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1.
Nat Commun ; 14(1): 6601, 2023 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-37857610

RESUMO

Immunogenomic loci remain poorly understood because of their genetic complexity and size. Here, we report the de novo assembly of a cattle genome and provide a detailed annotation of the immunogenomic loci. The assembled genome contains 143 contigs (N50 ~ 74.0 Mb). In contrast to the current reference genome (ARS-UCD1.2), 156 gaps are closed and 467 scaffolds are located in our assembly. Importantly, the immunogenomic regions, including three immunoglobulin (IG) loci, four T-cell receptor (TR) loci, and the major histocompatibility complex (MHC) locus, are seamlessly assembled and precisely annotated. With the characterization of 258 IG genes and 657 TR genes distributed across seven genomic loci, we present a detailed depiction of immune gene diversity in cattle. Moreover, the MHC gene structures are integrally revealed with properly phased haplotypes. Together, our work describes a more complete cattle genome, and provides a comprehensive view of its complex immune-genome.


Assuntos
Genoma , Genômica , Bovinos , Animais , Genoma/genética , Complexo Principal de Histocompatibilidade/genética , Imunoglobulinas , Genes de Imunoglobulinas
2.
Biomed Pharmacother ; 148: 112785, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35272138

RESUMO

Juglone (5 - hydroxy - 1, 4 - naphthalene diketone) is a kind of natural naphthoquinone, present in the roots, leaves, nut-hulls, bark and wood of walnut trees. Recent studies have found that Juglone has special significance in the treatment of cancer, which plays a significant role in the resistance of cancer cell proliferation, induction of cancer cell apoptosis, induction of autophagy, anti-angiogenesis and inhibition of cancer cell migration and invasion, etc. Additionally, its derivatives also play a tumor suppressive effect. In conclusion, Juglone and its derivatives have been identified as effective anticancer drugs. This paper reviews action mechanisms of Juglone and its derivatives in cancer treatment.


Assuntos
Peptidilprolil Isomerase de Interação com NIMA/antagonistas & inibidores , Naftoquinonas/farmacologia , Neoplasias/patologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , DNA Polimerase Dirigida por DNA/efeitos dos fármacos , Humanos , Naftoquinonas/química , Neovascularização Patológica , Espécies Reativas de Oxigênio
3.
Int Urol Nephrol ; 54(3): 499-508, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35050457

RESUMO

OBJECTIVE: The present study aimed to investigate the effects of an imbalance in the estrogen/androgen ratio on prostate fibrosis. METHODS: Different concentrations of dihydrotestosterone (DHT) or estradiol (E2) dissolved in corn oil were injected subcutaneously into the nape of the castrated Sprague-Dawley (SD) rats over 28 consecutive days. Masson's trichrome staining and immunohistochemical staining were performed to detect the content of collagen fibers and the expression of collagen I, fibronectin, and elastin in the rat prostate of each group, respectively. DHT + E2 at different concentrations was administered to human normal prostate stromal immortalized cells (WPMY-1 cells) for 1 week. The expression of collagen I, fibronectin, elastin, transforming growth factor-ß1 (TGF-ß1), Smad3, and Smad7 was detected by Western blotting (WB). Then, WPMY-1 cells treated with 10 nM DHT + 5 pM E2 were incubated with the TGF-ß/Smad pathway inhibitor SD208 for 1 week, after which collagen I, fibronectin, and elastin expression was detected by WB. RESULTS: Compared with the uncastrated control and corn oil injection groups, the collagen fiber content and collagen I and fibronectin expression were increased and elastin expression was decreased in the castrated rat prostate with corn oil injection group (p < 0.01). Compared to castrated corn oil injection group, collagen fiber content, collagen I, and fibronectin expression were significantly decreased, and elastin expression was significantly increased in the castrated rat prostate 0.15 mg/kg DHT treatment group (p < 0.01). Following treatment with 0.15 mg/kg DHT, the content of collagen fibers, and the expression of collagen I and fibronectin were increased, and the expression of elastin was decreased in the rat prostate with increasing concentrations of E2 treatment group compared to the 0.15 mg/kg DHT group (p < 0.05, p < 0.01). Following treatment with 0.05 mg/kg E2, the collagen fiber content and the expression of collagen I and fibronectin were decreased, and the expression of elastin was increased in the rat prostate with increasing DHT concentration treatment group compared to the 0.05 mg/kg E2 group (p < 0.05, p < 0.01). Compared with the Control group, the expression of collagen I, fibronectin, TGF-ß1 and Smad3 was decreased, and the expression of elastin and Smad7 was increased in WPMY-1 cells after treatment with 10 nM DHT (p < 0.01). Following treatment with 10 nM DHT, the expression of collagen I, fibronectin, TGF-ß1, and Smad3 was increased, and the expression of elastin and Smad7 was decreased in WPMY-1 cells with increasing E2 concentration treatment compared to the 10 nM DHT group (p < 0.05, p < 0.01). Following treatment with 5 pM E2, the expression of collagen I, fibronectin, TGF-ß1, and Smad3 was decreased, and elastin and Smad7 expression was increased with increasing DHT concentration compared to the 5 pM E2 group (p < 0.05, p < 0.01). Compared to the 10 nM DHT + 5 pM E2 group, the expressions of collagen I and fibronectin were decreased; the expression of elastin was increased in WPMY-1 cells after the supplement of TGF-ß/Smad pathway inhibitor SD208 group (p < 0.05, p < 0.01). CONCLUSIONS: An imbalance in the estrogen/androgen ratio may affect prostate fibrosis. E2 may activate the degree of prostate fibrosis. In contrast to the effect of E2, DHT may inhibit the degree of prostate fibrosis, which might involve the TGF-ß/Smad signaling pathway.


