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stem signaling pathway

Bahareh Rajaei, Mohammad Massumi, Michael Wheeler
The International Diabetic Federation estimated that 415 million adults currently have diabetes and 318 million adults had impaired glucose tolerance, putting them at high risk of developing diabetes in the future. In Type 1 Diabetes (T1D), the β cells are lost because of autoimmune reactions. Although islet transplantation has been a promising therapy for T1D, it is greatly limited by pancreatic donors. Here, we describe a protocol to generate glucose- responsive pancreatic β-like (GRPβ-L) cells from human-induced pluripotent stem (iPS) cells...
October 18, 2018: Current Protocols in Human Genetics
Leonard Y M Cheung, Akima S George, Stacey R McGee, Alexandre Z Daly, Michelle L Brinkmeier, Buffy S Ellsworth, Sally A Camper
Transcription factors and signaling pathways that regulate stem cells and specialized hormone-producing cells in the pituitary gland have been the subject of intense study and have yielded a mechanistic understanding of pituitary organogenesis and disease. Yet, the regulation of stem cell proliferation and differentiation, the heterogeneity among specialized hormone-producing cells, and the role of non-endocrine cells in the gland remain important, unanswered questions. Recent advances in single-cell RNA sequencing (scRNAseq) technologies provide new avenues to address these questions...
October 17, 2018: Endocrinology
T Jiang, J Chen, X Huang, Y Li, L Zhong
Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is the most fatal leukemia due to the BCR/ABL fusion protein. This fusion protein could induce the interleukin 6 (IL-6) expression in leukemia stem cells (LSCs), which sustain the stemness by binding IL-6R and activating Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. IL-6R was one of the targets of miR-451a, which was downregulated in LSCs by BCR/ABL. We aimed to investigate the relationship between miR-451a, IL-6R, and BCR/ABL in Ph+ ALL and create a strategy to treat this disease...
September 4, 2018: Neoplasma
Sabrina Boyrie, Caroline Delmas, Anthony Lemarié, Vincent Lubrano, Perrine Dahan, Laure Malric, José Luis, Julia Gilhodes, Marie Tosolini, Laetitia Mouly, Maxime Lehmann, Christine Toulas, Elizabeth Cohen-Jonathan Moyal, Sylvie Monferran
Despite post-operative radio-chemotherapy, glioblastoma systematically locally recurs. Tumors contacting the periventricular zone (PVZ) show earlier and more distant relapses than tumors not contacting the PVZ. Since glioblastoma stem-like cells (GSCs) have been proposed to play a major role in glioblastoma recurrence, we decided to test whether GSC migration properties could be different according to their anatomical location (PVZ+/PVZ-). For that purpose, we established paired cultures of GSCs from the cortical area (CT) and the PVZ of glioblastoma patient tumors...
September 18, 2018: Oncotarget
Radhakrishnan Vishnubalaji, Muthurangan Manikandan, Abdullah Aldahmash, Abdullah AlJarbou, Mohamad Habous, Dulaim Alhajeri, Raed Almannie, Musaad Alfayez, Nehad M Alajez, Saleh Binsaleh
BACKGROUND: Stem cell-based therapies have recently been explored in the field of erectile dysfunction (ED). However, the cellular and molecular phenotype of adipose derived stem cells (ADSCs) stromal vascular fraction (SVF) from ED patients remains largely unknown. Herein we compared the global gene expression profile in the SVF from ED patients and healthy individuals and identified altered signaling pathways between the two groups. METHODS: Samples (2-5g) of abdominal adipose tissue from ED patients (n=6) and healthy individual controls (n=3) undergoing elective cosmetic liposuction were collected...
October 17, 2018: Bioscience Reports
Zi-Quan Yang, Ya-Xun Men
OBJECTIVE: To observe the effect of cyclic equiaxial tensile strain in the early differentiation of bone marrow mesenchymal stem cells(BMSCs) into cartilage in mouse under conditions of two-dimensional culture, and to investigate the mechanism of cyclic equiaxial tensile strain in early chondrogenic differentiation. METHODS: Sixteen KM mouse aged 4 weeks were selected, male and female unlimited, with an average weight of 19.5 g (17 to 21 g). After extracting and isolating the BMSCs from KM mouse, then subculture the BMSCs to the 3rd generation...
September 25, 2018: Zhongguo Gu Shang, China Journal of Orthopaedics and Traumatology
Yan-Ping Huang, Tao-Bin He, Xian-Dan Cuan, Xuan-Jun Wang, Jiang-Miao Hu, Jun Sheng
2,3- O -acetylated-1,4- β -d-glucomannan (DOP-1-1) is a polysaccharide isolated from the stem of Dendrobium officinale . DOP-1-1 has been demonstrated to have remarkable immunomodulatory properties, but little is known about the influence of its structural diversity on bioactivity (and even less about the exact mechanism underlying its immune responses). First, DOP-1-1 was stabilized at different temperatures and pH conditions based on differential scanning calorimetry and size exclusion-chromatography⁻high-performance liquid chromatography...
