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https://www.readbyqxmd.com/read/28320131/epigenetic-and-gene-expression-alterations-of-foxp3-in-the-t-cells-of-eae-mouse-model-of-multiple-sclerosis
#1
Ali Noori-Zadeh, Seyed Alireza Mesbah-Namin, Ali Akbar Saboor-Yaraghi
Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination and neurodegeneration of the central nervous system. It has been shown that the regulatory T (Treg) cells are responsible for maintaining tolerance to self-antigens and can suppress the autoimmune process in several animal models such as experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Recent basic studies have demonstrated that forkhead box P (FOXP3) and BTB domain and CNC homolog 2 (BACH2) are the master transcription factors of these cells playing a pivotal role in the polarization of naïve T cells into Treg cells...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28320090/treatment-with-anti-programmed-cell-death-1-pd-1-antibody-restored-postoperative-cd8-t-cell-dysfunction-by-surgical-stress
#2
Zhirong Sun, Anrong Mao, Yun Wang, Yanjun Zhao, Jiawei Chen, Pingbo Xu, Changhong Miao
Millions of patients benefit from surgery and are exposed to surgical stress. However, ample studies suggest that surgical stress contributes to tumor recurrence or distant metastases. Surgical stress suppresses CD8+ T cells (CTL) function which is vital for eliminating the malignant cells. Anti-programmed cell death 1 (PD-1) therapy is an effective and safe treatment that increases survival rate of patients with multiple cancers, however, whether anti-PD-1 therapy is able to reverse the immunosuppression following surgery remains largely unknown...
March 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320089/mir-448-is-a-novel-prognostic-factor-of-lung-squamous-cell-carcinoma-and-regulates-cells-growth-and-metastasis-by-targeting-dclk1
#3
Changting Shan, Fan Fei, Fengzhu Li, Bo Zhuang, Yulong Zheng, Yufeng Wan, Jianhui Chen
MicroRNA-448 (miR-448) has been showed to be low-expressed and function as tumor suppressor in most human cancers. However, there are limited reports on the clinical significance and biological function of miR-448 in lung squamous cell carcinoma. In this study, we observed that miR-448 expression was decreased in lung squamous cell carcinoma tissues and cell lines. Meanwhile, miR-448 expression associated with differentiated degree, T classification (tumor size), N classification (lymph node metastasis), M classification (distant metastasis), clinical stage and prognosis of lung squamous cell carcinoma patients...
March 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320046/increased-insulin-resistance-and-glucagon-levels-in-mild-inactive-systemic-lupus-patients-despite-normal-glucose-tolerance
#4
Cíntia Nh Miyake, Bruno Gualano, Wagner S Dantas, Renato T Pereira, William Neves, Vanessa O Zambelli, Samuel K Shinjo, Rosa M Pereira, Elizabeth R Silva, Ana Lúcia Sá-Pinto, Eduardo Borba, Hamilton Roschel, Eloisa Bonfá, Fabiana B Benatti
OBJECTIVE: To assess insulin sensitivity in patients with systemic lupus erythematosus (SLE) in response to a meal tolerance test (MTT). METHODS: In this cross-sectional study, 33 adult females mild/inactive SLE and 16 age- and body mass index (BMI)-matched female healthy controls (CTRL) underwent a MTT and were assessed for insulin sensitivity and beta-cell function. Skeletal muscle protein expressions of total and membrane GLUT-4 were also evaluated (SLE, n=10; CTRL, n=5); muscle biopsies were performed after MTT...
March 20, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28320030/changes-in-regulatory-t-cell-levels-in-acute-cerebral-ischemia
#5
Xuerui Pang, Weidong Qian
Background Acute stroke causes intense and significant changes in the immune system as well as in the number and the ratio of various immune cells. Material and Methods Several large-scale studies have shown that ischemic stroke leaves the human body in a state of immunodepression. The regulatory T (Treg) cells may be strongly associated with a change of immune status. In this trial, we collected venous blood from a cohort of patients who were diagnosed with acute ischemic stroke within the last 24 hours (n = 139)...