Assuntos
Androgênios/análise , Estrogênios/análise , Próstata/química , Próstata/patologia , Transdução de Sinais/fisiologia , Proteínas Smad/fisiologia , Animais , Fibrose/etiologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta
4.
J Steroid Biochem Mol Biol ; 214: 105956, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34348182

RESUMO

BACKGROUND: The role of calcitriol (1,25-dihydroxyvitamin D3 or 1,25-(OH)2D3) in physiological processes, such as anti-fibrosis, anti-inflammation, and immunoregulation is known; however, its role in the remodeling of the glomerular capillary endothelium in rats with chronic renal failure (CRF) remains unclear. METHODS: Here, we analyzed the role/number of endothelial progenitor cells (EPCs), renal function, and pathological alterations in rats with CRF, and compared the results before and after supplementation with calcitriol in vivo. RESULTS: Amongst the three experimental groups (sham group, CRF group, and calcitriol-treated group (0.03 µg/kg/d), we observed substantially elevated cell adhesion and vasculogenesis in vivo in the calcitriol-treated group. Additionally, lower levels of serum creatinine (Scr) and blood urea nitrogen (BUN) was recorded in the calcitriol-treated group than the CRF group (p > 0.05). Calcitriol treatment also resulted in an improvement in renal pathological injury. CONCLUSIONS: Thus, calcitriol could ameliorate the damage of glomerular arterial structural and renal tubules vascular network integrity, maybe through regulating the number and function of EPCs in the peripheral blood of CRF rats. Treatment with it may improve outcomes in patients with renal insufficiency or combined cardiac insufficiency. Calcitriol could ameliorate CRF-induced renal pathological injury and renal dysfunction by remodeling of the glomerular capillary endothelium, thus, improving the function of glomerular endothelial cells.


Assuntos
Calcitriol/farmacologia , Creatinina/sangue , Células Progenitoras Endoteliais/efeitos dos fármacos , Falência Renal Crônica/tratamento farmacológico , Rim/efeitos dos fármacos , Insuficiência Renal Crônica/tratamento farmacológico , Animais , Nitrogênio da Ureia Sanguínea , Adesão Celular/efeitos dos fármacos , Células Progenitoras Endoteliais/patologia , Técnicas In Vitro , Rim/patologia , Falência Renal Crônica/patologia , Glomérulos Renais , Masculino , Ratos , Ratos Sprague-Dawley , Insuficiência Renal Crônica/patologia
5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(3): 477-484, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34018368

