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https://www.readbyqxmd.com/read/27913779/comparison-of-proliferative-and-immunomodulatory-potential-of-adipose-derived-mesenchymal-stem-cells-from-young-and-geriatric-cats
#1
Lara B Zajic, Tracy L Webb, Polly Webb, Jonathan W Coy, Steve W Dow, Jessica M Quimby
OBJECTIVES: The objective of this study was to compare the ability of adipose-derived mesenchymal stem cells (aMSC) generated from young vs geriatric cats to proliferate in culture, suppress lymphocyte proliferation and undergo senescence. METHODS: Adipose tissues from five young (<5 years) and six geriatric (>10 years) cats were harvested and cryopreserved for subsequent aMSC isolation and culture. aMSC proliferation in culture was compared via determination of time until passage two and by 3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay...
December 2, 2016: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/27913677/phlpping-through-history-a-decade-in-the-life-of-phlpp-phosphatases
#2
REVIEW
Agnieszka T Grzechnik, Alexandra C Newton
In the decade since their discovery, the PH domain leucine-rich repeat protein phosphatases (PHLPP) have emerged as critical regulators of cellular homeostasis, and their dysregulation is associated with various pathophysiologies, ranging from cancer to degenerative diseases, such as diabetes and heart disease. The two PHLPP isozymes, PHLPP1 and PHLPP2, were identified in a search for phosphatases that dephosphorylate Akt, and thus suppress growth factor signaling. However, given that there are over 200 000 phosphorylated residues in a single cell, and fewer than 50 Ser/Thr protein phosphatases, it is not surprising that PHLPP has many other cellular functions yet to be discovered, including a recently identified role in regulating the epigenome...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913604/conversion-of-t-cells-to-b-cells-by-inactivation-of-polycomb-mediated-epigenetic-suppression-of-the-b-lineage-program
#3
Tomokatsu Ikawa, Kyoko Masuda, Takaho A Endo, Mitsuhiro Endo, Kyoichi Isono, Yoko Koseki, Rinako Nakagawa, Kohei Kometani, Junichiro Takano, Yasutoshi Agata, Yoshimoto Katsura, Tomohiro Kurosaki, Miguel Vidal, Haruhiko Koseki, Hiroshi Kawamoto
In general, cell fate is determined primarily by transcription factors, followed by epigenetic mechanisms fixing the status. While the importance of transcription factors controlling cell fate has been well characterized, epigenetic regulation of cell fate maintenance remains to be elucidated. Here we provide an obvious fate conversion case, in which the inactivation of polycomb-medicated epigenetic regulation results in conversion of T-lineage progenitors to the B-cell fate. In T-cell-specific Ring1A/B-deficient mice, T-cell development was severely blocked at an immature stage...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913426/depletion-of-circulating-monocytes-suppresses-il-17-and-hmgb1-expression-in-mice-with-lps-induced-acute-lung-injury
#4
Zhilong Jiang, Qianlin Zhou, Chenlin Gu, Dandan Li, Lei Zhu
Acute lung injury/Acute Respiratory distress syndrome (ALI/ARDS) is an important cause of mortality in critically ill patients. Macrophages play an important role in the pathogenesis of ALI/ARDS. To investigate the role and underlying mechanisms of circulating monocytes and resident alveolar macrophages (AMs) in ALI/ARDS, we depleted circulating monocytes and AMs by clodronate-loaded liposome (CL) in lipopolysaccharide (LPS)-induced ALI/ARDS mouse model. Our results indicated that depletion of circulating monocytes by intravenous (i...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#5
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
November 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27913219/tbx2-regulates-anterior-neural-specification-by-repressing-fgf-signaling-pathway
#6
Gun-Sik Cho, Dong-Seok Park, Sun-Cheol Choi, Jin-Kwan Han
During early embryogenesis, FGF signals regulate the antero-posterior (AP) patterning of the neural plate by promoting posterior cell fates. In particular, BMP signal-mediated attenuation of FGF pathway plays a critical role in the determination of the anterior neural region. Here we show that Tbx2, a T-box transcriptional repressor regulates anterior neural specification by suppressing FGF8 signaling pathway in Xenopus embryo. Tbx2 is expressed in the anterior edge of the neural plate in early neurulae. Overexpression and knockdown of Tbx2 induce expansion and reduction in the expression of anterior neural markers, respectively...
