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Journal of Translational Medicine

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https://www.readbyqxmd.com/read/28202082/bone-morphogenetic-proteins-and-myostatin-pathways-key-mediator-of-human-sarcopenia
#1
Manuel Scimeca, Eleonora Piccirilli, Francesca Mastrangeli, Cecilia Rao, Maurizio Feola, Augusto Orlandi, Elena Gasbarra, Elena Bonanno, Umberto Tarantino
BACKGROUND: Sarcopenia, osteoporosis and osteoarthritis are the most frequent musculoskeletal disorders affecting older people. The main aim of this study was to test the hypothesis that the balance between BMPs and myostatin pathways regulates the age-related muscle degeneration in OP and OA patients. To this end, we investigated the relationship among the expression of BMP-2/4-7, myostatin and phosphorylated Smads1-5-8 and the muscle quality, evaluated in term of fibers atrophy and satellite cells activity...
February 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28202079/a-novel-cytoprotective-peptide-protects-mesenchymal-stem-cells-against-mitochondrial-dysfunction-and-apoptosis-induced-by-starvation-via-nrf2-sirt3-foxo3a-pathway
#2
Shuo Wang, Chao Zhang, Sidikejiang Niyazi, Long Zheng, Jiawei Li, Weitao Zhang, Ming Xu, Ruiming Rong, Cheng Yang, Tongyu Zhu
BACKGROUND: Mesenchymal stem cell (MSC) has been widely explored in the past decade as a cell-based treatment for various diseases. However, poor survival of adaptively transferred MSCs limits their clinical therapeutic potentials, which is largely ascribed to the nutrient starvation. In this study, we determined whether a novel kidney protective peptide CHBP could protect MSCs against starvation and invested the underlying mechanisms. METHODS: MSCs were subjected to serum deprivation and CHBP of graded concentrations was administered...
February 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28202074/exendin-4-in-combination-with-adipose-derived-stem-cells-promotes-angiogenesis-and-improves-diabetic-wound-healing
#3
Eunhui Seo, Jae Soo Lim, Jin-Bum Jun, Woohyuk Choi, In-Sun Hong, Hee-Sook Jun
BACKGROUND: Diminished wound healing is a major complication of diabetes mellitus and can lead to foot ulcers. However, there are limited therapeutic methods to treat this condition. Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, is known to have many beneficial effects on diabetes. In addition, mesenchymal stem cells are known to have wound healing effects. We investigated the effects of Ex-4 in combination with human adipose tissue-derived stem cells (ADSCs) on diabetic wound healing in a diabetic animal model...
February 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28202073/distinct-patterns-and-prognostic-values-of-tumor-infiltrating-macrophages-in-hepatocellular-carcinoma-and-gastric-cancer
#4
Jin-Qing Li, Xing-Juan Yu, Yong-Chun Wang, Li-Yun Huang, Chao-Qun Liu, Limin Zheng, Yu-Jing Fang, Jing Xu
BACKGROUND: Macrophages (Mφs) constitute a major component of the leukocyte infiltrate and perform distinct roles in different tumor microenvironments. This study aimed to characterize the distribution, composition and prognostic value of Mφs in hepatocellular carcinoma (HCC) and gastric cancer (GC). METHODS: Immunohistochemistry and immunofluorescence were used to identify Mφ subsets in HCC and GC tissues. Kaplan-Meier analysis and Cox regression models were applied to estimate the overall survival (OS) for HCC and GC patients...
February 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28202039/immune-modulation-of-some-autoimmune-diseases-the-critical-role-of-macrophages-and-neutrophils-in-the-innate-and-adaptive-immunity
#5
REVIEW
Kely Campos Navegantes, Rafaelli de Souza Gomes, Priscilla Aparecida Tártari Pereira, Paula Giselle Czaikoski, Carolina Heitmann Mares Azevedo, Marta Chagas Monteiro
Macrophages and neutrophils are key components involved in the regulation of numerous chronic inflammatory diseases, infectious disorders, and especially certain autoimmune disease. However, little is known regarding the contribution of these cells to the pathogenesis of autoimmune disorders. Recent studies have aimed to clarify certain important factors affecting the immunogenicity of these cells, including the type and dose of antigen, the microenvironment of the cell-antigen encounter, and the number, subset, and phenotype of these cells, which can prevent or induce autoimmune responses...