RESUMO

OBJECTIVE: To establish an experimental prostatitis animal model in Sprague-Dawley (SD) rats through induction by treatment of estrogen and androgen at different concentrations. METHODS: Fifty-three male SD rats aged 3 to 4 months were used in the study, and the castration model of male rats was established by excision of bilateral testes. The rats were randomly assigned to a blank group, a castration group and treatment groups receiving estrogen and androgen at different concentrations after castration, with 4 rats in each group. Dihydrotestosterone (DHT) and estradiol (E) were administered daily by subcutaneous injection to the treatment groups. All the rats were sacrificed by way of cervical dislocation after 1 month and the serum DHT and E concentrations of the rats in each group were assessed with ELISA. Prostate specimens were collected and the relative weight of the prostate of each group of rats was calculated. After HE staining of the prostate tissue, we observed with optic microscope structural changes in the prostate tissue and the state of prostatic inflammation in each group. Immunohistochemical examination was done to assess the expression of three inflammatory factors, transforming growth factor-ß1 (TGF-ß1), interleukin (IL)-6 and IL-8, in rat prostate tissues. RESULTS: The results of HE staining of rat prostate tissue showed that, compared with the blank group and castration group, the degree of inflammation increased significantly in the E0.05+DHT 0.5 mg/kg group and DHT0.15+E0.15 mg/kg group ( P<0.05). However, once the concentration of DHT exceeded 0.5 mg/kg, the degree of inflammation did not further aggravate. The results of immunohistochemical staining showed that when the concentration of exogenous E was constant, the expression of TGF-ß1 and IL-8 increased significantly in the E0.05+DHT 0.15 mg/kg group, E0.05+DHT 0.5 mg/kg group and E0.05+DHT 1.5 mg/kg group compared with that of the blank group ( P<0.05). In the E0.05+DHT 0.15 mg/kg group and E0.05+DHT 0.5 mg/kg group, the expression of TGF-ß1 and IL-8 increased significantly compared with that of the castration group ( P<0.05). Once the concentration of DHT reached 0.5 mg/kg, further increase in the concentration of DHT did not lead to any significant changes in the expression of TGF-ß1 or IL-8. In addition, when the concentration of exogenous DHT remained unchanged, the expressions of TGF-ß1, IL-6, and IL-8 increased significantly in the DHT0.15+E 0.05 mg/kg group and DHT0.15+E 0.5 mg/kg group, compared with that of the blank group and castration group ( P<0.05). CONCLUSION: Castration combined with treatment of different concentrations of estrogen and androgen could successfully induce the prostatitis model in SD rats.


Assuntos
Androgênios , Prostatite , Animais , Estrogênios , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Testosterona
6.
Asian J Androl ; 23(1): 64-68, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32930102

RESUMO

We conducted the present study to assess the correlation of the prostatic anatomical parameters, especially the ratio of peripheral zone thickness and transitional zone thickness, with clinical and uroflowmetry characteristics suggestive of benign prostate hyperplasia (BPH). A total of 468 consecutive patients with a detailed medical history were identified. All patients were evaluated by scoring subjective symptoms with the International Prostate Symptom Score (IPSS) and quality of life (QoL). The prostatic anatomical parameters were measured using transrectal ultrasonography, and postvoid residual urine and maximum flow rate (Qmax) values were also determined. Pearson's correlation analysis revealed that both total prostate volume (TPV; r = 0.160, P < 0.001) and transitional zone volume (TZV; r = 0.104, P = 0.016) increased with patients' age; however, no correlations were observed of TPV, TZV, transitional zone index (TZI), and transitional zone thickness (TZT) with IPSS or QoL (all P >0.05). Peripheral to transitional zone index (PTI) was found negatively correlated with total IPSS (r = -0.113, P = 0.024), storage IPSS (r = -0.103, P = 0.041), and voiding IPSS (r = -0.123, P = 0.014). As regards the uroflowmetry characteristics, PTI (r = 0.157, P = 0.007) was indicated to be positively correlated with Qmaxand negatively correlated with TZI (r = -0.119, P = 0.042) and TZT (r = -0.118, P = 0.045), but not correlated with TPV, TZV, or peripheral zone thickness (PZT) (all P > 0.05). Postvoid residual urine (PVR) had not correlated with all the prostatic anatomical variables (all P > 0.05). This is the first study that formally proposed the concept of PTI, which is an easy-to-measure prostate anatomical parameter which significantly correlates with total IPSS, storage IPSS, voiding IPSS, and Qmax, suggesting that PTI would be useful in evaluating and managing men with lower urinary tract symptoms (LUTS)/BPH. However, well-designed studies are mandatory to verify the clinical utility of PTI.


