Changes in polyphenolic content and antioxidant activity after thermal treatments of grape seed extract and grape pomace

This study was undertaken to investigate the effect of heat treatment on polyphenolic content and antioxidant activity in grape pomace (GP) and grape seed extract (GSE). GP and GSE were heat treated in a furnace or autoclaved at 100 °C for 15, 30 and 60 min. Structural modifications of the polyphenols during thermal processes were determined by HPLC–MS, and the antioxidant activity was determined by ABTS, DPPH and photochemiluminescence methods. In general, furnace thermal treatment of GSE and GP did not affect the total extractable polyphenols content, tannin content, procyanidin components and the antioxidant activity. Autoclave treatment caused an extensive hydrolysis of gallocatechin (70%), catechin (61%), epicatechin (65%), procyanidin B1 (75%) and procyanidin B2 (73%) in GSE, and an increase in gallic acid (71%), gallocatechin (100%) and epicatechin gallate (129%) in GP. Autoclave treatment did not affect the antioxidant activity of GSE or GP. It can be concluded that the effect of autoclave was more severe than furnace heat treatment modifying the phenolic profile in a different manner depending on the grape seed product used. These modifications were not related with changes in antioxidant activity.     

Mass Spectrometry-Based Disulfide Mapping of Lysyl Oxidase-like 2

Lysyl oxidase-like 2 (LOXL2) catalyzes the oxidative deamination of peptidyl lysines and hydroxylysines to promote extracellular matrix remodeling. Aberrant activity of LOXL2 has been associated with organ fibrosis and tumor metastasis. The lysine tyrosylquinone (LTQ) cofactor is derived from Lys653 and Tyr689 in the amine oxidase domain via post-translational modification. Based on the similarity in hydrodynamic radius and radius of gyration, we recently proposed that the overall structures of the mature LOXL2 (containing LTQ) and the precursor LOXL2 (no LTQ) are very similar. In this study, we conducted a mass spectrometry-based disulfide mapping analysis of recombinant LOXL2 in three forms: a full-length LOXL2 (fl-LOXL2) containing a nearly stoichiometric amount of LTQ, Δ1-2SRCR-LOXL2 (SRCR1 and SRCR2 are truncated) in the precursor form, and Δ1-3SRCR-LOXL2 (SRCR1, SRCR2, SRCR3 are truncated) in a mixture of the precursor and the mature forms. We detected a set of five disulfide bonds that is conserved in both the precursor and the mature recombinant LOXL2s. In addition, we detected a set of four alternative disulfide bonds in low abundance that is not associated with the mature LOXL2. These results suggest that the major set of five disulfide bonds is retained post-LTQ formation.     

HDAC8-Selective Inhibition by PCI-34051 Enhances the Anticancer Effects of ACY-241 in Ovarian Cancer Cells

HDAC6 is overexpressed in ovarian cancer and is known to be correlated with tumorigenesis. Accordingly, ACY-241, a selective HDAC6 inhibitor, is currently under clinical trial and has been tested in combination with various drugs. HDAC8, another member of the HDAC family, has recently gained attention as a novel target for cancer therapy. Here, we evaluated the synergistic anticancer effects of PCI-34051 and ACY-241 in ovarian cancer. Among various ovarian cancer cells, PCI-34051 effectively suppresses cell proliferation in wild-type p53 ovarian cancer cells compared with mutant p53 ovarian cancer cells. In ovarian cancer cells harboring wild-type p53, PCI-34051 in combination with ACY-241 synergistically represses cell proliferation, enhances apoptosis, and suppresses cell migration. The expression of pro-apoptotic proteins is synergistically upregulated, whereas the expressions of anti-apoptotic proteins and metastasis-associated proteins are significantly downregulated in combination treatment. Furthermore, the level of acetyl-p53 at K381 is synergistically upregulated upon combination treatment. Overall, co-inhibition of HDAC6 and HDAC8 through selective inhibitors synergistically suppresses cancer cell proliferation and metastasis in p53 wild-type ovarian cancer cells. These results suggest a novel approach to treating ovarian cancer patients and the therapeutic potential in developing HDAC6/8 dual inhibitors.     

