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https://www.readbyqxmd.com/read/29780805/stabilization-of-hypoxia-inducible-factor-1-alpha-augments-the-therapeutic-capacity-of-bone-marrow-derived-mesenchymal-stem-cells-in-experimental-pneumonia
#1
Naveen Gupta, Victor Nizet
Bone marrow-derived mesenchymal stem cells (MSCs) have therapeutic effects in experimental models of lung injury. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcriptional regulator that influences cellular metabolism, energetics, and survival under hypoxic conditions. The current study investigated the effects of stabilizing HIF-1α on the therapeutic capacity of MSCs in an experimental mouse model of bacterial pneumonia. HIF-1α stabilization was achieved by the small molecule prolyl-hydroxlase inhibitor, AKB-4924 (Aerpio Therapeutics, Inc...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29775181/porous-lithium-doped-hydroxyapatite-scaffold-seeded-with-hypoxia-preconditioned-bone-marrow-mesenchymal-stem-cells-for-bone-tissue-regeneration
#2
Donghai Li, Huifang Liu, Jinhai Zhao, Zhouyuan Yang, Xiaowei Xie, Zhun Wei, Dongzhe Li, Pengde Kang
Hydroxyapatite (HA) is a commonly used biomaterial in bone-tissue engineering, but pure HA is deficient in osteoinduction. In this study, we fabricated scaffolds of lithium-doped HA (Li-HA) and assess the bone generation enhancement of Li-HA scaffolds seeded with hypoxia-preconditioned bone-marrow mesenchymal stem cells (BMMSCs). We found that 1.5%Li-HA obtained optimal cell proliferation activity in vitro. In an in vivo study, Li-HA/BMSCs enhanced new bone formation, reducing the GSK-3β and increasing the β-catenin, but the angiogenic effect was not modified significantly...
May 18, 2018: Biomedical Materials
https://www.readbyqxmd.com/read/29755367/the-transcription-factor-hif-1-enhances-the-radio-resistance-of-mouse-mscs
#3
Irene Calvo-Asensio, Eugène T Dillon, Noel F Lowndes, Rhodri Ceredig
Mesenchymal stromal cells (MSCs) are multipotent progenitors supporting bone marrow hematopoiesis. MSCs have an efficient DNA damage response (DDR) and are consequently relatively radio-resistant cells. Therefore, MSCs are key to hematopoietic reconstitution following total body irradiation (TBI) and bone marrow transplantation (BMT). The bone marrow niche is hypoxic and via the heterodimeric transcription factor Hypoxia-inducible factor-1 (Hif-1), hypoxia enhances the DDR. Using gene knock-down, we have previously shown that the Hif-1α subunit of Hif-1 is involved in mouse MSC radio-resistance, however its exact mechanism of action remains unknown...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29753285/chitin-synthesis-inhibitors-promote-liver-cancer-cell-metastasis-via-interfering-with-hypoxia-inducible-factor-1%C3%AE
#4
Xia Ning, Yue Wang, Wei Yan, Guangke Li, Nan Sang
Chitin synthesis inhibitors (CSIs), as alternatives to conventional insecticides, have been in worldwide demand in recent years. However, little attention has been paid to the potential ecological safety and health risks of CSIs, especially their abilities to interfere with nonsexual hormone receptors such as hypoxia-inducible factor 1α (HIF-1α). In this work, we conducted a systematic study regarding the influence of CSIs on HIF-1α-related liver cancer cell metastasis. The dual-luciferase reporter gene assay revealed that two of fourteen CSIs exhibited dose-response HIF-1α agonistic activities at noncytotoxic concentrations with relative luciferase activity (RLA) values of 25...
May 3, 2018: Chemosphere
https://www.readbyqxmd.com/read/29749486/effects-of-obatoclax-combined-with-gemcitabine-on-the-biological-activity-of-pancreatic-cancer-cells-under-hypoxic-conditions
#5
Xin-Fang Hou, Shuai Li, Chen Wu, Ke Li, Shu-Ning Xu, Ju-Feng Wang
The present study aimed to investigate the effects of obatoclax (OBX) combined with gemcitabine (GEM) treatment on the proliferation, migration, invasion and epithelial‑mesenchymal transition (EMT) related proteins of pancreatic cancer cell line BxPC‑3 under hypoxic conditions. Protein expression levels of hypoxia‑inducible factor 1α (HIF‑1α) in BxPC‑3 pancreatic cancer cells under normoxic and hypoxic conditions were detected by western blotting. Cells were divided into four groups: Normoxia group, hypoxia group, OBX group and OBX + GEM group...
