Crepidiastrum denticulatum Extract Ameliorates Kidney Ischemia-Reperfusion Injury in Mice.

BACKGROUND: Crepidiastrum denticulatum (CD) is a well-known, traditionally consumed vegetable in Korea, which was recently reported to contain bioactive compounds with detoxification and antioxidant properties. Ischemia-reperfusion injury (IRI) is a major problem after renal transplantation. Furthermore, inflammatory responses to IRI exacerbate the resultant renal injury. In the present study, we investigated whether CD extract exhibits renoprotective effects against IR-induced acute kidney injury in mice. MATERIALS AND METHODS: Renal IRI was induced in male C57BL/6 mice by bilateral renal pedicle occlusion for 30 minutes followed by reperfusion for 48 hours. CD extract (75 mg/kg) was administered orally 5 days before IRI. RESULTS: Treatment with CD extract significantly decreased blood urea nitrogen and serum creatinine levels as well as kidney tubular injury. CD also prevented IRI-induced renal glutathione depletion and increased malondialdehyde levels. Western blotting and reverse transcriptase polymerase chain reaction indicated that CD extract significantly attenuates inducible nitric oxide synthase and toll-like receptor 2/4 protein levels 48 h after IRI. The expression of tumor necrosis factor-α and interleukin-1ß was significantly decreased in the CD extract treatment group. CONCLUSION: CD extract improved acute renal IRI through its antioxidant and anti-inflammatory effects. These findings suggest that CD extract is a potential therapeutic agent for acute ischemia-induced renal damage.

Protective Effect of Eupatilin Pretreatment Against Hepatic Ischemia-Reperfusion Injury in Mice.

BACKGROUND: Eupatilin, a pharmacologically active flavone derived from Artemisia species, is known to have antioxidant and antiinflammatory activities. Ischemia-reperfusion injury (IRI) is a major critical event that commonly occurs after liver transplantation and resection. Furthermore, inflammatory responses to IRI exacerbate the resultant hepatic injury. In this study, we investigated whether eupatilin protects against IR-induced acute liver injury in mice. MATERIALS AND METHODS: Partial (70%) hepatic IRI was induced in male C57BL/6 mice by portal triad pedicle occlusion for 90 minutes followed by reperfusion for 6 hours. Eupatilin (10 mg/kg body weight, oral) was administered 4 days before the IRI. RESULTS: Treatment with eupatilin significantly decreased serum alanine aminotransferase and serum aspartate aminotransferase as well as liver histologic changes. Eupatilin also prevented hepatic glutathione depletion and increased malondialdehyde levels induced by IRI. Western blotting indicated that eupatilin significantly increased the levels of heat shock protein and B-cell lymphoma 2 protein, attenuated inducible nitric oxide synthase, and cleaved caspase-3 levels 6 hours after IRI. The expression of the Toll-like receptor 2/4, and phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor was significantly decreased in the eupatilin pretreatment group. CONCLUSIONS: Eupatilin improved the acute hepatic IRI by reducing inflammation and apoptosis. These findings suggest that eupatilin is a promising therapeutic agent against acute IR-induced hepatic damage.

Protective Effect of Polydeoxyribonucleotide Against Renal Ischemia-Reperfusion Injury in Mice.

BACKGROUND: Polydeoxyribonucleotide (PDRN) is an A2A receptor agonist that induces vascular endothelial growth factor (VEGF) production during the pathological condition of low tissue perfusion. Ischemia-reperfusion injury (IRI) is a major problem after renal transplantation. In the present study, we investigated whether PDRN exhibits reno-protective effects against ischemia-reperfusion-induced acute kidney injury in mice. METHODS: Renal ischemia-reperfusion injury was induced in male C57BL/6 mice by bilateral renal pedicle occlusion for 30 minutes, followed by reperfusion for 48 hours. PDRN (8 mg/kg body weight intraperitoneally) was administered 30 minutes before IRI. RESULTS: Treatment with PDRN significantly decreased neutrophil gelatinase-associated lipocalin levels in the urine, blood urea nitrogen level, and serum creatinine levels as well as kidney tubular injury. Western blotting showed that PDRN significantly increased the levels of vascular endothelial growth factor and B-cell lymphoma protein and attenuated p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, inducible nitric oxide synthase, and Bcl-2-associated X protein levels 48 hours after IRI. CONCLUSIONS: Our findings suggest that PDRN is a potential therapeutic agent for acute ischemia-induced renal damage.

Red Ginseng Administration Before Islet Isolation Attenuates Apoptosis and Improves Islet Function and Transplant Outcome in a Syngeneic Mouse Marginal Islet Mass Model.

