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https://www.readbyqxmd.com/read/28346926/microbiota-and-obesity
#1
Erika Isolauri
Obesity is globally the most prevalent nutritional disorder. Multifaceted therapeutic approaches are called for to halt the cascade from neonatal adiposity/high birth weight to childhood excessive weight gain/adult obesity with comorbidities. Recent experimental and clinical data provide one new target for interventions aiming to close this vicious circle: the microbiota. An aberrant gut microbiota, dysbiosis, induces immune and metabolic disturbances both locally and, consequent upon impaired gut barrier function, also systemic low-grade inflammation, which is causally linked to insulin resistance...
2017: Nestlé Nutrition Institute Workshop Series
https://www.readbyqxmd.com/read/28346891/spatial-transcriptomics-paving-the-way-for-tissue-level-systems-biology
#2
REVIEW
Andreas E Moor, Shalev Itzkovitz
The tissues in our bodies are complex systems composed of diverse cell types that often interact in highly structured repeating anatomical units. External gradients of morphogens, directional blood flow, as well as the secretion and absorption of materials by cells generate distinct microenvironments at different tissue coordinates. Such spatial heterogeneity enables optimized function through division of labor among cells. Unraveling the design principles that govern this spatial division of labor requires techniques to quantify the entire transcriptomes of cells while accounting for their spatial coordinates...
March 24, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28346810/an-automated-multiplexed-hepatotoxicity-and-cyp-induction-assay-using-heparg-cells-in-2d-and-3d
#3
Lindsey M Ott, Karthik Ramachandran, Lisa Stehno-Bittel
Drug-induced liver injury (DILI) and drug-drug interactions (DDIs) are concerns when developing safe and efficacious compounds. We have developed an automated multiplex assay to detect hepatotoxicity (i.e., ATP depletion) and metabolism (i.e., cytochrome P450 1A [CYP1A] and cytochrome P450 3A4 [CYP3A4] enzyme activity) in two-dimensional (2D) and three-dimensional (3D) cell cultures. HepaRG cells were cultured in our proprietary micromold plates and produced spheroids. HepaRG cells, in 2D or 3D, expressed liver-specific proteins throughout the culture period, although 3D cultures consistently exhibited higher albumin secretion and CYP1A/CYP3A4 enzyme activity than 2D cultures...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346775/hyperinsulinism-causing-mutations-cause-multiple-molecular-defects-in-sur1-nbd1
#4
Claudia Paola Alvarez, Marijana Stagljar, D Ranjith Muhandiram, Voula Kanelis
The sulfonylurea receptor 1 (SUR1) protein forms the regulatory subunit in ATP sensitive K+ (KATP) channels in the pancreas. SUR proteins are members of the ATP-binding cassette (ABC) superfamily of proteins. Binding and hydrolysis of MgATP at the SUR nucleotide binding domains (NBDs) lead to channel opening. Pancreatic KATP channels play an important role in insulin secretion. SUR1 mutations that result in increased channel opening ultimately inhibit insulin secretion and lead to neonatal diabetes. In contrast, SUR1 mutations that disrupt trafficking and/or decrease gating of KATP channels cause congenital hyperinsulinism, where over secretion of insulin occurs even in the presence of low glucose...
March 27, 2017: Biochemistry
https://www.readbyqxmd.com/read/28346516/protective-immune-responses-against-schistosoma-mansoni-infection-by-immunization-with-functionally-active-gut-derived-cysteine-peptidases-alone-and-in-combination-with-glyceraldehyde-3-phosphate-dehydrogenase
#5
Hatem Tallima, Jan Dvořák, Sahira Kareem, Marwa Abou El Dahab, Nada Abdel Aziz, John Pius Dalton, Rashika El Ridi
BACKGROUND: Schistosomiasis, a severe disease caused by parasites of the genus Schistosoma, is prevalent in 74 countries, affecting more than 250 million people, particularly children. We have previously shown that the Schistosoma mansoni gut-derived cysteine peptidase, cathepsin B1 (SmCB1), administered without adjuvant, elicits protection (>60%) against challenge infection of S. mansoni or S. haematobium in outbred, CD-1 mice. Here we compare the immunogenicity and protective potential of another gut-derived cysteine peptidase, S...
