Search

Background: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide owing to its high rates of metastasis and recurrence. The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is ubiquitously overexpressed in several human cancers, including liver, ovary, lung, large intestine, gastric, bone marrow, and breast malignancies and is involved in the invasion and metastasis of cancer cells. Therefore, we aimed to determine the biological role and molecular mechanism of IQGAP3 in HCC.Methods: We used 120 archived clinical HCC samples, 9 snap-frozen HCC tumor tissues, and 4 normal liver tissues. Expression of IQGAP3 mRNA and protein in HCC cell lines (Hep3B, SMMC-7721, HCCC-9810, HepG2, BEL-7404, HCCLM3, QGY-7701, Huh7, and MHCC97H) and normal liver epithelial cells LO2 was examined by western blot, quantitative polymerase chain reaction, and immunohistochemistry. In addition, wound-healing and transwell matrix penetration assays were used to assess the migratory and invasive abilities of HCC cells, respectively.Results: Expression of the IQGAP3 was robustly upregulated in HCC cells and tissues. High expression of IQGAP3 in HCC correlated with aggressive clinicopathological features and was an independent poor prognostic factor for overall survival. Furthermore, ectopic expression of IQGAP3 markedly enhanced HCC cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) in vitro and promoted metastasis of orthotopic hepatic tumors in nude mice. Conversely, silencing endogenous IQGAP3 showed an opposite effect. Mechanistically, IQGAP3 promoted EMT and metastasis by activating TGF-β signaling.Conclusions: IQGAP3 functions as an important regulator of metastasis and EMT by constitutively activating the TGF-β signaling pathway in HCC. Our findings present new evidence of the role of IQGAP3 in EMT and metastasis, indicating its potential as a prognostic biomarker candidate and a therapeutic target against HCC. [ABSTRACT FROM AUTHOR]

Background: The effect of genetic variants on aspirin resistance (AR) remains controversial. We sought to assess the association of genetic variants with AR and early clinical outcomes in patients with acute ischemic stroke (IS).Methods: A total of 850 acute IS patients were consecutively enrolled. Platelet aggregation was measured before and after a 7-10 day aspirin treatment. The sequences of 14 variants of COX-1, COX-2, GPIb, GPIIIa, P2Y1 and P2Y12 were determined using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR). The primary outcome was early neurological deterioration (END) within 10 days of admission. The secondary outcome was a composite of early recurrent ischemic stroke (ERIS), myocardial infarction (MI) and death within 10 days of admission.Results: 175 (20.6%) patients were AR, 45 (5.3%) were aspirin semi-resistant, 121 (14.2%) developed END, 17 (0.2%) had ERIS, 2 (0.2%) died, and 6 (0.7%) had MI. Single locus analysis indicated that only rs1371097 was associated with AR. However, GMDR analysis indicated that the following three sets of gene-gene interactions were significantly associated with AR: rs20417CC/rs1371097TT/rs2317676GG; rs20417CC/rs1371097TT/rs2317676GG; rs20417CC/rs1371097CT/rs2317676AG. END occurred significantly more frequently in patients with AR or high-risk interactive genotypes. Moreover, AR and high-risk interactive genotypes were independently associated with END.Conclusion: Sensitivity of IS patients to aspirin and END may be multifactorial and is not significantly associated with a single gene polymorphism. Combinational analysis may useful for further insight into the genetic risks for AR. [ABSTRACT FROM AUTHOR]

Background: The maintenance of nucleus pulposus (NP) viability in vitro is difficult. The annulus fibrosus (AF) pathway reflects one nutrient transport channel and may have an important effect on NP viability in disc organ cultures. The present study describes a feasible disc pre-treatment involving the AF and investigates its efficacy in improving NP bioactivity in an in vitro disc bioreactor culture.Methods: Rabbit discs that were randomly assigned to the experimental group (EG) were pretreated via the surgical removal and controlled trypsinization of the outer AF. The discs in the control group (CG) did not receive any special treatment. All discs were organ-cultured in a self-developed bioreactor. Solute transport into the central NP was measured using a methylene blue solution. On days 7 and 14, histological properties, cell viability, cell membrane damage, gene expression and matrix composition within the NP in these two groups were compared with each other and with the corresponding parameters of fresh NP samples. Additionally, the structures of the outer AF and the cartilage endplate (CEP) following pre-treatment were also assessed.Results: The outer AF in the EG became disorganized, but no specific changes occurred in the CEP or the inner AF following pre-treatment. The discs in the EG exhibited increased penetration of methylene blue into the central NP. On days 7 and 14, the NP bioactivity in the EG was improved compared with that of the CG in terms of cell viability, cell membrane damage, gene expression profile and matrix synthesis. Moreover, cell viability and matrix synthesis parameters in the EG were more similar to those of fresh samples than they were to the same parameters in the CG on day 14.Conclusions: Using this disc pre-treatment, i.e., the surgical removal and controlled trypsinization of the outer AF, NP bioactivity was better maintained for up to 14 days in an in vitro disc bioreactor culture. [ABSTRACT FROM AUTHOR]

