Overexpression of JAM-A in Non-Small Cell Lung Cancer Correlates with Tumor Progression

The objective of the current study was to determine the clinical significance of junctional adhesion molecule A (JAM-A) in patients with non-small cell lung cancer (NSCLC) and the biological function of JAM-A in NSCLC cell lines. We showed that JAM-A is predominantly expressed in cell membranes and high expression of JAM-A occurred in 37% of lung tumor specimens compared to corresponding normal tissues. High expression of JAM-A was significantly correlated with TNM stage (P = 0.021), lymph node metastasis (P = 0.007), and decreased overall survival (P = 0.02), In addition, we observed that silencing JAM-A by small interfering RNA inhibited tumor cell proliferation and induced cell cycle arrest at the G1/S boundary. Western blotting analysis revealed that knockdown of JAM-A decreased the protein levels of cyclin D1, CDK4, 6, and P-Rb. Thus, JAM-A plays an important role in NSCLC progression.     

Mini-Incision versus Standard Incision Total Hip Arthroplasty Regarding Surgical Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Purpose

It remains controversial whether mini-incision (MI) benefits patients in total hip arthroplasty (THA). We performed a meta-analysis of randomized controlled trials (RCTs) to assess the effects of MI on surgical and functional outcomes in THA patients.

Methods

A systematic electronic literature search (up to May 2013) was conducted to identify RCTs comparing MI with standard incision (SI) THA. The primary outcome measures were surgical and functional outcomes. According to the surgical approach taken, MI THA patients were divided into four subgroups for sub-group meta-analysis. Standardized mean differences (SMDs) or risk differences (RDs) with accompanying 95% confidence intervals (CIs) were calculated and pooled using a fixed-effect or random-effect model according to the heterogeneity.

Results

A total of 14 RCTs involving THA 1,174 patients met the inclusion criteria. The trials were medium risk of bias. The overall meta-analysis showed MI THA reduced total blood loss (95% CI, -201.83 to -21.18; p=.02) and length of hospital stay ( 95% CI, -0.67 to -0.08; p=.01) with significant heterogeneity. However, subgroup meta-analysis revealed posterior MI THA had perioperative advantages of reduced surgical duration ( 95% CI, -8.45 to -2.67; P<.001), less blood loss ( 95% CI, -107.20 to -1.73; P=.04) and shorter hospital stay ( 95% CI, -0.74 to -0.06; p=.002) with low heterogeneity. There were no significant differences between MI and SI THA groups in term of pain medication dose, functional outcome (HHS), radiological outcome or complications (P>.05, respectively).

Conclusions

Although no definite overall conclusion can be arrived at on whether MI THA is superior to SI THA, posterior MI THA clearly result in a significant decrease in surgical duration, blood loss and hospital stay. It seems to be a safe minimally invasive surgical procedure without increasing the risk of component malposition or complications.     

Autophagy in Retinal Ganglion Cells in a Rhesus Monkey Chronic Hypertensive Glaucoma Model

Primary open angle glaucoma (POAG) is a neurodegenerative disease characterized by physiological intraocular hypertension that causes damage to the retinal ganglion cells (RGCs). In the past, RGC damage in POAG was suggested to have been attributed to RGC apoptosis. However, in the present study, we applied a model closer to human POAG through the use of a chronic hypertensive glaucoma model in rhesus monkeys to investigate whether another mode of progressive cell death, autophagy, was activated in the glaucomatous retinas. First, in the glaucomatous retinas, the levels of LC3B-II, LC3B-II/LC3B-I and Beclin 1 increased as demonstrated by Western blot analyses, whereas early or initial autophagic vacuoles (AVi) and late or degraded autophagic vacuoles (AVd) accumulated in the ganglion cell layer (GCL) and in the inner plexiform layer (IPL) as determined by transmission electron microscopy (TEM) analysis. Second, lysosome activity and autophagosome-lysosomal fusion increased in the RGCs of the glaucomatous retinas, as demonstrated by Western blotting against lysosome associated membrane protein-1 (LAMP1) and double labeling against LC3B and LAMP1. Third, apoptosis was activated in the glaucomatous eyes with increased levels of caspase-3 and cleaved caspase-3 and an increased number of TUNEL-positive RGCs. Our results suggested that autophagy was activated in RGCs in the chronic hypertensive glaucoma model of rhesus monkeys and that autophagy may have potential as a new target for intervention in glaucoma treatment.     

