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1.
J Periodontal Res ; 58(6): 1235-1247, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37712743

RESUMO

BACKGROUND: Periodontal ligament stem cells (PDLSCs) are the most potential cells in periodontal tissue regeneration and bone tissue regeneration. Our prior work had revealed that WD repeat-containing protein 72 (WDR72) was crucial for osteogenic differentiation of PDLSCs. Here, we further elucidated its underlying mechanism in PDLSC osteogenic differentiation. METHODS: Human PDLSCs, isolated and identified by flow cytometry, were prepared for osteogenic differentiation induction. Levels of WDR72, long non-coding RNA X-Inactive Specific Transcript (XIST), upstream stimulatory factor 2 (USF2), and osteogenic marker genes (Runx2, Osteocalcin, and Collagen I) in human PDLSCs and clinical specimens were detected by RT-qPCR. Protein expressions of WDR72, Runx2, Osteocalcin, and Colla1 were tested by Western blot. The interactions among the molecules were verified by RIP, RNA pull-down, ChIP, and luciferase reporter assays. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) and alizarin red staining (ARS). RESULTS: WDR72 was decreased in periodontal tissues of periodontitis patients, and overexpression reversed TNF-α-mediated suppressive effects on PDLSC osteogenic differentiation. Mechanically, XIST recruited the enrichment of USF2 to the WDR72 promoter region, thereby positively regulating WDR72. WDR72 silencing overturned XIST-mediated biological effects in PDLSCs. CONCLUSION: WDR72, regulated by the XIST/USF2 axis, enhances osteogenic differentiation of PDLSCs, implying a novel strategy for alleviating periodontitis.


Assuntos
Periodontite , RNA Longo não Codificante , Humanos , Diferenciação Celular , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Osteocalcina/metabolismo , Osteogênese , Ligamento Periodontal , Periodontite/metabolismo , Proteínas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Células-Tronco/metabolismo , Fatores Estimuladores Upstream/metabolismo
2.
Zhonghua Nan Ke Xue ; 28(1): 48-55, 2022 Jan.
Artigo em Zh | MEDLINE | ID: mdl-37459078

RESUMO

Objective: To evaluate the effect of Modified Shenqi Dihuang Decoction (MSDD) on human hormone-sensitive LNCaP prostate cancer cells and its action mechanism. METHODS: LNCaP prostate cancer cells were treated with MSDD, followed by detection of the proliferation and apoptosis of the cells by MTT assay and flow cytometry respectively and measurement of glucose uptake and lactate production by glucose uptake assay and colorimetry respectively. The expressions of the apoptosis-related proteins Bcl-2, Bax and cleaved-caspase-3, glycolysis-related proteins HK2, GLUT1, PKM2 and LDHA, and PI3K/AKT/mTOR pathway-related proteins in the LNCaP cells were determined by Western blot. The effect of MSDD on the LNCaP cells was observed with the glycolysis inducer oligomycin and the PI3K activator 740 Y-P. RESULTS: MSDD inhibited the proliferation, induced the apoptosis, increased the levels of Bax and cleaved-caspase 3 and decreased the level of Bcl-2 in the LNCaP cells in a dose-dependent manner. After MSDD intervention, the glucose uptake and lactate production in the LNCaP cells were significantly reduced, the expressions of HK2, GLUT1, PKM2 and LDHA and the phosphorylation levels of Akt, PI3K and mTOR were markedly suppressed. Oligomycin and 740 Y-P reversed the inhibitory effect of MSDD on the proliferation of the LNCaP cells, and 740 Y-P reversed that on glucose uptake, lactic acid production and the expressions of the glycolysis-related proteins HK2, GLUT1, PKM2 and LDHA in the LNCaP cells. CONCLUSIONS: Modified Shenqi Dihuang Decoction inhibits the proliferation of LNCaP prostate cancer cells by suppressing glycolysis and the PI3K/Akt/mTOR signaling pathway.