March 27, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28346491/a-genetic-switch-controls-the-production-of-flagella-and-toxins-in-clostridium-difficile
#6
Brandon R Anjuwon-Foster, Rita Tamayo
In the human intestinal pathogen Clostridium difficile, flagella promote adherence to intestinal epithelial cells. Flagellar gene expression also indirectly impacts production of the glucosylating toxins, which are essential to diarrheal disease development. Thus, factors that regulate the expression of the flgB operon will likely impact toxin production in addition to flagellar motility. Here, we report the identification a "flagellar switch" that controls the phase variable production of flagella and glucosylating toxins...
March 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28346486/grem1-is-expressed-in-the-cancer-associated-myofibroblasts-of-basal-cell-carcinomas
#7
Hye Sung Kim, Myung Soo Shin, Min Seok Cheon, Jae Wang Kim, Cheol Lee, Woo Ho Kim, Young Sill Kim, Bo Gun Jang
Cancer-associated fibroblasts (CAFs) play important roles in cancer progression through their complex interactions with cancer cells. The secreted bone morphogenetic protein antagonist, gremlin1 (GREM1) is expressed by the CAFs of basal cell carcinomas (BCCs), and promotes the growth of cancer cells. In this study, we investigated the expression of GREM1 mRNAs in various benign and malignant skin tumors, including various BCC subtypes. Analysis by RNA in situ hybridization (ISH) revealed that fibroblasts in the scar tissue expressed GREM1 and α-smooth muscle actin (α-SMA), whereas resident fibroblasts in the dermis of the normal skin did not express GREM1...
2017: PloS One
https://www.readbyqxmd.com/read/28346471/effect-of-functional-sympathetic-nervous-system-impairment-of-the-liver-and-abdominal-visceral-adipose-tissue-on-circulating-triglyceride-rich-lipoproteins
#8
Michael F La Fountaine, Christopher M Cirnigliaro, Steven C Kirshblum, Cristin McKenna, William A Bauman
BACKGROUND: Interruption of sympathetic innervation to the liver and visceral adipose tissue (VAT) in animal models has been reported to reduce VAT lipolysis and hepatic secretion of very low density lipoprotein (VLDL) and concentrations of triglyceride-rich lipoprotein particles. Whether functional impairment of sympathetic nervous system (SNS) innervation to tissues of the abdominal cavity reduce circulating concentrations of triglyceride (TG) and VLDL particles (VLDL-P) was tested in men with spinal cord injury (SCI)...
2017: PloS One
https://www.readbyqxmd.com/read/28346345/unconventional-transport-routes-of-soluble-and-membrane-proteins-and-their-role-in-developmental-biology
#9
Andrea Pompa, Francesca De Marchis, Maria Teresa Pallotta, Yoselin Benitez-Alfonso, Alexandra Jones, Kerstin Schipper, Kevin Moreau, Viktor Žárský, Gian Pietro Di Sansebastiano, Michele Bellucci
Many proteins and cargoes in eukaryotic cells are secreted through the conventional secretory pathway that brings proteins and membranes from the endoplasmic reticulum to the plasma membrane, passing through various cell compartments, and then the extracellular space. The recent identification of an increasing number of leaderless secreted proteins bypassing the Golgi apparatus unveiled the existence of alternative protein secretion pathways. Moreover, other unconventional routes for secretion of soluble or transmembrane proteins with initial endoplasmic reticulum localization were identified...
