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1.
Nutrients ; 16(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38337725

RESUMO

Betulinic acid (BetA), a triterpenoid derivative found abundantly in the plant kingdom, has emerged as a promising candidate for promoting longevity. Many research studies have shown its antioxidant, anti-inflammatory, antiviral, and anticancer activities, making it an interesting subject for investigating its potential influence on lifespan. This study aimed to investigate the effects of BetA on longevity and the mechanisms associated with it using the fruit fly Drosophila melanogaster as the organism model. The results showed that 50 µM BetA supplementation extended the mean lifespan of fruit flies by 13% in males and 6% in females without any adverse effects on their physiology, such as fecundity, feeding rate, or locomotion ability reduction. However, 50 µM BetA supplementation failed to increase the lifespan in mutants lacking functional silent information regulator 2 (Sir2) and Forkhead box O (FoxO)-null, implying that the longevity effect of BetA is related to Sir2 and FoxO activation. Our study contributes to the knowledge in the field of anti-aging research and inspires further investigations into natural compounds such as BetA to enhance organismal healthspan.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Masculino , Feminino , Drosophila melanogaster/fisiologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/farmacologia , Ácido Betulínico , Longevidade , Antioxidantes/farmacologia
2.
BMC Cancer ; 23(1): 1242, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38104103

RESUMO

BACKGROUND: Despite the diverse genetic mutations in head and neck cancer, the chemotherapy outcome for this cancer has not improved for decades. It is urgent to select prognostic factors and therapeutic targets for oropharyngeal cancer to establish precision medicine. Recent studies have identified PSMD1 as a potential prognostic marker in several cancers. We aimed to assess the prognostic significance of PSMD1 expression in oropharyngeal squamous cell carcinoma (OPSCC) patients using immunohistochemistry. METHODS: We studied 64 individuals with OPSCC tissue from surgery at Seoul National University Bundang Hospital between April 2008 and August 2017. Immunostaining analysis was conducted on the tissue microarray (TMA) sections (4 µm) for p16 and PSMD1. H-score, which scale from 0 to 300, was calculated from each nucleus, cytoplasm, and cellular expression. Clinicopathological data were compared with Chi-squared test, Fisher's exact test, t-test, and logistic regression. Survival data until 2021 were achieved from national statistical office of Korea. Kaplan-Meier method and cox-regression model were used for disease-specific survival (DSS) analysis. RESULTS: H-score of 90 in nucleus was appropriate cutoff value for 'High PSMD1 expression' in OPSCC. Tonsil was more frequent location in low PSMD1 group (42/52, 80.8%) than in high PSMD1 group (4/12, 33.3%; P = .002). Early-stage tumor was more frequent in in low PSMD1 group (45/52, 86.5%) than in high PSMD1 group (6/12, 50%; P = .005). HPV was more positive in low PSMD1 group (43/52, 82.7%) than in high PSMD1 group (5/12, 41.7%; P = .016). Patients with PSMD1 high expression showed poorer DSS than in patients with PSMD1 low expression (P = .006 in log rank test). In multivariate analysis, PSMD1 expression, pathologic T staging, and specimen age were found to be associated with DSS (P = .011, P = .025, P = .029, respectively). CONCLUSIONS: In our study, we established PSMD1 as a negative prognostic factor in oropharyngeal squamous cell carcinoma, indicating its potential as a target for targeted therapy and paving the way for future in vitro studies on drug repositioning.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Prognóstico , Carcinoma de Células Escamosas/patologia , Papillomavirus Humano 16/genética , Neoplasias Orofaríngeas/patologia , Neoplasias de Cabeça e Pescoço/complicações , Complexo de Endopeptidases do Proteassoma/metabolismo
3.
J Thorac Dis ; 14(4): 1009-1019, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35572885

