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1.
Int J Mol Sci ; 25(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731939

RESUMO

Myelodysplastic syndrome/neoplasm (MDS) comprises a group of heterogeneous hematopoietic disorders that present with genetic mutations and/or cytogenetic changes and, in the advanced stage, exhibit wide-ranging gene hypermethylation. Patients with higher-risk MDS are typically treated with repeated cycles of hypomethylating agents, such as azacitidine. However, some patients fail to respond to this therapy, and fewer than 50% show hematologic improvement. In this context, we focused on the potential use of epigenetic data in clinical management to aid in diagnostic and therapeutic decision-making. First, we used the F-36P MDS cell line to establish an azacitidine-resistant F-36P cell line. We performed expression profiling of azacitidine-resistant and parental F-36P cells and used biological and bioinformatics approaches to analyze candidate azacitidine-resistance-related genes and pathways. Eighty candidate genes were identified and found to encode proteins previously linked to cancer, chronic myeloid leukemia, and transcriptional misregulation in cancer. Interestingly, 24 of the candidate genes had promoter methylation patterns that were inversely correlated with azacitidine resistance, suggesting that DNA methylation status may contribute to azacitidine resistance. In particular, the DNA methylation status and/or mRNA expression levels of the four genes (AMER1, HSPA2, NCX1, and TNFRSF10C) may contribute to the clinical effects of azacitidine in MDS. Our study provides information on azacitidine resistance diagnostic genes in MDS patients, which can be of great help in monitoring the effectiveness of treatment in progressing azacitidine treatment for newly diagnosed MDS patients.


Assuntos
Azacitidina , Metilação de DNA , Síndromes Mielodisplásicas , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Metilação de DNA/efeitos dos fármacos , Humanos , Azacitidina/farmacologia , Azacitidina/uso terapêutico , Perfilação da Expressão Gênica/métodos , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Epigênese Genética/efeitos dos fármacos , Regiões Promotoras Genéticas
2.
Exp Dermatol ; 32(10): 1706-1716, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37421206

RESUMO

Melanoma is a notoriously radioresistant type of skin cancer. Elucidation of the specific mechanisms underlying radioresistance is necessary to improve the clinical efficacy of radiation therapy. To identify the key factors contributing to radioresistance, five melanoma cell lines were selected for study and genes that were upregulated in relatively radioresistant melanomas compared with radiosensitive melanoma cells determined via RNA sequencing technology. In particular, we focused on cyclin D1 (CCND1), a well known cell cycle regulatory molecule. In radiosensitive melanoma, overexpression of cyclin D1 reduced apoptosis. In radioresistant melanoma cell lines, suppression of cyclin D1 with a specific inhibitor or siRNA increased apoptosis and decreased cell proliferation in 2D and 3D spheroid cultures. In addition, we observed increased expression of γ-H2AX, a molecular marker of DNA damage, even at a later time after γ-irradiation, under conditions of inhibition of cyclin D1, with a response pattern similar to that of radiosensitive SK-Mel5. In the same context, expression and nuclear foci formation of RAD51, a key enzyme for homologous recombination (HR), were reduced upon inhibition of cyclin D1. Downregulation of RAD51 also reduced cell survival to irradiation. Overall, suppression of cyclin D1 expression or function led to reduced radiation-induced DNA damage response (DDR) and triggered cell death. Our collective findings indicate that the presence of increased cyclin D1 potentially contributes to the development of radioresistance through effects on RAD51 in melanoma and could therefore serve as a therapeutic target for improving the efficacy of radiation therapy.


