Effects of grape seed-derived proanthocyanidin B2 pretreatment on oxidative stress, endoplasmic reticulum stress and apoptosis of renal tubular epithelial cells in renal ischemia-reperfusion injury model of mice.

PURPOSE: To investigate the effect of grape seed-derived proanthocyanidin B2 (GSPB2) pretreatment on acute renal ischemia-reperfusion injury model of mice. METHODS: 50 mice were divided into 5 groups: Sham group: mice were treated with right nephrectomy. GSPB2 group: GSPB2 was injected intraperitoneally 45 min before right nephrectomy. IRI group: right kidney was resected and the left renal arteriovenous vessel was blocked for 45 min. GSPB2 + IRI group: GSPB2 was intraperitoneally injected 45 min before IRI established. GSPB2 + BRU + IRI group: GSPB2 and brusatol (BRU) were injected intraperitoneally 45 min before IRI established. Creatinine and urea nitrogen of mice were detected, and the kidney morphology and pathological changes of each group were detected by HE staining, PAS staining and transmission electron microscopy. Expressions of Nrf2, HO-1, GRP78, CHOP, and cleaved-caspase3 were detected by immunofluorescence staining and western blotting. RESULTS: Morphology and mitochondrial damages of kidney in GSPB2 + IRI group were significantly alleviated than those in IRI group. Expression levels of Nrf2 and HO-1 were significantly higher in GSPB2 + IRI group than those in IRI group. Expression levels of GRP78, CHOP and cleaved-caspase3 were significantly lower in GSPB2 + IRI group than those in IRI group. However, compared to GSPB2 + IRI group, protective effects of GSPB2 pretreatment were weakened in GSPB2 + BRU + IRI group. CONCLUSIONS: GSPB2 pretreatment could alleviate oxidative stress damage and reduce apoptosis of renal tubular epithelial cells, which might be related to activating the antioxidant system, up-regulating the expression of Nrf2 and HO-1, inhibiting the expressions of GRP78, CHOP and cleaved-caspase3. However, the protective effect could be reversed by brusatol.

Evaporative Deposition of Surfactant-Laden Nanofluid Droplets over a Silicon Surface.

Morphologies of evaporative deposition, which has been widely applied in potential fields, were induced by the competition between internal flows inside evaporating droplets. Controlling the pattern of deposition and suppressing the coffee-ring effect are essential issues of intense interest in the aspects of industrial technologies and scientific applications. Here, evaporative deposition of surfactant-laden nanofluid droplets over silicon was experimentally investigated. A ring-like deposition was formed after complete evaporation of sodium dodecyl sulfate (SDS)-laden nanofluid droplets with an initial SDS concentration ranging from 0 to 1.5 CMC. In the case of initial SDS concentrations above 1.3 CMC, no cracks were observed in the ring-like deposition, indicating that the deposition patterns of nanofluid droplets could be completely changed and cracks could be eliminated by sufficient addition of SDS. With the increase of the initial concentration of hexadecyl trimethylammonium bromide (CTAB), the width of the deposition ring gradually decreased until no ring-like structure was formed. On the contrary, with the increase of the initial Triton X-100 (TX-100) concentration, the width of the deposition ring gradually increased until a uniform deposition was generated. Moreover, when the initial TX-100 concentration was high, a "tree-ring-like" pattern was discovered. Besides, morphologies of evaporative pattern due to the addition of surfacants were qualitatively analyzed.

Gene Expression Analysis Reveals Key Genes and Signalings Associated with the Prognosis of Prostate Cancer.

