Pectinase-treated Panax ginseng ameliorates hydrogen peroxide-induced oxidative stress in GC-2 sperm cells and modulates testicular gene expression in aged rats

AbstractBackgroundTo investigate the effect of pectinase-treated Panax ginseng (GINST) in cellular and male subfertility animal models.MethodsHydrogen peroxide (H2O2)-induced mouse spermatocyte GC-2spd cells were used as an in vitro model. Cell viability was measured using MTT assay. For the in vivo study, GINST (200 mg/kg) mixed with a regular pellet diet was administered orally for 4 mo, and the changes in the mRNA and protein expression level of antioxidative and spermatogenic genes in young and aged control rats were compared using real-time reverse transcription polymerase chain reaction and western blotting.ResultsGINST treatment (50 μg/mL, 100 μg/mL, and 200 μg/mL) significantly (p < 0.05) inhibited the H2O2-induced (200 μM) cytotoxicity in GC-2spd cells. Furthermore, GINST (50 μg/mL and 100 μg/mL) significantly (p < 0.05) ameliorated the H2O2-induced decrease in the expression level of antioxidant enzymes (peroxiredoxin 3 and 4, glutathione S-transferase m5, and glutathione peroxidase 4), spermatogenesis-related protein such as inhibin-α, and specific sex hormone receptors (androgen receptor, luteinizing hormone receptor, and follicle-stimulating hormone receptor) in GC-2spd cells. Similarly, the altered expression level of the above mentioned genes and of spermatogenesis-related nectin-2 and cAMP response element-binding protein in aged rat testes was ameliorated with GINST (200 mg/kg) treatment. Taken together, GINST attenuated H2O2-induced oxidative stress in GC-2 cells and modulated the expression of antioxidant-related genes and of spermatogenic-related proteins and sex hormone receptors in aged rats.ConclusionGINST may be a potential natural agent for the protection against or treatment of oxidative stress-induced male subfertility and aging-induced male subfertility

High resolution crystal structure of PedB: a structural basis for the classification of pediocin-like immunity proteins

<p>Abstract</p> <p>Background</p> <p>Pediocin-like bacteriocins, ribosomally-synthesized antimicrobial peptides, are generally coexpressed with cognate immunity proteins in order to protect the bacteriocin-producer from its own bacteriocin. As a step for understanding the mode of action of immunity proteins, we determined the crystal structure of PedB, a pediocin-like immunity protein conferring immunity to pediocin PP-1.</p> <p>Results</p> <p>The 1.6 Å crystal structure of PedB reveals that PedB consists of an antiparallel four-helix bundle with a flexible C-terminal end. PedB shows structural similarity to an immunity protein against enterocin A (EntA-im) but some disparity to an immunity protein against carnobacteriocin B2 (ImB2) in both the C-terminal conformation and the local structure constructed by α3, α4, and their connecting loop. Structure-inspired mutational studies reveal that deletion of the last seven residues of the C-terminus of PedB almost abolished its immunity activity.</p> <p>Conclusion</p> <p>The fact that PedB, EntA-im, and ImB2 share a four-helix bundle structure strongly suggests the structural conservation of this motif in the pediocin-like immunity proteins. The significant difference in the core structure and the C-terminal conformation provides a structural basis for the classification of pediocin-like immunity proteins. Our mutational study using C-terminal-shortened PedBs and the investigation of primary sequence of the C-terminal region, propose that several polar or charged residues in the extreme C-terminus of PedB which is crucial for the immunity are involved in the specific recognition of pediocin PP-1.</p

Psoas Abscess Caused by Spontaneous Rupture of Colon Cancer

Spontaneous rupture of colon cancer, combined with psoas abscess formation, is rare. A 44-year-old male visited for back pain and left buttock mass. Abdominal computed tomography and magnetic resonance image revealed a large abscess in the left psoas muscle and in the left lower quadrant area. Ten days after incision and drainage, a skin defect around the left anterior superior iliac spine remained. A local flap was performed using a superficial skin graft. Ten days after the stitches had been removed, fecal discharge was observed around the anterior superior iliac spine at the flap site. An operation was performed by a general surgeon who had diagnosed this as a case of enterocutaneous fistula. Operative findings included a ruptured tumor mass in the descending colon, which was connected to a retroperitoneal abscess. Pathologic report findings determined adenocarcinoma of the resected colon. Herein, we report a case of psoas abscess resulting from perforating colon cancer

In vitro and in vivo Inhibitory Activity of NADPH Against the AmpC BER Class C β-Lactamase

β-Lactamase-mediated resistance to β-lactam antibiotics has been significantly threatening the efficacy of these clinically important antibacterial drugs. Although some β-lactamase inhibitors are prescribed in combination with β-lactam antibiotics to overcome this resistance, the emergence of enzymes resistant to current inhibitors necessitates the development of novel β-lactamase inhibitors. In this study, we evaluated the inhibitory effect of dinucleotides on an extended-spectrum class C β-lactamase, AmpC BER. Of the dinucleotides tested, NADPH, a cellular metabolite, decreased the nitrocefin-hydrolyzing activity of the enzyme with a Ki value of 103 μM in a non-covalent competitive manner. In addition, the dissociation constant (KD) between AmpC BER and NADPH was measured to be 40 μM. According to our in vitro susceptibility study based on growth curves, NADPH restored the antibacterial activity of ceftazidime against a ceftazidime-resistant Escherichia coli BER strain producing AmpC BER. Remarkably, a single dose of combinatory treatment with NADPH and ceftazidime conferred marked therapeutic efficacy (100% survival rate) in a mouse model infected by the E. coli BER strain although NADPH or ceftazidime alone failed to prevent the lethal bacterial infection. These results may offer the potential of the dinucleotide scaffold for the development of novel β-lactamase inhibitors

