IgG4-related sclerosing cholangitis associated with essential thrombocythemia: A case report.

BACKGROUND: The complexity of immunoglobulin G4 (IgG4)-related diseases and their potential connection to hematologic malignancies remains unclear. This article provided a review of the diagnosis and treatment of a patient with IgG4-related sclerosing cholangitis (SC) and essential thrombocythemia (ET), along with an analysis of relevant literature to enhance comprehension of this disease. CASE SUMMARY: A 56-year-old male was admitted to two hospitals with deteriorating jaundice and pruritus prior to hospitalization. Beyond our expectations, the patient was first diagnosed with IgG4-SC and ET with the Janus kinase 2 V617F mutation. Interestingly, the administration of acetate prednisone significantly resulted in improvements in both IgG4-SC and ET. Clinicians need to pay attention to immune disorders and inflammation as they contribute to the development of various disease phenotypes. CONCLUSION: When IgG4-SC is suspected without histopathological evidence, diagnostic therapy and long-term regular follow-up can lead to positive treatment outcomes. Clinicians should be mindful of the potential presence of concurrent hematologic diseases in patients with immune disorders.

[Mechanism of n-butanol extract of Pulsatilla Decoction in treating ulcerative colitis by activating BMP signaling pathway].

The study aimed to investigate the therapeutic effects of the n-butanol extract of Pulsatilla Decoction(BEPD) on ulcerative colitis(UC) via the bone morphogenetic protein(BMP) signaling pathway. C57BL/6 mice were divided into six groups: control, model, mesalazine, and BEPD low-, medium-, and high-dose groups. Except for the control group, the rest groups were treated with 3% dextran sulfate sodium(DSS) freely for seven consecutive days to establish the UC mouse model, followed by treatment with different concentrations of BEPD and mesalazine by gavage. The murine body weight and disease activity index(DAI) were recorded. After the mice were sacrificed, their colon tissues were collected for histological analysis. Alcian blue/periodic acid-Schiff(AB/PAS) staining was used to detect the number and mucus secretion status of goblet cells; immunohistochemistry was performed to measure the expression of ki67, cleaved caspase-3, mucin 2(Muc2), and matrix metalloproteinase-9(MMP9) in colon tissues; and immunofluorescence was used to analyze the expression of tight junction proteins in colon tissues, and enzyme linked immunosorbent assay(ELISA) was employed to quantify the levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1ß, and IL-6. Western blot was conducted to evaluate the expression of BMP pathway-related proteins in mouse colon tissues. Quantitative real-time PCR(qRT-PCR) was performed to measure the expression of genes related to goblet cell differentiation in mouse colon tissues. In addition, this study also examined the protective effect and underlying mechanism of BEPD-containing serum on lipopolysaccharide(LPS)-induced barrier damages in LS174T goblet cells in vitro. The results showed that BEPD significantly alleviated UC symptoms in mice, restored goblet cell diffe-rentiation function, promoted Muc2 secretion and tight junction protein expression, and suppressed inflammatory factor secretion while activating the BMP signaling pathway. Therefore, BEPD may exert its therapeutic effects on UC by activating the BMP signaling pathway, providing a new strategy for drug intervention in UC.

Successful treatment of veno-arterial extracorporeal membrane oxygenation complicated with left ventricular thrombus by intravenous thrombolysis: A case report.

BACKGROUND: Left ventricular thrombus is a rare condition, for which appropriate treatments are not extensively studied. Although it can be treated by thrombectomy, such surgery can be difficult and risky, and not every patient can tolerate the surgery. CASE SUMMARY: We report a case of a middle-aged man receiving veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for acute myocardial infarction who developed left ventricular thrombus despite systemic anticoagulation. After systemic thrombolysis with urokinase, the left ventricular thrombus disappeared, ECMO was successfully withdrawn 9 days later, and the patient recovered and was discharged from hospital. CONCLUSION: Systemic thrombolysis is a treatment option for left ventricular thrombus in addition to anticoagulation and thrombectomy.

[Mechanism of Shenling Baizhu Powder in alleviation of ulcerative colitis in mice based on high-throughput transcriptome sequencing].