November 29, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27912872/anti-allergic-potential-of-typhonium-blumei-inhibition-of-degranulation-via-suppression-of-pi3k-plc%C3%AE-2-phosphorylation-and-calcium-influx
#7
Michal Korinek, Kuan-Ming Chen, Yu-Han Jiang, Mohamed El-Shazly, Joel Stocker, Chon-Kit Chou, Tsong-Long Hwang, Yang-Chang Wu, Bing-Hung Chen, Fang-Rong Chang
BACKGROUND: Typhonium blumei Nicolson & Sivadasan (Araceae) is a traditional Chinese medicinal herb possessing detumescent, detoxifying, and anti-inflammatory activities. It is used in Taiwan as a folk medicine to treat cancer and inflammatory diseases. Typhonium blumei is usually not distinguished from Typhonium roxburghii Schott and they are commonly used interchangeably. PURPOSE: To evaluate and compare the anti-allergic and anti-inflammatory properties of T...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912762/regulation-of-effector-function-of-cns-autoreactive-cd4-t-cells-through-inhibitory-receptors-and-il-7r%C3%AE
#8
Patrick K Nuro-Gyina, Elizabeth L Rieser, Marissa C Granitto, Wei Pei, Yue Liu, Priscilla W Lee, Saba Aqel, Jian Zhang, Amy E Lovett-Racke, Michael K Racke, Yuhong Yang
BACKGROUND: Multiple sclerosis (MS) is a chronic CNS autoimmune disease characterized by inflammation, demyelination, and neuronal degeneration, where myelin-specific CD4 T cells play critical roles in the formation of acute MS lesions and disease progression. The suppression of IL-7Rα expression and the upregulation of inhibitory receptors (PD-1, etc.) are essential parts of the cell-intrinsic immunosuppressive program regulating T effector functions to prevent autoimmunity. However, little is known on the factors regulating IL-7Rα/PD-1 balance in myelin-specific CD4 T effector/memory cells during the development of CNS autoimmunity...
December 3, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27912145/chloroquine-cq-exerts-anti-breast-cancer-through-modulating-microenvironment-and-inducing-apoptosis
#9
Yanjun Zhang, Yu Cao, Xiaodan Sun, Yonghui Feng, Yunting Du, Fei Liu, Chunyun Yu, Feng Jin
CQ is an anti-malaria drug, which has been used for years. However, there are published articles about its activity in anti-cancers. The aim of this approach was to look at possibility and related mechanisms of anti-breast cancer (mouse breast cancer cell line 4T1) by CQ alone. The studies of anti 4T1 in vitro and in vivo by CQ were performed. The growth of 4T1 in vitro and in vivo, survival of mice post treatment with CQ, changes of immune parameters and microenvironment in mice were evaluated. Our results demonstrate that CQ could markedly inhibit growth of 4T1 in vitro through inducing apoptosis of cells, inhibiting secretion of TGF-β and prolong the mice survival in vivo through boosting immune system by upregulating CD8+ T cell, and through down-regulating tumor associated macrophages (TAM), myeloid derived suppressing cells (MDSC) and Tregs, in microenvironment of mice bearing tumor...
