Effects of emulsifier, betaine, and L-carnitine on growth performance, immune response, gut morphology, and nutrient digestibility in broiler chickens exposed to cyclic heat stress.

1. This experiment investigated the efficacy of varying doses of an emulsifier blend (EB; 0 and 1 g/kg of diet), betaine (BT; 0 and 1 g/kg of diet) and L-carnitine (CT; 0 and 0.5 g/kg of diet) in broilers subjected to circular heat stress (HS) conditions. A total of 1080 one-day-old male broiler chickens (Ross 308) were randomly assigned to one of nine treatment groups (six pens/treatment with 20 birds/pen) according to a completely randomised design. The thermoneutral control broiler chickens were housed at a comfortable temperature and fed a standard diet (no additives). The other eight groups were exposed to cyclic HS conditions (34°C) for 8 h (10:00-18:00).2. There were EB × BT × CT interactions for body weight (BW) at 24 d (P = 0.038) and average daily gain (ADG) during the 10-24 d period (P = 0.049), with the greatest values found with concurrent supplementation of three supplements.3. Inclusion of EB resulted in greater (P < 0.05) BW, ADG, European performance index, uniformity rate, primary antibody titres against sheep red blood cells (SRBC), duodenal villus height (VH) and villus surface area, digestible energy (DE) and the coefficient of apparent ileal digestibility (CAID) of dry matter, crude protein, and fat However, feed conversion ratio, mortality rate and heterophile to lymphocyte ratio were lower (P < 0.05).4. Dietary BT supplementation improved (P < 0.05) all performance indicators, primary antibody titres against SRBC and Newcastle disease virus, serum total antioxidant capacity, duodenal VH, Jejunal VH/crypt depth and the CAID of dry matter and crude protein. The effect of dietary supplementation with CT was limited to an increase (P < 0.05) in ADG (d 10-24) and a decrease (P < 0.05) in serum malondialdehyde concentration (42 d) and jejunal crypt depth (42 d).5. In conclusion, dietary supplementation of either EB or BT alone or in combination ameliorated some of the detrimental effects of HS on growth performance, immunity and intestinal health in broilers, while a minor positive effect on performance and antioxidant status was observed with CT supplementation.

Effect of fennel essential oil on performance, serum biochemistry, immunity, ileum morphology and microbial population, and meat quality of broiler chickens fed corn or wheat-based diet.

1. The effect of Foeniculi aetheroleum essential oil (EO) on growth performance, nutrient utilisation, serum biochemistry, immune response, ileum morphology, microbial population and meat quality of broiler chickens fed a corn- or wheat-based diet were determined.2. A total of 360 broiler chickens were arranged in a 2 × 2 factorial assay in a completely randomised design with six replicates and 15 birds per experimental unit. Birds were fed corn- or wheat-based diets supplemented with (200 mg/kg) or without fennel EO.3. Birds fed wheat-based diets had lower BWG and FCR during grower period and lower FI during finisher period as compared to those fed corn-based diet (P < 0.05) whereas addition of fennel EO decreased chickens BWG during finisher period and EPEF, both in wheat or in corn-based diets. Dietary treatments had no effect on serum glucose, triglyceride, cholesterol, LDL-cholesterol, AST, ALT, ALP, and MDA concentrations (P < 0.05).4. Antibody titres against avian influenza and sheep red blood cell antibody titres, crude protein and crude fat utilisation, villus height, crypt depth and epithelium thickness were not influenced by dietary treatments (P > 0.05). Inclusion of Fennel EO to the corn-based diet resulted in greater villus width and villus surface area while it reduced lamina propria thickness (P < 0.05). Fennel EO reduced ileal E. coli and Lactobacillus spp. populations (P < 0.05). Dietary treatments had no significant effect on meat pH, cooking loss, drip loss, crude protein, crude fat content and cholesterol concentration of breast and thigh meat, total phenolic and MDA concentrations, and breast meat sensory parameters (P > 0.05).5. These results showed that addition of fennel EO to wheat-based diets had a negative effect on chicken growth performance variables and decreased gut E. coli populations. However, immunity, meat quality and nutrient utilisation were not affected by dietary treatments.

Prognostic value of peptidyl-prolyl cis-trans isomerase 1 (PIN1) in human malignant tumors.

BACKGROUND: PIN1, a peptidyl-prolyl cis-trans isomerase, specifically can regulate phosphorylation of proteins on serine/threonine residues that precede proline and has critical roles in cell proliferation and transformation. Many studies have revealed that overexpression of PIN1 is involved in the malignant biological behavior of various cancers, but to date, no meta-analyses have evaluated PIN1 clinical and prognostic value in patients with malignant tumors. METHODS: We retrieved related articles from PubMed, Web of Science and Scopus databases up to April 20, 2019. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% CIs were used to estimate the correlation of PIN1 expression with clinicopathological characteristics and survival outcomes. The methodology was according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Cochrane Collaboration guidelines. RESULTS: A total of 20 studies containing 2574 patients with various tumors were included in this analysis. Pooled results showed that PIN1 overexpression was significantly associated with the advanced clinical stages of cancer (OR = 1.37, 95% CI 1.06-1.78), positive lymph node metastasis (OR = 1.65, 95% CI 1.15-2.37) and poor prognosis (HR = 2.40, 95% CI 1.55-3.74), although no correlation with poor differentiation was found. CONCLUSIONS: These results suggest that high expression of PIN1 can be considered as a risk factor for progression and invasion of malignant tumors and thus may serve as a promising therapeutic target and prognostic biomarker for human solid tumors.

