This study performed a meta-analysis of published trials to determine the effects of zinc addition on the immune response and production performance of broilers.

Biochemical recurrence (BCR) is important for measuring the oncological outcomes of patients who undergo radical prostatectomy (RP). Whether transurethral resection of the prostate (TURP) has negative postoperative effects on oncological outcomes remains controversial. The primary aim of our retrospective study was to determine whether a history of TURP could affect the postoperative BCR rate. We retrospectively reviewed patients with prostate cancer (PCa) who had undergone RP between January 2009 and October 2017. Clinical data on age, prostate volume, serum prostate-specific antigen levels (PSA), biopsy Gleason score (GS), metastasis stage (TNM), D'Amico classification, and American Society of Anesthesiologists (ASA) classification were collected. Statistical analyses including Cox proportional hazard models and sensitivity analyses which included propensity score matching, were performed, and the inverse-probability-of-treatment-weighted estimator and standardized mortality ratio-weighted estimator were determined. We included 1083 patients, of which 118 had a history of TURP. Before matching, the non-TURP group differed from the TURP group with respect to GS (P= 0.047), prostate volume (mean: 45.19 vs 36.00 ml, P < 0.001), and PSA level (mean: 29.41 vs 15.11 ng ml-1, P= 0.001). After adjusting for age, PSA level, T stage, N stage, M stage, and GS, the TURP group showed higher risk of BCR (hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.13-3.94, P= 0.004). After matching (ratio 1:4), patients who underwent TURP were still more likely to develop BCR according to the adjusted propensity score (HR: 2.00, 95% CI: 1.05-3.79, P= 0.034). Among patients with PCa, those with a history of TURP were more likely to develop BCR after RP.

The sperm nucleus is prone to sustain DNA damage before and after ejaculation. Distribution of the damage is not homogeneous, and the factors determining differential sensitivity among nuclear regions have not yet been characterized. Human sperm chromatin contains three structural domains, two of which are considered the most susceptible to DNA damage: the histone bound domain, harboring developmental related genes, and the domain associated with nuclear matrix proteins. Using a quantitative polymerase chain reaction (qPCR) approach, we analyzed the number of lesions in genes homeobox A3 (HOXA3), homeobox B5 (HOXB 5), sex-determining region Y (SRY)-box 2 (SOX2), β-GLOBIN, rDNA 18S, and rDNA 28S in human sperm after ultraviolet irradiation (400 μW cm-2, 10 min), H2O2treatment (250 mmol l-1, 20 min), and cryopreservation, which showed differential susceptibility to genetic damage. Differential vulnerability is dependent on the genotoxic agent and independent of the sperm nuclear proteins to which the chromatin is bound and of accessibility to the transcription machinery. Immunodetection of 8-hydroxy-2'-deoxyguanosine (8-OHdG) showed that the highest level of oxidation was observed after H2O2treatment. The distribution of oxidative lesions also differed depending on the genotoxic agent. 8-OHdG did not colocalize either with histone 3 (H3) or with type IIα + β topoisomerase (TOPO IIα + β) after H2O2treatment but matched perfectly with peroxiredoxin 6 (PRDX6), which is involved in H2O2metabolism. Our study reveals that the characteristics of the sperm head domains are responsible for access of the genotoxicants and cause differential degree of damage to nuclear areas, whereas chromatin packaging has a very limited relevance. The histone-enriched genes analyzed cannot be used as biomarkers of oxidative DNA damage.

Neuroinflammation is one of the critical events in neurodegenerative diseases, whereas microglia play an important role in the pathogenesis of neuroinflammation. In this study, we investigated the effects of a natural sesquiterpene lactone, 6-O-angeloylplenolin (6-OAP), isolated from the traditional Chinese medicine Centipeda minima (L.) A.Br., on neuroinflammation and the underlying mechanisms. We showed that treatment with lipopolysaccharide (LPS) caused activation of BV2 and primary microglial cells and development of neuroinflammation in vitro, evidenced by increased production of inflammatory cytokines TNF-α and IL-1β, the phosphorylation and nuclear translocation of NF-κB, and the transcriptional upregulation of COX-2 and iNOS, leading to increased production of proinflammatory factors NO and PGE2. Moreover, LPS treatment induced oxidative stress through increasing the expression levels of NOX2 and NOX4. Pretreatment with 6-OAP (0.5-4 μM) dose-dependently attenuated LPS-induced NF-κB activation and oxidative stress, thus suppressed neuroinflammation in the cells. In a mouse model of LPS-induced neuroinflammation, 6-OAP (5-20 mg·kg-1·d-1, ip, for 7 days before LPS injection) dose-dependently inhibited the production of inflammatory cytokines, the activation of the NF-κB signaling pathway, and the expression of inflammatory enzymes in brain tissues. 6-OAP pretreatment significantly ameliorated the activation of microglia and astrocytes in the brains. 6-OAP at a high dose caused a much stronger antineuroinflammatory effect than dexamethansone (DEX). Furthermore, we demonstrated that 6-OAP pretreatment could inhibit LPS-induced neurite and synaptic loss in vitro and in vivo. In conclusion, our results demonstrate that 6-OAP exerts antineuroinflammatory effects and can be considered a novel drug candidate for the treatment of neuroinflammatory diseases.