It is urgent to identify novel biomarkers for prostate cancer (PCa) prognosis and to understand the mechanisms regulating the tumorigenesis for PCa treatment. In this study, GSE17951 and TCGA were used to identify the differentially expressed genes (DEGs). Our study demonstrated that 1533 genes with increased expression and 2301 genes with decreased expression in PCa. Bioinformatics analysis data indicated that these up-regulated genes had an association with the modulation of mitotic nuclear division, sister chromatid cohesion, cell division, and cell cycle. Additionally, our results revealed downregulated genes took part in modulating extracellular matrix organization, angiogenesis, signal transduction, and Ras signaling pathway. Hub upregulated and downregulated PPI networks were identified by protein-protein interaction (PPI) network analysis and MCODE analysis. Of note, 12 cell cycle regulators, comprising CCNB1, CCNB2, PLK1, TTK, AURKA, CDC20, BUB1, PTTG1, CDC45, CDC25C, CCNA2, and BUB1B, were demonstrated to function crucially in PCa development. By detecting their expression in PCa cell lines, we confirmed that these cell cycle regulator expressions were heightened in PCa cells. GEPIA databases analysis showed that higher expression of these cell cycle regulators was correlated to shorter disease-free survival (DFS) time in PCa samples. Our findings collectively suggested targeting cell cycle pathways may offer novel prognosis and treatment biomarkers for PCa.

PEG modification enhances the in vivo stability of bioactive proteins immobilized on magnetic nanoparticles.

OBJECTIVE: To increase the in vivo stability of bioactive proteins via optimized loading methods. RESULTS: ß-Glucosidase (ß-Glu), as a model protein, was immobilized on magnetic nanoparticles(denoted as MNP-ß-Glu) by chemical coupling methods and was further modified by poly(ethylene glycol) (PEG) molecules (denoted as MNP-ß-Glu-PEG) to increase its stability. The physicochemical properties of the as-prepared nanohybrids, including the particle size, zeta potential, and enzyme activity, were well characterized. The proper MNP/ß-Glu feed ratio was important for optimizing the particle size. Analysis of enzyme activity showed that the stability of immobilized ß-Glu compared with free ß-Glu was lower in deionized water and higher in blood serum at 37 °C. MNP-ß-Glu-PEG retained 77.9% of the initial activity within 30 days at 4 °C, whereas the free enzyme retained only 58.2%. Pharmacokinetic studies of Sprague-Dawley (SD) rats showed that the MNP-ß-Glu-PEG group retained a higher enzyme activity in vivo (41.46% after 50 min) than the MNP-ß-Glu group (0.03% after 50 min) and the ß-Glu group (0.37% after 50 min). Moreover, in contrast to the MNP-ß-Glu group, the enzyme activity was not fully synchronous with the decrease in the Fe concentration in the MNP-ß-Glu-PEG group. CONCLUSIONS: All findings indicated that the method of immobilization on magnetic nanoparticles and PEG modification is promising for the application of bioactive proteins in vivo.

Primary prostate cancer synchronous with renal cell carcinoma: clinical experience and literature review.

The objective of this study was to report the diagnosis and treatment results of primary prostate adenocarcinoma (PRAD) concurrent in a patient with renal cell carcinoma (RCC), and to review the relative literature. A 62-year-old man was admitted to our hospital with chief complaint of a painless, incidentally found renal mass for one year. RCC was initially found by computed tomography (CT) scan, but prostate cancer was incidentally found by abnormal prostate-specific antigen (PSA) level results. The post-nephrectomy pathology assay reported clear RCC with positive staining of vimentin, cluster of differentiation 10 (CD10), carbonic anhydrase IX (CA-IX), paired box 8 (Pax-8), epithelial membrane antigen (EMA), and Ki67 labeling index (Ki67 LI). Magnetic resonance imaging (MRI) revealed uneven signals in the right peripheral zone of the prostate. Both prostate biopsy and post-prostatectomy pathology examination revealed prostate acinar adenocarcinoma with positive staining of P504S and Ki67 LI. The patient has been in periodic follow-up and has remained in good general condition without any evidence of recurrence to date. To the best of our knowledge, the present report is the only case of systematically described pre- and post-therapy laboratory, pathology, and imaging examination results. Our report together with published studies suggest that increased awareness of synchronous PRAD risk will enable early detection and prompt therapies in patients with RCC.

[Source Profiles of Volatile Organic Compounds (VOCs) from Typical Solvent-based Industries in Beijing].