High-throughput transcriptome sequencing was used to study the mechanism of Shenling Baizhu Powder(SLBZP) in the alleviation of the dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) in mice. The mouse model of DDS-induced UC was treated with SLBZP by gavage. The changes in general state, disease activity index(DAI), and colon length were observed. The hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissues of mice. Enzyme-linked immunosorbent assay(ELISA) was used to determine the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1ß, IL-6, IL-4, and IL-10 in the serum and tissues of mice. The differentially expressed genes in the control group, the model group, and the SLBZP group were analyzed by high-throughput transcriptome sequencing, and the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were conducted on the differentially expressed genes. The results showed that after intragastric administration of SLBZP, the symptoms of diarrhea and bloody stool were improved, and the disease active index(DAI) score was reduced. SLBZP effectively reduced the inflammatory cell infiltration and goblet cell loss in the colonic mucosal tissue, reduced the levels of TNF-α, IL-1ß, IL-6 in the serum and colon tissue, and increased the levels of IL-4 and IL-10 in the serum and colon tissue. There were 25 differential genes in SLBZP vs the model group, which were significantly enriched in immune response, immune system process, immunoglobulin production, and other biological processes. KEGG pathway analysis showed that the differential genes were enriched in signaling pathways such as neomycin, kanamycin, and gentamicin biosynthesis, cytokine-cytokine receptor interaction, primary immunodeficiency, and IgA synthesis of the intestinal immune network. This study shows that SLBZP may alleviate UC through immune regulation.

Exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation after traumatic brain injury.

Exosomes derived from bone marrow mesenchymal stem cells can inhibit neuroinflammation through regulating microglial phenotypes and promoting nerve injury repair. However, the underlying molecular mechanism remains unclear. In this study, we investigated the mechanism by which exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation. Our in vitro co-culture experiments showed that bone marrow mesenchymal stem cells and their exosomes promoted the polarization of activated BV2 microglia to their anti-inflammatory phenotype, inhibited the expression of proinflammatory cytokines, and increased the expression of anti-inflammatory cytokines. Our in vivo experiments showed that tail vein injection of exosomes reduced cell apoptosis in cortical tissue of mouse models of traumatic brain injury, inhibited neuroinflammation, and promoted the transformation of microglia to the anti-inflammatory phenotype. We screened some microRNAs related to neuroinflammation using microRNA sequencing and found that microRNA-181b seemed to be actively involved in the process. Finally, we regulated the expression of miR181b in the brain tissue of mouse models of traumatic brain injury using lentiviral transfection. We found that miR181b overexpression effectively reduced apoptosis and neuroinflamatory response after traumatic brain injury and promoted the transformation of microglia to the anti-inflammatory phenotype. The interleukin 10/STAT3 pathway was activated during this process. These findings suggest that the inhibitory effects of exosomes derived from bone marrow mesenchymal stem cells on neuroinflamation after traumatic brain injury may be realized by the action of miR181b on the interleukin 10/STAT3 pathway.

MTDH antisense oligonucleotides reshape the immunosuppressive tumor microenvironment to sensitize Hepatocellular Carcinoma to immune checkpoint blockade therapy.

Immune checkpoint blockade (ICB) therapy is an important treatment option for individuals with cancer, but it has certain limitations. Identifying a better target that can overcome tumor immune escape and stimulate T cell activity is critical. This research aimed to delve into the molecular mechanism underlying the immunoregulatory function of metadherin (MTDH), which is a novel and potential therapeutic target in hepatocellular cancer (HCC). A small interfering RNA library was screened using the luciferase reporter assay and PD-L1 promoter. The Cancer Genome Atlas database and HCC tissues were used to investigate the relationship between MTDH and PD-L1. The association between MTDH and ß-catenin/lymphoid enhancer binding factor (LEF-1) was discovered by co-immunoprecipitation. The chromatin immunoprecipitation assay was used to investigate the interaction of MTDH with the PD-L1 promoter when LEF-1 expression was silenced. Locked nucleic acid antisense oligonucleotides (ASOs) were used to inhibit MTDH. We utilized in vitro co-cultures and in vivo syngeneic tumor development experiments to confirm the effectiveness of MTDH ASO combined with PD-1 monoclonal antibody (mAb). MTDH was demonstrated to be a PD-L1 modulator. MTDH increased PD-L1 expression and upregulated PD-L1 transcriptional activity through ß-catenin/LEF-1 signaling. More importantly, MTDH ASO improved the anti-PD-1 response and increased cytotoxic T-cell infiltration in PD-1 mAb-treated malignancies. MTDH effectively predicts the therapeutic efficacy of ICB therapy. Our results imply that combining MTDH ASO with PD-1 mAb could be a promising therapeutic strategy for HCC. In addition, MTDH is a potential novel biomarker for predicting the effectiveness of immune checkpoint inhibitor treatment.