October 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Yuqin Zhang, Guohong Yan, Chengtao Sun, Lihong Nan, Xiaoying Wang, Wei Xu, Kedan Chu
Compound 3R-(4'-hydroxyl-3'-O-β-D-glucopyranosyl phenyl)-dihydro isocoumarin (GDC) is a natural isocoumarin, recently isolated from the stems of H. paniculiflorum. However, we know little about the effects of GDC on rheumatoid arthritis (RA). This study aims to investigate the protective effects and potential mechanisms of GDC against LPS-induced inflammation in vitro. Fibroblast-like synoviocytes (FLSs) obtained from synovial tissue of rats were induced by lipopolysaccharide (LPS) and treated with GDC. Cell viability was determined by mitochondrial-respiration-dependent3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay...
October 17, 2018: Inflammation
Ameer L Elaimy, Arthur M Mercurio
Vascular endothelial growth factor (VEGF) stimulates endothelial cells to promote both developmental and pathological angiogenesis. VEGF also directly affects tumor cells and is associated with the initiation, progression, and recurrence of tumors, as well as the emergence and maintenance of cancer stem cells (CSCs). Studies have uncovered the importance of the transcriptional regulators YAP and TAZ in mediating VEGF signaling. For example, VEGF stimulates the GTPase activity of Rho family members and thereby alters cytoskeletal dynamics, which contributes to the activation of YAP and TAZ...
October 16, 2018: Science Signaling
Yu-Shui Ma, Zhong-Wei Lv, Fei Yu, Zheng-Yan Chang, Xian-Ling Cong, Xiao-Ming Zhong, Gai-Xia Lu, Jian Zhu, Da Fu
BACKGROUND: There is increasing evidence that liver cancer stem cells (LCSCs) contribute to hepatocellular carcinoma (HCC) initiation and progression. MicroRNA (miRNA) plays a significant functional role by directly regulating respective targets in LCSCs-triggered HCC, however, little is known about the function of the miRNA-302 family in LCSCs. METHODS: MiRNAs microarray was used to detect the miRNAs involved in LCSCs maintenance and differentiation. Biological roles and the molecular mechanism of miRNA-302a/d and its target gene E2F7 were detected in HCC in vitro...
October 16, 2018: Journal of Experimental & Clinical Cancer Research: CR
Eran Zimran, Alla Keyzner, Camelia Iancu-Rubin, Ronald Hoffman, Marina Kremyanskaya
Despite the dramatic progress made in the treatment of patients with myelofibrosis since the introduction of the JAK1/2 inhibitor ruxolitinib, a therapeutic option that can modify the natural history of the disease and prevent evolution to blast-phase is still lacking. Recent investigational treatments including immunomodulatory drugs and histone deacetylase inhibitors benefit some patients but these effects have proven modest at best. Several novel agents do show promising activity in preclinical studies and early-phase clinical trials...
October 16, 2018: Expert Review of Hematology
Nicholas White, Shelly Sakiyama-Elbert
Due to the nature of the biological response to traumatic spinal cord injury, there are very limited therapeutic options available to patients. Recent advances in cell transplantation have demonstrated the therapeutic potential of transplanting supportive cell types following spinal cord injury. In particular, pluripotent stem cell derived neural cells are of interest for the future investigation. Use of pluripotent stem cells as the source allows many cell types to be produced from a population that can be expanded in vitro...
October 15, 2018: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Zhonghao Tao, Shihua Tan, Wen Chen, Xin Chen
Despite advances in the prevention and therapeutic modalities of ischemic heart disease, morbidity and mortality post-infarction heart failure remain big challenges in modern society. Stem cell therapy is emerging as a promising therapeutic strategy. Stem cell homing, the ability of stem cells to find their destination, is receiving more attention. Identification of specific cues and understanding the signaling pathways that direct stem cells to targeted destination will improve stem cell homing efficiency...
October 15, 2018: Journal of Cardiovascular Translational Research
Hisham F Bahmad, Tarek H Mouhieddine, Reda M Chalhoub, Sahar Assi, Tarek Araji, Farah Chamaa, Muhieddine M Itani, Amaly Nokkari, Firas Kobeissy, Georges Daoud, Wassim Abou-Kheir
Nervous system tumors represent some of the highly aggressive cancers in both children and adults, particularly neuroblastoma and glioblastoma. Many studies focused on the pathogenic role of the Akt pathway and the mechanistic target of Rapamycin (mTOR) complex in mediating the progression of various types of cancer, which designates the Akt/mTOR signaling pathway as a master regulator for cancer. Current studies are also elucidating the mechanisms of cancer stem cells (CSCs) in replenishing tumors and explicating the strong correlation between the Akt/mTOR pathway and CSC biology...
