Extracellular HSP70/HSP70-PCs Promote Epithelial-Mesenchymal Transition of Hepatocarcinoma Cells

Background

Extracellular heat shock protein 70 and peptide complexes (eHSP70/HSP70-PCs) regulate a variety of biological behaviors in tumor cells. Whether eHSP70/HSP70-PCs are involved in the epithelial-mesenchymal transition (EMT) of tumor cells remains unclear.

Aims

To determine the effects of eHSP70/HSP70-PCs on EMT of hepatocarcinoma cells.

Methods

The expressions of E-cadherin, HSP70, α-smooth muscle actin protein (α-SMA) and p-p38 were detected immunohistochemically in liver cancer samples. Immunofluorescence, western blotting and real-time RT-PCR methods were used to analyze the effects of eHSP70/HSP70-PCs on the expressions of E-cadherin, α-SMA and p38/MAPK in vivo.

Results

HSP70, E-cadherin, α-SMA and p-p38 were elevated in hepatocellular carcinoma tissues. The expression of HSP70 was positively correlated with malignant differentiated liver carcinoma. The expressions of HSP70, α-SMA and p-p38 correlated with recurrence-free survival after resection. eHSP70/HSP70-PCs significantly promoted the expressions of α-SMA and p-p38 and reduced the expressions of E-cadherin in vivo. The effect was inhibited by SB203580.

Conclusion

The expressions of HSP70, E-cadherin, α-SMA and p-p38 may represent indicators of malignant potential and could discriminate the malignant degree of liver cancer. eHSP70/HSP70-PCs play an important role in the EMT of hepatocellular carcinoma via the p38/MAPK pathway.     

Comparative Characteristics of Porous Bioceramics for an Osteogenic Response In Vitro and In Vivo

Porous calcium phosphate ceramics are used in orthopedic and craniofacial applications to treat bone loss, or in dental applications to replace missing teeth. The implantation of these materials, however, does not induce stem cell differentiation, so suitable additional materials such as porous calcium phosphate discs are needed to influence physicochemical responses or structural changes. Rabbit adipose-derived stem cells (ADSC) and mouse osteoblastic cells (MC3T3-E1) were evaluated in vitro by the MTT assay, semi-quantitative RT-PCR, and immunoblotting using cells cultured in medium supplemented with extracts from bioceramics, including calcium metaphosphate (CMP), hydroxyapatite (HA) and collagen-grafted HA (HA-col). In vivo evaluation of the bone forming capacity of these bioceramics in rat models using femur defects and intramuscular implants for 12 weeks was performed. Histological analysis showed that newly formed stromal-rich tissues were observed in all the implanted regions and that the implants showed positive immunoreaction against type I collagen and alkaline phosphatase (ALP). The intramuscular implant region, in particular, showed strong positive immunoreactivity for both type I collagen and ALP, which was further confirmed by mRNA expression and immunoblotting results, indicating that each bioceramic material enhanced osteogenesis stimulation. These results support our hypothesis that smart bioceramics can induce osteoconduction and osteoinduction in vivo, although mature bone formation, including lacunae, osteocytes, and mineralization, was not prominent until 12 weeks after implantation.     

GNB3, eNOS,and Mitochondrial DNA Polymorphisms Correlate to Natural Longevity in a Xinjiang Uygur Population

Background

In centenarian populations, application of the positive biology approach (examination of positive phenotypes in aging) has revealed that mitochondrial DNA (mtDNA) mutation accumulation may be linked to human longevity; however, the role of guanine nucleotide-binding protein (G protein) abnormalities modulated by G-protein beta-3 (GNB3) and nitrate (NO2) production associated with endothelial nitric oxide synthase (eNOS), commonly appearing in age-related diseases, remains undetermined.

Objective

The association between the mtDNA 5178A/C, mtDNA 10398A/G, GNB3 C825T, and eNOS polymorphisms and longevity in a Uygur population (Xinjiang region, China) were investigated.

Methods

A total of 275 experimental subjects aged ≥100 or with 4 generations currently living were screened for inclusion in the centenarian (>100 years) and nonagenarian groups (90–100 years), and 112 65–70 year old control subjects were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine mtDNA 5178A/C, mtDNA 10398A/G, GNB3 C825T, and eNOS. Associations between polymorphic loci, genotypes, and longevity were analyzed.

