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Hikmat Al-Hashimi, Travis Chiarelli, Erik A Lundquist, Matthew Buechner
Regulation of luminal diameter is critical to the function of small single-celled tubes, of which the seamless tubular excretory canals of Caenorhabditis elegans provide a tractable genetic model. Mutations in several sets of genes exhibit the Exc phenotype, in which canal luminal growth is visibly altered. Here, a focused reverse genomic screen of genes highly expressed in the canals found 18 genes that significantly affect luminal outgrowth or diameter. These genes encode novel proteins as well as highly conserved proteins involved in processes including gene expression, cytoskeletal regulation, and vesicular and transmembrane transport...
March 18, 2019: G3: Genes—Genomes—Genetics
QiangQiang Wang, LingYan Wu, Muhammad Waqqas Hasan, MingMin Lu, WenJuan Wang, RuoFeng Yan, LiXin Xu, XiaoKai Song, XiangRui Li
BACKGROUND: Hepatocellular carcinoma-associated antigen 59 (HCA59), which is one of the most important excretory/secretory products of Haemonchus contortus (HcESPs), is known to have antigenic functions. However, its immunomodulatory effects on host cells are poorly understood. METHODS: Here, we cloned the HCA59 gene and expressed the recombinant protein of HCA59 (rHCA59). Binding activities of rHCA59 to goat peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) were checked by immunofluorescence assay (IFA) and the immunoregulatory effects of rHCA59 on cytokine secretions, cell migration, cell proliferation, nitric oxide production, and changes in expression of genes in related pathways were observed by co-incubation of rHCA59 with goat PBMCs and DCs...
March 14, 2019: Parasites & Vectors
Rachel A Stern, Paul E Mozdziak
Comparative aspects of ammonia toxicity, specific to liver and skeletal muscle and skeletal muscle metabolism between avian and mammalian species are discussed in the context of models for liver disease and subsequent skeletal muscle wasting. The purpose of this review is to present species differences in ammonia metabolism and to specifically highlight observed differences in skeletal muscle response to excess ammonia in avian species. Ammonia, which is produced during protein catabolism and is an essential component of nucleic acid and protein biosynthesis, is detoxified mainly in the liver...
March 12, 2019: Journal of Animal Physiology and Animal Nutrition
Xuemin Jin, Yong Yang, Xue Bai, Haining Shi, Wenbao Zhang, Zhuangzhi Zhang, Wanzhong Jia, Jiaojiao Lin, Mingyuan Liu, Xiaolei Liu
BACKGROUND: Therapeutic potential of helminth have been shown to have a protective effect on immune-mediated diseases such as Crohn's disease (CD), which is associated with increased production of T helper cell type 1. However, helminth therapy is unacceptable to patients due to side-effects and the fear of parasites. As helminths regulate the cellular immune responses through innate cells such as dendritic cells (DCs), cellular immunotherapy has been considered a therapeutic option to treat CD...
March 7, 2019: International Immunopharmacology
Zaher A Radi
Anatomically, the kidneys are paired, bean-shaped (in most mammals), excretory organs that lie in the retroperitoneum. High blood flow to the kidneys, together with high oxygen consumption, makes them more vulnerable to exposure, via the circulation, and subsequent injury related to high concentrations of xenobiotics and chemicals. In preclinical drug development and safety assessment of new investigational drugs, changes in kidney structure and/or function following drug administration in experimental laboratory animals need to be put in context with interspecies differences in kidney functional anatomy, physiology, spontaneous pathologies, and toxicopathological responses to injury...
March 7, 2019: International Journal of Toxicology
Eman Salah, Sheldon I Bastacky, Edwin K Jackson, Stevan P Tofovic
Estradiol may antagonize the adverse cardiovascular effects of angiotensin II (Ang II). We investigated the effects of 2-methoxyestradiol (2-ME), a nonestrogenic estradiol metabolite, on Ang II-induced cardiovascular and renal injury in male rats. First, we determined the effects of 2-ME on Ang II-induced acute changes in blood pressure, renal hemodynamics, and excretory function. Next, we investigated the effects of 2-ME and 2-hydroxyestardiol (2-HE) on hypertension and cardiovascular and renal injury induced by chronic infusion of Ang II...
March 2019: Journal of Cardiovascular Pharmacology
Xiao-Cui Luo, Zhen-Huang Chen, Jian-Bo Xue, Dong-Xiao Zhao, Chen Lu, Yi-Hong Li, Song-Min Li, Ya-Wen Du, Qun Liu, Ping Wang, Mingyuan Liu, Liquan Huang
The parasitic helminth Trichinella spiralis , which poses a serious health risk to animals and humans, can be found worldwide. Recent findings indicate that a rare type of gut epithelial cell, tuft cells, can detect the helminth, triggering type 2 immune responses. However, the underlying molecular mechanisms remain to be fully understood. Here we show that both excretory-secretory products (E-S) and extract of T. spiralis can stimulate the release of the cytokine interleukin 25 (IL-25) from the mouse small intestinal villi and evoke calcium responses from tuft cells in the intestinal organoids, which can be blocked by a bitter-taste receptor inhibitor, allyl isothiocyanate...
