Dual siRNA-Loaded Cell Membrane Functionalized Matrix Facilitates Bone Regeneration with Angiogenesis and Neurogenesis.

Vascularization and innervation play irreplaceable roles in bone regeneration and bone defect repair. However, the reconstruction of blood vessels and neural networks is often neglected in material design. This study aims to design a genetically functionalized matrix (GFM) and enable it to regulate angiogenesis and neurogenesis to accelerate the process of bone defect repair. The dual small interfering RNA (siRNA)-polyvinylimide (PEI) (siRP) complexes that locally knocked down soluble vascular endothelial growth factor receptor 1 (sFlt-1) and p75 neurotrophic factor receptor (p75NTR ) are prepared. The hybrid cell membrane (MM) loaded siRP is synthesized as siRNA@MMs to coat on polylactone (PCL) electrospun fibers for mimicking the natural bone matrix. The results indicates that siRNA@MMs could regulate the expression of vascular-related and neuro-related cytokines secreted by mesenchymal stem cells (MSCs). GFMs promote the expression of osteogenic differentiation through paracrine function in vitro. GFMs attenuates inflammation and promotes osseointegration by regulating the coupling of vascularization and innervation in vivo. This study uses the natural hybrid cell membrane to carry genetic material and assist in the vascularization and innervation function of two siRNA. The results present the significance of neuro-vascularized organoid bone and may provide a promising choice for the design of bone tissue engineering scaffold.

Palbociclib plus endocrine therapy in hormone receptor-positive and HER2 negative metastatic breast cancer: a multicenter real-world study in the northwest of China.

BACKGROUND: Real-world data of Palbociclib are insufficient in China. This study aimed to investigate the treatment pattern and real-world outcomes in hormone receptor positive and human epidermal growth factor 2 receptor negative (HR+/HER2-) metastatic breast cancer (MBC) patients treated with Palbociclib in the northwest of China. METHODS: HR+/HER2- MBC patients who received Palbociclib in 8 centers from July 2017 to September 2019 were retrospectively included in this study. Real-world objective response rate (ORR), progression-free survival (PFS) and safety profiles were analyzed. The survival curves were plotted by the Kaplan-Meier method to analyze PFS, which was verified by the log-rank test. RESULTS: In total, 211 women were eligible for the analysis. A total of 85 patients (40.3%), 78 (37.0%), and 48 (22.7%) received Palbociclib in the first-, second-, third- or later-line setting, respectively. 46 patients achieved partial response and 145 patients experienced stable disease, with an ORR of 21.8% and a disease control rate of 90.5%. Following a median follow-up period of 14.2 months, the median PFS was 12.2 months (95% confidence interval, 10.1-14.3 m), and the median overall survival was not reached. Early Palbociclib initiation, sensitivity or acquired resistance to endocrine therapy, estrogen receptor and progesterone receptor double positivity, less than 3 metastatic sites, without visceral metastasis, bone metastasis only, without prior chemotherapy or endocrine therapy were associated with a prolonged PFS in MBC (All P < 0.05). The most common grade 3 or 4 adverse events (AE) was neutropenia (36.5%), and the most common nonhematologic AE was fatigue (10.9%). No patient experienced AE leading to treatment discontinuation. CONCLUSION: Palbociclib plus endocrine therapy exhibited favorable effectiveness and manageable toxicities in the real-world setting, supporting their use in Chinese patients with HR+/HER2 - MBC.

Suspension state and shear stress enhance breast tumor cells EMT through YAP by microRNA-29b.

