Assessment of SWI/SNF chromatin remodeling complex related genes as potential biomarkers and therapeutic targets in pan-cancer.

Recent research has uncovered a surprisingly high occurrence of aberrant expression and mutations in the genes that encode subunits of the SWI/SNF chromatin-remodeling complexes (SCRC). Nevertheless, the carcinogenic effects of aberrant expression and mutations in SWI/SNF genes have only been acknowledged in recent times, resulting in a comparatively limited understanding of these modifications. In this study, we comprehensively analyzed the expression difference, somatic mutation, potential biological pathways, stromal or immune cell infiltration, and drug sensitivity of SCRC-related genes (SCRGs) in pan-cancer. Furthermore, the evolutionary trend, prognostic signature, and immunotherapy response of SCRGs in kidney renal clear cell carcinoma (KIRC) were also evaluated. The expression of SCRGs was changed in 13 out of 14 tumor types, strongly linked to prognosis, and mutated in 30.9% of tumor patients. SCRGs were also closely associated with immune-related pathways and tumor metastasis pathways. The expression of SCRGs was positively associated with the immune score or stromal score but negatively correlated with Tumor purity. Three potential drugs (FK866, Ispinesib mesylate, and WZ3105) were identified to target the SCRGs. In KIRC, scRNA-seq analysis showed that the enrichment of SCRC and the communication frequency with immune cells were significantly declined during tumor cell progression. A prognostic signature was constructed in KIRC and was effective in predicting the prognosis for KIRC. Aberrant expression of eleven prognostic genes identified from the KIRC prognostic signature and the cytotoxicity of FK866 and Ispinesib mesylate to KIRC were verified by qRT-PCR and CCK-8 assay, respectively. Our study identified SCRGs as potential biomarker and therapeutic targets, providing new insights into SCRC for tumor-targeted therapy.

Hypoxia Stimulates PYGB Enzymatic Activity to Promote Glycogen Metabolism and Cholangiocarcinoma Progression.

Cholangiocarcinoma (CCA) displays enhanced glycolysis, pivotal for fulfilling the heightened energy demands intrinsic to its malignant progression. Recent research has indicated that endogenous glycogen rather than exogenous glucose acts as the major carbon source for glycolysis, highlighting the need to better understand the regulation of glycogen homeostasis in CCA. Here, through comprehensive integrative analysis, we identified that glycogen phosphorylase brain form (PYGB), the main enzyme involved in glycogen homeostasis, was markedly upregulated in CCA tissues, serving as an independent prognostic indicator for human CCA patients. Moreover, elevated PYGB expression potentiated cholangiocarcinogenesis and augmented CCA cell proliferation in both organoid and xenograft models. Hypoxia stimulated PYGB activity in a phosphoglycerate kinase 1 (PGK1)-dependent manner, leading to glycogenolysis and the subsequent release of glucose-6-phosphate (G6P) and thereby facilitating aerobic glycolysis. Notably, a virtual screening pinpointed the beta-blocker carvedilol as a potent pharmacological inhibitor of PYGB that could attenuate CCA progression. Collectively, these findings position PYGB as a promising prognostic biomarker and therapeutic target for CCA.

Diagnostic accuracy of low-dose dual-input computed tomography perfusion in the differential diagnosis of pulmonary benign and malignant ground-glass nodules.

