herbal medicine. Even though it has been traditionally used to treat inflammation- and toxicity-related diseases, the effects of ethanol extract of O. japonicus (OJE) on acetaminophen (N-acetyl-p-aminophenol, APAP) overdose-induced hepatotoxicity have not been determined yet. AIM OF THE STUDY: The present study was aimed to investigate the effects of OJE against APAP-induced acute liver injury (ALI) and explore the underlying mechanisms. MATERIALS AND METHODS: Mice were treated orally with OJE (50, 100, or 200 mg/kg) for seven days before APAP (300 mg/kg) injection. After 12 h of APAP treatment, serum and liver tissues were collected. An in vitro system using primary hepatocytes was also applied in this study. RESULTS: Pretreatment with OJE, especially at a dose of 200 mg/kg, reduced APAP overdose-induced ALI in mice, as evidenced by decreased serum alanine/aspartate aminotransferase levels, histopathological damage, and inflammation. Consistently, OJE pretreatment reduced the gene transcription of cytochrome P450 (CYP) 3A11 and CYP1A2 in livers of mice injected with or without APAP, at least in part, via inactivation of nuclear receptor pregnane X receptor (PXR). Furthermore, the role of PXR in mediating the OJE regulation of CYPs was confirmed in primary hepatocytes, which showed that OJE pretreatment inhibited PXR activity and APAP hepatotoxicity enhanced by pregnenolone 16α-carbonitrile, a mouse agonist of PXR. Besides, the antioxidative activity provided by OJE, involving increases in hepatic glutathione (GSH) content and decreases in malondialdehyde levels, has been shown to exert hepatoprotective effects in normal and injured livers. Moreover, APAP-activated c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in mice liver were indirectly inhibited by pretreatment with OJE. CONCLUSIONS: Taken together, our findings showed that OJE attenuated APAP-induced ALI by decreasing APAP-metabolizing enzymes via inactivation of PXR and the restoration of hepatic GSH content. Therefore, OJE could be a promising hepatoprotective agent.

A 12-week, randomized, double-blind study to evaluate the efficacy and safety of liver function after using fermented ginseng powder (GBCK25).

BACKGROUND: Recently, clinical research has suggested that red ginseng components play a role in liver protection and combating fatigue. However, fermented ginseng has not been analyzed for liver-protective or anti-fatigue effects. OBJECTIVE: This study evaluates the positive effects of fermented ginseng powder (GBCK25) on liver function. METHODS: Ninety participants with elevated alanine aminotransferase levels (35 ≤ ALT ≤1 05 IU/L) were randomized to one of three groups. The participants were treated with GBCK25 tablets at a dose of 500 mg/day (high dose), 125 mg/day (low dose), or placebo group daily for 12 weeks. The primary outcomes included changes in ALT and gamma-glutamyl transferase (GGT) levels. The secondary outcomes included changes in aspartate amino-transferase (AST), high-sensitivity C-reactive protein (hs-CRP), multidimensional fatigue scale, lipid profile, and antioxidant markers. RESULTS: In male subjects, after 12 weeks of low-dose GBCK25 (125 mg) supplementation, the GGT (P = 0.036) and hs-CRP (P = 0.021) levels decreased significantly more than those in the placebo group. High-dose GBCK25 (500 mg) supplementation significantly decreased the fatigue score compared with the placebo group. There were no clinically significant differences between the groups when studying any safety parameter. CONCLUSION: Our results suggest that GBCK25 supplementation has beneficial effects on liver function. TRIAL REGISTRATION: This study was registered at Clinical Trials.gov (NCT03260543).

Orostachys japonicus A. Berger (Crassulaceae) Exerts Antidiabetic Activity by Improving Glucose and Lipid Levels in Type 2 Diabetic Mice.

