[Establishment of Rat Prostatitis Model through Induction with Estrogen and Androgen at Different Concentrations].

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.

[Bladder outlet obstruction index alone is not reliable for the diagnosis of benign prostate hyperplasia].

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.

Metabolism, pharmacokinetics, and hepatic disposition of xanthones and saponins on Zhimu treatments for exploratively interpreting the discrepancy between the herbal safety and timosaponin A3-induced hepatotoxicity.

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.

Role of GPR30 in estrogen-induced prostate epithelial apoptosis and benign prostatic hyperplasia.

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.

Chinese medicine CGA formula ameliorates DMN-induced liver fibrosis in rats via inhibiting MMP2/9, TIMP1/2 and the TGF-ß/Smad signaling pathways.

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.

Expression of SOCSs in human prostate cancer and their association in prognosis.

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.

[In vitro studies of 2 µm laser treatment of benign prostatic hyperplasia].

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.

[New understanding of dog's prostatic urethral re-epithelial underwent two-micron laser prostatic vaporesection].

OBJECTIVE: To study the re-epithelialization of dog's prostate urethra after two-micron laser resection of the prostate (TmLRP) and the role of CK34 (CK34ßE12)-positive cells in this process. METHODS: TmLRP were performed in 15 elder male dogs and wound specimens harvested at Days 3, 7 and 14 respectively. Immunohistochemical staining was performed to determine the expression levels of CK34 and prostate specific antigen (PSA) in prostatic urethra urothelial cells. RESULTS: There was no CK34-positive cells in surgical wounds after 3 days while a cluster of CK34-positive cells were found to cover surgical wounds after 7 days, and these cells attached to residual prostate tissues. At Day 14 post-operation, positive expression of CK34 was found in basal cells of newborn urothelium. CONCLUSION: Prostate tissues are the important organizations for re-epithelialization of prostatic urethra after benign prostate hyperplasia surgery, and CK34-positive basal cells play an important role in this process.

[Effects of distance between residence and hemodialysis unit on cardiovascular complications and treatments of maintenance hemodialysis patients].

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.

De novo genome assembly depicts the immune genomic characteristics of cattle.

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.

Anti-diabetic effects of TongGuanWan, a Chinese traditional herbal formula, in C57BL/KsJ-db/db mice.

In the present study, the anti-diabetic effects of a traditional Chinese medicinal formula extract, TongGuanWan, were investigated in type 2 diabetic animals. It was orally administered to C57BL/KsJ-db/db mice once a day for 4 weeks at the doses of 62, 125, and 250 mg/kg body weight. TongGuanWan significantly lowered the blood glucose and glycosylated haemoglobin levels as well as improved the glucose tolerance in db/db mice. The serum triglyceride levels in the db/db mice were significantly decreased, whereas the high-density lipoprotein cholesterol levels were significantly increased, after treatment with this herbal formula. TongGuanWan also markedly decreased the animals' body weights compared to those of the control db/db group but did not alter food intake. The effects of TongGuanWan were compared to those of the drug rosiglitazone. In addition, five main constituents of TongGuanWan, mangiferin, berberine, cinnamic aldehyde, timosaponin BII, and timosaponin AIII, were quantified using high performance liquid chromatography coupled with a diode array and an evaporative light scattering detector (HPLC-DAD-ELSD). These results suggest that TongGuanWan may be useful for the treatment of type 2 diabetes.

Effects of Puerariae Radix Extract on Endotoxin Receptors and TNF-α Expression Induced by Gut-Derived Endotoxin in Chronic Alcoholic Liver Injury.