Results

165 included subjects (M∶F = 107∶58; mean age = 97±3 years; mean age 100–113 years) were assigned to the centenarian (M∶F = 46/19; n = 65) and nonagenarian groups (M∶F = 61/39; n = 100). Associations between mtDNA C5178A and A10398G polymorphisms with longevity in the centenarian group with mtDNA genotype frequencies 5178A and 10398G were 66.79% and 36.8%.

Conclusions

Applying the overwhelming longevity observed in Uygur populations, these findings demonstrate that mtDNA 5178A/C and 10398A/G, GNB3 C825T, and eNOS polymorphisms are useful as a genetic basis for longevity.     

Synthesis of Coral-Like Tantalum Oxide Films via Anodization in Mixed Organic-Inorganic Electrolytes

We report a simple method to fabricate nano-porous tantalum oxide films via anodization with Ta foils as the anode at room temperature. A mixture of ethylene glycol, phosphoric acid, NH₄F and H₂O was used as the electrolyte where the nano-porous tantalum oxide could be synthesized by anodizing a tantalum foil for 1 h at 20 V in a two–electrode configuration. The as-prepared porous film exhibited a continuous, uniform and coral-like morphology. The diameters of pores ranged from 30 nm to 50 nm. The pores interlaced each other and the depth was about 150 nm. After calcination, the as-synthesized amorphous tantalum oxide could be crystallized to the orthorhombic crystal system. As observed in photocatalytic experiments, the coral-like tantalum oxide exhibited a higher photocatalytic activity for the degradation of phenol than that with a compact surface morphology, and the elimination rate of phenol increased by 66.7%.     

Insulin Resistance Is an Independent Determinate of ED in Young Adult Men

Background

Insulin resistance (IR) triggers endothelial dysfunction, which contributes to erectile dysfunction (ED) and cardiovascular disease.

Aim

To evaluate whether IR was related to ED in young adult patients.

Methods

A total of 283 consecutive men complaining of ED at least six months were enrolled, with a full medical history, physical examination, and laboratory tests collected. Quantitative Insulin Sensitivity Check Index (QUICKI) was used to determine IR. The severity of ED was assessed by IIEF-5 questionnaire. Endothelial function was assessed by ultrasonographic examination of brachial artery flow mediated dilation (FMD).

Results

IR was detected in 52% patients. Subjects with IR had significant higher total cholesterol, triglycerides, low density lipoprotein-cholesterol (LDL-c), glycated haemoglobin (HBA1c), high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI), but showed significant lower IIEF-5 score, FMD%, high density lipoprotein -cholesterol (HDL-c), testosterone, sex hormone binding globulin (SHBG) levels than patients without IR. Multiple regression analysis showed QUICKI and testosterone were independent predictors of IIEF-5 score. Furthermore, the incidence of IR was correlated with the severity of ED.

Conclusions

Compared with other CVFs, IR was found as the most prevalent in our subjects. Besides, IR was independently associated with ED and its severity, suggesting an adverse effect of insulin resistance on erectile function.     

Impact of Functional Constipation on Health-Related Quality of Life in Preschool Children and Their Families in Xi’an,China

Aim

Functional constipation (FC) is one of the common diseases among children. The aim of this study was to investigate the health-related quality of life (HRQOL) in preschool children diagnosed with FC and the impact of the condition on affected families.

Methods

In this cross-sectional, case-control study, 152 children aged 3–6 years with FC, 176 healthy children aged 3–6 years without FC, and their primary caregivers were selected. Chinese versions of the PedsQL^TM 4.0 Generic Core Scale and the Family Impact Module (FIM) were used to assess childhood HRQOL and the impact of FC on family members, respectively. HRQOL scores were compared between children with FC and healthy children. In addition, a multiple step-wise regression with demographic variables of children and their caregivers, family economic status, duration and symptoms of FC, as independent variables, was used to determine factors that influenced HRQOL in children and had impacted caregivers.