Assuntos
Próstata/patologia , Hiperplasia Prostática/patologia , Idoso , Humanos , Masculino , Próstata/anatomia & histologia , Próstata/diagnóstico por imagem , Hiperplasia Prostática/diagnóstico por imagem , Estudos Retrospectivos , Ultrassonografia , Urodinâmica
7.
Zhonghua Nan Ke Xue ; 26(6): 513-517, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-33356039

RESUMO

OBJECTIVE: To evaluate the clinical application value of the bladder outlet obstruction index (BOOI) in the diagnosis of BPH. METHODS: We retrospectively analyzed the urodynamic parameters and BOOI of 199 cases of BPH diagnosed from July 2016 to September 2018, which were divided into a BOO (n = 119), a suspected BOO (n = 39) and a non-BOO group (n = 41) based on the BOOI. We obtained the prostate volume (PV), IPSS, IPSS-voiding symptom score (IPSS-VS), quality of life score (QOL), maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR) from the patients, compared them among the three groups and analyzed their correlation to BOOI using Pearson's linear correlation analysis. RESULTS: No statistically significant differences were observed in age (P = 0.195), PSA (P = 0.380), IPSS (P = 0.380), IPSS-VS (P = 0.380), QOL (P = 0.380), Qmax (P = 0.380) and PVR (P = 0.912) among the three groups of patients, but PV was remarkably larger in the BOO than in the suspected BOO and non-BOO groups (ï¼»58.8 ± 30.0ï¼½ vs ï¼»49.8 ± 33.9ï¼½ and ï¼»45.5 ± 26.0ï¼½ ml, P = 0.031). Pearson's linear correlation analysis showed that BOOI was not correlated significantly to IPSS (r = -0.020, P = 0.778), IPSS-VS (r= -0.013, P = 0.853), QOL (r = -0.107, P = 0.132), Qmax (r = -0.130, P = 0.066) or PVR (r = -0.056, P = 0.433), nor obviously to PV (|r| = 0.178<0.4) though with P = 0.012. CONCLUSIONS: BOOI is not significantly correlated to PV, IPSS, IPSS-VS, QOL, Qmax or PVR, and therefore BOO cannot be diagnosed exclusively with BOOI.


Assuntos
Hiperplasia Prostática , Obstrução do Colo da Bexiga Urinária , Humanos , Masculino , Hiperplasia Prostática/complicações , Hiperplasia Prostática/diagnóstico , Qualidade de Vida , Estudos Retrospectivos , Obstrução do Colo da Bexiga Urinária/diagnóstico , Urodinâmica
8.
Steroids ; 160: 108655, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32439406

RESUMO

The BF3·Et2O-catalysed acetolysis of steroid sapogenins diosgenin, sarsasapogenin and tigogenin in dichloromethane as the solvent instead of acetic anhydride afforded (20S)- and (20R)-22,26-epoxycholestanes (compounds 1 and 2). 22S-23-Acetylsapogenins (compounds 4) were synthesized stereospecifically from 20R-22,26-epoxycholestanes (compounds 2) in good yield. The rearrangement of 22S-23-acetylsapogenins (compounds 4) afforded novel disubstituted dihydropyran furostanol frameworks. Exhaustive NMR characterization of the obtained compounds is provided. Additionally, the structures of the critical compounds (6a and 7a) were unequivocallyconfirmed by single crystal X-ray diffraction studies.


Assuntos
Sapogeninas/síntese química , Boranos , Catálise , Óxido de Etileno , Conformação Molecular , Sapogeninas/química , Estereoisomerismo
9.
Acta Pharmacol Sin ; 39(12): 1923-1934, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29795136

RESUMO

Timosaponin A3, a saponin in Zhimu, elicited hepatotoxicity via oxidative stress. However, the clinical medication of Zhimu has been historically regarded as safe, probably associated with the antioxidants it contains. However, the related information on the in vivo levels of timosaponin A3 and antioxidants remained unclear on Zhimu treatments. Therefore, a combination of the in vitro metabolism, including microbiota-mediated and liver-mediated metabolism, and in vivo pharmacokinetics and hepatic disposition, was conducted for three xanthones (neomangiferin, mangiferin, and norathyriol) and three saponins (timosaponin B2, timosaponin B3, and timosaponin A3) on Zhimu treatments. Consequently, following oral administration of Zhimu decoction to rats, those saponins and xanthones were all observed in the plasma with severe liver first-pass effect, where mangiferin was of the maximum exposure. Despite the ignorable content in the herb, timosaponin A3 elicited sizable hepatic exposure as the microbiota-mediated metabolite of saponins in Zhimu. The similar phenomenon also occurred to norathyriol, the microbiota-mediated metabolite of xanthones. However, the major prototypes in Zhimu were of limited hepatic exposure. We deduced the hepatic collection of norathyriol, maximum circulating levels of mangiferin, and timosaponin B2 and mangiferin interaction may directly or indirectly contribute to the whole anti-oxidation of Zhimu, and then resisted the timosaponin A3-induced hepatotoxicity. Thus, our study exploratively interpreted the discrepancy between herbal safety and timosaponin A3-induced hepatotoxicity. However, given the considerable levels and slow eliminated rate of timosaponin A3 in the liver, more attention should be paid to the safety on the continuous clinical medication of Zhimu in the future.