Assuntos
Ciclina D1 , Reparo do DNA , Melanoma , Rad51 Recombinase , Humanos , Apoptose , Linhagem Celular Tumoral , Ciclina D1/genética , Ciclina D1/metabolismo , Melanoma/genética , Melanoma/radioterapia , Rad51 Recombinase/genética , Rad51 Recombinase/metabolismo , Tolerância a Radiação/genética
3.
Int J Mol Sci ; 24(15)2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37569769

RESUMO

Fine needle aspiration cytology (FNAC) is a useful tool in the evaluation of lymphadenopathy. It is a safe and minimally invasive procedure that provides preoperative details for subsequent treatment. It can also diagnose the majority of malignant tumors. However, there are some instances where the diagnosis of tumors remains obscure. To address this, we re-analyzed the misinterpreted patients' samples using mRNA sequencing technology and then identified the characteristics of non-Hodgkin's lymphoma that tend to be under-diagnosed. To decipher the involved genes and pathways, we used bioinformatic and biological analysis approaches, identifying the response to oxygen species, inositol phosphate metabolic processes, and peroxisome and PPAR pathways as possibly being involved with this type of tumor. Notably, these analyses identified FOS, ENDOG, and PRKAR2B as hub genes. cBioPortal, a multidimensional cancer genomics database, also confirmed that these genes were associated with lymphoma patients. These results thus point to candidate genes that could be used as biomarkers to minimize the false-negative rate of FNAC diagnosis. We are currently pursuing the development of a gene chip to improve the diagnosis of lymphadenopathy patients with the ultimate goal of improving their prognosis.


Assuntos
Linfadenopatia , Linfoma , Neoplasias , Humanos , Biópsia por Agulha Fina , Técnicas Citológicas
4.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36674495

RESUMO

Precise prediction of radioresistance is an important factor in the treatment of colorectal cancer (CRC). To discover genes that regulate the radioresistance of CRCs, we analyzed an RNA sequencing dataset of patient-originated samples. Among various candidates, IGFL2-AS1, a long non-coding RNA (lncRNA), exhibited an expression pattern that was well correlated with radioresistance. IGFL2-AS1 is known to be highly expressed in various cancers and functions as a competing endogenous RNA. To further investigate the role of IGFL2-AS1 in radioresistance, which has not yet been studied, we assessed the amount of IGFL2-AS1 transcripts in CRC cell lines with varying degrees of radioresistance. This analysis showed that the more radioresistant the cell line, the higher the level of IGFL2-AS1 transcripts-a similar trend was observed in CRC samples. To directly assess the relationship between IGFL2-AS1 and radioresistance, we generated a CRC cell line stably expressing a small hairpin RNA (shRNA) targeting IGFL2-AS1. shRNA-mediated knockdown of IGFL2-AS1 decreased radioresistance and cell migration in vitro, establishing a functional role for IGFL2-AS1 in radioresistance. We also showed that downstream effectors of the AKT pathway played crucial roles. These data suggest that IGFL2-AS1 contributes to the acquisition of radioresistance by regulating the AKT pathway.


Assuntos
Neoplasias Colorretais , RNA Longo não Codificante , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/metabolismo
5.
Curr Microbiol ; 79(11): 340, 2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36209171

RESUMO

Strain KSB-15 T was isolated from an orchard soil that had been contaminated with the insecticide dichlorodiphenyltrichloroethane for about 60 years. The 16S rRNA gene sequence of this strain showed the highest sequence similarities with those of Oleiharenicola alkalitolerans NVTT (95.3%), Opitutus terrae PB90-1 T (94.8%), and Oleiharenicola lentus TWA-58 T (94.7%) among type strains, which are members of the family Opitutaceae within the phylum Verrucomicrobia. Strain KSB-15 T was an obligate aerobe, Gram-negative, non-motile, coccoid or short rod with the cellular dimensions of 0.37-0.62 µm width and 0.43-0.72 µm length. The strain grew at temperatures between 15-37 °C (optimum, 25 °C), at a pH range of 5.0-11.0 (optimum, pH 6.0), and at a NaCl concentration of 0-3% (w/v) (optimum, 0%). It contained menaquinone-7 (MK-7) as the major isoprenoid quinone (94.1%), and iso-C15:0 (34.9%) and anteiso-C15:0 (29.0%) as the two major fatty acids. The genome of strain KSB-15 T was composed of one chromosome with a total size of 4,320,198 bp, a G + C content of 64.3%, 3,393 coding genes (CDS), 14 pseudogenes, and 52 RNA genes. The OrthoANIu values, In silico DDH values and average amino acid identities between strain KSB-15 T and the members of the family Opitutaceae were 71.6 ~ 73.0%, 19.0 ~ 19.9%, and 55.9 ~ 62.0%, respectively. On the basis of our polyphasic taxonomic study, we conclude that strain KSB-15 T should be classified as a novel genus of the family Opitutaceae, for which the name Horticcoccus luteus gen. nov., sp. nov. is proposed.The type strain is KSB-15 T (= KACC 22271 T = DSM 113638 T).


