PARVB deficiency alleviates cisplatin-induced tubular injury by inhibiting TAK1 signaling.

Cisplatin-induced renal tubular injury largely restricts the wide-spread usage of cisplatin in the treatment of malignancies. Identifying the key signaling pathways that regulate cisplatin-induced renal tubular injury is thus clinically important. PARVB, a focal adhesion protein, plays a crucial role in tumorigenesis. However, the function of PARVB in kidney disease is largely unknown. To investigate whether and how PARVB contributes to cisplatin-induced renal tubular injury, a mouse model (PARVB cKO) was generated in which PARVB gene was specifically deleted from proximal tubular epithelial cells using the Cre-LoxP system. In this study, we found depletion of PARVB in proximal tubular epithelial cells significantly attenuates cisplatin-induced renal tubular injury, including tubular cell death and inflammation. Mechanistically, PARVB associates with transforming growth factor-ß-activated kinase 1 (TAK1), a central regulator of cell survival and inflammation that is critically involved in mediating cisplatin-induced renal tubular injury. Depletion of PARVB promotes cisplatin-induced TAK1 degradation, inhibits TAK1 downstream signaling, and ultimately alleviates cisplatin-induced tubular cell damage. Restoration of PARVB or TAK1 in PARVB-deficient cells aggravates cisplatin-induced tubular cell injury. Finally, we demonstrated that PARVB regulates TAK1 protein expression through an E3 ligase ITCH-dependent pathway. PARVB prevents ITCH association with TAK1 to block its ubiquitination. Our study reveals that PARVB deficiency protects against cisplatin-induced tubular injury through regulation of TAK1 signaling and indicates targeting this pathway may provide a novel therapeutic strategy to alleviate cisplatin-induced kidney damage.

CHILKBP protects against podocyte injury by preserving ZO-1 expression.

Glomerular diseases afflict millions of people and impose an enormous burden on public healthcare costs worldwide. Identification of potential therapeutic targets for preventing glomerular diseases is of considerable clinical importance. CHILKBP is a focal adhesion protein and modulates a wide array of biological functions. However, little is known about the role of CHILKBP in glomerular diseases. To investigate the function of CHILKBP in maintaining the structure and function of podocytes in a physiologic setting, a mouse model (CHILKBP cKO) was generated in which CHILKBP gene was conditionally deleted in podocytes using the Cre-LoxP system. Ablation of CHILKBP in podocytes resulted in massive proteinuria and kidney failure in mice. Histologically, typical podocyte injury including podocyte loss, foot process effacement, and glomerulosclerosis was observed in CHILKBP cKO mice. Mechanistically, we identified ZO-1 as a key junctional protein that interacted with CHILKBP. Loss of CHILKBP in podocytes exhibited a significant reduction of ZO-1 expression, leading to abnormal actin organization, aberrant slit diaphragm protein expression and compromised podocyte filtration capacity. Restoration of CHILKBP or ZO-1 in CHILKBP-deficient podocytes effectively alleviated podocyte injury induced by the loss of CHILKBP in vitro and in vivo. Finally, we showed the glomerular expression of CHILKBP and ZO-1 was decreased in patients with proteinuric kidney diseases. Our findings reveal a novel signaling pathway consisting of CHILKBP and ZO-1 that plays an essential role in maintaining podocyte homeostasis and suggest novel therapeutic approaches to alleviate glomerular diseases.

Spherical crown diffraction model by occlusion utilizing for a curved holographic display.

The information of occlusion culling in the spherical holography has been ignored or discarded for a long time. However, the information of the occlusion could be utilized, which has never been considered before. In this paper, a spherical crown diffraction model for a curved holographic display is proposed by occlusion utilizing. In the proposed spherical crown diffraction model, the method of occlusion utilizing is realized firstly, which is based on an optical-path-select function to remain the desired light information. Based on the method of occlusion utilizing, a spherical crown diffraction model for curve holographic display is proposed by further analyzing the optical propagation geometry relationship. This proposed diffraction model not only retains the advantage of a conventional diffraction model with a large view angle of 360°in the azimuth direction, but also improves the view angle in the latitude direction. Besides, the proposed model by occlusion utilizing has higher optical utilization than that model by occlusion culling. Furthermore, the effectiveness and feasibility of the proposed model are verified by numerical simulations. To our knowledge, it is the first time that a method and an application are proposed to utilize the occlusion.