3.
Zhonghua Nan Ke Xue ; 27(2): 161-166, 2021 Feb.
Artigo em Zh | MEDLINE | ID: mdl-34914334

RESUMO

OBJECTIVE: To observe the clinical effect of Modified Shenqi Dihuang Decoction (MSDD) on bone metastasis of hormone-sensitive PCa after castration. METHODS: Seventy-six hormone-sensitive PCa patients with bone metastasis were randomly divided into a control and an MSDD group of an equal number, the former treated by maximal androgen blockade (MAB) and the latter with MSDD in addition to MAB, both for 6 months. Comparisons were made between the two groups of patients in their TCM symptom scores, quality of life (QOL) scores and the incidence rates of castration resistance, bone metastasis and adverse events. RESULTS: Totally, 64 of the patients were included in the statistical analysis. Compared with the controls, the MSDD group showed significantly lower rates of castration resistance (71.87% vs 28.12%, P < 0.05) and new bone and visceral metastases (40.63% vs 18.75%, P < 0.05) and level of serum alkaline phosphatase after treatment (ï¼»328.5 ± 170.6ï¼½ vs ï¼»318.5 ± 165.8ï¼½ U/L, P < 0.05), as well as lower scores in the TCM symptoms of frequent micturition (2.05 ± 0.51 vs 1.64 ± 0.66, P < 0.05), loss of appetite (1.95 ± 0.48 vs 1.41 ± 0.39, P < 0.05), fatigue (2.59 ± 0.68 vs 1.39 ± 0.58, P < 0.05), back pain (1.76 ± 0.41 vs 1.26 ± 0.38, P < 0.05), weight loss (1.88 ± 0.75 vs 1.26 ± 0.80, P < 0.05) and self-evaluation (1.89 ± 0.58 vs 1.54 ± 0.63, P < 0.05), but a higher score in the physical status (Karnofsky Performance Scale) (70.45 ± 12.16 vs 79.87 ± 11.23, P < 0.05). There were no statistically significant differences in the Numeric Rating Scale for Pain score and the incidence of adverse events between the two groups of patients. CONCLUSIONS: Modified Shenqi Dihuang Decoction can effectively improve the QOL and TCM symptom scores of the patients with hormone-sensitive PCa after androgen castration, enhance the efficacy of modern drugs in the treatment of hormone-sensitive PCa, decrease the incidence of metastasis, improve the patient's serum indicators, reduce the pain associated with bone metastasis, and improve the patient's quality of life.


Assuntos
Neoplasias da Próstata , Qualidade de Vida , Castração , Medicamentos de Ervas Chinesas , Hormônios , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico
4.
World J Urol ; 34(5): 679-85, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26318636

RESUMO

PURPOSE: To investigate the feasibility and effectiveness of three-dimensional laparoscopic partial nephrectomy with selective segmental artery clamping (3D-LPNSSAC) comparing with the conventional two-dimensional laparoscopic partial nephrectomy (2D-LPN). METHODS: Between November 2012 and March 2014, 90 patients with cT1 renal tumor at Shanghai General Hospital were enrolled in our study, which were randomly divided into two groups: the 3D-LPNSSAC group (n = 45) and 2D-LPN group (n = 45). The perioperative variables, including operative time, dissecting time, suturing time, blood loss, warm ischemia time (WIT), preoperative and postoperative renal functions, were recorded and analyzed. In addition, the oncological outcomes and complications were also evaluated. RESULTS: All the LPNs were performed successfully without conversion to radical nephrectomy or open surgery, only three cases were converted to total renal artery clamping during 3D-LPNSSAC. There were no significant differences in operative time and dissecting time between the groups, while the suturing time was shorter during 3D-LPNSSAC (P < 0.01). The technique was associated with higher blood loss (P < 0.01). The technique of 3D-LPNSSAC significantly reduced WIT (P = 0.04), and better postoperative ipsilateral renal function could be obtained during 3D-LPNSSAC (P < 0.01). During a mean follow-up time of 16.8 months (range 5.5-22.5 months), the complication rate was 8.8 % (8/90) and no tumor reoccurrence was detected. CONCLUSIONS: 3D-LPNSSAC is a feasible and safe technique for treating selective renal tumors, presenting with the beneficial clinical outcomes of reduced suturing time, shorter WIT and better postoperative ipsilateral renal function.


Assuntos
Imageamento Tridimensional , Neoplasias Renais/cirurgia , Laparoscopia , Nefrectomia/métodos , Cirurgia Assistida por Computador , Constrição , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Artéria Renal
5.
Environ Toxicol ; 31(3): 261-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25213187

RESUMO

This study was the first to investigate the genetic abnormalities and structural dysplasia of anorectal malformations (ARMs) in male rats induced by di(n-butyl) phthalate (DBP). DBP was administered to timed-pregnant rats to establish the ARM rat model. The incidence of ARMs in male offspring was 39.5%. In neonatal period, decreased body weight and anogenital distance were observed. The general image and histological analysis of male offspring confirmed the presence of ARMs. Anatomical examination of the ARM male rats revealed the dysplasia in solid organs (heart-lung, liver, spleen, and kidney). The decreases of serum testosterone concentration and androgen receptor expression in terminal rectum were indicative of the antiandrogenic effects of DBP. Moreover, significant decreased mRNA expressions of these androgen-related genes such as sonic hedgehog, Gli2, Gli3, bone morphogenetic protein 4, Wnt5a, Hoxa13, Hoxd13, fibroblast growth factor 10, and fibroblast growth factor receptor 2 were found in terminal rectum of the ARM male pubs. These results demonstrated that development of ARM rats was impaired by maternal exposure to DBP. The antiandrogenic effects of DBP disturbing the androgen-related signaling networks might play an important role in the occurrence of ARMs.


