[Analysis of clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues].

Objective: To explore the clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues. Methods: A retrospective analysis was performed according to different data types. An independent sample t-test, Mann-Whitney U test, chi-square test, or Fisher's exact probability method were used. Chronic hepatitis B patients followed up for four years were collected from the follow-up case database of the Department of Infectious Diseases of Zhongshan Third Hospital from January 2009 to December 2018 and were divided into two groups, A and B, with 87 and 145 cases respectively, according to the duration of HBeAg-negativity≤ 3 and persistent positivity >3 years. Statistical analysis was conducted on the age, gender, family history, baseline, follow-up visit duration, liver function, and other data among the two patient groups. Results: There were no statistically significant differences in gender, age, family history of liver cirrhosis, family history of liver cancer, liver cirrhosis condition before treatment, fatty liver disease combined condition before treatment, baseline HBsAg, anti-HBc, alanine aminotransferase, albumin, or total bilirubin between the two groups of patients (P > 0.05). HBV DNA and HBeAg were significantly higher in group B than those in group A at baseline, with P≤0.001. Aspartate aminotransferase and γ-glutamyl transferase were significantly higher in group A than those in group B at baseline. The proportion of family history of hepatitis B was significantly higher in group B (69.0%) than that in group A (50.6%) among the two groups of patients, and the difference was statistically significant (P = 0.005). The proportion of mothers with hepatitis B was significantly higher in group B (25.5%) than in group A (11.5%), P = 0.010. During the treatment process, the HBV DNA quantification was significantly higher in group B than that in group A at 0.5 and 1 years (P≤0.002). The proportion of HBV DNA <100IU/ml was also significantly different at six months and one year (χ(2)=30.327, P < 0.001 and χ(2)=11.779, P = 0.001). The HBsAg level was higher in group B than that of group A in the second and fourth years, P < 0.05. During the entire treatment process, the HBeAg level was significantly higher in group B than that in group A (P < 0.001). A total of seven cases developed liver cirrhosis or cancer during follow-up, including three cases in group A and four cases in group B (P > 0.05). Conclusion: HBeAg-positive patients with chronic hepatitis B have persistent HBeAg positivity when treated with long-term nucleos(t)ide analogues. Accordingly, a greater proportion of this kind of patient family and mothers have a remarkable history of hepatitis B and a reduced HBV DNA relapse rate in the early stages (within a year or less).

[Multi-omics combined test performance effectiveness on opportunistic screening of high-risk liver cancer population].

Objective: To validate the performance of a multi-omics combined test for early screening of high-risk liver cancer populations. Methods: 173 high-risk patients with liver cancer were prospectively screened in a real-world setting, and 164 cases were finally enrolled. B-ultrasound, alpha-fetoprotein (AFP), and HCC screens were conducted in all patients. A multi-omics early screening test was performed for liver cancer in combination with multi-gene methylation, TP53/TERT/CTNNB1 mutations, AFP, and abnormal prothrombin (PIVKA-II). Differences in rates were compared using the chi-square test, adjusted chi-square test, or Fisher's exact probability method for count data. A non-parametric rank test (Mann-Whitney) was used to compare the differences between the two groups of data. Results: The HCCscreen detection had a sensitivity of 100% for liver cancer screening, 93.8% for liver cancer and precancerous diseases, 34.1% for positive predictive value, 99.2% for negative predictive value, and 0.89 for an area under the curve (AUC). Parallel detection of AFP, AFP+B-ultrasound, and methylation+mutation had a sensitivity/specificity and AUC of 31.3%/88.5% (AUC=0.78), 56.3%/88.2% (AUC=0.86), and 81.3%/82.4 % (AUC=0.84). At the same time, the disease severity range was significantly correlated with the methylation+mutation score, HCCscreen score, or positive detection rate (PDR). There was no significant correlation between AFP serum levels and methylation+mutation or HCCscreen scores, while there was a significant linear correlation between methylation+mutation scores and HCCscreen scores (r = 0.73, P < 0.001). Conclusion: In real-world settings, HCCscreen shows high sensitivity for screening opportunistic, high-risk liver cancer populations. Furthermore, it may efficaciously detect liver cancer and precancerous diseases, with superior performance to AFP and AFP+ultrasound. Hence, HCCscreen has the potential to become an effective screening tool that is superior to existing screening methods for high-risk liver cancer populations.

