SCARA5 as a downstream factor of PCAT29, inhibits proliferation, migration, and invasion of bladder cancer.

Scavenger receptor class A, member 5 (SCARA5) has been identified a novel tumor suppressor in several cancers. However, the functional and underlying mechanism of SCARA5 in bladder cancer (BC) need investigation. Here, we found SCARA5 expression was downregulated in both BC tissues and cell lines. Low SCARA5 in BC tissues was associated with a shorter overall survival. Moreover, SCARA5 overexpression reduced BC cell viability, colony formation, invasion, and migration. Further investigation demonstrated that the expression of SCARA5 was negatively regulated by miR-141. Furthermore, the long non-coding RNA prostate cancer associated transcript 29 (PCAT29) inhibited the proliferation, invasion, and migration of BC cells by sponging miR-141. Luciferase activity assays revealed that PCAT29 targeted miR-141 and miR-141 targeted SCARA5. In conclusion, SCARA5, as a downstream factor of the PCAT29/miR-141 axis, inhibited the proliferation, migration, and invasion of BC cells. These findings provide novel insights into the detailed molecular mechanisms of BC development.

PDCD5 inhibits progression of renal cell carcinoma by promoting T cell immunity: with the involvement of the HDAC3/microRNA-195-5p/SGK1.

BACKGROUND: Epigenetics exerts a vital role in the onset and development of renal cell carcinoma (RCC). Mounting evidence has shed light on the significance of human immune system in response to tumor infiltrating T cells. Hereby, we sought to unmask the immunomodulatory role of histone deacetylase 3 (HDAC3) and its potential upstream molecule, programmed cell death 5 (PDCD5) in RCC. METHODS: RCC and adjacent non-cancerous tissues were clinically resected from 58 patients, in which the expression profile of microRNA-195-5p (miR-195-5p), PDCD5, HDAC3, and serum glucocorticoid-inducible kinase 1 (SGK1) was determined by RT-qPCR and Western blot analysis. Their relations were investigated by a series of luciferase assays in combination with ChIP and co-IP. RCC cells (A498) were intervened using gain- and loss-of-function approaches, followed by cell proliferation evaluation. After co-culture with CD3+ T cells, flow cytometry and interferon-γ (IFN-γ) determination were performed. A xenograft tumor mouse model was developed for in vivo validation. RESULTS: PDCD5 was downregulated in RCC tissues and A498 cells. Upregulation of HDAC3, as well as of SGK1, resulted in suppression of A498 cell proliferation and promotion of T cell activation as evidenced by higher IFN-γ expression. Re-expression of PDCD5 downregulated HDAC3, causing a subsequent upregulation of miR-195-5p, while miR-195-5p could inversely modulate its target gene, SGK1. The regulatory mechanism appeared to be functional in vivo. CONCLUSION: Our results highlight the possible manipulation by PDCD5 on RCC cell proliferation and T cell activation, which provides new clues to better understand the immune balance in RCC progression.

BMSC-derived exosomal lncRNA PTENP1 suppresses the malignant phenotypes of bladder cancer by upregulating SCARA5 expression.

LncRNAs can be transported to tumor cells where they exert regulatory effects by bone marrow mesenchymal stem cells (BMSC)-derived exosomes. Here, we aimed to investigate the functional mechanism of BMSC-derived exosomal lncRNA PTENP1 in the progression of bladder cancer (BC). Methods of BMSC were identified by detecting surface markers through flow cytometry. Exosomes from BMSC were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blot analysis of exosome markers. Cellular internalization of BMSC-derived exosomes (BMSC-Exo) into BC cells was detected by confocal microscopy. CCK-8, colony formation, flow cytometry, wound healing, and transwell assays were adopted to estimate cell proliferation, apoptosis, migration, and invasion abilities, respectively. Interplay between miR-17 and lncRNA PTENP1 or SCARA5 was verified by dual-luciferase reporter, RNA pull down, and/or RNA immunoprecipitation (RIP) assays. Tumor xenograft assay was conducted in nude mice to study the role of exosomal lncRNA PTENP1 in BC progression in vivo. We showed exosomal lncRNA PTENP1 can be delivered into and suppress the malignant phenotypes of BC cells. LncRNA PTENP1 was identified as a sponge of miR-17, and SCARA5 was identified as a target gene of miR-17. The exosomes derived from PTENP1-overexpressing BMSC (BMSCOE-PTENP1-Exo) abolished the promotive effects of miR-17 overexpression or SCARA5 knockdown on the malignant phenotypes of BC cells. Moreover, exosomal lncRNA PTENP1 was demonstrated to inhibit BC tumor growth in nude mice by miR-17/SCARA5 axis. In conclusion, BMSC-derived exosomal PTENP1 suppressed the BC progression by upregulating the expression of SCARA5 via sponging miR-17, offering a potential novel therapeutic target for BC therapy.

