Runx2 activates hepatic stellate cells to promote liver fibrosis via transcriptionally regulating Itgav expression.

BACKGROUNDS AND AIMS: As a central event during liver fibrosis, hepatic stellate cells (HSC) have been thought to be a potential therapeutic target for liver fibrosis. Previous studies have shown that runt-related transcription factor 2 (Runx2) is associated with the development of non-alcoholic fatty liver disease, while its specific role in HSC activation and hepatic fibrosis remains elusive. APPROACH AND RESULTS: In this study, we found that Runx2 expression was significantly upregulated in human liver fibrosis with different aetiologies. Runx2 expression was also gradually elevated in mouse liver during fibrosis, and Runx2 was mainly expressed in the activated HSC. Knockdown of Runx2 in HSC markedly alleviated CCl4 -induced, 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced or methionine-choline deficient (MCD)-induced liver fibrosis, while hepatic overexpression of Runx2 via HBAAV-Runx2 or VA-Lip-Runx2 injection exacerbated CCl4 -induced liver fibrosis. In vitro analysis demonstrated that Runx2 promoted HSC activation and proliferation, whereas Runx2 knockdown in HSC suppressed these effects. RNA-seq and Runx2 ChIP-seq analysis demonstrated that Runx2 could promote integrin alpha-V (Itgav) expression by binding to its promoter. Blockade of Itgav attenuated Runx2-induced HSC activation and liver fibrosis. Additionally, we found that cytokines (TGF-ß1, PDGF, EGF) promote the expression and nuclear translocation of Runx2 through protein kinase A (PKA) in HSC. CONCLUSIONS: Runx2 is critical for HSC activation via transcriptionally regulating Itgav expression during liver fibrosis, and may be a promising therapeutic target for liver fibrosis.

T-cell exhaustion signatures characterize the immune landscape and predict HCC prognosis via integrating single-cell RNA-seq and bulk RNA-sequencing.

Background: Hepatocellular carcinoma (HCC), the third most prevalent cause of cancer-related death, is a frequent primary liver cancer with a high rate of morbidity and mortality. T-cell depletion (TEX) is a progressive decline in T-cell function due to continuous stimulation of the TCR in the presence of sustained antigen exposure. Numerous studies have shown that TEX plays an essential role in the antitumor immune process and is significantly associated with patient prognosis. Hence, it is important to gain insight into the potential role of T cell depletion in the tumor microenvironment. The purpose of this study was to develop a trustworthy TEX-based signature using single-cell RNA-seq (scRNA-seq) and high-throughput RNA sequencing, opening up new avenues for evaluating the prognosis and immunotherapeutic response of HCC patients. Methods: The International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases were used to download RNA-seq information for HCC patients. The 10x scRNA-seq. data of HCC were downloaded from GSE166635, and UMAP was used for clustering descending, and subgroup identification. TEX-related genes were identified by gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). Afterward, we established a prognostic TEX signature using LASSO-Cox analysis. External validation was performed in the ICGC cohort. Immunotherapy response was assessed by the IMvigor210, GSE78220, GSE79671, and GSE91061cohorts. In addition, differences in mutational landscape and chemotherapy sensitivity between different risk groups were investigated. Finally, the differential expression of TEX genes was verified by qRT-PCR. Result: 11 TEX genes were thought to be highly predictive of the prognosis of HCC and substantially related to HCC prognosis. Patients in the low-risk group had a greater overall survival rate than those in the high-risk group, according to multivariate analysis, which also revealed that the model was an independent predictor of HCC. The predictive efficacy of columnar maps created from clinical features and risk scores was strong. Conclusion: TEX signature and column line plots showed good predictive performance, providing a new perspective for assessing pre-immune efficacy, which will be useful for future precision immuno-oncology studies.

CYP2E1-dependent upregulation of SIRT7 is response to alcohol mediated metastasis in hepatocellular carcinoma.