Assuntos
DDT , Inseticidas , Aminoácidos , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácidos Graxos/química , Filogenia , Quinonas , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Cloreto de Sódio , Solo , Terpenos , Verrucomicrobia/genética , Vitamina K 2/química
7.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360546

RESUMO

Promyelocytic leukemia (PML) protein is the core component of subnuclear structures called PML nuclear bodies that are known to play important roles in cell survival, DNA damage responses, and DNA repair. Fanconi anemia (FA) proteins are required for repairing interstrand DNA crosslinks (ICLs). Here we report a novel role of PML proteins, regulating the ICL repair pathway. We found that depletion of the PML protein led to the significant reduction of damage-induced FANCD2 mono-ubiquitination and FANCD2 foci formation. Consistently, the cells treated with siRNA against PML showed enhanced sensitivity to a crosslinking agent, mitomycin C. Further studies showed that depletion of PML reduced the protein expression of FANCA, FANCG, and FANCD2 via reduced transcriptional activity. Interestingly, we observed that damage-induced CHK1 phosphorylation was severely impaired in cells with depleted PML, and we demonstrated that CHK1 regulates FANCA, FANCG, and FANCD2 transcription. Finally, we showed that inhibition of CHK1 phosphorylation further sensitized cancer cells to mitomycin C. Taken together, these findings suggest that the PML is critical for damage-induced CHK1 phosphorylation, which is important for FA gene expression and for repairing ICLs.


Assuntos
Quinase 1 do Ponto de Checagem/metabolismo , Proteína do Grupo de Complementação A da Anemia de Fanconi/metabolismo , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Proteína do Grupo de Complementação G da Anemia de Fanconi/metabolismo , Anemia de Fanconi/patologia , Regulação da Expressão Gênica , Quinase 1 do Ponto de Checagem/genética , Dano ao DNA , Reparo do DNA , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação G da Anemia de Fanconi/genética , Células HeLa , Humanos , Fosforilação , Ubiquitinação
8.
Int J Mol Sci ; 22(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946516

RESUMO

Endothelial progenitor cells (EPCs) are specialized cells in circulating blood, well known for their ability to form new vascular structures. Aging and various ailments such as diabetes, atherosclerosis and cardiovascular disease make EPCs vulnerable to decreasing in number, which affects their migration, proliferation and angiogenesis. Myocardial ischemia is also linked to a reduced number of EPCs and their endothelial functional role, which hinders proper blood circulation to the myocardium. The current study shows that an aminopyrimidine derivative compound (CHIR99021) induces the inhibition of GSK-3ß in cultured late EPCs. GSK-3ß inhibition subsequently inhibits mTOR by blocking the phosphorylation of TSC2 and lysosomal localization of mTOR. Furthermore, suppression of GSK-3ß activity considerably increased lysosomal activation and autophagy. The activation of lysosomes and autophagy by GSK-3ß inhibition not only prevented replicative senescence of the late EPCs but also directed their migration, proliferation and angiogenesis. To conclude, our results demonstrate that lysosome activation and autophagy play a crucial role in blocking the replicative senescence of EPCs and in increasing their endothelial function. Thus, the findings provide an insight towards the treatment of ischemia-associated cardiovascular diseases based on the role of late EPCs.