February 28, 2019: Proceedings of the National Academy of Sciences of the United States of America
Katja Venko, Marjana Novič
Phenols are the most abundant naturally accessible antioxidants present in a human normal diet. Since numerous beneficial applications of phenols as preventive agents in various diseases were revealed, the evaluation of phenols bioavailability is of high interest of researchers, consumers and drug manufacturers. The hydrophilic nature of phenols makes a cell membrane penetration difficult, which imply an alternative way of uptake via membrane transporters. However, the structural and functional data of membrane transporters are limited, thus the in silico modelling is really challenging and urgent tool in elucidation of transporter ligands...
February 27, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
John M Opitz, Marcia L Feldkamp, Lorenzo D Botto
Recent advances have now made it possible to speak of gastroschisis narrowly in morphogenetic terms invoking the Rittler-Beaudoin (R-B) model. This proceeds from the appreciation of gastroschisis as a congenital intestinal herniation (without cover or liver) within the primordial umbilical ring, mostly to the right side of a normally formed umbilical cord. Presently, it is unresolved whether this visceral prolapse represents failure of ring closure before return of the physiological hernia into the abdomen or rupture of the delicate amniotic/peritoneal membrane at the ring's edge to the right of the cord...
February 28, 2019: Birth Defects Research
Chelsea N Davis, Helen Phillips, John J Tomes, Martin T Swain, Toby J Wilkinson, Peter M Brophy, Russell M Morphew
BACKGROUND: Robust protocols for the isolation of extracellular vesicles (EVs) from the rest of their excretory-secretory products are necessary for downstream studies and application development. The most widely used purification method of EVs for helminth pathogens is currently differential centrifugation (DC). In contrast, size exclusion chromatography (SEC) has been included in the purification pipeline for EVs from other pathogens, highlighting there is not an agreed research community 'gold standard' for EV isolation...
February 27, 2019: PLoS Neglected Tropical Diseases
T Jiang, W Li, D Lin, J Wang, F Liu, Z Ding
AIM: To analyse the imaging features of metanephric adenoma (MA) and their pathological correlation. MATERIALS AND METHODS: The imaging findings in 11 patients with MA were studied retrospectively. Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) findings were studied in seven, 11, and six patients, respectively. The enhancement pattern, attenuation, lesion location, size, cystic or solid appearance, capsule sign, and presence of calcifications were evaluated...
February 22, 2019: Clinical Radiology
Martha-Spyridoula Katsarou, Maria Papasavva, Rozana Latsi, Nikolaos Drakoulis
Hereditary Hemochromatosis (HH) is an autosomal recessive genetic disease, characterized by an excessively increased absorption of dietary iron. Excess iron can be accumulated because of the lack of an effective excretory mechanism leading to toxic effects. HH is one of the most common genetic disorders in individuals of European descent. Genetic polymorphisms of the HFE gene (rs1800562, rs1799945 and rs1800730) also affect the normal activity of another protein, hepcidin, a negative regulator of iron homeostasis...
2019: Vitamins and Hormones
I Potters, L Van Duffel, G Broeckx, E Bottieau
We report a case of intestinal schistosomiasis in a patient who had not travelled outside Europe after migrating 20 years ago. Images of the Schistosoma mansoni eggs are shown that confirm the active nature of the infection.
February 20, 2019: Clinical Microbiology and Infection
Hakim Azizi, Hadi Mirzaeei, Amin Bagheri, Ali Bazi, Ali Khamesipour, Hajar Yaghoobi, Aliyar Mirzapour, Mehrdad Khatami, Samira Elikaee
BACKGROUND: Fasciolosis is a zoonotic parasitic disease imposing a heavy load of livestock losses worldwide. PURPOSE: We aimed to evaluate immune-stimulatory effects of naloxone (NLX), an opioid receptor antagonist, in combination with alum in mice vaccinated with excretory-secretory antigens (E/S) of Fasciola hepatica. METHODS: 8-week-old female BALB/c mice were subcutaneously vaccinated using E/S antigens of F. hepatica. Experimental groups (14 mice per group) included: vaccine (E/S antigen), alum vaccine (E/S antigen plus alum), NLX vaccine (E/S antigen plus NLX), and alum-NLX vaccine (E/S antigen plus a mixture of alum-NLX)...