Orostachys japonicus A. Berger and Momordica charantia Linn have been widely used as an alternative medicine. Recently, patients with type 2 diabetes (T2D) have paid increasing attention to medical nutrition therapy due to its safety and cost-effectiveness. Therefore, we have developed a new health functional food that consists of a mixed extract of O. japonicus and M. charantia. The aim of this study is designed to assess the antidiabetic efficacy of O. japonicus and M. charantia extracts (OME, in an 8:2 ratio), especially focusing on the effects of O. japonicus via in vivo and in vitro experiments. Seven-week-old C57BL/Ksj-db/db (db/db; a genetic animal model of T2D) mice were used for inducing diabetes. Mice were administered with various concentrations of OME (OME 0, 100, 200, or 400 mg/kg/day) for 6 weeks. Metabolic parameters, fasting blood glucose and glycosylated hemoglobin levels were measured. Histopathologic analysis and the levels of serum or hepatic biochemicals were assessed to evaluate diabetic liver injury and steatosis. The expression levels of lipogenic and gluconeogenic genes were determined by quantitative real-time polymerase chain reaction. Activation of Akt was assessed by western blot analysis. Administration of OME significantly improved metabolic parameters in db/db mice, and also reduced diabetic liver injury and steatosis were observed by OME administration in db/db mice as confirmed by histopathologic and serum or hepatic biochemical analysis. Consistently, treatment of OME significantly increased Akt activation resulting in decreased expression levels of lipid-accumulation or gluconeogenesis-related genes. Similar results were observed in in vitro experiments using single extract of O. japonicus and using OME. OME has antidiabetic effects with increased insulin sensitivity, and may be a safe alternative therapy for the management of T2D.

Fermented ginseng, GBCK25, ameliorates steatosis and inflammation in nonalcoholic steatohepatitis model.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is one of the chronic inflammatory liver diseases and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The main purpose of this study was to clarify the effects of GBCK25 fermented by Saccharomyces servazzii GB-07 and pectinase, on NASH severity in mice. METHODS: Six-wk-old male mice were fed either a normal diet (ND) or a Western diet (WD) for 12 wks to induce NASH. Each group was orally administered with vehicle or GBCK25 once daily at a dose of 10 mg/kg, 20 mg/kg, 100 mg/kg, 200 mg/kg, or 400 mg/kg during that time. The effects of GBCK25 on cellular damage and inflammation were determined by in vitro experiments. RESULTS: Histopathologic analysis and hepatic/serum biochemical levels revealed that WD-fed mice showed severe steatosis and liver injury compared to ND-fed mice. Such lesions were significantly decreased in the livers of WD-fed mice with GBCK25 administration. Consistently, mRNA expression levels of NASH-related inflammatory-, fibrogenic-, and lipid metabolism-related genes were decreased in the livers of WD-fed mice administered with GBCK25 compared to WD-fed mice. Western blot analysis revealed decreased protein levels of cytochrome P450 2E1 (CYP2E1) with concomitantly reduced activation of c-Jun N-terminal kinase (JNK) in the livers of WD-fed mice administered with GBCK25. Also, decreased cellular damage and inflammation were observed in alpha mouse liver 12 (AML12) cells and RAW264.7 cells, respectively. CONCLUSION: Administration of GBCK25 ameliorates NASH severity through the modulation of CYP2E1 and its associated JNK-mediated cellular damage. GBCK25 could be a potentially effective prophylactic strategy to prevent metabolic diseases including NASH.

GBCK25, fermented ginseng, attenuates cardiac dysfunction in high fat diet-induced obese mice.

The fermentation of medicinal herbs facilitated by microbes is assumed to exert promising therapeutic efficacy on the absorption, bioavailability, and pharmacological effects by speeding up the making or conversion of active constituents into their metabolites. We examined the cardioprotective potential of fermented ginseng, GBCK25, against high-fat diet (HFD)-induced metabolic and functional illnesses as following the essential analysis such as electrocardiographic parameters, alterations of body and organ weights, and echocardiographic studies. The results exhibited that body weights were significantly reduced and the gain of different organ weights were partly eased by GBCK25 treatment. Echocardiography results proposed the amelioration of heart function through normalized levels of left ventricle systolic pressure, ejection fraction, and fractional shortening. These outcomes deliver straight confirmation that GBCK25 could be a potential nutraceutical source for the relief of HFD-induced obesity mediated cardiac dysfunctions.

Tumescent local anesthetic technique for inguinal hernia repairs.