March 20, 2017: Journal of Neurological Surgery. Part A, Central European Neurosurgery
https://www.readbyqxmd.com/read/28319890/one-year-follow-up-of-clinical-metabolic-and-oxidative-stress-profile-of-morbid-obese-patients-after-laparoscopic-sleeve-gastrectomy-8-oxo-dg-as-a-clinical-marker
#6
Lidia Monzo-Beltran, Antonio Vazquez-Tarragón, Concha Cerdà, Paula Garcia-Perez, Antonio Iradi, Carlos Sánchez, Benjamin Climent, Carmen Tormos, Antonio Vázquez-Prado, Javier Girbés, Nuria Estáñ, Sebastián Blesa, Raquel Cortés, Felipe J Chaves, Guillermo T Sáez
Obesity has grown worldwide over the last few decades. In its different degrees, obesity is accompanied by many clinical and biochemical alterations reflecting the pathological condition of various body tissues. Among the mechanisms underlying the pathogenesis of obesity and associated complications, oxidative stress (OS) may be playing an important role. In the present study, we have characterized at systemic level the degree of OS status in a group of morbid obese patients (BMI>40kg/m(2)) at basal sate and its modulation during one year after bariatric surgery using the laparoscopic sleeve gastrectomy (LSG) technique...
February 14, 2017: Redox Biology
https://www.readbyqxmd.com/read/28319732/an-antigen-to-remember-regulation-of-b-cell-memory-in-health-and-disease
#7
REVIEW
Aleta Pupovac, Kim L Good-Jacobson
Vaccine success relies on the formation of immunity. Humoral immunity is critical and is mediated by long-lived antibody-secreting cells and memory B cells (MBCs). Chronic infectious diseases cause a significant global burden of disease; pathogens that evade the immune system can cause phenotypical and functional changes to immune memory populations. Thus, recent studies have focused on MBC subset function. IgM(+) MBCs have emerged as important early responders in malaria. Atypical MBCs have functional qualities associated with exhaustion in chronic infectious diseases, but the requirements for their formation and where they localize remains unknown...
March 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319730/deconstructing-the-germinal-center-one-cell-at-a-time
#8
REVIEW
Chad R Dufaud, Louise J McHeyzer-Williams, Michael G McHeyzer-Williams
Successful vaccination relies on driving the immune response towards high specificity, affinity and longevity. Germinal centers facilitate the evolution of antigen-specific B cells by iterative rounds of diversification, selection, and differentiation to memory and plasma cells. Experimental evidence points to B cell receptor affinity and amount of antigen presented to follicular helper T cells as main drivers of clonal evolution. Concurrent studies suggest that modifiers of cognate contact, temporal mechanisms, and stochastic factors can also shape diversity and influence differentiation to memory and plasma cells, but molecular pathways driving these selection decisions are unresolved...
March 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319634/late-onset-bexarotene-induced-cd4-lymphopenia-in-a-cutaneous-t-cell-lymphoma-patient
#9
Karin Eshagh, Laura S Romero, Jessica K So, Xianfeng Frank Zhao
Various infections, autoimmune diseases, medications, and total-body irradiation are known factors associated with CD4 lymphopenia, defined as a CD4 T-cell count below 300 cells/mL or less than 20% of total lymphocytes. We report a rare case of a patient with cutaneous T-cell lymphoma (CTCL) who developed profound CD4 lymphopenia in the setting of long-term bexarotene therapy. Bexarotene is a third-generation retinoid that inhibits epithelial cell proliferation and is approved for treatment of advanced CTCL (stages IIB-IVB) in adult patients who have failed at least 1 prior systemic therapy...
February 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28319610/capillary-k-sensing-initiates-retrograde-hyperpolarization-to-increase-local-cerebral-blood-flow
#10
Thomas A Longden, Fabrice Dabertrand, Masayo Koide, Albert L Gonzales, Nathan R Tykocki, Joseph E Brayden, David Hill-Eubanks, Mark T Nelson
Blood flow into the brain is dynamically regulated to satisfy the changing metabolic requirements of neurons, but how this is accomplished has remained unclear. Here we demonstrate a central role for capillary endothelial cells in sensing neural activity and communicating it to upstream arterioles in the form of an electrical vasodilatory signal. We further demonstrate that this signal is initiated by extracellular K(+) -a byproduct of neural activity-which activates capillary endothelial cell inward-rectifier K(+) (KIR2...