This study aimed to evaluate the value of low-dose dual-input computed tomography perfusion (CTP) imaging in the differential diagnosis of benign and malignant pulmonary ground-glass opacity nodules (GGO). A retrospective study was conducted in patients with GGO who underwent CTP in our hospital from January 2021 to October 2023. All nodules were confirmed via pathological analysis or disappeared during follow-up. Postprocessing analysis was conducted using the dual-input perfusion mode (pulmonary artery and bronchial artery) of the body perfusion software to measure the perfusion parameters of the pulmonary GGOs. A total of 101 patients with pulmonary GGOs were enrolled in this study, including 43 benign and 58 malignant nodules. The dose length product of the CTP (348 mGy.cm) was < 75% of the diagnostic reference level of the unenhanced chest CT (470 mGy.cm). The effective radiation dose was 4.872 mSV. The blood flow (BF), blood volume (BV), mean transit time (MTT), and flow extraction product (FEP) of malignant nodules were higher than those of the benign nodules (p < 0.05). The FEP had the highest accuracy for the diagnosis of malignant nodules (area under the curve [AUC] = 0.821, 95% confidence interval [CI]: 0.735-0.908) followed by BV (AUV = 0.713, 95% CI 0.608-0.819), BF (AUC = 0.688, 95% CI 0.587-0.797), and MTT (AUC = 0.616, 95% CI 0.506-0.726). When the FEP was ≥ 19.12 mL/100 mL/min, the sensitivity was 91.5% and the specificity was 62.8%. To distinguish between benign nodules and malignant nodules, the AUC of the combination of BV and FEP was 0.816 (95% CI 0.728-0.903), whereas the AUC of the combination of BF, BV, MTT, and FEP was 0.814 (95% CI 0.729-0.900). Low-dose dual-input perfusion CT was extremely effective in distinguishing between benign from malignant pulmonary GGOs, with FEP exhibiting the highest diagnostic capability.

Mesenchymal stem cells with p38 mitogen-activated protein kinase interference ameliorate mouse ischemic stroke.

Mesenchymal stem cells (MSCs) have been widely used in the treatment of ischemic stroke. However, factors such as high glucose, oxidative stress, and aging can lead to the reduced function of donor MSCs. The p38 mitogen-activated protein kinase (MAPK) signaling pathway is associated with various functions, such as cell proliferation, apoptosis, senescence, differentiation, and paracrine secretion. This study examined the hypothesis that the downregulation of p38 MAPK expression in MSCs improves the prognosis of mice with ischemic stroke. Lentiviral vector-mediated short hairpin RNA (shRNA) was constructed to downregulate the expression level of p38 MAPK in mouse bone marrow-derived MSCs. The growth cycle, apoptosis, and senescence of MSCs after infection were examined. A mouse model of ischemic stroke was constructed. After MSC transplantation, the recovery of neurological function in the mice was evaluated. Lentivirus-mediated shRNA significantly downregulated the mRNA and protein expression levels of p38 MAPK. The senescence of MSCs in the p38 MAPK downregulation group was significantly reduced, but the growth cycle and apoptosis did not significantly change. Compared with the control group, the infarct volume was reduced, and the neurological function and the axonal remodeling were improved in mice with ischemic stroke after transplantation of MSCs with downregulated p38 MAPK. Immunohistochemistry confirmed that in the p38 MAPK downregulation group, apoptotic cells were reduced, and the number of neuronal precursors and the formation of white matter myelin were increased. In conclusion, downregulation of p38 MAPK expression in MSCs improves the therapeutic effect in mice with ischemic stroke, an effect that may be related to a reduction in MSC senescence. This method is expected to improve the efficacy of MSCs in patients, especially in patients with underlying diseases such as diabetes, thus providing a basis for clinical individualized treatment for cerebral infarction.

mTORC2 promotes pancreatic cancer progression and parp inhibitor resistance.

Pancreatic cancer is one of the most aggressive cancers with a median survival time of less than 5 months, and conventional chemotherapeutics are the main treatment strategy. Poly(ADP-ribose) polymerase (PARP) inhibitors have been recently approved for BRCA1/2-mutant pancreatic cancer, opening a new era for targeted therapy for this disease. However, most pancreatic cancer patients carry wild-type BRCA1/2 with resistance to PARP inhibitors. Here, we reported that mammalian target of rapamycin complex 2 (mTORC2) kinase is overexpressed in pancreatic cancer tissues and promotes pancreatic cancer cell growth and invasion. Moreover, we found that knockdown of the mTORC2 obligate subunit Rictor sensitized pancreatic cancer cells to the PARP inhibitor olaparib. Mechanistically, we showed that mTORC2 positively regulates homologous recombination (HR) repair by modulating BRCA1 recruitment to DNA double-strand breaks (DSBs). In addition, we confirmed that combination treatment with the mTORC2 inhibitor PP242 and the PARP inhibitor olaparib synergistically inhibited pancreatic cancer growth in vivo. Thus, this study provides a novel target and strategy for optimizing PARP inhibitor efficiency in pancreatic cancers.