Kudzu (Pueraria lobata) is one of the earliest medicinal plants used to treat alcohol abuse in traditional Chinese medicine for more than a millennium. However, little is known about its effects on chronic alcoholic liver injury. Therefore, the present study observed the effects of puerariae radix extract (RPE) on chronic alcoholic liver injury as well as Kupffer cells (KCs) activation to release tumor necrosis factor alpha (TNF-α) induced by gut-derived endotoxin in rats and macrophage cell line. RPE was observed to alleviate the pathological changes and lipids deposition in liver tissues as well as the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic gamma-glutamyl transpeptidase (GGT) activity. Meanwhile, RPE inhibited KCs activation and subsequent hepatic TNF-α expression and downregulated the protein expression of endotoxin receptors, lipopolysaccharide binding protein (LBP), CD14, Toll-like receptor (TLR) 2, and TLR4 in chronic alcohol intake rats. Furthermore, an in vitro study showed that RPE inhibited the expression of TNF-α and endotoxin receptors, CD14 and TLR4, induced by LPS in RAW264.7 cells. In summary, this study demonstrated that RPE mitigated liver damage and lipid deposition induced by chronic alcohol intake in rats, as well as TNF-α release, protein expression of endotoxin receptors in vivo or in vitro.

[Protective effect of breviscapine on human hepatocytes under hypoxia/re-oxygenation and its possible mechanism].

OBJECTIVE: To explore the protective effect of breviscapine on human hepatocytes (L-02) under hypoxia/re-oxygenation (H/R) and elucidate its possible mechanism. METHODS: A in vitro model of H/R was employed to mimic H/R injury of graft organ. L-02 cells were randomly divided into 3 groups: control, H/R and breviscapine treatment (pre-treated with breviscapine and H/R). After a 10 h hypoxic culturing under 1% O(2), 94% N(2) and 5% CO(2), L-02 cells received oxygen for 1, 2, 4, 8, 16 and 24 h respectively. MICA mRNA and protein levels were detected by quantitative real-time polymerase chain reaction (PCR) and Western blot. And the activity of natural killer (NK) cell cytotoxicity for L-02 was measured by lactate dehydrogenase (LDH) release assay. After blocking I/R treatment with NKG2D antibody, the activity of NK cell cytotoxicity for L-02 was detected. RESULTS: After 10 h hypoxia, MICA mRNA and protein levels significantly increased from 1 h, stayed up-regulated until 8 h and then went back to normal level after reoxygenation versus the control group. The activity of NK cell cytotoxicity for L-02 under the treatment of H/R increased markedly from 1 h post-reoxygenation and stayed up-regulated from 1 h to 8 h versus the control group. After hypoxia, L-02 cells were blocked with NKG2D antibody and the NK cell cytotoxicity for L-02 significantly decreased versus the I/R group. The administration of breviscapine significantly lowered the mRNA and protein levels of MICA in L-02 under I/R and then significantly decreased the NK cell cytotoxicity. CONCLUSION: The process of I/R may mediate the NK cell cytotoxicity activity toward to L-02 by inducing a strong increase of MICA at mRNA and protein levels in L-02 cells. And the administration of Breviscapine significantly reduces the NK cell cytotoxicity for L-02 under I/R through the down-regulated expression of MICA.

Molecular biological mechanism of action in cancer therapies: Juglone and its derivatives, the future of development.

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.

Imbalance in the estrogen/androgen ratio may affect prostate fibrosis through the TGF-ß/Smad signaling pathway.

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.

[Influences of erectile functions in benign prostatic hyperplasia patients by two micro (thulium) laser resection of prostate-tangerine technique].

