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1.
Mar Drugs ; 21(10)2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37888466

RESUMO

Prolonged thymic involution results in decreased thymopoiesis and thymic output, leading to peripheral T-cell deficiency. Since the thymic-dependent pathway is the only means of generating fully mature T cells, the identification of strategies to enhance thymic regeneration is crucial in developing therapeutic interventions to revert immune suppression in immunocompromised patients. The present study clearly shows that fish collagen peptides (FCPs) stimulate activities of thymic epithelial cells (TECs), including cell proliferation, thymocyte adhesion, and the gene expression of thymopoietic factors such as FGF-7, IGF-1, BMP-4, VEGF-A, IL-7, IL-21, RANKL, LTß, IL-22R, RANK, LTßR, SDF-1, CCL21, CCL25, CXCL5, Dll1, Dll4, Wnt4, CD40, CD80, CD86, ICAM-1, VCAM-1, FoxN1, leptin, cathepsin L, CK5, and CK8 through the NF-κB signal transduction pathway. Furthermore, our study also revealed the cytoprotective effects of FCPs on TECs against cyclophosphamide-induced cellular injury through the NF-κB signaling pathway. Importantly, FCPs exhibited a significant capability to facilitate thymic regeneration in mice after cyclophosphamide-induced damage via the NF-κB pathway. Taken together, this study sheds light on the role of FCPs in TEC function, thymopoiesis, and thymic regeneration, providing greater insight into the development of novel therapeutic strategies for effective thymus repopulation for numerous clinical conditions in which immune reconstitution is required.


Assuntos
NF-kappa B , Timócitos , Humanos , Camundongos , Animais , NF-kappa B/metabolismo , Citoproteção , Timo , Células Epiteliais , Colágeno/metabolismo , Expressão Gênica , Proliferação de Células , Ciclofosfamida/efeitos adversos
2.
Cancer Manag Res ; 15: 1111-1121, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37822733

RESUMO

Purpose: The diagnostic value of preoperative hematological changes in endometrial cancer (EC) remains unclear. This study aimed to assess the role of preoperative hematologic parameters in differentiating EC from benign endometrial lesions in postmenopausal women with endometrial masses. Methods: Preoperative laboratory variables were retrospectively reviewed in patients with malignant or benign endometrial lesions, and the significance of intergroup differences was assessed. Receiver operating characteristic curves were used to analyze the optimal cut-off values for each variable. Logistic regression analysis was used to identify the variables predicting the presence of endometrial malignancy. Results: Preoperative laboratory variables of 176 patients (84 EC and 92 benign lesions) with endometrial masses were analyzed. Significant differences were observed between malignant and benign lesions in terms of WBC count, ANC, MCV, MPV, PDW, CA125, NLR, PMR, LMR, and SII (P < 0.05). Multivariate analyses showed that a high WBC count, high ANC, low MCV, low MPV, low PDW, high CA125, high NLR, high PMR, high LMR, and high SII independently predicted the presence of endometrial malignancy. Conclusion: The combination markers, MPV+PDW+NLR, had good discriminatory power for the presence of malignancy (AUC 0.797). Our results suggest that hematologic markers could be useful for the differentiation of malignant and benign endometrial lesions.

3.
Minerva Obstet Gynecol ; 75(3): 236-242, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36786781

RESUMO

BACKGROUND: The aim of this study was to compare the effects of a 12-week course and four repeated 12-week courses of daily 5 mg ulipristal acetate (UPA) on reducing the volume and relieving symptoms of uterine fibroids. METHODS: From 2016 to 2019, 287 female patients with uterine fibroids diagnosed using ultrasonography were recruited. The patients received four 12-week course treatments of daily UPA administration in the first and fourth sessions, respectively. During the first and fourth courses of UPA, we measured the volume of the fibroids using ultrasonography to study the effect on volume reduction. The measured outcomes included symptomatic relief and adverse effects. RESULTS: After the first UPA treatment course, menorrhagia was improved in 82.2% of patients. A total of 59.5% of patients were responsive to treatment, and the volume of the three largest fibroids decreased from 160.9 cm3 to 104.6 cm3. After the fourth treatment course, 87.4% of patients reported decreased bleeding. A total of 67.2% of patients were responsive to treatment, and the volume of the three largest fibroids decreased from 171.7 cm3 to 106.5 cm3. In 64 (38.1%) patients in group A and 36 (30.3%) in group B, the fibroid volume increased. Among them, 72% of patients showed improved symptoms. CONCLUSIONS: Uterine bleeding, pain, and reduced fibroid volume were adequately regulated in patients with symptomatic fibroids with four repeated 12-week courses of daily UPA.