March 20, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28319586/short-term-exercise-training-alters-leukocyte-chemokine-receptors-in-obese-adults
#11
Julianne C Barry, Svetlana Simtchouk, Cody Durrer, Mary E Jung, Jonathan P Little
Obesity is characterized by chronic low-grade inflammation driven by activation and tissue infiltration of circulating leukocytes. Although exercise has anti-inflammatory effects, the impact of exercise on mediators of leukocyte migration is unclear. PURPOSE: To determine the impact of high intensity interval training (HIIT) versus moderate intensity continuous training (MICT), in the absence of weight/fat loss, on circulating chemokines and leukocyte chemokine receptors. METHODS: Thirty-seven inactive obese adults were randomized to two weeks (10 sessions) of HIIT or MICT with fasting blood samples collected before and after training...
March 18, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28319565/bone-marrow-graft-versus-host-disease-in-major-histocompatibility-complex-matched-murine-reduced-intensity-allogeneic-hemopoietic-cell-transplantation
#12
Kifah Shahin, Zamil Mattar, Pablo Silveira, Wei-Hsun Hsu, Linda Bendall, Derek Hart, Kenneth F Bradstock
BACKGROUND: Most clinical allogeneic hemopoietic cell transplants (alloHCT) are now performed using reduced intensity conditioning (RIC) instead of myeloablative (MAC) conditioning, however, the biology underlying this treatment remains incompletely understood. METHODS: We investigated a murine model of major histocompatibility complex (MHC)-matched multiple minor histocompatibility antigen mismatched alloHCT, using bone marrow (BM) cells and splenocytes from B6 (H-2) donor mice transplanted into BALB...
March 18, 2017: Transplantation
https://www.readbyqxmd.com/read/28319486/igg4-related-disease
#13
Emanuele Bozzalla Cassione, John H Stone
PURPOSE OF REVIEW: Remarkable insights have been gleaned recently with regard to the pathophysiology of IgG4-related disease (IgG4-RD). These findings have direct implications for the development of targeted strategies for the treatment of this condition. RECENT FINDINGS: Oligoclonal expansions of cells of both the B and T lymphocyte lineages are present in the blood of patients with IgG4-RD. Oligoclonal expansions of plasmablasts are a good biomarker for disease activity...
March 17, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28319462/late-effects-of-exposure-to-ionizing-radiation-and-age-on-human-thymus-morphology-and-function
#14
Reiko Ito, Laura P Hale, Susan M Geyer, Jie Li, Andrew Sornborger, Junko Kajimura, Yoichiro Kusunoki, Kengo Yoshida, Marcel R M van den Brink, Seishi Kyoizumi, Nancy R Manley, Kei Nakachi, Gregory D Sempowski
The thymus is essential for proper development and maintenance of a T-cell repertoire that can respond to newly encountered antigens, but its function can be adversely affected by internal factors such as pregnancy and normal aging or by external stimuli such as stress, infection, chemotherapy and ionizing radiation. We have utilized a unique archive of thymus tissues, obtained from 165 individuals, exposed to the 1945 atomic bomb blast in Hiroshima, to study the long-term effects of receiving up to ∼3 Gy dose of ionizing radiation on human thymus function...
March 20, 2017: Radiation Research
https://www.readbyqxmd.com/read/28319449/non-clinical-study-examining-aav8-tbg-hldlr-vector-associated-toxicity-in-chow-fed-wild-type-and-ldlr-rhesus-macaques
#15
Jenny A Greig, Maria P Limberis, Peter Bell, Shu-Jen Chen, Roberto Calcedo, Daniel J Rader, James M Wilson
Vectors based on adeno-associated virus serotype 8 (AAV8) have been evaluated in several clinical trials of gene therapy for hemophilia B with encouraging results. In preparation for a Phase 1 clinical trial of AAV8 gene therapy for the treatment of homozygous familial hypercholesterolemia (HoFH), the safety of the clinical candidate vector, AAV8.TBG.hLDLR, was evaluated in wild-type rhesus macaques and macaques heterozygous for a nonsense mutation in the low-density lipoprotein receptor (LDLR) gene (LDLR(+/-))...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28319448/rationale-and-design-of-a-phase-1-clinical-trial-to-evaluate-hsv-g207-alone-or-with-a-single-radiation-dose-in-children-with-progressive-or-recurrent-malignant-supratentorial-brain-tumors
#16
Alicia M Waters, James M Johnston, Alyssa T Reddy, John Fiveash, Avi Madan-Swain, Kara Kachurak, Asim K Bag, G Yancey Gillespie, James M Markert, Gregory K Friedman