September 11, 2018: Oncotarget
Sara Soltanian, Hesam Dehghani
BORIS (CTCFL) is a DNA binding protein which is involved in tumorigenesis. Although, there are different opinions on the level of gene expression and function of BORIS in normal and cancer tissues, the results of many studies have classified BORIS as a protein belonging to cancer/testis (CT) genes, which are identified as a group of genes that are expressed normally in testis, and abnormally in various types of cancers. In testis, BORIS induces the expression of some male germ cell/testis specific genes, and plays crucial roles during spermatogenesis and production of sperm...
2018: Cancer Cell International
Courtney M Schaal, Namrata Bora-Singhal, Durairaj Mohan Kumar, Srikumar P Chellappan
BACKGROUND: Lung cancer is the leading cause of cancer related deaths and its incidence is highly correlated with cigarette smoking. Nicotine, the addictive component of tobacco smoke, cannot initiate tumors, but can promote proliferation, migration, and invasion of cells in vitro and promote tumor growth and metastasis in vivo. This nicotine-mediated tumor promotion is facilitated through the activation of nicotinic acetylcholine receptors (nAChRs), specifically the α7 subunit. More recently, nicotine has been implicated in promoting self-renewal of stem-like side-population cells from lung cancers...
October 15, 2018: Molecular Cancer
Zhaoting Yang, Chengye Zhang, Wenbo Qi, Yanhua Xuan, Yan Cui
The role of Hedgehog (HH)/ glioma-associated oncogene homolog 1 (GLI1) pathway has been implicated in a variety of cancer entities, and the targeted pathway inhibition mediated by GLI1 is of therapeutic relevance. However, its oncogenicity and cross-talks with other cancer pathways including PI3K/Akt/NFκB, which modulates the HH/GLI1 signal strength, have rarely been explored in colorectal adenocarcinoma. We assessed the expression of GLI1 and its relationship with other cancer stemness genes, cell cycle markers, epithelial-mesenchymal transition (EMT), PI3K/Akt/NFκB signaling pathway genes, and HIF1α in 100 paraffin-embedded colorectal adenocarcinoma tissue samples using immunohistochemistry...
October 12, 2018: Experimental Cell Research
Ganming Deng, Kaiqun Li, Siwei Chen, Peisheng Chen, Haonan Zheng, Bin Yu, Kairui Zhang
Tendon repair follows a slow course of early inflammatory, proliferative and remodeling phases, which commonly results in the failure and loss of normal biomechanical properties. Previous studies have demonstrated that tendon‑derived stem cells (TDSCs) are vital healing cells and that mRNA expression of anti‑inflammatory cytokine interleukin (IL)‑10 is significantly upregulated at the late inflammatory phase. To explore how IL‑10 may impact tendon healing, the present study investigated the in vitro effects of IL‑10 on TDSCs isolated from rat Achilles tendons...
October 10, 2018: Molecular Medicine Reports
Zhengzheng Liu, Weilu Kuang, Qin Zhou, Yingying Zhang
The positive correlation between the number of M2 phenotype TAMs (M2‑TAMs) and tumour development suggests a supportive role of M2‑TAMs in glioma progression. In the present study, the molecular link between glioma cells and M2‑TAMs was investigated and it was demonstrated that transforming growth factor‑β1 (TGF‑β1) secreted by M2‑TAMs is key in facilitating the stemness and migration of glioma cells. Cluster of differentiation (CD)133 and CD44, markers for the M2 phenotype, were assessed by western blotting...
October 9, 2018: International Journal of Molecular Medicine
Prajwal Boddu, Gautam Borthakur, Mythili Koneru, Xuelin Huang, Kiran Naqvi, William Wierda, Prithviraj Bose, Elias Jabbour, Zeev Estrov, Jan Burger, Yesid Alvarado, April Deshmukh, Ami Patel, Antonio Cavazos, Lina Han, Jorge E Cortes, Hagop Kantarjian, Michael Andreeff, Marina Konopleva
Background: The CXCR4/SDF-1α axis plays a vital role in the retention of stem cells within the bone marrow and downstream activation of cell survival signaling pathways. LY2510924, a second generation CXCR4, showed significant anti-leukemia activity in a murine AML model. Methods: We conducted a phase I study to determine the safety and toxicity of LY2510924, idarubicin and cytarabine (IA) combination therapy in relapsed/refractory (R/R) AML. Eligible patients were 18-70 years of age receiving up to salvage 3 therapy...
2018: Frontiers in Oncology
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