Effectiveness of arthroscopic management of idiopathic shoulder stiffness: A meta-analysis.

BACKGROUND: Persisting shoulder stiffness adversely affects quality of life by causing pain and motion restrictions especially in patients with diabetes. OBJECTIVE: The aim of this study was to evaluate the outcomes of arthroscopic capsular release in patients with idiopathic shoulder stiffness. METHOD: A literature search was conducted in electronic databases and studies were selected by following precise eligibility criteria. Random-effects meta-analyses were performed to estimate the changes at latest follow-up in scores of the Constant, American Shoulder and Elbow Surgeons (ASES), and University of California at Los Angelis (UCLA) scales, Visual Analogue Scale (VAS), and shoulder range of motion. RESULTS: Nineteen studies were included. The follow-up duration was 42 months [95% confidence interval (CI): 32, 51]. Improvements in scores of the Constant, ASES, UCLA scales, and VAS were 48.3 [95% CI: 38.0, 58.6], 44.6 [95% CI: 24.6, 64.6], 19.3 [95% CI: 16.6, 22.0], and -6.1 [95% CI: -6.9, -5.4] respectively (P< 0.05 all). Improvements in the shoulder range of motion were: abduction 82.0 [95% CI: 65.0, 98.9]; forward flexion 75.9 [95% CI: 59.7, 92.1]; external rotation 43.2 [95% CI: 37.5, 49.0]; and internal rotation 25.4 [95% CI: 15.2, 35.5] degrees; P< 0.05 all). CONCLUSION: Arthroscopic capsular release effectively improves shoulder function in patients with idiopathic shoulder stiffness.

Repeated postoperative adjuvant TACE after curative hepatectomy improves outcomes of patients with HCC.

BACKGROUND AND AIMS: To gain a clear picture of the influence of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on recurrence after curative resection for HCC. MATERIAL AND METHODS: According to the inclusion criteria and the exclusion criteria, the clinical data of 118 patients with HCC at Qilu Hospital, Shan Dong University between January 2011 and August 2013, who were treated by curative hepatectomy and postoperative TACE (two groups of patients received TACE once or twice, respectively) or by curative hepatectomy alone were retrospectively studied. RESULTS: The three-year survival (RFS) rate was 51.7% for the whole study population. The three-year relapse-free RFS rates were 73.0% and 55.0% for the patients who received two and one postoperative adjuvant TACE treatments, groups respectively, and 29.3% for the hepatectomy alone group. The three-year RFS of the patients who received postoperative adjuvant TACE once was significantly higher than that of the patients who received hepatectomy alone (p = .024). And the outcome of patients with two adjuvant TACE treatments was better than that of patients who received one treatment (p = .033). CONCLUSIONS: Repeated postoperative adjuvant TACE seems to be a promising treatment for HCC that might delay tumor recurrence and improve the RFS rates of patients after curative hepatectomy.

MiR-590 Suppresses Proliferation and Induces Apoptosis in Pancreatic Cancer by Targeting High Mobility Group A2.