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer-related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy, and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor-specific tropism and potential efficacy in the treatment of malignant brain tumors...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28319404/encapsulation-of-an-ep67-conjugated-ctl-peptide-vaccine-in-nanoscale-biodegradable-particles-increases-the-efficacy-of-respiratory-immunization-and-affects-the-magnitude-and-memory-subsets-of-vaccine-generated-mucosal-and-systemic-cd8-t-cells-in-a-diameter
#17
Bala Vamsi Krishna Karuturi, Shailendra B Tallapaka, Pravin Yeapuri, Stephen M Curran, Sam D Sanderson, Joseph A Vetro
The diameter of biodegradable particles used to co-encapsulate immunostimulants and subunit vaccines affects the magnitude of memory CD8(+) T cells generated by systemic immunization. Possible effects on the magnitude of CD8(+) T cells generated by mucosal immunization or memory subsets that potentially correlate more strongly with protection against certain pathogens, however, are unknown. In this study, we conjugated our novel host-derived mucosal immunostimulant, EP67, to the protective MCMV CTL epitope, pp89, through a lysosomal protease-labile double arginine linker (pp89-RR-EP67) and encapsulated in PLGA 50:50 micro- or nanoparticles...
March 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28319389/potential-antiosteoporotic-natural-product-lead-compounds-that-inhibit-17%C3%AE-hydroxysteroid-dehydrogenase-type-2
#18
Anna Vuorinen, Roger T Engeli, Susanne Leugger, Fabio Bachmann, Muhammad Akram, Atanas G Atanasov, Birgit Waltenberger, Veronika Temml, Hermann Stuppner, Liselotte Krenn, Sylvin B Ateba, Dieudonné Njamen, Rohan A Davis, Alex Odermatt, Daniela Schuster
17β-Hydroxysteroid dehydrogenase type 2 (17β-HSD2) converts the active steroid hormones estradiol, testosterone, and 5α-dihydrotestosterone into their weakly active forms estrone, Δ(4)-androstene-3,17-dione, and 5α-androstane-3,17-dione, respectively, thereby regulating cell- and tissue-specific steroid action. As reduced levels of active steroids are associated with compromised bone health and onset of osteoporosis, 17β-HSD2 is considered a target for antiosteoporotic treatment. In this study, a pharmacophore model based on 17β-HSD2 inhibitors was applied to a virtual screening of various databases containing natural products in order to discover new lead structures from nature...
March 20, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28319275/mrf-ann-a-machine-learning-approach-for-automated-er-scoring-of-breast-cancer-immunohistochemical-images
#19
T Mungle, S Tewary, D K DAS, I Arun, B Basak, S Agarwal, R Ahmed, S Chatterjee, C Chakraborty
Molecular pathology, especially immunohistochemistry, plays an important role in evaluating hormone receptor status along with diagnosis of breast cancer. Time-consumption and inter-/intraobserver variability are major hindrances for evaluating the receptor score. In view of this, the paper proposes an automated Allred Scoring methodology for estrogen receptor (ER). White balancing is used to normalize the colour image taking into consideration colour variation during staining in different labs. Markov random field model with expectation-maximization optimization is employed to segment the ER cells...
March 20, 2017: Journal of Microscopy
https://www.readbyqxmd.com/read/28319114/internally-tagged-ubiquitin-a-tool-to-identify-linear-polyubiquitin-modified-proteins-by-mass-spectrometry
#20
Katarzyna Kliza, Christoph Taumer, Irene Pinzuti, Mirita Franz-Wachtel, Simone Kunzelmann, Benjamin Stieglitz, Boris Macek, Koraljka Husnjak
Ubiquitination controls a plethora of cellular processes. Modifications by linear polyubiquitin have so far been linked with acquired and innate immunity, lymphocyte development and genotoxic stress response. Until now, a single E3 ligase complex (LUBAC), one specific deubiquitinase (OTULIN) and a very few linear polyubiquitinated substrates have been identified. Current methods for studying lysine-based polyubiquitination are not suitable for the detection of linear polyubiquitin-modified proteins. Here, we present an approach to discovering linear polyubiquitin-modified substrates by combining a lysine-less internally tagged ubiquitin (INT-Ub...
March 20, 2017: Nature Methods
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