Macromolecular Nano-Assemblies for Enhancing the Effect of Oxygen-Dependent Photodynamic Therapy Against Hypoxic Tumors.

In oxygen (O2)-dependent photodynamic therapy (PDT), photosensitizers absorb light energy, which is then transferred to ambient O2, and subsequently cytotoxic singlet oxygen (1O2) is generated. Therefore, the availability of O2 and the utilization efficiency of generated 1O2 are two significant factors that influence the effectiveness of PDT. However, tumor microenvironments (TMEs) characterized by hypoxia and limited utilization efficiency of 1O2 resulting from its short half-life and short diffusion distance significantly restrict the applicability of PDT for hypoxic tumors. To address these challenges, numerous macromolecular nano-assemblies (MNAs) have been designed to relieve hypoxia, utilize hypoxia or enhance the utilization efficiency of 1O2. Herein, we provide a comprehensive review on recent advancements achieved with MNAs in enhancing the effectiveness of O2-dependent PDT against hypoxic tumors.

Downregulation of VEGFA accelerates AGEs-mediated nucleus pulposus degeneration through inhibiting protective mitophagy in high glucose environments.

Intervertebral disc degeneration (IVDD) contributes largely to low back pain. Recent studies have highlighted the exacerbating role of diabetes mellitus (DM) in IVDD, mainly due to the influence of hyperglycemia (HG) or the accumulation of advanced glycation end products (AGEs). Vascular endothelial growth factor A (VEGFA) newly assumed a distinct impact in nonvascular tissues through mitophagy regulation. However, the combined actions of HG and AGEs on IVDD and the involved role of VEGFA remain unclear. We confirmed the potential relation between VEGFA and DM through bioinformatics and biological specimen detection. Then we observed that AGEs induced nucleus pulposus (NP) cell degeneration by upregulating cellular reactive oxygen species (ROS), and HG further aggravated ROS level through breaking AGEs-induced protective mitophagy. Furthermore, this adverse effect could be strengthened by VEGFA knockdown. Importantly, we identified that the regulation of VEGFA and mitophagy were vital mechanisms in AGEs-HG-induced NP cell degeneration through Parkin/Akt/mTOR and AMPK/mTOR pathway. Additionally, VEGFA overexpression through local injection with lentivirus carrying VEGFA plasmids significantly alleviated NP degeneration and IVDD in STZ-induced diabetes and puncture rat models. In conclusion, the findings first confirmed that VEGFA protects against AGEs-HG-induced IVDD, which may represent a therapeutic strategy for DM-related IVDD.

Curcuminoids Modulated the IL-6/JAK/STAT3 Signaling Pathway in LoVo and HT-29 Colorectal Cancer Cells.

BACKGROUND: Curcuminoids, including curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin, are natural polyphenolic compounds that exhibit various biological properties, such as antioxidant, anti-inflammatory, and anticancer activities. Dysregulation of the interleukin (IL)-6-mediated Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway is closely associated with the development of colorectal cancer (CRC). METHODS: Here, we have evaluated the modulation of the IL-6/JAK/STAT3 pathway of curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin in LoVo and HT-29 colorectal cancer cells with a single molecular array (Simoa), western blot analysis, real-time polymerase chain reaction (PCR), and pathway analysis system. RESULTS: The study showed that curcuminoids suppressed the amount of IL-6 in LoVo and HT-29 colorectal cancer cells. Meanwhile, curcuminoids inhibited the expression of inflammation regulator-related microRNA (miRNA). We also found that the expression of total STAT3 was downregulated by curcuminoids. Moreover, the pathway analysis system showed that curcuminoids inactivated the JAK/STAT3 signaling pathway. Taken together, we demonstrated that the anti-cancer activities of curcuminoids against colorectal cancer are due to the modulation of the IL-6/JAK/STAT3 cascade. CONCLUSION: Curcuminoids could be a promising anti-cancer agent for the treatment of human colorectal cancer.

Single-Cell Diagnosis of Cancer Drug Resistance through the Differential Endocytosis of Nanoparticles between Drug-Resistant and Drug-Sensitive Cancer Cells.