February 20, 2019: Acta Parasitologica
Jinglong Chen, Fuli Ma, Xiangrui Li, Ruqian Zhao, Xiaojing Yang
Haemonchus contortus is a highly pathogenic gastrointestinal nematode of small ruminant animals. In modern intensive farming, livestock often suffer from different types of stress. However, whether host stress hormones influence H. contortus infection is largely unknown. Therefore, we treated H. contortus with norepinephrine (NE) and analyzed the changes in its excretory/secretory products (ESPs). Label-free quantitative proteomic analysis was used to identify differences in body proteins and ESPs between the control and NE-treated groups...
February 20, 2019: Parasitology Research
Vasti Aguayo, Bianca N Valdés Fernandez, Madeline Rodríguez-Valentín, Caleb Ruiz-Jiménez, Marcos J Ramos-Benítez, Loyda B Méndez, Ana M Espino
Parasitic helminths and helminth-derived molecules have demonstrated to possess powerful anti-inflammatory properties and confirmed therapeutic effects on inflammatory diseases. The helminth Fasciola hepatica has been reported to suppress specific Th1 specific immune responses induced by concurrent bacterial infections, thus demonstrating its anti-inflammatory ability in vivo. In this study, we demonstrate that native F. hepatica glutathione S-transferase (nFhGST), a major parasite excretory-secretory antigen, majorly comprised of Mu-class GST isoforms, significantly suppresses the LPS-induced TNFα and IL1β of mouse bone-marrow derived macrophages in vitro and the pro-inflammatory cytokine/chemokine storm within C57BL/6 mice exposed to lethal doses of LPS increasing their survival rate by more than 85%...
February 19, 2019: Scientific Reports
Heidi Coy, Kevin Hsieh, Willie Wu, Mahesh B Nagarajan, Jonathan R Young, Michael L Douek, Matthew S Brown, Fabien Scalzo, Steven S Raman
PURPOSE: Currently, all solid enhancing renal masses without microscopic fat are considered malignant until proven otherwise and there is substantial overlap in the imaging findings of benign and malignant renal masses, particularly between clear cell RCC (ccRCC) and benign oncocytoma (ONC). Radiomics has attracted increased attention for its utility in pre-operative work-up on routine clinical images. Radiomics based approaches have converted medical images into mineable data and identified prognostic imaging signatures that machine learning algorithms can use to construct predictive models by learning the decision boundaries of the underlying data distribution...
February 18, 2019: Abdominal Radiology
Peter Lykke Eriksen, Michael Sørensen, Henning Grønbæk, Stephen Hamilton-Dutoit, Hendrik Vilstrup, Karen Louise Thomsen
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a major health concern affecting 25% of the world's population. It is generally held that a fatty liver does not influence liver function, but quantitative measurements of metabolic liver functions have not been systematically performed. We aimed to study selected hepatocellular metabolic functions in patients with different stages of NAFLD. METHODS: Twenty-five non-diabetic, biopsy-proven NAFLD patients [12 with simple steatosis; 13 with non-alcoholic steatohepatitis (NASH)] and ten healthy controls were included in a cross-sectional study...
February 12, 2019: Clinics and Research in Hepatology and Gastroenterology
Eleni Karakike, Evangelos J Giamarellos-Bourboulis
Hemophagocytic lymphohistocytosis (HLH) is characterized by fulminant cytokine storm leading to multiple organ dysfunction and high mortality. HLH is classified into familial (fHLH) and into secondary (sHLH). fHLH is rare and it is due to mutations of genes encoding for perforin or excretory granules of natural killer (NK) cells of CD8-lymphocytes. sHLH is also known as macrophage activation syndrome (MAS). Macrophage activation syndrome (MAS) in adults is poorly studied. Main features are fever, hepatosplenomegaly, hepatobiliary dysfunction (HBD), coagulopathy, cytopenia of two to three cell lineages, increased triglycerides and hemophagocytosis in the bone marrow...
2019: Frontiers in Immunology
Luke J Norbury, Katarzyna Basałaj, Piotr Bąska, Alicja Sielicka, Anna Zawistowska-Deniziak, Huan Yong Yap, Przemysław Wilkowski, Agnieszka Wesołowska, Halina Wędrychowicz
Phage display technology to produce recombinant monoclonal antibodies or antibody fragments permits the identification of sought after antibodies in short time frames at low cost along with direct and rapid selection for antibody characteristics. Monoclonal antibodies can facilitate the identification and characterisation of parasite molecules that function at the host-parasite interface to help understand at the molecular level the biology of the parasite and disease progression, which often leads to new drug targets, diagnostic antigens or vaccine candidates...
February 11, 2019: Experimental Parasitology
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