RESUMO

Background: There have been few studies to verify factors associated with a false-negative interferon-gamma release assay (IGRA) in patients with tuberculous pleurisy. We investigated the clinical relevance of false-negative results of the blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and its risk factors in patients diagnosed with pleural tuberculosis (TB). Methods: Medical records of 650 pleural TB patients in a tertiary hospital between January 2009 and December 2020 were reviewed retrospectively. Patients who underwent the blood QFT-GIT assay and pleural fluid analysis before starting anti-TB medication were included. Results: Of 199 patients with pleural TB who were performed QFT-GIT assay, 36 (18.1%) were false-negative results. These patients tended to be older than those with a positive result (P=0.060). The QFT-GIT-false-negative group of had significantly more comorbidities such as end-stage renal disease (ESRD), haematological cancer or pneumoconiosis than the QFT-GIT-positive group. Hypoproteinaemia and pH >6 in pleural fluid were associated with a false-negative QFT-GIT. Of the 199 patients, 163 (81.9%) were cured or completed anti-TB treatment; 13 patients (6.5%) died. The QFT-GIT-negative patients had significantly worse outcomes including mortality [unfavourable outcome: 33.3% (12/36 patients) in QFT-GIT-negative groups vs. 14.7% (24/163 patients) in QFT-GIT-positive groups, P<0.017; overall mortality: 16.7% (6/36 patients) vs. 4.3% (7/163 patients), respectively, P<0.015]. Conclusions: In pleural TB, a false-negative QFT-GIT result was 18.1% in a country of intermediate TB incidence. This discordant result in GFT-GIT was associated with ESRD, pneumoconiosis, hypoproteinaemia and a poor outcome. Clinicians should keep in mind the possibility of false-negativity in the blood IGRA test, especially in specific situations and its impact on TB outcome in managing patients with pleural TB.

4.
Adv Biosyst ; 4(7): e1900248, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32558394

RESUMO

Many studies utilizing animal models have revealed the genetic and pharmacogenetic modulators of the rate of organismal aging. However, finding routes for healthy aging during extended life remains one of the largest questions. With regards to an antiaging reagent, it has been shown that natural phytochemical syringaresinol (SYR) delays cellular senescence by activating sirtuin1 (SIRT1). Here, it is found that SYR treatment results in metabolic changes similar to those observed during dietary restriction (DR). The DR mimetic effects are mediated by FoxO3a-dependent SIRT1 activation and insulin/insuline growth factor-1 signaling modulation. The direct binding of SYR-FoxO3a is identified and this could partially explain the DR-like phenotype. The report gives a clue as to how the longevity gene involves the DR pathway and suggests that natural phytochemicals applied as a geroprotector mimics DR effects.


Assuntos
Materiais Biomiméticos/farmacologia , Restrição Calórica , Proteína Forkhead Box O3/metabolismo , Compostos Fitoquímicos/farmacologia , Animais , Reprogramação Celular , Camundongos , Sirtuína 1/metabolismo
5.
Urology ; 136: 190-195, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31730940

RESUMO

OBJECTIVE: To provide the anatomy of the puboprostatic ligament and related structures to save urogenital competence after prostatectomy. MATERIALS AND METHODS: Pelvic areas of 31 adult cadavers were dissected to figure out the shape, number, and location of the puboprostatic ligaments. RESULTS: The puboprostatic ligament was the most important support structure between the pubic bone and prostate gland. Puboprostatic ligaments were bilaterally single (61.3%), bilaterally double (19.4%), or mixed (19.4%). Ligaments were mostly I-shaped (53.8%). If ligaments had extra attachment to or from the arcuate line, the ligaments were λ-shaped (36.3%), or Y-shaped (8.8%). In one case, the ligament had a central fusion with an irregular shape. I-shaped puboprostatic ligaments were observed more frequently in specimens with double ligaments, while λ-shaped puboprostatic ligaments were observed more frequently in the cases with single ligaments. The average distance between both puboprostatic ligaments was 8.1 mm at the pubic site and 14.2 mm at the prostate site. The distance was narrower when the specimen had double puboprostatic ligaments on both sides. The neurovascular bundle ran beneath the puboprostatic ligament. If the ligament was the λ-shaped type, the neurovascular bundle frequently pierced the lateral band of the ligament. CONCLUSION: Puboprostatic ligaments hold and stabilize the prostate against the pubic bone. It is believed that a pelvis with bilateral, double puboprostatic ligaments would have advantages in urogenital competence. The morphologic data of the shape, multiplicity, and location of the PPLs would help to make a plan to approach the prostate.