Single-cell diagnosis of cancer drug resistance is highly relevant for cancer treatment, as it can be used to identify the subpopulations of drug-resistant cancer cells, reveal the sensitivity of cancer cells to treatment, and monitor the progress of cancer drug resistance. However, simple and effective methods for cancer drug resistance detection at the single-cell level are still lacking in laboratory and clinical studies. Inspired by the fact that nanoparticles with diverse physicochemical properties would generate distinct and specific interactions with drug-resistant and drug-sensitive cancer cells, which have distinctive molecular signatures, here, we have synthesized a library of fluorescent nanoparticles with various sizes, surface charges, and compositions (SiO2 nanoparticles (SNPs), organic PS-co-PAA nanoparticles (ONPs), and ZIF-8 nanoparticles (ZNPs)), thus demonstrating that the composition has a critical influence on the interaction of nanoparticles with drug-resistant cancer cells. Furthermore, the clathrin/caveolae-independent endocytosis of ZNPs together with the P-glycoprotein-related decreased cell membrane fluidity resulted in a lower cellular accumulation of ZNPs in drug-resistant cancer cells, consequently causing the distinct cellular accumulation of ZNPs between the drug-resistant and drug-sensitive cancer cells. This difference was further quantified by detecting the fluorescence signals generated by the accumulation of nanoparticles at the single-cell level via flow cytometry. Our findings provide another insight into the nanoparticle-cell interactions and offer a promising platform for the diagnosis of cancer drug resistance of various cancer cells and clinical cancer samples at the single-cell level.

Roles of MT-ND1 in Cancer.

The energy shift toward glycolysis is one of the hallmarks of cancer. Complex I is a vital enzyme complex necessary for oxidative phosphorylation. The mitochondrially encoded NADH: ubiquinone oxidoreductase core subunit 1 (MT-ND1) is the largest subunit coded by mitochondria of complex I. The present study summarizes the structure and biological function of MT-ND1. From databases and literature, the expressions and mutations of MT-ND1 in a variety of cancers have been reviewed. MT-ND1 may be a biomarker for cancer diagnosis and prognosis. It is also a potential target for cancer therapy.

Ameliorating Osteoarthritis in Mice Using Silver Nanoparticles.

Knee osteoarthritis (KOA) is one of the most commonly encountered degenerative diseases of the joints in people over 45 years of age. Currently, there are not any effective therapeutics for KOA,and the only end-point strategy is total knee arthroplasty (TKA); therefore, KOA is associated with economic burdens and societal costs. The immune inflammatory response is involved in the occurrence and development of KOA. We previously established a mouse model of KOA using type II collagen. Hyperplasia of the synovial tissue was present in the model, alongside a large number of infiltrated inflammatory cells. Silver nanoparticles have substantial anti-inflammatory effects and have been widely used in tumor therapy and surgical drug delivery. Therefore, we evaluated the therapeutic effects of silver nanoparticles in a collagenase II-induced KOA model. The experimental results showed that silver nanoparticles significantly reduced synovial hyperplasia and the infiltration of neutrophils in the synovial tissue. Hence, this work demonstrates the identification of a novel strategy for OA and provides a theoretical basis for preventing the progress of KOA.

Molecular fingerprints of nuclear genome and mitochondrial genome for early diagnosis of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer with high morbidity and mortality rates. Due to the heterogeneity of LUAD, its characteristics remain poorly understood. Exploring the clinical and molecular characteristics of LUAD is challenging but vital for early diagnosis. METHODS: This observational and validation study enrolled 80 patients and 13 healthy controls. Nuclear and mtDNA-captured sequencings were performed. RESULTS: This study identified a spectrum of nuclear and mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with diagnosis. The correlation coefficient for somatic mutations in cfDNA and patient-matched tumor tissues was high in nuclear and mitochondrial genomes. The mutation number of highly mutated genes was evaluated, and the Least Absolute Shrinkage and Selection Operator (LASSO) established a diagnostic model. Receiver operating characteristic (ROC) curve analysis explored the diagnostic ability of the two panels. All models were verified in the testing cohort, and the mtDNA panel demonstrated excellent performance. This study identified somatic mutations in the nuclear and mitochondrial genomes, and detecting mutations in cfDNA displayed good diagnostic performance for early-stage LUAD. Moreover, detecting somatic mutations in the mitochondria may be a better tool for diagnosing early-stage LUAD. CONCLUSIONS: This study identified specific and sensitive diagnostic biomarkers for early-stage LUAD by focusing on nuclear and mitochondrial genome mutations. This also further developed an early-stage LUAD-specific mutation gene panel for clinical utility. This study established a foundation for further investigation of LUAD molecular pathogenesis.