Long-term alcohol use is a confirmed risk factor of liver cancer tumorigenesis and metastasis. Multiple mechanisms responsible for alcohol related tumorigenesis have been proposed, including toxic reactive metabolite production, oxidative stress and fat accumulation. However, mechanisms underlying alcohol-mediated liver cancer metastasis remain largely unknown. We have previously demonstrated that SIRT7 regulates chemosensitivity by altering a p53-dependent pathway in human HCC. In the current study, we further revealed that SIRT7 is a critical factor in promoting liver cancer metastasis. SIRT7 expression is associated with disease stage and high SIRT7 predicts worse overall and disease-free survival. Overexpression of SIRT7 promotes HCC cell migration and EMT while knockdown of SIRT7 showed opposite effects. Mechanistically, we found that SIRT7 suppresses E-Cadherin expression through FOXO3-dependent promoter binding and H3K18 deacetylation. Knockdown of FOXO3 abolished the suppressive effect of SIRT7 on E-cadherin transcription. More importantly, we identified that alcohol treatment upregulates SIRT7 and suppresses E-cadherin expression via a CYP2E/ROS axis in hepatocytes both in vitro and in vivo. Antioxidant treatment in primary hepatocyte or CYP2E1-/- mice fed with alcohol impaired those effects. Reducing SIRT7 activity completely abolished alcohol-mediated promotion of liver cancer metastasis in vivo. Taken together, our data reveal that SIRT7 is a pivotal regulator of alcohol-mediated HCC metastasis.

Causal roles of circulating adiponectin in osteoporosis and cancers.

Circulating adiponectin has some association with the risk of osteoporosis and cancers, but their causal relationships remains elusive. Mendelian randomization (MR) study was used to explore the causal roles of circulating adiponectin in osteoporosis and cancers by using genome-wide association studies (GWASs) associated with circulating adiponectin, osteoporosis and cancers. Fifteen single nucleotide polymorphisms (SNPs) were used as instrumental variables for circulating adiponectin. Genetic predisposition to high circulating adiponectin was strongly associated with low femoral neck bone mineral density (FN-BMD, beta-estimate: -0.015, 95% CI: -0.023 to -0.006, SE: 0.004, P-value = 0.001), low forearm BMD (FA-BMD, beta-estimate: -0.027, 95% CI: -0.050 to -0.004, SE: 0.012, P-value = 0.023) and increased risk of breast cancer (beta-estimate: 0.011, 95% CI: 0.001 to 0.022, SE: 0.005, P-value = 0.031). There was limited evidence of the associations between circulating adiponectin and other outcomes (i.e. lumbar spine BMD [LS-BMD], colorectal cancer, liver cancer, lung cancer, bone cancer and prostate cancer). This study provides robust evidence that high circulating adiponectin is causally associated with low FN-BMD, low FA-BMD and increased risk of breast cancer, which may provide new insight to prevent and treat osteoporosis and breast cancer.

Effect of Surgical Timing on the Refracture Rate after Percutaneous Vertebroplasty: A Retrospective Analysis of at Least 4-Year Follow-Up.

INTRODUCTION: The effect of surgical timing on vertebral refracture rate and mortality remains elusive after percutaneous kyphoplasty (PKP) or percutaneous vertebroplasty (PVP), and we aim to assess the impact of surgical timing on vertebral refracture rate and mortality in patients undergoing percutaneous vertebroplasty. METHODS: We did a retrospective cohort study of patients who underwent PKP or PVP because of osteoporotic vertebral compression fracture (OVCF) between April 1, 2014 and March 31, 2016. The primary outcome measure was the incidence of vertebral refracture. Secondary outcomes included the mortality and chronic back pain. RESULTS: The rate of vertebral refracture was significantly lower in early surgical timing group than that in late surgical timing group (HR 2.415, 95% CI 1.318-4.427; P = 0.004). We found that the bone mineral density (BMD) was only the risk factor to increase the vertebral refracture rate after vertebroplasty (P = 0.001). In addition, there was similar mortality between the two groups (15.7% in early surgical timing group versus 10% in late surgical timing group). Male patients (27.3%, 12/44) had higher mortality compared to female patients (10.6%, 20/189), while the mortality was higher in patients with cerebral infarction (25%, 3/12) than those without cerebral infarction (12.1%, 17/140). CONCLUSIONS: Surgical timing significantly affects the vertebral refracture rate after PKP or PVP, which is also influenced by BMD. The mortality after the surgery is not affected by the surgical timing, but gender and cerebral infarction may be the risk factors of mortality.