WITHDRAWN: SCARA5 regulated by MEG3/miR-141 axis attenuates proliferation, migration and invasion of bladder cancer.

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Hepatectomy for spontaneous rupture of hepatocellular carcinoma without portal triad clamping.

Hepatectomy without portal triad clamping may decrease the incidence of liver injury; however, the effects of hepatectomy without portal triad clamping in the treatment of spontaneous rupture of hepatocellular carcinoma (SRHCC) remain unclear. The aims of the present study were to evaluate the therapeutic value of hepatectomy without portal triad clamping in the treatment of patients with SRHCC. The present study retrospectively reviewed patients with SRHCC who received hepatectomy without portal triad clamping (non-clamping group) and the therapeutic efficacy was compared with that of 20 patients with SRHCC undergoing the same surgery in the presence of portal triad clamping (clamping group). Following hepatectomy, the non-clamping group exhibited a significantly lower incidence of acute liver failure compared with the clamping group (P<0.05). No significant differences in operative time, intra-operative blood loss, disease-free or overall survival times between the two groups were identified (all P>0.05). At 1 week and 2 weeks after surgery, the non-clamping group exhibited significantly lower alanine aminotransferase, aspartate aminotransferase and total bilirubin serum levels compared with the clamping group (all P<0.05). Hepatectomy without portal triad clamping may decrease the incidence of liver injury and liver failure in patients with SRHCC, suggesting that it may be a safe and effective therapeutic strategy.

Protective effect of low-molecular-weight heparin on pancreatic encephalopathy in severe acute pancreatic rats.

BACKGROUND AND AIMS: Pancreatic encephalopathy (PE) is a severe complication and significant cause of death in patients with severe acute pancreatitis (SAP). We have reported previously that low-molecular-weight heparin (LMWH) treatment could reduce incidence of PE in SAP patients. Our objective here was to investigate the protective effect of LMWH and its mechanism on PE in SAP rats. METHODS: SD rats were randomly divided into three groups: (1) Sham-operation (S) group, (2) SAP group, and (3) LMWH treatment (LMWH) group. LMWH was administrated 4 h after the SAP model conducted. The levels of serum amylase, myelin basic protein (MBP), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), brain water content, occurrence of apoptosis, and pathological changes of pancreas and brain were measured at 1 day after models were set up in the SAP and S groups, and 1 day after LMWH treatment was administrated in the LMWH group. RESULTS: (1) The levels of serum amylase, TNF-α, and IL-6 in the SAP group were increased significantly more than those in the S and LMWH groups (all P < 0.001), as were the levels of serum MBP in the SAP group compared to those in the S and LMWH groups (P < 0.01, <0.05 respectively). However, while the level of serum amylase and IL-6 in the LMWH group were significantly increased compared to those in the S group (P < 0.05, <0.001 respectively), the levels of TNF-α and MBP showed no significant difference between the LMWH and S groups (all P > 0.05). (2) The brain water content in the SAP group was significantly increased compared to the S group and LMWH group (P < 0.01, <0.05 respectively). (3) Neuronal apoptosis, demyelination, and mitochondrial vacuolation in neuronal cells were observed in the SAP group; in contrast, in the LMWH group, significantly lower rates of neuronal apoptosis, demyelination and mitochondrial edema were observed in neuronal cells. CONCLUSIONS: The protective effect of LMWH on PE progression in SAP rats might result from inhibition of inflammatory activation and reduction of the occurrence of neuronal apoptosis.

Effect of lower-molecular weight heparin in the prevention of pancreatic encephalopathy in the patient with severe acute pancreatitis.