Assuntos
Ligamentos/anatomia & histologia , Próstata/anatomia & histologia , Prostatectomia/métodos , Osso Púbico/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Cadáver , Humanos , Masculino , Pessoa de Meia-Idade
6.
EMBO Mol Med ; 12(1): e10880, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31709755

RESUMO

Molecular programs involved in embryogenesis are frequently upregulated in oncogenic dedifferentiation and metastasis. However, their precise roles and regulatory mechanisms remain elusive. Here, we showed that CDK1 phosphorylation of TFCP2L1, a pluripotency-associated transcription factor, orchestrated pluripotency and cell-cycling in embryonic stem cells (ESCs) and was aberrantly activated in aggressive bladder cancers (BCs). In murine ESCs, the protein interactome and transcription targets of Tfcp2l1 indicated its involvement in cell cycle regulation. Tfcp2l1 was phosphorylated at Thr177 by Cdk1, which affected ESC cell cycle progression, pluripotency, and differentiation. The CDK1-TFCP2L1 pathway was activated in human BC cells, stimulating their proliferation, self-renewal, and invasion. Lack of TFCP2L1 phosphorylation impaired the tumorigenic potency of BC cells in a xenograft model. In patients with BC, high co-expression of TFCP2L1 and CDK1 was associated with unfavorable clinical characteristics including tumor grade, lymphovascular and muscularis propria invasion, and distant metastasis and was an independent prognostic factor for cancer-specific survival. These findings demonstrate the molecular and clinical significance of CDK1-mediated TFCP2L1 phosphorylation in stem cell pluripotency and in the tumorigenic stemness features associated with BC progression.


Assuntos
Proteína Quinase CDC2/metabolismo , Carcinogênese , Células-Tronco Embrionárias/citologia , Proteínas Repressoras/metabolismo , Neoplasias da Bexiga Urinária/patologia , Animais , Diferenciação Celular , Feminino , Humanos , Masculino , Camundongos , Fosforilação , Estudos Retrospectivos , Bexiga Urinária/patologia
7.
Theranostics ; 8(20): 5610-5624, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555567

RESUMO

Rationale: Mesenchymal stem cell (MSC) therapy may be a novel approach to improve interstitial cystitis/bladder pain syndrome (IC/BPS), an intractable disease characterized by severe pelvic pain and urinary frequency. Unfortunately, the properties of transplanted stem cells have not been directly analyzed in vivo, which hampers elucidation of the therapeutic mechanisms of these cells and optimization of transplantation protocols. Here, we monitored the behaviors of multipotent stem cells (M-MSCs) derived from human embryonic stem cells (hESCs) in real time using a novel combination of in vivo confocal endoscopic and microscopic imaging and demonstrated their improved therapeutic potency in a chronic IC/BPS animal model. Methods: Ten-week-old female Sprague-Dawley rats were instilled with 10 mg of protamine sulfate followed by 750 µg of lipopolysaccharide weekly for 5 weeks. The sham group was instilled with phosphate-buffered saline (PBS). Thereafter, the indicated dose (0.1, 0.25, 0.5, and 1×106 cells) of M-MSCs or PBS was injected once into the outer layer of the bladder. The distribution, perivascular integration, and therapeutic effects of M-MSCs were monitored by in vivo endoscopic and confocal microscopic imaging, awake cystometry, and histological and gene expression analyses. Results: A novel combination of longitudinal intravital confocal fluorescence imaging and microcystoscopy in living animals, together with immunofluorescence analysis of bladder tissues, demonstrated that transplanted M-MSCs engrafted following differentiation into multiple cell types and gradually integrated into a perivascular-like structure until 30 days after transplantation. The beneficial effects of transplanted M-MSCs on bladder voiding function and the pathological characteristics of the bladder were efficient and long-lasting due to the stable engraftment of these cells. Conclusion: This longitudinal bioimaging study of transplanted hESC-derived M-MSCs in living animals reveals their long-term functional integration, which underlies the improved therapeutic effects of these cells on IC/BPS.


