Search

Highlights • Mitophagy was activated after cerebral ischemia and reperfusion and reached the highest level at 24 h after reperfusion. • Autophagy occurred in diverse components of the neurovascular unit. • The PINK1/Parkin/p62 signalling pathway was involved in cerebral ischemia-reperfusion injury. Abstract This study examined the course of mitophagy following cerebral ischemia with reperfusion and the role of the PTEN-induced kinase 1 (PINK1)/Parkin/p62 signalling pathway. The middle cerebral artery of male Sprague-Dawley rats was occluded for 90 min and was followed by different time-points of reperfusion. Cerebral infarct areas were detected by 2,3,5-triphenyl tetrazolium chloride staining, while brain damage was observed by haematoxylin and eosin staining. Levels of LC3, Beclin1 and LAMP-1 were estimated by western blots. LC3B location was observed in various cells in the neurovascular unit. In addition, PINK1 accumulation in damaged mitochondria and Parkin/p62 mitochondrial translocation were investigated by double immunofluorescence staining. Finally, the levels of PINK1, Parkin and p62 expression in mitochondrial fractions were estimated by western blots. Cerebral ischemia with different time-points of reperfusion resulted in infarct in the territory of the middle cerebral artery accompanied by overall brain damage. In addition, we found up-regulation of LC3B, Beclin1, and LAMP-1, as well as mitophagy activation after reperfusion, with peak expression of these proteins at 24 h after reperfusion. Electron microscopy and immunofluorescence indicated that LC3B was primarily located in neurons, although lower levels of expression were found in astrocytes and even less in vascular endothelial cells. Moreover, significant increases in PINK1 accumulation in the outer membrane of mitochondria and increased Parkin/p62 mitochondrial translocation were shown at 24 h after reperfusion. These findings suggest that the PINK1/Parkin/p62 signalling pathway was involved in the pathophysiological processes following ischemia and reperfusion. [ABSTRACT FROM AUTHOR]

We investigated whether Xiao-Xu-Ming decoction reduced mitophagy activation and kept mitochondrial function in cerebral ischemia-reperfusion injury. Rats were randomly divided into 5 groups: sham, ischemia and reperfusion (IR), IR plus XXMD (60 g/kg/day) (XXMD60), IR plus cyclosporin A (10 mg/kg/day) (CsA), and IR plus vehicle (Vehicle). Focal cerebral ischemia and reperfusion models were induced by middle cerebral artery occlusion (MCAO). Cerebral infarct areas were measured by triphenyl tetrazolium chloride staining. Cerebral ischemic injury was evaluated by hematoxylin and eosin staining (HE) and Nissl staining. Ultrastructural features of mitochondria and mitophagy in the penumbra of the ischemic cortex were observed by transmission electron microscopy. Mitophagy was detected by immunofluorescence labeled with LC3B and VDAC1. Autophagy lysosome formation was observed by immunofluorescence labeled with LC3B and Lamp1. The expression of LC3B, Beclin1, and Lamp1 was analyzed by Western blot. The rats subjected to MCAO showed worsened neurological score and cell ischemic damage. These were all significantly reversed by XXMD or CsA. Moreover, XXMD/CsA notably downregulated mitophagy and reduced the increase in LC3, Beclin1, and Lamp1 expression induced by cerebral ischemia and reperfusion. The findings demonstrated that XXMD exerted neuroprotective effect via downregulating LC3, Beclin1, Lamp1, and mitochondrial p62 expression level, thus leading to the inhibition of mitophagy. [ABSTRACT FROM AUTHOR]