Except for biochemical effects, suspension state (Sus) is proved to induce epithelial-mesenchymal transition (EMT) of circulating tumor cells (CTCs) mechanically. However, the difference between the effects of the mechanical microenvironment in capillaries (simplified as shear stress (SS) and Sus) and single Sus on EMT is unclear, nor the underlying mechanism. Here, breast tumor cells (BTCs) were loaded with Sus and SS to mimic the situation of CTCs stimulated by these two kinds of mechanics. It was demonstrated that the EMT of BTCs was enhanced by Sus and SS and the mechanotransductor yes-associated protein (YAP) was partially cytoplasmic stored with microRNA (miR)-29b decreased, which was detected by miR sequencing. Though it couldn't possess a feedback regulation, YAP promoted miR-29b expression and posttranscriptionally regulated BTCs EMT through miR-29b, where transforming growth factor ß involved. Analysis of clinical database showed that high miR-29b expression was beneficial to high survival rate stabilizing its role of tumor suppressor. This study discovers the mechanism that Sus and SS promote BTCs EMT by YAP through miR-29b posttranscriptionally and highlight the potential of YAP and miR-29b in tumor therapy. The combination of suspension state and shear stress promotes transforming growth factor ß involved epithelial-mesenchymal transition by yes-associated protein through microRNA-29b.

A biomechanical view of epigenetic tumor regulation.

The occurrence and development of tumors depend on a complex regulation by not only biochemical cues, but also biomechanical factors in tumor microenvironment. With the development of epigenetic theory, the regulation of biomechanical stimulation on tumor progress genetically is not enough to fully illustrate the mechanism of tumorigenesis. However, biomechanical regulation on tumor progress epigenetically is still in its infancy. Therefore, it is particularly important to integrate the existing relevant researches and develop the potential exploration. This work sorted out the existing researches on the regulation of tumor by biomechanical factors through epigenetic means, which contains summarizing the tumor epigenetic regulatory mode by biomechanical factors, exhibiting the influence of epigenetic regulation under mechanical stimulation, illustrating its existing applications, and prospecting the potential. This review aims to display the relevant knowledge through integrating the existing studies on epigenetic regulation in tumorigenesis under mechanical stimulation so as to provide theoretical basis and new ideas for potential follow-up research and clinical applications. Mechanical factors under physiological conditions stimulate the tumor progress through epigenetic ways, and new strategies are expected to be found with the development of epidrugs and related delivery systems.

Prognostic and clinicopathological value of Slug protein expression in breast cancer: a systematic review and meta-analysis.

BACKGROUND: Many studies have reported the relationship between prognosis and Slug protein expression in breast cancer patients, but the results are discrepant. Therefore, there is a need for meta-analyses with high statistical power to investigate and further explore their relationship. METHODS: We used PubMed, Embase, the Cochrane Library, Scopus, MEDLINE, and the Web of Science to find studies on breast cancer and Slug. Overall survival (OS) and disease-free survival (DFS) were the study's primary endpoints. We pooled hazard ratios (HRs) and odds ratios (ORs) to assess the association between Slug protein expression and prognostic and clinicopathological parameters. This study was performed using STATA version 14.0 for data analysis. (Stata Corporation, TX, USA). RESULTS: We conducted a literature search by searching six online databases. Ultimately, we obtained eight studies including 1458 patients through strict exclusion criteria. The results showed that increased Slug protein expression resulted in poorer OS (HR = 2.21; 95% CI = 1.47-3.33; P < 0.001) and DFS (HR = 2.03; 95% CI = 1.26-3.28; P = 0.004) in breast cancer patients. In addition, the results suggested that breast cancer patients with increased Slug protein expression had a higher TNM stage (I-II vs III-IV; OR = 0.42; 95% CI = 0.25-0.70; P = 0.001), a greater tendency to have axillary lymph node metastases (N+ vs N0; OR = 2.16; 95% CI = 1.31-3.56; P = 0.003) and were more prone to estrogen receptor deficiency (positive vs negative; OR = 0.67; 95% CI = 0.45-0.99; P = 0.042). However, Slug protein expression was not associated with age, histological grade, tumor size, progesterone receptor status, or human epidermal growth factor receptor 2 status in breast cancer patients. CONCLUSION: This meta-analysis showed that elevated Slug protein expression may be related to poor outcomes in patients with breast cancer. Therefore, Slug is not only an indicator of patient survival but may also become a new target for breast cancer therapy.

Suspension state regulates epithelial-to-mesenchymal transition and stemness of breast tumor cells.