Assuntos
Contraceptivos Hormonais , Leiomioma , Menorragia , Norpregnadienos , Neoplasias Uterinas , Feminino , Humanos , Leiomioma/diagnóstico por imagem , Leiomioma/tratamento farmacológico , Menorragia/etiologia , Menorragia/induzido quimicamente , Norpregnadienos/uso terapêutico , Neoplasias Uterinas/tratamento farmacológico , Contraceptivos Hormonais/uso terapêutico , Anticoncepcionais Femininos , Resultado do Tratamento , Adulto , Pessoa de Meia-Idade
4.
Int J Mol Sci ; 23(7)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35409294

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP) is a frequently used plasticizer that may be linked to the development of endometriosis, a common gynecological disorder with a profound impact on quality of life. Despite its prevalence, vital access to treatment has often been hampered by a lack of understanding of its pathogenesis as well as reliable disease models. Recently, epithelial-mesenchymal transition (EMT) has been suggested to have a significant role in endometriosis pathophysiology. In this study, we found that DEHP treatment enhanced proliferation, migration, and inflammatory responses, along with EMT and stemness induction in human endometrial and endometriotic cells. The selective transforming growth factor-ß (TGF-ß) receptor type 1/2 inhibitor LY2109761 reversed the DEHP-induced cell proliferation and migration enhancement as well as the increased expression of crucial molecules involved in inflammation, EMT, and stemness, indicating that DEHP-triggered phenomena occur via the TGF-ß/Smad signaling pathway. Our study clearly defines the role of DEHP in the etiology and pathophysiological mechanisms of endometriosis and establishes an efficient disease model for endometriosis using a biomimetic 3D cell culture technique. Altogether, our data provide novel etiological and mechanistic insights into the role of DEHP in endometriosis pathogenesis, opening avenues for developing novel preventive and therapeutic strategies for endometriosis.


Assuntos
Dietilexilftalato , Endometriose , Proliferação de Células , Dietilexilftalato/metabolismo , Dietilexilftalato/toxicidade , Endometriose/patologia , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Feminino , Humanos , Ácidos Ftálicos , Qualidade de Vida , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fatores de Crescimento Transformadores/metabolismo
5.
Reprod Sci ; 27(2): 681-689, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31942708

RESUMO

The activation of dormant primordial follicles and ovarian angiogenesis has been attempted as a new treatment strategy for age-related ovarian aging. This study examined whether visfatin rescues age-related fertility decline in female mice aged 18 months, and whether this effect relates to the mTOR/PI3K signaling pathways for activation of primordial follicles and ovarian angiogenesis. Female mice were intraperitoneally injected with 0.1 ml of 500 ng/ml or 1000 ng/ml of visfatin three times at intervals of 2 days, and both ovaries were provided for H&E staining. In another experiment, the mice were superovulated with pregnant mare's serum gonadotropin and human chorionic gonadotropin, and were mated with males. After 18 h, zygotes were collected and cultured for 4 days, and numbers and embryo developmental competency of zygotes retrieved were evaluated. The expression of mTOR/PI3K signaling pathway regulated genes (4EBP1, S6K1, and RPS6) and angiogenic factors (VEGF, visfatin, and SDF-1α) in the ovary were examined. As well, visfatin-treated mice were mated with male mice for 2 weeks, and the pregnancy outcome was monitored up to 3 weeks. Visfatin significantly increased the total numbers of follicles compared with control. Numbers of zygotes retrieved, blastocyst formation rate, and pregnancy rate were significantly increased at 500 ng/ml of visfatin (2.83%, 40.0%, and 80%, respectively) compared with control (0, 0, and no pregnancy). Ovarian expressions of S6K1, RPS6, VEGF, visfatin, and SDF-1α were significantly stimulated at 500 ng/ml of visfatin. These results show that visfatin treatment of an optimal dose rescues age-related decline in fertility, possibly by stimulating mTOR/PI3K signaling.