March 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28346226/a-tlr9-dependent-checkpoint-governs-b-cell-responses-to-dna-containing-antigens
#10
Vishal J Sindhava, Michael A Oropallo, Krishna Moody, Martin Naradikian, Lauren E Higdon, Lin Zhou, Arpita Myles, Nathaniel Green, Kerstin Nündel, William Stohl, Amanda M Schmidt, Wei Cao, Stephanie Dorta-Estremera, Taku Kambayashi, Ann Marshak-Rothstein, Michael P Cancro
Mature B cell pools retain a substantial proportion of polyreactive and self-reactive clonotypes, suggesting that activation checkpoints exist to reduce the initiation of autoreactive B cell responses. Here, we have described a relationship among the B cell receptor (BCR), TLR9, and cytokine signals that regulate B cell responses to DNA-containing antigens. In both mouse and human B cells, BCR ligands that deliver a TLR9 agonist induce an initial proliferative burst that is followed by apoptotic death. The latter mechanism involves p38-dependent G1 cell-cycle arrest and subsequent intrinsic mitochondrial apoptosis and is shared by all preimmune murine B cell subsets and CD27- human B cells...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346102/phage-display-derived-ligand-for-mucosal-transcytotic-receptor-gp-2-promotes-antigen-delivery-to-m-cells-and-induces-antigen-specific-immune-response
#11
Inam Ullah Khan, Jiansheng Huang, Rui Liu, Jingbo Wang, Jun Xie, Naishuo Zhu
Successful oral immunization depends on efficient delivery of antigens (Ags) to the mucosal immune induction site. Glycoprotein-2 (GP-2) is an integral membrane protein that is expressed specifically on M cells within follicle-associated epithelium (FAE) and serves as transcytotic receptor for luminal Ags. In this study, we selected peptide ligands against recombinant human GP-2 by screening a phage display library and evaluated their interaction with GP-2 in vitro and ex vivo. Selected peptides were conjugated to the C-terminal of enhanced green fluorescence protein (EGFP) and evaluated for their ability to induce an immune response in mice...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346015/the-role-of-exosomes-derived-from-cerebrospinal-fluid-of-spinal-cord-injury-in-neuron-proliferation-in-vitro
#12
Fan-Long Kong, Xiao-Ping Wang, Ya-Nan Li, Hai-Xu Wang
Exosomes is a key component of cell paracrine secretion and can exert important effects in various disease models. However, the role of exosomes in neuron repair of spinal cord injury (SCI) has rarely been reported. In this study, Exosomes were isolated from cerebrospinal fluid of SCI and normal, and incubated neuron in vitro respectively to research its biological function in cell proliferation. The results demonstrated these exosomes all expressed CD9, CD63, CD81, Alix and Tsg101; however, only exosomes derived from cerebrospinal fluid of SCI could promote proliferation of neuron via ERK signaling pathway, and decrease cell apoptosis...
March 27, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28345941/the-roles-of-negative-affect-and-goal-adjustment-capacities-in-breast-cancer-survivors-associations-with-physical-activity-and-diurnal-cortisol-secretion
#13
Andree L Castonguay, Carsten Wrosch, Catherine M Sabiston
OBJECTIVE: This study examined whether within-person changes of breast cancer survivors' high-arousal negative affect (e.g., feeling scared, upset, anxious, or guilty) could predict high levels of diurnal cortisol secretion and moderate-to-vigorous physical activity (MVPA). In addition, goal adjustment capacities (goal disengagement and goal reengagement) were expected to buffer the effect of negative affect on cortisol and to increase its effect on MVPA. METHOD: High-arousal negative affect, self-reported MVPA, area-under-the-curve of diurnal cortisol secretion, and goal adjustment capacities were assessed in a longitudinal sample of 145 female breast cancer survivors...
April 2017: Health Psychology: Official Journal of the Division of Health Psychology, American Psychological Association
https://www.readbyqxmd.com/read/28345876/engineering-cellular-microenvironments-with-photo-and-enzymatically-responsive-hydrogels-toward-biomimetic-3d-cell-culture-models
#14
Roger Y Tam, Laura J Smith, Molly S Shoichet
Conventional cell culture techniques using 2D polystyrene or glass have provided great insight into key biochemical mechanisms responsible for cellular events such as cell proliferation, differentiation, and cell-cell interactions. However, the physical and chemical properties of 2D culture in vitro are dramatically different than those found in the native cellular microenvironment in vivo. Cells grown on 2D substrates differ significantly from those grown in vivo, and this explains, in part, why many promising drug candidates discovered through in vitro drug screening assays fail when they are translated to in vivo animal or human models...