OBJECTIVE: To observe the influences of erectile dysfunction (ED) by age, prostate size and lower urinary tract symptom (LUTS) undergoing two micro (thulium) laser resection of prostate-tangerine technique (TmLRP-TT). METHODS: A total of 50 BPH (benign prostatic hyperplasia) patients underwent TmLRP-TT with a 70 W laser power. The patient prostate volume, international prostatic symptomatic score (IPSS), maximal flow rate and international index of erectile function (IIEF-5) were assessed preoperatively. A retrospective assessment was made after surgery and at a 6-month follow-up. They were divided into 2 groups according to prostate volume ≤ 50 or > 50 ml, age ≤ 65 yrs or > 65 yrs, IIEF-5 ≤ 20 or > 21 and IPSS ≤ 27 or > 27 respectively. The postoperative influences of erection by age, prostate size and LUTS were observed. RESULTS: Significant differences existed between pre-operation and 6 months post-operation in terms of IPSS (25.35 ± 5.6 vs 9.52 ± 3.1, P < 0.01) and maximal flow rate (6.51 ± 1.21 vs 13.4 ± 2.7 ml/s, P < 0.01). There was no difference between pre-operation and 6 months post-operation (34 vs 32 cases, χ(2) = 0.673, P = 0.603). The patients with prostate volume >50 ml group had 9 additional ED cases while those with IPSS >27 group contained 11 fewer ED cases. There were significant differences between both groups (χ(2) = 5.255, P = 0.002; χ(2) = 11.560, P = 0.001 respectively). BPH patients aged over 65 years old were more likely to suffer ED than those under 65 years old (χ(2) = 5.882, P = 0.015). However, there was no significant difference in age in terms of suffering postoperative ED (χ(2) = 3.125, P = 0.077). CONCLUSION: TmLRP-TT can significantly improve LUTS in BPH patients. The presence of large volume prostate is an independent risk factor for an increased number of ED patients after TmLRP-TT. LUTS is an independent risk factor for ED. And TmLRP-TT may improve the ED patients with severe LUTS.

Effects of calcitriol on peripheral endothelial progenitor cells and renal renovation in rats with chronic renal failure.

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.

Prostatic anatomical parameters correlate with clinical characteristics suggestive of benign prostatic hyperplasia.

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.

Characterization of anti-Coxsackie virus B3 constituents of Radix Astragali by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

To profile the anti-Coxsackie virus B3 constituents of Radix Astragali, an HPLC-DAD-MS(n) analytical method, combined with an in vivo test, has been developed to identify the constituents of the active part, which has been demonstrated to have potency to inhibit the proliferation of virus in cardiac muscle, alleviate infraction in heart and elevate the survival rate of the animal. By comparing their retention time and MS data with those obtained from the authentic compounds and the published data, a total of 19 compounds, including 11 isoflavonoids and eight saponins, were identified, among which one pterocarpane glucoside was reported for the first time. The present study provides an approach to rapidly screening bioactive constituents in traditional Chinese medicines.

[Urinary connective tissue growth factor as a biomarker chronic allograft nephropathy in a rat model].

OBJECTIVE: To determine whether urinary connective tissue growth factor (CTGF) can be a molecular marker for chronic allograft nephropathy (CAN) in a rat model. METHODS: F344 rat renal grafts were orthotopically transplanted into Lewis rats (n = 24). Lewis rats underwent sham operation as control group (n = 12). Kidney grafts were harvested at Weeks 4, 8, 12 and 16 respectively. Serum creatinine (SCr) was measured. The CAN grades were evaluated according to the Banff 97 schema. The expressions of CTGF in kidney, serum and urine were determined by Western blot and competitive indirect ELISA. Spearman correlation analysis was used to compare CTGF expression and the development of CAN. RESULTS: The expression of CTGF in the graft group was markedly elevated in comparison with the control group. Statistics analysis of CTGF protein in kidney detected by Western blot showed significant differences between these five groups (0.33 ± 0.05 for control, 0.55 ± 0.02 for Week 4, 0.80 ± 0.03 for Week 8, 0.90 ± 0.03 for Week 12 and 1.14 ± 0.11 for Week 16, P < 0.01). Both urine and serum CTGF increased by Week 4 and maintained a high level up to Week 16. The urinary CTGF of renal allografts was (2.9 ± 0.7), (12.9 ± 3.6), (32.3 ± 11.4) and (31.0 ± 8.9) ng/mg creatinine for Weeks 4, 8, 12 and 16 respectively. The urinary levels were positively correlated with SCr, Banff scores and expression of CTGF in the graft kidney (r = 0.848, 0.874, 0.747, all P < 0.01). CONCLUSIONS: CTGF plays a significant role in the pathological changes of CAN after kidney transplantation. Urinary CTGF has the potential as a biomarker for predicting the clinical course of CAN.