BACKGROUND: Transplantation of isolated islets is a promising treatment for diabetes. Red ginseng (RG) is steamed ginseng and has been reported to enhance insulin secretion-stimulating and anti-apoptotic activities in pancreatic ß-cells. In this study, we examined the hypothesis that pre-operative RG treatment enhances islet cell function and anti-apoptosis and investigated whether RG improves islet engraftment by transplant of a marginal mass of syngeneic islets pretreated with RG in diabetic mice. METHODS: Balb/c mice were randomly divided into 2 groups, and 1 group was administered RG (400 mg/kg/day orally) for 7 days before islet isolation. In vitro islet viability and function were assessed. After cytokine treatment, cell viability, function, and apoptosis of islet cells were analyzed. Furthermore, we studied the effects of RG in a syngeneic islet graft model. A marginal mass of syngeneic mouse islets was transplanted into diabetic hosts. RESULTS: Islet pretreatment with RG showed 1.4-fold higher glucose-induced insulin secretion than did control islets. RG pretreatment upregulated B-cell lymphoma 2 (Bcl-2) expression and downregulated Bcl-associated X protein (BAX), caspase-3, and inducible nitric oxide synthase (iNOS) expression. Glucose-induced insulin release, NO, and apoptosis were significantly improved in RG-pretreated islets compared with cytokine-treated islets. RG-pretreated mice exhibited improved marginal mass islet graft survival compared with controls. CONCLUSIONS: These results suggest that pre-operative RG administration enhanced islet function before transplantation and attenuated cytokine-induced damage associated with apoptosis. These studies indicate that inhibition of apoptosis by RG significantly improved islet cell and graft function after isolation and transplantation, respectively.

Primary esophageal mucosa-associated lymphoid tissue lymphoma diagnosed by using stacked forceps biopsy.

Non-Hodgkin lymphoma involving the esophagus is very rare. Only a few cases have been reported in the English literature to date, and it accounts for less than 1% of all cases of gastrointestinal lymphoma. As this malignancy manifests as a submucosal tumor, pathological diagnosis by using a simple endoscopic biopsy alone is difficult. Therefore, surgical biopsy, endoscopic mucosal resection, and endoscopic ultrasound-guided fine-needle aspiration have been used in most cases. Herein, we report a case of esophageal mucosa-associated lymphoid tissue lymphoma in a 49-year-old man, which involved the use of a stacked forceps biopsy to obtain adequate samples for pathological analysis; the use of the stacked forceps biopsy method is unlike those used in previous cases. The patient received cyclophosphamide, vincristine, and prednisolone chemotherapy; he achieved a complete response. In addition, we review the literature relevant to this case.

5,7-dihydroxy-3,4,6-trimethoxyflavone attenuates ischemic damage and apoptosis in mouse islets.

BACKGROUND: The transplantation of isolated pancreatic islets is a promising treatment for diabetes. 5,7-dihydroxy-3,4,6-trimethoxyflavone (Eupatilin), a pharmacologically active flavone derived from the Artemisia plant species, has been reported to have antioxidant and anti-inflammatory activities. This study examines the hypothesis that preoperative eupatilin treatment can attenuate ischemic damage and apoptosis before islet transplantation. METHODS: Islets isolated from Balb/c mice were randomly divided into 2 groups, and cultured in medium supplemented with or without eupatilin. In vitro islet viability and function were assessed. After treatment with a cytokine cocktail consisting of tumor necrosis factor (TNF)-α, interferon (INF)-γ, and interleukin (IL)-1ß, islet cell viability, function, and apoptotic status were determined. The glutathione (GSH) and nitrous oxide (NO) levels were also measured. Proteins related to apoptosis were analyzed using Western blotting. RESULTS: There was no difference in cell viability between the 2 groups. Islets cultured in the medium supplemented with eupatilin showed 1.4-fold higher glucose-induced insulin secretion than the islets cultured in the medium without eupatilin. After treatment with a cytokine cocktail, glucose-induced insulin release and the total insulin content of the islets were significantly improved in eupatilin-pretreated islets compared with islets not treated with eupatilin. Apoptosis was significantly decreased, and GSH levels were elevated in the eupatilin-pretreated group. Cytokine-only treated islets produced significantly higher levels of NO, iNOS, and caspase-3 than islets pretreated with eupatilin before cytokine treatment. CONCLUSIONS: These results suggest that preoperative eupatilin administration enhances islet function before transplantation and attenuates the cytokine-induced damage associated with NO production and apoptosis.

Protective effect of eupatilin against renal ischemia-reperfusion injury in mice.

