BCAR4 facilitates trastuzumab resistance and EMT in breast cancer via sponging miR-665 and interacting with YAP1.

Breast cancer antiestrogen resistance 4 (BCAR4) has been suggested that can modulate cell behavior, resulting in tumorigenesis and chemoresistance. However, the underlying mechanisms of BCAR4 in trastuzumab resistance (TR) is still elusive. Here, we explored the function and the underlying mechanism of BCAR4 involving in TR. We found that BCAR4 is significantly upregulated in trastuzumab-resistant BC cells. Knockdown of BCAR4 could sensitize the BC cells to trastuzumab and suppress epithelial-mesenchymal transition (EMT). Mechanically, BCAR4 promotes yes-associated protein 1 (YAP1) expression by competitively sponging miR-665, to activated TGF-ß signaling. Reciprocally, YAP1 could occupy the BCAR4 promoter to enhance its transcription, suggesting that there exists a positive feedback regulation between YAP1 and BCAR4. Targeting the BCAR4/miR-665/YAP1 axis may provide a novel insight of therapeutic approaches for TR in BC.

Schwann cell-seeded scaffold with longitudinally oriented micro-channels for reconstruction of sciatic nerve in rats.

To provide a more permissive environment for axonal regeneration, Schwann cells (SCs) were introduced into a collagen-chitosan scaffold with longitudinally oriented micro-channels (L-CCH). The SC-seeded scaffold was then used for reconstruction of a 15-mm-long sciatic nerve defect in rats. The axonal regeneration and functional recovery were examined by a combination of walking track analysis, electrophysiological assessment, Fluoro-Gold retrograde tracing, as well as morphometric analyses to both regenerated axons and target muscles. The findings showed that SCs adhered and migrated into the L-CCH scaffold and displayed a longitudinal arrangement in vitro. Axonal regeneration as well as functional recovery was in the similar range between SCs-seeded scaffold and autograft groups, which were superior to those in L-CCH scaffold alone group. These indicate that the SCs-seeded L-CCH scaffold, which resembles the microstructure as well as the permissive environment of native peripheral nerves, holds great promise in nerve regeneration therapies.

Genetic Analysis of a Family with Multiple Incidences of Prostate Cancer.

A family with multiple members diagnosed with prostate cancer was identified, and genetic variants were analyzed. Three brothers were diagnosed with prostate cancer. Germline variants in BRCA1, BRCA2, TINF2, and CD19 were found through next-generation DNA sequencing using a hereditary cancer panel. The BRCA1 G275D variant was present in patients, but absent in the healthy member. An ELAC2 variant was found in 1 patient. Several mutations were predicted to be deleterious by a set of computation programs. Multiple gene mutations might contribute to the overall predisposition to prostate cancer in the family. Even in cases with potentially deleterious variants in BRCA1 or BRCA2, there could be diverse clinical manifestations.

Significance of preoperative calculation of uterine weight as an indicator for preserving the uterus in pelvic reconstructive surgery.

Recently, increasing evidence has shown that uterus preservation is beneficial for pelvic organ prolapse (POP) patients, both physiologically and psychologically. However, the preoperative indicators for uterus preservation have rarely been examined. The current study was designed to determine the relationship between the preoperative evaluated uterus weight and the operation selection (preserving the uterus or not) in pelvic reconstructive surgery (PRS) using vaginal meshes. First, in a series of 96 patients undergoing hysterectomy, the uterine weight was calculated by preoperative ultrasound measurements, and was then compared with the postoperative actual weight of the uterus. Subsequently, in a series of 65 patients undergone PRS using vaginal meshes and preserving the uterus, the uterine weight was calculated by preoperative ultrasound measurements. Lastly, in a series of 43 patients with a uterine weight > 56.12 g who had undergone PRS using vaginal meshes, the operation success rate in patients with a preserved uterus was compared to patients for whom the uterus was not preserved. The results showed that uterus weight can be evaluated by ultrasound and used as a preoperative indicator for whether the uterus should be preserved or not in PRS when using vaginal meshes. It was indicated that preoperative evaluation of uterine weight is beneficial for surgical planning and guidance.

Hydrogen-rich saline promotes motor functional recovery following peripheral nerve autografting in rats.

Despite the application of nerve grafts and considerable microsurgical innovations, the functional recovery across a long peripheral nerve gap is generally partial and unsatisfactory. Thus, additional strategies are required to improve nerve regeneration across long nerve gaps. Hydrogen possesses antioxidant and anti-apoptotic properties, which could be neuroprotective in the treatment of peripheral nerve injury; however, such a possibility has not been experimentally tested in vivo. The aim of the present study was to investigate the effectiveness of hydrogen-rich saline in promoting nerve regeneration after 10-mm sciatic nerve autografting in rats. The rats were randomly divided into two groups and intraperitoneally administered a daily regimen of 5 ml/kg hydrogen-rich or normal saline. Axonal regeneration and functional recovery were assessed through a combination of behavioral analyses, electrophysiological evaluations, Fluoro-Gold™ retrograde tracings and histomorphological observations. The data showed that rats receiving hydrogen-rich saline achieved better axonal regeneration and functional recovery than those receiving normal saline. These findings indicated that hydrogen-rich saline promotes nerve regeneration across long gaps, suggesting that hydrogen-rich saline could be used as a neuroprotective agent for peripheral nerve injury therapy.