[Clinicopathological and molecular genetic characteristics of nodular fasciitis in unusual sites].

Objective: To study the clinicopathological, immunophenotypic and molecular genetic characteristics of nodular fasciitis (NF) in unusual sites. Methods: A total of 50 cases of NF diagnosed between January 2015 and January 2021 were reviewed in the Department of Pathology, Henan Provincial People's Hospital, and the clinical and pathologic data were analyzed. Among them, 14 cases from unusual sites were included in this study. Immunohistochemical (IHC) staining was used to detect the expression of related proteins, and fluorescence in situ hybridization (FISH) was used to detect the breakage of the USP6 gene. Results: There were seven males and seven females in the 14 NF respectively. The lesions were located in the extremities, perineum, breast, wrist joints, the gap between lumbar vertebra 4/5, and in eight cases there was involvement of unusual tissues (six cases in skeletal muscle, one case in nerve root, and one case was intravascular). The tumor boundary was unclear with infiltrating growth. Spindle-shaped myofibroblasts were arranged in bundles or chaotically, with mild pleomorphic, small nucleoli and various mitotic figures. The tumor stroma showed collagenization to myxoid degeneration with erythrocyte extravasation and infiltration of inflammatory cells. IHC staining showed that the spindle cells expressed SMA focally or partially, and p16 diffusely and strongly. FISH showed that 12 of 14 cases had USP6 gene breakage, and two of them occurred in the intrathoracic skeletal muscle with the red signal amplification of USP6 gene. Conclusions: NF in unusual sites shows similar clinicopathological and genetic characteristics to classic NF, but the tumor mostly has infiltrating borders, non-specific and strong expression of p16, and USP6 red signal amplification. The pathological diagnosis of NF in rare sites should be highly vigilant.

[Research advances in the treatment of liver failure with mesenchymal stem cell-derived exosomes].

Liver failure is a serious clinical syndrome in which multiple pathogenic factors exceed the liver's self-repair capability, resulting massive hepatocellular necrosis, rapid disease progression and high mortality. Liver transplantation is the most effective method for the treatment of liver failure, but it has disadvantages, such as insufficient liver donor and high cost. The clinical efficacy of mesenchymal stem cells in liver failure have been validated, but its application has been limited to certain extent. Cell-free-based therapies, especially mesenchymal stem cell-derived exosomes, has become a research hotspot in recent years. This paper reviews the research advances in the treatment of liver failure with the use of mesenchymal stem cell-derived exosomes.

[Efficacy analysis of selective genicular artery embolization in the treatment of knee pain secondary to osteoarthritis].

