Insights into the role of adipose-derived stem cells and secretome: potential biology and clinical applications in hypertrophic scarring.

Scar tissue is the inevitable result of repairing human skin after it has been subjected to external destructive stimuli. It leads to localized damage to the appearance of the skin, accompanied by symptoms such as itching and pain, which reduces the quality of life of the patient and causes serious medical burdens. With the continuous development of economy and society, there is an increasing demand for beauty. People are looking forward to a safer and more effective method to eliminate pathological scarring. In recent years, adipose-derived stem cells (ADSCs) have received increasing attention from researchers. It can effectively improve pathological scarring by mediating inflammation, regulating fibroblast proliferation and activation, and vascular reconstruction. This review focuses on the pathophysiological mechanisms of hypertrophic scarring, summarizing the therapeutic effects of in vitro, in vivo, and clinical studies on the therapeutic effects of ADSCs in the field of hypertrophic scarring prevention and treatment, the latest application techniques, such as cell-free therapies utilizing ADSCs, and discussing the advantages and limitations of ADSCs. Through this review, we hope to further understand the characterization of ADSC and clarify the effectiveness of its application in hypertrophic scarring treatment, so as to provide clinical guidance.

The Wnt/ß-catenin signaling pathway inhibits osteoporosis by regulating the expression of TERT: an in vivo and in vitro study.

Our study was performed to investigate whether the Wingless and int-1 (Wnt) signaling pathway promotes osteogenic differentiation and inhibits apoptosis in bone marrow mesenchymal stem cells (BMSCs) by regulating telomerase reverse transcriptase (TERT) expression. An in vivo model of osteoporosis (OP) in C57BL/6J mice by bilateral ovariectomy (OVX) and an in vitro model of H2O2-induced BMSCs were established separately. Western blotting was used to detect the expression of the pathway-related proteins TERT, ß-catenin, and phosphorylated-glycogen synthase kinase-3beta (p-GSK3ß)/GSK3ß, the osteogenic-related markers osteopontin (OPN), bone morphogenetic protein 2 (BMP2), and runt-related transcription factor 2 (Runx2), and the apoptosis-related indicators B-cell lymphoma-2 (Bcl-2) and BAX. Osteoblastic phenotypes were also evaluated by alkaline phosphatase (ALP) staining and serum ALP activity assays. Osteogenic differentiation phenotypes in mice were verified by H&E staining, micro-CT, and parameter analysis of the femur. Western blotting results showed that the expression of the pathway-related proteins TERT, ß-catenin, p-GSK3ß/GSK3ß was reduced in OVX mice and H2O2-induced BMSCs, accompanied by downregulated protein expression of osteogenic-related markers and antiapoptotic indicators and upregulated protein expression of apoptotic proteins compared to those in the control group. Mechanistic studies showed that the activation of Wnt signaling pathway in BMSCs promoted ß-catenin translocation to the nucleus, as verified by immunofluorescence and facilitated colocalization between ß-catenin and TERT, as verified by double-labeling immunofluorescence, thereby promoting osteogenic differentiation and reducing apoptosis. In summary, our experiments confirmed that the GSK3ß/ß-catenin/TERT pathway could regulate the osteogenic differentiation and apoptosis of BMSCs and that TERT might be a promising target for the future treatment of osteoporosis.

Study on the Swelling Characteristics of the Offshore Natural Gas Hydrate Reservoir.

The swelling characteristics of porous media in the offshore natural gas hydrate reservoir have an important effect on the stability of the reservoir. In this work, the physical property and the swelling of porous media in the offshore natural gas hydrate reservoir were measured. The results show that the swelling characteristics of the offshore natural gas hydrate reservoir are influenced by the coupling of the montmorillonite content and the salt ion concentration. The swelling rate of porous media is directly proportionate to water content and the initial porosity, and inversely proportionate to salinity. Compared with water content and salinity, the initial porosity has much obvious influence on the swelling, which the swelling strain of porous media with the initial porosity of 30% is three times more than that of montmorillonite with the initial porosity of 60%. Salt ions mainly affect the swelling of water bound by porous media. Then, the influence mechanism of the swelling characteristics of porous media on the structural characteristics of reservoir was tentatively explored. It can provide a basic date and scientific basis for furthering the mechanical characteristics of the reservoir in the hydrate exploitation in the offshore gas hydrate reservoir.