Assuntos
Cistite Intersticial/diagnóstico por imagem , Cistite Intersticial/terapia , Microscopia Intravital/métodos , Células-Tronco Mesenquimais/citologia , Bexiga Urinária/diagnóstico por imagem , Animais , Modelos Animais de Doenças , Feminino , Transplante de Células-Tronco Mesenquimais , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/transplante , Ratos , Ratos Sprague-Dawley
8.
Leukemia ; 32(12): 2672-2684, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29789652

RESUMO

Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro-angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation. SHC-MSCs showed DNA demethylation in pluripotency, germline, and imprinted genes similarly to very small embryonic-like stem cells, suggesting a potential mutual relationship. Genome-wide DNA methylome and transcriptome analyses indicated that genes related to immune modulation, cell adhesion, and the cell cycle were up-regulated in SHC-MSCs. Particularly, polo-like kinase-1 (PLK1), zinc-finger protein-143, dehydrogenase/reductase-3, and friend-of-GATA2 play a key role in the beneficial effects of SHC-MSCs. Administration of SHC-MSCs or PLK1-overexpressing MSCs significantly ameliorated symptoms of graft-versus-host disease (GVHD) in a humanized mouse model, resulting in significantly improved survival, less weight loss, and reduced histopathologic injuries in GVHD target organs compared with naïve MSC-infused mice. Collectively, our findings suggest that SHC-MSCs can improve the clinical treatment of allogeneic conflicts, including GVHD.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Hipóxia/imunologia , Células-Tronco Mesenquimais/imunologia , Animais , Adesão Celular/imunologia , Ciclo Celular/imunologia , Linhagem Celular , Proliferação de Células/fisiologia , Humanos , Leucócitos Mononucleares , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos , Camundongos Endogâmicos NOD , Linfócitos T/imunologia , Regulação para Cima/imunologia
9.
Int Neurourol J ; 22(Suppl 1): S34-45, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29385783

RESUMO

PURPOSE: To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. METHODS: To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. RESULTS: Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. CONCLUSIONS: This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.

10.
Oncol Rep ; 38(6): 3481-3488, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29039612

RESUMO

Contemporary research has focused on the function of long non-coding RNAs (lncRNAs) in carcinogenesis. However, the involvement of the lncRNA, steroid receptor RNA activator (SRA), in cervical carcinogenesis remains to be elucidated. In the present study, we investigated the bio-functional consequences of lncRNA SRA knockdown in vitro. To verify the role of lncRNA SRA in cell proliferation, migration, and invasion, lncRNA RNA interference was utilized to knock down lncRNA SRA expression in cervical cancer cell lines, resulting in our discovery that lncRNA SRA knockdown inhibited cell proliferation, cell migration and tumor invasion in the cervical cancer cell lines. Additionally, in vitro experiments using the lncRNA SRA-knockdown cervical cancer cell lines revealed that lncRNA SRA is a strong inducer and modulator of the expression of genes related to epithelial-mesenchymal transition and the NOTCH signaling pathway. In conclusion, our findings demonstrated that lncRNA SRA is highly correlated with cancer progression and cervical cancer cell proliferation and migration. Furthermore, these results indicate that lncRNA SRA may be a potential therapeutic target and prognostic marker for cervical malignancy.


Assuntos
Biomarcadores Tumorais/genética , Carcinogênese/genética , Proteínas de Transporte/genética , Proliferação de Células/genética , Neoplasias do Colo do Útero/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Invasividade Neoplásica/genética , Receptores Notch/genética , Transdução de Sinais/genética , Neoplasias do Colo do Útero/patologia
11.
Korean J Parasitol ; 55(4): 375-384, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28877568