Inhibitory Activities of Rare Ginsenoside Rg4 on Cecal Ligation and Puncture-Induced Sepsis

Sepsis is an uncontrolled response to inflammatory infection and is associated with high levels of mortality and morbidity. Rg4 is a rare ginsenoside mainly found in the leaves of Panax ginseng C. A. Meyer and the major protopanaxatriol-type ginsenoside of black ginseng. In this study, we determined whether Rg4 affects cecal ligation and puncture (CLP)-induced sepsis. Animals were separated into the following six groups: control group, CLP-operated group, CLP plus maslinic acid (MA), and CLP plus Rg4 (5, 10, or 15 mg/kg). Survival rate, body weight changes, inflammatory cytokines, and histological analyses were assessed. Human endothelial cells were activated with the high-mobility group box 1 (HMGB1) protein and Rg4. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used to assess inflammation and gene expression, respectively. After CLP surgery, the Rg4-administered group exhibited a higher survival rate and body weight compared with the untreated control group. Rg4 treatment reduced cytokine levels, including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, as well as nitric oxide (NO) levels and renal inflammation. After Rg4 treatment of HMGB1-activated cells, the expressions of toll-like receptor (TLR) 4 and TNF-α were decreased, and the activation of phosphoinositide 3-kinase (PI3K)/AKT signaling increased cell viability. In summary, Rg4 inhibited inflammation and exhibited a protective effect against CLP-induced sepsis, thereby reinforcing cell survival against septic responses.     

Anti-Inflammatory Effect of Sparstolonin B through Inhibiting Expression of NF-κB and STAT-1

Sparstolonin B (SsnB), which is found in Sparganium stoloniferum, prevents the synthesis of inflammatory mediators and is related to functional pathways of survival. In this study, we assessed the possible protective functions of SsnB on lipopolysaccharide (LPS)-induced inflammatory responses. We determined the functions of SsnB on controlling heme oxygenase (HO)-1, cyclooxygenase (COX-)2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). Furthermore, the distinct function of SsnB on the expression of iNOS and well-known pro-inflammatory mediators, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, were assessed in the pulmonary histological status of LPS-injected mice. SsnB upregulated the HO-1 production, inhibited luciferase-NF-κB interaction, and lowered COX-2/PGE2 and iNOS/NO, which lead to the reduction of STAT-1 phosphorylation. Moreover, SsnB enhanced the nuclear translocation of Nrf2, elevated the binding activity between Nrf2 and antioxidant response elements (AREs), and weakened IL-1β expression on LPS-treated HUVECs. SsnB-suppressed iNOS/NO synthesis was restored by the process of the RNAi inhibition of HO-1. In experiment with an LPS-injected animal model, SsnB remarkably decreased the iNOS expression in the pulmonary biostructure and TNF-α level in the bronchoalveolar lavage fluid (BALF). Therefore, these results demonstrate that SsnB is responsible for inflammation ameliorative activity by controlling iNOS through inhibition of both NF-κB expression and p-STAT-1. Therefore, SsnB could be a candidate for promoting novel clinical substances to remedy pathologic inflammation.     

Ototoxicity of drugs

The paper included the most current information about the mechanisms of ototoxicity of five groups of the most popular drugs: a) antibiotics, b) chemotherapeutics (cytostatic) agents, c) loop diuretics, d) salicylate and nonsteroidal anti-inflammatory drugs, as well as e) progestagen contraceptives minimized or even prevented by thoughtful selection of drug, attention to risk factors and careful patient monitoring.     

滞后阻尼结构的复模态综合技术及其界面自由度的减缩

本文在Craig固定界面模态综合法基础上提出了一个针对滞后阻尼结构的复模态综合方法。算例说明该方法不仅在频率上,而且在振型上都具有较好的精度。本文还探讨了综合自由度的进一步减缩。     

Diagnostic problems in epidural hematoma of the posterior cranial fossa

Posttraumatic posterior cranial fossa haematoma is a rare occurrence. In our material it accounted for 1.5% of all intracranial haematomas. Due to its infrequency and diagnostic difficulties these patients are referred with delay to neurosurgeons and often die with signs of brain stem lesion. The reported case was a 25-year-old man with this haematoma and considerable diagnostic difficulties were encountered despite the application of modern imaging techniques. These difficulties hamper the qualification of the patient for operation which is the method of choice in these cases.     

新型铸造用酚醛树脂粘结剂的生产工艺

苯酚、苯基苯酚、尿素与甲醛的反应产物进一步与糖醇缩聚生成新型铸造用改性酚醛树脂粘结剂。该粘结剂具有粘结强度高、低氨、低粘度等优点。其工艺技术已应用于工业生产。