Copper Increases the Sensitivity of Cholangiocarcinoma Cells to Tripterine by Inhibiting TMX2-Mediated Unfolded Protein Reaction Activation.

Chemotherapy-induced adaptive resistance is a significant factor that contributes to low therapeutic efficacy in tumor cells. The unfolded protein response (UPR) is a key mechanism in the development of drug resistance and serves as a critical reactive system for endoplasmic reticulum stress. Cu(II) can reduce the abundance of 60S ribosomal subunits and inhibit rRNA processing, leading to a decrease in the translation efficiency of the GRP78/BiP mRNA, which serves as a primary sensor for UPR activation. In this study, CuET-Lipid@Cela, composed of CuET and tripterine (Cela), demonstrates a significant synergistic antitumor effect on cholangiocarcinoma (CCA) cells. RNA-Seq is used to investigate the underlying mechanism, which suggests that the transmembrane protein 2 (TMX2) gene may be crucial in Cu(II) regulation of UPR by inhibiting the activation of GRP78/BiP and PERK/eIF2α. The synergistic antitumor efficacy of CuET-Lipid@Cela via inhibition of TMX2 is also confirmed in a myrAKT/YapS127A plasmid-induced primary CCA mouse model, providing new insights into the reversal of acquired chemotherapy-induced resistance in CCA.

Kinematic alignment versus mechanical alignment in total knee arthroplasty: An up-to-date meta-analysis.

PURPOSE: The purpose of this meta-analysis was to compare the efficacy and imaging parameters of kinematic alignment (KA) and mechanical alignment (MA) in total knee arthroplasty (TKA) and to evaluate whether patients undergoing KA-TKA benefited more than those undergoing MA-TKA. METHODS: Studies comparing the efficacy of KA-TKA and MA-TKA were included after searching and screening in the database, including PubMed, Embase, Web of Science and Cochrane Database Library. A total of 1420 patients were enrolled in the study, with 736 MA-TKA and 738 KA-TKA. The primary outcomes were postoperative knee function scores including KSS series, WOMAC, KOOS and OKS. Secondary outcomes included the operative time, the length of hospital stay, knee extension/flexion angle, and some imaging parameters. The risk of bias for included studies was assessed using the Cochrane Collaborative risk-of-bias assessment tool or the Newcastle-Ottawa Scale(NOS). RESULTS: Sixteen studies were included in this meta-analysis (11 randomized controlled studies and 5 cohort studies). Primary outcomes: Knee Society score (KSS, MD = 8.36, 95% Cl: 0.83-15.90) and combined KSS (MD = 15.24, 95% CI: 5.41-25.07) were higher in KA-TKA than in MA-TKA, and other functional scores were not statistically significant in KA-TKA and MA-TKA, including knee injury and osteoarthritis outcome score (KOOS), Oxford knee score (OKS), Knee Function score (KFS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes: KA-TKA resulted in smaller medial proximal tibial angle (MPTA) and lateral distal femoral angle (LDFA) compared to MA-TKA. For other outcome measures, KA-TKA showed similar results compared to MA-TKA, including hip-knee-ankle (HKA) angle, extension/flexion angle, tibial component slope angle, joint line orientation angle (JLOA), the operation time, the length of hospital stay and ligament release rate. CONCLUSIONS: In our analysis results, patients undergoing KA-TKA benefit as much as patients undergoing MA-TKA. KA may be a viable reference in total knee replacement.

Application of CT Scan in Diagnosis of Iliac-Femoral Vein Thrombosis after Hip Replacement.