Objectives. To investigate the safety and feasibility of sorafenib neoadjuvant therapy combined with retroperitoneoscopic radical nephrectomy (RRN) in treating T2 large renal cell carcinoma (RCC). Methods. Retrospectively analyzed 5 cases (2 males and 3 females, aged 52-73 years) of T2 stage large RCC who receive preoperative sorafenib targeted treatment (400 mg bid for 1-3 months) and RRN between March, 2013, and July, 2014. Patient information, therapeutic regimen, drug adverse effect, tumor changes before and after surgery, and perioperative parameters were recorded. Results. During the sorafenib therapy adverse effects included 2 cases of hypertension (Grade I toxicity), 1 case of hand-foot syndrome (Grade I), and 1 case of diarrhea (Grade II), which were all tolerable for patients. CT scan and histopathological tests confirmed significant reduction in the longest dimension (LD) and medium density (MD) of the tumor after therapy as well as tumor hemorrhage, necrosis, and cystic degeneration. All 5 patients received RRN surgery successfully around 2 weeks after drug discontinuation with only 1 case of perioperative complication. Conclusions. Sorafenib neoadjuvant therapy could significantly reduce the size and aggressiveness of T2 large renal tumors, thus reducing the operative challenge and enabling patients who were previously disqualified for operation to receive surgical treatment. [ABSTRACT FROM AUTHOR]

The prostate adenocarcinoma of the Copenhagen rat (R3327) is recognized as a suitable model for human prostate carcinoma. In this study, we sequenced its complete mitogenome and total length of the genome was 16,310 bp (GenBank Accession Number KM820831). It contains 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. This mitochondrial genome sequence will provide new genetic resource into prostate adenocarcinoma disease. [ABSTRACT FROM PUBLISHER]

Ethnopharmacological relevance Acupuncture attenuates neuronal damages following ischemia. Aim of the study The purpose of the present study was to investigate the beneficial effects of acupuncture on hypoxia–ischemia induced brain damages in neonatal rats. Materials and methods Male postnatal 7 days rats were randomly divided into 3 groups: sham control (sham), hypoxia–ischemia (HI), and HI plus acupuncture treatment (HI+Acu). The rats in HI and HI+Acu groups were submitted to model of neonatal HI, established by occluding the left common carotid artery followed by a 3.5 h period of hypoxia (8% O 2 –92% N 2 ). At 24 h after HI, animals were stimulated by acupuncture treatment once a day and the treatment continued during 4 weeks, 5 days/week. Behavioral functions, learning and memory ability, and body weight were observed at different time-points after HI. DNA fragmentation assay were performed with TUNEL staining to evaluate apoptosis and expression levels of mitochondrial Bcl-2, mitochondrial Bax, Cleaved caspase 3, Cleaved caspase 9 in the damaged hippocampus were detected by western blotting 28 days following HI. GDNF, BDNF levels in hippocampus were also determined. Results The results showed that acupuncture significantly promoted growth and development, improved neurobehavioral function, learning and memory ability after 20 days' treatment. Furthermore, we obtained one interesting finding that acupuncture attenuated cellular apoptosis and up-regulated GDNF and BDNF levels in hippocampus. Conclusions All of these results suggest that acupuncture as a potential treatment may exert neuroprotective effects via inhibiting cellular apoptosis, increased GDNF and BDNF expression levels in rat hippocampus experiencing HI. [ABSTRACT FROM AUTHOR]

Prostate cancer is a highly prevalent disease in older men of the western world. MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression via posttranscriptional inhibition of protein synthesis. To identify the diagnostic potential of miRNAs in prostate cancer, we downloaded the miRNA expression profile of prostate cancer from the GEO database and analysed the differentially expressed miRNAs (DE-miRNAs) in prostate cancerous tissue compared to non-cancerous tissue. Then, the targets of these DE-miRNAs were extracted from the database and mapped to the STRING and KEGG databases for network construction and pathway enrichment analysis. We identified a total of 16 miRNAs that showed a significant differential expression in cancer samples. A total of 9 target genes corresponding to 3 DE-miRNAs were obtained. After network and pathway enrichment analysis, we finally demonstrated that miR-20 appears to play an important role in the regulation of prostate cancer onset. MiR-20 as single biomarker or in combination could be useful in the diagnosis of prostate cancer. We anticipate our study could provide the groundwork for further experiments.