Assuntos
Antioxidantes/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Saponinas/metabolismo , Esteroides/efeitos adversos , Xantonas/metabolismo , Administração Oral , Animais , Antioxidantes/farmacocinética , Asparagaceae/química , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Saponinas/efeitos adversos , Saponinas/farmacocinética , Esteroides/metabolismo , Esteroides/farmacocinética , Espectrometria de Massas em Tandem/métodos , Xantonas/farmacocinética
10.
Biochem Biophys Res Commun ; 487(3): 517-524, 2017 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-28412354

RESUMO

Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17ß-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca2+ release from the endoplasmic reticulum, increased the mitochondrial Ca2+ concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca2+ release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP3) pathway, and this was abolished by treatment with the GPR30 antagonist G15. The release of cytochrome c and activation of caspase-3 in response to GPR30 activation were observed. Data generated from the analysis of animal models and human clinical samples indicate that treatment with the GPR30 agonist relieves testosterone propionate (TP)-induced prostatic epithelial hyperplasia, and that the abundance of GPR30 is negatively associated with prostate volume. On the basis of these results, we propose a novel regulatory mechanism whereby estrogen induces the apoptosis of PECs via GPR30 activation. Inhibition of this activation is predicted to lead to abnormal PEC accumulation, and to thereby contribute to BPH pathogenesis.


Assuntos
Apoptose/efeitos dos fármacos , Estrogênios/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/patologia , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Benzodioxóis/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cães , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Próstata/citologia , Hiperplasia Prostática/metabolismo , Quinolinas/farmacologia , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/genética , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/genética , Relação Estrutura-Atividade
11.
Biosci Rep ; 37(2)2017 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-28119492

RESUMO

The present study aims to explore the correlation of human leucocyte antigen (HLA)-DQ and tumour necrosis factor (TNF)-α gene polymorphisms with ocular myasthenia gravis (OMG) combined with thyroid-associated ophthalmopathy (TAO). From March 2009 to March 2015, 56 OMG patients complicated with TAO (OMG + TAO group), 134 patients diagnosed with OMG only (OMG group) and 236 healthy individuals (control group) were enrolled in the present study. PCR-sequence specific primer (PCR-SSP) was used for HLA-DQ genotyping and PCR-restriction fragment length polymorphism (PCR-RFLP) for TNF-α genotyping. ELISA kit was applied to detect acetylcholine receptor antibody (AchRAb) level and chemiluminescence immunoassay (CLIA) to measure thyroid-associated antibody (T-Ab) level. Logistic regression analysis was carried out to analyse the risk factors for OMG combined with TAO. DQA1*0103 showed lower frequency in the OMG group than in the control group. DQA1*0301 showed increased and DQB1*0601 showed decreased frequency in the OMG + TAO group. DQB1*0501 showed higher frequency in the OMG and OMG + TAO groups than in the control group. Patients carrying TNF-α -863C > A (CA + AA) might confront with greater risks of OMG combined with TAO. Frequency of DQA1*0103/*0301 and DQB1*0501/*0601, and TNF-α -863C > A, -238G > A and -308G > A were associated with the levels of AchRAb and T-Ab. TNF-α -863C > A (CA + AA) and high level of T-Ab were risk factors for OMG combined with TAO. Our results demonstrate that TNF-α -863 polymorphism is possibly correlated with the risk of OMG combined with TAO.