Based on the knowledge of the previous film, the CT scan was used to diagnose the disease of women and men after the diagnosis of atherosclerosis by scanning the CT microscope. This article first examines the existing medical procedures in China, highlighting the advantages and disadvantages of various systems in terms of usability and user experience. Combined with the actual needs of hospitals, this paper developed a set of preoperative intelligent measurement system (MIPS) based on pattern recognition for total skeletal joint replacement. It is beneficial for doctors to better observe the lesions of patients before surgery and carry out necessary operations in the PATIENT DR film. In the process, the model is used to identify the patient, and the patient is given a fake score based on the characteristics of the DR film. In nonsymptomatic patients, 13.5% had muscle contraction > 50%, 2.0% had muscle contraction 70%, and the mean pelvic area was 23.48%. The left ventricular muscle has a 45.0% contraction rate, the left ventricle has a 70% contraction, and the median contraction rate is 47.58%. The right muscle, which is inserted between the right artery and the inner lymphatic artery, is the most common type of compression of the right muscle, accounting for 59.26%. In terms of the mean muscle contraction rate on the right side, patients with DVT with right muscles were higher than patients with DVT with left ventricles (48.54% to 22.29%, P < 0.001). The mean incidence of left ventricular DVT patients was higher than that of right ventricular DVT patients (71.88% versus 45.83% P < 0.0011).

Postoperative survival analysis of hepatocellular carcinoma patients with liver cirrhosis based on propensity score matching.

OBJECTIVE: Most hepatocellular carcinoma (HCC) patients in China have some degree of liver cirrhosis. The effect of cirrhosis on the long-term prognosis of HCC patients after hepatectomy is still unclear. This study aimed to investigate the effect of liver cirrhosis on the prognosis of HCC patients after hepatectomy. METHODS: Data from patients who underwent hepatectomy and had pathologically confirmed HCC were retrospectively collected. The patients' clinical pathological data were recorded. Propensity score matching (PSM) was used to eliminate the influence of potential confounding factors. The Kaplan-Meier method was used to calculate the recurrence-free survival (RFS) and overall survival (OS) rates, and Cox regression analysis was used to screen for independent risk factors affecting OS and RFS. RESULTS: A total of 1381 HCC patients who were initially treated with hepatectomy were included, including 797 patients with liver cirrhosis. The RFS and OS rates in the group with cirrhosis were significantly lower than those in the group without cirrhosis (after PSM, RFS: P < 0.001; OS: P = 0.001). Subgroup analysis showed that among patients with Barcelona Clinic Liver Cancer (BCLC) stage 0-B disease, RFS and OS were significantly lower in those with cirrhosis than in those without cirrhosis (both P < 0.05); while in patients with stage C disease, there was no significant difference between those with and without cirrhosis. In the group with cirrhosis, alpha-fetoprotein (AFP) > 400, intraoperative blood loss, tumor diameter > 5 cm, satellite lesions, and large vessel invasion were independent risk factors for RFS, while albumin-bilirubin (ALBI) grade, neutrophil-to-lymphocyte ratio (NLR), tumor diameter > 5 cm, satellite lesions, microvascular invasion, and macrovascular invasion were independent risk factors for OS. CONCLUSION: HCC with liver cirrhosis has specific characteristics. Compared with patients without cirrhosis, patients with cirrhosis have worse long-term survival after surgery. In addition, the independent risk factors for RFS and OS are different between patients with cirrhosis and without cirrhosis; liver cirrhosis is an independent risk factor for the long-term prognosis of HCC patients, especially patients with BCLC stage 0-B disease after hepatectomy.

The association between changes in multifidus muscle morphology and back pain scores following discectomy surgery for lumbar disc herniation: a systematic review and meta-analysis.

PURPOSE: To evaluate the impact of discectomy on back muscles (e.g. multifidus muscle (MM)) morphology in patients with lumbar disc herniation (LDH) following discectomy surgery, address the association of back muscles morphology with pain score preoperatively and post-operatively, and investigate the relationships between the changes from pre- to post-operative back muscles measurements and pain score (primary outcome) and disability score (secondary outcome) change following discectomy if any. METHODS: We searched three online databases for randomized controlled trials (RCTs) and observational studies. In LDH patients, eligible for discectomy surgery, pre- and post-operative and the changes from pre- to post-operative of back and/or leg pain with Visual Analogue Scale (VAS) and multifidus muscle morphology, were considered as primary outcomes. Cochrane Risk-of-Bias 2 tool and Newcastle-Ottawa Scale (NOS) were used to assess the methodological quality of RCTs and observational studies, respectively. Standardize mean difference (SMD) with 95% confidence intervals (CI) was evaluated. A meta-regression analysis was conducted. GRADE approach was used to summarize the strength of evidence. RESULTS: One RCT and five observational studies were included in the analysis of 489 patients with LDH undergoing discectomy surgery. The mean overall follow-up was 64.9 weeks (6 to 148.7 weeks). There was a significant negative relationship between the change from pre- to post-operative cross-sectional area (CSA) in MM and change in VAS back pain [regression coefficient = -0.01, (95% CI = -0.02, -0.01), p = 0.044] after discectomy surgery. No significant relationship between preoperative CSA in MM and preoperative/post-operative clinical (any of the follow-up periods) scores could be established. CONCLUSION: The results of this study found very low-quality grade evidence for an association between higher reduction of CSA in MM and less reductions of back pain scores following discectomy surgery for patients with LDH. Due to the heterogeneity and methodological limitations, further studies will improve understanding and aid preoperative counselling.