Assuntos
Anus Imperfurado/induzido quimicamente , Anus Imperfurado/genética , Dibutilftalato , Animais , Animais Recém-Nascidos , Malformações Anorretais , Anus Imperfurado/sangue , Anus Imperfurado/patologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/patologia , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Testosterona/sangue
6.
Eur J Orthop Surg Traumatol ; 23(2): 219-24, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23412455

RESUMO

BACKGROUND: Many previous studies have focused on the postoperative complication of postoperative knee pain, infection, knee prosthesis loosening, periprosthetic fractures, and so on. There have been few studies focused on postoperative ecchymosis formation surrounding the wound of the TKA site. A certain degree of effect on the early functional recovery of the patients may occur due to the mental stress caused by the ecchymosis, which raises doubts regarding the success of the surgery. Therefore, it is particularly important to understand the risk factors for postsurgical ecchymosis formation after TKA, and specific measures for preventing ecchymosis should be taken. In this study, we reviewed the record of patients who received TKAs in our hospital, and a comprehensive analysis and assessment was conducted regarding 15 clinical factors causing postsurgical ecchymosis formation. METHODS: The records of 102 patients who received unilateral TKAs between January 2007 and May 2010 were retrospectively analyzed. Patients were divided into two groups based on the occurrence of ecchymosis. RESULTS: Of the 102 patients, 14 (13.7%) developed ecchymosis. Blood transfusion and drainage catheter clamping during the first few postoperative hours had a significant impact on the development of ecchymosis (p < 0.05). There was no difference in age, BMI, operation time, pre- and postoperative platelet count, and length of postoperative anticoagulant therapy between the two groups. Multivariate logistic regression revealed major risk factors for ecchymosis were postoperative blood transfusion (odds ratio (OR) = 15.624) and drainage catheter clamping (OR 14.237) (both, p < 0.05). CONCLUSION: Blood transfusion and drainage catheter clamping after TKA due to excessive blood suction were associated with higher risks for ecchymosis formation surrounding the surgical site.


Assuntos
Artroplastia do Joelho/efeitos adversos , Drenagem/efeitos adversos , Equimose/etiologia , Complicações Pós-Operatórias/etiologia , Reação Transfusional , Idoso , Artroplastia do Joelho/métodos , Catéteres/efeitos adversos , Drenagem/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos
7.
J Biomed Sci ; 19: 73, 2012 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-22889374

RESUMO

BACKGROUND: Enterovirus 71 (EV71) is a highly infectious agent that plays an etiological role in hand, foot, and mouth disease. It is associated with severe neurological complications and has caused significant mortalities in recent large-scale outbreaks. Currently, no effective vaccine or specific clinical therapy is available against EV71. METHODS: Unmodified 21 nucleotide small interfering RNAs (siRNAs) and classic 2'-modified (2'-O-methylation or 2'-fluoro modification) siRNAs were designed to target highly conserved 5' untranslated region (UTR) of the EV71 genome and employed as anti-EV71 agents. Real-time TaqMan RT-PCR, western blot analysis and plaque assays were carried out to evaluate specific viral inhibition by the siRNAs. RESULTS: Transfection of rhabdomyosarcoma (RD) cells with siRNAs targeting the EV71 genomic 5' UTR significantly delayed and alleviated the cytopathic effects of EV71 infection, increased cell viability in EV71-infected RD cells. The inhibitory effect on EV71 replication was sequence-specific and dosage-dependent, with significant corresponding decreases in viral RNA, VP1 protein and viral titer. Appropriate 2'-modified siRNAs exhibited similar RNA interference (RNAi) activity with dramatically increased serum stability in comparison with unmodified counterparts. CONCLUSION: Sequences were identified within the highly conserved 5' UTR that can be targeted to effectively inhibit EV71 replication through RNAi strategies. Appropriate 2'-modified siRNAs provide a promising approach to optimizing siRNAs to overcome barriers on RNAi-based antiviral therapies for broader administration.