Background: To investigate whether the retroperitoneal or transperitoneal approach is preferable for right-sided laparoscopic donor nephrectomy (R-LDN)., Material/methods: We retrospectively compared the donor and recipient outcomes of R-LDNs performed with a standard transperitoneal approach (n=21) or a semi-open retroperitoneal approach (n=32)., Results: Patient demographics were similar between groups. The semi-open retroperitoneal group had shorter operative time (89.5 min vs. 105 min, p<0.001), shorter WIT (102 s vs. 120 s, p<0.001), and longer renal veins (2.5 cm vs. 2.2 cm, p<0.001). No conversions to open procedures occurred. There were no significant differences in the blood loss, length of hospital stay, or donor complication rate between the 2 groups. All grafts functioned adequately, and there were no significant differences in graft function, first-week hemodialysis, and serum creatinine level at discharge between the 2 groups The recipient complication rate was similar between the 2 groups (9.4% vs. 9.5%, p=0.986)., Conclusions: The semi-open retroperitoneal approach is safe and effective for R-LDN. Further study is required to evaluate long-term graft function.

Background: Laparoscopic dismembered pyeloplasty is technically feasible for ureteropelvic junction (UPJ) obstruction although it is still challenged by its technical difficulty and time-consuming. In this study, we compared the initial results of retroperitoneal laparoscopic pyeloplasty versus a combined laparoscopic dissection and open reconstruction through a small incision in the treatment of UPJ obstruction., Methods: Sixty-four patients with primary UPJ obstruction underwent pyeloplasty: 32 patients underwent laparoscopic procedure and 32 patients underwent open assisted laparoscopic surgery including two steps, ie, laparoscopic dissection of the UPJ transperitoneally and then pyeloplasty via an extended small incision. The demographic data and intraoperative, postoperative and follow-up conditions of patients were compared between the two groups., Results: Preoperative data were comparable in the patients of the two groups. The operative time was shorter (60.9 minutes vs 157.7 minutes, P < 0.0001) and the complication rate was lower (9.4% vs 31.3%, P < 0.05) in the open assisted group than in the laparoscopic group. The estimated blood loss (42.3 ml vs 47.8 ml), time to have normal diet (37.6 hours vs 33.8 hours), and hospital stay (6.7 days vs 6.2 days) were equivalent. The operative success rate was 97% for the open assisted group and 91% for the laparoscopic group., Conclusions: The procedure of combined small incision with laparoscopy for UPJ obstruction is technically easy, and the results are promising. It can be used as an alternative to conventional procedures.

Objective: To report initial experience with laparoscopic radical cystectomy in 43 patients with invasive bladder carcinoma., Methods: From December 2003 to October 2006, 29 men and 14 women underwent laparoscopic radical cystectomy with extracorporeal-assisted urinary diversion for transitional cell carcinoma of the bladder (n=40), adenocarcinoma (n=2) and squamous cell arcinoma (n=1). We report the specific technical details and present initial results of our series., Results: The mean operative time of laparoscopic radical cystectomy with pelvic lymph node dissection was 195.4 min, the mean blood loss 273.7 ml, and the transfusion rate 6.9%. Two procedures converted to open techniques. Lymphadenectomy detected lymph node metastasis in three patients., Conclusions: We demonstrate that the combination of laparoscopic radical cystectomy and extracorporeal urinary diversion is possible and remains a safe, feasible, and repeatable surgical technique. The laparoscopic surgery with extracorporeal urinary reconstruction is emerging as a viable alternative to open radical cystectomy while characterized by less trauma, short recovery time and low complications. Intermediate oncologic outcomes are encouraging and comparable to those of open series. To determine the oncologic outcome long-time follow-up will be necessary.