Objective: To evaluate the efficacy and safety of selective genicular artery embolization for the treatment of the knee pain secondary to osteoarthritis. Methods: From October 2020 to July 2021, 17 patients (23 knees) aged (68±7) years with moderate to severe knee pain secondary to knee osteoarthritis were prospectively included in the General Hospital of Ningxia Medical University. There were 6 males and 11 females included in this research. Patients were assessed with knee pain, stiffness, and function with the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline, using the Kellgren-Lawrence (K-L) grading to evaluate the severity of KOA, and using the Magnetic Resonance Knee Osteoarthritis Score (MOAKS) to evaluate the MR imaging characteristics of the affected knee. Selective genicular artery embolization (GAE) was performed in all patients. The patients were followed up for 6 months after the procedure. Patients were assessed with the VAS score and WOMAC scale at 1 d, 1 week and 1, 3 and 6 months after the procedure to evaluate the clinical outcomes, including the improvement of knee joint pain, stiffness and function, as well as the occurrence of adverse reactions. Results: Three to seven genicular artery branches were superselected and embolized in 23 knees, and 4 to 7 genicular artery branches were embolized in 7 patients with K-L grade 4. The clinical improvement was 95.6% (22/23) at 1 month, 86.9% (20/23) at 3 months, and 91.3% (21/23) at 6 months. Twenty-three knees completed the 6-month follow-up, and the VAS score, WOMAC pain score, and total WOMAC score at 1, 3, and 6 months after surgery were (2.5±1.3), (3.4±2.4), and (19.7±9.8) points, (3.0±1.8), (4.5±3.4), and (22.3±11.3) points, (2.8±1.5), (4.1±3.0), and (20.5±11.0) points, which were lower than the (6.6±0.9), (11.4±2.6) and (47.0±12.0) points at baseline (all P<0.001). During the follow-up period, 7 patients had adverse reactions: 3 cases had skin ecchymosis in the femoral artery puncture area, 4 cases had knee joint stiffness and pain within 1 day after operation, which were relieved spontaneously in 1 week, 6 patients had joint clicking during extension and flexion activities after operation, of which 3 cases subsided spontaneously within 3 months after operation. None of the patients had major procedure-related adverse events. Conclusion: GAE has a high clinical improvement rate and a low incidence of adverse reactions in the treatment of the pain secondary to knee osteoarthritis, which provides a new treatment option for patients who fail to respond to conservative treatment.

[Clinical application of serum Golgi protein 73 in patients with chronic liver diseases].

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.

[Advances in the study of mesenchymal stem cells for end-stage liver disease].

End-stage liver disease refers to the advanced stage of liver disease caused by various chronic liver damage. Orthotopic liver transplantation is the most important final treatment option, but liver transplantation is still limited by many factors at present. Stem cell transplantation therapy has attracted widespread attention as a potential treatment for end-stage liver disease. This article reviews the research progress of mesenchymal stem cell therapy in end-stage liver disease.

MicroRNA-1269a promotes the occurrence and progression of osteosarcoma by inhibiting TGF-ß1 expression.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MicroRNA-1269a promotes the occurrence and progression of osteosarcoma by inhibiting TGF-ß1 expression, by S.-N. Yu, Y.-Y. Miao, B.T. Zhang, Y.-M. Dai, L. Liu, Z.-L. Gao, G.-F. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (3): 972-981-DOI: 10.26355/eurrev_201902_16984-PMID: 30779063" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16984.

[Quantitative evaluation of early stage blood flow change status after radiofrequency ablation based on multi-slice spiral CT whole-liver perfusion imaging on small hepatocellular carcinoma].

Objective: To investigate the blood flow change status in early stage tumor-related areas of hepatocellular carcinoma and its clinical significance after radiofrequency ablation using multi-slice spiral CT whole-liver perfusion imaging technology. Methods: 21 cases of primary liver cancer that underwent CT-guided radiofrequency ablation were included. CT perfusion scans were divided into four groups according to the time points of CT scans (before surgery, immediately after surgery and 1 and 3 month after surgery), and then blood perfusion parameters of the corresponding areas of the tumor were measured. Statistical analysis was performed using two independent samples of non-parametric Wilcoxon rank-sum test. The differences of blood perfusion parameters between tumor or ablation lesion and background liver parenchyma, paratumor tissue or inflammatory response zone were compared before, immediately and 1 and 3 months after surgery, respectively. Results: (1) The hepatic arterial perfusion (HAP) and hepatic arterial perfusion index (HPI) of cancerous liver tumors and background liver parenchyma was significantly increased (P < 0.01). The total liver perfusion (TLP) was higher than the background liver parenchyma (P = 0.01 < 0.05). The time to peak (TTP) was significantly lower than background liver parenchyma (P < 0.01); (2) The perfusion parameters of HAP, PVP and TLP were lower than the background liver parenchyma in the complete ablation lesions immediately after radiofrequency ablation and 1 and 3 months after surgery, and the difference was statistically significant (P < 0.05); (3) The inflammatory response zone of ablation lesions of HAP, HPI, and TLP were gradually decreased with the extended postoperative time and TTP was gradually increased, while PVP did not change significantly; (4) HAP, HPI, and TTP were compared between the tumor and the tumor inflammatory response zone immediately after surgery, and 1 and 3 months after surgery, and the difference was statistically significant (P < 0.01). However, there was no statistically significant difference between PVP and TLP (P > 0.05). Conclusion: CT whole-liver perfusion imaging can precisely evaluate the early stage blood flow change status in peritumor and tumors before and after radiofrequency ablation and then objectively evaluate tumor's blood supply and therapeutic effect on hepatocellular carcinoma.