BACKGROUND: Pancreatic ductal adenocarcinoma is a common malignancy with high morbidity. MicroRNAs have been demonstrated to be critical posttranscriptional regulators in tumorigenesis. This study aimed to investigate the effect of microRNA-590 on the proliferation and apoptosis of pancreatic ductal adenocarcinoma. MATERIAL AND METHODS: The expression of microRNA-590 and high mobility group AT-hook 2 were examined in clinical pancreatic ductal adenocarcinoma tissues. Pancreatic ductal adenocarcinoma cell line Capan-2 was employed and transfected with microRNA-590 mimics or inhibitor. The correlation between microRNA-590 and high mobility group AT-hook 2 was verified by luciferase reporter assay. Cell viability and apoptosis were detected by MTT and flow cytometry assay. The protein level of high mobility group AT-hook 2, AKT, p-AKT, mTOR, and phosphorylated mTOR were analyzed by Western blotting. RESULTS: MicroRNA-590 was found to be negatively correlated with the expression of high mobility group AT-hook 2 in pancreatic ductal adenocarcinoma tissues. Further studies identified high mobility group AT-hook 2 as a direct target of microRNA-590. Moreover, overexpression of microRNA-590 downregulated expression of high mobility group AT-hook 2, reduced cell viability, and promoted cell apoptosis, while knockdown of miR-590 led to an inverse result. MicroRNA-590 also suppressed the phosphorylation of AKT and mTOR without altering total AKT and mTOR levels. CONCLUSION: Our study indicated that microRNA-590 negatively regulates the expression of high mobility group AT-hook 2 in clinical specimens and in vitro. MicroRNA-590 can inhibit cell proliferation and induce cell apoptosis in pancreatic ductal adenocarcinoma cells. This regulatory effect of microRNA-590 may be associated with AKT signaling pathway. Therefore, microRNA-590 has the potential to be used as a biomarker for predicting the progression of pancreatic ductal adenocarcinoma.

TWIST1 transcriptionally regulates glycolytic genes to promote the Warburg metabolism in pancreatic cancer.

Reprogrammed glucose metabolism is essential for tumor initiation and development, especially for pancreatic ductal adenocarcinoma (PDAC). Most cancer cells rely on aerobic glycolysis, a phenomenon termed "the Warburg effect", to support uncontrolled proliferation and evade apoptosis. However, the direct regulators of the Warburg effect remain areas of active investigation. In this study, we found that the highly conserved transcription factor, TWIST1, is a crucial regulator of aerobic glycolysis in PDAC. Genetic silencing of TWIST1 significantly inhibited the glycolytic phenotypes of PDAC cells as revealed by reduced glucose uptake, lactate production, and extracellular acidification rate, which can be restored by re-expression of siRNA-resistant TWIST1. Moreover, tamoxifen-inducible expression of TWIST1 promoted the Warburg metabolism of PDAC cells. Mechanistically, by luciferase reporter assay and chromatin immunoprecipitation experiment, we showed that TWIST1 can directly increase the expression of several glycolytic genes, including SLC2A1, HK2, ENO1, and PKM2. Of note, the transcriptional regulation by TWIST1 was not dependent on HIF1α or c-Myc. In The Cancer Genome Atlas and Gene Expression Omnibus accession GSE15471, we confirmed that TWIST1 was closely associated with the glycolysis pathway. Collectively, our findings indicate that TWIST1 is likely to act as important regulator of the Warburg effect in PDAC.

Chronic active EBV infection associated with NK cell lymphoma and hemophagocytic lymphohistiocytosis in a 27-year-old woman: A case report.

RATIONALE: Chronic active Epstein-Barr virus infection (CAEBV) is a common infectious disease that often affects multiple organs or systems. However, it is liable to be neglected and misdiagnosed owing to its insidious onset, lack of specific findings in the early phase, and a general lack of awareness among clinicians. PATIENT CONCERNS:: a 27-year-old woman case has been described who was initially misdiagnosed as drug-induced liver injury due to onset presentation of mild splenomegaly, recurrent liver dysfunction, and disputable pathological evidence of liver biopsy. DIAGNOSES: CAEBV complicated with natural killer (NK) cell lymphoma and hemophagocytic lymphohistiocytosis (HLH) was diagnosed by in situ hybridization of liver tissue section with EBV-encoded RNA -1 probe and flow cytometry of bone marrow. INTERVENTIONS: After admission, the patient received symptomatic treatment and antiviral therapy (combination of acyclovir and foscarnet sodium) as well as adjuvant treatment (thymosin alpha 1 and methylprednisolone); later, the patient received etoposide and dexamethasone for diagnosis of EBV associated HLH. Subsequently, the disease progressed to NK cell lymphoma and the patient received the revised EPOCH chemotherapy regimen [etoposide (100 mg/d, d1-5), dexamethasone (7.5 mg/d, d1-5; 5 mg/d, d6-14), cyclophosphamide (0.8 g/d, d1-2), and pegaspargase (3750 u/d, tid, d1-2)]. OUTCOMES: Although the patient received a series of therapies and other comprehensive measures, finally she died of gastrointestinal hemorrhage and multiple organ failure. LESSONS: Liver is one of the main target organs of EBV infection. In the clinical setting of unexplained fever and liver injury, it is necessary to be aware of CAEBV, as well as its fatal complication such as EBV associated NK cell lymphoma and HLH.