Transient receptor potential channel TRPV4 mediates TGF-β1-induced differentiation of human ventricular fibroblasts

Background: Cardiac fibroblasts (CFs) are principal extracellular matrix-producing cells. In response to injury, CFs transdifferentiate into myofibroblasts. Intracellular calcium (Ca2+) signaling, involved in fibroblast proliferation and differentiation, is activated in fibroblasts through transient receptor potential (TRP) channels, but the function of these channels has not been investigated in human ventricular CFs. Under evaluation in this study, was the role of TRP channels in the differentiation of human ventricular CFs induced by transforming the growth factor beta (TGF-β), a pro-fibrotic cytokine. Methods: Human ventricular CFs were used in this study. The differentiation of CFs into myofibroblast was induced with TGF-β and was identified by the expression of smooth muscle actin. Results: Results indicate that Ca2+ signaling was an essential component of ventricular CF dif­ferentiation. CFs treated with TGF-β demonstrated increased expression of a TRP channel, TRPV4, both at the mRNA and protein levels, which corresponded with CF-myofibroblast trans-differentiation, as evidenced by the upregulation of α-smooth muscle actin, a myofibroblast marker, and plasminogen activator inhibitor-1, which are fibrogenesis markers. An agonist of TRPV4 induced the conversion of CFs into myofibroblasts, whereas it’s antagonist as well a Ca2+ chelating agent reduced it, indicating that the Ca2+ influx throughTRPV4 is required for CF trans-differentiation. Overall, these results dem­onstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway. Conclusions: Overall, these results demonstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway

Predictive value of progression-related gene classifier in primary non-muscle invasive bladder cancer

<p>Abstract</p> <p>Background</p> <p>While several molecular markers of bladder cancer prognosis have been identified, the limited value of current prognostic markers has created the need for new molecular indicators of bladder cancer outcomes. The aim of this study was to identify genetic signatures associated with disease prognosis in bladder cancer.</p> <p>Results</p> <p>We used 272 primary bladder cancer specimens for microarray analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Microarray gene expression analysis of randomly selected 165 primary bladder cancer specimens as an original cohort was carried out. Risk scores were applied to stratify prognosis-related gene classifiers. Prognosis-related gene classifiers were individually analyzed with tumor invasiveness (non-muscle invasive bladder cancer [NMIBC] and muscle invasive bladder cancer [MIBC]) and prognosis. We validated selected gene classifiers using RT-PCR in the original (165) and independent (107) cohorts. Ninety-seven genes related to disease progression among NMIBC patients were identified by microarray data analysis. Eight genes, a progression-related gene classifier in NMIBC, were selected for RT-PCR. The progression-related gene classifier in patients with NMIBC was closely correlated with progression in both original and independent cohorts. Furthermore, no patient with NMIBC in the good-prognosis signature group experienced cancer progression.</p> <p>Conclusions</p> <p>We identified progression-related gene classifier that has strong predictive value for determining disease outcome in NMIBC. This gene classifier could assist in selecting NMIBC patients who might benefit from more aggressive therapeutic intervention or surveillance.</p

Impact of multivessel versus single-vessel disease on the association between low diastolic blood pressure and mortality after acute myocardial infarction with revascularization

Background: Previous studies demonstrated a J-shaped relationship between low diastolic blood pressure (DBP) and adverse clinical outcomes in patients with acute myocardial infarction (AMI) that was sensitive to revascularization. Hypothesized herein, was that this relationship differs between patients with multivessel disease (MVD) and those with single-vessel disease due to differing degrees of myocardial ischemic burden. Methods: Among 9,983 AMI patients from the Korea Acute Myocardial Infarction Registry database who underwent percutaneous coronary intervention and were followed up for a median duration of 3.2 years, average on-treatment DBP was calculated at admission, discharge, and every scheduled visit and divided into these parameters: &lt; 70 mmHg, 70–74 mmHg, 75–79 mmHg, and ≥ 80 mmHg. The relationship between average on-treatment DBP and clinical outcomes including all-cause death, cardiovascular (CV) death, non-CV death, and hospitalization for heart failure was analyzed using the Cox regression models adjusted for clinical covariates. Results: In patients with MVD, all-cause death (hazard ratio [HR]: 1.47; 95% confidence interval [CI]: 1.06–2.04, p = 0.012) and CV death (HR: 1.59; 95% CI: 1.02–2.46, p = 0.027) were significantly increased in patients with a DBP &lt; 70 mmHg, showing a J-shaped relationship. However, these findings were not significant for single-vessel disease. On a sensitivity analysis excluding subjects with a baseline SBP &lt; 120 mmHg, an increased risk of a low DBP &lt; 70 mmHg remained in MVD. Conclusions: The J-shaped relationship between low DBP and adverse clinical outcomes in AMI patients who underwent revascularization persisted in MVD, which has a high ischemic burden. These high-risk patients require cautious treatment