RESUMO

Trichomonas vaginalis is a pathogen that triggers severe immune responses in hosts. T. vaginalis α-actinin 2, Tvα-actinin 2, has been used to diagnose trichomoniasis. This study was undertaken to examine the role of Tvα-actinin 2 as an antigenic molecule to induce immune responses from humans. Western blot analysis using anti-Tvα-actinin 2 antibodies indicated its presence in the secreted proteins of T. vaginalis. ELISA was employed to measure cytokine production by vaginal epithelial cells, prostate cells, mouse dendritic cells (DCs), or T cells stimulated with T. vaginalis or Tvα-actinin 2 protein. Both T. vaginalis and rTvα-actinin 2 induced cytokine production from epithelial cell lines, including IL-10. Moreover, CD4+CD25- regulatory T cells (Treg cells) incubated with rTvα-actinin 2-treated DCs produced high levels of IL-10. These data indicate that Tvα-actinin 2 modulates immune responses via IL-10 production by Treg cells.


Assuntos
Actinina/imunologia , Células Dendríticas/imunologia , Interações Hospedeiro-Parasita/imunologia , Interleucina-10/biossíntese , Linfócitos T Reguladores/imunologia , Trichomonas vaginalis/imunologia , Animais , Anticorpos Antiprotozoários/imunologia , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/imunologia , Humanos , Camundongos Endogâmicos BALB C , Compostos Orgânicos/imunologia
12.
J Microbiol Biotechnol ; 27(10): 1844-1854, 2017 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-28838225

RESUMO

Trichomonas vaginalis is a pathogen that triggers severe immune responses in hosts. T. vaginalis α-actinin 2 (Tvα-actinin 2) has been used to diagnose trichomoniasis. Tvα-actinin 2 was dissected into three parts; the N-terminal, central, and C-terminal portions of the protein (#1, #2, and #3, respectively). Western blot of these Tvα-actinin 2 proteins with pooled patients' sera indicated that #2 and #3, but not #1, reacted with those sera. Immunofluorescence assays of two different forms of T. vaginalis (trophozoites and amoeboid forms), using anti-Tvα-actinin 2 antibodies, showed localization of Tvα-actinin 2 close to the plasma membranes of the amoeboid form. Fractionation experiments indicated the presence of Tvα-actinin 2 in cytoplasmic, membrane, and secreted proteins of T. vaginalis. Binding of fluorescence-labeled Trichomonas to vaginal epithelial cells and prostate cells was decreased in the antibody blocking experiment using anti-Tvα-actinin 2 antibodies. Pretreatment of T. vaginalis with anti-rTvα-actinin 2 antibodies also resulted in reduction in its cytotoxicity. Flow cytometry, ligand-binding immunoblotting assay, and observation by fluorescence microscopy were used to detect the binding of recombinant Tvα-actinin 2 to human epithelial cell lines. Specifically, the truncated N-terminal portion of Tvα-actinin 2, Tvα-actinin 2 #1, was shown to bind directly to vaginal epithelial cells. These data suggest that α-actinin 2 is one of the virulence factors responsible for the pathogenesis of T. vaginalis by serving as an adhesin to the host cells.


Assuntos
Actinina/fisiologia , Trichomonas vaginalis/metabolismo , Actinina/genética , Antígenos de Protozoários/genética , Antígenos de Protozoários/fisiologia , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Linhagem Celular , Células Epiteliais , Feminino , Regulação da Expressão Gênica , Humanos , Proteínas Recombinantes , Tricomoníase/imunologia , Trichomonas vaginalis/genética , Trichomonas vaginalis/imunologia , Trofozoítos , Vagina , Fatores de Virulência
13.
Int J Mol Med ; 40(3): 739-747, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28677769