April 26, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29741670/cadmium-exposure-inhibits-branching-morphogenesis-and-causes-alterations-consistent-with-hif-1%C3%AE-inhibition-in-human-primary-breast-organoids
#6
Sabrina A Rocco, Lada Koneva, Lauren Y M Middleton, Tasha Thong, Sumeet Solanki, Sarah Karram, Kowit Nambunmee, Craig Harris, Laura S Rozek, Maureen A Sartor, Yatrik M Shah, Justin A Colacino
Developmental cadmium exposure in vivo disrupts mammary gland differentiation, while exposure of breast cell lines to cadmium causes invasion consistent with the epithelial-mesenchymal transition (EMT). The effects of cadmium on normal human breast stem cells have not been measured. Here, we quantified the effects of cadmium exposure on reduction mammoplasty patient-derived breast stem cell proliferation and differentiation. Using the mammosphere assay and organoid formation in 3D hydrogels, we tested two physiologically relevant doses of cadmium, 0...
May 7, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29731878/conversion-of-epithelial-to-mesenchymal-transition-to-mesenchymal-to-epithelial-transition-is-mediated-by-oxygen-concentration-in-pancreatic-cancer-cells
#7
Shuo Chen, Xi Chen, Wei Li, Tao Shan, Wan Run Lin, Jiancang Ma, Xijuan Cui, Wenbin Yang, Gang Cao, Yiming Li, Li Wang, Ya'an Kang
Tumor metastasis is accompanied by a two-stage process of epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET). Currently, the exact mechanisms underlying EMT-MET conversion are unclear. In the present study, the mechanisms by which primary sites (hypoxic) and homing sites (normoxic or hyperoxic) participate in EMT-MET conversion were evaluated. Pancreatic cancer cells were grown under different oxygenation conditions. Cell morphology and epithelial (E)-cadherin and vimentin expression were examined...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29731777/the-hypoxia-mimetic-agent-cobalt-chloride-differently-affects-human-mesenchymal-stem-cells-in-their-chondrogenic-potential
#8
Gabriella Teti, Stefano Focaroli, Viviana Salvatore, Eleonora Mazzotti, Laura Ingra', Antonio Mazzotti, Mirella Falconi
Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl2 ) imitates hypoxia in vitro by stabilizing hypoxia-inducible factor-alpha (HIF-1 α ), which is the master regulator in the cellular adaptive response to hypoxia. In this study, the influence of CoCl2 on the chondrogenic potential of human MSCs, isolated from dental pulp, umbilical cord, and adipose tissue, was investigated...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29726060/differential-regulation-of-human-bone-marrow-mesenchymal-stromal-cell-chondrogenesis-by-hypoxia-inducible-factor-1%C3%AE-hydroxylase-inhibitors
#9
Dheraj K Taheem, Daniel A Foyt, Sandra Loaiza, Silvia A Ferreira, Dusko Ilic, Holger W Auner, Agamemnon E Grigoriadis, Gavin Jell, Eileen Gentleman
The transcriptional profile induced by hypoxia plays important roles in the chondrogenic differentiation of marrow stromal/stem cells (MSC) and is mediated by the Hypoxia Inducible Factor complex. However, various compounds can also stabilise HIF's oxygen-responsive element, HIF-1α, at normoxia and mimic many hypoxia-induced cellular responses. Such compounds may prove efficacious in cartilage tissue engineering, where microenvironmental cues may mediate functional tissue formation. Here, we investigated three HIF stabilising compounds, which each have distinct mechanisms of action, to understand how they differentially influenced the chondrogenesis of human bone marrow-derived MSC (hBM-MSC) in vitro...
May 3, 2018: Stem Cells
https://www.readbyqxmd.com/read/29725266/repair-of-critical-sized-mandible-defects-in-aged-rat-using-hypoxia-preconditioned-bmscs-with-up-regulation-of-hif-1%C3%AE
#10
Jiankang Zhang, Zhuozhuo Feng, Junjun Wei, Yunbo Yu, Jie Luo, Jing Zhou, Yi Li, Xiaohui Zheng, Wei Tang, Lei Liu, Jie Long, Xiaoyu Li, Wei Jing
The repair of bone defects in the geriatric population remains a challenge for modern medicine. Transplantation of bone marrow mesenchymal stem cells (BMSCs) combined with or without biomaterials has been a promising approach to bone restoration and regeneration. Typically, the transplanted BMSCs are cultured under normoxic conditions (21% O2 and 10% serum medium) in vitro . However, the micro-environment of bone defect area is much more severe, in which lower physiological oxygen tension (<1%) and tissue ischemia were present...