Assuntos
Enterovirus Humano A/genética , Infecções por Enterovirus , RNA Interferente Pequeno/genética , Replicação Viral/genética , Regiões 5' não Traduzidas/genética , Linhagem Celular , Sequência Conservada , Enterovirus Humano A/química , Infecções por Enterovirus/genética , Infecções por Enterovirus/terapia , Infecções por Enterovirus/virologia , Humanos , RNA Interferente Pequeno/química , Rabdomiossarcoma/genética , Rabdomiossarcoma/virologia , Transfecção
8.
Asian J Androl ; 23(6): 640-647, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135173

RESUMO

To evaluate outcomes between extraperitoneal robotic single-port radical prostatectomy (epR-spRP) and extraperitoneal robotic multiport radical prostatectomy (epR-mpRP) performed with the da Vinci Si Surgical System, comparison was performed between 30 single-port (SP group) and 26 multiport (MP group) cases. Comparisons included operative time, estimated blood loss (EBL), hospital stay, peritoneal violation, pain scores, scar satisfaction, continence, and erectile function. The median operation time and EBL were not different between the two groups. In the SP group, the median operation time of the first 10 patients was obviously longer than that of the latter 20 patients (P < 0.001). The median postoperative hospital stay in the SP group was shorter than that in the MP group (P < 0.001). The rate of peritoneal damage in the SP group was less than that in the MP group (P = 0.017). The pain score and overall need for pain medications in the SP group were lower than those in the MP group (P < 0.001 and P = 0.015, respectively). Patients in the SP group were more satisfied with their scars than those in the MP group 3 months postoperatively (P = 0.007). At 3 months, the cancer control, recovery of erectile function, and urinary continence rates were similar between the two groups. It is safe and feasible to perform epR-spRP using the da Vinci Si surgical system. Therefore, epR-spRP can be a treatment option for localized prostate cancer. Although epR-spRP still has a learning curve, it has advantages for postoperative pain and self-assessed cosmesis. In the absence of the single-port robotic surgery platform, we can still provide minimally invasive surgery for patients.


Assuntos
Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Medicina Perioperatória/instrumentação , Prostatectomia/instrumentação , Procedimentos Cirúrgicos Robóticos/normas , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Medicina Perioperatória/normas , Medicina Perioperatória/estatística & dados numéricos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos
9.
Medicine (Baltimore) ; 99(36): e22028, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899057

RESUMO

Comparison of different anticoagulants in blood management and complications with tranexamic acid (TXA) in total hip arthroplasty (THA) is unclear. Our aim was to compare the efficacy and safety among receiving nadroparin calcium, enoxaparin sodium or rivaroxaban after TXA in THA.150 patients undergoing primary unilateral THA were received 15 mg/kg intravenous TXA (IV-TXA) before skin incision, followed by 1 of nadroparin calcium (Group A), enoxaparin sodium (Group B), or rivaroxaban (Group C) randomly during hospitalization. The primary outcome was hidden blood loss (HBL). Other outcomes such as the maximum hemoglobin (Hb) drop, total blood loss (TBL), the volume of drainage, transfusion rate, length of hospital stay (LOS), and complications were also compared.There were no statistically significant differences in HBL, the maximum hemoglobin (Hb) drop, transfusion rate, and complications among 3 groups. LOS was significantly higher for patients in Group B than Group A (P = .026). Neither deep venous thrombosis (DVT) nor pulmonary embolism (PE) occurred in any group.There were no differences in efficacy and safety in patients undergoing THA receiving nadroparin calcium, enoxaparin sodium, or rivaroxaban after anti-fibrinolysis with TXA.


Assuntos
Anticoagulantes/efeitos adversos , Antifibrinolíticos/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Ácido Tranexâmico/efeitos adversos , Administração Intravenosa , Idoso , Anticoagulantes/administração & dosagem , Antifibrinolíticos/administração & dosagem , Artroplastia de Quadril/efeitos adversos , Transfusão de Sangue/estatística & dados numéricos , China/epidemiologia , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Feminino , Hemoglobinas/análise , Hospitalização , Humanos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Nadroparina/administração & dosagem , Nadroparina/efeitos adversos , Sangue Oculto , Estudos Retrospectivos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Segurança , Ácido Tranexâmico/administração & dosagem , Resultado do Tratamento
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 2019-2023, 2019 Dec.
Artigo em Zh | MEDLINE | ID: mdl-31839077

RESUMO

Abstract  Tumor cells avoid immune surveillance by overexpressing ligands of checkpoint receptors on tumor cells or adjacent cells, resulting in inability or exhaustion of T cells. Numerous studies have shown that lymphoma cells highly expressed programmed cell death ligand-1 (PD-L1), suggesting that PD-1 may become an important target for lymphoma treatment. By targeting the PD-1 protein, the cellular activity of T cells will be significantly enhanced, and the tumor growth will be inhibited. Recently, antibodies against PD-1 have shown high efficacy and safety in the clinical studies of lymphoma, which are expected to become the targeted therapeutic drugs for lymphoma. In order to deeply understand the application of PD-1 antibody in treatment of lymphoma, this review briefly summaries the present state of lymphoma studies, the action mechanism and preparation method of PD-1 antibody in clinical treatment of lymphoma.