Magnolol exerts anticancer activity in hepatocellular carcinoma cells through regulating endoplasmic reticulum stress-mediated apoptotic signaling.

INTRODUCTION: Magnolol (Mag), a biologically active compound isolated from the root and stem bark of Magnolia officinalis, has been reported to induce apoptosis in several cancer cell lines in vitro. In the present study, we aimed to determine the anticancer effects of Mag on hepatocellular carcinoma (HCC) cells. MATERIALS AND METHODS: The HepG2 cells were treated with varying concentrations of Mag (10, 20, and 30 µM) for 48 hours. The effects of Mag on the proliferation, migration, invasion, apoptosis and cell cycle progression of HepG2 cells were respectively detected by MTT assay, transwell assays, and flow cytometric analysis. A HepG2 cell-based tumor-bearing model was established to evaluate the effect of Mag on HCC tumor growth in vivo. The protein expression levels were determined by Western blot analysis. RESULTS: Our results showed that Mag inhibited the proliferation, migration, and invasion of HepG2 cells in vitro in a dose-dependent manner. In addition, Mag reduced the HCC tumor volume and weight in the mouse xenograft model. Subsequent studies showed that Mag induced apoptosis in HepG2 cells, accompanied by a loss in mitochondrial membrane potential, cytochrome c release, and induction of endoplasmic reticulum stress. Furthermore, inhibition of the endoplasmic reticulum stress by CHOP knockdown restored the effects of Mag in HepG2 cells. CONCLUSION: The present study highlighted the possibility of using Mag as a novel therapeutic drug for HCC treatment.

Application of pancreaticojejunostomy with one-layer suture in pancreaticoduodenectomy: A retrospective cohort study.

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most common critical complication after pancreaticoduodenectomy (PD) and a primary reason for increased mortality and morbidity after PD. To perform a safe pancreaticojejunostomy (PJ), a fast and simple technique of duct-to-mucosa PJ with one-layer suture was devised at our institution. MATERIALS AND METHODS: We conducted a retrospective analysis of 81 successive cases of PD performed at our hospital from March 2012 to August 2016. Data of perioperative parameters were collected for all PD cases. RESULTS: A total of 17 (21.0%) cases of morbidity occurred after PD, including 5 (6.1%) cases of POPF (grade A), 8 (9.8%) cases of delayed gastric emptying, 1 (1.2%) case of abdominal infection, and 3 (3.7%) cases of incision infection. The median operative time for the PJ was 7 min. No mortality or relaparotomy was observed. CONCLUSION: Our technique could significantly reduce the incidence of POPF and other complications after PD and may be a promising technique for pancreaticoenteric anastomosis.

Long non-coding RNA FEZF1-AS1 promotes cell invasion and epithelial-mesenchymal transition through JAK2/STAT3 signaling pathway in human hepatocellular carcinoma.

Long non-coding RNAs (lncRNAs) have emerged as key regulators in the development of hepatocellular carcinoma (HCC). In the present study, we explored the expression profile and biological role of lncRNA FEZF1-AS1 in HCC. We observed remarkable upregulation of FEZF1-AS1 in HCC tissues and cell lines, and high FEZF1-AS1 expression was correlated with aggressive phenotypes and poor prognosis of HCC patients. Furthermore, we found that FEZF1-AS1 knockdown markedly inhibited the proliferation of HCC cells by inducing cell cycle arrest. In addition, FEZF1-AS1 knockdown suppressed HCC tumor growth in vivo. Moreover, FEZF1-AS1 knockdown inhibited the migration and invasion of HCC cells through suppression of JAK2/STAT3 signaling-mediated epithelial-mesenchymal transition (EMT). In conclusion, the present study for the first time demonstrated that FEZF1-AS1 serves as an oncogenic lncRNA in human HCC and implicated FEZF1-AS1 as a valuable therapeutic target for HCC treatment.