Based on the demand for a volatile organic compounds (VOCs) emissions inventory for Beijing and for the reduction in VOC emissions, the three major solvent-based industries of automobile manufacturing, furniture manufacturing, and publication printing were selected for this study. In each case, emissions link negative pressure sampling was used in combination with laboratory-based GC-MS/FID to obtain the VOC spectra. The results show that there are significant differences in the emission of VOCs from the main stages of automobile manufacturing. Specifically, the paint-coating process was dominated by the emission of oxygenated VOCs and aromatic hydrocarbons, accounting for 71.26% and 27.14% of total VOC emissions, respectively. The proportion of aromatic hydrocarbons emitted during the varnishing process was very large (84.10%), which were mainly composed of the benzene series. The differences in VOC emissions during different stages of the furniture manufacturing process were small, mainly consisting of oxygenated VOCs and aromatic hydrocarbons, which accounted for 55.08% and 18.98% of the total, respectively. Of these, alcohols and esters were the main components. VOCs emitted from different stages of the publication printing process could not be monitored separately. Thus, the VOCs in the mixed exhaust gas from this process were mainly composed of alkanes and oxygenated VOCs, which accounted for 47.29% and 44.57% of the total emissions, respectively.

Enzalutamide alleviates anxiety and depression as well as improves quality of life compared to bicalutamide in metastatic castration-resistant prostate cancer patients: a cohort study.

BACKGROUND: This study aimed to evaluate the efficacy of enzalutamide compared with bicalutamide on anxiety, depression and quality of life (QoL) in metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: Totally 134 mCRPC patients were consecutively enrolled and baseline data were documented, among whom 53 patients received enzalutamide as Enzalutamide group, while 81 patients received bicalutamide as Bicalutamide group. Anxiety and depression were assessed by Hospital Anxiety and Depression Scale (HADS) as well as Zung Self-Rating Anxiety/Depression Scale (SAS/SDS), and QoL was assessed by Functional Assessment of Cancer Therapy (FACT)-General/Prostate (FACT-G/FACT-P) questionnaires at W0 (baseline), W12, W24, W36, W48 and W60. RESULTS: No difference of HADS-anxiety (HADS-A), SAS, HADS-depression (HADS-D), SDS, FACT-G or FACT-P score at baseline was observed between Enzalutamide group and Bicalutamide group. Both HADS-A score and SAS score were decreased at W48 and W60 in Enzalutamide group compared to Bicalutamide group. HADS-D score was reduced at W60 and SDS score was attenuated at W48 and W60 in Enzalutamide group compared to Bicalutamide group. As to QoL assessments, FACT-G score disclosed no difference at each visit between Enzalutamide group and Bicalutamide group, while FACT-P score was decreased at W60 in Enzalutamide group compared to Bicalutamide group. In addition, the reduction of HADS-A, SAS, HADS-D, SDS, FACT-G and FACT-P scores from W0 to W60 were all higher in in Enzalutamide group compared to Bicalutamide group. CONCLUSIONS: In conclusion, enzalutamide presents with better efficacy on alleviating anxiety and depression, as well as improving QoL in mCRPC patients compared to bicalutamide.

G protein-coupled receptor kinase 2 inhibition improves erectile function through amelioration of endothelial dysfunction and oxidative stress in a rat model of type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is a common cause of erectile dysfunction (ED). It has been demonstrated that G protein-coupled receptor kinase 2 (GRK2) overexpression contributes to diabetic endothelial dysfunction and oxidative stress, which also underlies ED in T2DM. We hypothesized that GRK2 overexpressed and attenuated endothelial function of the cavernosal tissue in a rat model of T2DM. T2DM rats were established by feeding with a high-fat diet (HFD) for 2 weeks and then administering two intraperitoneal (IP) injections of a low dose of streptozotocin (STZ), followed by continuous feeding with a HFD for 6 weeks. GRK2 was inhibited by IP injection of paroxetine, a selective GRK2 inhibitor, after STZ injection. Insulin challenge tests, intracavernous pressure (ICP), GRK2 expression, the protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) pathway, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit gp91phox, nitric oxide (NO), reactive oxygen species (ROS) production, and apoptosis in cavernosal tissue were examined. Less response to insulin injection was observed in T2DM rats 2 weeks after HFD. Markedly increased GRK2 expression, along with impaired Akt/eNOS pathway, reduced NO production, increased gp91phox expression and ROS generation, increased apoptosis and impaired erectile function were found in T2DM rats. Inhibition of GRK2 with paroxetine ameliorated Akt/eNOS signaling, restored NO production, downregulated NADPH oxidase, subsequently inhibited ROS generation and apoptosis, and ultimately preserved erectile function. These results indicated that GRK2 upregulation may be an important mechanism underlying T2DM ED, and GRK2 inhibition may be a potential therapeutic strategy for T2DM ED.

Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury.

BACKGROUND: Cavernous nerve injury (CNI) causes fibrosis and loss of smooth muscle cells (SMCs) in the corpus cavernosum and leads to erectile dysfunction, and lysyl oxidase (LOX) activation has been found to play an important role in fibrotic diseases. AIM: To evaluate the role of LOX in penile fibrosis after bilateral CNI (BCNI). METHODS: Rats underwent BCNI or a sham operation and were treated with vehicle or ß-aminopropionitrile, a specific LOX activity inhibitor. 30 days after BCNI, rats were tested for erectile function before penile tissue harvest. LOX and extracellular matrix component expression levels in the corpus cavernosum, including matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), fibronectin (FN), collagen (COL) I, and COL IV, were evaluated by real-time quantitative polymerase chain reaction and western blot. Corporal fibrosis was evaluated by Masson trichrome staining. Localization of LOX and SMC content in the corpus cavernosum were assessed by immunohistochemistry. OUTCOMES: Ratio of intracavernous pressure to mean arterial blood pressure; LOX, MMPs, TIMPs, COL I, COL IV, and FN expression; penile fibrosis; penile SMC content. RESULTS: After BCNI, there was an increase in penile LOX expression and activity, increased penile fibrosis, decreased SMC content, and impaired erectile function. TIMP1, TIMP2, COL I, COL IV, and FN expression was markedly upregulated, whereas the enzyme activity of MMPs was decreased after BCNI. ß-Aminopropionitrile treatment, at least in part, prevented a decrease in the ratio of intracavernous pressure to mean arterial blood pressure, decreased penile expression of TIMP1, TIMP2, COL I, COL IV, and FN, increased MMP activity, prevented corporal fibrosis, and preserved SMC content. CLINICAL TRANSLATION: LOX over-activation contributes to penile fibrosis and LOX inhibition could be a promising strategy in preventing the progression of CNI-induced erectile dysfunction. STRENGTHS AND LIMITATIONS: This is the 1st study to demonstrate the role of LOX activation in penile fibrosis. However, the exact mechanism of how LOX influences extracellular matrix protein synthesis and SMC content preservation awaits further investigation. CONCLUSION: CNI induced LOX over-activation in cavernous tissue, and inhibition of LOX preserved penile morphology and improved erectile function in a rat model of BCNI. Wan Z-H, Li G-H, Guo Y-L, et al. Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury. J Sex Med 2018;15:304-313.

Catalytic Asymmetric Construction of the Tryptanthrin Skeleton via an Enantioselective Decarboxylative [4 + 2] Cyclization.

The first catalytic asymmetric construction of the tryptanthrin skeleton has been established, taking advantage of a palladium(0)/chiral ligand-catalyzed enantioselective decarboxylative [4 + 2] cyclization of vinyl benzoxazinanones with isatins. This reaction has not only provided a direct and efficient method for constructing chiral tryptanthrin skeleta in high yields and excellent enantioselectivities (up to 97% yield, >99% ee) but also represents the first catalytic asymmetric decarboxylative cyclization of vinyl benzoxazinanones with isatins.

Substrate-Controlled Regioselective Arylations of 2-Indolylmethanols with Indoles: Synthesis of Bis(indolyl)methane and 3,3'-Bisindole Derivatives.