OBJECTIVE: To study the effect of lower-molecular weight heparin in the prevention of pancreatic encephalopathy (PE) in the patient with severe acute pancreatitis (SAP). METHODS: Two hundred sixty-five SAP patients were randomly divided into 2 groups: (1) conventional treatment group (C group, n = 130) and (2) conventional treatment plus lower-molecular weight heparin treatment group (LT group, n = 135). The clinical parameters, laboratory parameters and computed tomographic (CT) score of pancreatic necrosis (CTSPN), incidence of PE, and mortality in the 2 groups were compared. RESULTS: On admission, all the clinical parameters, laboratory parameters, and CTSPN in the 2 groups were not significantly different (P > 0.05). However, 1 to 2 weeks after treatment, the symptoms and signs improvement rate, the levels of blood and urine amylase, the CT score, and the Acute Physiology and Chronic Health Evaluation II score in the LT group were obviously lower than those in the C group (P < 0.05-0.01), and PE occurrence rate, mortality, and mean hospital stay in LT group were obviously lower than those in the C group (P < 0.05-0.01). CONCLUSIONS: Lower-molecular weight heparin can enhance the effect of conventional treatment of SAP and can markedly decrease the PE incidence and improve the survival rate of SAP. Lower-molecular weight heparin is a simple, safe, less expensive, and effective method for treatment of SAP. It can be used in every hospital.

Low molecular weight heparin in the treatment of severe acute pancreatitis: a multiple centre prospective clinical study.

OBJECTIVE: To study the effect of low molecular weight heparin (LMWH) in the treatment of severe acute pancreatitis (SAP). METHODS: A total of 265 SAP patients were randomly divided into two groups: firstly, the conventional treatment group (C group, n = 130; and secondly the conventional treatment plus the LMWH treatment group (LT group, n = 135). The clinical parameters, laboratory parameters and computed tomography (CT) score of pancreatic necrosis (CTSPN) in the two groups were compared. RESULTS: On admission, all the clinical parameters, laboratory parameters and CTSPN in the two groups were not significantly different (p > 0.05). However, after treatment, in LT group, the clinical presentation improvement rate and laboratory parameters improvement were significantly higher than those in C group (p < 0.05-0.01), and the acute physiology and chronic health evaluation (APACHE) II score, complication rate, mortality and mean hospital stay in LT group were obviously lower than those in C group (p < 0.05-0.01). The CT score in LT group was much lower than that in C group (p < 0.05). Two weeks after treatment FBI decreased obviously in C group, but not in LT group, and no haemorrhagic complications occurred. CONCLUSIONS: LMWH can enhance the effect of conventional treatment for SAP, and can markedly decrease the mortality of SAP. LMWH is a simple, safe, economic and effective method for treatment of SAP. It is can be used in every hospital.

Effect of low molecular weight heparin on pancreatic micro-circulation in severe acute pancreatitis in a rodent model.

BACKGROUND: Alleviation of microcirculation disorders in severe acute pancreatitis (SAP) can improve survival rates, and low molecular weight heparin (LMWH) is well known to have potent ameliorative effect on microcirculation disorders caused by anti-coagulant activity. The aim of this study was to investigate the effects of LMWH on pancreatic microcirculation in SAP in rats. METHODS: SD rats were randomly divided into 3 groups: sham operation (S) group, SAP group, and LMWH treatment (LT) group. The concentrations of serum amylase, tumor necrosis factor-alpha (TNF-alpha), endothelin-1 (ET-1), pancreatic ultrastructure were examined at 24 hours after the models were set up in each group. RESULTS: Compared with S group, the concentration of serum amylase, ET-1, and TNF-alpha in SAP group were significantly increased (P < 0.001); After LMWH treatment, the concentration of serum amylase, ET-1, TNF-alpha were decreased significantly compared with SAP group (P < 0.001, 0.01, 0.001, respectively). On electron microscopy, the microthrombosis in LT group was significantly less than that in SAP group. The 3-day survival rate in SAP group (25.0%) was significantly lower than that in S group (100.0%, P < 0.05) and in LT group (87.5%, P < 0.05). CONCLUSIONS: The disorder of pancreatic microcirculation may be involved in the inflammatory response of rats with SAP. LMWH can effectively improve the survival rate of SAP, and alleviate the severity of microcirculation disorders through its antithrombin effects and down-regulate the levels of serum ET-1 and TNF-alpha.

Effect of normothermic liver ischemic preconditioning on the expression of apoptosis-regulating genes C-jun and Bcl-XL in rats.