Assuntos
Oftalmopatia de Graves/genética , Antígenos HLA-DQ/genética , Miastenia Gravis/genética , Fator de Necrose Tumoral alfa/genética , Adulto , Análise de Variância , Biomarcadores/sangue , Feminino , Genótipo , Oftalmopatia de Graves/sangue , Oftalmopatia de Graves/imunologia , Humanos , Modelos Logísticos , Masculino , Miastenia Gravis/sangue , Miastenia Gravis/imunologia , Polimorfismo Genético , Receptores Nicotínicos/sangue , Fatores de Risco
12.
Acta Pharmacol Sin ; 37(6): 783-93, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27133300

RESUMO

AIM: Chinese medicine CGA formula consists of polysaccharide from Cordyceps sinensis mycelia (CS-PS), gypenosides and amygdalin, which is derived from Fuzheng Huayu (FZHY) capsule for treating liver fibrosis. In this study we attempted to confirm the therapeutic effects of CGA formula in dimethylnitrosamine (DMN)-induced liver fibrosis in rats, and to identify the mechanisms of anti-fibrotic actions. METHODS: Rats were injected with DMN (10 mg·kg(-1)·d(-1), ip) for 3 consecutive days per week over a 4-week period. The rats then were orally administered with CGA formula (CS-PS 60 mg·kg(-1)·d(-1), gypenosides 50 mg·kg(-1)·d(-1) and amygdalin 80 mg·kg(-1)·d(-1)) daily in the next 2 weeks. CS-PS, gypenosides or amygdalin alone were administered as individual component controls, whereas colchicine and FZHY were used as positive controls. Serum biomarkers were measured. Hepatic injury, collagen deposition and stellate cell activation were examined. The MMP activities, expression of TIMP protein and proteins involved in the TGF-ß1/Smad signaling pathways in liver tissues were assayed. RESULTS: In DMN-treated rats, administration of CGA formula significantly decreased serum ALT, AST and total bilirubin and hepatic hydroxyproline levels, increased serum albumin level, and attenuated liver fibrosis as shown by histological examination. Furthermore, these effects were comparable to those caused by administration of FZHY, and superior to those caused by administration of colchicine or the individual components of CGA formula. Moreover, administration of CGA formula significantly decreased the protein levels of α-SMA, TGF-ß1, TGF-ß1 receptor (TßR-I), p-TßR-I, p-TßR-II, p-Smad2, p-Smad3, TIMP1 and TIMP2, as well as MMP2 and MMP9 activities in liver tissues of DMN-treated rats. CONCLUSION: Chinese medicine CGA formula ameliorates DMN-induced liver fibrosis in rats, and this effect was likely associated with the down-regulation of MMP2/9 activities, TIMP1/2 protein expression and the TGF-ß1/Smad signaling pathways in the liver.


Assuntos
Amigdalina/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Fígado/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Amigdalina/química , Animais , Cordyceps/química , Dimetilnitrosamina , Medicamentos de Ervas Chinesas/química , Gynostemma/química , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Proteínas Smad/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Fator de Crescimento Transformador beta/metabolismo
14.
Int Urol Nephrol ; 47(5): 815-22, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25862237

RESUMO

OBJECTIVE: Pentoxifylline (PTF) has anti-inflammatory properties, which may be beneficial for diabetic nephropathy (DN). A meta-analysis was conducted to assess the additive effect of pentoxifylline and its safety among patients with type 2 DN under blockade of angiotensin system. DATA SOURCES: Relevant studies were searched from PubMed, CBM, EMBASE, CENTRAL and Cochrane renal group specialized register. SELECTION CRITERIA: All RCTs that compared the benefits and harms of pentoxifylline and ACEI/ARB with ACEI/ARB alone for DN were included. DATA EXTRACTION AND ANALYSIS: Pertinent data were extracted independently by two authors. Meta-analyses were performed when more than one study provided data on a comparable outcome. Standard mean differences (SMDs) for proteinuria and albuminuria, mean differences (MDs) for systolic blood pressure (SBP), diastolic blood pressure (DBP), HbA1c, serum creatinine (Scr), creatinine clearance (CrCl) and urine tumor necrosis factor-alpha (UTNF-α), 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed with the I (2) test. Adverse effects were assessed using descriptive techniques. RESULTS: Eight studies including 587 patients with a median duration of 5 months were identified. Compared with ACEI/ARB alone, the combination of PTF and ACEI/ARB significantly reduced proteinuria (SMD 0.76, 95% CI 0.52-0.99), albuminuria (SMD 0.36, 95% CI 0.12-0.59) and UTNF-α (MD 1.56 ng/g, 95% CI 0.09-3.03). However, no statistically significant changes were observed for SBP, DBP, HbA1c, Scr and CrCl. The most frequent adverse effects in patients treated with PTF were gastrointestinal symptoms (28/298) and dizziness (7/298), but in most cases, these symptoms were mild, only six participants withdrew due to intractable nausea and vomiting. CONCLUSIONS: Pentoxifylline can significantly provide additive antiproteinuric effect independent from the decrease in BP or improvement in glycemic control in DN patients under blockade of angiotensin system. Further large, multicenter, high-quality studies with long duration are necessary to prove whether it really has renoprotective effects in this patient population.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Pentoxifilina/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Albuminúria/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Pressão Sanguínea , Creatinina/sangue , Quimioterapia Combinada/métodos , Hemoglobinas Glicadas/metabolismo , Humanos , Pentoxifilina/efeitos adversos , Inibidores de Fosfodiesterase/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Asian J Androl ; 17(5): 831-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25652631