PURPOSE: We evaluated the adequacy and feasibility of a tumescent solution containing lidocaine and bupivacaine for inguinal hernia repairs. METHODS: The medical records of 146 consecutive inguinal hernia patients with 157 hernia repairs using the tumescent local anesthesia technique performed by a single surgeon between September 2009 and December 2013 were retrospectively reviewed. RESULTS: The mean operation time (±standard deviation) and hospital stay were 64.5 ± 17.6 minutes and 2.7 ± 1.5 days. The postoperative complication rate was 17.8%. There were four cases of recurrences (2.5%) at a mean follow-up of 24 ± 14 months. CONCLUSION: Our results suggest that local anesthesia with the tumescent technique is an effective and safe modality for inguinal hernia repairs.

Severe acute pancreatitis due to tamoxifen-induced hypertriglyceridemia with diabetes mellitus.

The side effects of tamoxifen are generally mild, including the effect on lipoprotein metabolism. However, there are few cases of severe tamoxifen induced hypertriglyceridemia. Hypertriglyceridemia is a marked risk factor for acute pancreatitis and approximately 2% to 5% of cases of acute pancreatitis are related to drugs. We report on tamoxifen-induced hypertriglyceridemia and acute pancreatitis in a 40 years old woman with type 2 diabetes mellitus occurred by dexamethasone. She was treated with insulin infusion and fenofibrate, and goserelin acetate was started instead of tamoxifen after discharge from the hospital. Also, probable pathogenic hypotheses about the correlation between tamoxifen and dexamethasone induced type 2 diabetes mellitus on severe acute pancreatitis are provided. Clinicians should take care of risks of severe acute pancreatitis on using tamoxifen, especially for patients with dexamethasone induced diabetes mellitus. These individuals should undergo pre-post tamoxifen lipid screening and careful history taking of drugs, including dexamethasone.

Circulating cell-free DNA as a promising biomarker in patients with gastric cancer: diagnostic validity and significant reduction of cfDNA after surgical resection.

PURPOSE: The aim of this study is to determine whether levels of circulating free DNA (cfDNA) increase according to cancer progression, whether they are restored after surgical resection, and to evaluate cfDNA in gastric cancer patients as a useful biomarker. METHODS: A case-control study design was used. Thirty gastric cancer patients and 34 healthy subjects were enrolled from two hospitals in South Korea. The plasma cfDNA of patients with gastric cancer were obtained before surgery and 24 hours after surgery, and then analyzed by a quantitative, real-time polymerase chain reaction. Plasma samples were also obtained from the control group. RESULTS: The mean levels of cfDNA in the healthy control group, patients with early gastric cancer, and with advanced gastric cancer were 79.78 ± 8.12 ng/mL, 106.88 ± 12.40 ng/mL, and 120.23 ± 10.08 ng/mL, respectively (P < 0.01). Sensitivity was 96.67% and specificity was 94.11% when the cutoff value was 90 ng/mL. Variables representing the tumor burden such as tumor size, T stage, TNM stage, and curative resection are also associated with the levels of cfDNA. The levels of cfDNA in the 24-hour-after-surgery group decreased significantly (112.17 ± 13.42 ng/mL vs. 77.93 ± 5.94 ng/mL, P < 0.001) compared to the levels of cfDNA in the preoperation group. CONCLUSION: The changes in the levels of cfDNA can act as reliable biomarkers to detect cancer early, to predict tumor burden, estimate curative resection and even prognosis.

A Peterson's hernia and subsequent small bowel volvulus: surgical reconstruction utilizing transverse colon as a new Roux-en-Y limb - 1 case.

Peterson's hernia is an internal hernia that can occur after Roux-en-Y anastomosis. It often accompanies small bowel volvulus and is prone to strangulation. Reconstruction of intestinal continuity after massive small bowel resection in a patient who undergoes near total gastrectomy and Roux-en-Y anastomosis can be difficult. A 74-year-old man who had undergone a near total gastrectomy and Roux-en-Y gastrojejunostomy for stomach cancer presented with abdominal pain. The preoperative computed tomography showed strangulated small bowel volvulus. During the emergent laparotomy, we found a strangulated Peterson's hernia with small bowel volvulus. After resection of the necrotized intestine, we made a new Roux-en-Y anastomosis connecting the remnant stomach and the jejunum with a transverse colon segment. We were safely able to connect the remnant stomach and the jejunum by making a new Roux-en-Y anastomosis utilizing a transverse colon segment as a new Roux-limb by two stage operation.