The genomic distribution map of human papillomavirus in Western China.

Human papillomavirus (HPV) has been confirmed as the causative agent for cervical cancer. In this study, a total of 301 880 women were recruited from four different regions of Western China, with 301 880 exfoliated cervical cell samples collected from women for DNA isolation and purification. The HPV genotype was tested by polymerase chain reaction. The overall HPV prevalence rate, high-risk (HR) HPV infection rate, low-risk (LR) HPV infection rate and mixed HPV infection rate was 18.24%, 79.14%, 12.56% and 8.30%, respectively. The four most common HR HPV subtypes were HPV-52, 16, 58 and 53, which accounted for 20.49%, 19.93%, 14.54% and 10.01%, respectively. In LR HPV genotype, HPV-6 ranked the highest (28.17%), followed by HPV-81 (9.09%) and HPV-11 (3.78%). HPV genotype subgroup analysis also showed that single-type infection was the most common (77.26%) among HPV-positive individuals. Among multi-infection genotypes, double infection was the most common with frequencies of 76.04%. The overall prevalence of HPV is high in Western China, whose distribution demonstrates different patterns across different ages and regions. Viral genotypes HPV 53, 6 were frequently detected in this population, which is worth of significant clinical attention.

Addition of Celebrex and Pregabalin to Ropivacaine for Posterior Spinal Surgery: A Randomized, Double-Blinded, Placebo-Controlled Trial.

BACKGROUND: Serious pain commonly occurs after posterior spinal surgery. This study aims to evaluate the effect of preemptive and multimodal analgesia using celebrex, pregabalin and ropivacaine on pain control after this surgery. METHODS: Ninety-three patients undergoing posterior spinal surgery were enrolled in this prospective, randomized, double-blind, placebo-controlled clinical trial. All patients were treated with patient- controlled analgesia (PCA, intravenous tramadol hydrochloride and flurbiprofen) as required. They were randomized to combination analgesia intervention (oral celebrex, pregabalin and subcutaneous infiltration of ropivacaine), ropivacaine intervention (only subcutaneous infiltration of ropivacaine), and control intervention (placebo). We compared postoperative visual analog scale (VAS) scores and PCA dose among the three groups. RESULTS: The VAS scores were significantly lower in the combination analgesia group than in the control group at 0 h, 2 h, 12 h, 24 h, 3 d, 5 d, 7 d and 14 d after posterior spinal surgery, while combination analgesia was also superior to ropivacaine in terms of VAS scores at 24 h and 14 d postoperatively. The combination analgesia group was also associated with significantly reduced PCA consumption compared with the control group, but there was no statistical difference in PCA consumption between the ropivacaine group and control group. CONCLUSION: Combination analgesia using celebrex, pregabalin and ropivacaine is effective and safe to alleviate pain after posterior spinal surgery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry No. ChiCTR2000031236.

Comprehensive evaluation of risk factors for lymph node metastasis in patients with papillary thyroid carcinoma.