OBJECTIVES: The mechanical forces on circulating tumor cells (CTCs) should not be ignored in blood and it is more essential that CTCs can overcome and utilize the mechanical interaction to acquire the ability of distant metastasis. At present there are few studies on how suspension mechanics regulates the behavior of tumor cells. The aim of the study was to explore the effects of suspension state on the epithelial-mesenchymal transition (EMT) and stemness of breast CTCs and the molecular mechanisms involved. RESULTS: Suspension state could regulate the program of EMT in breast cancer cells, which supported the complex dynamic concept of EMT. It is that the Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) signaling pathway was activated by suspension state in MCF-7 cells instead of MDA-MB-231 cells. In addition, suspension state increased the stemness of breast cancer cells from different aspects. CONCLUSION: The study highlighted the emergence of hybrid epithelial/mesenchymal (E/M) state during hematogenous metastasis and the plasticity of CTCs caused by cancer stem cells, further providing novel insights into clinical monitoring of CTCs and therapeutic strategies.

MGF E peptide improves anterior cruciate ligament repair by inhibiting hypoxia-induced cell apoptosis and accelerating angiogenesis.

Severe hypoxic microenvironment endangers cell survival of anterior cruciate ligament (ACL) fibroblasts and is harmful to ACL repair and regeneration. In the current study, we explored the effects of mechanogrowth factor (MGF) E peptide on the hypoxia-induced apoptosis of ACL fibroblasts and relevant mechanisms. It demonstrated that severe hypoxia promoted hypoxia-inducible factor-1α (HIF-1α) expression and caused cell apoptosis of ACL fibroblasts through increasing caspase 3/7/9 messenger RNA (mRNA), cleaved caspase 3 and proapoptotic proteins expression levels but decreasing antiapoptotic proteins expression levels. Fortunately, MGF E peptide effectively protected ACL fibroblasts against hypoxia-induced apoptosis through regulating caspase 3/7/9 mRNA, cleaved caspase 3 and apoptosis-relevant proteins expression levels. Simultaneously, mitochondrial, @@@MEK-ERK1/2 (extracellular-signal-regulated kinase 1/2), and phosphoinositide-3-kinase-protein kinase B (PI3K-Akt) pathways were involved in MGF E peptide regulating hypoxia-induced apoptosis of ACL fibroblasts. In rabbit ACL rupture model, MGF E peptide also decreased HIF-1α expression levels, cell apoptosis, and facilitated cell proliferation. In addition, MGF could accelerate angiogenesis after ACL injury probably owing to its recruitment of proangiogenesis cells by stromal cell-derived factor 1α/CXCR4 axis and stimulation of vascular endothelial growth factor α expression level. In conclusion, our findings suggested that MGF E peptide could be utilized for ACL repair and regeneration and supplied experimental support for its application in clinical ACL treatment as a potential strategy.

Suspension state increases reattachment of breast cancer cells by up-regulating lamin A/C.

Extravasation is a rate-limiting step of tumor metastasis, for which adhesion to endothelium of circulating tumor cells (CTCs) is the prerequisite. The suspension state of CTCs undergoing detachment from primary tumor is a persistent biomechanical cue, which potentially regulates the biophysical characteristics and cellular behaviors of tumor cells. In this study, breast tumor cells MDA-MB-231 in suspension culture condition were used to investigate the effect of suspension state on reattachment of CTCs. Our study demonstrated that suspension state significantly increased the adhesion ability of breast tumor cells. In addition, suspension state markedly promoted the formation of stress fibers and focal adhesions and reduced the motility in reattached breast cancer cells. Moreover, lamin A/C was reversibly accumulated at posttranscriptional level under suspension state, improving the cell stiffness of reattached breast cancer cells. Disruption of actin cytoskeleton by cytochalasin D caused lamin A/C accumulation. Conversely, decreasing actomyosin contraction by ROCK inhibitor Y27632 reduced lamin A/C level. Knocking down lamin A/C weakened the suspension-induced increase of adhesion, and also abolished the suspension-induced decrease of motility and increase of stress fibers and focal adhesion in reattaching tumor cells, suggesting a crucial role of lamin A/C. In conclusion, it was demonstrated that suspension state promoted the reattachment of breast tumor cells by up-regulating lamin A/C via cytoskeleton disruption. These findings highlight the important role of suspension state for tumor cells in tumor metastasis.