Assuntos
Senescência Celular/efeitos dos fármacos , Células Progenitoras Endoteliais/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Autofagia/efeitos dos fármacos , Células Cultivadas , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Serina-Treonina Quinases TOR/metabolismo
9.
Biochem Biophys Res Commun ; 515(4): 600-606, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31178140

RESUMO

Colorectal cancer is one of the leading causes of cancer-related deaths. Due to relapse after current therapy regimens, cancer stem cells (CSCs) are being studied to target this small tumor-initiating population. Anterior gradient 2 (AGR2), a disulfide isomerase protein, is a well-known pro-oncogenic/metastatic oncogene overexpressed in various tumor tissues, including colon cancer. We found that AGR2 was a novel stem cell marker that was regulated by the canonical Wnt/ß-catenin pathway in colon CSCs. AGR2 was highly co-expressed with surface stem cell markers in spheroidal culture. Silencing of AGR2 resulted in decreased sphere-forming ability and down-regulated expression of stem cell markers, whereas the opposite effects were seen with AGR2 overexpression. Moreover, patients with high ß-catenin and AGR2 expression showed lower overall survival than those with low expression. In conclusion, our study describes a novel role for AGR2 as a stem cell marker that is highly regulated by canonical Wnt/ß-catenin signaling in colorectal cancer.


Assuntos
Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Mucoproteínas/metabolismo , Células-Tronco Neoplásicas/metabolismo , Proteínas Oncogênicas/metabolismo , Via de Sinalização Wnt , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Inativação Gênica , Células HCT116 , Células HEK293 , Humanos , Metástase Neoplásica , Transdução de Sinais , Esferoides Celulares , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
10.
Biochem Biophys Res Commun ; 516(1): 149-156, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31202462

RESUMO

Anterior gradient protein 2 homolog (AGR2) belongs to the disulfide isomerase family of endoplasmic reticulum proteins. Itis overexpressed in several types of solid tumors, including tumors of the prostate, lung, and pancreas. However, the role of AGR2 in breast cancer and the regulatory mechanisms underlying AGR2 protein expressionare not fullyunderstood. We demonstrated that AGR2 levels are increased under hypoxic conditions and in breast cancer tumors. Mechanistically, Twist1 binds to, and activates the AGR2 promoter via an E-box sequence. Under hypoxic conditions, the increased expression of ARG2 is attenuated when Twist1 levels are reduced by shRNA. Conversely, Twist1 overexpression fully reverses decreased AGR2 levels upon HIF-1α knockdown. Notably, AGR2 is required for Twist1-induced proliferation, migration, and invasion of breast cancer cells. Collectively, these findings extend our understanding of AGR2 regulation in breast cancer and may contribute to development of Twist1-AGR2 targeting therapeutics for breast cancer.


Assuntos
Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Mucoproteínas/genética , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Proteína 1 Relacionada a Twist/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Pessoa de Meia-Idade , Regiões Promotoras Genéticas
11.
Mar Drugs ; 17(7)2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31277207

RESUMO

The purpose of the present study is to improve the endothelial progenitor cells (EPC) activation, proliferation, and angiogenesis using enzyme-aided extraction of fucoidan by amyloglucosidase (EAEF-AMG). Enzyme-aided extraction of fucoidan by AMG (EAEF-AMG) significantly increased EPC proliferation by reducing the reactive oxygen species (ROS) and decreasing apoptosis. Notably, EAEF-AMG treated EPCs repressed the colocalization of TSC2/LAMP1 and promoted perinuclear localization of mTOR/LAMP1 and mTOR/Rheb. Moreover, EAEF-AMG enhanced EPC functionalities, including tube formation, cell migration, and wound healing via regulation of AKT/Rheb signaling. Our data provided cell priming protocols to enhance therapeutic applications of EPCs using bioactive compounds for the treatment of CVD.