RESUMO

Engraftment and homing of mesenchymal stem cells (MSCs) are modulated by priming factors including the bioactive lipid sphingosine-1-phosphate (S1P), by stimulating CXCR4 receptor signaling cascades. However, limited in vivo efficacy and the remaining priming molecules prior to administration of MSCs can provoke concerns regarding the efficiency and safety of MSC priming. Here, we showed that valproic acid (VPA), a histone deacetylase inhibitor, enforced the priming effect of S1P at a low dosage for human umbilical cord-derived MSCs (UC-MSCs). A DNA-methylation inhibitor, 5-azacytidine (5-Aza), and VPA increased the expression of CXCR4 in UC-MSCs. In particular, UC-MSCs primed with a suboptimal dose (50 nM) of S1P in combination with 0.5 mM VPA (VPA+S1P priming), but not 1 µM 5-Aza, significantly improved the migration activity in response to stromal cell-derived factor 1 (SDF-1) concomitant with the activation of both MAPKp42/44 and AKT signaling cascades. Both epigenetic regulatory compounds had little influence on cell surface marker phenotypes and the multi-potency of UC-MSCs. In contrast, VPA+S1P priming of UC-MSCs potentiated the proliferation, colony forming unit-fibroblast, and anti-inflammatory activities, which were severely inhibited in the case of 5-Aza treatment. Accordingly, the VPA+S1P-primed UC-MSCs exhibited upregulation of a subset of genes related to stem cell migration and anti-inflammation response. Thus, the present study demonstrated that VPA enables MSC priming with S1P at a low dosage by enhancing their migration and other therapeutic beneficial activities. This priming strategy for MSCs may provide a more efficient and safe application of MSCs for treating a variety of intractable disorders.


Assuntos
Movimento Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Lisofosfolipídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Esfingosina/análogos & derivados , Ácido Valproico/farmacologia , Humanos , Células-Tronco Mesenquimais/citologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores CXCR4/biossíntese , Esfingosina/farmacologia
14.
World J Mens Health ; 34(1): 34-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27169127

RESUMO

PURPOSE: Due to the increasing numbers of radical prostatectomies (RP) performed for prostate cancer, a substantial and increasing number of patients suffer from postoperative urinary incontinence and erectile dysfunction (ED). The objective of our study was to see whether an inflatable penile prosthesis implantation could control urinary incontinence for patients with the dual problems of ED and incontinence. MATERIALS AND METHODS: From March 2010 through May 2015, 25 post-RP patients were referred to our clinic with ED or incontinence. The degree of incontinence was classified according to the International Consultation on Incontinence Questionnaire-Short Form. Inflatable penile prostheses were implanted in all 25 patients. RESULTS: For one month after implantation, partial or full inflation was performed progressively to control urine leakage. Of 18 patients, 13 patients were categorized with mild or moderate stress incontinence. All 13 patients obtained control of incontinence with partial inflation (30% to 60%) and all reported satisfactory outcomes. Five out of the 18 patients were categorized with severe total incontinence. Three of the 5 patients could tolerate incontinence with full inflation on and off. Thirteen patients out of the total of 18 (72.2%) had their incontinence controlled by an inflating penile prosthesis. CONCLUSIONS: An inflatable penile prosthesis is highly recommended as an initial procedure, especially in patients with the dual problems of ED and incontinence.

15.
Int J Syst Evol Microbiol ; 66(5): 1996-2001, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26883120

RESUMO

Two novel actinobacteria, designated strains Gsoil 097T and Gsoil 818T, isolated from soil of a ginseng field, South Korea, were characterized by a polyphasic approach to clarify their taxonomic positions. They were Gram-reaction-positive, aerobic, non-spore-forming and rod-shaped. Phylogenetic analysis based on 16S rRNA gene sequences indicated that both isolates belong to the genus Marmoricola and were related most closely to Marmicola solisilvae KIS18-7T (99.1 and 98.3 % similarity, respectively), Marmicola terrae JOS5-1T (97.9 and 97.9 %), Marmicola scoriae Sco-D01T (97.8 and 97.1 %) and Marmicola aequoreus SST-45T (97.5 and 97.0 %). The G+C content of the genomic DNA was 68.8 and 70.0 mol%, respectively. Both strains were characterized chemotaxonomically as having ll-2,6-diaminopimelic acid in the cell-wall peptidoglycan, MK-8(H4) as the predominant menaquinone and C17 : 1ω6c, C18 : 1ω9c, C18 : 0 10-methyl and iso-C16 : 0 as major fatty acids. These chemotaxonomic data supported the affiliation of both strains to the genus Marmoricola. However, levels of DNA-DNA relatedness between the two strains and closely related type strains of Marmoricola species were less than 30 %. Moreover, the results of physiological and biochemical tests allowed the phenotypic differentiation of strains Gsoil 097T and Gsoil 818T from other Marmoricola species with validly published names. Therefore, the two isolates represent two novel species, for which the names Marmoricola ginsengisoli sp. nov. (type strain Gsoil 097T = KACC 14267T = DSM 22772T) and Marmoricola pocheonensis sp. nov. (type strain Gsoil 818T = KACC 14275T = DSM 22773T) are proposed.