Quantitative detection of circulating MT-ND1 as a potential biomarker for colorectal cancer.

Liquid biopsy represents a diagnostic and monitoring tool and the circulating cell-free mitochondrial DNA (mtDNA) plays a vital role in tumor diagnosis and dynamic assessment. Colorectal cancer (CRC) is one of the most common fatal cancers worldwide. Mitochondrially encoded NADH dehydrogenase subunit 1 (MT-ND1) encodes the biggest subunit of respiratory complex I of mtDNA, and mutations in the MT-ND1 are common in CRC. We sought to determine if mutations in circulating MT-ND1 could be a potential biomarker for colorectal cancer. In this study, twenty-two CRC patients at Zhujiang Hospital were included. We mainly used droplet digital PCR to determine the mutation status of MT-ND1, combined with clinical data. In the experiment in vivo, cell-free mtDNA generally presented high concordance with tumor tissues. By quantitative PCR, the MT-ND1 content of plasma in CRC patients was significantly higher than that in healthy individuals (58.01 vs. 0.64, p=0.027). The detection of circulating MT-ND1 content and variants (m.3606 A>G, m.3970 C>T, m.4071 C>T, m.4086 C>T) in cfDNA showed a good correlation with predicted tumor response and progression to chemotherapy. In conclusion, the content and variants of circulating MT-ND1 may become a versatile tool for the diagnosis and monitoring of colorectal cancer.

Dual-probe fluorescent biosensor based on T7 exonuclease-assisted target recycling amplification for simultaneous sensitive detection of microRNA-21 and microRNA-155.

Effective and simultaneous monitoring of the abnormal expression of certain microRNAs (miRNAs), especially for miRNA-21 and miRNA-155, can indicate drug resistance in lung cancer. In this work, T7 exonuclease (T7 Exo)-assisted target recycling amplification coupled with the extensive fluorescence quenching of graphene oxide (GO) was designed for the simultaneous detection of miRNA-21 and miRNA-155 using FAM- and ROX-labeled single-strand DNA probes. Through this method, the variable emission intensities of FAM and ROX caused by the introduction of miRNA-21 and miRNA-155, respectively, were obtained with high sensitivity. The method exhibited excellent analytical performance for simultaneous detection of miRNA-21 and miRNA-155 without cross-interference. The linear range was from 0.005 nM to 5 nM over three orders of magnitude, with detection limits as low as 3.2 pM and 4.5 pM for miRNA-21 and miRNA-155, respectively. Furthermore, the recovery (92.49-103.67%) and relative standard deviation (RSD < 4.8%) of the standard addition test of miRNA-21 and miRNA-155 in human plasma suggested the potential for drug resistance warning in clinical practice via this simple strategy. A homogeneous T7 Exo-assisted signal amplification combined with GO quenching platform was developed for accurate, sensitive and simultaneous analysis of miRNA-21 and miRNA-155 for drug resistance warning in lung cancer. This simple method exhibited a wide linear range and low LODs for miR-21 and miR-155.

Investigation of the dissolution and diffusion properties of interstitial oxygen at grain boundaries in body-centered-cubic iron by the first-principles study.