Assuntos
Células Progenitoras Endoteliais/efeitos dos fármacos , Glucana 1,4-alfa-Glucosidase/metabolismo , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Progenitoras Endoteliais/metabolismo , Humanos , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa/metabolismo , Cicatrização/efeitos dos fármacos
12.
Mar Drugs ; 17(6)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234277

RESUMO

Cardiac progenitor cells (CPCs) are resident stem cells present in a small portion of ischemic hearts and function in repairing the damaged heart tissue. Intense oxidative stress impairs cell metabolism thereby decreasing cell viability. Protecting CPCs from undergoing cellular apoptosis during oxidative stress is crucial in optimizing CPC-based therapy. Histochrome (sodium salt of echinochrome A-a common sea urchin pigment) is an antioxidant drug that has been clinically used as a pharmacologic agent for ischemia/reperfusion injury in Russia. However, the mechanistic effect of histochrome on CPCs has never been reported. We investigated the protective effect of histochrome pretreatment on human CPCs (hCPCs) against hydrogen peroxide (H2O2)-induced oxidative stress. Annexin V/7-aminoactinomycin D (7-AAD) assay revealed that histochrome-treated CPCs showed significant protective effects against H2O2-induced cell death. The anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and Bcl-xL were significantly upregulated, whereas the pro-apoptotic proteins BCL2-associated X (Bax), H2O2-induced cleaved caspase-3, and the DNA damage marker, phosphorylated histone (γH2A.X) foci, were significantly downregulated upon histochrome treatment of hCPCs in vitro. Further, prolonged incubation with histochrome alleviated the replicative cellular senescence of hCPCs. In conclusion, we report the protective effect of histochrome against oxidative stress and present the use of a potent and bio-safe cell priming agent as a potential therapeutic strategy in patient-derived hCPCs to treat heart disease.


Assuntos
Miócitos Cardíacos/efeitos dos fármacos , Naftoquinonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Anexina A5/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/farmacologia , Miócitos Cardíacos/metabolismo , Traumatismo por Reperfusão/induzido quimicamente , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Federação Russa , Proteína X Associada a bcl-2/metabolismo
13.
Biochem Biophys Res Commun ; 499(3): 675-680, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29604275

RESUMO

Mesenchymal stem cells (MSCs) are multipotent progenitor cells with self-renewing properties; thus, transplanting functionally enhanced MSCs might be a promising strategy for cell therapy against ischemic diseases. However, extensive oxidative damage in ischemic tissue affects the cell fate of transplanted MSCs, eventually resulting in cell damage and autophagic cell death. Oleuropein (OLP) is a bioactive compound isolated from olives and olive oil that harbors antioxidant properties. This study aimed to investigate the potential cytoprotective effects of OLP against oxidative stress and autophagic cell death in MSCs. We found that short-term priming with OLP attenuated H2O2-induced apoptosis by regulating the pro-apoptotic marker Bax and the anti-apoptotic markers Bcl-2 and Mcl-1. Notably, OLP inhibits H2O2 -induced autophagic cell death by modulating autophagy-related death signals, including mTOR (mammalian target of rapamycin), ULK1 (unc-51 like autophagy activating kinase 1), Beclin-1, AMPK (AMP-activated protein kinase), and LC3 (microtubule-associated protein 1a/1b-light chain 3). Our data suggest that OLP might reduce H2O2-induced autophagy and cell apoptosis in MSCs by regulating both the AMPK-ULK axis and the Bcl-2-Mcl-1 axis. Consequently, short-term cell priming with OLP might enhance the therapeutic effect of MSCs against ischemic vascular diseases, which provides an important potential improvement for emerging therapeutic strategies.


Assuntos
Tecido Adiposo/patologia , Autofagia/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Iridoides/farmacologia , Células-Tronco Mesenquimais/patologia , Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Células Cultivadas , Citoproteção/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Glucosídeos Iridoides , Iridoides/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Korean J Physiol Pharmacol ; 22(2): 203-213, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29520173

RESUMO

Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.