Fully integrated on-line strategy for highly sensitive proteome profiling of 10-500 mammalian cells.

Recent development in proteomic sample preparation using nanofluidic devices has made single-cell proteome profiling possible. However, these nanofluidic devices require special expertise and costly nanopipetting instruments. They are also specially designed for single cells, are not well-suited for profiling rare samples consisting of a few hundred mammalian cells, arguably a more common need that remains a great challenge. Herein, we developed an easy-to-use and scalable device for processing low-input samples, which combined the merits of previously reported rare cell proteomic reactor (RCPR) and mixed-mode simple and integrated spintip-based proteomics technology, as an alternative to nanofluidic devices. All steps of proteomics sample preparation, including protein preconcentration, impurity removal, reduction, alkylation, digestion, and desalting, were fully integrated in our workflow, and the device can be directly connected to online nanoLC-MS system after processing the rare samples. Using the developed 3-frit mixed-mode RCPR, we identified on average 946 ± 158, 2 998 ± 106, and 3 934 ± 85 protein groups in data-dependent acquisition (DDA) mode from 10, 100, and 500 fluorescence-activated cell sorting (FACS)-sorted 293T cells, respectively. As an illustrative application of this technology, we performed a label-free proteome comparison of 500 FACS-sorted mouse cochlear hair cells of two different ages. On average, 2 595 ± 230 and 2 042 ± 120 protein groups were quantified in the juvenile and the adult samples in DDA mode, respectively, achieving dynamic ranges of over 6 orders of magnitude for both.

Migfilin promotes autophagic flux through direct interaction with SNAP29 and Vamp8.

Autophagy plays a crucial role in cancer cell survival by facilitating the elimination of detrimental cellular components and the recycling of nutrients. Understanding the molecular regulation of autophagy is critical for developing interventional approaches for cancer therapy. In this study, we report that migfilin, a focal adhesion protein, plays a novel role in promoting autophagy by increasing autophagosome-lysosome fusion. We found that migfilin is associated with SNAP29 and Vamp8, thereby facilitating Stx17-SNAP29-Vamp8 SNARE complex assembly. Depletion of migfilin disrupted the formation of the SNAP29-mediated SNARE complex, which consequently blocked the autophagosome-lysosome fusion, ultimately suppressing cancer cell growth. Restoration of the SNARE complex formation rescued migfilin-deficiency-induced autophagic flux defects. Finally, we found depletion of migfilin inhibited cancer cell proliferation. SNARE complex reassembly successfully reversed migfilin-deficiency-induced inhibition of cancer cell growth. Taken together, our study uncovers a new function of migfilin as an autophagy-regulatory protein and suggests that targeting the migfilin-SNARE assembly could provide a promising therapeutic approach to alleviate cancer progression.

Kindlin-2 enhances c-Myc translation through association with DDX3X to promote pancreatic ductal adenocarcinoma progression.

Rationale: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid tumor, with extremely low survival rates. Identifying key signaling pathways driving PDAC progression is crucial for the development of therapies to improve patient response rates. Kindlin-2, a multi-functional protein, is involved in numerous biological processes including cell proliferation, apoptosis and migration. However, little is known about the functions of Kindlin-2 in pancreatic cancer progression in vivo. Methods: In this study, we employ an in vivo PDAC mouse model to directly investigate the role of Kindlin-2 in PDAC progression. Then, we utilized RNA-sequencing, the molecular and cellular assays to determine the molecular mechanisms by which Kindlin-2 promotes PDAC progression. Results: We show that loss of Kindlin-2 markedly inhibits KrasG12D-driven pancreatic cancer progression in vivo as well as in vitro. Furthermore, we provide new mechanistic insight into how Kindlin-2 functions in this process, A fraction of Kindlin-2 was localized to the endoplasmic reticulum and associated with the RNA helicase DDX3X, a key regulator of mRNA translation. Loss of Kindlin-2 blocked DDX3X from binding to the 5'-untranslated region of c-Myc and inhibited DDX3X-mediated c-Myc translation, leading to reduced c-Myc-mediated glucose metabolism and tumor growth. Importantly, restoration of the expression of either the full-length Kindlin-2 or c-Myc, but not that of a DDX3X-binding-defective mutant of Kindlin-2, in Kindlin-2 deficient PDAC cells, reversed the inhibition of glycolysis and pancreatic cancer progression induced by the loss of Kindlin-2. Conclusion: Our studies reveal a novel Kindlin-2-DDX3X-c-Myc signaling axis in PDAC progression and suggest that inhibition of this signaling axis may provide a promising therapeutic approach to alleviate PDAC progression.