Risk factors associated with the detection and missed diagnosis of colorectal flat adenoma: a Chinese multicenter observational study.

OBJECTIVES: Flat colorectal adenomas have a high risk of malignancy; however, their detection is often difficult due to their flat morphology. In this retrospective, large-scale study, we investigated the prevalence and characteristics of flat adenomas in a population in China. METHODS: We analyzed the data collected for 16951 consecutive patients who underwent colonoscopy at four participating hospitals between September 2013 and September 2015. All colonoscopies were performed without magnification. RESULTS: Among the 1,6951 patients, 2938 (17.3%) had adenoma and 796 (4.7%) had flat adenomas. The detection of flat adenoma showed a weak correlation with the detection of adenoma (r = 0.666). Multivariable logistic regression analysis revealed the following independent factors influencing the detection of flat adenomas: patient-related factors of age, presence of warning symptoms, history of adenomas and bowel preparation as well as endoscopist-related factors of endoscopist's level of proficiency, number of colonoscopy operators and withdrawal time. CONCLUSIONS: The prevalence of flat adenomas in our study on Chinese patients was consistent with that reported from other countries. Factors conducive to the detection of flat adenomas were patient age of > 60 years, warning symptoms, history of adenoma, good bowel preparation, experienced endoscopist, single-operator colonoscopy and colonoscopy withdrawal time of >6 min.

[LKB1 regulates epithelial-mesenchymal transition in Peutz-Jeghers hamartoma and intestinal epithelial cells].

OBJECTIVE: To investigate the molecular mechanism by which LKB1 regulates epithelial-mesenchymal transition (EMT) in Peutz-Jeghers hamartoma and intestinal epithelial cells. METHODS: Immunohistochemistry was used to detect gene expression of LKB1, E-cadherin, and vimentin in 20 hamartoma tissues and 10 normal intestinal tissues, and collagen fiber deposition was analyzed using Masson trichrome staining. Normal intestinal epithelial NCM460 cells were transfected with LKB1 shRNA plasmid or negative control via lentiviral vectors, and the role of LKB1 in cell polarization and migration were determined using CCK8 and Transwell assays. Western blotting, quantitative real-time PCR (qPCR) and immunofluorescence were used to assess the alterations of EMT markers in the cells with LKB1 knockdown. RESULTS: Compared with normal intestinal tissues, hamartoma polyps showed significantly decreased LKB1 and E-cadherin expressions and increased vimentin expression with increased collagen fiber deposition. The cells with LKB1 knockdown exhibited enhanced cell proliferation and migration activities (P<0.01). Western blot analysis, qPCR and immunofluorescence all detected decreased E-cadherin and increased N-cadherin, vimentin, Snail, and Slug expressions in the cells with LKB1 knockdown. CONCLUSION: s LKB1 deficiency triggers EMT in intestinal epithelial cells and Peutz-Jeghers hamartoma, suggesting that EMT can serve as the therapeutic target for treatment of Peutz-Jeghers syndrome.

MOXIBUSTION ALLEVIATES GASTRIC PRECANCEROUS LESIONS IN RATS BY PROMOTING CELL APOPTOSIS AND INHIBITING PROLIFERATION-RELATED ONCOGENES.

BACKGROUND: It is well known that gastric mucosa dysplasia and intestinal metaplasia are gastric precancerous lesions (GPL). Moxibustion treatment of Liangmen (ST21) and Zusanli (ST36) alleviated the inflammatory response and dysplasia of gastric mucosa in our previous study. The purpose of this study was to further examine the underlying mechanism of moxibustion treatment of ST21 and ST36 on GPL. MATERIALS AND METHODS: Sixty SD rats were divided into five groups and rats with GPL were treated with either moxibustion (ST), moxibustion (Sham), or vitacoenzyme. B-cell lymphoma 2 (bcl-2), tumor protein p53 (P53) and cellular Myc (C-MYC), which are related to cell apoptosis, proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), argyrophilic nucleolar organizer region proteins (Ag-NORs), which are associated with cell proliferation, and cell signaling proteins, nuclear factor kappa B (NF-κB), epidermal growth factor receptor (EGFR) and phosphorylated extracellular signal regulated kinase (p-ERK), were measured after moxibustion treatment. RESULTS: Compared with Control group, gastric mucosa in GPL group showed abnormal mucosal proliferation and pathological mitotic figure, the mRNA expression of bcl-2, P53 and C-MYC increased significantly (P < 0.01), the protein expression of PCNA, VEGF, Ag-NORs and the activity of NF-κß as well as EGFR/ERK signaling proteins also increased significantly (P < 0.01). Moxibustion treatment decreased gastric mucosal proliferation and pathological mitotic figure, down-regulated the mRNA expression of bcl-2, P53, C-MYC (P < 0.01), decreased the protein expression of PCNA, VEGF, Ag-NORs and the activity of NF-κß as well as EGFR/ERK signaling proteins significantly (P < 0.01). But moxibustion treatment of Sham didn't show the same effect on GPL. CONCLUSION: Moxibustion treatment inhibited cell apoptosis and reduced gastric mucosa dysplasia by inhibiting the expression of bcl-2, P53, C-MYC and decreased the activity of NF-κß as well as EGFR/ERK signaling proteins.