15.
J Phys Ther Sci ; 28(3): 816-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27134364

RESUMO

[Purpose] The purpose of the present study was to examine the effects of toe-spread (TS) exercises and hip external rotator strengthening exercises for pronated feet on lower extremity muscle activities during stair-walking. [Subjects and Methods] The participants were 20 healthy adults with no present or previous pain, no past history of surgery on the foot or the ankle, and no foot deformities. Ten subjects performed hip external rotator strengthening exercises and TS exercises and the remaining ten subjects performed only TS exercises five times per week for four weeks. [Results] Less change in navicular drop height occurred in the group that performed hip external rotator exercises than in the group that performed only TS exercises. The group that performed only TS exercises showed increased abductor hallucis muscle activity during both stair-climbing and -descending, and the group that performed hip external rotator exercises showed increased muscle activities of the vastus medialis and abductor hallucis during stair-climbing and increased muscle activity of only the abductor hallucis during stair-descending after exercise. [Conclusion] Stair-walking can be more effectively performed if the hip external rotator muscle is strengthened when TS exercises are performed for the pronated foot.

16.
J Phys Ther Sci ; 28(3): 1003-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27134401

RESUMO

[Purpose] This study aimed to determine the effect of abdominal muscle activities and the activation ratio related to trunk stabilization to compare the effects between the abdominal drawing-in maneuver and lumbar stabilization exercises on an unstable base of support. [Subjects and Methods] Study subjects were 20 male and 10 female adults in their 20s without lumbar pain, who were equally and randomly assigned to either the abdominal drawing-in maneuver group and the lumbar stabilization exercise group. Abdominal muscle activation and ratio was measured using a wireless TeleMyo DTS during right leg raise exercises while sitting on a Swiss ball. [Results] Differences in rectus abdominis, external oblique abdominis, and internal oblique abdominis muscle activation were observed before and after treatment. Significant differences were observed between the groups in the muscle activation of the external oblique abdominis and internal oblique abdominis, and the muscle activation ratio of external oblique abdominis/rectus abdominis and internal oblique abdominis/rectus abdominis. [Conclusion] Consequently trunk stability exercise enhances internal oblique abdominis activity and increases trunk stabilization. In addition, the abdominal drawing-in maneuver facilitates the deep muscle more than LSE in abdominal muscle. Therefore, abdominal drawing-in maneuver is more effective than lumbar stabilization exercises in facilitating trunk stabilization.

17.
Eur Arch Otorhinolaryngol ; 272(10): 2969-77, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25182391

RESUMO

The purpose of this study is to evaluate the feasibility of small intestinal submucosa (SIS) application on the parathyroid autotransplantation in a rat model of hypoparathyroidism. The rats were divided into four groups: NC (no procedure, n = 5), PTX (total parathyroidectomy, n = 6), PT (total parathyroidectomy and parathyroid autotransplantation, n = 10) and PT + SIS group (total parathyroidectomy and parathyroid autotransplantation with SIS, n = 10). The levels of parathyroid hormone (PTH), calcium, and phosphorous were measured on 0, 3, 7, 21, 56 and 84 days after surgery. PTH level was expressed as median (interquartile range) and histological and immunohistochemical examinations were performed. PTH levels were significantly decreased to "not detectable level" from day 3 in PTX group. PTH was not detected in both PT and PT + SIS groups on the 21st day. On the 56th day, PTH levels were increased in both groups: 3 out of 8 rats (37.5%) in the PT group, 6 out of 9 rats (66.7%) in the PT + SIS group. The PTH level was fully recovered to its preoperative range on the day 84 as 6 of 8 rats (75%) of the PT group and 7 of 9 rats (77.8%) of the PT + SIS group were recovered; the PTH levels were 117.84 and 178.36 pg/ml, respectively. The neo-vascularization was well observed around the parathyroid tissue, and the number of new vessels formed was higher in the PT + SIS group (15 vessels/high power field) as compared to the PT group (10 vessels/high power field). This study showed the feasibility and the treatment effect of SIS as the success rate of autotransplantation of parathyroid tissue was significantly increased without severe inflammatory response in hypothyroidism animal model.