Multiple myeloma (MM) is an incurable cancer that derives pro-survival/proliferative signals from the bone marrow (BM) niche. Novel agents targeting not only cancer cells, but also the BM-niche have shown the greatest activity in MM. Histone deacetylases (HDACs) are therapeutic targets in MM and we previously showed that HDAC3 inhibition decreases MM proliferation both alone and in co-culture with bone marrow stromal cells (BMSC). In this study, we investigate the effects of HDAC3 targeting in BMSCs. Using both BMSC lines as well as patient-derived BMSCs, we show that HDAC3 expression in BMSCs can be induced by co-culture with MM cells. Knock-out (KO), knock-down (KD), and pharmacologic inhibition of HDAC3 in BMSCs results in decreased MM cell proliferation; including in autologous cultures of patient MM cells with BMSCs. We identified both quantitative and qualitative changes in exosomes and exosomal miRNA, as well as inhibition of IL-6 trans-signaling, as molecular mechanisms mediating anti-MM activity. Furthermore, we show that HDAC3-KD in BM endothelial cells decreases neoangiogenesis, consistent with a broad effect of HDAC3 targeting in the BM-niche. Our results therefore support the clinical development of HDAC3 inhibitors based not only on their direct anti-MM effects, but also their modulation of the BM microenvironment.

Glioma is the most lethal nervous system cancer. Recent studies have made great efforts to study the occurrence and development of glioma, but the molecular mechanisms are still unclear. This study was designed to reveal the molecular mechanisms of glioma based on protein-protein interaction network combined with machine learning methods. Key differentially expressed genes (DEGs) were screened and selected by using the protein-protein interaction (PPI) networks.

Our aim in this study was to develop quality indicators (QIs) for outpatient parenteral antimicrobial therapy (OPAT) care that can be used as metrics for quality assessment and improvement.

Microglia cells are the immune effector in the Central Nervous System (CNS). However, studies have showed that they contribute more to glioma progression than to its elimination. Rutin and its aglycone quercetin are flavonoids present in many fruits as well as plants and have been demonstrated to bear anti-inflammatory, antioxidant and antitumor properties also to human glioblastoma cell lines. Previous studies also demonstrated that rutin, isolated from the Brazilian plant Dimorphandra mollis Bent., presents immunomodulatory effect on astrocytes and microglia. In this study, we investigate the antitumor and immunomodulatory properties of rutin and its aglycone quercetin on the viability of glioma cells alone and under direct and indirect interaction with microglia. Flavonoid treatment of rat C6 glioma cells induced inhibition of proliferation and migration, and also induced microglia chemotaxis that was associated to the up regulation of tumor necrosis factor (TNF) and the down regulation of Interleukin 10 (IL-10) at protein and mRNA expression levels, regulation of mRNA expression for chemokines CCL2, CCL5 and CX3CL1, and Heparin Binding Growth Factor (HDGF), Insulin-like growth factor (IGF) and Glial cell-derived neurotrophic factor (GDNF) growth factors. Treatment of human U251 and TG1 glioblastoma cells with both flavonoids also modulated negatively the expression of mRNA for IL-6 and IL-10 and positively the expression of mRNA for TNF characterizing changes to the immune regulatory profile. Treatment of microglia and C6 cells either in co-cultures or during indirect interaction, via conditioned media from glioma cells treated with flavonoids or via conditioned media from microglia treated with flavonoids reduced proliferation and migration of glioma cells. It also directed microglia towards an inflammatory profile with increased expression of mRNA for IL-1β, IL-6, IL-18 and decreased expression of mRNA for nitric oxide synthase 2 (NOS2) and prostaglandin-endoperoxide synthase 2 (PTGS2), arginase and transforming growth factor beta (TGF-β), as well as Insulin-like growth factor (IGF). Treatment of U251 cells with flavonoids also reduced tumorigenesis when the cells were xenotransplanted in rat brains, and directed microglia and also astrocytes in the microenvironment of tumor cell implantation as well as in the brain parenchyma to a not favorable molecular inflammatory profile to the glioma growth, as observed in cultures. Together these results demonstrate that the flavonoid rutin and its aglycone quercetin present antiglioma effects related to the property of modulating the microglial inflammatory profile and may be considered for molecular and preclinical studies as adjuvant molecules for treatment of gliomas.