Effects of I125 seed stent implantation combined with arterial infusion chemoembolization on tumor markers, p53 expression, and prognosis in patients with cholangiocarcinoma.

Cholangiocarcinoma is a common malignant tumor. Advanced treatment is difficult and the prognosis is poor. It is of great significance to find an effective method to treat cholangiocarcinoma and improve the prognosis of patients. Therefore, 78 patients with cholangiocarcinoma treated in our hospital were divided into group A and group B according to different treatment methods. The clinical effect, bilirubin, tumor size, bile duct patency time, tumor marker level To evaluate the therapeutic effect of I125 seed stent implantation combined with arterial infusion chemoembolization in patients with cholangiocarcinoma. The results showed that I125 seed stent implantation combined with TACE in the treatment of patients with cholangiocarcinoma can play an obvious clinical effect, effectively reduce the level of tumor markers and p53, reduce tumor lesions, improve the survival rate of patients, and play an important role in tumor treatment.

A Novel Parameter for Fatigue Damage Assessment of Laser-Repaired Nickel-Based Alloy.

The fatigue damage assessment of laser-repaired components is critical to their service safety. However, since laser repairing is an advanced green remanufacturing technology, the current research on its fatigue mechanical behavior and fatigue damage evaluation methods is still immature. In addition, the relevant models used for the fatigue damage evaluation can only indicate the fatigue limit of components, which cannot describe the damage accumulation process of the components during the fatigue testing. Therefore, there is an urgent need to develop a fatigue damage evaluation method that can describe the fatigue damage accumulation and evolution to reveal the damage evolution mechanism during the fatigue test. In this study, based on the 3D-DIC technique, new damage parameters, i.e., strain average value and strain standard deviation, are proposed to quantitatively describe the damage status of the nickel-based components during the stress-based fatigue process. Then, based on the new damage parameters, a strain average value/strain standard deviation damage curve method is proposed to describe the damage status evolution of the components during the fatigue testing and evaluate its fatigue damage. For example, in the tensile fatigue test, the strain average value/strain standard deviation damage curves of the substrate component and the laser-repaired component can be divided into two damage stages. In the first damage stage, the damage increases slowly with the increase in the cycle number, whereas in the second damage stage, the damage increases rapidly with the increase in the cycle number. At this time, there is a demarcation point between the first damage stage and second damage stage in the strain average value damage curve and strain standard deviation damage curve. The cycle number of the demarcation point can be used as a reference value for the fatigue failure of the laser-repaired component. In addition, the electron backscatter diffraction (EBSD) technique was used to verify the validity of the evaluation results from the novel damage parameters.

Long non-coding RNA AFAP1-AS1 promotes thyroid cancer progression by sponging miR-204-3p and upregulating DUSP4.

Long non-coding RNA actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) shows crucial regulatory function in tumor progression. Nonetheless, the biological function and underlying mechanism of AFAP1-AS1 in the progression of thyroid cancer is still unclear. Expressions of AFAP1-AS1, miR-204-3p and DUSP4 were quantified utilizing quantitative real-time polymerase chain reaction and/or western blot. In loss-of-function and gain-of-function assays, cell proliferation, migration and invasion were appraised by CCK-8 assay, wound healing assay, Transwell migration and invasion assays, respectively. Luciferase reporter assay was employed for validating the interaction between miR-204-3p and AFAP1-AS1 or the 3'UTR of dual specificity phosphatase 4 (DUSP4). AFAP1-AS1 was highly expressed in thyroid cancer tissues and cell lines. Highly expressed AFAP1-AS1 was in association with advanced TNM stage and positive lymph node metastasis. Knockdown of AFAP1-AS1 suppressed the proliferation, migration and invasion of thyroid cancer cells, and overexpression of AFAP1-AS1 induced a reversed effect. MiR-204-3p was targetedly repressed by AFAP1-AS1, and miR-204-3p could negatively regulate DUSP4 expression. AFAP1-AS1 augmented the expression of DUSP4 via repressing miR-204-3p, and the effects of AFAP1-AS1 overexpression on thyroid cancer cells were also partly abolished by miR-204-3p restoration. In summary, AFAP1-AS1 facilitates thyroid cancer cell proliferation, migration and invasion by regulating miR-204-3p/DUSP4 axis.