A substrate-controlled regioselective arylation of 2-indolylmethanols with indoles has been established, which efficiently afforded bis(indolyl)methane and 3,3'-bisindole derivatives in high yields and with a broad substrate scope (up to 98% yield, 36 examples). This approach will not only provide an important strategy for the diversified synthesis of bis(indolyl)methane and 3,3'-bisindole derivatives but also serve as a good example for substrate-controlled regioselective reactions.

Catalytic Enantioselective and Regioselective [3+3] Cycloadditions Using 2-Indolylmethanols as 3 C Building Blocks.

The first catalytic asymmetric cycloaddition using 2-indolylmethanols as 3C building blocks has been established by a chiral phosphoric acid-catalyzed enantioselective and regioselective [3+3] cycloaddition of 2-indolylmethanols with azomethine ylides, which constructed biologically important tetrahydro-γ-carboline frameworks in high yields and excellent enantioselectivities (up to 83 % yield, 99:1 e.r.). This reaction not only represents the first application of 2-indolylmethanols as 3C building blocks in catalytic asymmetric cycloadditions, but also has established an abnormal regioselectivity in indolylmethanol-involved transformations.

Diastereo- and enantioselective construction of an indole-based 2,3-dihydrobenzofuran scaffold via catalytic asymmetric [3+2] cyclizations of quinone monoimides with 3-vinylindoles.

The first catalytic asymmetric [3+2] cyclization of quinone monoimides with olefins has been established, which employed 3-vinylindoles as a class of competent olefins and spiro-chiral phosphoric acid as a powerful chiral catalyst, leading to chemo-, diastereo- and enantioselective construction of a biologically important 2,3-dihydrobenzofuran framework with optical purity (up to 99% yield, >95 : 5 dr, 96 : 4 er).

Calpain Inhibition Improves Erectile Function in a Rat Model of Cavernous Nerve Injury.

INTRODUCTION: Erectile dysfunction (ED) after cavernous nerve (CN) injury remains difficult to treat. Calpain plays a critical role in causing neurodegenerative diseases. This study aimed to evaluate whether calpain inhibition preserves erectile function in a rat model of CN injury. MATERIALS AND METHODS: Rats underwent sham surgery or CN crush injury. The CN-crushed rats were treated with vehicle or MDL-28170, a specific calpain inhibitor. At 1, 2, 3, and 7 days post-surgery, major pelvic ganglia (MPG) were harvested, followed by the measurement of erectile function, respectively. At 28 days, penile tissue and distal CN were harvested, followed by the measurement of erectile function in rats. Calpain activity in MPG and corpus cavernosum, as well as TGF-ß1/Smad2 and collagen content in corpus cavernosum, were measured by western blot. Neuronal nitric oxide synthase (nNOS) was observed by immunohistochemistry. RESULTS: Increased calpain activity was observed in MPG and corpus cavernosum. CN crush markedly attenuated the erectile responses and nNOS expression in CN, and these were improved by MDL-28170 treatment. Furthermore, treatment prevented increased TGF-ß1/Smad2 and collagen expression in corpus cavernosum. CONCLUSIONS: Our results suggested that calpain activation plays a role in pathogenesis of CN injury-associated ED. Calpain inhibition could be a novel approach for preventing the development of ED following CN injury.

[Studies on the effect of Ginkgo biloba extracts on NF-kappaB pathway].

OBJECTIVE: To investigate NF-kappaB and IkappaBalpha activities in HL-60 induced by TNF-alpha in order to understand the molecular mechanism of GbE in asthma treatment. METHODS: The amount of IkappaBalpha in HL-60 cells stimulated by TNF-alpha and GbE was measured by western blotting. Plasmid pNF-kappaB-LuC was transfected and NF-kappaB activity was analyzed by measuring the expression level of luciferase. RESULTS: It showed in the luciferase assay that the activity of NF-kappaB could significantly be suppressed in HL-60 cells after the pretreatment with CGbE. However, the phosphorylation and subsequent degradation of IKBalpha induced by TNF-alpha can not be inhibited in HL-60 cells even we prolonged the treatment time or increased the concentration of GhE. CONCLUSION: GhE can suppress the NF-kappaB gene expression actively on independent of NIK/ IKK/ IkappaBalpha pathway in HL-60 cells.