This study assessed the MRI findings of strangulated small bowel obstruction (SBO) and mesenteric venous occlusion (MVO) in a rabbit model using 3T MRI.

Recently, the use of 3D real inversion recovery (3D-real IR) imaging has been proposed for the evaluation of endolymphatic hydrops (EH). This method shows similar contrast between the endolymphatic and perilymphatic spaces and surrounding bone compared with the hybrid of reversed image of positive endolymph signal and native image of perilymph signal multiplied with heavily T2-weighted MR cisternography (HYDROPS-Mi2) image. We measured the volume of the endolymphatic space using 3D-real IR and HYDROPS-Mi2 images, and compared the measurements obtained with both techniques.

To investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health.

Although five-alpha reductase inhibitor (5-ARI) is one of standard treatment for benign prostatic hyperplasia (BPH) or alopecia, potential complications after 5-ARI have been issues recently. This study aimed to investigate the risk of depression after taking 5-ARI and to quantify the risk using meta-analysis.

Polycystic ovary syndrome (PCOS) is a complex gynecological endocrine disease commonly occurred in women of childbearing age. The main hallmark of PCOS includes elevated androgen production and insulin resistance (IR). Liuwei Dihuang Pills (LWDH Pills), a commonly prescribed traditional Chinese medicine (TCM) is widely used as a tonic prescription to treat diabetes, female menopause syndrome and other symptoms with'Kidney-Yin' deficiency. It has been reported the effects LWDH pills on PI3K/Akt signaling pathway in T2DM treatment. Recent studies have also indicated that the treatment of menopausal syndrome may be associated with the ovarian sexual hormone levels regulated by LWDH pills to alleviate female infertility. However, its potential benefits on PCOS have not been fully elucidated.

Muskoxen (Ovibos moschatus) are an integral component of Arctic biodiversity. Given low genetic diversity, their ability to respond to future and rapid Arctic change is unknown, although paleontological history demonstrates adaptability within limits. We discuss status and limitations of current monitoring, and summarize circumpolar status and recent variations, delineating all 55 endemic or translocated populations. Acknowledging uncertainties, global abundance is ca 170 000 muskoxen. Not all populations are thriving. Six populations are in decline, and as recently as the turn of the century, one of these was the largest population in the world, equaling ca 41% of today's total abundance. Climate, diseases, and anthropogenic changes are likely the principal drivers of muskox population change and result in multiple stressors that vary temporally and spatially. Impacts to muskoxen are precipitated by habitat loss/degradation, altered vegetation and species associations, pollution, and harvest. Which elements are relevant for a specific population will vary, as will their cumulative interactions. Our summaries highlight the importance of harmonizing existing data, intensifying long-term monitoring efforts including demographics and health assessments, standardizing and implementing monitoring protocols, and increasing stakeholder engagement/contributions.

Surgical implantation of cellular grafts into the brain is of increasing importance, as stem cell-based therapies for Parkinson and other diseases continue to develop. The effect of grafting technique on development and survival of the graft has received less attention. Rate and method of graft delivery may impact the cell viability and success of these therapies. Understanding the final location of the graft with respect to the intended target location is also critical.