A transcription factor signature predicts the survival of patients with adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine cancer that manifests as abdominal masses and excessive steroid hormone levels and is associated with poor clinical outcomes. Transcription factors (TFs) deregulation is found to be involved in adrenocortical tumorigenesis and cancer progression. This study aimed to construct a TF-based prognostic signature for the prediction of survival of ACC patients. METHODS: The gene expression profile and clinical information for ACC patients were downloaded from The Cancer Genome Atlas (TCGA, training set) and Gene Expression Omnibus (GEO, validation set) datasets after obtained 1,639 human TFs from a previously published study. The univariate Cox regression analysis was applied to identify the survival-related TFs and the LASSO Cox regression was conducted to construct the TF signature based on these survival-associated TFs candidates. Then, multivariate analysis was used to reveal the independent prognostic factors. Furthermore, Gene Set Enrichment Analysis (GSEA) was performed to analyze the significance of the TFs constituting the prognostic signature. RESULTS: LASSO Cox regression and multivariate Cox regression identified a 13-TF prognostic signature comprised of CREB3L3, NR0B1, CENPA, FOXM1, E2F2, MYBL2, HOXC11, ZIC2, ZNF282, DNMT1, TCF3, ELK4, and KLF6. The risk score based on the TF signature could classify patients into low- and high-risk groups. Kaplan-Meier analyses showed that patients in the high-risk group had significantly shorter overall survival (OS) compared to the low-risk patients. Receiver operating characteristic (ROC) curves showed that the prognostic signature predicted the OS of ACC patients with good sensitivity and specificity both in the training set (AUC > 0.9) and the validation set (AUC > 0.7). Furthermore, the TF-risk score was an independent prognostic factor. CONCLUSIONS: Taken together, we identified a 13-TF prognostic marker to predict OS in ACC patients.

A fourteen-lncRNA risk score system for prognostic prediction of patients with non-small cell lung cancer.

Growing evidence has underscored long non-coding RNAs (lncRNAs) serving as potential biomarkers for cancer prognosis. However, systematic tracking of a lncRNA signature for prognosis prediction in non-small cell lung cancer (NSCLC) has not been accomplished yet. Here, comprehensive analysis with differential gene expression analysis, univariate and multivariate Cox regression analysis based on The Cancer Genome Atlas (TCGA) database was performed to identify the lncRNA signature for prediction of the overall survival of NSCLC patients. A risk-score model based on a 14-lncRNA signature was identified, which could classify patients into high-risk and low-risk groups and show poor and improved outcomes, respectively. The receiver operating characteristic (ROC) curve revealed that the risk-score model has good performance with high AUC value. Multivariate Cox's regression model and stratified analysis indicated that the risk-score was independent of other clinicopathological prognostic factors. Furthermore, the risk-score model was competent for the prediction of metastasis-free survival in NSCLC patients. Moreover, the risk-score model was applicable for prediction of the overall survival in the other 30 caner types of TCGA. Our study highlighted the significant implications of lncRNAs as prognostic predictors in NSCLC. We hope the lncRNA signature could contribute to personalized therapy decisions in the future.

Knockdown of long noncoding RNA GAS5 protects human cardiomyocyte-like AC16 cells against high glucose-induced inflammation by inhibiting miR-21-5p-mediated TLR4/NF-κB signaling.

Diabetic cardiomyopathy (DCM) is a common cause of disability and death among diabetic patients. In this study, we aimed to identify the functional role of long noncoding RNA GAS5 in human cardiomyocyte-like AC16 cells under high glucose (HG) condition. The results showed that HG treatment induced damage in AC16 cells by decreasing cell viability and increasing cell apoptosis. We also found that HG increased GAS5 expression in AC16 cells and knockdown of GAS5 protected AC16 cells from HG-induced injury. Furthermore, we confirmed that GAS5 could competitively bind with miR-21-5p and miR-21-5p inhibition alleviated the beneficial effects of GAS5 knockdown against HG stimulation. TLR4 was identified as a target of miR-21-5p in AC16 cells, and GAS5 knockdown alleviated HG-induced inflammation partly by inhibiting miR-21-5p-mediated TLR4/NF-κB signaling. Our results suggested that GAS5/miR-21-5p axis may serve as a candidate therapeutic target for DCM.