Triptolide improves nerve regeneration and functional recovery following crush injury to rat sciatic nerve.

Recently, accumulating data have demonstrated that triptolide exhibits neurotrophic and neuroprotective properties. However, the role of triptolide in repair and regeneration of peripheral nerve injury (PNI) has rarely been performed. The current study was designed to observe the possible beneficial effect of triptolide on promoting peripheral nerve regeneration in rats. Rats with sciatic nerve crush injury were administered daily with triptolide for 7 days. Axonal regeneration was evaluated by morphometric analysis and Fluoro-gold retrograde tracing. Motor functional recovery was evaluated by walking track analysis, electrophysiological assessment and histological appearance of target muscles. Levels of pro-inflammatory cytokines within injured nerves were also determined. The results demonstrated that triptolide was capable of promoting peripheral nerve regeneration. Additionally, triptolide significantly decreased the levels of pro-inflammatory cytokines within injured nerves. These findings indicate the possibility of developing triptolide as a therapeutic agent for PNI. The neuroprotective effects of triptolide might be associated with its anti-inflammatory properties.

Salidroside promotes peripheral nerve regeneration following crush injury to the sciatic nerve in rats.

Salidroside (SDS), a phenylpropanoid glycoside isolated from Rhodiola rosea L., has been reported to be neuroprotective in vitro, which raises the possibility of using SDS as a neuroprotective agent after nerve injuries. In the present study, the possibly beneficial effect of SDS on promoting nerve regeneration after sciatic nerve crush injury in rats was investigated. Rats with sciatic nerve crush injury were administered intraperitoneally daily with 5 or 10 mg/kg body weight of SDS for 4 weeks. Rats that received mecobalamin or saline were considered as a positive or a negative control, respectively. Morphometric analysis of regenerated nerves and Fluoro-Gold retrograde tracing was used to evaluate axonal regeneration, whereas walking track analysis, electrophysiological assessment, and histological appearance of target muscles were carried out to evaluate the recovery of motor function. The results showed that SDS achieved functionally successful nerve regeneration in the rat sciatic nerve crush injury model, indicating that SDS holds potential as a neuroprotective agent for peripheral nerve therapies.

Prognostic significance of APE1 cytoplasmic localization in human epithelial ovarian cancer.

Cytoplasmic localization of apurinic/apyrimidinic endonuclease 1 (APE1) correlates with different tumorigenic processes and poor prognosis in several cancer types. However, rare investigation into the prognosis value of cytoplasmic localization of APE1 was provided in ovarian cancer. The present study examined for the first time the cytoplasmic localization of APE1 in epithelial ovarian cancer (EOC) by immunohistochemistry. The relationship between cytoplasmic localization of APE1 and clinicopathological parameters, as well as the correlation between cytoplasmic localization of APE1 and prognosis, was investigated. We found that cytoplasmic positivity was significantly higher in EOCs with low tumor differentiation (P = 0.002) and was significantly higher in advanced Federation International of Gynecology and Obstetrics (FIGO) stage (III + IV) patients compared to that in early FIGO stage (I + II) patients (40.7% vs. 11.8%; P = 0.002). No significant difference was observed in APE1 pattern referring to age, tumor size, family history, histological type, ascites, and lymphatic metastasis (P > 0.05). In addition, a lower survival rate was found in patients with cytoplasmic positive localization of APE1 compared to that in patients with cytoplasmic negative localization (P < 0.05). All these findings suggest that cytoplasmic localization of APE1 is associated with tumor progression and might be a valuable prognostic marker for EOC.

Omentum-wrapped scaffold with longitudinally oriented micro-channels promotes axonal regeneration and motor functional recovery in rats.

BACKGROUND: Tissue-engineered nerve scaffolds hold great potential in bridging large peripheral nerve defects. However, insufficient vascularization of nerve scaffolds limited neural tissues survival and regeneration, which hampered the successful implantation and clinical application of nerve scaffolds. The omentum possesses a high vascularization capacity and enhances regeneration and maturation of tissues and constructs to which it is applied. However, combined application of nerve scaffolds and omentum on axonal regeneration and functional recovery in the treatment of large peripheral nerve defects has rarely been investigated thus far. METHODS: In the present study, an omentum-wrapped collagen-chitosan scaffold was used to bridge a 15-mm-long sciatic nerve defect in rats. Rats that received nerve autografts or scaffolds alone were served as positive control or negative control, respectively. The axonal regeneration and functional recovery were examined by a combination of walking track analysis, electrophysiological assessment, Fluoro-Gold (FG) retrograde tracing, as well as morphometric analyses to both regenerated nerves and target muscles. FINDINGS: The results demonstrated that axonal regeneration and functional recovery were in the similar range between the omentum-wrapping group and the autograft group, which were significantly better than those in the scaffold alone group. Further investigation showed that the protein levels of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were significantly higher in the omentum-wrapping group than those in the scaffold alone group in the early weeks after surgery. CONCLUSION: These findings indicate that the omentum-wrapped scaffold is capable of enhancing axonal regeneration and functional recovery, which might be served as a potent alternative to nerve autografts. The beneficial effect of omentum-wrapping on nerve regeneration might be related with the proteins produced by omentum.