PMEPA1 interference activates PTEN/PI3K/AKT, thereby inhibiting the proliferation, invasion and migration of pancreatic cancer cells and enhancing the sensitivity to gemcitabine and cisplatin.

To explore the biological activity of transmembrane prostateandrogen induced RNA (PMEPA1) in human pancreatic cancer (hPAC) cells and its drug sensitivity to gemcitabine (GEM) and cisplatin (DDP). Gene Expression Profiling Interactive Analysis (GEPIA) and Cancer Cell Line Encyclopedia (CCLE) were consulted to indicate the expression of PMEPA1 in hPAC tissues and cells. Quantitative real-time PCR (RT-qPCR) and western blot were performed to verify the indication. RT-qPCR and western blot also detected the expressions of PTEN/PI3K/AKT before and after transfection of PMEPA1 siRNA plasmids. Cell counting Kit-8 (CCK-8) and EdU staining were performed to examine cell proliferation before and after transfection of phosphatase and tensin homologue delet2ed on chromosome ten (PTEN) siRNA plasmids. Transwell and wound healing detected the invasion and migration of hPAC cells. The expressions of MMP-2 and MMP-9 were detected by western blot. After GEM or DDP treatment, cell viability was observed by commercial kits and cell apoptosis by flow cytometry. GEPIA and CCLE predicted increased expression of PMEPA1 in hPAC tissues and cells, which was confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot. PMEPA1 was also shown to be associated with disease-free survival. Transfection of PMEPA1 siRNA plasmids affected the expressions of PTEN/PI3K/AKT. PMEPA1 interference inhibited the proliferation, invasion and migration of hPAC cells. Furthermore, PMEPA1 interference also enhanced the sensitivity of hPAC cells to GEM and DDP via PTEN interference. PMEPA1 interference inhibits the proliferation, invasion and migration of pancreatic cancer cells and enhances the sensitivity to GEM and cisplatin by activating PTEN/PI3K/AKT signaling.

Role of long intergenic non-protein coding RNA 00152 in pancreatic cancer glycolysis via the manipulation of the microRNA-185-5p/Krüppel-like factor 7 axis.

The current study set out to investigate the role of long intergenic non-protein coding RNA (LINC) 00152 in pancreatic cancer (PC) cell glycolysis with the microRNA (miR)-185-5p/Krüppel-like factor 7 (KLF7) axis. Firstly, PC tissues and cells as well as the control ones were collected from 53 PC patients, and assessed for LINC00152 expression patterns. Besides, PC cells with the most differentially expressed LINC00152 were selected for further experiments. When LINC00152 was silenced or overexpressed, PC cell glucose consumption, lactic acid production, adenosine triphosphate and levels of glycolysis-associated enzymes were detected. In addition, the binding relation between LINC00152 and miR-185-5p as well as the target relation between miR-185-5p and KLF7 was clarified and validated. Additionally, xenograft transplantation was performed to confirm the in vitro experiments. It was found that LINC00152 was over-expressed in PC, and it predicted a poor prognosis. Besides, LINC00152 knockdown inhibited PC cell glycolysis. Moreover, LINC00152 could specifically targeted miR-185-5p. Meanwhile, LINC00152 exhaustion blocked PC cell glycolysis through the up-regulation of miR-185-5p. Lastly, LINC00152 inhibition targeted miR-185-5p to quench KLF7, therefore suppressing PC cell tumorigenesis and glycolysis. Collectively, our findings indicated that silencing LINC00152 restricted PC cell glycolysis via promoting miR-185-5p and reducing KLF7.