Changes in female sexual function following anterior with and without posterior vaginal mesh surgery for the treatment of pelvic organ prolapse.

INTRODUCTION: Comparison of female sexual function following anterior and total transvaginal mesh (TVM) surgery has never been reported. AIM: To compare the sexual function after anterior and total TVM repair for the treatment of pelvic organ prolapse (POP). MAIN OUTCOME MEASURES: The short forms of Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7), and the Female Sexual Function Index (FSFI). METHODS: One hundred and sixty-five women with symptomatic POP stages II to IV defined by the POP quantification (POP-Q) staging system underwent TVM procedures at our hospitals. Seventy women were included because they were sexually active and had complete follow-up. All subjects were divided into the anterior group (anterior TVM; N=39) and total group (anterior and posterior TVM; N=31). Preoperative and postoperative assessments included pelvic examination using the POP-Q system, urodynamic study, and a personal interview to evaluate urinary and sexual symptoms with the short forms of UDI-6 and IIQ-7, and the FSFI. RESULTS: There was no difference between the two groups as for age, parity, diabetes, hypertension, concomitant procedures, and success rates for TVM and mid-urethral sling in this study (P>0.05). Regarding the POP-Q analysis, there was a significant improvement at points Aa, Ba, C, Ap, and Bp (P<0.05) in both groups except for total vaginal length (P>0.05). The preoperative scores of UDI-6 and IIQ-7 were significantly higher in the total group (P<0.01), and the UDI-6 and IIQ-7 scores showed significant decreases in both groups postoperatively (P<0.01). After TVM surgery, the score of the dyspareunia domain worsened significantly in both groups (P<0.05), and the deteriorated lubrication domain was noted only in the total group (P=0.042). CONCLUSIONS: TVM procedure creates an effective anatomical restoration of POP, but individual domains of FSFI may worsen. Compared with the anterior group, women of the total group had worse quality of life in term of urinary symptoms preoperatively, and experienced a greater sexual impairment on lubrication following surgery.

Epidemiology of group B Streptococcus ST-17 clone in pregnant women of South Taiwan.

OBJECTIVES: We aimed to utilize a simple molecular assay to simultaneously detect both group B Streptococcus (GBS) and virulent ST-17 rectovaginal colonization. We also attempted to estimate the prevalence of maternal GBS and ST-17 carriers and to evaluate their seasonal association. SUBJECTS AND METHODS: We used an optimized multiplex PCR method employing scp-B and ST-17 primers to analyze DNA extracted from rectovaginal swabs of 3,064 cases collected over 3 years. The incidence trends, seasonal variations, and temperature preference were analyzed. RESULTS: The overall prevalence of maternal colonization for GBS and ST-17 clone were 13.25 and 2.48%, respectively. The ST-17 to GBS ratio was 18.72%. The occurrence of ST-17 colonization was significantly associated with seasonal variations with a preference for lower temperatures. CONCLUSIONS: We developed a novel multiplex PCR method suitable for the simultaneous detection of GBS and ST-17 clone. The phenomenon of lower temperature preference for ST-17 clone necessitates further investigation. The epidemiological data for GBS and ST-17 incidence are especially important to establish a public policy for universal GBS screening in the future.

Effects of Elevated CO2 on the Fitness of Three Successive Generations of Lipaphis erysimi.

To assess the effect of elevated CO2 on the development, fecundity, and population dynamic parameters of L. erysimi, the age-stage, two-sex life table was used to predict the individual fitness and population parameters of three successive generations of L. erysimi in this study. The results show that a significantly longer total pre-adult stage before oviposition (TPOP) was observed in the third generation compared with the first generation of L. erysimi under the 800 µL/L CO2 treatment. The fecundity is significantly lower in the 800 µL/L CO2 treatment than that in the 400 µL/L CO2 treatment in the third generation of L. erysimi, which indicates that elevated CO2 had a negative effect on the individual fitness parameters of L. erysimi. Additionally, the life expectancy (exj) is significantly lower under the 800 µL/L CO2 treatment than that under the 400 µL/L CO2 treatment in the three successive generations. A significantly higher intrinsic rate of increase (r) and finite rate of increase (λ) were found in the second generation compared with those in the first and third generations of L. erysimi under the 800 µL/L CO2 treatment. Moreover, significantly lower r and λ were observed under the 800 µL/L CO2 treatment compared with those under the 400 µL/L and 600 µL/L CO2 treatments in the first generation of L. erysimi, which indicates that elevated CO2 has a short-term effect on the population parameters (r and λ) of L. erysimi. Our experiment can provide the data for the comprehensive prevention and control of L. erysimi in the future with increasing CO2 levels.