[Value and related factors of preoperative diagnosis of extramural vascular invasion of rectal cancer by 3.0T magnetic resonance imaging].

Objective: To evaluate the value of preoperative diagnosis of extramural vascular invasion (EMVI) of rectal cancer with 3.0T high-resolution magnetic resonance imaging (MRI) and the MRI-related factors of EMVI in rectal cancer. Methods: The clinical and imaging data of 40 patients with rectal cancer were retrospectively analyzed. The postoperative pathological diagnosis was used as the gold standard to evaluate the diagnostic efficacy of preoperative diagnosis of EMVI of rectal cancer by high-resolution MRI, and to analyze the relationship between the EMVI and clinical and MRI features. Results: Of the 40 patients, 19 cases were diagnosed as positive EMVI and 21 were negative by MRI. Pathological diagnosis of EMVI was positive in 10 cases and negative in 30 cases. The sensitivity, specificity and accuracy of MRI in the diagnosis of EMVI were 100%, 70.0% and 77.5%, respectively. Preoperative MRI and postoperative pathology were moderately consistent in the diagnosis of EMVI in rectal cancer (Kappa=0.538, P<0.001). Pathological EMVI positivity were related to tumor size under MRI examination (P=0.028), degree of differentiation (P<0.001), depth of invasion (P=0.002), lymph node metastasis (P=0.001), liver metastasis (P=0.011), tumor apparent diffusion coefficient (ADC) value (P=0.010) and exponential apparent diffusion coefficient (eADC) value (P=0.003). It also related to extramural nerve invasion by pathological examination (P=0.005). Conclusion: According to the EMVI imaging score of rectal cancer, preoperative MRI has a high value in the diagnosis of EMVI of rectal cancer.

MicroRNA-1269a promotes the occurrence and progression of osteosarcoma by inhibit-ing TGF-ß1 expression.

OBJECTIVE: MicroRNAs are endogenous, non-coding small RNAs that are capable of regulating biological and pathological processes. Previous studies have shown that microRNA-1269a serves as an oncogene. However, the role of microRNA-1269a in the pathogenesis of osteosarcoma (OS) has not been reported. The aim of this work was to investigate the expression characteristics of microRNA-1269a in OS and to further study its regulatory effects on the malignant progression of OS. PATIENTS AND METHODS: The expression of microRNA-1269a in 61 pairs of OS tissues and para-cancerous tissues was detected by quantitative Real Time-polymerase Chain Reaction (qRT-PCR). Chi-square test was used to analyze the relationship between microRNA-1269a expression and the characteristics of OS patients, including age, sex, clinical stage and distant metastasis. Subsequently, microRNA-1269a expression in OS cell lines was detected as well. After knockdown of microRNA-1269a by constructing relevant small interference RNA, biological performances of MG63 and U2OS cells were accessed by cell counting kit-8 (CCK-8), colony formation and transwell assay. Meanwhile, the protein expressions of key genes in the EMT/Smad pathway were detected by Western blot. Finally, si-TGF-ß1 (transforming growth factor-ß1) was transfected into OS cells, and cell migration and invasion were detected by transwell assay. RESULTS: MicroRNA-1269a was highly expressed in OS tissues compared with para-cancerous tissues. High expression of microRNA-1269a was positively correlated with young OS patients and high rate of distant metastasis, whereas was not correlated with age, sex and Enneking stage. Kaplan-Meier survival curves showed that high expression of microRNA-1269a was significantly associated with poor prognosis of OS. The knockdown of microRNA-1269a in MG63 and U2OS cells significantly inhibited cell proliferation, migration and invasion. Meanwhile, microRNA-1269a knockdown in OS cells markedly downregulated the expressions of TGF-ß1, p-Smad2, p-Smad3, N-cad, Vimentin and MMP9. Furthermore, TGF-ß1 knockdown remarkably decreased migratory and invasive abilities of OS cells. CONCLUSIONS: MicroRNA-1269a is highly expressed in OS, which is remarkably correlated with tumor stage, distant metastasis and poor prognosis of OS. In addition, microRNA-1269a promotes the malignant progression of OS by regulating TGF-ß1 expression.