Effect of substrate stiffness on hepatocyte migration and cellular Young's modulus.

Hepatic fibrosis progress accompanied by an unbalanced extracellular matrix (ECM) degradation and deposition leads to an increased tissue stiffness. Hepatocytes interplay with all intrahepatic cell populations inside the liver. However, how hepatocytes migration and cellular Young's modulus influenced by the substrate stiffness are not well understood. Here, we established a stiffness-controllable in vitro cell culture model by using a polyvinyl alcohol (PVA) hydrogel that mimicked the same physical stiffness as a fibrotic liver. Three levels of stiffness were used in our experiment that corresponded to the stiffness levels found in normal liver tissue (4.5 kPa), the early (19 kPa) and late stages (37 kPa) of fibrotic liver tissues. Cytoskeleton of hepatocyte was influenced by substrate stiffness. Soft substrate promoted the cellular migration and directionality. The cellular Young's modulus firstly increased and then decreased with increasing substrate stiffness. Integrin-ß1 and ß-catenin expression on cytomembrane were up-regulated and down-regulated with the increase of substrate stiffness, respectively. Our data not only suggested that hepatocytes were sensitive to substrate stiffness, but also suggested that there may be a potential relationship among substrate stiffness, cellular Young's modulus and the dynamic balance of integrin-ß1 and ß-catenin pathways. These results may provide us a new insight in mechanism investigation of mechano-dependent diseases, especially like fibrosis related diseases.

ERK1/2 and Akt phosphorylation were essential for MGF E peptide regulating cell morphology and mobility but not proangiogenic capacity of BMSCs under severe hypoxia.

Severe hypoxia inhibits the adhesion and mobility of bone marrow-derived mesenchymal stem cells (BMSCs) and limits their application in bone tissue engineering. In this study, CoCl2 was used to simulate severe hypoxia and the effects of mechano-growth factor (MGF) E peptide on the morphology, adhesion, migration, and proangiogenic capacity of BMSCs under hypoxia were measured. It was demonstrated that severe hypoxia (500-µM CoCl2 ) significantly caused cell contraction and reduced cell area, roundness, adhesion, and migration of BMSCs. RhoA and ROCK1 expression levels were upregulated by severe hypoxia, but p-RhoA and mobility-relevant protein (integrin ß1, p-FAK and fibronectin) expression levels in BMSCs were inhibited. Fortunately, MGF E peptide could restore all abovementioned indexes except RhoA expression. MEK-ERK1/2 pathway was involved in MGF E peptide regulating cell morphological changes, mobility, and relevant proteins (except p-FAK). PI3K-Akt pathway was involved in MGF E peptide regulating cell area, mobility, and relevant proteins. Besides, severe hypoxia upregulated vascular endothelial growth factor α expression but was harmful for proangiogenic capacity of BMSCs. Our study suggested that MGF E peptide might be helpful for the clinical application of tissue engineering strategy in bone defect repair. SIGNIFICANCE OF THE STUDY: Sever hypoxia impairs bone defect repair with bone marrow-derived mesenchymal stem cells (BMSCs). This study proved that mechano-growth factor E (MGF E) peptide could improve the severe hypoxia-induced cell contraction and decline of cell adhesion and migration of BMSCs. Besides, MGF E peptide weakened the effects of severe hypoxia on the cytoskeleton arrangement- and mobility-relevant protein expression levels in BMSCs. The underlying molecular mechanism was also verified. Finally, it was confirmed that MGF E peptide showed an adverse effect on the expression level of vascular endothelial growth factor α in BMSCs under severe hypoxia but could make up for this deficiency through accelerating cell proliferation.

Gene expression profiling of human hepatocytes grown on differing substrate stiffness.