Kindlin-2 promotes Src-mediated tyrosine phosphorylation of androgen receptor and contributes to breast cancer progression.

Androgen receptor (AR) signaling plays important roles in breast cancer progression. We show here that Kindlin-2, a focal adhesion protein, is critically involved in the promotion of AR signaling and breast cancer progression. Kindlin-2 physically associates with AR and Src through its two neighboring domains, namely F1 and F0 domains, resulting in formation of a Kindlin-2-AR-Src supramolecular complex and consequently facilitating Src-mediated AR Tyr-534 phosphorylation and signaling. Depletion of Kindlin-2 was sufficient to suppress Src-mediated AR Tyr-534 phosphorylation and signaling, resulting in diminished breast cancer cell proliferation and migration. Re-expression of wild-type Kindlin-2, but not AR-binding-defective or Src-binding-defective mutant forms of Kindlin-2, in Kindlin-2-deficient cells restored AR Tyr-534 phosphorylation, signaling, breast cancer cell proliferation and migration. Furthermore, re-introduction of phosphor-mimic mutant AR-Y534D, but not wild-type AR reversed Kindlin-2 deficiency-induced inhibition of AR signaling and breast cancer progression. Finally, using a genetic knockout strategy, we show that ablation of Kindlin-2 from mammary tumors in mouse significantly reduced AR Tyr-534 phosphorylation, breast tumor progression and metastasis in vivo. Our results suggest a critical role of Kindlin-2 in promoting breast cancer progression and shed light on the molecular mechanism through which it functions in this process.

Comparison of the changes in sexual function of premenopausal and postmenopausal women following transvaginal mesh surgery.

INTRODUCTION: The effect of transvaginal mesh (TVM) surgery on sexual function between premenopausal and postmenopausal women remains controversial. AIM: To compare the changes in sexual function of premenopausal and postmenopausal women following TVM repair. METHODS: One hundred and fifty-two consecutive women with symptomatic pelvic organ prolapse (POP) stages II to IV were referred for TVM procedures at our hospitals. Sixty-eight women were included because they were sexually active and had complete follow-up. All subjects were divided into the premenopausal (N = 36) and postmenopausal (N = 32) groups. Preoperative and postoperative assessments included pelvic examination using the POP quantification (POP-Q) system and a personal interview with the Female Sexual Function Index (FSFI), Urogenital Distress Inventory (UDI-6), and Incontinence Impact Questionnaire (IIQ-7). MAIN OUTCOME MEASURES: The FSFI, UDI-6, and IIQ-7 questionnaires. RESULTS: The mean age, rates of hypertension, and previous hysterectomy were significantly higher in the postmenopausal group (P < 0.05) compared with the premenopausal group. As for the POP-Q analysis, there was a significant improvement at points Aa, Ba, C, Ap, and Bp (P < 0.001) in both groups except for total vaginal length (P > 0.05). Similarly, the UDI-6 and IIQ-7 scores significantly decreased postoperatively (P < 0.01). After POP surgery, the score of the dyspareunia domain decreased significantly in the premenopausal group (P < 0.01) but was not the case for the postmenopausal group (P > 0.05). There were no significant changes in other domains and total scores in both groups (P > 0.05). However, higher rates of worsening dyspareunia and total scores were noted in the premenopausal group (P = 0.03 vs. 0.033). CONCLUSION: TVM procedure is effective for the anatomical restoration of POP. However, individual domain of FSFI such as dyspareunia may worsen in the premenopausal women. Additionally, our results revealed that over one third of premenopausal women could have a worsening sexuality domain postoperatively, with significantly higher rate of deteriorated dyspareunia and total FSFI scores than postmenopausal women.

Modulation of tumorigenesis and oestrogen receptor-alpha expression by cell culture conditions in a stem cell-derived breast epithelial cell line.