Assuntos
Linfoma , Anticorpos Monoclonais , Apoptose , Antígeno B7-H1 , Humanos , Receptor de Morte Celular Programada 1
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 23(2): 192-4, 2006 Apr.
Artigo em Zh | MEDLINE | ID: mdl-16604495

RESUMO

OBJECTIVE: To study the gene mutation of collagen, type I, alpha 1 (COL1A1) associated with the clinical characterization of a Chinese family with type I osteogenesis imperfecta (OI). METHODS: Polymerase chain reaction, DNA sequencing and restriction endonuclaese analysis were used to check all the members in the family with OI and 50 normal control people for detecting the mutation of COL1A1 gene. RESULTS: A 2461G>A (G821S) mutation was found and identified in COL1A1 gene of OI patients, to whom the individual clinical characterization was displayed, however. And the other members in the family with OI and the control did not have such gene mutation as 2461G>A. CONCLUSION: The mutation of COL1A1 gene is one of the OI etiologic causes in China. There is no simple universal linkage between such gene changes and OI phenotype, but which not only involved in the OI genotype but the genetic background as well.


Assuntos
Povo Asiático/genética , Colágeno Tipo I/genética , Osteogênese Imperfeita/genética , Sequência de Bases , China , Cadeia alfa 1 do Colágeno Tipo I , Análise Mutacional de DNA , Humanos , Mutação , Linhagem
12.
Zhonghua Yi Xue Za Zhi ; 86(3): 170-3, 2006 Jan 17.
Artigo em Zh | MEDLINE | ID: mdl-16638323

RESUMO

OBJECTIVE: Osteogenesis imperfecta (OI) is a congenital disease of connective tissue of increased bone fragility and low bone mass, most often caused by single amino acid substitution of glycine residues in the collagen, type I, alpha 1 protein (COL1A1) gene or the collagen, type I, alpha 2 protein (COL1A2) gene, encoding type I procollagen chains. We describe here the clinical, biochemical, and molecular characterization of a family with type I OI in China and would like to explore whether the biochemical characterization of OI in China is different from that in other countries. METHODS: Through clinical research, we study the clinical characteristic of the OI household. Genomic DNA was isolated from peripheral blood lymphocytes of the proband and his family members by saturation hydroxybenzene-chloroform methods; amplification of target COL1A1 gene by Polymerase chain reaction with 23 pairs of different primers; purification; direct sequencing of the Polymerase chain reaction product. According to the mutation site, we took restriction enzyme analysis to 50 normal control people. RESULTS: We found a G and A heterozygosis mutation at the exon 48 causing an a1 (I) p. G1157D substitution in the proband and his sister who is also a sufferer of OI. At the same time, other normal people in the family and other normal control people do not have this change. CONCLUSION: This is the first delineation of an aspartic acid substitution in new site of the a1 (I) chain causing nonlethal osteogenesis imperfecta. Only nine aspartic acid substitution in type I collagen has been fully reported in the world. Now we revealed a new nosogenesis of OI. Since only few of nucleotide changes in type I collagen glycine codons would result in an aspartic acid substitution, these are predicted to be infrequent. Furthermore, it is possible to suggest that nosogenesis of OI in china is different from other countries.


Assuntos
Colágeno Tipo I/genética , Mutação , Osteogênese Imperfeita/genética , Sequência de Bases , Criança , Colágeno/genética , Cadeia alfa 1 do Colágeno Tipo I , Análise Mutacional de DNA , Feminino , Genes Dominantes , Humanos , Masculino , Linhagem
13.
Reprod Toxicol ; 61: 169-76, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27079746

RESUMO

Anorectal malformations in combination with hypospadias (ARMs & hypospadias) are a type of complex congenital malformations. The underlying mechanisms of this deformity are largely unknown. In this study, we comprehensively characterized the dysplasia, histological malformations, and genetic changes of ARMs & hypospadias in male rats after maternal exposure to di-n-butyl phthalate (DBP) by gastric intubation at doses of 850mg/kg bw/day during GD11-15. On postnatal day 1, anatomical and histopathological analysis confirmed combined malformations of the genital tubercle (GT), terminal rectum (TR) and testes. DBP-induced dysplasia was also seen in the kidney, lung, spleen, heart and liver of ARMs & hypospadias male rats. Moreover, decreased levels of serum testosterone, as well as reduced expression of genes related to the androgen signaling pathway (Cyp11a1, Hsd3b, Scarb1, Star, AR, Srd5a2) were found in the testes of ARMs & hypospadias male rats after DBP exposure as compared to untreated controls. Further, decreased mRNA levels of Shh, Fgf10, Gli2, Gli3, Bmp4, Wnt5a, Hoxa13, Hoxd13, Fgfr2 and AR were observed in TR and GT in the ARMs & hypospadias group. These results provide evidence that prenatal exposure to DBP can lead to combined anorectal and urogenital malformations as well as dysplasia of the testes.