A Meta-Analysis of Randomized Controlled Trials Concerning the Efficacy of Transversus Abdominis Plane Block for Pain Control After Laparoscopic Cholecystectomy.

Background and Purpose: Transverse abdominis plane (TAP) block has been suggested to reduce post-operative pain after laparoscopic cholecystectomy (LC). However, the literature is divided on whether ultrasound (USG)-guided TAP block is effective for pain control after LC. The present meta-analysis therefore evaluated the efficacy of USG-guided TAP block vs. controls and port site infiltration for pain control after LC. Methods: A comprehensive literature search of online academic databases was performed for published randomized controlled trials (RCTs) for studies published to January 31, 2021. The primary outcome analyzed was post-operative pain score at 0, 6, 12, and 24 h post-surgery, both during rest and while coughing. Secondary outcomes included morphine consumption and post-operative nausea and vomiting (PONV) incidence. Results: A total of 23 studies with data on 1,450 LC patients were included in our meta-analysis. A reduction in pain intensity at certain post-operative timepoints was observed for USG-guided TAP block patients compared to control group patients. No reduction in pain intensity was observed for patients receiving USG-guided TAP block patients vs. conventional Port site infiltration. Conclusion: This meta-analysis concludes that TAP block is more effective than a conventional pain control, but not significatively different from another local incisional pain control that is port site infiltration. Additional prospective randomized controlled trials are required to further validate our findings.

MicroRNA-487a-3p inhibits the growth and invasiveness of oral squamous cell carcinoma by targeting PPM1A.

Oral squamous cell carcinoma (OSCC) forms the majority of the entire cancerous tumors which occur in the mouth. Current treatment advances, such as surgical resection, chemotherapy, and radiotherapy, have significantly helped reduce OSCC. However, the overall patient survival rate remains relatively low. MiRNAs, a non-coding RNA group, are essential for multiple biological functions, which are essential for the progression of cancer, including survival of the cell, migration, multiplication, differentiation, and apoptosis. The study aimed to explore the existing association between miR-487a-3p and PPM1A and elucidating their role in modulation of proliferation in OSCC cell lines. In this study, we used CAL-27 and TCA-8113 OSCC cell lines and human samples to validate our results. The manifestation of miR-487a-3p and PPM1A was checked using quantitative real-time PCR. The miR-487a-3p and PPM1A binding was investigated through western blot assay and dual-luciferase reporter gene. Functional experiments, including colony formation, CCK-8, and transwell experimentations, were undertaken to validate cells' growth and invasion activities. According to the results, the expression of miR-487a-3p is regulated in the OSCC cell lines compared to normal cells. Moreover, the mimicking of miR-487a-3p significantly reduces the OSCC cell growth and invasion, and PPM1A overexpression exerts oncogenic effects and hinders the anti-oncogenic effects of miR-487a-3p. In conclusion, the study demonstrated that miR-487a-3p might act as a tumor suppressor by inhibiting the growth and invasion of OSCC via regulating PPM1A expression.

Platelet-Derived Growth Factor Stimulated Migration of Bone Marrow Mesenchymal Stem Cells into an Injectable Gelatin-Hydroxyphenyl Propionic Acid Matrix.

