The JMJD family of histone demethylase and their intimate links to cardiovascular disease.

The incidence rate and mortality rate of cardiovascular disease rank first in the world. It is associated with various high-risk factors, and there is no single cause. Epigenetic modifications, such as DNA methylation or histone modification, actively participate in the initiation and development of cardiovascular diseases. Histone lysine methylation is a type of histone post-translational modification. The human Jumonji C domain (JMJD) protein family consists of more than 30 members. JMJD proteins participate in many key nuclear processes and play a key role in the specific regulation of gene expression, DNA damage and repair, and DNA replication. Importantly, increasing evidence shows that JMJD proteins are abnormally expressed in cardiovascular diseases, which may be a potential mechanism for the occurrence and development of these diseases. Here, we discuss the key roles of JMJD proteins in various common cardiovascular diseases. This includes histone lysine demethylase, which has been studied in depth, and less-studied JMJD members. Furthermore, we focus on the epigenetic changes induced by each JMJD member, summarize recent research progress, and evaluate their relationship with cardiovascular diseases and therapeutic potential.

New therapeutic schedule for prostatic cancer-3 cells with ET-1 RNAi and Endostar.

BACKGROUND: Endothelin-1 and Endostar are both significant for the progression, proliferation, metastasis and invasion of cancer. In this paper, we studied the effect of ET-1 RNAi and Endostar in PC-3 prostatic cancer cells. MATERIALS AND METHODS: The lentiviral vector was used in the establishment of ET-1 knockdown PC-3 cells. Progression and apoptosis were assessed by CKK-8 and flow cytometry, respectively. Transwell assay was used to estimate invasion and signaling pathways were studied by Western blotting. RESULTS: ET-1 mRNA and protein in ET-1 knockdown PC-3 cells were reduced to 26.4% and 22.4% compared with control group, respectively. ET-1 RNAi and Endostar both were effective for the suppression of progression and invasion of PC-3 cells. From Western blotting results, the effects of ET-1 regulation and Endostar on PC-3 cells were at least related to some signaling pathways involving PI3K/Akt/Caspase-3, Erk1/2/Bcl-2/Caspase-3 and MMPs (MMP-2 and MMP-9). Furthermore, combined treatment of ET-1RNAi and Endostar was found to be more effective than single treatment. CONCLUSIONS: Both ET-1 RNAi and Endostar can inhibit the progression and invasion of PC-3 cells, but combined treatment might be a better therapeutic schedule.

Contralateral ureteral metastasis 4 years after radical nephrectomy.

INTRODUCTION: Metastasis of renal cell carcinoma to the contralateral ureter is extremely rare. To date, only 50 cases of metastatic RCC to the ureter have been reported, among whom 6 cases occur at the contralateral site. We herein report a rare case of metastatic RCC in the contralateral ureter 4 years after radical nephrectomy. PRESENTATION OF CASE: A 74-year-old man presented with gross, painless hematuria for one month. Computed tomography scan confirmed that a 1.5 cm × 0.5 cm tumor occurred in the contralateral distal ureter. A 3.5 cm segment of ureter was resected and a uretero-vesical anastomosis with psoas hitch was accomplished. DISCUSSION: The reappearance of hematuria after radical nephrectomy is the most common manifestation of the metastasis to the bladder or ureter. The mechanism of metastasis is not clear. In pathology, vimentin and cytokeratins might help to differentiate between metastatic clear cell renal cell carcinoma and clear cell transitional cell carcinoma. CONCLUSION: Metastasis of renal cell carcinoma to the contralateral ureter is rare. Early recognition is extremely important in protecting the remaining renal function and prolonging life-expectancy for post-nephrectomy patients. Complete metastectomy suitable anastomosis have been shown to improve survival.

[A comparative study on different doses of cernilton for preventing the clinical progression of benign prostatic hyperplasia].

OBJECTIVE: To compare the efficacy and safety of different doses of cernilton in preventing the clinical progression of benign prostatic hyperplasia (BPH). METHODS: A total of 240 BPH patients with the International Prostate Symptom Score (IPSS) >7 were equally allocated to an experimental and a control group and treated with oral cernilton (Prostate), the former at the dose of 750 mg, the latter at 375 mg, both twice a day for 4 years. Changes, of IPSS, prostate volume, postvoid residual urine, maximum flow rate (Qmax), prostate specific antigen (PSA), the incidence of urine retention and the rate of surgery were compared between the two groups after the treatment. RESULTS: In the experimental group, the IPSS, prostate volume, postvoid residual urine and Qmax were 10.5 +/- 5.6, (29.2 +/- 9.5) ml, (15.2 +/- 3.1) ml and (16.2 +/- 4.5) ml/s after the treatment, as compared with 20.1 +/- 4.1, (37.8 +/- 12.5) ml, (42.5 +/- 6.6) ml and (10.0 +/- 3.5) mVs before the treatment, while in the control group, the four indexes were 14.9 +/- 4.3 vs 19.2 +/- 3.8, (34.7 +/- 9.8) ml vs (37.1 +/- 11.9) ml, (25.6 +/- 4.6) ml vs (41.8 +/- 6.1) ml and (13.5 +/- 4.1) ml/s vs (10.2 +/- 3.8) ml/s, with a more obvious improvement in the experimental group than in the control after the 4-year treatment (P < 0.0001). Compared with pre-treatment, the IPSS and Qmax were improved 3 months (16.7 +/- 3.9, P < 0. 000 1) and 6 months ([13.2 +/- 4.1] ml/s, P < 0. 0001) respectively after the treatment in the experimental group, compared with 6 months (17.6 +/- 3.3, P = 0.0010) and 9 months ([12.0 +/- 3.7] ml/s, P = 0.0005) in the control; the prostate volume was improved 1 year after the treatment in the former ( [ 15.6 +/- 3.2 ] ml,P = 0.0487) but not at 4 years in the latter ([25.6 +/- 4.6] ml,P = 0.1040). The postvoid residual urine was improved at 3 months in both the experimental ([38.7 +/- 6.1] ml, P < 0.000 1) and the control group ([40.2 +/- 5.5] ml, P = 0.0422). The incidence of urine retention was lower in the former than in the latter (5 vs 16 person-times, P = 0.0147), and so was the rate of surgery (2 vs 8 person-times, P = 0.046 2). There were no significant differences in PSA between the pre-and post-treatment either in the experimental (P = 0.349 6) or in the control group (P = 0.3805). No toxical and adverse effects were observed. CONCLUSION: Long-term administration of cernilton at the dose of 750 mg may achieve faster and more obvious efficacy than at 375 mg in improving symptomatic BPH and preventing the clinical progression of BPH, with no adverse events.