Toxicological evaluation of z24, a novel indolin-2-ketone compound, in cultured human liver cells using toxicogenomic techniques.

The current study was designed to investigate the toxicity of 3Z-3-[((1)H-pyrrol-2-yl)-methylidene]-1-(1-piperidinylmethyl)-1, 3-2H-indol-2-one (Z24), a novel synthetic indolin-2-ketone small molecule compound, using toxicogenomic techniques (complementary DNA [cDNA] microarray). Bioinformatic analysis suggested that the main functions of genes with altered expression were consistent with liver cell regeneration, apoptosis, metabolism of energy and fat, and the death receptor (DR)-mediated apoptosis-signaling pathway. Death receptor 4, Bcl-2, Bcl-xl, caspase 3, and cytochrome C, which are involved in the DR-mediated apoptosis-signaling pathway, were altered after Z24 treatment as determined by Western blotting analysis. When hepatocarcinoma cell line (HepG2 cells) treated with Z24 at 0.248 mmol/L for 24 hours, DNA fragmentation reached a maximum, and examination of cell morphology showed typical signs of apoptosis. These results indicate that Z24 can initiate apoptosis in hepatocytes, which in turn causes hepatotoxicity. A possible toxicological mechanism is that apoptosis was induced in hepatocytes by initiating the DR-mediated signal transduction pathway. Apoptosis of hepatocytes might lead to impairment of energy and lipid metabolism and provoke hepatocyte necrosis or inflammation, resulting in hepatotoxicity.

Study of a novel indolin-2-ketone compound Z24 induced hepatotoxicity by NMR-spectroscopy-based metabonomics of rat urine, blood plasma, and liver extracts.

Antiangiogenic compound has been believed to be an ideal drug in the current cancer biological therapy, but the angiogenesis inhibitors suffer setback for unknown toxicity now. A novel synthetic indolin-s-ketone small molecular compound, 3Z-3-[((1)H-pyrrol-2-yl)-methylidene]-1-(1-piperidinylmethyl)-1,3-2H-indol-2-one (Z24) can inhibit angiogenesis in new blood vessels. The hepatotoxicity effects of Z24 oral administration (dosed at 60, 130 and 200 mg/kg) have been investigated in female Wistar rats by using metabonomic analysis of (1)H NMR spectra of urine, plasma and liver extracts, as well as by clinical chemistry analysis, liver histopathology and electron micrographs examination. The (1)H NMR spectra of the biofluids were analyzed visually and via pattern recognition by using principal component analysis. The metabonomic trajectory analysis on the time-related hepatotoxicity of Z24 was carried out based on the (1)H NMR spectra of urine samples, which were collected daily predose and postdose over an 8-day period. Urinary excretion of citrate, lactate, 2-oxo-glutarate and succinate increased following Z24 dosing. Increased plasma levels of lactate, TMAO and lipid were observed, with concomitant decrease in the level of glucose and phosphatidylcholine. Metabolic profiling on aqueous soluble extracts of liver tissues with the high dose level of Z24 showed an increase in lactate and glutamine, together with a decrease in glucose, glycogen and choline. On the other hand, studies on lipid soluble extracts of liver tissues with the high dose level of Z24 showed increased level in lipid triglycerides and decreased level in unsaturated fatty acids and phosphatidylcholine. Moreover, the most notable effect of Z24 on the metabolism was the reduction in the urinary levels of creatinine and TMAO and the increase in acetate, citrate, succinate and 2-oxo-glutamate with time dependence. The results indicate that in rats Z24 inhibits mitochondrial function through altering the energy and lipid metabolism, which results in the accumulation of free fatty acids and lactate because of the lack of aerobic respiration. These data show that the metabonomic approach represents a promising new technology for the toxicological mechanism study.