AIM: To explore the expression of apoptosis-regulating genes C-jun and Bcl-XL after normothermic liver ischemic preconditioning and its protective effect on hepatocytes in the rat. METHODS: Wistar rats are randomly divided into sham operation group (S group, n = 10), ischemic reperfusion group (IR group, n = 10) and ischemic preconditioning group (IP group, n = 10). After dissection of the hepatoduodenal ligament in S group, and after 30-min reperfusion in IR group and in IP group, the samples of liver tissue were taken for studying the hepatocellular apoptosis, the expressions of C-jun mRNA, Bcl-XL mRNA and their proteins, and morphologic changes at 0, 3, 6, 20 h. Meanwhile the venous blood samples were drawn at 3, 6 and 20 h for testing ALT, AST and LDH. RESULTS: The levels of ALT, AST and LDH in IR group and IP group were significantly higher than those in S group. Hepatocellular apoptosis was significantly increased in both IR group and IP group, especially in IR group. Expressions of C-jun mRNA and protein were significantly increased in IR group compared with those in both IP group and S group, but no significant difference between IP group and S group (P>0.05). Expressions of Bcl-XL mRNA and protein in IR group and S group were not significant (P>0.05), but were significantly increased in IP group compared with those in both S group and IR group. Patch necrosis of hepatocytes because of severe injury could be seen in IR group microscopically, and the ultrastructural changes were irreversible. Meanwhile in IP group, no hepatocellular necrosis occurred, and the ultrastructural changes were reversible because of mild injury. CONCLUSION: (1) IP can protect the rat liver from normothermic IR injury by modulation of the expression of apoptosis-regulating genes C-jun and Bcl-XL; (2) IR injury may activate the apoptosis of hepatocytes by increasing the expression of apoptosis-inducing gene C-jun; (3) IP may prohibit the apoptosis of hepatocytes by increasing the expression of apoptosis-inhibitory gene Bcl-XL.

[Surgical treatment of recurrent laryngeal nerve injury caused by thyroid operation].

OBJECTIVE: To study the surgical treatment of recurrent laryngeal nerve (RLN) injury caused by thyroid operation. METHODS: From 1970 to 2001, 50 patients with RLN injury were caused by thyroid operation. The causes, location, type, operative procedures and follow-up were retrospectively analyzed. RESULTS: Unilateral RLN injury occurred in 46 cases and bilateral nerve injury in 4 cases. The RLN injuries were located within 2cm below the point of RLN entering to throat in 45 nerves (83.3%), other places in 6 nerves (11.3%), and unknown location in 3 nerves (5.4%). Transection of the nerve was found in 19 nerves (36.5%), suture or scare pressing the nerve in 35 nerves (64.8%). All the injured nerves were repaired surgically. Meanwhile all 4 patients with bilateral RLN injuries underwent tracheotomy. Of the 50 cases, 44 cases (88.0%) were followed up for more than 1.5 years. Among the 44 followed-up patients, phonation was restored to normal or obvious improvement in 42 cases (95.5%), and improvement in 2 (4.5%). Of the 35 patients with 39 nerves underwent indirect or direct laryngoscopy, the affected vocal cord movement entirely recovered in 21 cords (53.8%), partially recovered in 7 cords (17.9%), uncovered in 11 cords (28.3%). There was no relation between the recovery of phonation or vocal cord movement with the timing or the procedure of repairing operation. CONCLUSIONS: The location of most RLN injuries caused by thyroid surgery are just below the point of RLN entering to throat, and most are mechanical injury, and need operation to resolve the cause. Once the RLN injury is made, an operation should be performed as early as possible.

[Non-recurrent laryngeal nerve during thyroid surgery: a report of 4 cases and literature review].

OBJECTIVE: To investigate clinical significance of non-recurrent laryngeal nerve. METHODS: Clinical data from 4 cases of non-recurrent laryngeal nerve and related literature review was made to acknowledge its incidence, variant types and matters concerned during thyroid surgery. RESULTS: Seven hundred and nineteen recurrent laryngeal nerves were exposed during 2156 thyroid operations in Xiangya Hospital, from which 4 were confirmed to hold non-recurrent laryngeal nerves (0.56%). Two cases were found on the right side and the other 2 on the left. Among the 4 cases, 3 (patients) were found to have non-recurrent laryngeal nerves during reoperation because of voice horse after the first operation. The other one was recognized during the first operation. CONCLUSIONS: Non-recurrent laryngeal nerve, a rare anomaly, is very vulnerable during thyroid surgery. Knowing the related knowledge of the non-recurrent laryngeal nerve and its types is helpful to avoid its damage during thyroid surgery.