BACKGROUND INFORMATION: The common phenotypes of cancer and stem cells suggest that cancers arise from stem cells. Oestrogen is one of the few most important determinants of breast cancer, as shown by several lines of convincing evidence. We have previously reported a human breast epithelial cell type (Type 1 HBEC) with stem cell characteristics and ER alpha (oestrogen receptor alpha) expression. A tumorigenic cell line, M13SV1R2, was developed from this cell type after SV40 (simian virus 40) large T-antigen transfection and X-ray irradiation. The cell line, however, was not responsive to oestrogen for cell growth or tumour development. In the present study, we tested the hypothesis that deprivation of growth factors and hormones may change the tumorigenicity and oestrogen response of this cell line. RESULTS: The M13SV1R2 cells lost their tumorigenicity after culturing in a growth factor/hormone-deprived medium for >10 passages (referred to as R2d cells) concomitant with the expression of two tumour suppressor genes, namely those coding for maspin and alpha 6 integrin. However, these cells acquired oestrogen responsiveness in cell growth and tumour development. By immunocytochemistry, Western blotting and flow cytometry analysis, oestrogen treatment of R2d cells was found to induce many important effects related to breast carcinogenesis, namely: (i) the emergence of a subpopulation of cells expressing CD44+/high/CD24-/low breast tumour stem cell markers; (ii) the induction of EMT (epithelial-to-mesenchymal transition); (iii) the acquisition of metastatic ability; and (iv) the expression of COX-2 (cyclo-oxygenase-2) through a CD44-mediated mechanism. CONCLUSION: An oestrogen-responsive cell line with ER alpha and CD44+/CD24-/low expression can be derived from breast epithelial stem cells. The tumorigenicity and oestrogen response of these cells could depend on the cell culture conditions. The findings of this study have implications in regard to the origins of (1) ER alpha-positive breast cancers, (2) CD44+/CD24-/low breast tumour stem cells and (3) the metastatic ability of breast cancer.

Predictors of improved overactive bladder symptoms after transvaginal mesh repair for the treatment of pelvic organ prolapse: predictors of improved OAB after POP repair.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to identify the predictors of improved overactive bladder (OAB) symptoms after transvaginal mesh repair. METHODS: Eighty women with pelvic organ prolapse (POP) stage II to IV reporting OAB symptoms were scheduled for transvaginal mesh procedures. Preoperative and postoperative assessments included a bladder diary, urodynamics, and a personal interview about urinary symptoms. RESULTS: Sixty-three (78.8%) women experienced improvement of OAB symptoms (Improvement group), and 17 (21.2%) women remained unchanged or worsened (Persistence group) postoperatively. A univariate analysis of patients' characteristics showed no difference between two groups regarding parity, diabetes, hypertension, prolapse status, preoperative urodynamic parameters, and urinary symptoms (P > 0.05). However, the age (P = 0.042) and preoperative detrusor overactivity (DO) (P = 0.03) were two significant predictors of postoperative OAB improvement. CONCLUSIONS: Women with POP may experience improvement of their OAB symptoms after transvaginal mesh repair. Both age and DO were two predictors in our univariate analysis, and the latter was the only significant predictor of symptom relief after adjusting age factor.

Comparison of clinical outcome and urodynamic findings using "Perigee and/or Apogee" versus "Prolift anterior and/or posterior" system devices for the treatment of pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: This study aims to compare clinical outcome using the Perigee/Apogee® vs. Prolift® devices for the treatment of pelvic organ prolapse (POP). METHODS: One hundred and eight women with POP stages II to IV were scheduled for either Perigee/Apogee® (Perigee group; n = 60) or Prolift® device (Prolift group; n = 48). Preoperative and postoperative assessments included pelvic examination, urodynamic study, and a personal interview about urinary and sexual symptoms. RESULTS: Despite different follow-up period (20 months for the Perigee group vs. 12 months for Prolift group; P < 0.01), the success rates for two groups were comparable (P > 0.05). Postoperative points Aa and Ba of Prolift group were significantly higher than the other group (P < 0.01). The prevalences of detrusor overactivity and urinary symptoms decreased significantly postoperatively in both groups (P < 0.05). Comparisons of all operative complications revealed no significant differences between the two groups (P > 0.05). CONCLUSIONS: Perigee/Apogee® and Prolift® devices for POP repair have comparable success rates, mesh-related morbidities, and similar impacts on functional outcome.

Magnetic Resonance Imaging Segmentation on the Basis of Boundary Tracking Algorithm in Lung Cancer Surgery.