Background: Dengue virus is transmitted by mosquito around the tropical and sub-tropical regions. There was a large-scale dengue epidemic in Guangdong province, China during 2014 and around fifty thousands dengue fever cases, including six deaths, have been reported. In this study, we aimed to understand the clinical characteristics of hospitalized patients with laboratory-confirmed dengue virus (DENV) infection and determined the origin of the virus from the outbreak.Methods: We have summarized the data from 138 hospitalized patients who were laboratory confirmed for dengue infection in Guangzhou city. Patients were classified as either non-severe dengue fever or severe dengue fever according to the guidelines from the WHO. Viral serotypes were determined by real time RT-PCR. Genetic sequences of the envelope and non-structural genes were amplified and analyzed from the serum samples of eleven patients.Results: Co-circulation of dengue serotype 1 and 2 were identified from the outbreak. Patients infected by serotype 1 or 2 showed similar clinical features. Patients with severe dengue fever showed prolonged hospitalization and significant impairment of organ functions. Four samples from serotype 1 and five samples from serotype 2 were closely related respectively and clustered with Guangzhou isolates from previous years. The remaining isolates of serotype 1 were related to viruses found in Malaysia, India, Bangladesh and Singapore.Conclusion: The phylogenetic grouping of Guangdong isolates suggests that dengue is no longer an imported disease in China. Analysis of the isolates obtained in this study together with the size of the outbreak are suggestive of endemic circulation in Guangdong province. [ABSTRACT FROM AUTHOR]

Background: Many researches have investigated the changes associated with immobilization-induced osteoarthritis (OA). However, there are only few studies focusing on the effect of unilateral knee immobilization on cartilage matrix changes in the contralateral mobile knee. The aim of the present study was to investigate the influence of immobilization on the cartilage matrix in the contralateral mobile knees in a rabbit model of OA induced by immobilization.Methods: Right knees (experimental knees) of eighteen mature female rabbits were immobilized at an extension of 180° with orthopedic casting tape for 2, 4, or 8 weeks. Left knees (contralateral knees) of the immobilized rabbits were not subjected to immobilization. The knees of six non-immobilized rabbits were designated as control knees. Following immobilization, cartilage specimens from the medial femoral condyle underwent macroscopic, histological, immunohistochemical, and biochemical evaluations.Results: Roughness of cartilage surface was detected in the experimental knees at 2 weeks, and cartilage degeneration was further developed. In the contralateral knee, cartilage showed degenerative changes after 4 weeks. Safranin-O staining and glycosaminoglycan (GAG) contents were reduced in the experimental knees following immobilization and in the contralateral intact knees after 4 and 8 weeks. Type II collagen staining was gradually reduced, type I collagen accumulation was obviously detected in the upper and middle layers of cartilage in experimental knees after 8 weeks, and the collagen orientation was gradually disorganized in both knees at 4 and 8 weeks. For both experimental and contralateral knees, collagen contents were significantly decreased at 8 weeks, and Mankin and Osteoarthritis Research Society International (OARSI) scores increased over time.Conclusion: OA developed in the contralateral intact knee with the progress of OA in the immobilized knee in a rabbit model of immobilization-induced OA. [ABSTRACT FROM AUTHOR]

Background: Mast cells promote the progression of experimental tumors and might be a valuable therapeutic target. However, the relevant clinical evidence is still controversial. This study analyzed the relationship between the distribution of mast cells and the survival of patients with colon cancer to study whether mast cells contribute to tumor progression.Materials and Methods: Ninety-three cases of pathologically confirmed primary cancer tissues matched with adjacent normal mucosa, metastases of regional-draining lymph nodes and regional-draining lymph nodes without metastases were collected from stage IIIB colon carcinoma patients between January 1997 and July 2004 at the Cancer Center of Sun Yat-Sen University. Tryptase-positive mast cells were counted. The relationships of the distribution of mast cells with clinicopathologic parameters and 5-year survival were analyzed.Results: Although the mast cell count in the mucosa adjacent to the primary colon cancer was significantly higher than that in the stroma of the primary colon cancer, no difference in mast cell counts was observed between the stroma in lymph node metastasis and the lymph tissue adjacent to the metastasis. Additionally, the mast cell count in the regional-draining lymph node without the invasion of cancer cells was significantly higher than that in the stroma of lymph node metastasis and adjacent lymph tissue. However, none of those mast cell counts was related to 5-year survival.Conclusion: Although mast cell count varied with location, none of the mast cell counts was related to 5-year survival, suggesting that mast cells do not contribute to the progression of stage IIIB colon cancer. [ABSTRACT FROM AUTHOR]