Assuntos
Envelhecimento/fisiologia , Citocinas/fisiologia , Fertilidade/fisiologia , Neovascularização Fisiológica , Nicotinamida Fosforribosiltransferase/fisiologia , Ovário/fisiologia , Animais , Feminino , Camundongos Endogâmicos C57BL , Oócitos/fisiologia , Ovário/enzimologia , Gravidez
6.
Taiwan J Obstet Gynecol ; 58(3): 423-427, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31122536

RESUMO

OBJECTIVES: To evaluate the feasibility and safety of two-port myomectomy using bag-contained manual morcellation compared to three-port myomectomy using power morcellation. MATERIAL AND METHODS: A retrospective chart review was conducted for 428 cases of either two-port or three-port laparoscopic myomectomy performed by single operator in the university hospital between January 2011 and December 2016. RESULTS: The cohorts of three-port myomectomy with power morcellation was consisted of two hundred and forty-eight patients. One hundred and eighty patients underwent two-port myomectomy with manual morcellation in contained bag. Two-port group showed shorter hospital stay (5.16 ± 1.39 d vs. 4.83 ± 1.19 d, p = 0.001), less estimated blood loss (61.8 ± 58.2 mL vs. 50.2 ± 52.4 mL, p = 0.001), and higher hemoglobin level at postoperative day 1 (10.7 ± 1.17 g/dL vs. 11.0 ± 1.14 g/dL, p = 0.028) with statistical significance. Morcellation time (25.8 ± 9.30 min vs. 18.9 ± 10.11 min, p = 0.001) and total operative time (82.4 ± 30.19 min vs. 76.4 ± 25.47 min, p = 0.047) were also significantly shorter in two-port group. There were no identified spillages of fibroids, ruptures of specimen bag during manual morcellation in two-port myomectomy. In both groups, there were no cases of leiomyosarcoma diagnosed postoperatively. CONCLUSION: Two-port laparoscopic myomectomy with bag-contained manual morcellation is a feasible and safe alternative for three-port with power morcellation. Its surgical outcomes were shown to be superior to conventional laparoscopic myomectomy according to our study but further evaluation in near future is needed.


Assuntos
Leiomioma/cirurgia , Morcelação/instrumentação , Miomectomia Uterina/métodos , Neoplasias Uterinas/cirurgia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Duração da Cirurgia , Estudos Retrospectivos
7.
Mol Med Rep ; 18(2): 2499-2505, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29901153

RESUMO

It is well known that prostaglandin (PG) E2 and PGF2α are secreted in copious amounts from the menstruating uterus. The aim of the present study was to determine whether PGs affect the growth of uterine leiomyomas (ULs) to the same extent as estrogen or progesterone (P4). The present study evaluated the expression of eight microRNAs (miRNAs) by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) through treatment with estradiol (E2), P4, PGE2, PGF2α and each antagonist or cyclooxygenase­2 (COX­2) inhibitor of cultured leiomyoma and myometrial cells (LC and MC, respectively). The eight miRNAs were divided into two groups according to their primary biological action, namely apoptosis­regulating miRNAs (let­7a, miR­21, miR­26a and miR­200a) and inflammation­regulating miRNAs (miR­29b, miR­93, miR­106b and miR­100b). PGE2 induced significantly higher expression of the 3 anti­apoptotic miRs, let­7a, miR­16a and miR­200a, in LC when compared with the non­treated control or E2. PGE2 significantly promoted a greater expression of let­7a and miR­26a in LC when compared with P4. Overall, PGE2 exerted the highest anti­apoptotic and anti­inflammatory effect in LC, which was comparable with E2. It was not observed among the inflammation­regulating miRNAs in LC. PGF2α did not exert effects as prominent as those of PGE2. In MC, PGs and sex steroids exerted no similar effects on MC compared with LC. The present study demonstrated that PGE2 levels during menstruation may affect the growth of preexisting ULs without affecting the normal myometrium. Therefore, the control of secretion of PGs from the menstruating uterus or the administration of antagonists may be an alternative therapy for inhibiting the growth of ULs.