This work was to study the guiding value of magnetic resonance imaging (MRI) based on the target region boundary tracking algorithm in lung cancer surgery. In this study, the traditional boundary tracking algorithm was optimized, and the target neighborhood point boundary tracking method was proposed. The iterative method was used to binarize the lung MRI image, which was applied to the MRI images of 50 lung cancer patients in hospital. The patients were divided into two groups as the progression-free survival (PFS) and overall survival (OS) of surgical treatment group (experimental group, n = 25) and nonsurgical treatment group (control group, n = 25). The experimental group received surgical resection, while the control group received systemic chemotherapy. The results showed that the traditional boundary tracking algorithm needed to manually rejudge whether the concave and convex parts of the image were missing. The target boundary tracking algorithm can effectively avoid the leakage of concave and convex parts and accurately locate the target image contour, fast operation, without manual intervention. The PFS time of the experimental group (325 days) was significantly higher than that of the control group (186 days) (P < 0.05). The OS time of the experimental group (697 days) was significantly higher than that of the control group (428 days) (P < 0.05). Fisher exact probability method was used to test the total survival time of patients in the two groups, and the tumor classification and treatment group had significant influence on the OS time (P < 0.05). The target boundary tracking algorithm in this study can effectively locate the contour of the target image, and the operation speed was fast. Surgical resection of lung cancer can improve the PFS and OS of patients.

Overexpressed LINC00467 promotes the viability and proliferation yet inhibits apoptosis of gastric cancer cells via raising ITGB3 level.

Long non-coding RNA (lncRNA) LINC00467 plays a proto-oncogenic role in non-small cell lung cancer. However, its effect and modulatory mechanism in gastric cancer (GC) are unknown. Thereby, we elucidated the mechanism of LINC00467 in GC. LINC00467 level in GC tissues was assessed by bioinformatic analysis, and clinicopathological parameters from GC patients were collected. The levels of LINC00467, integrin subunit beta 3 (ITGB3), proliferating cell nuclear antigen (PCNA), cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase 1 (PARP1) in tissue samples or treated GC cells were assessed by quantitative real-time polymerase chain reaction (qRT-PCR), fluorescence in situ hybridization (FISH), or Western blot. The viability, proliferation and apoptosis of GC cells were detected by methyl thiazolyl tetrazolium assay, colony formation assay, and flow cytometry. Levels of LINC00467 and ITGB3 were up-regulated in GC, and highly expressed LINC00467 was positively associated with tumor size, differentiation, N stage, and T stage in GC patients. LINC00467 was enriched in cytoplasm of GC cells, and overexpressed LINC00467 promoted the viability and proliferation as well as levels of ITGB3 and PCNA, while suppressing the apoptosis and levels of cleaved caspase-3 and cleaved PARP1 in GC cells. Besides, the effects of shLINC00467 on inhibiting cell viability, proliferation of GC cells and PCNA level and promoting apoptosis as well as levels of cleaved caspase-3 and cleaved PARP1 were all partially reversed by overexpressed ITGB3. Overexpressed LINC00467 enhanced the viability and proliferation but inhibited apoptosis of GC cells via increasing ITGB3 level.

The impact of simulated birth trauma and ovariectomy on the gene expression of detrusor muscarinic receptors in female rats.

INTRODUCTION AND HYPOTHESIS: This study aims to investigate the effects of simulated birth trauma and ovariectomy on detrusor muscarinic receptors (M2 and M3), urethral neuronal nitric oxide synthase (nNOS), and estrogen receptor beta (ER beta). METHODS: Forty primiparous rats were equally divided into five groups: group A--delivery, group B--delivery plus ovariectomy, group C--delivery plus balloon dilatation for 2 h, group D--delivery plus balloon dilatation for 4 h, and group E--delivery plus balloon dilatation for 2 h plus ovariectomy. The gene expression of M2, M3, nNOS, and ER beta were assessed by reverse transcription polymerase chain reaction. RESULTS: Significant decreases in mRNA expression of M2 receptors and nNOS (P < 0.05), and a significant increase in M3 mRNA expression (P < 0.05) were observed in groups D and E when compared with group A. CONCLUSIONS: Ovariectomy following birth trauma may synergistically impact the function of urinary tract, this being possibly related to the modification of the gene expression of muscarinic receptors.

PINCH-1 interacts with myoferlin to promote breast cancer progression and metastasis.