Background: Chemoresistance to temozolomide (TMZ) is a major challenge in the treatment of glioblastoma (GBM). We previously found that miR-519a functions as a tumor suppressor in glioma by targeting the signal transducer and activator of transcription 3 (STAT3)-mediated autophagy oncogenic pathway. Here, we investigated the effects of miR-519a on TMZ chemosensitivity and autophagy in GBM cells. Furthermore, the underlying molecular mechanisms and signaling pathways were explored. Methods: In the present study, two stable TMZ-resistant GBM cell lines were successfully generated by exposure of parental cells to a gradually increasing TMZ concentration. After transfecting U87-MG/TMZ and U87-MG cells with miR-519a mimic or inhibitor, a series of biochemical assays such as MTT, apoptosis, and colony formation were performed to determine the chemosensitive response to TMZ. The autophagy levels in GBM cells were detected by transmission electron microscopy, LC3B protein immunofluorescence, and Western blotting analysis. Stable knockdown and overexpression of miR-519a in GBM cells were established using lentivirus. A xenograft nude mouse model and in situ brain model were used to examine the in vivo effects of miR-519a. Tumor tissue samples were collected from 48 patients with GBM and were used to assess the relationship between miR-519a and STAT3 expression. Results: TMZ treatment significantly upregulated miR-519a in U87-MG cells but not in U87-MG/TMZ cells. Moreover, the expression of miR-519a and baseline autophagy levels was lower in U87-MG/TMZ cells as compared to U87-MG cells. miR-519a dramatically enhanced TMZ-induced autophagy and apoptotic cell death in U87-MG/TMZ cells, while inhibition of miR-519a promoted TMZ resistance and reduced TMZ-induced autophagy in U87-MG cells. Furthermore, miR-519a induced autophagy through modification of STAT3 expression. The in vivo results showed that miR-519a can enhance apoptosis and sensitized GBM to TMZ treatment by promoting autophagy and targeting the STAT3/Bcl-2/Beclin-1 pathway. In human GBM tissues, we found an inverse correlation between miR-519a and STAT3 expression. Conclusions: Our results suggested that miR-519a increased the sensitivity of GBM cells to TMZ therapy. The positive effects of miR-519a may be mediated through autophagy. In addition, miR-519a overexpression can induce autophagy by inhibiting STAT3/Bcl-2 pathway. Therefore, a combination of miR-519a and TMZ may represent an effective therapeutic strategy in GBM. [ABSTRACT FROM AUTHOR]

Background: The incidence of syphilis is increasing in many parts of the world. Clinicians may have limited experience in the diagnosis when the clinical appearance is unusual. If early diagnosis is not made and prompt treatment not given, then the disease may remain quiescent until more serious symptoms or systemic involvement develops.Case Presentation: We report the first case of a delayed diagnosis of syphilis with a ten-year history of persistent rupioid psoriasis-like lesions. Acute monoarthritis and high fever together with aggravation of skin lesions led to a careful clinical examination. Skin biopsies demonstrated syphilis spirochetes on immunohistochemical stain, and syphilis serological titers were positive. Standard treatment with benzathine penicillin brought a partial and transient improvement. A complete clinical and serological resolution of the disease was achieved by a prolonged and repeated penicillin treatment combined with methylprednisolone. A 7-year follow-up of the patient proved a full recovery.Conclusion: Our case highlights the fact that clinical signs of syphilis can be diverse and complicated. Unusual clinical manifestations can happen in an immunocompetent individual. Treatment strategy may need to be adjusted in a difficult case. [ABSTRACT FROM AUTHOR]

Background: Injuries affect all age groups but have a particular impact on young people. To evaluate the incidence of non-fatal, unintentional, injuries among undergraduates in Wenzhou, China, assess the burden caused by these injuries, and explore the associated risk factors for unintentional injuries among these undergraduates, we conducted a college-based cross-sectional study.Methods: Participants were selected by a multi-stage random sampling method, and 2,287 students were asked whether they had had an injury in the last 12 months; the location, cause, and consequences of the event. The questionnaire included demographic and socioeconomic characteristics, lifestyle habits, and the scale of type A behaviour pattern (TABP). Multivariate logistic regression models were used; crude odds ratios (ORs), adjusted ORs and their 95% confidence intervals (CIs) were estimated, with students having no injuries as the reference group.Results: The incidence of injuries among undergraduates in Wenzhou was 18.71 injuries per 100 person-years (95%CI: 17.12~20.31 injuries per 100 person-years). Falls were the leading cause of injury, followed by traffic injuries, and animal/insect bites. Male students were more likely to be injured than female students. Risk factors associated with unintentional injuries among undergraduates were: students majoring in non-medicine (adjusted OR: 1.53; 95% CI: 1.19-1.96); type A behaviour pattern (adjusted OR: 2.99; 95% CI: 1.45-6.14); liking sports (adjusted OR: 1.86; 95% CI: 1.41-2.45).Conclusions: Injuries have become a public health problem among undergraduates. Falls were the major cause of non-fatal injury. Therefore, individuals, families, schools and governments should promptly adopt preventive measures aimed at preventing and controlling morbidity due to non-fatal injury, especially among students identified to be at high-risk; such as male students with type A behaviour pattern who like sports. [ABSTRACT FROM AUTHOR]