With the increasing incidence of papillary thyroid cancer (PTC), it is important to risk-stratify patients who may have a more aggressive tumor biology. The present study aimed to evaluate the risk factors for lymph node metastasis (LNM) in patients with PTC, which may provide a significant reference for clinical diagnosis and treatment. In total, 1,045 patients with PTC [313 with PT microcarcinoma (PTMC) and 732 with non-PTMC] between August 2016 and August 2019 were investigated. The B-type Raf kinase (BRAF) V600E mutation was tested in all samples. The clinical data (sex, age, tumor location, sample type and pathological features) were retrospectively analyzed. Logistic regression analysis was performed to evaluate independent risk factors for LNM. A total of 181/313 (57.8%) PTMC cases and 145/732 (19.8%) non-PTMC cases had a BRAF V600E mutation. In the PTMC cases, significant differences in sex and sample type were identified (BRAF V600E mutation vs. wild-type). In the non-PTMC cases, significant differences in sex and age were identified (BRAF V600E mutation vs. wild-type). Female sex and tumor diameter ≤1 cm were significant independent predictors of LNM in PTC. In PTMC, female sex was a significant independent predictor of LNM. A bilateral tumor was an independent protective factor for LNM in PTC, PTMC and non-PTMC. The BRAF V600E mutation rate of ultrasound-guided fine-needle aspiration cytology was higher compared with FFPE in PTMC (P=0.018). In contrast to previous studies, the results of the present study suggested that being female and having a tumor of diameter ≤1 cm were risk factors for LNM, and that the BRAF wild-type of PTMC may be more aggressive than other types. Notably, the position of the tumor in the bilateral thyroid was also an independent protective factor for LNM. Therefore, ultrasound-guided fine-needle aspiration should be recommended for gene analysis (BRAF V600E) in PTMC. In addition, clinicians should consider an individualized treatment according to gene mutations, sex, age, tumor size and the location of the tumor, in order to achieve an improved therapeutic efficacy.

Tranexamic Acid for Blood Loss after Transforaminal Posterior Lumbar Interbody Fusion Surgery: A Double-Blind, Placebo-Controlled, Randomized Study.

BACKGROUND: Transforaminal lumbar interbody fusion (TLIF) may result in significant blood loss and an increase in blood transfusion. Though tranexamic acid (TXA) is widely studied for the hemostasis of arthroplasty, there is little information on the use of TXA for TLIF surgery. METHODS: This prospective randomized, double-blind, placebo-controlled trial was conducted to study the influence of TXA (intravenous bolus of 10 mg/kg 15 minutes before skin incision followed by intravenous infusion of 6-8 mg/kg/h up to a total dose of 15 mg/kg during the surgery) on the blood loss and Enhanced Recovery After Surgery (ERAS) after TLIF surgery. 40 patients were randomized into two groups: TXA group (tranexamic acid) and control group (placebo). Baseline characteristics were comparable between the TXA group and the control group before the surgery. Outcomes assessed included blood loss, total postoperative drainage, time for drainage removal, time to ambulation, hospital stay after surgery, postoperative hemoglobin (Hb) one day after surgery, and adverse events. RESULTS: Compared to patients in the control group after TLIF surgery, patients in the TXA group have significantly reduced intraoperative hemorrhage and time to ambulation after surgery but show similar hospital stay, postoperative drainage, time for drainage removal, postoperative Hb one day after surgery, and adverse events. CONCLUSIONS: TXA shows important ability in controlling blood loss and promoting the ERAS after TLIF surgery.

Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: observational and Mendelian randomisation study.

OBJECTIVES AND METHODS: With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them. RESULTS: Lower eBMD were observed in patients with PsA than in controls in both model0 (ß-coefficient=-0.014, p=0.0006) and model1 (ß-coefficient=-0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (ß-coefficient=-0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture. CONCLUSIONS: The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.

Effect and mechanism of ginsenoside Rg1-regulating hepatic steatosis in HepG2 cells induced by free fatty acid.

Ginsenoside Rg1 (G-Rg1) is a bioactive phytochemical that has been found to be beneficial for the treatment of several diseases including nonalcoholic fatty liver disease (NAFLD). But there is a lack of literature reporting the effect of G-Rg1 on lipid metabolism balance in NAFLD. We investigated the effect and mechanism of G-Rg1 on lipid metabolism in vitro. We found that G-Rg1 decreased the levels of TG, TC, and MDA, and increased activity of SOD. Results of RT-PCR and western blotting showed that supplementation with G-Rg1 downregulated the expression of PPAR γ, FABP1, FATP2/5, CD36, SREBP1 c, and FASN, while the expression of PPAR ɑ, CPT1, ACOX1, MTTP, and ApoB100 was upregulated, after induction by a free fatty acid. Taken together, we conclude that G-Rg1 inhibits lipid synthesis and lipid uptake, and enhances lipid oxidation and lipid export to reduce hepatic steatosis of HepG2 cells by regulating PPAR ɑ and PPAR γ expression.