February 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28193233/tacrolimus-in-the-prevention-of-adverse-pregnancy-outcomes-and-diabetes-associated-embryopathies-in-obese-and-diabetic-mice
#6
Ahmad J H Albaghdadi, Melanie A Hewitt, Samantha M Putos, Michael Wells, Terence R S Ozolinš, Frederick W K Kan
BACKGROUND: T2DM is a high-risk pregnancy with adverse fetal and maternal outcomes including repeated miscarriages and fetal malformations. Despite the established association between placental insufficiency and poor maternal Th1-adaptability to the development of pregnancy complications in T2DM, there have been no established data to assess benefits of pre-pregnancy immunosuppression relative to gestational outcomes in T2DM. We hypothesized that pre-pregnancy macrolide immune suppression can re-establish normal placental development and uterine vascular adaptation in a mouse model of obesity-associated T2DM...
February 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28193231/association-of-osteopontin-with-specific-prognostic-factors-and-survival-in-adjuvant-breast-cancer-trials-of-the-hellenic-cooperative-oncology-group
#7
Amanda Psyrri, Konstantine T Kalogeras, Ralph M Wirtz, George Kouvatseas, Georgia Karayannopoulou, Anna Goussia, Flora Zagouri, Elke Veltrup, Eleni Timotheadou, Helen Gogas, Angelos Koutras, Georgios Lazaridis, Christos Christodoulou, George Pentheroudakis, Panagiota Economopoulou, Apostolos Laskarakis, Petroula Arapantoni-Dadioti, Anna Batistatou, Maria Sotiropoulou, Gerasimos Aravantinos, Pavlos Papakostas, Paris Kosmidis, Dimitrios Pectasides, George Fountzilas
BACKGROUND: The shift towards an earlier diagnosis of breast cancer (BC) highlights the need for biomarkers that would identify patients at risk for relapse and metastatic spread and indicate the potential value of additional treatment strategies. Osteopontin (OPN) is a matricellular protein that has been suggested to be a potential biomarker in BC. In the present study, we used archived BC patient samples to assess the clinical utility of OPN. METHODS: Formalin-fixed paraffin-embedded tumor tissue samples from 975 patients were collected from two large phase III randomized adjuvant chemotherapy trials (HE10/97 and HE10/00) that included patients with high risk BC...
February 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28193225/the-active-metabolite-of-leflunomide-a77-1726-attenuates-inflammatory-arthritis-in-mice-with-spontaneous-arthritis-via-induction-of-heme-oxygenase-1
#8
Su-Jin Moon, Eun-Kyung Kim, Joo Yeon Jhun, Hee Jin Lee, Weon Sun Lee, Sang-Hi Park, Mi-La Cho, Jun-Ki Min
BACKGROUND: Leflunomide is a low-molecular-weight compound that is widely used in the treatment of rheumatoid arthritis. Although leflunomide is thought to act through the inhibition of the de novo pyrimidine synthesis, the molecular mechanism of the drug remains largely unknown. We investigated the antiarthritis effects and mechanisms of action of the active metabolite of leflunomide, A77 1726, in interleukin-1 receptor antagonist-knockout (IL-1Ra-KO) mice. METHODS: 14- to 15-week-old male IL-1Ra-KO mice were treated with 10 or 30 mg/kg A77 1726 via intraperitoneal injection three times per week for 6 weeks...
February 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28183349/hif-1%C3%AE-inhibitor-echinomycin-reduces-acute-graft-versus-host-disease-and-preserves-graft-versus-leukemia-effect
#9
Yushi Yao, Lei Wang, Jihao Zhou, Xinyou Zhang
BACKGROUND: Acute graft-versus-host disease (aGVHD) remains a major obstacle against favorable clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T helper cells including Th17 play key roles in aGVHD pathogenesis. Donor regulatory T cell (Tregs) adoptive therapy reduces aGVHD without weakening graft-versus-leukemia effect (GVL) in both mouse and human, although the purification and ex vivo expansion of Tregs in clinical scenarios remain costly and technically demanding...