Identification of candidate prostate cancer biomarkers in prostate needle biopsy specimens using proteomic analysis.

Although serum prostate specific antigen (PSA) is a well-established diagnostic tool for prostate cancer (PCa) detection, the definitive diagnosis of PCa is based on the information contained in prostate needle biopsy (PNBX) specimens. To define the proteomic features of PNBX specimens to identify candidate biomarkers for PCa, PNBX specimens from patients with PCa or benign prostatic hyperplasia (BPH) were subjected to comparative proteomic analysis. 2-DE revealed that 52 protein spots exhibited statistically significantly changes among PCa and BPH groups. Interesting spots were identified by MALDI-TOF-MS/MS. The 2 most notable groups of proteins identified included latent androgen receptor coregulators [FLNA(7-15) and FKBP4] and enzymes involved in mitochondrial fatty acid beta-oxidation (DCI and ECHS1). An imbalance in the expression of peroxiredoxin subtypes was noted in PCa specimens. Furthermore, different post-translationally modified isoforms of HSP27 and HSP70.1 were identified. Importantly, changes in FLNA(7-15), FKBP4, and PRDX4 expression were confirmed by immunoblot analyses. Our results suggest that a proteomics-based approach is useful for developing a more complete picture of the protein profile of PNBX specimen. The proteins identified by this approach may be useful molecular targets for PCa diagnostics and therapeutics.

[Value of spiral CT in diagnosis of cystic renal cell carcinoma].

OBJECTIVE: To investigate the image features and the diagnostic value of spiral CT for cystic renal cell carcinoma. METHODS: The clinical data and CT manifestations of 17 operated and pathologically proven cystic renal cell carcinoma were retrospectively analyzed. There were 12 males and 5 females with an average age of 47.3 years (33 - 82 years). Plain and contrast CT scan (Siemens somatom) single layer sensation 16 layer spiral CT had been performed before operation. The image of artery phase (30 - 40 s), venous (60 - 70 s) and excretory (120 - 180 s) were respectively obtained after contrast administration. Various image reconstructions were done using Siemens Wizard workstation based on the raw images. RESULTS: It was found that 5 cystic renal cell cancers located in the right kidney and 12 in the left kidney. The long dimension of the tumor arranged from 21 - 100 mm with an average of 57 mm. The tumor looked like a round or round-like shape with density similar to fluid on plain CT scan. Some cystic renal carcinomas had a thick wall. Some had single or multiple cystic spaces filled with fluid of different densities. Some had infiltrated out of kidney surface or into renal sinus. Some showed enhanced nodules on the wall. CONCLUSION: Cystic renal cell carcinoma has its own specific morphologic features in spiral CT scan. Spiral CT may be very helpful in the diagnosis of cystic renal cell carcinoma before operation.

[The study of diagnosis and treatment of interstitial cystitis].

OBJECTIVE: To discuss the diagnosis and treatment interstitial cystitis (IC). METHODS: The clinical date of 10 cases of IC (all women) were analyzed. Their age ranged from 31 to 63 years, with a mean of 41 years. Their courses ranged from 1.5 to 7 years, with a mean of 3.4 years. The symptom criteria of the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) was met for IC and no patients had Hunner's ulcer. Potassium sensitivity tests (PST) were performed in all cases. Eight were positive. The O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) was used as treatment outcome measures. ICSI score was from 9 to 20 (mean, 14 +/- 4) at baseline. All the patients were treated with hydrodistention initially. Efficacy was evaluated at 1 month after hydrodistention. The patients who failed to respond to the treatment and recurrence after the treatment were treated by oral or intravesical therapy. RESULTS: The 10 cases were followed up for 3 to 26 months (mean, 7.8 months) after hydrodistention. Five patients obtained symptom relief. Among them, symptom significantly relieved or disappeared in 2, with the score decreased > 7; symptom partially relieved in 3, with the score decreased > 3. Five cases failed to respond to the treatment. Two cases had recurrence 3 and 6 months after the treatment. The effective rate was 50%. The ICSI score was decreased to 11 +/- 6 at 1 month (t = 4.394, P < 0.05) after the treatment. Those who failed to respond or recurrence after hydrodistention were treated by other methods. Two case were treated with oral Pentosan Polysulfate, effective. Three cases were treated with amitriptylin, 2 effective. Three cases were treated with intravesical Dimethyl sulfoxide plus heparin plus dexamethasone, all effective. CONCLUSIONS: The diagnosis of IC should meet the symptom criteria of the NIDDK. PST has significant high positive rate in IC patient, which can be used not only for diagnosis but also for instruction. There are a lot of strategies in the management of patients with IC. Hydrodistention is the first choice.