OBJECTIVE: To study the effects of different substrate stiffness on human hepatocytes using RNA sequencing (RNA-Seq) technology. The stiffness was corresponding to physiology and pathology stiffness of liver tissues. RESULTS: With the aid of RNA-Seq technology, our study characterizes the transcriptome of hepatocytes cultured on soft, moderate, stiff and plastic substrates. Compared to soft substrate, our RNA-Seq results revealed 1131 genes that were up-regulated and 2534 that were down-regulated on moderate substrate, 1370 genes that were up-regulated and 2677 down-regulated genes on stiff substrate. Functional enrichment analysis indicated that differentially expressed genes were associated with the regulation of actin cytoskeleton, focal adhesion, tight junction, adherens junction as well as antigen processing and presentation. RNA-Seq results were further verified by a quantitative real-time reverse transcriptase polymerase chain reaction. CONCLUSION: Our study provides a comprehensive picture of the gene expression landscape in hepatocytes grown on different substrate stiffness, offering insights into the role of substrate stiffness in hepatic pathology.

Mechano growth factor E peptide inhibits invasion of melanoma cells and up-regulates CHOP expression via endoplasmic reticulum stress.

OBJECTIVE: To evaluate the effects of mechano growth factor E peptide (MGF) on the invasive properties of melanoma cells. RESULTS: Melanoma cells (GLL19) were treated with 10, 20 and 30 ng MGF/ml for 24 h. Their invasive properties were investigated by transwell assay. Cytoskeleton reorganization was assessed via staining with phalloidin-FITC; lysyl oxidase (LOX) family gene expression was tested by qRT-PCR, and western blotting was used to detect expression of the matrix metalloproteinases (MMPs) and endoplasmic reticulum (ER) stress. MGF decreased the invasive capabilities of melanoma cells and induced changes in cytoskeleton distribution. MGF also down-regulated the expression of MMPs and up-regulated the expression of the cell apoptosis-related protein CHOP by inducing ER stress. CONCLUSIONS: MGF can decrease the invasive properties of melanoma cells and induce ER stress, promoting cell apoptosis. Thus, MGF represents a novel strategy for the potential treatment of patients presenting with cutaneous melanoma.

MGF E peptide pretreatment improves collagen synthesis and cell proliferation of injured human ACL fibroblasts via MEK-ERK1/2 signaling pathway.

Injured anterior cruciate ligament (ACL) is hard to heal due to the poor proliferative potential of ACL fibroblasts. To verify whether mechano-growth factor (MGF) E peptide can restore the cell proliferation of injured ACL fibroblasts, ACL fibroblasts pretreated with MGF E peptide were subjected to injurious stretch and the outcomes were evaluated at 0 and 24 h. After injured, the type III collagen synthesis was increased at 0 h while inhibited at 24 h. The matrix metalloproteinase-2 (MMP-2) activity/expression was up-regulated, but the cell proliferation was inhibited. Fortunately, exogenous MGF E peptide decreased the type I/III collagen synthesis at 0 h but improved the type III collagen synthesis at 24 h. It decreased the MMP-2 activity/expression of injured ACL fibroblasts. Besides, MGF E peptide accelerated the cell proliferation via MEK-ERK1/2 signaling pathway. Our results implied that MGF E peptide pretreatment could provide a new efficient approach for ACL regeneration.

The effects and mechanisms of SLC34A2 on maintaining stem cell-like phenotypes in CD147+ breast cancer stem cells.