Localized pseudomembranous colitis in the cecum and ascending colon mimicking acute appendicitis.

A 61-year-old male was admitted to our hospital due to right lower abdominal pain and watery diarrhea for 3 d. Beginning 3 wk before he arrived in our hospital, he took 3(rd)-generation cephalosporin (cefixime) for 2 wk due to chronic left ear otitis media. Colonoscopic examination revealed yellowish patches of ulcerations and swelling covered with thick serosanguineous exudate in the cecum and ascending colon. After 7 d of oral metronidazole treatment, his symptoms completely disappeared. We report a case of localized pseudomembranous colitis in the cecum and ascending colon mimicking acute appendicitis associated with cefixime.

Differences in the Survival of Gastric Cancer Patients after Gastrectomy according to the Medical Insurance Status.

PURPOSE: In Korea, the entire population must enroll in the national health insurance system, and those who are classified as having a lower socioeconomic status are supported by the medical aid system. The aim of this study was to evaluate the association of the medical insurance status of gastric cancer patients with their survival after gastrectomy. MATERIALS AND METHODS: A total of 247 patients who underwent surgical treatment for gastric cancer between January 1999 and December 2010 at the Seoul Medical Center were evaluated. Based on their medical insurance status, the patients were classified into two groups: the national health insurance registered group (n=183), and the medical aid covered group (n=64). The survival rates were calculated using the Kaplan-Meier method. RESULTS: The median postoperative duration of hospitalization was longer in the medical aid covered group and postoperative morbidity and mortality were higher in the medical aid group than in the national health insurance registered group (P<0.05). The overall 5-year survival rate was 43.9% in the medical aid covered group and 64.3% in the national health insurance registered group (P=0.001). CONCLUSIONS: The medical insurance status reflects the socioeconomic status of a patient and can influence the overall survival of gastric cancer patients. A more sophisticated analysis of the difference in the survival time between gastric cancer patients based on their socioeconomic status is necessary.

Urachal cyst presenting with huge abscess formation in adults.

Urachal disease, a disorder where embryonic remnant of the cloaca and the allantois present after birth as a midline fibrous cord, is usually detected in infancy and childhood. But urachal disease in adults is rare. We report a case of a huge abscess derived from a urachal cyst in an adult. A 52-year-old man presented with peri-umbilical distension and abdominal pain for 2 weeks. Ultrasonography and abdominal computed tomography scan demonstrated a huge abscess derived from the abdominal wall. After prompt incision and drainage, the remaining abscess cavity was removed completely under general anesthesia. Pathologic report was consistent with urachal duct cyst, and the patient was discharged in a week without complication.

Clinical Correlation between Gastric Cancer Type and Serum Selenium and Zinc Levels.

PURPOSE: We conducted this study to study the clinical correlation between the characteristics of gastric cancer and serum selenium and zinc levels. MATERIALS AND METHODS: The following data were measured in the baseline serum selenium and zinc levels of 74 patients with curative gastrectomy subsequent to confirmed gastric cancer, from March 2005 to August 2012. RESULTS: Among the 74 gastric cancer patients, 53 patients were male. Mean serum selenium and zinc levels were 118.7±33.1 ug/L and 72.2±24.3 ug/dl, respectively. Seven patients (9.5%) showed lower selenium level, and 33 patients (44.6%) showed lower zinc level. Serum Selenium level was 99.1±31.8 ug/L in cardia cancer group (10 cases) and 121.8±32.4 ug/L in non-cardia cancer group (64 cases)(P=0.044). According to tumor gross type, zinc level was 78.7±29.6 ug/dl in early gastric cancer (33) and 66.9±17.8 ug/dl in advanced gastric cancer (41) (P=0.064). CONCLUSIONS: The serum selenium level was highly correlated with the location of gastric cancer. The serum zinc level was lower in advanced gastric cancer.