Assuntos
Leiomioma/genética , MicroRNAs/genética , Prostaglandinas/genética , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Leiomioma/metabolismo , Leiomioma/patologia , MicroRNAs/classificação , Miométrio/metabolismo , Miométrio/patologia , Progesterona/genética , Prostaglandinas/classificação
8.
Clin Exp Reprod Med ; 45(1): 25-30, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29662822

RESUMO

OBJECTIVE: This study conducted a preliminary examination of the effects of three-area laser-assisted zona thinning (LAZT) during the cleavage stage of embryo development on the hatching process in human in vitro fertilization-embryo transfer (IVF-ET) with subjects of advanced female age or frozen-thawed (FT) embryos. METHODS: Eight-cell stage embryos were treated with LAZT in three areas of the zona pellucida at 120° intervals. The control group was embryos without LAZT. Of the 72 consecutive fresh cycles and the 28 FT embryo transfer cycles, the patients in 55 fresh cycles and 17 FT cycles declined LAZT, and those cycles were defined as the control group. RESULTS: In the fresh cycles, the pregnancy rates were similar in the LAZT and control groups. However, in the FT cycles, the pregnancy rate was significantly higher in the LAZT group than in the control group (45.5% in the LAZT group vs. 23.5% in the control group, p<0.05). CONCLUSION: These results show that multi-area LAZT resulted in significantly improved pregnancy outcomes in human 8-cell embryos compared to controls.

9.
J Menopausal Med ; 24(3): 196-203, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30671413

RESUMO

OBJECTIVES: This study was aimed to establish the most effective premature ovarian failure (POF) mouse model using Cyclophosphamide (CTX), busulfan (Bu), and cisplatin considering treatment duration of anticancer drugs and natural recovery time. METHODS: POF was induced by intraperitoneally injecting CTX (120 mg/kg)/Bu (12 mg/kg) for 1 to 4 weeks or cisplatin (2 mg/kg) for 3 to 14 days to C57BL/6 female mice aged 6 to 8 weeks. Controls were injected with equal volume of saline for the same periods. Body weight was measured every week, and ovarian and uterine weights were measured after the last injection of anticancer drug. To assess ovarian function, POF-induced mice were superovulated with pregnant mare serum gonadotropin and human chorionic gonadotropin, and then mated with male. After 18 hours, zygotes were retrieved and cultured for 4 days. Finally, the mice were left untreated for a period of times after the final injection of anticancer drug, and the time for natural recovery of ovarian function was evaluated. RESULTS: After 2 weeks of CTX/Bu injection, ovarian and uterine weights, and ovarian function were decreased sharply. Cisplatin treatment for 10 days resulted in a significant decrease in ovarian and uterine weight, and ovarian function. When POF was induced for at least 2 weeks for CTX/Bu and for at least 10 days for cisplatin, ovarian function did not recover naturally for 2 weeks and 1 week, respectively. CONCLUSIONS: These results suggest that CTX/Bu should be treated for at least 2 weeks and cisplatin for at least 10 days to establish the most effective primary ovarian insufficiency mouse model.

10.
J Menopausal Med ; 23(1): 74-76, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28523263

RESUMO

Autoamputated ovary with mature cystic teratoma (MCT) is a rarely reported gynecologic entity with an unknown prevalence. A 34-year-old woman referred to our clinic for presumed left ovarian tumor. Pelvic examination, ultrasonography and computed tomography scan revealed a 5-cm, cystic ovarian mass with calcification and fat component, and tumor markers were as follows, cancer antigen (CA) 125; 10.4 U/mL, CA19-9; 2 U/mL. Laparoscopy was performed. The mass was identified in the left adnexal region without any ligamentous or direct connection with the pelvic organs. The right ovary was normal. However, the left ovary and the tube could not be identified in its proper anatomical location. The mass was successfully removed with sharp and blunt dissection. A review of histopathologic study revealed a MCT. The patient became pregnant within seven months and gave birth to a healthy baby by cesarean section. We present a rare case of an autoamputated ovary with MCT.