February 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28183315/pyruvate-kinase-m2-and-the-mitochondrial-atpase-inhibitory-factor-1-provide-novel-biomarkers-of-dermatomyositis-a-metabolic-link-to-oncogenesis
#10
Fulvio Santacatterina, María Sánchez-Aragó, Marc Catalán-García, Glòria Garrabou, Cristina Nuñez de Arenas, Josep M Grau, Francesc Cardellach, José M Cuezva
BACKGROUND: Metabolic alterations play a role in the development of inflammatory myopathies (IMs). Herein, we have investigated through a multiplex assay whether proteins of energy metabolism could provide biomarkers of IMs. METHODS: A cohort of thirty-two muscle biopsies and forty plasma samples comprising polymyositis (PM), dermatomyositis (DM) and sporadic inclusion body myositis (sIBM) and control donors was interrogated with monoclonal antibodies against proteins of energy metabolism using reverse phase protein microarrays (RPPA)...
February 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28183348/optimized-creation-of-glioblastoma-patient-derived-xenografts-for-use-in-preclinical-studies
#11
Doreen William, Christina Susanne Mullins, Björn Schneider, Andrea Orthmann, Nora Lamp, Mathias Krohn, Annika Hoffmann, Carl-Friedrich Classen, Michael Linnebacher
BACKGROUND: Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in adults, highlighting the need for novel treatment strategies. Patient derived xenografts (PDX) represent a valuable tool to accomplish this task. METHODS: PDX were established by implanting GBM tissue subcutaneously. Engraftment success was compared between NMRI Foxn1(nu) and NOD/SCID as well as between fresh and cryopreserved tissue. Established PDX were analyzed histologically and molecularly...
February 9, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28178989/individualized-analysis-reveals-cpg-sites-with-methylation-aberrations-in-almost-all-lung-adenocarcinoma-tissues
#12
Haidan Yan, Qingzhou Guan, Jun He, Yunqing Lin, Juan Zhang, Hongdong Li, Huaping Liu, Yunyan Gu, Zheng Guo, Fei He
BACKGROUND: Due to the heterogeneity of cancer, identifying differentially methylated (DM) CpG sites between a set of cancer samples and a set of normal samples cannot tell us which patients have methylation aberrations in a particular DM CpG site. METHODS: We firstly showed that the relative methylation-level orderings (RMOs) of CpG sites within individual normal lung tissues are highly stable but widely disrupted in lung adenocarcinoma tissues. This finding provides the basis of using the RankComp algorithm, previously developed for differential gene expression analysis at the individual level, to identify DM CpG sites in each cancer tissue compared with its own normal state...
February 8, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28178980/novel-neuro-audiological-findings-and-further-evidence-for-twnk-involvement-in-perrault-syndrome
#13
Monika Ołdak, Dominika Oziębło, Agnieszka Pollak, Iwona Stępniak, Michal Lazniewski, Urszula Lechowicz, Krzysztof Kochanek, Mariusz Furmanek, Grażyna Tacikowska, Dariusz Plewczynski, Tomasz Wolak, Rafał Płoski, Henryk Skarżyński
BACKGROUND: Hearing loss and ovarian dysfunction are key features of Perrault syndrome (PRLTS) but the clinical and pathophysiological features of hearing impairment in PRLTS individuals have not been addressed. Mutations in one of five different genes HSD17B4, HARS2, LARS2, CLPP or TWNK (previous symbol C10orf2) cause the autosomal recessive disorder but they are found only in about half of the patients. METHODS: We report on two siblings with a clinical picture resembling a severe, neurological type of PRLTS...
February 8, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28148308/opening-editorial
#14
EDITORIAL
Seah H Lim
No abstract text is available yet for this article.
February 1, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28137295/a-phase-ii-trial-of-stereotactic-body-radiotherapy-with-concurrent-anti-pd1-treatment-in-metastatic-melanoma-evaluation-of-clinical-and-immunologic-response
#15
Katrien De Wolf, Vibeke Kruse, Nora Sundahl, Mireille van Gele, Ines Chevolet, Reinhart Speeckaert, Lieve Brochez, Piet Ost
BACKGROUND: Antibodies blocking programmed cell death 1 (PD-1) have encouraging responses in patients with metastatic melanoma. Response to anti-PD-1 treatment requires pre-existing CD8+ T cells that are negatively regulated by PD-1-mediated adaptive immune resistance. Unfortunately, less than half of melanoma tumours have these characteristics. Combining anti-PD-1 treatment with other immunomodulating treatments to activate CD8+ T cells is therefore of vital importance to increase response rates and long-term survival benefit in melanoma patients...