Risk factors for the exacerbation of patients with 2019 Novel Coronavirus: A meta-analysis.

Many studies have reported the risk factors for exacerbations in patients with 2019 novel coronavirus (2019-nCoV). This study aims to perform the meta-analysis of risk factors for the exacerbation of the novel coronavirus-infected pneumonia (NCIP). PubMed, Embase and Google scholar have been searched. We included the cohort studies involving risk factors for the exacerbation of NCIP. This meta-analysis compared the risk factors of patients between intensive care (ICU) group and non-ICU group. Two cohort studies were included in this study. After comparing the patients between intensive care (ICU) group and non-ICU group, several important factors were found to significantly increase the risk of exacerbations in patients with NCIP, and they included hypertension (RR=2.34; 95% CI=1.21 to 4.51; P=0.01), cardiovascular diseases (RR=2.28; 95% CI=1.13 to 4.58; P=0.02), COPD (RR=7.65; 95% CI=1.24 to 47.13; P=0.03), dyspnea (RR=2.89; 95% CI=2.05 to 4.08; P<0.00001), myalgia or fatigue (RR=1.24; 95% CI=1.01 to 1.52; P=0.04), but several factors such as gender, Huanan Seafood Wholesale Market exposure, diabetes, chronic liver disease, malignancy, fever, cough, expectoration, headache and diarrhoea appeared to have no obvious effect on the exacerbation of pneumonia. In addition, as the exacerbation of pneumonia, some complications had the high probability to occur according to the meta-analysis of acute respiratory distress syndrome (ARDS) (RR=13.95; 95% CI=6.20 to 31.41; P<0.00001), shock (RR=24.29; 95% CI=4.66 to 126.69; P=0.0002), acute cardiac injury (RR=10.32; 95% CI=3.05 to 34.96; P=0.0002) and acute kidney injury (RR=5.90; 95% CI=1.32 to 26.35; P=0.02) between two groups. Several risk factors were confirmed to significantly improve the risk of exacerbation in patients with NCIP, which was very important for the exacerbation prediction and treatment of these patients.

Ginsenoside Rg1 alleviates ANIT-induced intrahepatic cholestasis in rats via activating farnesoid X receptor and regulating transporters and metabolic enzymes.

Ginsenoside Rg1 is an active ingredient extracted from the roots of ginsenoside, and an α-naphthylisothiocyanate (ANIT)-induced rat model of intrahepatic cholestasis was used to investigate the protective effect of Rg1 on cholestasis. 48 SD male rats were randomly divided into 6 groups: control group, model group, UDCA group (ursodeoxycholic acid), low-dose Rg1 group (10 mg/kg), medium-dose Rg1 group (20 mg/kg) and high-dose Rg1 group (40 mg/kg). The model group, the UDCA group and all the Rg1 group were then intragastrically administered with 80 mg/kg ANIT, and the control group were given equal volume of olive oil. Then the pathological changes in liver tissue were observed, the secretion of bile in the bile duct was measured, and the biochemical markers in serum were quantified, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyl transfer peptidase (GTP) and the content of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA). The contents of inflammatory mediators in serum were quantified, including tumor necrosis factor (TNF-α), γ-interferon (IFN-γ) and interleukin-1ß (IL-1ß). The contents of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in liver homogenate were quantified. Expression of farnesoid X receptor (FXR), transporters and metabolic enzymes in liver tissue was monitored. Rg1 treatment improved liver tissue pathological damage, promoted bile secretion and significantly reduced serum levels of the intrahepatic cholestasis markers ALT, AST, ALP, GTP, TBIL, DBIL and TBA. Rg1 increased the activity of SOD and GSH-Px in liver homogenate, while, reducing the serum levels of MDA and inflammatory mediators. Rg1 also regulated the expression of FXR, bile acid transporters and metabolic enzymes. Overall, Rg1 alleviated liver injury by improving secretion of bile and normalizing the activity of enzymes in the serum. The protective mechanism appeared to be related to the activation of FXR and regulation of liver transporters and metabolic enzymes.