RESUMO

The purpose of this study is to characterize the re-epithelialization of wound healing in canine prostatic urethra and to evaluate the effect of this re-epithelialization way after two-micron laser resection of the prostate (TmLRP). TmLRP and partial bladder neck mucosa were performed in 15 healthy adult male crossbred canines. Wound specimens were harvested at 3 days, and 1, 2, 3, and 4 weeks after operation, respectively. The histopathologic characteristics were observed by hematoxylin and eosin staining. The expression of cytokeratin 14 (CK14), CK5, CK18, synaptophysin (Syn), chromogranin A (CgA), uroplakin, transforming growth factor-ß1 (TGF-ß1 ), and TGF-ß type II receptor in prostatic urethra wound were examined by immunohistochemistry and real-time polymerase chain reaction, respectively. Van Gieson staining was performed to determine the expression of collagen fibers in prostatic urethra and bladder neck would. The results showed that the re-epithelialization of the prostatic urethra resulted from the mobilization of proliferating epithelial cells from residual prostate tissue under the wound. The proliferating cells expressed CK14, CK5, but not CK18, Syn, and CgA and re-epithelialize expressed uroplakin since 3 weeks. There were enhanced TGF-ß1 and TGF-ß type II receptor expression in proliferating cells and regenerated cells, which correlated with specific phases of re-epithelialization. Compared with the re-epithelialization of the bladder neck, re-epithelialization of canine prostatic urethra was faster, and the expression of collagen fibers was relatively low. In conclusion, re-epithelialization in canine prostatic urethra resulted from prostate basal cells after TmLRP and this re-epithelialization way may represent the ideal healing method from anatomic repair to functional recovery after injury.


Assuntos
Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Terapia a Laser , Próstata/citologia , Reepitelização/fisiologia , Uretra/citologia , Animais , Cães , Masculino , Próstata/fisiologia , Próstata/cirurgia , Uretra/fisiologia , Uretra/cirurgia , Cicatrização/fisiologia
16.
Zhonghua Yi Xue Za Zhi ; 93(30): 2351-4, 2013 Aug 13.
Artigo em Chinês | MEDLINE | ID: mdl-24300200

RESUMO

OBJECTIVE: To compare the speed of vaporization of human prostatic tissue with benign prostatic hyperplasia (BPH) and depth of tissue damage using 70 and 120 W 2 µm laser devices. METHODS: Fresh prostatic tissue specimens were obtained from 5 patients by open prostatectomy and divided into separate groups (70 and 120 W) based on the energy of laser output (70 and 120 W respectively). Trials were performed in acryl basin containing 0.9% saline at 37 °C. And then each prostate gland in vitro was vaporizated similarly as routine transurethral 2 µm laser vaporesection. 70 W and 120 W power were applied for prostatic vaporesection. The 2 µm laser vaporization proportion and vaporesection speed were calculated postoperatively. Prostatic tissue was embedded for histological evaluation. After hematoxylin and eosin (H & E) staining and nicotinamide adenine dinucleotide-reduced (NADH) measurement, depth of coagulation zone and necrotic tissue layer were measured. The results of prostatic tissue between two groups were compared. RESULTS: With increasing output power, the speed (mean ± SD) of vaporesection of human prostatic tissue increased from (5.21 ± 0.66) g/5 min at 70 W to (10.84 ± 1.23) g/5 min at 120 W. Significant differences existed in the speed of vaporesection, resection and vaporization between 120 W and 70 W devices (P = 0.000). The proportion of vaporization mode was 81% at 70 W and 87% at 120 W during prostatic vaporesection. There was a stable penetration/coagulation depth with increasing power output for (0.98 ± 0.13)/(0.30 ± 0.09) mm at 70 W and (0.99 ± 0.12)/(0.31 ± 0.08) mm at 120 W. There were no significant differences in penetration and coagulation depth between 120 W and 70 W (P > 0.05). CONCLUSIONS: Both 120 and 70 W 2 µm Laser devices yield excellent performance and security in vaporizated human prostate tissue. The 120 W 2 µm laser offers significantly higher vaporesection rates than 70 W power. And vaporization mode is a predominant procedure of prostatic vaporesection.