Oxidation corrosion of steel is a universal problem in various industries and severely accelerated in nuclear reactors. First-principles calculations are performed to explore the dissolution and diffusion properties of interstitial oxygen in the body-centered-cubic iron grain boundaries Σ3〈110〉(111) and Σ5〈001〉(310). Solution energies indicate that interstitial oxygen atoms prefer to dissolve in body-centered-cubic iron, and energetically segregate to grain boundaries. Energy barriers show that oxygen atoms would segregate towards Σ3〈110〉(111) with a low energy barrier. However, they concentrate to the transition region of Σ5〈001〉(310) due to the high-energy barrier in the transition zone. When O atoms arrive at grain boundaries, they would stay there due to the larger solution energy and diffusion energy barrier in grain boundaries compared to that in the defect-free Fe bulk. These results indicate that O atoms would prefer to diffuse through the bulk, and oxidize grain boundaries. This study provides insight into oxidation phenomena in experiments and necessary parameters for future studies on the oxidation of steel under irradiation in nuclear reactors.

LncRNA SPRY4­IT1 promotes progression of osteosarcoma by regulating ZEB1 and ZEB2 expression through sponging of miR­101 activity.

Long non­coding (lnc)RNA sprouty receptor tyrosine kinase signalling antagonist 4­intronic transcript 1 (SPRY4­IT1) has been demonstrated to serve a critical role in the tumorigenesis of osteosarcoma (OS); however, the specific underlying mechanism remains unclear. The aim of the present study was to examine the interactions between SPRY4­IT1 and its downstream effectors, to determine if any of the interactions contributed to SPRY4­IT1­mediated proliferation, migration and invasion in cancer cells. A signalling cascade which involved SPRY4­IT1, miR­101 and zinc finger E­box­binding homeoboxes (ZEBs) was examined in the present study. Intracellular SPRY4­IT1 and miR­101 expression levels were altered through transfection to assess their effect on proliferation, cell cycle progression, survival, migration and invasion. A dual­luciferase assay was utilized to determine the association between SPRY4­IT1/miR­101 and ZEBs/miR­101 and nude mouse xenograft experiments were performed to determine the effect of SPRY4­IT1 in vivo. The results indicated that the SPRY4­IT1 levels were negatively associated with miR­101 expression levels in OS cells, an association which was not observed in the normal osteoblast cells. SPRY4­IT1 knockdown or miR­101 overexpression reduced proliferation, cell cycle progression, survival, migration and invasion of MG­63 and U2OS cells. SPRY4­IT1 knockdown was accompanied by increased expression of miR­101 and E­cadherin levels, as well as decreased expression levels of ZEB1/2 and other epithelial­mesenchymal transition­associated proteins. Simultaneous knockdown of SPRY4­IT1 and inhibition of miR­101 partially reversed the anti­tumour effects of SPRY4­IT1 inhibition in vitro. Consistent with these findings, short hairpin RNA targeting SPRY4­IT1 also hindered xenograft tumour growth and altered the levels of miR­101, ZEB1/2 and E­cadherin in vivo. Dual­luciferase reporter assays demonstrated that SPRY4­IT1 may have regulated the expression of ZEB1 and ZEB2 by sponging miR­101. In conclusion, SPRY4­IT1 inhibition increased miR­101 levels, resulting in downregulation of ZEB1/2 expression and thus exerting anti­tumour effects in OS.

A new method to predict the outcome of the volar locked plate treatment for distal radius fracture.

BACKGROUND: Volar locked plate for distal radius fracture is one of the common procedures performed in trauma surgery. There are already some factors which can be used to predict the functional outcome after volar locked plating for distal radius fracture. However their limitations caused that the outcomes couldn't be satisfactorily predicted. Better factors for predicting the prognosis more precisely are of great interest. The aim of this study is to introduce such a new factor. METHODS: A total of 56 patients suffered from unilateral distal radius fracture were managed operatively with the volar locked plate. Before operation, all CT scans of the distal radius were obtained. The ratios of soft tissue circumference to bone circumference at the watershed line in the distal radius were calculated based on the preoperative CT scans. Outcomes were evaluated after operation. The correlations between the ratio and the outcomes were analyzed using single factor linear regression analysis. RESULTS: Statistically significant linear relationships between the ratio and flexion degrees, extension degrees also patient-rated wrist evaluation (PRWE) scores were discovered. With the increase of the ratios, the flexion and extension range increased and the PRWE scores declined. CONCLUSIONS: There are obvious linear relationships between the ratio and postoperative wrist flexion-extension degrees also PRWE scores when using volar locked plating for distal radius fracture. So the ratio can be used as a predictor aiding surgeons to predict the outcome.