Comparison of Minimally Invasive and Open Transforaminal Lumbar Interbody Fusion for Lumbar Disc Herniation: A Retrospective Cohort Study.

BACKGROUND This cohort study compared the efficacy and safety of minimally invasive versus open transforaminal lumbar interbody fusion (Mis-TLIF versus Open-TLIF) for lumbar disc herniation with radiculopathy. MATERIAL AND METHODS From July 2016 to September 2017, we recruited 37 patients suffering from lumbar disc herniation with radiculopathy. Seventeen patients underwent Mis-TLIF (Mis group) and 20 patients underwent Open-TLIF (Open group). Baseline characteristics were similar between the 2 groups before surgery. We compared postoperative clinical and radiological outcomes between the 2 groups. RESULTS Compared to patients in the Open group, patients in the Mis group has significantly less intraoperative hemorrhage, drainage fluid, time to go, and hospital stay after surgery, but had longer operation times (P<0.05). These 2 groups had similar postoperative hemoglobin reduction and drain removal time. In addition, the postoperative back and leg pain and intervertebral height reduction at 3 months after surgery in the Mis group were remarkably lower than those in the Open group. There was no significant difference in postoperative Oswestry disability index (ODI) or intervertebral height change immediately after surgery and at 1 month postoperatively between the 2 groups. CONCLUSIONS Mis-TLIF shows some benefits in lumbar disc herniation compared to Open-TLIF in terms of intraoperative hemorrhage, drainage fluid, time to go, hospital stay after surgery, and postoperative back and leg pain.

Biofunctionalized peptide nanofiber-based composite scaffolds for bone regeneration.

Bone tissue had moderate self-healing capabilities, but biomaterial scaffolds were required for the repair of some defects such as large bone defects. Peptide nanofiber scaffolds demonstrated important potential in regenerative medicine. Functional modification and controlled release of signal molecules were two significant approaches to increase the bioactivity of biofunctionalized peptide nanofiber scaffolds, but peptide scaffolds were limited by insufficient mechanical strength. Thus, it was necessary to combine peptide scaffolds with other materials including polymers, hydroxyapatite, demineralized bone matrix (DBM) and metal materials based on the requirement of different bone defects. As the development of peptide-based composite scaffolds continued to evolve, ultimate translation to the clinical environment may allow for improved therapeutic outcomes for bone repair.

Designer bFGF-incorporated d-form self-assembly peptide nanofiber scaffolds to promote bone repair.

d-Form and l-form peptide nanofiber scaffolds can spontaneously form stable ß-sheet secondary structures and nanofiber hydrogel scaffolds, and hold some promise in hemostasis and wound healing. We report here on the synthetic self-assembling peptide d-RADA16 and l-RADA16 are both found to produce stable ß-sheet secondary structure and nanofiber hydrogel scaffolds based on circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM) and rheology analysis etc. d-RADA16 hydrogel and l-RADA16 hydrogel can enhance obvious bone repair in femoral condyle defects of the Sprague-Dawley (SD) rat model compared to PBS treatment. Based on micro-computed tomography (CT), it was revealed that d-RADA16 hydrogel and l-RADA16 hydrogel were capable to obtain the extensive bone healing. Histological evaluation also found that these two hydrogels facilitate the presence of more mature bone tissue within the femoral condyle defects. Additionally, d-RADA16 hydrogel showed some potential in storing and releasing basic-fibroblast growth factor (bFGF) which was able to further promote bone regeneration based on micro-CT analysis. These results indicate that d-form peptide nanofiber hydrogel have some special capacity for bone repair.

Cripto-1 Promotes the Epithelial-Mesenchymal Transition in Esophageal Squamous Cell Carcinoma Cells.

Esophageal carcinoma is a major public health problem worldwide and one of the most aggressively malignant neoplasms. Although considerable diagnostic and therapeutic progress has been made in recent years, the prognosis of EC patients still remains dismal due to high rates of recurrence/metastasis and invasion. Previous studies have demonstrated that Epithelial mesenchymal transition (EMT) is proposed as a critical mechanism for the acquisition of malignant phenotypes by epithelial cells. Several lines of evidence have shown that Cripto-1 plays an important oncogenic role during tumorigenesis by promoting EMT. The aim of our study was to evaluate the significance of Cripto-1 which plays a role in EMT and its metastasis in esophageal carcinoma. Data of this study suggest that Cripto-1 overexpression is connected with the tumorigenesis and progression of esophageal carcinoma; shRNA might be feasible for the inhibition of the invasion and metastasis of esophageal carcinoma.