Assuntos
Dibutilftalato/toxicidade , Exposição Materna/efeitos adversos , Plastificantes/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Animais , Animais Recém-Nascidos , Malformações Anorretais/induzido quimicamente , Proteínas de Ligação a DNA/genética , Feminino , Hipospadia/induzido quimicamente , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Gravidez , Ratos Sprague-Dawley , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptores Androgênicos/genética , Testículo/anormalidades , Testículo/efeitos dos fármacos , Testosterona/sangue
14.
Reprod Toxicol ; 61: 75-81, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26948521

RESUMO

This study was to compare the alterations of androgen cascades in di-n-butyl phthalate (DBP)-exposed male offspring without hypospadias (undeformed) versus those with hypospadias. To induce hypospadias in male offspring, pregnant rats received DBP via oral gavage at a dose of 750mg/kg BW/day during gestational days 14-18. The mRNA expression levels of genes downstream of the androgen signaling pathway, such as androgen receptor (AR) and Srd5a2, in testes of undeformed rat pups were similar to those in controls; in hypospadiac rat pups these levels were significantly lower than those of control pups. In contrast, both undeformed and hypospadiac rats had decreased serum testosterone levels, reduced mRNA expression of key enzymes in the androgen synthetic pathway in the testes, and ablated genes of developmental pathways, such as Shh, Bmp4, Fgf8, Fgf10 and Fgfr2, in the genital tubercle (GT) as compared to those in DBP-unexposed controls, albeit hypospadiac rats had a more severe decrement than those of undeformed rats. Although other possibilities cannot be excluded, our findings suggest that the relatively normal levels of testosterone-AR-Srd5a2 may contribute to the resistance to DBP toxicity in undeformed rats. In conclusion, our results showed a potential correlation between decreased testosterone levels, reduced mRNA expression of AR and Srd5a2 and the occurrence of hypospadias in male rat offspring prenatally exposed to DBP.


Assuntos
Dibutilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Hipospadia , Plastificantes/toxicidade , Efeitos Tardios da Exposição Pré-Natal , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Animais , Feminino , Hipospadia/sangue , Hipospadia/genética , Hipospadia/patologia , Masculino , Proteínas de Membrana/genética , Gravidez , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Receptores Androgênicos/genética , Testículo/efeitos dos fármacos , Testículo/patologia , Testosterona/sangue , Uretra/anormalidades
15.
Toxicology ; 338: 77-85, 2015 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-26514922

RESUMO

Previous study have demonstrated that not only the anorectal development but also the general conditions of anorectal malformations (ARMs) male rats are severely affected by di-n-butyl phthalate (DBP) maternal exposure. However, the mechanisms underlying DBP-induced congenital defects remain elusive. Reportedly, Fgf10/Fgfr2 and androgen receptor (AR) are pivotal for the development of multiple organs. In this study, we therefore investigated the expression of Fgf10/Fgfr2 together with AR in the terminal rectum and multiple organs of ARM male rats induced by in utero exposure to DBP. DBP was administered to pregnant rats to establish the model and the incidence of ARMs in male offspring was 39.5%. On postnatal day(PND)1, the gross photograph and histopathological staining confirmed the abnormal manifestations in these organs of newborn ARMs. Decreased anogenital distance, body weight and serum testosterone level were observed in ARM male offspring. The reduced expression of Fgf10/Fgfr2 mRNA and protein was seen in terminal rectum and kidney, spleen, liver, heart in ARM male rats, whereas the reduced expression of AR was only observed in the kidney and terminal rectum. Our findings suggest the potential involvement of altered Fgf10/Fgfr2 signaling and AR in pathogenesis of local and systemic development defects in ARMs male rats induce by DBP.


Assuntos
Canal Anal/anormalidades , Anus Imperfurado/induzido quimicamente , Dibutilftalato/toxicidade , Fator 10 de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptores Androgênicos/metabolismo , Reto/anormalidades , Reto/efeitos dos fármacos , Canal Anal/metabolismo , Animais , Animais Recém-Nascidos , Malformações Anorretais , Anus Imperfurado/genética , Anus Imperfurado/metabolismo , Peso Corporal , Feminino , Fator 10 de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Exposição Materna/efeitos adversos , Gravidez , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptores Androgênicos/genética , Reto/metabolismo , Transdução de Sinais/efeitos dos fármacos , Testosterona/sangue
16.
Asian J Androl ; 16(5): 774-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24875824