November 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27912079/a-humanized-mouse-model-for-hiv-2-infection-and-efficacy-testing-of-a-single-pill-triple-drug-combination-anti-retroviral-therapy
#10
Shuang Hu, Charles Preston Neff, Dipu Mohan Kumar, Yuichiro Habu, Sarah R Akkina, Takahiro Seki, Ramesh Akkina
While HIV-2 is a causative agent for AIDS in addition to the better studied HIV-1, there is currently no suitable animal model for experimental studies for HIV-2 infection and evaluating promising drugs in vivo. Here we evaluated humanized mice for their susceptibility to HIV-2 infection and tested a single-pill three drug formulation of anti-retrovirals (NRTIs abacavir and lamivudine, integrase inhibitor dolutegravir) (trade name, Triumeq(R)). Our results showed that hu-mice are susceptible to HIV-2 infection showing persistent viremia and CD4 T cell loss, key hallmarks of AIDS pathogenesis...
November 29, 2016: Virology
https://www.readbyqxmd.com/read/27911796/egr2-and-egr3-in-regulatory-t-cells-cooperatively-control-systemic-autoimmunity-through-ltbp3-mediated-tgf-%C3%AE-3-production
#11
Kaoru Morita, Tomohisa Okamura, Mariko Inoue, Toshihiko Komai, Shuzo Teruya, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by multiorgan inflammation induced by autoantibodies. Early growth response gene 2 (Egr2), a transcription factor essential for T-cell anergy induction, controls systemic autoimmunity in mice and humans. We have previously identified a subpopulation of CD4(+) regulatory T cells, CD4(+)CD25(-)LAG3(+) cells, that characteristically express both Egr2 and LAG3 and control mice model of lupus via TGF-β3 production. However, due to the mild phenotype of lymphocyte-specific Egr2-deficient mice, the presence of an additional regulator has been speculated...
November 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911718/attacking-hiv-1-rna-versus-dna-by-sequence-specific-approaches-rnai-versus-crispr-cas
#12
REVIEW
Elena Herrera-Carrillo, Ben Berkhout
Human immunodeficiency virus type 1 (HIV-1) infection can be effectively controlled by potent antiviral drugs, but this never results in a cure. The patient should therefore take these drugs for the rest of his/her life, which can cause drug-resistance and adverse effects. Therefore, more durable therapeutic strategies should be considered, such as a stable gene therapy to protect the target T cells against HIV-1 infection. The development of potent therapeutic regimens based on the RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats (CRISPR-Cas) mechanisms will be described, which can be delivered by lentiviral vectors...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#13
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27910751/recent-advances-in-pharmacotherapeutic-paradigm-of-mild-to-recalcitrant-atopic-dermatitis
#14
Zahid Hussain, Shariza Sahudin, Hnin Ei Thu, Ahmad Nazrun Shuid, Syed Nasir Abbas Bukhari, Endang Kumolosasi
Atopic dermatitis (AD) is a common, chronic skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin E (IgE), T lymphocytes, and mast cells. The key factors responsible for the pathophysiology of this disease are immunological disorders and defects in epidermal barrier properties. Pruritus, intense itching, psychological stress, deprived physical and mental performance, and sleep disturbance are the hallmark features of this dermatological disorder. Preventive interventions such as educational programs, avoidance of allergens, and exclusive care toward the skin could play a partial role in suppressing the symptoms...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27910206/balance-between-il-3-and-type-iinterferons-and-their-interrelationship-with-fasl-dictates-lifespan-and-effector-functions-of-human-basophils
#15
B R Hagmann, A Odermatt, T Kaufmann, C A Dahinden, M Fux
BACKGROUND: In contrast to eosinophils and neutrophils, the regulation of the lifespan of human basophils is poorly defined, with the exception of the potent anti-apoptotic effect of IL-3 that also promotes pro-inflammatory effector functions and phenotypic changes. Type I IFNs (IFN-α, IFN-β), which are well known for their anti-viral activities, have the capacity to inhibit allergic inflammation. OBJECTIVE: To elucidate whether type I IFNs have the potential to abrogate the lifespan and/or effector functions of human basophils...