Assuntos
Terapia a Laser/métodos , Hiperplasia Prostática/cirurgia , Idoso , Humanos , Técnicas In Vitro , Masculino , Próstata/patologia , Resultado do Tratamento
17.
Zhonghua Yi Xue Za Zhi ; 93(22): 1734-6, 2013 Jun 11.
Artigo em Chinês | MEDLINE | ID: mdl-24124682

RESUMO

OBJECTIVE: To explore the effects of etiological classification and the distance between residence and hemodialysis unit on cardiovascular complications and treatments in maintenance hemodialysis (MHD) patients. METHODS: A total of 756 MHD patients were collected from 12 hemodialysis centers of Guiyang, China between January 2011 and May 2012. Their distribution characteristics and correlations were based on medical records. And statistical analyses were performed. RESULTS: The ratio of males and females was 1.45: 1. And their mean age was (49.1 ± 14.7) years old. And 496 (65.6%) cases suffered from cardiovascular complications. The analysis of multi-factor Logistic regression revealed that distance between residence and dialysis unit was an independent risk factor of cardiovascular complications. The group of the farthest distance ( > 30 km) had the worst influence on dialysis adequacy Kt/V score, urea clearance rate, dialysis frequency and time per week. And the levels of blood phosphorus, triglyceride and cholesterol in the fourth group had marked elevations. It had a significant positive correlation with distance (P < 0.05). CONCLUSION: The distance between residence and dialysis unit is an independent risk factor of cardiovascular complications in MHD patients. The farthest distance ( > 30 km) has the greatest influence on dialysis adequacy.


Assuntos
Cardiopatias/epidemiologia , Diálise Renal , Insuficiência Renal Crônica/epidemiologia , Adulto , Feminino , Cardiopatias/complicações , Unidades Hospitalares de Hemodiálise , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Características de Residência , Fatores de Risco , Meios de Transporte , Resultado do Tratamento
20.
Mol Cell Biochem ; 381(1-2): 51-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23666742

RESUMO

Suppressors of cytokine signaling (SOCS) proteins have been identified as negative feedback regulators of cytokine-mediated signaling in various tissues, and demonstrated to play critical roles in tumorigenesis and tumor development of different cancers. The involvement of SOCSs in human prostate cancer (PCa) has not been fully elucidated. Thus, the aim of this study is to investigate the expression patterns and the clinical significance of SOCSs in PCa. The expression changes of SOCSs at mRNA and protein levels in human PCa tissues compared with adjacent benign prostate tissues were, respectively, detected by using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) and immunohistochemistry analyses. The associations of SOCSs expression with clinicopathological features and clinical outcome of PCa patients were further statistically analyzed. Among SOCSs, both QRT-PCR and immunohistochemistry analyses found that SOCS2 expression was upregulated (at mRNA level: change ratio = 1.98, P = 0.031; at protein level: 5.12 ± 0.60 vs. 2.68 ± 0.37, P = 0.016) and SOCS6 expression was downregulated (at mRNA level: change ratio = -1.65, P = 0.008; at protein level: 3.03 ± 0.32 vs. 4.0.72 ± 0.39, P = 0.004) in PCa tissues compared with those in non-cancerous prostate tissues. In addition, the upregulation of SOCS2 in PCa tissues was correlated with the lower Gleason score (P < 0.001), the absence of metastasis (P < 0.001) and the negative PSA failure (P = 0.009); the downregulation of SOCS6 tended to be found in PCa tissues with the higher Gleason score (P = 0.016), the advanced pathological stage (P = 0.007), the positive metastasis (P = 0.020), and the positive PSA failure (P = 0.032). Furthermore, both univariate and multivariate analyses showed that the downregulation of SOCS2 was an independent predictor of shorter biochemical recurrence-free survival. Our data offer the convincing evidence for the first time that the dysregulation of SOCS2 and SOCS6 may be associated with the aggressive progression of PCa. SOCS2 may be potential markers for prognosis in PCa patients.


Assuntos
Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Próstata/metabolismo , Próstata/patologia
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