11.
Obstet Gynecol Sci ; 60(1): 118-123, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28217683

RESUMO

Lymphoepithelioma-like carcinoma (LELC) of the uterine cervix is exceedingly uncommon. We herein report a rare case of cervical LELC. A 45-year-old woman was admitted to gynecology department with vaginal bleeding for one month. Liquid-based cytology revealed atypical endometrial cells, not otherwise specified on her cervix. On a hysteroscopy, an endocervical mass was identified and the pathologic result was consistent with poorly differentiated squamous cell carcinoma. Magnetic resonance imaging and positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography revealed a 3.1-cm endocervical mass without distant metastasis or enlarged lymph nodes. The International Federation of Gynecology and Obstetrics stage was IB1. A radical hysterectomy and bilateral pelvic lymph node dissection were performed. The pathologic diagnosis was a poorly differentiated carcinoma, showing features of LELC. She has been followed for 8 months without adjuvant treatment since the surgery, during which time there has been no evidence of tumor recurrence or metastasis.

12.
Taiwan J Obstet Gynecol ; 55(1): 35-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26927245

RESUMO

OBJECTIVE: The purpose of this study was to compare clinical outcomes of conventional laparoscopic surgery and laparoendoscopic single-site surgery (LESS) in the surgical treatment of tubal ectopic pregnancy. MATERIAL AND METHODS: A total of 156 patients were diagnosed with ectopic pregnancies by ultrasonography and serum ß-human chorionic gonadotrophin (ß-hCG) levels at Pusan National University Yangsan Hospital from January 2009 through December 2013. We excluded 28 patients who only received medical treatment, 15 patients who underwent surgery by laparotomy for severe hypovolemic shock, and 30 patients who presented with less than 1 L of hemoperitoneum. Of the 83 patients with massive hemoperitoneum, 38 patients had LESS performed while the remaining 45 patients underwent conventional laparoscopic surgery. RESULTS: In this study, there were no statistically significant differences in clinical outcomes in either surgical method except for operative time. Operative time of LESS was significantly shorter than conventional surgery for patients with more than 500 mL of hemoperitoneum. CONCLUSION: LESS is a safe and feasible surgical approach in the treatment of tubal ectopic pregnancy. At the same time, LESS has been shown to be more effective than conventional laparoscopic surgery in handling massive hemoperitoneum of more than 1 L, which is a common complication of ectopic pregnancy.


Assuntos
Hemoperitônio/complicações , Laparoscopia/métodos , Gravidez Tubária/cirurgia , Adulto , Gonadotropina Coriônica Humana Subunidade beta/sangue , Feminino , Humanos , Duração da Cirurgia , Gravidez , Gravidez Tubária/sangue , Gravidez Tubária/diagnóstico por imagem , Ultrassonografia
13.
J Menopausal Med ; 22(3): 184-187, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28119900

RESUMO

We report a non-puerperal uterine inversion with nulliparous women caused by huge pedunculated submucosal fibroid. Massive bleeding from protruding mass through vagina brought the heart to stop in 42-year-old nulliparous woman. She became cardiopulmonary resuscitation survivor in emergency room and then underwent laparotomy which ended in successful myomectomy rather than hysterectomy considering her demand for future fertility. Meticulous and adequate fluid therapy and transfusion was also administered to recover from hypovolemic status. Pathologic report confirmed benign submucosal fibroid with degeneration, necrosis and abscess formation. Thus, clinician should be aware of uterine inversion when encountered with huge protruding vaginal mass and consider uterus-preserving management as surgical option when the future fertility is concerned.

14.
Stem Cells ; 33(5): 1490-500, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25537795

RESUMO

The Lnk adaptor protein is a strong negative regulator that affects self-renewal of hematopoietic stem cells and vascular repair in injured tissues. However, the signaling mechanisms through which these proteins influence the vascular regeneration function of endothelial progenitor cells (EPCs) remain unknown. In this study, we investigated the effect of Lnk-targeted small interfering RNA (si-lnk) on the clonogenic proliferative potential and vascular regenerative function of EPCs and the activation of the JAK/STAT3 signaling pathway. Treatment with stem cell factor (SCF) increased the clonogenic proliferation of si-lnk EPCs. Importantly, activation of the JAK2/STAT3 pathway was enhanced in SCF-sensitized si-lnk EPCs. In a hind limb model of ischemia, transplantation of si-lnk EPCs increased the blood flow ratio, capillary density, proliferation, and survival of transplanted cells, and the secretion of pivotal angiogenic cytokines at ischemic sites. These results provide strong evidence that si-lnk regulates the clonogenic proliferative potential of EPCs through the activation of the JAK2/STAT3 signaling pathway, thereby accelerating angiogenesis and promoting repair in injured hind limb ischemia. Stem Cells 2014;33:1490-1500.