Purpose: To present our experience in laparoscopic radical cystectomy with extracorporeal urinary diversion for treatment of Chinese bladder cancer patients., Methods: Between January 2003 and November 2005, 41 men and 5 women with organ-confined muscle-invasive transitional cell carcinoma of the bladder underwent laparoscopic radical cystectomy with the Bricker-type urinary diversion. The age range was 36-71 years. Laparoscopic radical cystectomy and bilateral pelvic lymphadenectomy were performed using five fan-shaped ports by a transperitoneal approach. An ileal conduit diversion was created through the site of specimen retrieval which was the second port at the region of the right pararectus., Results: 46 radical cystectomies with Bricker-type ileal conduits were performed. No conversion to open surgery was necessary. Mean operating time was 220 min (range 120-249 min) for laparoscopic radical cystectomy and 75 min (range 65-120 min) for creating the ileal conduits. Mean estimated blood loss was 276 ml (range 155-567 ml). Two of the 46 patients needed blood transfusion (400 ml each). Mean days to ambulation and oral intake was 4.1 (range 3-5 days) and 3.5 (range 3-6 days), respectively. Mean hospital stay was 17.6 days (range 12-35 days). Mean follow-up was 6.1 months (range 3-19 months). Histopathological examination of the specimens revealed stage T2N0M0 in 18 cases, T3aN0M0 in 14, T3bN0M0 in 9 and T3bN1M0 in 5 (TNM staging). WHO grading: G1 in 2 cases, G2 in 26 cases and G3 in 18 cases. Pelvic metastases appeared in one case and 44 patients are alive and free of disease. Intravenous pyelogram at 3 weeks postoperatively shows no evidence of upper urinary obstruction in 45 patients., Conclusion: Despite technical difficulties, laparoscopic radical cystectomy with Bricker-type urinary diversion is feasible. With more experience in the surgical technique, laparoscopic radical cystectomy with extracorporeal urinary diversion can become an alternative treatment of choice in the selected patients with organ- confined bladder cancer in China., (Copyright 2007 S. Karger AG, Basel.)

Objective: To discuss the clinical experience of laparoscopic radical prostatectomy by extraperitoneal approach., Methods: Five patients with localized prostate cancer underwent laparoscopic radical prostatectomy by extraperitoneal approach. The surgical procedure included the excision of the prostate, seminal vesicles, ampulla ductus deferentis and part of the bladder neck, followed by urethrovesical anastomosis., Results: All the operations were successful. The mean operation time was 350 minutes (ranging from 270 to 420 mm); the mean estimated blood loss was 480 ml (ranging from 250 to 600 ml). The bowel activity was recovered with 48 hours after surgery. The patients were ambulant between the 2nd and 3rd postoperative days. The mean hospital stay was 8. 5 days (ranging from 7 to 12 days). The 3-8 months follow-up found no incontinence of urine; of the 3 preoperatively potent patients, 2 were able to have sexual intercourse; strictured stoma was reported in only 1 case., Conclusion: The extraperitoneal laparoscopic radical prostatectomy, keeping the procedure out of the peritoneal cavity, with small incision and rapid recovery, may be considered as a promising surgical method for patients with localized prostate cancer.

Objective: To investigate the relationship between cyclooxygenase-2 (COX-2) mRNA expression and the biological behaviors of prostate carcinoma (PCa)., Methods: The expression of COX-2 mRNA was detected by RT-PCR method in 32 samples of PCa and the COX-2/GAPDH value was determined. Seven normal prostate tissues were served as control., Results: The expression of COX-2 mRNA in normal tissue of 7 control cases was all negative. There was statistical correlation between the COX-2/GAPDH and the Gleason scores of PCa. There also showed statistical correlation between the COX-2/GAPDH and the stages of PCa., Conclusion: COX-2 mRNA play an important role in occurrence and progression of the PCa. COX-2 is a tumor marker which may be the possible prognostic factor of PCa.

Objective: To evaluate the efficacy and feasibility of laparoscopic aid in upper urinary reconstructive operation., Methods: Fifty-eight patients with ureteropelvic junction obstruction, 5 patients with upper ureter polypous, 2 patients with upper ureter stenosis, and 13 patients with upper ureter lithiasis underwent upper urinary reconstructive operation with laparoscopic aid described as follows:an incision 1 cm long was made, a 10 mm trocar and a 30 degrees laparoscope were wt in, the part with lesion was isolated and resected, and then pyeloplasty or end-to-end anastomosis of ureter was performed., Results: The mean operative time was 33 minutes (25-45 minutes). The mean blood loss was 20 ml (15-25 ml). Complications such as urinary leakage and infection were observed. The double J stent was removed at 1 month after the operation. Follow-up for 3 to 15 months in 20 cases showed alleviation of hydronephrosis., Conclusion: An effective and safe method with less wound and operative time, combination of laparoscopic aid and open surgery in upper urinary reconstructive operation helps avoid difficult laparoscopic operation, does not increase trauma of the abdominal wall, and is worth promoting clinically.