[Effect and mechanism of ginsenoside Rg1 as an alcoholic hepatitis treatment in a rat model].

OBJECTIVE: To observe the effect of Rgl treatment on prognosis of alcoholic hepatitis using a rat model. METHODS: Female Sprague-Dawley rats were radomly divided into four groups:unmodeled control, untreated model, Rgl-treated model, and dexamethasone (DXM)-treated model. The model groups were generated by intragastric injection of alcohol. The unmodeled control group was given an equal dosage of normal saline by the same route. After model establishment, the Rg1 treatment group and the DXM treatment group were administered a 120-hour treatment of Rgl or DXM; the unmodeled controls were administered normal saline on the same schedule. All rats were then fasted for 120 hours and venous blood samples were collected for detection of serum aspartate aminotransferase (AST), alanine transaminase (ALT), total bilirubin (TBil), albumin (Alb), tumor necrosis factor-alpha (TNFat) and interleukin 6 (IL-6). Markers of liver inflammation were measured by immunohistochemistry, western blotting, and real-time quantitative reverse transcription PCR. Fat and apoptosis indices were assessed by hematoxylin-eosin staining and TUNEL assay, respectively. The t-test and F test were used for statistical analyses. RESULTS: The model group showed remarkably more liver steatosis (over one-third of the tissue) than the unmodeled control group, indicating proper establishment of alcoholic liver disease in the modeled rats. The AST, ALT, TBil, and IL-6 levels were significantly higher in the untreated model group than in the Rgl-treated group and the DXM-treated group. The values were significantly different between the Rg1-treated group and the DXM-treated group:ALT, 69.19+/-8.00 U/L vs.102.88+/-5.16 U/L; TBil, 0.36+/-0.07 µmol/L vs.1.20+/-0.18 µmol/L; IL-6, 126.50+/-6.50 U/ml vs.169.19+/-7.68 U/ml; TNFa, 268.31+/-13.19 µg/L vs.318.94+/-7.87 µg/L (all P less than 0.05). Expression of caspase3 and caspase8 was significantly higher in the model group than in the Rgltreated group and the DXM-treated group (both P<0.05). The apoptosis index was significantly lower in the Rgltreated group and the DXM-treated group than in the model group (both P<0.05). The mRNA and protein expression of caspase3, caspase8 and NF-kB were significantly lower in the Rgl-treated group and the DXM-treated group than in the model group (allP less than 0.05), and the levels of all were significantly lower in the Rgl-treated group cornered to the DXM-treated group (all P<0.05). Conehision In rats with alcoholic hepatitis, Rg1 can significantly relieve pathological injury, improve liver function by blocking the apoptotic pathway, and inhibit release of inflammatory cytokines.

Ginsenosides Rg1 from Panax ginseng: A Potential Therapy for Acute Liver Failure Patients?

Acute liver failure (ALF) is a rapidly progressing critical illness with a high mortality rate. Circulating inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), play a significant role in the pathophysiology of ALF through promoting hepatocellular apoptosis. Ginsenoside Rg1, the primary active ingredient in Panax ginseng (also termed Asian or Korean ginseng), has been reported to inhibit TNF-α production and has been shown to significantly attenuate liver fibrosis development. Here, we assessed ginsenoside Rg1's potential as a therapy for ALF by investigating the effect of ginsenoside Rg1 treatment on circulating inflammatory markers, hepatocellular apoptosis, and relevant apoptotic signaling pathways in a well-established murine ALF model. We found that ginsenoside Rg1 significantly reduces liver damage in a murine ALF model through inhibiting TNF-α-induced, caspase-dependent hepatocellular apoptosis. These results support the further investigation of ginsenoside Rg1 as a therapeutic candidate for ALF.