Assuntos
Células Progenitoras Endoteliais/metabolismo , Membro Posterior/irrigação sanguínea , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Isquemia/terapia , Transdução de Sinais , Cordão Umbilical/citologia , Cicatrização , Proteínas Adaptadoras de Transdução de Sinal , Animais , Proliferação de Células/efeitos dos fármacos , Autorrenovação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/transplante , Marcação de Genes , Membro Posterior/patologia , Isquemia/patologia , Isquemia/fisiopatologia , Janus Quinase 2/metabolismo , Masculino , Proteínas de Membrana , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Células-Tronco/farmacologia , Regulação para Cima/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/efeitos dos fármacos
15.
J Menopausal Med ; 20(1): 21-31, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25371888

RESUMO

OBJECTIVES: To examine the effect of diazoxide on hypoxia-induced soluble fms-like tyrosin kinase-1 (sFlt-1) release in JEG-3 choriocarcinoma cells. METHODS: Cells were cultured under normoxia (20% O2) or hypoxia (1% O2), and expression of sFlt-1 mRNA and protein release was determined by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) assays and enzyme-linked immunosorbent assay (ELISA). RESULTS: Tumor necrosis factor-alpha (TNF-α) as well as hypoxia stimulated sFlt-1 release and diazoxide inhibited both of them. The selective inhibitor of mitochondrial adenosine triphosphat (ATP)-sensitive K(+) channel opener (KATP) 5-hydroxydecanoate (5-HD) completely reversed the diazoxide-induced inhibition of hypoxia-stimulated sFlt-1 release. qRT-PCR and Western blot analyses showed that diazoxide up-regulated the heme oxygenase-1 (HO-1) expression. In addition, the HO-1 inducer cobalt protoporphyrin (CoPP) and the metabolic product of HO-1 bilirubin mimicked diazoxide to inhibit sFlt-1 release and reactive oxygen species (ROS) production under hypoxia, whereas the HO-1 inhibitor zinc protoporphyrin IX (ZnPP IX) antagonized the effect of diazoxide. In cells transfected with the HO-1 siRNA, diazoxide did not exert any effect on sFlt-1 release and ROS production under hypoxia. CONCLUSION: These results, taken together, strongly suggest that up-regulation of the HO-1 expression is the crucial mechanism responsible for the diazoxide-induced inhibition of the sFlt-1 release and ROS production under hypoxia.

16.
J Menopausal Med ; 20(2): 57-68, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25371895

RESUMO

OBJECTIVES: We examined the effect of sildenafil citrate on advanced glycation end products (AGEs)-induced soluble fms-like tyrosine kinase 1 (sFlt-1) release in JEG-3 choriocarcinoma cells. METHODS: Cells were incubated with control bovine serum albumin (BSA) or AGEs-BSA, and expression of sFlt-1 mRNA and protein release was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. AGEs-BSA increased sFlt-1 mRNA expression and protein release in a dose-dependent manner. RESULTS: Sildenafil citrate suppressed sFlt-1 mRNA expression and protein release in cells treated with AGEs-BSA in a dose-dependent manner. Likewise, it inhibited the increase of reactive oxygen species (ROS) production and NF-κB activity in these cells. Cobalt protoporphyrin (CoPP) and bilirubin also inhibited sFlt-1 release and ROS production in cells treated with AGEs-BSA, whereas zinc protoporphyrin IX (ZnPP IX) antagonized the effect of sildenafil citrate. In cells transfected with the heme oxygenase-1 (HO-1) siRNA, sildenafil citrate failed to inhibit the sFlt-1 release and ROS production. CONCLUSION: These results strongly suggest that sildenafil citrate inhibits sFlt-1 release and ROS production in cells treated with AGEs-BSA through upregulation of the HO-1 expression in JEG-3 cells.