Bone marrow mesenchymal stem cells (bMSCs) are responsible in the repair of injured tissue through differentiation into multiple cell types and secretion of paracrine factors, and thus have a broad application profile in tissue engineering/regenerative medicine, especially for the musculoskeletal system. The lesion due to injury or disease may be a closed irregular-shaped cavity deep within tissue necessitating an injectable biomaterial permissive of host (endogenous) cell migration, proliferation and differentiation. Gelatin-hydroxyphenyl propionic acid (Gtn-HPA) is a natural biopolymer hydrogel which is covalently cross-linked by horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) in situ and can be delivered to the lesion by needle injection. Growth factors and cytokines can be directly incorporated into the gel or into nano- and micro-particles, which can be employed for sustained release of biomolecules while maintaining their bioactivity. In this study, we selected polyelectrolyte complex nanoparticles (PCNs) prepared with dextran sulfate and chitosan as the carrier for platelet-derived growth factor (PDGF)-BB and stromal cell-derived factor (SDF)-1α, which have been tested effectively in recruiting stem cells. Our in vitro results showed a high degree of viability of bMSCs through the process of Gtn-HPA covalent cross-linking gelation. The Gtn-HPA matrix was highly permissive of bMSC migration, proliferation, and differentiation. PDGF-BB (20 ng/mL) directly incorporated into the gel and, alternatively, released from PCNs stimulated bMSC migration and proliferation. There were only small differences in the results for the direct incorporation of PDGF into the gel compared with its release from PCNs, and for increased doses of the growth factor (200 ng/mL and 2 µg/mL). In contrast, SDF-1α elicited an increase in migration and proliferation only when released from PCNs; its effect on migration was notably less than PDGF-BB. The in vitro results demonstrate that PDGF-BB substantially increases migration of bMSCs into Gtn-HPA and their proliferation in the gel, and that these benefits can be derived from incorporation of a relatively low dose of the growth factor directly into the gel. These findings commend the use of Gtn-HPA/PDGF-BB as an injectable therapeutic agent to treat defects in musculoskeletal tissues.

Construction of an integrated human osteosarcoma database, HOsDb, based on literature mining, microarray analysis, and database retrieval.

BACKGROUND: Osteosarcoma (OS) is the most frequent primary malignancy of bone with a high incidence in adolescence. This study aimed to construct a publicly available, integrated database of human OS, named HOsDb. METHODS: Microarray data, current databases, and a literature search of PubMed were used to extract information relevant to human OS-related genes and their transcription factors (TFs) and single nucleotide polymorphisms (SNPs), as well as methylation sites and microRNAs (miRNAs). This information was collated for constructing the HOsDb. RESULTS: In total, we identified 7191 OS tumor-related genes, 763 OS metastasis-related genes, and 1589 OS drug-related genes, corresponding to 190,362, 21,131, and 41,135 gene-TF pairs, respectively, 3,749,490, 358,361, and 767,674 gene-miRNA pairs, respectively; and 28,386, 2532, and 3943 SNPs, respectively. Additionally, 240 OS-related miRNAs, 1695 genes with copy number variations in OS, and 18 genes with methylation sites in OS were identified. These data were collated to construct the HOsDb, which is available at www.hosdatabase.com. Users can search OS-related molecules using this database. CONCLUSION: The HOsDb provides a platform that is comprehensive, quick, and easily accessible, and it will enrich our current knowledge of OS.

Precise therapeutic effect of self-assembling gold nanocluster-PTEN complexes on an orthotropic model of liver cancer.

PURPOSE: Presently, liver cancer is still one of the malignant tumors with high mortality. As far as the treatment of liver cancer is concerned, the most effective method is still liver transplantation. But every year, many liver cancer patients die from the lack of a proper liver transplant, or from waiting for a liver transplant. Therefore, it is very important to find new and effective treatment for patients with liver cancer. METHODS: Herein, the cell model and the orthotropic liver tumor mice model have been performed to verify the results of our treatment. We found that the in situ synthesized gold nanocluster-PTEN (GNC-PTEN) complexes can effectively target and realize the fluorescence imaging of the liver tumor. RESULTS: GNC-PTEN complexes could inhibit the proliferation, invasion, and metastasis of liver cancer cells. And the results also showed that GNC-PTEN complexes could be well targeted liver tumor at 6 h and the liver tumor in mice group treated with GNC-PTEN complexes almost disappeared. CONCLUSION: This is a simply and effectively method to realize liver cancer imaging and inhibition. This may raise the possibility for the accurate image/diagnosis and simultaneously efficient treatment of liver cancer in the relevant clinic application.

Long non­coding RNA CASC2 suppresses pancreatic cancer cell growth and progression by regulating the miR­24/MUC6 axis.