Antitumor activity of Ad-IU2, a prostate-specific replication-competent adenovirus encoding the apoptosis inducer, TRAIL.

In this study, we analyzed the preclinical utility and antitumor efficacy of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) delivered by Ad-IU2, a prostate-specific replication-competent adenovirus (PSRCA), against androgen-independent prostate cancer. Through transcriptional control of adenoviral early genes E1a, E1b and E4, as well as TRAIL by two bidirectional prostate-specific enhancing sequences (PSES), the expression of TRAIL and adenoviral replication was limited to prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA)-positive cells. Ad-IU2 induced fivefold greater apoptosis selectively in PSA/PSMA-positive CWR22rv and C4-2 cells than an oncolytic adenoviral control. Furthermore, prolonged infection with Ad-IU2 reversed TRAIL resistance in LNCaP cells. Ad-IU2 showed superior killing efficiency in PSA/PSMA-positive prostate cancer cells at doses five- to eight-fold lower than required by a PSRCA to produce a similar effect; however, this cytotoxic effect was not observed in non-prostatic cells. As an enhancement of its therapeutic efficacy, Ad-IU2 exerted a TRAIL-mediated bystander effect through direct cell-to-cell contact and soluble factors such as apoptotic bodies. In vivo, Ad-IU2 markedly suppressed the growth of subcutaneous androgen-independent CWR22rv xenografts compared with a PSRCA at 6 weeks after treatment (3.1- vs 17.1-fold growth of tumor). This study shows the potential clinical utility of a PSRCA armed with an apoptosis-inducing ligand.

Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoter.

Enzyme pro-drug suicide gene therapy has been hindered by inefficient viral delivery and gene transduction. To further explore the potential of this approach, we have developed AdIU1, a prostate-restricted replicative adenovirus (PRRA) armed with the herpes simplex virus thymidine kinase (HSV-TK). In our previous Ad-OC-TK/ACV phase I clinical trial, we demonstrated safety and proof of principle with a tissue-specific promoter-based TK/pro-drug therapy using a replication-defective adenovirus for the treatment of prostate cancer metastases. In this study, we aimed to inhibit the growth of androgen-independent (AI), PSA/PSMA-positive prostate cancer cells by AdIU1. In vitro the viability of an AI- PSA/PSMA-expressing prostate cancer cell line, CWR22rv, was significantly inhibited by treatment with AdIU1 plus GCV (10 microg ml(-1)), compared with AdIU1 treatment alone and also cytotoxicity was observed following treatment with AdIU1 plus GCV only in PSA/PSMA-positive CWR22rv and C4-2 cells, but not in the PSA/PSMA-negative cell line, DU-145. In vivo assessment of AdIU1 plus GCV treatment revealed a stronger therapeutic effect against CWR22rv tumors in nude mice than treatment with AdIU1 alone, AdE4PSESE1a alone or in combination with GCV. Our results demonstrate the therapeutic potential of specific-oncolysis and suicide gene therapy for AI-PSA/PSMA-positive prostate cancer gene therapy.

Functional hepatocyte-like cells derived from human bone marrow mesenchymal stem cells on a novel 3-dimensional biocompatible nanofibrous scaffold.

AIM: To supporting growth and functional differentiation of adult stem cells into hepatocytes in a well-controlled manner, we performed differentiation of human bone marrow mesenchymal stem cells (hBMSCs) to hepatocytes-like cells on a constructed 3-dimensional (3D) nanofibrous biocompatible scaffold. METHODS: After characterization of the hBMSCs isolated from human bone marrow, the performance of the cells seeded and their proliferation on the scaffold was evaluated by scanning electron microscopy (SEM) and 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Different approaches such as immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR), and biochemical assays were used to estimate the ability of hBMSC-derived cells to express hepatocyte-specific markers. RESULTS: Scanning electron micrographs and MTT analysis revealed the cells were able to expand and remained biologically and metabolically active for 21 days. Immunocytochemical analysis of albumin and alfa-fetoprotein showing the accumulation of these markers in differentiated cells was confirmed by RT-PCR. Additional markers such as cytochrome P450 3A4, cytokeratin-18, and cytokeratin-19 detected by RT-PCR showed progressive expression during 3 weeks of differentiation on 3D scaffold. The hepatocyte-like cells displayed several characteristics of metabolic functions as judged by production of albumin, urea, transferrin, serum glutamic pyruvic transaminase (SGPT), and serum oxaloacetate aminotransferase (SGOT). Levels of above-mentioned markers, except SGOT in differentiated cells on scaffold, were found to be significantly greater than in the 2D culture system (p<0.05). CONCLUSION: Overall data suggest that the engineered nanofibrous scaffold is a conductive matrix for functional hBMSC-derived hepatocyte-like cells and is promising for maintenance of hepatocytes suitable for implantation.

Nanofibrous poly(epsilon-caprolactone)/poly(vinyl alcohol)/chitosan hybrid scaffolds for bone tissue engineering using mesenchymal stem cells.

In the present study, based on a biomimetic approach, novel 3D nanofibrous hybrid scaffolds consisting of poly(epsilon-caprolactone), poly(vinyl alcohol), and chitosan were developed via a multi-jet electrospinning method. The influence of chemical, physical, and structural properties of the scaffolds on the differentiation of mesenchymal stem cells into osteoblasts, and the proliferation of the differentiated cells were investigated. Osteogenically induced cultures revealed that cells were well-attached, penetrated into the construct and were uniformly distributed. The expression of early and late phenotypic markers of osteoblastic differentiation was upregulated in the constructs cultured in osteogenic medium.