RESUMO

Some published evidence has revealed that the dendritic cells can interact with pathogens that exist in the inner foreskin. This information provides a new vision that pathogens could play a role through the redundant prepuce; numerous studies have failed to find pathogens in prostates of patients who had chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, no studies have reported an association between foreskin length and CP/CPPS. Hence, we conducted a retrospective case-control study of clinical data from 322 CP/CPPS patients (case group) and 341 nonCP/CPPS patients (control group). Demographic characteristics, lifestyle factors, and foreskin lengths were collected and analyzed. Multivariate logistic regression was adopted to calculate the odds of foreskin length for CP/CPPS. According to the multivariate logistic regression results, when the foreskin length covered up more than half of the glans penis, the odds for CP/CPPS were higher with an increased foreskin (odds ratio (OR): 1.66, 95% confidence interval (CI): 1.04-2.66). In comparison, when the glans penis was completely covered by the foreskin, the OR value increased to 1.86 (95% CI, 1.2-2.88). The study results showed an association between foreskin length and the odds of CP/CPPS. When the foreskin length covered up more than half of the glans penis, there were greater odds for CP/CPPS. This possible mechanism might result from interaction between pathogens and DCs in the inner foreskin, consequently activating T-cells to mediate allergic inflammation in the prostate and producing the autoimmunizations causing CP/CPPS.


Assuntos
Prepúcio do Pênis/anatomia & histologia , Prostatite , Adolescente , Adulto , Estudos de Casos e Controles , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Tamanho do Órgão , Pênis/anatomia & histologia , Estudos Retrospectivos , Adulto Jovem
17.
Asian J Androl ; 14(4): 560-5, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22504876

RESUMO

To derive a precise estimation of the associations between the cytochrome P450 1B1 (CYP1B1) 4326C/G variants and prostate cancer (PCa) risk or aggressiveness, a meta-analysis was performed using all eligible published studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association in seven literature studies with 2788 cases and 2968 controls. In the overall analysis, no significant association was found between the CYP1B1 4326C/G polymorphism and PCa risk, but ethnicity subgroup analyses and a case-source analysis revealed significant associations. The 4326G allele showed a significant association with increased PCa risk in Asians (OR=1.52, 95% CI: 1.20-1.92), and significant associations were also observed in a heterozygote comparison (OR=1.40, 95% CI: 1.03-1.89), a homozygote comparison (OR=2.38, 95% CI: 1.31-4.33) and in a dominant genetic model (OR=1.52, 95% CI: 1.14-2.01). Moreover, the 4326G allele was also significantly correlated with an increased risk of sporadic PCa (OR=1.13, 95% CI: 1.04-1.24), and significant associations were observed in a heterozygote comparison (OR=1.16, 95% CI: 1.02-1.33), a homozygote comparison (OR=1.24, 95% CI: 1.03-1.49) and a dominant genetic model (OR=1.19, 95% CI: 1.05-1.34). The overall analyses and all subgroup analyses showed no significant association between the 4326C/G polymorphism and PCa aggressiveness. Our meta-analysis showed that CYP1B1 4326G allele is significantly associated with an increased PCa risk in Asians and in sporadic PCa cases.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Povo Asiático/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Alelos , Intervalos de Confiança , Citocromo P-450 CYP1B1 , Heterozigoto , Homozigoto , Humanos , Masculino , Razão de Chances , Polimorfismo Genético , Neoplasias da Próstata/etnologia , Fatores de Risco
18.
Zhongguo Gu Shang ; 22(4): 271-3, 2009 Apr.
Artigo em Zh | MEDLINE | ID: mdl-19408755

RESUMO

OBJECTIVE: To investigate the molecular mechanism of TFE (total flavone of epimedium) in the treatment of osteoporosis, and then provide experimental evidence for modernization and further development of TFE as an traditional Chinese medicine. METHODS: Sixty healthy female SD rats with aged 4 months were randomly divided into three groups (including control group in which rats received sham surgery, OVX group in which ovariectomized rats didn't give any medicine after the removal of ovaries and TFE group in which ovariectomized rats administrated TFE), 20 rats in each group. Compared bone mineral density (BMD) between before operation and at 4th week after operation in order to verify the establishment of osteoporotic model (criteria: BMD decreased more than 20% at 4th week after operation). The rats in TEF group were administrated total flavone of epimedium(concentration 30 mg/ml, 10 ml/kg, qd) orally for 4 weeks. After this, killed rats to harvest the lower part of the femur and detected BMD again. Applying the reverse transcriptase-polymerase chain reaction technique (RT-PCR) to detect expression of OPG, OPGL mRNA in bone tissue. RESULTS: (1) At 4th week after ovariectomy, the mean BMD of lumbar vertebra in TFE group fell to (0.084 +/- 0.020) g/cm2. Administrated with TFE for 4 weeks,the BMD increased to (0.112 +/- 0.009) g/cm2. There was significant improvement compare with the OVX group (P < 0.05). (2) Compared between OVX group and TFE group, The OPG mRNA expression of TFE group obviously enhanced. There was significant difference in statistics (P < 0.05). However,the promotion for OPGL mRNA expression were detected between OVX group and TFE group,there was no significant difference in statistics (P > 0.05). CONCLUSION: This study showed that TFE could inhibit differentiation and maturation of osteoclast through enhancing OPG mRNA expression, accordingly,to treat osteoporosis.