Recent evidence indicates that the long non­coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is involved in tumorigenesis of several types of cancer through targeting microRNAs (miRs); however, the molecular mechanism of CASC2 in pancreatic cancer remains elusive. In the present study, the expression levels of CASC2, miR­24 and mucin 6 (MUC6) were measured in pancreatic cancer specimens and cell lines by reverse transcription­quantitative PCR. Western blotting was used to determine the protein expression levels of MUC6, Integrin ß4 (ITGB4), phosphorylated (p)­focal adhesion kinase (FAK) and several epithelial­to­mesenchymal transition markers in pancreatic cancer cells. MTT, colony formation, wound healing, Transwell and flow cytometry assays were performed to detect cell proliferation, colony formation, migration, invasion and apoptosis, respectively, in vitro. Morphological changes of pancreatic cancer cells were assessed by light microscopy. The interactions between CASC2, miR­24 and MUC6 were assessed by the dual­luciferase reporter assay. A tumor xenograft model was generated to investigate tumor growth in vivo. CASC2 and MUC6 were downregulated, and miR­24 was upregulated in pancreatic cancer specimens and cell lines. Functionally, CASC2 overexpression or miR­24 knockdown suppressed pancreatic cancer cell proliferation, colony formation, migration and invasion, and promoted apoptosis. Additionally, they altered cell­cell adhesion as demonstrated by the attenuated ITGB4, p­FAK and N­cadherin protein levels, as well as morphological changes. Mechanistically, CASC2 sponged miR­24 and activated its downstream target MUC6 to suppress pancreatic cancer growth and progression. CASC2 exerted tumor­suppressive functions in pancreatic cancer through the miR­24/MUC6 axis, which may be a promising target for pancreatic cancer therapy.

miRNA-339-5p Plays an Important Role in Invasion and Migration of Pancreatic Cancer Cells.

BACKGROUND This study aimed to investigate the role of miRNA-339-5p in pancreatic cancer cell invasion and migration. MATERIAL AND METHODS The differences between exosomal miRNAs of PANC02 and PANC02-H7 were studied by microarray analysis. We measured miRNA-339-5p expression in different groups; differences in cell invasion and migration were evaluated using the Transwell and wound healing assays and expression of relative proteins (E-cadherin, vimentin and ZNF689) was measured by WB assay. The correlation between miRNA-339-5p and ZNF689 expression was evaluated by luciferase reporter gene assay. RESULTS Compared with PANC02 exosome, microarray analysis indicated that miRNA-339-5p mRNA expression was significantly suppressed (P<0.001) in the PANC02-H7 exosome. Supplementation with miR-339-5p mimics led to a significant decrease in the invasion cell number and wound healing rate (P<0.001), with significantly enhanced E-cadherin expression and suppressed vimentin expression (P<0.001). However, transfection of a miR-339-5p inhibitor led to a significant increase in the invasion cell number and wound healing rate (P<0.001), with significantly suppressed E-cadherin expression and increased vimentin expression (P<0.001). Luciferase reporter gene assay demonstrated ZNF689 gene to be the target of miR-339-5p in the PANC02-H7 cell. With miR-339-5p and ZNF689 transfection, the invasion cell number and wound healing rate were significantly increased compared with those in the miR-339-5p group (P<0.001), with significantly increased expression of ZNF689 and vimentin and suppressed E-cadherin expression (P<0.001). CONCLUSIONS miR-339-5p suppresses the invasion and migration of pancreatic cancer cells via direct regulation of ZNF689 in vitro.

In situ biosynthesized gold nanoclusters inhibiting cancer development via the PI3K-AKT signaling pathway.

Nanomaterials have made great breakthroughs in drug delivery. However, in previous studies, nanomaterials have been mostly used as vehicles to transport drugs into tumors. Herein, we first found that the in situ biosynthesized gold nanoparticles (Au NCs) can inhibit cancer development via the inhibition of some signaling pathways. Classical cell phenotypic assay tests and orthotropic liver tumor model both showed that the in situ biosynthesized Au NCs could inhibit tumor development. With the help of the RNA-seq analysis, we found that the in situ biosynthesized Au NCs could significantly inhibit the PI3K-AKT signaling pathway, thus effectively impeding tumor development. This facile and effective tumor targeting theranostics in vivo can effectively cure cancers in future clinical applications.