[Diagnostic value of computed tomographic perfusion imaging of whole liver for quantitative assessment of blood flow state in liver cancer after transcatheter arterial chemoembolization].

Objective: To investigate the diagnostic value of whole liver CT perfusion imaging in the quantitative evaluation of hemodynamic changes before and after transcatheter arterial chemoembolization (TACE). Methods: Twenty-six patients with hepatocellular carcinoma underwent TACE therapies were recruited. Whole -liver computed tomographic perfusion imaging (CTPI) was performed 2~3 days before TACE and 1 month after TACE. We measured the following perfusion parameters: hepatic arterial perfusion (HAP), portal venous perfusion (PVP), total liver perfusion (TLP), hepatic arterial perfusion index (HAPI), and time-to-peak (TTP).The F-test, t-test and Rank sum test were used for statistical analysis. Results: A total of 34 HCC lesions were detected. According to the deposition of lipiodol after TACE, they were divided into a lipiodol dense group (21) and a lipiodol light group (13). The length of hepatocellular carcinoma lesions after TACE showed a decreasing trend compared with preoperative TACE. The lesions in the lipiodol dense group had smaller lesions than those in the lipiodol light group. The preoperative and postoperative longitudinal diameters were (3.12 ± 0.58) cm vs. (1.93 ± 0.79) cm, (2.98 ± 2.01) cm vs. (2.58 ± 2.00) cm, the differences were statistically significant (t = 15.1, 8.65, P < 0.05). The preoperative HAP and HPI of the lipiodol dense group were the highest, and the peritumoral within 1cm was higher than that of the surrounding liver parenchyma. The PVP, TLP, and TTP were highest in the surrounding of liver parenchyma, and 1 cm higher than the tumor area in the background. The corresponding perfusion parameters were statistically significant (P < 0.05); HAP and HPI were 1 cm higher than the surrounding liver parenchyma. After the operation, PVP, TLP and TTP were lower than the background liver parenchyma, the difference was statistically significant (P < 0.05); HAP and HPI decreased by 1 cm after the operation, and the PVP, TLP, and TTP increased. There was no significant difference after operation in the blood perfusion of background liver parenchyma (P ˃ 0.05). The HAP and HPI decreased, and the PVP and TTP increased in the lipiodol light group after operation (P < 0.05). There was no significant difference between the other two regions (P ˃ 0.05). Conclusion: There was no blood perfusion in the lipiodol deposition area after TACE. The perfusion volume of hepatic artery in the peritumoral 1 cm and lipiodol light group decreased and the portal venous perfusion increased. CTPI can quantitatively evaluate blood perfusion state, which is of great significance for the determination of treatment plans before TACE treatment to assume the postoperative therapeutic effect in liver cancer.

[Impression of direct-acting antiviral agents in the treatment of recurrent hepatocellular carcinoma related to chronic hepatitis C].

The treatment of chronic hepatitis C has gradually entered into the era of direct-acting antiviral agents (DAAs) from the era of pegylated interferon-α combined with ribavirin, which has a high curative effect, good tolerability, and complete patient-friendly oral form of administration. Sustained virologic response (SVR) acquired by pegylated interferon-α plus ribavirin therapy has been widely recognized by scholars in reducing the recurrence of primary liver cancer and liver cancer, especially in cirrhotic patients. The clinical application time of DAAs is short and its report is inconsistent with the increase or decrease of primary liver cancer and liver cancer recurrence. Simultaneously, the effect of SVR in people with hepatocellular carcinoma on DAAs seems to be different from those in patients without hepatocellular carcinoma. This article reviews some of the existing reports in order to increase the understanding of DAAs and liver cancer and serve the long-term benefit of clinical treatment.

TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK-STAT signaling pathway.

We have previously observed the downregulation of TMEM2 in the liver tissue of patients with chronic hepatitis B virus (HBV) infection and in HepG2.2.15 cells with HBV genomic DNA. In the present study, we investigated the role and mechanism of TMEM2 in HepG2 and HepG2.2.15 during HBV infection HepG2 and HepG2.2.15. HepG2 shTMEM2 cells with stable TMEM2 knockdown and HepG2 TMEM2 and HepG2.2.15 TMEM2 cells with stable TMEM2 overexpression were established using lentivirus vectors. We observed reduced expression of TMEM2 in HBV-infected liver tissues and HepG2.2.15 cells. HBsAg, HBcAg, HBV DNA, and HBV cccDNA levels were significantly increased in HepG2 shTMEM2 cells but decreased in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells compared with naive HepG2 cells. On the basis of the western blotting results, the JAK-STAT signaling pathway was inhibited in HepG2 shTMEM2 cells but activated in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells. In addition, reduced and increased expression of the antiviral proteins MxA and OAS1 was observed in TMEM2-silenced cells (HepG2 shTMEM2 cells) and TMEM2-overexpressing cells (HepG2 TMEM2 and HepG2.2.15 TMEM2 cells), respectively. The expression of Interferon regulatory factor 9 (IRF9) was not affected by TMEM2. However, we found that overexpression and knockdown of TMEM2, respectively, promoted and inhibited importation of IRF9 into nuclei. The luciferase reporter assay showed that IRF9 nuclear translocation affected interferon-stimulated response element activities. In addition, the inhibitory effects of TMEM2 on HBV infection in HepG2 shTMEM2 cells was significantly enhanced by pre-treatment with interferon but significantly inhibited in HepG2.2.15 TMEM2 cells by pre-treatment with JAK1 inhibitor. TMEM2 inhibits HBV infection in HepG2 and HepG2.2.15 by activating the JAK-STAT signaling pathway.

Expression profiles of variation integration genes in bladder urothelial carcinoma.

Bladder cancer is a common cancer worldwide and its incidence continues to increase. There are approximately 261,000 cases of bladder cancer resulting in 115,000 deaths annually. This study aimed to integrate bladder cancer genome copy number variation information and bladder cancer gene transcription level expression data to construct a causal-target module network of the range of bladder cancer-related genomes. Here, we explored the control mechanism underlying bladder cancer phenotype expression regulation by the major bladder cancer genes. We selected 22 modules as the initial module network to expand the search to screen more networks. After bootstrapping 100 times, we obtained 16 key regulators. These 16 key candidate regulatory genes were further expanded to identify the expression changes of 11,676 genes in 275 modules, which may all have the same regulation. In conclusion, a series of modules associated with the terms 'cancer' or 'bladder' were considered to constitute a potential network.

A stress-induced cellular aging model with postnatal neural stem cells.

Aging refers to the physical and functional decline of the tissues over time that often leads to age-related degenerative diseases. Accumulating evidence implicates that the senescence of neural stem cells (NSCs) is of paramount importance to the aging of central neural system (CNS). However, exploration of the underlying molecular mechanisms has been hindered by the lack of proper aging models to allow the mechanistic examination within a reasonable time window. In the present study, we have utilized a hydroxyurea (HU) treatment protocol and effectively induced postnatal subventricle NSCs to undergo cellular senescence as determined by augmented senescence-associated-ß-galactosidase (SA-ß-gal) staining, decreased proliferation and differentiation capacity, increased G0/G1 cell cycle arrest, elevated reactive oxygen species (ROS) level and diminished apoptosis. These phenotypic changes were accompanied by a significant increase in p16, p21 and p53 expression, as well as a decreased expression of key proteins in various DNA repair pathways such as xrcc2, xrcc3 and ku70. Further proteomic analysis suggests that multiple pathways are involved in the HU-induced NSC senescence, including genes related to DNA damage and repair, mitochondrial dysfunction and the increase of ROS level. Intriguingly, compensatory mechanisms may have also been initiated to interfere with apoptotic signaling pathways and to minimize the cell death by downregulating Bcl2-associated X protein (BAX) expression. Taken together, we have successfully established a cellular model that will be of broad utilities to the molecular exploration of NSC senescence and aging.