The cancer stem cell (CSC) hypothesis has gained significant recognition in describing tumorigenesis. Identification of the factors critical to development of breast cancer stem cells (BCSCs) may provide insight into the improvement of effective therapies against breast cancer. In this study, we aim to investigate the biological function of SLC34A2 in affecting the stem cell-like phenotypes in BCSCs and its underlying mechanisms. We demonstrated that CD147+ cells from breast cancer tissue samples and cell lines possessed BCSC-like features, including the ability of self-renewal in vitro, differentiation, and tumorigenic potential in vivo. Flow cytometry analysis showed the presence of a variable fraction of CD147+ cells in 9 of 10 tumor samples. Significantly, SLC34A2 expression in CD147+ BCSCs was enhanced compared with that in differentiated adherent progeny of CD147+ BCSCs and adherently cultured cell line cells. In breast cancer patient cohorts, SLC34A2 expression was found increased in 9 of 10 tumor samples. By using lentiviral-based approach, si-SLC34A2-transduced CD147+ BCSCs showed decreased ability of sphere formation, cell viability in vitro, and tumorigenicity in vivo, which suggested the essential role of SLC34A2 in CD147+ BCSCs. Furthermore, PI3K/AKT pathway and SOX2 were found necessary to maintain the stemness of CD147+ BCSCs by using LY294002 or lentiviral-si-SOX2. Finally, we indicated that SLC34A2 could regulate SOX2 to maintain the stem cell-like features in CD147+ BCSCs through PI3K/AKT pathway. Therefore, our report identifies a novel role of SLC34A2 in BCSCs' state regulation and establishes a rationale for targeting the SLC34A2/PI3K/AKT/SOX2 signaling pathway for breast cancer therapy.

Regulation of matrix stiffness on the epithelial-mesenchymal transition of breast cancer cells under hypoxia environment.

Substrate stiffness and hypoxia are associated with tumor development and progression, respectively. However, the synergy of them on the biological behavior of human breast cancer cell is still largely unknown. This study explored how substrate stiffness regulates the cell phenotype, viability, and epithelial-mesenchymal transition (EMT) of human breast cancer cells MCF-7 under hypoxia (1% O2). TRITC-phalloidin staining showed that MCF-7 cells transformed from round to irregular polygon with stiffness increase either in normoxia or hypoxia. While being accompanied with the upward tendency from a 0.5- to a 20-kPa substrate, the percentage of cell apoptosis was significantly higher in hypoxia than that in normoxia, especially on the 20-kPa substrate. Additionally, it was hypoxia, but not normoxia, that promoted the EMT of MCF-7 by upregulating hypoxia-inducible factor-1α (HIF-1α), vimentin, Snail 1, and matrix metalloproteinase 2 (MMP 2) and 9 (MMP 9), and downregulating E-cadherin simultaneously regardless of the change of substrate stiffness. In summary, this study discovered that hypoxia and stiffer substrate (20 kPa) could synergistically induce phenotype change, apoptosis, and EMT of MCF-7 cells. Results of this study have an important significance on further exploring the synergistic effect of stiffness and hypoxia on the EMT of breast cancer cells and its molecular mechanism.

Gene expression profiling analysis of the effects of low-intensity pulsed ultrasound on induced pluripotent stem cell-derived neural crest stem cells.

Low-intensity pulsed ultrasound (LIPUS) is a noninvasive technique that has been shown to affect cell proliferation, migration, and differentiation and promote the regeneration of damaged peripheral nerve. Our previous studies had proved that LIPUS can significantly promote the neural differentiation of induced pluripotent stem cell-derived neural crest stem cells (iPSCs-NCSCs) and enhance the repair of rat-transected sciatic nerve. To further explore the underlying mechanisms of LIPUS treatment of iPSCs-NCSCs, this study reported the gene expression profiling analysis of iPSCs-NCSCs before and after LIPUS treatment using the RNA-sequencing (RNA-Seq) method. It was found that expression of 76 genes of iPSCs-NCSCs cultured in a serum-free neural induction medium and expression of 21 genes of iPSCs-NCSCs cultured in a neuronal differentiation medium were significantly changed by LIPUS treatment. The differentially expressed genes are related to angiogenesis, nervous system activity and functions, cell activities, and so on. The RNA-seq results were further verified by a quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). High correlation was observed between the results obtained from qRT-PCR and RNA-Seq. This study presented new information on the global gene expression patterns of iPSCs-NCSCs after LIPUS treatment and may expand the understanding of the complex molecular mechanism of LIPUS treatment of iPSCs-NCSCs.

Enforced expression of hsa-miR-125a-3p in breast cancer cells potentiates docetaxel sensitivity via modulation of BRCA1 signaling.