A dual-label time-resolved fluorescence immunoassay for screening of osteoporosis based on simultaneous detection of C-terminal telopeptide (ß-CTX) and aminoterminal propeptide (P1NP) of type I procollagen.

Osteoporosis is a disease where increased bone weakness increases the risk of a broken bone. Until a broken bone occurs, there are typically no symptoms. Osteoporosis affects more than 75 million people in the United States, Europe and Japan. The diagnosis of osteoporosis is primarily determined by measuring bone mineral density using dual-energy X-ray absorptiometry, but for men under 50 years of age, premenopausal women should not be made on the basis of densitometric criteria alone. Bone biomarkers are a useful tool in detecting osteoporotic. A two-step dual-label time-resolved fluorescence immunoassay (TRFIA) was developed for the simultaneous detection of serum C-terminal telopeptide (ß-CTX) and amino-terminal propeptide (P1NP) of Type I procollagen in a single run. The performance of this assay was first evaluated using clinical serum samples, and then compared with commercialized kits. The sensitivity of this assay for ß-CTX was 1 ng/L (dynamic range, 0-1000 ng/L), and the sensitivity for P1NP detection was 1 µg/L (dynamic range, 1-1000 µg/L). High correlation coefficients (R) were obtained between the present dual-label TRFIA and commercially available kits (R = 0.99 for ß-CTX and P1NP). The present dual-label TRFIA has high sensitivity, specificity and accuracy in clinical sample analysis. It is a good alternative to the single-label diagnostic methods.

Aquaporin-3 Attenuates Oxidative Stress-Induced Nucleus Pulposus Cell Apoptosis Through Regulating the P38 MAPK Pathway.

BACKGROUND/AIMS: Previous studies have shown that oxidative damage is a main contributor to disc nucleus pulposus (NP) cell apoptosis. Aquaporin-3 (AQP-3) facilitates reactive oxygen species (ROS) scavenging and thus alleviates oxidative injury in other cells. This study aims to investigate the role and mechanism of AQP-3 in regulating NP cell apoptosis under oxidative damage. METHODS: Rat NP cells were treated with H2O2 for 48 hours, while control NP cells were free of H2O2. Recombinant AQP-3 lentiviral vectors were used to investigate the effect of enhanced AQP-3 expression levels in NP cells. NP cell apoptosis was assessed by flow cytometry, caspase-3 activity, gene expression of apoptosis-related molecules (Bax, Bcl-2 and caspase-3), and protein expression of cellular apoptosis markers (cleaved PARP and cleaved caspase-3). Additionally, intracellular ROS content and activity of the p38 MAPK pathway were evaluated. RESULTS: Compared with the control NP cells, oxidative damage in the treatment cells significantly increased cell apoptosis ratios and caspase-3 activity, upregulated gene expression of Bax and caspase-3, downregulated gene expression of Bcl-2, and increased protein expression of cleaved PARP and cleaved caspase-3, as well as increased intracellular ROS content and activity of the p38 MAPK pathway. However, AQP-3 overexpression partly alleviated cell apoptosis, decreased intracellular ROS content, and inhibited the p38 MAPK pathway in NP cells under oxidative damage. CONCLUSION: Oxidative damage can significantly downregulate AQP-3 expression. Enhancing AQP-3 expression in NP cells partly attenuates cellular apoptosis through regulating the p38 MAPK pathway under oxidative damage.

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture.