2018: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29713350/sphingosine-1-phosphate-receptor-1-is-required-for-mmp-2-function-in-bone-marrow-mesenchymal-stromal-cells-implications-for-cytoskeleton-assembly-and-proliferation
#11
Chiara Sassoli, Federica Pierucci, Alessia Tani, Alessia Frati, Flaminia Chellini, Francesca Matteini, Ambra Vestri, Giulia Anderloni, Daniele Nosi, Sandra Zecchi-Orlandini, Elisabetta Meacci
Bone marrow-derived mesenchymal stromal cell- (BM-MSC-) based therapy is a promising option for regenerative medicine. An important role in the control of the processes influencing the BM-MSC therapeutic efficacy, namely, extracellular matrix remodelling and proliferation and secretion ability, is played by matrix metalloproteinase- (MMP-) 2. Therefore, the identification of paracrine/autocrine regulators of MMP-2 function may be of great relevance for improving BM-MSC therapeutic potential. We recently reported that BM-MSCs release the bioactive lipid sphingosine 1-phosphate (S1P) and, here, we demonstrated an impairment of MMP-2 expression/release when the S1P receptor subtype S1PR1 is blocked...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29706185/hypoxia-induced-emt-a-review-on-the-mechanism-of-tumor-progression-and-metastasis-in-oscc
#12
REVIEW
Joel P Joseph, M K Harishankar, Aruthra Arumugam Pillai, Arikketh Devi
Hypoxia, a condition of low oxygen tension in tissues, has emerged as a crucial factor in tumor pathophysiology. Hypoxic microenvironment gives rise to altered cellular metabolism and triggers varied molecular responses. These responses promote tumor progression and confer radiation resistance and chemo resistance to tumors. The predominant molecules that are associated with hypoxia research are the hypoxia inducible factors (HIFs). HIFs are known to regulate a large group of genes that are involved in cell survival, proliferation, motility, metabolism, pH regulation, extracellular matrix function, inflammatory cell recruitment and angiogenesis by inducing the expression of their downstream target genes...
May 2018: Oral Oncology
https://www.readbyqxmd.com/read/29693273/the-role-of-hif-1%C3%AE-in-the-tgf-%C3%AE-2-mediated-epithelial-to-mesenchymal-transition-of-human-lens-epithelial-cells
#13
Rooban B Nahomi, Ram H Nagaraj
Human lens epithelial cells (HLE) undergo mesenchymal transition and become fibrotic during posterior capsule opacification (PCO), which is a frequent complication after cataract surgery. TGF-β2 has been implicated in this fibrosis. Previous studies have focused on the role of hypoxia-inducible factor-1α (HIF-1α) in fibrotic diseases, but the role of HIF-1α in the TGF-β2-mediated fibrosis in HLE is not known. TGF-β2 treatment (10 ng/mL, 48 h) increased the HIF-1α levels along with the EMT markers in cultured human lens epithelial cells (FHL124 cells)...
April 25, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29656700/hif-2%C3%AE-ilk-is-involved-in-mesenchymal-stromal-cell-angiogenesis-in-multiple-myeloma-under-hypoxic-conditions
#14
Xiaoying Zhang, Yinhui Xu, Hongbo Liu, Pan Zhao, Yafang Chen, Zhijie Yue, Zhiqing Zhang, Xiaofang Wang
Mesenchymal stromal cells are proven to be likely induce the angiogenic response in multiple myeloma and thus represent an enticing target for antiangiogenesis therapies for multiple myeloma. Substantial evidence indicates that angiogenesis in multiple myeloma is complex and involves direct production of angiogenic cytokines by abnormal plasma cells and these B-cell neoplasia generated pathophysiology change within the microenvironment. In this study, we demonstrated that mesenchymal stromal cells cultured with U266/Lp-1 under hypoxic conditions resulted in an increased α-smooth muscle actin expression and high productive levels of both hypoxia-inducible factor-2α and integrin-linked kinase proteins...
January 1, 2018: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29652803/hypoxia-supports-epicardial-cell-differentiation-in-vascular-smooth-muscle-cells-through-the-activation-of-the-tgf%C3%AE-pathway
#15
Jiayi Tao, Joey V Barnett, Michiko Watanabe, Diana Ramírez-Bergeron
Epicardium-derived cells (EPDCs) are an important pool of multipotent cardiovascular progenitor cells. Through epithelial-to-mesenchymal-transition (EMT), EPDCs invade the subepicardium and myocardium and further differentiate into several cell types required for coronary vessel formation. We previously showed that epicardial hypoxia inducible factor (HIF) signaling mediates the invasion of vascular precursor cells critical for patterning the coronary vasculature. Here, we examine the regulatory role of hypoxia (1% oxygen) on EPDC differentiation into vascular smooth muscle cells (VSMCs)...