Epigenetic gene inactivation by microRNAs (miRNAs) plays a key role in malignant transformation, prevention of apoptosis, drug resistance and metastasis. It has been shown that miR-125a is down-regulated in HER2-amplified and HER2-overexpressing breast cancers (BCa), and this miRNA is believed to serve as an important tumor suppressor. miR-125a has two mature forms: hsa-miR-125a-3p and hsa-miR-125a-5p. However, the functional details of these miRNAs in BCa, particularly during pathogenesis of drug resistance, remain largely unexplored. Herein, we reported that hsa-miR-125a-3p expression was significantly reduced in chemoresistant BCa tissues and in experimentally established chemoresistant BCa cells. hsa-miR-125a-3p knockdown promoted cell proliferation and compromised docetaxel (Dox)-induced cell death, whereas overexpression of hsa-miR-125a-3p attenuated Dox chemoresistance in BCa cells. From a mechanistic standpoint, hsa-miR-125a-3p directly targeted 3'-untranslated regions (3'-UTRs) of breast cancer early onset gene 1 (BRCA1) and inhibits its protein expression via translational repression mechanism. In addition, suppression of BRCA1 expression by siRNA treatment effectively improved hsa-miR-125a-3p deficiency-triggered chemoresistance in BCa cells. Collectively, these findings suggest that hsa-miR-125a-3p may function as a tumor suppressor by regulating the BRCA1 signaling, and reintroduction of hsa-miR-125a-3p analogs could be a potential adjunct therapy for advanced/chemoresistant BCa.

Predictive value of HLA-G and HLA-E in the prognosis of colorectal cancer patients.

HLA-G and HLA-E are non-classical HLA Ib molecules. Recently, increasingly more reports have shown that HLA-G is highly expressed in different malignancies. In this article, we detected the expression levels of HLA-G and HLA-E in primary colorectal cancer patients. Our results showed that 70.6% and 65.7% of the colorectal cancer tissues had positive HLA-G or HLA-E expression, respectively, and that 46.1% positively expressed both molecules. We also analyzed the correlations between the expression levels of HLA-G, HLA-E or both combined and the clinical outcomes of the patients. Kaplan-Meier analysis results showed that the expression levels of HLA-G or HLA-E alone and the combined expression of both molecules were all statistically correlated with the overall survival of colorectal cancer patients. Cox multivariate analysis showed that only HLA-G expression can serve as independent factor for OS. Our results also showed that the expression of HLA-E was significantly correlated with tumor metastasis.

Background-free 3D chemical imaging based on polarization coherent Raman holography.

We report on a holographic coherent anti-Stokes Raman scattering imaging by using polarization discrimination for nonresonant background suppression. With reduced polarization scrambling effect under weakly focused excitation, nonresonant background-free coherent Raman imaging is demonstrated. A fast chemically selective imaging is achieved in a three-dimensional volume of 70 µm ×70 µm ×100 µm in 2 s.

In vivo repair of rat transected sciatic nerve by low-intensity pulsed ultrasound and induced pluripotent stem cells-derived neural crest stem cells.

OBJECTIVES: To evaluate the effects of the combination of low-intensity pulsed ultrasound (LIPUS) and induced pluripotent stem cells-derived neural crest stem cells (iPSCs-NCSCs) on the regeneration of rat transected sciatic nerve in vivo. RESULTS: Tissue-engineered tubular nerve conduit was fabricated by electrospinning aligned nanofibers in longitudinal direction. This sustained the iPSCs-NCSCs and could be used as a bridge in rat transected sciatic nerve. Treatment with 0.3 W cm(-2) LIPUS for 2 weeks and 5 min per day significantly improved the sciatic functional index, static sciatic function index and nerve conduction velocity of rat sciatic nerve. Histological analysis showed that there were more regenerative new blood vessels and new neurofilaments, higher expression level of ß-III tubulin (Tuj1) in the experimental group seeded with iPSCs-NCSCs and stimulated with LIPUS. CONCLUSION: Combination of LIPUS with iPSCs-NCSCs promoted the regeneration and reconstruction of rat transected sciatic nerve and is an efficient and cost-effective method for peripheral nerve regeneration.