BACKGROUND/AIMS: An adequate matrix production of nucleus pulposus (NP) cells is an important tissue engineering-based strategy to regenerate degenerative discs. Here, we mainly aimed to investigate the effects and mechanism of mechanical compression (i.e., static compression vs. dynamic compression) on the matrix synthesis of three-dimensional (3D) cultured NP cells in vitro. METHODS: Rat NP cells seeded on small intestinal submucosa (SIS) cryogel scaffolds were cultured in the chambers of a self-developed, mechanically active bioreactor for 10 days. Meanwhile, the NP cells were subjected to compression (static compression or dynamic compression at a 10% scaffold deformation) for 6 hours once per day. Unloaded NP cells were used as controls. The cellular phenotype and matrix biosynthesis of NP cells were investigated by real-time PCR and Western blotting assays. Lentivirus-mediated N-cadherin (N-CDH) knockdown and an inhibitor, LY294002, were used to further investigate the role of N-CDH and the PI3K/Akt pathway in this process. RESULTS: Dynamic compression better maintained the expression of cell-specific markers (keratin-19, FOXF1 and PAX1) and matrix macromolecules (aggrecan and collagen II), as well as N-CDH expression and the activity of the PI3K/Akt pathway, in the 3D-cultured NP cells compared with those expression levels and activity in the cells grown under static compression. Further analysis showed that the N-CDH knockdown significantly down-regulated the expression of NP cell-specific markers and matrix macromolecules and inhibited the activation of the PI3K/Akt pathway under dynamic compression. However, inhibition of the PI3K/Akt pathway had no effects on N-CDH expression but down-regulated the expression of NP cell-specific markers and matrix macromolecules under dynamic compression. CONCLUSION: Dynamic compression increases the matrix synthesis of 3D-cultured NP cells compared with that of the cells under static compression, and the N-CDH-PI3K/Akt pathway is involved in this regulatory process. This study provides a promising strategy to promote the matrix deposition of tissue-engineered NP tissue in vitro prior to clinical transplantation.

Partial hepatectomy promotes implanted mouse hepatic tumor growth by activating hedgehog signaling.

OBJECTIVE: To investigate the role hedgehog signaling (Hh) in the growth of implanted hepatic tumors after partial hepatectomy (PH) in mice. METHODS: H22 cells were implanted to the scapula of 2 BALB/c (nu/nu) nude mice and tumor developed in 2 weeks. 40 nude mice were randomized into 4 groups: non-hepatectomy group (Sham operation group), 30% hepatectomy group, 70% hepatectomy group, and 70% hepatectomy with cyclopamine (Hh inhibitor). The hepatectomy model of nude mice was established. After hepatectomy, the tumor tissues incised from the scapula were implanted to the rest of the livers of the 4 groups. After 2 weeks, the tumor formation rates and the volumes of the implanted tumors were compared. Hh related proteins and downstream cytokine VEGF were tested by Western blot and Immunohistochemistry. All the data were analyzed to explore the role of Hh in the growth of tumor after PH. RESULTS: The volumes of the implanted tumors after liver resection were significantly higher in the 70% PH group than those in 0% and 30% PH groups; meanwhile, we also found that expression of the Hh ligand Indian Hh, its downstream transcription factor protein Gli-1, and its target VEGF were remarkably increased after PH, especially in the 70% PH group. Additionally, applying the Hh inhibitor cyclopamine to mice that underwent 70% PH significantly inhibited the growth of implanted tumors. CONCLUSIONS: The Hh signaling pathway was activated after PH and promoted liver regeneration. The growth of implanted hepatic tumors was also accelerated after PH via paracrine signaling.

N-Cadherin-Mediated Activation of PI3K/Akt-GSK-3ß Signaling Attenuates Nucleus Pulposus Cell Apoptosis Under High-Magnitude Compression.

BACKGROUND/AIMS: Mechanical overloading-induced nucleus pulposus (NP) apoptosis plays an important role in the pathogenesis of intervertebral disc degeneration. N-cadherin (N-CDH)-mediated signaling preserves normal NP cell phenotype. This study aims to investigate the effects of N-CDH on NP cell apoptosis under high-magnitude compression and the underlying mechanism behind this process. METHODS: Rat NP cells seeded on scaffold were perfusion-cultured using a self-developed perfusion bioreactor for 5 days and experienced different magnitudes (2% and 20% compressive deformation, respectively) of compression at a frequency of 1.0 Hz for 4 hours once per day. The un-loaded NP cells were used as controls. Lentivirus-mediated N-CDH overexpression and inhibitor LY294002 were used to further investigate the role of N-CDH and PI3K/Akt pathway under high-magnitude compression, respectively. NP cell apoptosis was evaluated by caspase-3 activity measured using a commercial kit, flow cytometry, and expression of apoptosis-related molecules analyzed by real-time PCR and western blotting assays. RESULTS: High-magnitude compression significantly increased apoptotic NP cells, caspase-3 activity and expression of pro-apoptotic molecules (Bax and caspase-3/cleaved caspase-3), but decreased expression of anti-apoptotic molecule (Bcl-2). High-magnitude compression decreased expression of N-CDH, p-Akt and p-GSK-3ß. However, N-CDH overexpression attenuated NP cell apoptosis and increased expression of p-Akt and p-GSK-3ß under high-magnitude compression. Further analysis showed that inhibition of the PI3K/Akt pathway suppressed NP cell apoptosis and decreased expression of p-GSK-3ß, but had no significant effects on N-CDH expression under high-magnitude compression. CONCLUSION: N-CDH can attenuate NP cell apoptosis through activating the PI3K/Akt-GSK-3ß signaling under high-magnitude compression.