Assuntos
Epimedium/química , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Osteoprotegerina/genética , Ovariectomia , Ligante RANK/genética , Animais , Densidade Óssea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Flavonas , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos
19.
Artigo em Zh | MEDLINE | ID: mdl-21186634

RESUMO

AIM: To study the relation between Respiratory Syncytial Virus infection and asthma development by measuring airway responsiveness (AR) and M2R function. METHODS: Guinea pigs (n = 34) were randomly divided into 4 groups: Hep-2/NS group (group A, n = 9), RSV/NS group (group B, n =9), Hep-2/OVA group (group C, n = 8) and RSV/OVA group(group D, n = 8). On day 21 after infection we tested AR and M2R. Then counted eosinophils in BALF and observed pathological change. RESULTS: Intraairway pressure(IP mmH20) of group B had no significant difference with group A(P > 0.01), and the extent of IP decrease also had no difference between groups A and B (P > 0. 05), but IP of C group were much higher than group A (P<0.05), with extent of IP decrease lower than group A (P < 0.05). And IP of group D were higher than group C (P < 0.01), with the extent of IP decrease much lower than group C (P < 0.05). CONCLUSION: RSV infection could enhance OVA-induced M2R dysfunction, then develop AHR.


Assuntos
Asma/fisiopatologia , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/fisiopatologia , Infecções por Vírus Respiratório Sincicial/imunologia , Animais , Asma/imunologia , Asma/virologia , Hiper-Reatividade Brônquica/virologia , Feminino , Cobaias , Masculino , Ovalbumina/imunologia , Distribuição Aleatória , Receptor Muscarínico M2/fisiologia , Vírus Sinciciais Respiratórios/imunologia
20.
Zhonghua Er Ke Za Zhi ; 47(7): 523-6, 2009 Jul.
Artigo em Zh | MEDLINE | ID: mdl-19951516

RESUMO

OBJECTIVE: To isolate the prevalent strain of enterovirus 71 (EV71) in Xi'an area in 2008, and compare the concordance of viral isolation, reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescent technique in detecting EV71, find the fast and effective method for detection, and analyze the differences between the EV71 strains isolated from Xi'an and Fuyang, Anhui. METHOD: Virus isolation and RT-PCR were carried out on vesicle fluid and throat swab specimens that were collected from the patients with hand-foot-and-mouth disease, RD and HEp-2 cell lines were used for viral isolation. The virus was identified by using immunofluorescence technique. Nucleotide sequencing was performed on positive product of RT-PCR, and compared with EV71 isolated from Fuyang in 2008, then submitted to Genbank. RESULT: Among the 56 samples of throat swab inoculated on RD and HEp-2 cells, the positive rates were 5.4% (3/56) and 1.8% (1/56), respectively. Among the 56 samples of vesicle fluid inoculated on RD and HEp-2 cells, the positive rates were 12.5% ( 7/56 ) and 5.4% (3/56), respectively. Cytopathic effect of RD and HEp-2 cells appeared on days 7 and 10, respectively. The positive rates of RT-PCR on throat swab and vesicle fluid samples were 21.4% (12/56) and 33.9% (19/56), respectively. Cytopathic effect was found in cell culture for 14 cases and immunofluorescence, showed that 9 of them were infected with EV71. The authors obtained the EV71 strain prevalent in Xi'an during 2008. The nucleotide sequence was submitted to the NCBI Genbank and gained the accession number EU812461. CONCLUSION: The EV71 in Xi'an prevalent during 2008 may have a weaker epithelial tropism. Comparison of the EV71 strain isolated from Xi'an with EU703812, EU703813 and EU703814 isolated from Fuyang, Anhui showed that the homology was 97%-98%. RT-PCR is an important method for rapid detection of EV71.


Assuntos
Enterovirus Humano A/classificação , Enterovirus Humano A/isolamento & purificação , Doença de Mão, Pé e Boca/virologia , Secreções Corporais/virologia , Linhagem Celular Tumoral , Criança , China/epidemiologia , Enterovirus Humano A/genética , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Dados de Sequência Molecular , Faringe/virologia , RNA Viral , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência do Ácido Nucleico
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