[Androgen receptor and SMRT].

OBJECTIVE: To explore the interaction between androgen receptor (AR) and silencing mediator for retinoid and thyroid hormone receptor (SMRT) and their interaction site. Methods We recombined and constructed AR, SMRT gene and gene fragments, in vitro translated 35S fusion proteins to investigate the relationship between AR and SMRT using transient transfection, mammalian two-hybrid test, GST pull-down assay, and indirect immunofluorescence staining. Results AR possessed an intrinsic transcriptional repression activity and AR interacted directly with SMRT. One interactive surface on AR was mapped to the ligand-binding domain (LBD), and the presence of DNA binding domain enhanced this interaction. The binding surface on SMRT was mapped to the carboxyl-terminal nuclear receptor interacting domain (ID), and mutation of the LXXXIXXXI/L corepressor motif within this domain interferred with the interaction. CONCLUSION: LBD domain on the AR can interact with ID2 motif on the SMRT.

[Expression and transcription of inducible nitric oxide synthase in the liver ischemic preconditioning in rats].

OBJECTIVE: To investigate the changes in transcription and expression of inducible nitric oxide synthase (NOS2) in the liver ischemic preconditioning (IP), and to determine the role of nitric oxide (NO) synthetic pathway in the liver IP in rats. METHODS: We randomly divided 131 Sprague Dawley rats into 3 groups: ischemia/reperfusion (I/R) group (n=52), IP group (n=41), and sham operation (S) group (n=38). Plasm NO concentration and the transcription and expression of NOS2 were detected 2 hours, 24 hours, and 1 week after the operation. RESULTS: (1) In the IP group, the NO concentrations at the 2nd hour, the 24th hour, and 1 week were significantly higher than those in the S group (P < 0.05, P < 0.01, P < 0.01, respectively) and the NO concentrations at the 2nd hour and the 24th hour were obviously higher than those in I/R group (all P < 0.01). In the I/R group, the NO concentration at the 2nd hour was significantly lower than that in the S group (P < 0.05); there was no significant difference between the I/R group and the S group 24 hours after the operation (P > 0.05), and the NO concentration 1 week after the operation was obviously higher than that in the S group (P < 0.05). (2) In the IP group, the transcription of NOS2 2 and 24 hours after the operation were significantly increased compared with that in the I/R group (all P < 0.05) , but after 1 week, the transcription was not statistically different between the IP group and the I/R group (P > 0.05). (3) In the IP group, the expressions of NOS2 after 2 and 24 hours were obviously higher than those in the I/R group (P < 0.05) and the S group (P < 0.05), but the expression between the IR group and the S group was not significantly different (P > 0.05); after 1 week, the expressions of NOS2 in IP group and I/R group were weakly positive (P > 0.05) , and those in S group were negative (P > 0.05). Conclusion The transcription and the expression of liver NOS2 increase after the liver received ischemic preconditioning in rats. That the peak phases of transcription and expression of NOS2 are ahead of time may be related to the early protective effect of the liver IP.

[Surgical management of serious hepatic injuries].

OBJECTIVE: To explore an effective method of treating serious hepatic injuries. METHODS: A retrospective analysis was conducted on 92 consecutive cases of serious hepatic injuries during recent 21 years. RESULTS: Eighty-four cases were treated with operation, and 8 cases with nonoperation management (NOM). Of these patients, 77 (83.5%) were healed, and 15 (16.5%) died. There were complications in 30 patients (31.5%). Hospital stay was 22.3 days. CONCLUSION: Ultrasonography is a valuable diagnostic measure for hepatic injuries. When hemodynamic was stable, CT scanning was especially necessary for patients with complex injuries. Hemostasis is a key measure during operation. Debridement of nonviable hepatic parenchyma is effective management for the decrease of operative complications. If hypotension cannot be corrected actively, clamping of the upper abdominal aorta is an effective measure for patients with hepatic injuries. Serious hepatic injuries can be treated with NOM selectively.