Interferon-ß gene-modified human bone marrow mesenchymal stem cells attenuate hepatocellular carcinoma through inhibiting AKT/FOXO3a pathway.

OBJECTIVE: This study aims to investigate the using of bone marrow mesenchymal stem cells (BMSCs) genetically engineered to produce interferon-ß (IFN-ß) as a gene delivery system to treat hepatocellular carcinoma (HCC) in vitro and in vivo. METHODS: To measure the effects on tumour cell growth in vitro, IFN-ß-producing BMSCs (BMSC/IFN-ß) were co-cultured with the HCC cell line HepG2 and Huh7. Enzyme-linked immunosorbent assay (ELISA) was used to detect the IFN-ß secretion in the BMSC culture condition medium (CM). The effect of BMSC/IFN-ß on HCC cells proliferation was examined both in vitro and in vivo by using MTT, colony formation assay, BrdU staining, cell cycle analysis, and xenografted NOD/SCID mouse tumour model. To examine the impact of BMSC/IFN-ß on the AKT/FOXO3a signalling, RT-PCR and western blotting were performed. RESULTS: The BMSC/IFN-ß cells can stably secrete high levels of IFN-ß. Both MTT and colony forming assay showed that HCC cells had a lower growth rate when cultured in BMSC/IFN-ß-CM as compared with that in BMSC/vector-CM or DMEM culture group. Co-culture with BMSC/IFN-ß-CM dramatically decreased the percentages of cells with incorporated BrdUrd. In BMSC/IFN-ß-CM-treated HCC cells, the proportion of G1-phase cells increased but it decreased in the S phase of the cell. The BMSC/IFN-ß inhibited HCC growth in NOD/SCID mice and proved the survival period of these mice. Compared with the control group, p21 and p27 expression of hepatoma cells increased, whereas cyclin D1 and phosphorylation of Rb expression decreased when co-cultured with BMSC/IFN-ß-CM. It was associated with suppression of Akt activity and enhanced transcriptional activity of FOXO3a. CONCLUSION: The IFN-ß gene-modified BMSCs can effectively inhibit the proliferation of HCC cells in vitro and in vivo through inhibiting AKT/FOXO3a pathway. These results indicate that BMSC/IFN-ß are a powerful anticancer cytotherapeutic tool for HCC.

The PPI network and cluster ONE analysis to explain the mechanism of bladder cancer.

BACKGROUND: Bladder cancer is a common cancer worldwide whose incidence continues to increase. It is estimated that there are 261,000 cases of bladder cancer resulting in 115,000 deaths worldwide. AIM: Although some studies can be initiated using small local tissue collections, high quality collection of fresh tissues from new clinical trials will be crucial for proper evaluation of associations with clinical outcome. For superficial bladder cancer, identification of tumors that will progress has long been perceived as a potential application of genetic studies. MATERIALS AND METHODS: In our study, we constructed the Protein-Protein Interactions (PPI) network using the Cytoscape and detected some network modeling clusters. In addition, we enriched GO categories among these genes in the first cluster and detected a pathway i.e. Spliceosome (hsa03040). Most Gene Ontology (GO) categories and Spliceosome were closely to RNA splicing and cellular macromolecular complex (CMC) assembly, which indicates that the mutation of RNA splicing and CMC assembly maybe important factors causing bladder cancer. RESULTS: In our study, these clusters of GO:0034622, GO:0006397 and GO:0034621 in bladder cancer belong to cellular macromolecular complex assembly, which may play an important role in the occurrence of cancer cells. CONCLUSIONS: It is a great significance for the detection and treatment of bladder cancer to understand the mechanism of RNA splicing and CMC assembly.