BACKGROUND: Eupatilin, a pharmacologically active flavone derived from Artemisia species, is known to have antioxidant and anti-inflammatory activities. Ischemia-reperfusion injury (IRI) is a major complication after renal transplantation, with inflammatory responses to IRI exacerbating the resultant renal injury. In the present study, we investigated whether eupatilin exhibits renoprotective activities against ischemia-reperfusion-induced acute kidney injury in mice. MATERIALS AND METHODS: Renal IRI was induced in male C57BL/6 mice by bilateral renal pedicle occlusion for 30 minutes followed by reperfusion for 48 hours. Eupatilin (10 mg/kg body weight p.o.) was administered 4 days before IRI. RESULTS: Treatment with eupatilin significantly decreased neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels in urine, blood urea nitrogen level, and serum creatinine levels, as well as kidney tubular injury. Western blotting indicated that eupatilin significantly increased the levels of heat shock protein 70 and B-cell lymphoma protein, and it attenuated inducible nitric oxide synthase, Bcl-2-associated X protein, and caspase-3 levels 48 hours after IRI. CONCLUSION: Our findings suggest that eupatilin is a promising therapeutic agent against acute ischemia-induced renal damage.

Ginsenoside Rg3 enhances islet cell function and attenuates apoptosis in mouse islets.

BACKGROUND: The transplantation of isolated islets is thought to be an attractive approach for curative treatment of diabetes mellitus. Panax ginseng has been used in oriental countries for its pharmacologic effects, such as antidiabetic and antiinflammatory activities. 20(S)-ginsenoside Rg3 (Rg3), an active ingredient of ginseng saponins, has been reported to enhance insulin secretion-stimulating and antiapoptotic activities in pancreatic beta cells. We performed this study to examine the hypothesis that preoperative Rg3 administration can enhance islet cell function and antiapoptosis before islet transplantation. METHODS: Balb/c mice were randomly divided into 2 groups according to the administration of Rg3 after islet isolation. Mouse islets were cultured in medium supplemented with or without Rg3. In vitro, islet viability and function were assessed. After treatment of islets with a cytokine cocktail (tumor necrosis factor α, interferon-γ, and interleukin-1ß), cell viability, function, and apoptosis were assessed. RESULTS: Cell viability was similar between the 2 groups. Islets cultured in medium supplemented with Rg3 showed 2.3-fold higher glucose-induced insulin secretion than islets cultured in medium without Rg3. After treatment with a cytokine cocktail, glucose-induced insulin release, total insulin content of islets, and apoptosis were significantly improved in Rg3-treated islets compared with cytokine-treated islets. Cytokine-treated islets produced significantly higher levels of nitric oxide (NO) than islets treated with Rg3. CONCLUSIONS: These results suggest that preoperative Rg3 administration enhanced islet function before islet transplantation and attenuated both cytokine-induced damage associated with NO production and apoptosis. Rg3 administration might be a prospective management to enhanced islet function and ameliorate early inflammation after transplantation.

The expression of p16 (INK4a) and Ki-67 in relation to high-risk human papilloma viral load and residual disease after conization with positive margins.

The purpose of this study was to investigate the correlations between high-risk human papillomavirus (HPV) load and p16 (INK4a) or Ki-67, and to identify biomarkers that may predict residual disease after conization with positive margins. The following samples were analyzed: 49 paraffin-embedded specimens from patients with cervical intraepithelial neoplasia (CIN), including 12 CIN 2 conization specimens and 37 CIN 3 conization specimens. Immunohistochemical analysis was performed with antibodies to p16 (INK4a) and Ki-67. Hybrid Capture II testing was used to detect high-risk HPV DNA. The mean HPV loads within each of the p16 (INK4a)-staining cases were 9.5 (relative light units/positive control) RLU/PC for negative staining, 531.8 RLU/PC for 1+ staining, 140.2 RLU/PC for 2+ staining, and 545.1 RLU/PC for 3+ staining. HPV loads differed significantly according to p16 (INK4a) expression (P = 0.0021). The mean HPV loads within Ki-67 staining cases were 28.2 RLU/PC for 1+ staining, 189.6 RLU/PC for 2+ staining, and 563.3 RLU/PC for 3+ staining. HPV loads differed significantly according to Ki-67 expression (P = 0.0259). The expression of p16 (INK4a) (P = 0.0012) and Ki-67 (P = 0.0006) were significantly associated with the CIN grade. In univariate and multiple logistic regression analysis, age, parity, cytology, lesion grade in the cone, high-risk HPV load, and the expression of p16 (INK4a) and Ki-67 were not significantly associated with residual lesions after conization with positive margins (P > 0.05). In conclusion, high-risk HPV load showed significant differences according to the expression of p16 (INK4a) and Ki-67, while none of the prognostic factors were significantly associated with residual disease after conization with positive margins.