January 31, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28137276/towards-standardization-of-next-generation-sequencing-of-ffpe-samples-for-clinical-oncology-intrinsic-obstacles-and-possible-solutions
#16
Maxim Ivanov, Konstantin Laktionov, Valery Breder, Polina Chernenko, Ekaterina Novikova, Ekaterina Telysheva, Sergey Musienko, Ancha Baranova, Vladislav Mileyko
BACKGROUND: Next generation sequencing has a potential to revolutionize the management of cancer patients within the framework of precision oncology. Nevertheless, lack of standardization decelerated entering of the technology into the clinical testing space. Here we dissected a number of common problems of NGS diagnostics in oncology and introduced ways they can be resolved. METHODS: DNA was extracted from 26 formalin fixed paraffin embedded (FFPE) specimens and processed with the TrueSeq Amplicon Cancer Panel (Illumina Inc, San Diego, California) targeting 48 cancer-related genes and sequenced in single run...
January 31, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28137271/microwave-ablation-combined-with-ok-432-induces-th1-type-response-and-specific-antitumor-immunity-in-a-murine-model-of-breast-cancer
#17
Li Li, Wei Wang, Hong Pan, Ge Ma, Xinyi Shi, Hui Xie, Xiaoan Liu, Qiang Ding, Wenbin Zhou, Shui Wang
BACKGROUND: Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced immune responses are mostly weak, and the immunomodulation effects of MWA in breast cancer are unclear. Immunostimulant OK-432 can induce tumor-specific T-cell responses and may augment the immunity induced by MWA...
January 31, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28125988/inhibitory-effect-of-a-novel-peptide-h-rn-on-keratitis-induced-by-lps-or-poly-i-c-in-vitro-and-in-vivo-via-suppressing-nf-%C3%AE%C2%BAb-and-mapk-activation
#18
Shaopin Zhu, Xun Xu, Lili Wang, Li Su, Qing Gu, Fang Wei, Kun Liu
BACKGROUND: Keratitis is a common cause of blindness. Current anti-inflammatory drugs used in keratitis have profound side effects. Small peptides derived from endogenous proteins potentially display both desired efficiency and safety. We identified an 11-amino-acid peptide, H-RN, from hepatocyte growth factor (HGF), an endogenous protein with anti-inflammatory properties. We evaluated the effects of H-RN in keratitis in vitro and in vivo. METHODS: In vitro, corneal fibroblasts were stimulated with LPS or poly(I:C), surrogates for bacteria and viruses...
January 26, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28114956/near-infrared-fluorescent-imaging-of-brain-tumor-with-ir780-dye-incorporated-phospholipid-nanoparticles
#19
Shihong Li, Jennifer Johnson, Anderson Peck, Qian Xie
BACKGROUND: Near-IR fluorescence (NIRF) imaging is becoming a promising approach in preclinical tumor detection and clinical image-guided oncological surgery. While heptamethine cyanine dye IR780 has excellent tumor targeting and imaging potential, its hydrophobic property limits its clinical use. In this study, we developed nanoparticle formulations to facilitate the use of IR780 for fluorescent imaging of malignant brain tumor. METHODS: Self-assembled IR780-liposomes and IR780-phospholipid micelles were prepared and their NIRF properties were characterized...
January 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28109298/neuroregenerative-potential-of-intravenous-g-csf-and-autologous-peripheral-blood-stem-cells-in-children-with-cerebral-palsy-a-randomized-double-blind-cross-over-study
#20
Wee-Jin Rah, Young-Ho Lee, Jin-Hwa Moon, Hyun-Ju Jun, Hye-Ryeong Kang, Hani Koh, Hye Jung Eom, Ji Young Lee, Young Jun Lee, Ji Young Kim, Yun-Young Choi, Kyeongil Park, Mi Jung Kim, Seung-Hyun Kim
OBJECTIVE: We performed a randomized, double-blind, cross-over study to assess the neuroregenerative potential of intravenous granulocyte colony-stimulating factor (G-CSF) followed by infusion of mobilized peripheral blood mononuclear cells (mPBMCs) in children with cerebral palsy (CP). METHODS: Children with non-severe CP were enrolled in this study. G-CSF was administered for 5 days, then mPBMCs were collected by apheresis and cryopreserved. One month later (M1), recipients were randomized to receive either mPBMCs or a placebo infusion, and these treatment groups were switched at 7 months (M7) and observed for another 6 months (M13)...
January 21, 2017: Journal of Translational Medicine
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