April 13, 2018: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29644003/overexpression-of-plod3-promotes-tumor-progression-and-poor-prognosis-in-gliomas
#16
Chia-Kuang Tsai, Li-Chun Huang, Wen-Chiuan Tsai, Shih-Ming Huang, Jiunn-Tay Lee, Dueng-Yuan Hueng
High-grade gliomas are the most threatening brain tumors due to aggressive proliferation and poor prognosis. Thus, utilizing genetic glioma biomarkers to forecast prognosis and guide clinical management is crucial. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) modulates cancer progression and metastasis. However, its detailed function in cancer remains largely uninvestigated. PLOD3 expression was evaluated with real-time PCR in glioblastoma (GBM) cell lines and by Gene Expression Omnibus dataset analysis and immunohistochemistry of glioma tissues...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29643458/pro-inflammatory-cytokines-activate-hypoxia-inducible-factor-3%C3%AE-via-epigenetic-changes-in-mesenchymal-stromal-stem-cells
#17
Francesca Cuomo, Antonietta Coppola, Chiara Botti, Ciro Maione, Amalia Forte, Lucia Scisciola, Giuseppina Liguori, Ilaria Caiafa, Matilde Valeria Ursini, Umberto Galderisi, Marilena Cipollaro, Lucia Altucci, Gilda Cobellis
Human mesenchymal stromal/stem cells (hMSCs) emerged as a promising therapeutic tool for ischemic disorders, due to their ability to regenerate damaged tissues, promote angiogenesis and reduce inflammation, leading to encouraging, but still limited results. The outcomes in clinical trials exploring hMSC therapy are influenced by low cell retention and survival in affected tissues, partially influenced by lesion's microenvironment, where low oxygen conditions (i.e. hypoxia) and inflammation coexist. Hypoxia and inflammation are pathophysiological stresses, sharing common activators, such as hypoxia-inducible factors (HIFs) and NF-κB...
April 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29620169/lutein-inhibits-proliferation-invasion-and-migration-of-hypoxic-breast-cancer-cells-via-downregulation-of-hes1
#18
Yuan Li, Yuekun Zhang, Xiaosa Liu, Mingchen Wang, Peng Wang, Jianbo Yang, Shanfeng Zhang
An intratumoral hypoxic microenvironment is frequently observed in solid tumors, including breast cancer. Lutein, a plant-derived compound and non-vitamin A carotenoid, has been demonstrated to possess multiple protective properties including anti-inflammation, anti-oxidative stress and antitumor effects. The main objective of the present research was to elucidate the involvement of lutein in the production of reactive oxygen species (ROS) under hypoxia, the activation of hairy and enhancer of split 1 (HES1), and the proliferation, invasion and migration of breast cancer cells...
March 23, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29604553/stereological-and-molecular-studies-on-the-combined-effects-of-photobiomodulation-and-human-bone-marrow-mesenchymal-stem-cell-conditioned-medium-on-wound-healing-in-diabetic-rats
#19
Abdollah Amini, Ramin Pouriran, Mohammad-Amin Abdollahifar, Hojjat Allah Abbaszadeh, Seyed Kamran Ghoreishi, Sufan Chien, Mohammad Bayat
We investigated the effects of conditioned medium (CM) from human bone marrow mesenchymal stem cells (h BMMSC)s and pulse wave photobiomodulation (PW PBM), applied alone or in combination, on the stereological parameters and gene expression of some growth factors, during wound healing in a streptozotocin (STZ)-induced rat model of type one diabetes mellitus (T1DM). T1DM was induced in 72 rats and two incisions were made in each animal. The rats were assigned to one of four groups: a control (placebo) group, a Laser group (890 nm, 80 Hz, 0...
May 2018: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29599336/glycine-is-a-predictor-for-a-suppressive-effect-of-fucoxanthinol-on-colonosphere-formation-under-hypoxia
#20
Masaru Terasaki, Yuki Ogawa, Tetsuya Endo, Hayato Maeda, Junichi Hamada, Kazumi Osada, Kazuo Miyashita, Michihiro Mutoh
BACKGROUND/AIM: Fucoxanthinol (FxOH), a metabolite of fucoxanthin, is known to inhibit tumorigenicity of human colorectal cancer stem cells (CCSCs) and their sphere formation. Hypoxic conditions and hypoxia-inducible factors (HIFs) are essential to maintain the stemness of CCSCs. We investigated effects of FxOH on sphere formation, intercellular energy metabolites in colonospheres formed from human colorectal HT-29 cells under hypoxic conditions. RESULTS: FxOH at 50 μM suppressed HIF1α expression and activation of integrin, mitogen-activated protein kinase (MAPK), Wingless/integrated (WNT) and signal transducer and activator of transcription (STAT) signals...
April 2018: Anticancer Research
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