Sinus tarsi approach versus extensile lateral approach for displaced intra-articular calcaneal fracture: a meta-analysis of current evidence base.

BACKGROUND: The extensile lateral approach (ELA) has been widely performed for displaced intra-articular calcaneal fractures (DIACFs), and wound complications remain a significant problem. As a minimal incision technique, the sinus tarsi approach (STA) was designed to overcome this disadvantage. There were already many reports about this approach but the conclusions were not completely consistent. Based on the current evidence, we performed this meta-analysis to compare the STA with ELA in the management of DIACF and expected to draw a certain and meaningful conclusion. METHODS: All potentially relevant randomized controlled trials (RCTs) and cohort studies (CSs) were searched in the databases of PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrial.gov. The desirable outcomes including wound complications, excellent and good rate, secondary surgery rate and Böhler's angle were extracted. RCT studies were assessed using the Risk of Bias Tool recommended by the Cochrane Collaboration, and cohort studies were evaluated using the Newcastle-Ottawa Scale. The data of RCTs and cohorts were pooled respectively using the fixed-effect model or random-effect model. Mean differences with 95% confidence intervals (CIs) were calculated for continuous data, and relative risks (RRs) with 95% CIs were calculated for dichotomous data. Statistical heterogeneity was assessed with the Q test and I 2 . Sensitivity analysis was developed to assess the reliability of pooled results. RESULTS: Seven studies including two RCTs and five CSs were eligible for the meta-analysis. No matter RCTs or CSs, the pooled data all showed that STA group had a lower incidence of wound complications than that in the ELA group and no significant difference was found in excellent and good rate and the recovery of Böhler's angle between the two groups. The CSs also showed that the STA group had a lower incidence of secondary surgeries than that in the ELA group. CONCLUSIONS: Through a STA, we not only can reduce the problems in wound healing but also achieve nearly the same adequate restoration of DIACF along with the similar functional outcomes compared with through an ELA.

Lnc-ATB contributes to gastric cancer growth through a MiR-141-3p/TGFß2 feedback loop.

The long noncoding RNA (lncRNA) ATB is an important regulator in human tumors. Here, we aimed to investigate the potential molecular mechanisms of lnc-ATB in gastric cancer (GC) tumorigenesis. RT-qPCR analysis was used to detect lnc-ATB expression level in 20 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANTs). Moreover, the biological role of lnc-ATB was determined in vitro. We found that lnc-ATB was significantly upregulated in GC tissues compared to lnc-ATB expression in ANTs. These high lnc-ATB expression levels predicted poor prognosis in GC patients. Low levels of lnc-ATB inhibited GC cell proliferation and cell cycle arrest in vitro. Lnc-ATB was found to directly bind miR-141-3p. Moreover, TGF-ß actives lnc-ATB and TGF-ß2 directly binds mir-141-3p. Finally, we demonstrated that lnc-ATB fulfilled its oncogenic roles in a ceRNA-mediated manner. Our study suggests that lnc-ATB promotes tumor progression by interacting with miR-141-3p and that Lnc-ATB may be a valuable prognostic predictor for GC. In conclusion, the positive feedback loop of lnc-ATB/miR-141-3p/TGF-ß2 may be a potential therapeutic target for the treatment of GC.