March 27, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28345813/effect-of-the-interaction-between-mir-200b-3p-and-dnmt3a-on-cartilage-cells-of-osteoarthritis-patients
#15
Jian Wu, Yunjuan Tao, Anquan Shang, Weiwei Wang, Yujie Zhang, Liqing Hu, Jun Wang, Yuan Wang, Naizhou Guo
The aim of this research is to explore the effect of miR-200b-3p targeting DNMT3A on the proliferation and apoptosis of osteoarthritis (OA) cartilage cells. Quantitative RT-PCR was performed to analyse the expression of miR-200b-3p, DNMT3A, MMP1, MMP3, MMP9, MMP13 and COL II in normal and OA cartilage tissues. The dual-luciferase reporter assay and Western blot assay were conducted to confirm the targeting relationship between miR-200b-3p and DNMT3A. We also constructed eukaryotic expression vector to overexpress miR-200b-3p and DNMT3A...
March 27, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28345794/the-relationship-between-the-biovars-and-the-antimicrobial-resistance-of-ureaplasma-urealyticum-in-female-patients-with-urogenital-infections
#16
Yan Zhang, Chuan Hua, Su-Li Li
BACKGROUND: Ureaplasma urealyticum is considered as one of the main pathogens found in women with urogenital infection. This study aimed to investigate the relationship between the biovars, serovars, and their antimicrobial resistance against antibiotics in female patients with urogenital infection. METHODS: Two hundred and forty-six cervical secretion samples (125 female outpatients as the patient group, 121 healthy female subjects as the control group) were first collected and analyzed for U...
March 27, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28345790/metabolic-responses-to-exogenous-ghrelin-in-obesity-and-early-after-roux-en-y-gastric-bypass-in-humans
#17
Robyn A Tamboli, Joseph Antoun, Reem M Sidani, B Austin Clements, Emily A Eckert, Pam Marks-Shulman, Bruce D Gaylinn, D Brandon Williams, Ronald H Clements, Vance L Albaugh, Naji N Abumrad
AIMS: Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS: We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg(-1) min(-1) ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and two weeks after RYGB...
March 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28345602/a-primary-human-macrophage-enteroid-co-culture-model-to-investigate-mucosal-gut-physiology-and-host-pathogen-interactions
#18
Gaelle Noel, Nicholas W Baetz, Janet F Staab, Mark Donowitz, Olga Kovbasnjuk, Marcela F Pasetti, Nicholas C Zachos
Integration of the intestinal epithelium and the mucosal immune system is critical for gut homeostasis. The intestinal epithelium is a functional barrier that secludes luminal content, senses changes in the gut microenvironment, and releases immune regulators that signal underlying immune cells. However, interactions between epithelial and innate immune cells to maintain barrier integrity and prevent infection are complex and poorly understood. We developed and characterized a primary human macrophage-enteroid co-culture model for in-depth studies of epithelial and macrophage interactions...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345543/use-of-first-phase-insulin-secretion-in-early-diagnosis-of-thyroid-diabetes-and-type-2-diabetes-mellitus
#19
Li-Heng Meng, Yao Huang, Jia Zhou, Xing-Huan Liang, Jing Xian, Li Li, Ying-Fen Qin
BACKGROUND: A relationship between hyperthyroidism and insulin secretion in type 2 diabetes mellitus (T2DM) has been reported. Therefore, this study explored the use of first-phase insulin secretion in the differential diagnosis of thyroid diabetes (TDM) and T2DM. METHODS: In total, 101 patients with hyperthyroidism were divided into hyperthyroidism with normal glucose tolerance (TNGT), hyperthyroidism with impaired glucose regulation (TIGR), and diabetes (TDM) groups...
April 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28345525/tolerance-of-monocytes-and-macrophages-in-response-to-bacterial-endotoxin
#20
Ewelina Wiśnik, Ewa Pikus, Piotr Duchnowicz, Maria Koter-Michalak
Monocytes belong to myeloid effector cells, which constitute the first line of defense against pathogens, also called the nonspecific immune system and play an important role in the maintenance of tissue homeostasis. In response to stimulation, monocytes differentiate into macrophages capable of microorganism phagocytosis and secrete factors that play a key role in the regulation of immune responses. However excessive exposure of monocytes/macrophages to the lipopolysaccharide (LPS) of Gram negative bacteria leads to the acquisition of immune tolerance by these cells...
March 7, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
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