Assuntos
Actinomycetales/classificação , Panax/microbiologia , Filogenia , Microbiologia do Solo , Actinomycetales/genética , Actinomycetales/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , DNA Ribossômico/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
16.
J Sep Sci ; 38(24): 4276-85, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26500147

RESUMO

For the first time, electromembrane extraction combined with liquid chromatography and tandem mass spectrometry was applied for the determination of urinary benzene, toluene, ethylbenzene, and xylene metabolites. S-Phenylmercapturic acid, hippuric acid, phenylglyoxylic acid, and methylhippuric acid isomers were extracted from human urine through a supported liquid membrane consisting of 1-octanol into an alkaline acceptor solution filling the inside of a hollow fiber by application of an electric field. Various extraction factors were investigated and optimized using response surface methodology, the statistical method. The optimum conditions were established to be 300 V applied voltage, 15 min extraction time, 1500 rpm stirring speed, and 5 mM ammonium acetate (pH 10.2) acceptor solution. The method was validated with respect to selectivity, linearity, accuracy, precision, limit of detection, limit of quantification, recovery, and reproducibility. The results showed good linearity (r(2) > 0.995), precision, and accuracy. The extract recoveries were 52.8-79.0%. Finally, we applied this method to real samples and successfully measured benzene, toluene, ethylbenzene, and xylene metabolites.


Assuntos
Derivados de Benzeno/urina , Cromatografia Líquida , Espectrometria de Massas em Tandem , Tolueno/urina , Urinálise/instrumentação , Urinálise/métodos , Xilenos/urina , Humanos , Limite de Detecção , Estrutura Molecular , Microextração em Fase Sólida
17.
J Gastric Cancer ; 15(2): 147-50, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26161290

RESUMO

Gastric volvulus is an uncommon clinical entity. There are three types of gastric volvulus; organoaxial, mesenteroaxial and combined type. This condition can lead to a closed-loop obstruction or strangulation. Traditional surgical therapy for gastric volvulus is based on an open approach. Here we report a successful case of a patient with chronic gastric volvulus with a laparoscopic treatment. A 79-year-old woman came to the emergency department with epigastric pain accompanied by nausea for 2 weeks. Abdominal computed tomography revealed markedly distended stomach with transposition of gastroesophageal Junction and gastric antrum. Barium meal study revealed presence of the antrum was folded over 180 degrees that was located above gastroesophageal junction. We attempted an endoscopic reduction, but it was unsuccessful. The patient got laparoscopic anterior gastropexy. Based on our result, laparoscopic gastropexy can be considered as a good choice of the treatment for gastric volvulus.

18.
Ann Hematol ; 94(1): 153-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25062720

RESUMO

Pulmonary infections are a major cause of morbidity and mortality in patients with hematologic malignancy. Bronchoscopy is at present still the traditional first investigation in immunosuppressed patients that have developed pulmonary infiltrates. There is limited data available on the validity of fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) to determine the etiology of pulmonary infiltrates with concurrent hematologic malignancy. We retrospectively analyzed the microbiological results of 206 bronchoscopic examinations and treatment changes used in 187 patients with hematologic malignancy and pulmonary infiltrates. Bacteria, fungi, and viruses were found in 85 (41.3 %), 49 (23.8 %), and 55 (28.6 %) of cases, respectively, and overall yield of bronchoscopy was 65.0 %. We compared the microbiological findings with respect to neutropenia, hematopoietic stem cell transplantation (HSCT) status, and the type of malignancy. There were significantly more bacterial and viral infections detected in post-HSCT patients, and more viruses were detected in patients without neutropenia. Galactomannan (GM) was measured in 149 BAL samples. With a GM index threshold of ≥0.5, the sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of the BAL GM assay were 93.94 %, 86.21 %, 65.96 %, and 98.04 %, respectively. Treatment was modified in 62 cases (30.1 %). There was no significant relationship of treatment modification with the underlying disease, HSCT, or neutropenia. Bronchoscopy with BAL is a valuable diagnostic tool to determine the etiology and appropriate treatment in patients with hematologic malignancy and pulmonary infiltrates. A BAL GM test is recommended when invasive pulmonary aspergillosis is suspected.