November 5, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27910159/staphylococcus-aureus-derived-membrane-vesicles-exacerbate-skin-inflammation-in-atopic-dermatitis
#16
S H Jun, J H Lee, S I Kim, C W Choi, T I Park, H R Jung, J W Cho, S H Kim, J C Lee
BACKGROUND: Skin colonization or infection with Staphylococcus aureus is known to trigger aggravation of atopic dermatitis (AD). However, the exact mechanisms by which S. aureus can worsen AD are unknown. OBJECTIVE: We investigated whether and how S. aureus-derived membrane vesicles (MVs) contribute to worsening of AD. METHODS: Immunohistochemical and immunoelectron microscopic analyses were performed to detect staphylococcal protein A (SPA) in the epidermis of AD lesions...
November 5, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27909722/expression-of-soluble-programmed-death-1-protein-in-peripheral-blood-regulatory-t-cells-and-its-effects-on-rheumatoid-arthritis-progression
#17
Chun-Feng Ren, Ya-Xin Zhao, Chun-Feng Hou, Luan Luan, Guo-Qing Duan, Shu-Jie Li, Jian-Hong Zhao
The present study aimed to investigate the role of the soluble programmed death‑1 (sPD-1) protein, which is released by peripheral blood regulatory T cells (Treg) during the progression of rheumatoid arthritis (RA). From October 2012 to May 2014, 82 RA patients (RA group) and 90 healthy volunteers (healthy controls; HC) were recruited. Cluster of differentiation (CD)4, CD25 and forkhead/winged helix transcription factor p3 (Foxp3) and expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and Foxp3 were detected by flow cytometry...
November 28, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27909336/c-terminal-truncated-hbv-x-promotes-hepato-oncogenesis-through-inhibition-of-tumor-suppressive-%C3%AE-catenin-bambi-signaling
#18
Seok Lee, Mi-Jin Lee, Jun Zhang, Goung-Ran Yu, Dae-Ghon Kim
C-terminal-truncated hepatitis B virus (HBV) X (HBx) (ctHBX) is frequently detected in hepatocellular carcinoma (HCC) through HBV integration into the host genome. However, the molecular mechanisms underlying ctHBx-associated oncogenic signaling have not yet been clarified. To elucidate the biological role of ctHBx in hepato-oncogenesis, we functionally analyzed ctHBx-mediated regulation of the activin membrane-bound inhibitor bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) through transforming growth factor-β (TGF-β) or β-catenin (CTNNB1) in HCC cells and in an animal model, and we compared its role to that of the full-length HBx protein...
December 2, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27908931/filling-the-tank-keeping-antitumor-t-cells-metabolically-fit-for-the-long-haul
#19
REVIEW
Greg M Delgoffe
Discoveries in tumor immunology and subsequent clinical advances in cancer immunotherapy have revealed that the immune system is not oblivious to tumor progression but heavily interacts with developing neoplasia and malignancy. A major factor preventing immune destruction is the establishment of a highly immunosuppressive tumor microenvironment (TME), which provides architecture to the tumor, supports indirect means of immunosuppression such as the recruitment of tolerogenic cells like regulatory T cells and myeloid-derived suppressor cells (MDSC), and represents a zone of metabolically dearth conditions...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27908889/microrna-146a-induces-lineage-negative-bone-marrow-cell-apoptosis-and-senescence-by-targeting-polo-like-kinase-2-expression
#20
Shanming Deng, Huilan Wang, Chunling Jia, Shoukang Zhu, Xianming Chu, Qi Ma, Jianqin Wei, Emily Chen, Wei Zhu, Conrad J Macon, Dushyantha T Jayaweera, Derek M Dykxhoorn, Chunming Dong
OBJECTIVE: Lineage-negative bone marrow cells (lin- BMCs) are enriched in endothelial progenitor cells and mediate vascular repair. Aging-associated senescence and apoptosis result in reduced number and functionality of lin- BMCs, impairing their prorepair capacity. The molecular mechanisms underlying lin- BMC senescence and apoptosis are poorly understood. MicroRNAs (miRNAs) regulate many important biological processes. The identification of miRNA-mRNA networks that modulate the health and functionality of lin- BMCs is a critical step in understanding the process of vascular repair...
December 1, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
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