Results

Scores of physical, emotional, social and school functions, and summary scales were significantly lower in children with FC than in healthy children (p < 0.05). Physical, emotional, social, cognitive, and communication scores for caregivers, as well as daily activities and relationships for families of children with FC, were significantly lower than those of caregivers and families with healthy children (p < 0.05). Children’s ages, duration of FC, symptoms of FC, the child-caregiver relationship, family economic status, and caregiver education level emerged as the main factors influencing HRQOL in children, caregivers, and family members.

Conclusions

FC had a significant impact on HRQOL of affected children and their caregivers, as well as their family functions. Social characteristics of children and caregivers, duration and symptoms of FC and family economic status significantly affected HRQOL of children and caregivers, as well as family functions of children with FC.     

Comparison of Endoscopic Ultrasonography and Multislice Spiral Computed Tomography for the Preoperative Staging of Gastric Cancer - Results of a Single Institution Study of 610 Chinese Patients

Background

This study compared the performance of endoscopic ultrasonography (EUS) and multislice spiral computed tomography (MSCT) in the preoperative staging of gastric cancer.

Methodology/Principal Findings

A total of 610 patients participated in this study, all of whom had undergone surgical resection, had confirmed gastric cancer and were evaluated with EUS and MSCT. Tumor staging was evaluated using the Tumor-Node-Metastasis (TNM) staging and Japanese classification. The results from the imaging modalities were compared with the postoperative histopathological outcomes. The overall accuracies of EUS and MSCT for the T staging category were 76.7% and 78.2% (P=0.537), respectively. Stratified analysis revealed that the accuracy of EUS for T1 and T2 staging was significantly higher than that of MSCT (P<0.001 for both) and that the accuracy of MSCT in T3 and T4 staging was significantly higher than that of EUS (P<0.001 and 0.037, respectively). The overall accuracy of MSCT was 67.2% when using the 13th edition Japanese classification, and this percentage was significantly higher than the accuracy of EUS (49.3%) and MSCT (44.6%) when using the 6th edition UICC classification (P<0.001 for both values).

Conclusions/Significance

Our results demonstrated that the overall accuracies of EUS and MSCT for preoperative staging were not significantly different. We suggest that a combination of EUS and MSCT is required for preoperative evaluation of TNM staging.     

A Meta-Analysis of Anti-Vascular Endothelial Growth Factor Remedy for Macular Edema Secondary to Central Retinal Vein Occlusion

Background

Central retinal vein occlusion (CRVO) associates with severe vision outcome and no proven beneficial treatment. Our meta-analysis intended to appraise the efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents in macular edema (ME) following CRVO.

Methods

Data were collected and analyzed by Review Manager 5.2.1. We employed a random-effects model to eliminate between-study heterogeneity. N_fs (called fail-safe number) was calculated to evaluate the publication bias.

Results

We included 5 trials consisting 323 cases and 281 controls. Primary outcomes showed that overall comparison of anti-VEGF agents with placebo control yielded a 374% and 136% increased tendency for a gain of 15 letters or more on Early Treatment Diabetic Retinopathy Study (ETDRS) chart (95% confidence interval [95% CI]: 2.43–9.23; P<0.00001; I² = 59%, 95% CI: 1.60–3.49; P<0.0001; I² = 0%, respectively) at 6 and 12 months. Secondary outcomes showed that a 90% and 77% decreased risk at 6 and 12 months for a loss of 15 letters or more. The overall mean difference showed a statistically significance in best-corrected visual acuity (BCVA) on each time point. However, changes of central retinal thickness (CRT) lost significance at 12 months after 6-month as-needed treatment. The incidence of adverse events (AEs) had no statistical difference between anti-VEGF and placebo groups. Subgroup analyses indicated that patients receiving Aflibercept got the highest tendency to gain 15 letters or more (OR = 9.78; 95% CI: 4.43–21.56; P<0.00001). Age controlled analysis suggested a weaken tendency of BCVA improvement in age over 50 (MD = 12.26; 95% CI: 7.55–16.98; P<0.00001). Subgroup analysis by clinical classification showed a strengthen difference of BCVA changes at 6 months in ischemic type (MD = 19.65 letters, 95% CI: 13.15 to 26.14 letters, P<0.00001).

Conclusions

Our results showed that anti-VEGF agents were superior to placebo in CRVO-ME treatment with no statistically significant AEs, especially in younger people and for ischemic type.