Assuntos
Lavagem Broncoalveolar/métodos , Broncoscopia/métodos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/microbiologia , Pulmão/microbiologia , Pulmão/virologia , Adolescente , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/microbiologia , Líquido da Lavagem Broncoalveolar/virologia , Feminino , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/microbiologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/microbiologia , Estudos Retrospectivos , Adulto Jovem
19.
Dermatol Surg ; 41(1): 87-93, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25521099

RESUMO

BACKGROUND: Deactivation of the corrugator supercilii for the treatment of unintentional glabellar lines requires high selectivity to avoid sensory complications. OBJECTIVE: The aim of this study was to delineate the topographic anatomy of facial and trigeminal nerves in relation to the corrugator supercilii to improve the selectivity and safety of deactivation of the corrugator supercilii muscle. MATERIALS AND METHODS: The number, courses, and attachments of the facial nerve to the corrugator supercilii muscle were investigated by dissection of 27 cadaveric hemifaces. Twelve cadaveric hemiforehead flaps were stained using a modified Sihler method to trace the supraorbital and supratrochlear branches. RESULTS: On average, 1.8 branches of the facial nerve at the zygomatic arch were associated with the corrugator supercilii muscle through 1 (29.3%) or 2 terminal rami (70.7%). The trigeminal nerve gave off 7.7 supraorbital and 5.1 supratrochlear branches emerging from orbit. The majority of the supraorbital branches became intramuscular branches (60.4%), whereas the majority of the supratrochlear branches became superficial branches (67.8%). CONCLUSION: Resection of the muscle may damage the intramuscular trigeminal branches, leading to sensory changes. The course of the facial nerve branches to the corrugator supercilii muscle was much more predictable at their distal part than the proximal part.


Assuntos
Nervo Facial/anatomia & histologia , Testa/inervação , Músculo Esquelético/inervação , Nervo Trigêmeo/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cadáver , Corantes , Feminino , Humanos , Masculino , Microdissecção , Pessoa de Meia-Idade , Ritidoplastia , Envelhecimento da Pele , Coloração e Rotulagem/métodos
20.
Biogerontology ; 15(2): 153-64, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24337961

RESUMO

Viscum album coloratum (Korean mistletoe) is a semi-parasitic plant that grows on various trees and has a variety of biological functions such as immunomodulation, apoptosis, and anti-tumor activity. In this study, we investigated the effects of Korean mistletoe extract (KME) on lifespan in experimental models using Caenorhabditis elegans and Drosophila melanogaster. Supplementation of KME at 50 µg/ml extended the mean survival time by 9.61 and 19.86 % in worms and flies, respectively. The longevity benefit of KME was not due to reduced feeding, reproduction, and/or locomotion in flies and worms. The supplementation of KME also did not increase resistance to various stresses including heat shock, oxidative, or starvation stresses. Furthermore, KME did not further extend the lifespan of flies fed a dietary restricted diet but did increase the expression of Sir2, one of the target genes of dietary restriction, suggesting that KME may function as a putative dietary restriction mimetic. These results also suggest that the longevity promoting effects of KME may be an example of mild stress-induced hormesis.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Drosophila melanogaster/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Viscum album/química , Animais , Restrição Calórica , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Feminino , Expressão Gênica/efeitos dos fármacos , Genes de Insetos , Histona Desacetilases/genética , Masculino , Medicina Tradicional Coreana , Extratos Vegetais/farmacologia , Sirtuínas/genética , Estresse Fisiológico/efeitos dos fármacos
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