Major depressive disorder (MDD) is one of the most common psychiatric disorders characterized by major depressive episodes. Although great efforts have been made to develop antidepressant drugs that target the monoaminergic system, these drugs are effective in only approximately 50% of MDD patients. In this study, we established a model of depression in PC12 cells using corticosterone to investigate the effect of ketamine and nuclear factor-κB (NF-κB) on the cell viability, apoptosis, levels of pro-inflammatory cytokines, apoptosis-related molecules, and enzymes of the Krebs cycle. PC12 cells were divided into control (no treatment, NC), ketamine treatment (KT), ketamine treatment with the inhibition of NF-κB (KI), and ketamine treatment with the overexpression of NF-κB (KO) group. Blood serum samples were collected from patients with MDD (n = 10) and healthy controls (n = 10) between 2015 and 2017. Ketamine significantly increased the viability and decreased the apoptosis of PC12 cells in KT and KI vs. NC group, but not in KO group. The levels of anti-apoptotic molecules and Krebs cycle enzymes were significantly increased in KI vs. KT group, while the levels of pro-apoptotic molecules and pro-inflammatory cytokines were decreased in KI vs. KT group. In addition, the levels of pro-inflammatory cytokines in the serum of MDD patients were significantly increased. The antidepressant effect of ketamine was enhanced in KI and reduced in KO group. Our results indicate that ketamine exerts its antidepressant effect via the inhibition of apoptosis and inflammation and the activation of the Krebs cycle in PC12 cells. NF-κB might be a potential therapeutic target in MDD.

DC-SIGN is previously focused on its physiologic and pathophysiologic roles in immune cells. Little is known about whether DC-SIGN is expressed in malignant epithelial cells and how DC-SIGN participates in tumor progression. Here we showed that DC-SIGN expression was increased in metastatic colorectal cancer (CRC) cell lines and patient tissues. The overall survival in CRC patients with positive DC-SIGN was remarkably reduced. Gain of DC-SIGN function facilitated the CRC metastases both in vitro and in vivo, and this effect was reversed by miR-185. DC-SIGN and Lyn interacted physically, and Lyn maintained the stability of DC-SIGN in cells. DC-SIGN activation recruited Lyn and p85 to form the DC-SIGN-Lyn-p85 complex, which promoted CRC metastasis by increasing PI3K/Akt/β-catenin signaling in tyrosine kinase Lyn-dependent manner. Furthermore, activation of DC-SIGN promoted the transcription of MMP-9 and VEGF by increasing PI3K/Akt/β-catenin signaling, and induced TCF1/LEF1-mediated suppression of miR-185. Our findings reveal the presence of the DC-SIGN-TCF1/LEF1-miR-185 loop in cancer cells with metastatic traits, implying that it may represent a new pathogenic mechanism of CRC metastasis. This character of the loop promises to provide new targets for blocking CRC invasive and metastatic activity.

Despite acknowledged benefits of residents in nursing homes spending time outdoors, little is known about factors related to their use of outdoor space. This systematic review summarizes reported barriers and enablers to nursing home residents' use of outdoor spaces.

Readthrough therapy relies on the use of small molecules that enable premature termination codons in mRNA open reading frames to be misinterpreted by the translation machinery, thus allowing the generation of full-length, potentially functional proteins from mRNA carrying nonsense mutations. In patients with hemophilia A, nonsense mutations potentially sensitive to readthrough agents represent approximately 16% of the point mutations. The aim of this study was to measure the readthrough effect of different compounds and to analyze the influence of premature termination codon context in selected nonsense mutations causing hemophilia A. To this end, primary fibroblasts from three patients with hemophilia A caused by nonsense mutations (p.W1586X, p.Q1636X and p.R1960X) and Chinese hamster ovary (CHO) cells transfected with 12 different plasmids encoding mutated F8 (p.Q462X, p.Q1705X, p.Q1764X, p.W274X, p.W1726X, p.W2015X, p.W2131X, p.R1715X, p.R1822X, p.R1960X, p.R2071X and p.R2228X) were treated with gentamicin, geneticin, PTC124, RTC13 or RTC14. Responses were assessed by analyzing not only F8 mRNA expression and FVIII biosynthesis (FVIII antigen by ELISA, western blot and immunofluorescence) but also the FVIII activity (by chromogenic assay). In the patients' fibroblasts, readthrough agents neither stabilized F8 mRNA nor increased FVIII protein or activity to detectable levels. In CHO cells, only in five of the 12 F8 variants, readthrough treatment increased both FVIII antigen and activity levels, which was associated with a reduction in intracellular accumulation of truncated forms and an increase in full-length proteins. These results provide experimental evidence of genetic context dependence of nonsense suppression by readthrough agents and of factors predicting responsiveness.

Although increased reactive oxygen species (ROS) generation is a major mechanism leading to cardiac remodeling in diabetes mellitus, research into the effects of anti-oxidation on diabetic cardiac remodeling remains scarce and controversial. Glucagon-like peptide-1 (GLP-1) shows potential anti-oxidative effects besides lowering blood glucose. The objective of this research was to investigate the effects of GLP-1 on cardiac remodeling and the molecular mechanism involved in diabetes mellitus.