Assuntos
Hipoparatireoidismo/etiologia , Hipoparatireoidismo/cirurgia , Intestino Delgado/cirurgia , Glândulas Paratireoides/transplante , Transplante Autólogo/métodos , Animais , Cálcio/metabolismo , Modelos Animais de Doenças , Estudos de Viabilidade , Hipoparatireoidismo/metabolismo , Mucosa Intestinal/cirurgia , Masculino , Hormônio Paratireóideo/metabolismo , Paratireoidectomia , Ratos , Ratos Sprague-Dawley
18.
J Phys Ther Sci ; 27(11): 3515-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26696728

RESUMO

[Purpose] The objective of this study was to examine the effect of step climbing exercise on the walking ability of stroke patients. [Subjects and Methods] Among hospitalized stroke patients, 24 were selected based on the study criteria and randomly divided into two groups: an experimental group (12 patients) and a control group (12 patients). The patients in both groups participated in 15-minute exercise sessions three times a week for eight weeks. To analyze the effect of the exercise, muscle strength, the Timed Up and Go test, and step length were measured before and after the exercise. [Results] step climbing exercise improved the muscle strength in the lower limbs of the stroke patients, as well as their Timed Up and Go results and step lengths. [Conclusion] The effects were similar to a stair gait exercise, and thus, step climbing may be more broadly applied to the treatment of stroke patients.

19.
J Phys Ther Sci ; 27(5): 1391-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26157227

RESUMO

[Purpose] This study compared the use of the Maitland mobilization and Kaltenborn mobilization techniques for improving pain and range of motion in patients with frozen shoulders. [Subjects and Methods] The subjects were 20 patients with frozen shoulder who visited Hospital H, Ulsan, Korea. The subjects were divided randomly into two groups to receive Maitland or Kaltenborn mobilization to the affected shoulder. Grade III anteroposterior oscillation and posterior translation were used for the Maitland and Kaltenborn mobilization groups, respectively. Pain and range of motion of external and internal rotation were evaluated pre- and post-intervention in both groups. Paired t-tests were used to compare the pre- and post-intervention results in both groups, and independent t-tests were used to compare groups. [Results] Both groups exhibited significant decreases in pain post-intervention. Moreover, the range of motion of internal and external rotation increased significantly post-intervention in both groups. However, there was no significant difference between groups with respect to pain improvement or range of motion. [Conclusion] The posterior Maitland and Kaltenborn mobilization techniques are effective for improving pain and range of motion in frozen shoulder patients. Therefore, we recommend both techniques for such patients.

20.
J Phys Ther Sci ; 27(2): 367-70, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25729169

RESUMO

[Purpose] The purpose of this study was to examine the effects of selective exercise for the deep abdominal muscles (SEDA) and lumbar stabilization exercise (LSE) on the thickness of the transversus abdominis and postural maintenance on an unstable base of support. [Subjects and Methods] The subjects of this study were 20 male and 10 female adults in their 20s without lumbar pain. They were equally and randomly assigned to a SEDA group and a LSE group. The thickness of the transversus abdominis was measured using ultrasound imaging during rest and drawing-in. The thickness of the transversus abdominis was measured when subjects raised their right and left legs while lying on a Swiss ball. [Results] Initially, there were no differences between the two groups. After the intervention, significant differences were observed in all parameters. A significant interaction between group and period was not found for any parameters. [Conclusion] In conclusion, both SEDA and LSE thickened the transversus abdominis, which is a deep abdominal muscle, thereby adjusting posture, and stabilizing the trunk. These exercises increased the thickness of the deep abdominal muscles. They are important exercises for improving the stability of athletes or patients who need postural adjustment.

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