Degradable Chitosan-Collagen Composites Seeded with Cells as Tissue Engineered Heart Valves.

BACKGROUND: Degradable collagen-chitosan composite materials have been used to fabricate tissue engineered heart valves. The aims of this study were to demonstrate that the collagen-chitosan composite scaffolds are cytocompatible, and endothelial cells can be differentiated from bone marrow mesenchymal stem cells (BMSCs) when seeded onto the scaffolds. The adhesion and biological activities of the seeded cells were also investigated. METHODS: Collagen-chitosan composite material was used as the cell matrix, and smooth muscle cells, fibroblasts and BMSCs were used as seed cells. After four weeks of in vitro culture, the smooth muscle cells, fibroblasts, and BMSCs were sequentially seeded into the collagen-chitosan composite material. After four weeks in culture, the cellular density and activity were assessed on segments of the tissue engineered heart valve scaffolds to determine the cell viability and proliferation in the collagen-chitosan composite material. RESULTS: The tissue engineered heart valves stained positively for both smooth muscle actin and endothelial cell factor VIII, suggesting that the seeded cells were in fact smooth muscle cells, fibroblasts, and endothelial cells. The 6-ketone prostaglandin content, as measured by radioimmunoassay, of the collagen-chitosan cell culture fluid was higher than that of the serum-free medium (P <0.01). Light and electron microscopy showed that the seeded cells had shapes similar to the morphology of smooth muscle cells, fibroblasts, and endothelial cells. CONCLUSIONS: Endothelial cells can be differentiated from BMSCs when seeded onto the collagen-chitosan composite scaffolds. The seeded cells retained their biological activity after being cultured in vitro and seeded into the collagen-chitosan composite material.

lincRNA-p21 inhibits invasion and metastasis of hepatocellular carcinoma through Notch signaling-induced epithelial-mesenchymal transition.

AIM: Emerging evidence has showed that long non-coding RNA (lncRNA) play an important role in the occurrence and development of various cancers. In the present study, the expression level of lincRNA-p21 was investigated in hepatocellular carcinoma (HCC), and its role in invasion of HCC was also explored. METHODS: The lincRNA-p21 levels in human HCC tumor tissue and cell lines HepG2 and SMMC-7721 were determined by real-time polymerase chain reaction. Transfected HCC cells with pcDNA-lincRNA-p21 or si-lincRNA-p21 for overexpression or downregulation of lincRNA-p21, the Notch signaling and epithelial-mesenchymal transition (EMT)-related proteins and cell invasion were measured by western blot and Transwell assay, respectively. A tumor xenotransplant mouse model was also established to investigate the role of lincRNA-p21 in tumor metastasis in vivo. RESULTS: The lincRNA-p21 expression was downregulated in HCC tissue and cells. Overexpression of lincRNA-p21 inhibited Notch singling and EMT, while its downregulation led to the reverse result. The invasion of HCC cell was also inhibited by pcDNA-lincRNA-p21, and activation of Notch signaling reversed this effect. In vivo, overexpression of lincRNA-p21 decreased the tumor metastasis, as well. CONCLUSION: lincRNA-p21 was downregulated in HCC and lincRNA-p21 overexpression contributed to the inhibition of tumor invasion through mediating Notch signaling induced EMT.