17.
Toxicol Lett ; 231(1): 1-8, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25180886

RESUMO

Carrageenan (CGN), a widely used food additive, has been shown to injure the epithelial barrier in animal models. This type of damage is a clinical feature of inflammatory bowel disease (IBD) in humans. In the present study, the effects of CGN on pro-apoptotic responses associated with macrophage inhibitory cytokine 1 (MIC-1) regulation in human enterocytes were evaluated. CGN up-regulated the expression of MIC-1 that promoted epithelial cell apoptosis. Although MIC-1 induction was dependent on pro-apoptotic p53 protein, the pro-survival protein activating transcription factor 3 (ATF3) was negatively regulated by p53 expression. However, MIC-1 enhanced the expression of the pro-survival protein ATF3 in enterocytes exposed to CGN. Functionally, MIC-1-mediated epithelial cell apoptosis was counteracted by the pro-survival action of ATF3 in response to CGN exposure. These findings demonstrated that the counterbalance between MIC-1 and ATF3 is critical for deciding the fate of enterocytes under the food chemical stress.


Assuntos
Fator 3 Ativador da Transcrição/metabolismo , Apoptose/efeitos dos fármacos , Carragenina/toxicidade , Enterócitos/efeitos dos fármacos , Aditivos Alimentares/toxicidade , Fator 15 de Diferenciação de Crescimento/metabolismo , Animais , Enterócitos/metabolismo , Enterócitos/patologia , Células HCT116 , Humanos , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Transfecção , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
18.
PLoS One ; 9(8): e106310, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25166961

RESUMO

INTRODUCTION: Despite the crucial role of endothelial progenitor cells (EPCs) in vascular regeneration, the specific interactions between EPCs and hematopoietic cells remain unclear. METHODS: In EPC colony forming assays, we first demonstrated that the formation of EPC colonies was drastically increased in the coculture of CD34+ and CD34- cells, and determined the optimal concentrations of CD34+ cells and CD34- cells for spindle-shaped EPC differentiation. RESULTS: Functionally, the coculture of CD34+ and CD34- cells resulted in a significant enhancement of adhesion, tube formation, and migration capacity compared with culture of CD34+ cells alone. Furthermore, blood flow recovery and capillary formation were remarkably increased by the coculture of CD34+ and CD34- cells in a murine hind-limb ischemia model. To elucidate further the role of hematopoietic cells in EPC differentiation, we isolated different populations of hematopoietic cells. T lymphocytes (CD3+) markedly accelerated the early EPC status of CD34+ cells, while macrophages (CD11b+) or megakaryocytes (CD41+) specifically promoted large EPC colonies. CONCLUSION: Our results suggest that specific populations of hematopoietic cells play a role in the EPC differentiation of CD34+ cells, a finding that may aid in the development of a novel cell therapy strategy to overcome the quantitative and qualitative limitations of EPC therapy.


Assuntos
Antígenos CD34/metabolismo , Células Progenitoras Endoteliais/fisiologia , Sangue Fetal/citologia , Membro Posterior/irrigação sanguínea , Isquemia/terapia , Animais , Diferenciação Celular , Células Cultivadas , Técnicas de Cocultura , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Modelos Animais de Doenças , Células Progenitoras Endoteliais/citologia , Sangue Fetal/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
19.
J Menopausal Med ; 19(3): 139-42, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25371880

RESUMO

Primary vaginal cancer combined with uterine prolapse is very rare. We present a case of 80-year-old postmenopausal women complaints of something coming out per vagina for the past 20 years, along with blood stained discharge, foul odor leukorrhea, and severe pelvic pain for the last 3 months. A 4 × 5 cm ulcer was present on middle third of vaginal wall with marked edema and ulceration of surrounding tissue. The prolapse was reduced under intravenous sedation in operating room. On gynecologic examination, uterus was normal in size, no adnexal mass was examined, and both parametrium were thickened. Papanicolaou smear was normal. Biopsy of the ulcer at vaginal wall revealed invasive squamous cell carcinoma of vagina. Magnetic Resonance Imaging of abdomen and pelvis showed left hydronephrosis and liver metastasis. Positron emission tomography (PET)/computed tomography (CT) revealed metastasis to lung, liver and iliac bone. She died from progression of disease one month after diagnosis.

20.
J Menopausal Med ; 19(3): 147-50, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25371882

RESUMO

Uterine leiomyoma is one of the most common gynecological tumor, whereas acute torsion of the uterine leiomyoma is very rare. We report a case of subserosal leiomyoma that was first detected by ultrasonography, and further confirmed as torsion of subserosal leiomyoma by laparoscopic surgery.

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