PINCH-1 is a cytoplasmic component of the cell-extracellular matrix (ECM) adhesion machine that is frequently overexpressed in cancer. The functions and mechanism of PINCH-1 in cancer, however, remain to be determined. Here, we show that PINCH-1 interacts with myoferlin, a transmembrane protein that is critical for cancer progression. High expression of both PINCH-1 and myoferlin correlates with poor clinical outcome in human breast cancer patients. Ablation of PINCH-1 from breast cancer cells diminished myoferlin level and suppressed breast cancer cell proliferation, migration, and endothelial cell tube formation in vitro and breast tumor growth, angiogenesis and metastasis in vivo. Mechanistically, PINCH-1 controls myoferlin level through its interaction with myoferlin and regulation of its ubiquitination and proteasome-dependent degradation. Functionally, re-expression of PINCH-1, but not that of a myoferlin-binding defectiveΔLIM2 mutant, effectively reversed the inhibition of myoferlin expression and breast cancer progression induced by loss of PINCH-1. Finally, restoration of myoferlin expression was sufficient to reverse PINCH-1-deficiency induced inhibition on breast cancer progression. These results reveal a PINCH-1-myoferlin signaling axis that is critical for breast cancer progression and suggest a new strategy for therapeutic control of breast cancer.

Comparison of tension-free vaginal tape and transobturator tape procedure for the treatment of stress urinary incontinence.

PURPOSE OF REVIEW: The aim of this review was to assess the recent evidence on the effectiveness and complications of tension-free vaginal tape (TVT) and transobturator tape (TOT) procedures for female stress urinary incontinence between January 2008 and March 2009. RECENT FINDINGS: A meta-analysis of recent studies revealed that the short-term objective cure rate was borderline worse in the TOT group compared with TVT [odds ratio (OR) 0.62; 95% confidence interval (CI) 0.37-1.00; P = 0.05]. Bladder perforation (OR 12.23; 95% CI 2.86-52.34) was significantly more common, whereas groin/thigh pain was significantly less in the TVT group (OR 0.32; 95% CI 0.11-0.92; P = 0.022). Postoperative urinary retention was slightly more in women undergoing TVT than those undergoing TOT (OR 1.6; 95% CI 0.90-3.12; P = 0.06). The rates of vaginal erosion (OR 0.34; 95% CI 0.09-1.33), de-novo urgency (OR 1.21; 95% CI 0.52-2.79) and urinary tract infection (OR 0.88; 95% CI 0.56-1.38) were comparable in both procedures. In addition, TVT appeared to be more obstructive than TOT, as evidenced by ultrasonographic and urodynamic findings. Changes in sexual function need further investigation because this issue has not been well studied for either sling procedure. SUMMARY: TOT has the advantages over TVT with shorter operative time and a relatively lower complication rate. For women with intrinsic sphincter deficiency, however, TVT appears to be a better option because it is more obstructive.

[Functional significance of TGF-beta1 signal transduction pathway in oral squamous cell carcinoma].

OBJECTIVE: The aim of this study was to investigate the expression of transforming growth factor-beta1 (TGF-beta1) and its signaling pathway molecules in oral squamous cell carcinoma (OSCC) and analyze the association between these factors and genesis and metastasis of OSCC. METHODS: The express of TGF-beta1, TbetaRI, TbetaRII and Smad4, a pivotal downstream molecule of its signaling, in 10 normal oral mucosa tissues and 108 OSCC was detected by SP immunohistochemistry, and thier correlation with genesis and metastasis of OSCC were assessed. RESULTS: The expressions of TbetaRII and Smad4 were lower in the tumors (34.3%, 38.9%) than those in the normal oral epithelium (80.0%, 100.0%, P < 0.05). The positive expression rates of TGF-beta1 and TbetaRI in the normal oral epithelium and OSCC were not significantly different (P > 0.05). There was an inverse correlation between TGF-beta1, Smad4, TbetaRII, TbetaRI expression and clinical stages (P < 0.01). The expression of TGF-beta1 was related with histological differentiation and tumor localization (P < 0.05). There was a relationship beteween Smad4 expression and histological differentiation and lymph node metastasis (P < 0.05). The expression of TbetaRII in the samples with lymph node metastasis was less than that in the ones without lymph node metastasis (P < 0.01), although there was no association between expression of TbetaRII and lymph node metastasis status. CONCLUSION: There is an important relationship between the abnormal TGF-beta1/Smad4 signal pathway and genesis and development of OSCC, while the low expressed Smad4 and TbetaRII may promote the metastasis of OSCC.