A Potential Relationship among Beta-Defensins Haplotype,SOX7 Duplication and Cardiac Defects

Objective

To determine the pathogenesis of a patient born with congenital heart defects, who had appeared normal in prenatal screening.

Methods

In routine prenatal screening, G-banding was performed to analyse the karyotypes of the family and fluorescence in situ hybridization was used to investigate the 22q11.2 deletion in the fetus. After birth, the child was found to be suffering from heart defects by transthoracic echocardiography. In the following study, sequencing was used to search for potential mutations in pivotal genes. SNP-array was employed for fine mapping of the aberrant region and quantitative real-time PCR was used to confirm the results. Furthermore, other patients with a similar phenotype were screened for the same genetic variations. To compare with a control, these variations were also assessed in the general population.

Results

The child and his mother each had a region that was deleted in the beta-defensin repeats, which are usually duplicated in the general population. Besides, the child carried a SOX7-gene duplication. While this duplication was not detected in his mother, it was found in two other patients with cardiac defects who also had the similar deletion in the beta-defensin repeats.

Conclusion

The congenital heart defects of the child were probably caused by a SOX7-gene duplication, which may be a consequence of the partial haplotype of beta-defensin regions at 8p23.1. To our knowledge, this is the first congenital heart defect case found to have the haplotype of beta-defensin and the duplication of SOX7.     

Functional Recovery of Denervated Skeletal Muscle with Sensory or Mixed Nerve Protection: A Pilot Study

Functional recovery is usually poor following peripheral nerve injury when reinnervation is delayed. Early innervation by sensory nerve has been indicated to prevent atrophy of the denervated muscle. It is hypothesized that early protection with sensory axons is adequate to improve functional recovery of skeletal muscle following prolonged denervation of mixed nerve injury. In this study, four groups of rats received surgical denervation of the tibial nerve. The proximal and distal stumps of the tibial nerve were ligated in all animals except for those in the immediate repair group. The experimental groups underwent denervation with nerve protection of peroneal nerve (mixed protection) or sural nerve (sensory protection). The experimental and unprotected groups had a stage II surgery in which the trimmed proximal and distal tibial nerve stumps were sutured together. After 3 months of recovery, electrophysiological, histological and morphometric parameters were assessed. It was detected that the significant muscle atrophy and a good preserved structure of the muscle were observed in the unprotected and protective experimental groups, respectively. Significantly fewer numbers of regenerated myelinated axons were observed in the sensory-protected group. Enhanced recovery in the mixed protection group was indicated by the results of the muscle contraction force tests, regenerated myelinated fiber, and the results of the histological analysis. Our results suggest that early axons protection by mixed nerve may complement sensory axons which are required for promoting functional recovery of the denervated muscle natively innervated by mixed nerve.     

Genome-Wide Transcriptional Response of Silkworm (Bombyx mori) to Infection by the Microsporidian Nosema bombycis

Microsporidia have attracted much attention because they infect a variety of species ranging from protists to mammals, including immunocompromised patients with AIDS or cancer. Aside from the study on Nosema ceranae, few works have focused on elucidating the mechanism in host response to microsporidia infection. Nosema bombycis is a pathogen of silkworm pébrine that causes great economic losses to the silkworm industry. Detailed understanding of the host (Bombyx mori) response to infection by N. bombycis is helpful for prevention of this disease. A genome-wide survey of the gene expression profile at 2, 4, 6 and 8 days post-infection by N. bombycis was performed and results showed that 64, 244, 1,328, 1,887 genes were induced, respectively. Up to 124 genes, which are involved in basal metabolism pathways, were modulated. Notably, B. mori genes that play a role in juvenile hormone synthesis and metabolism pathways were induced, suggesting that the host may accumulate JH as a response to infection. Interestingly, N. bombycis can inhibit the silkworm serine protease cascade melanization pathway in hemolymph, which may be due to the secretion of serpins in the microsporidia. N. bombycis also induced up-regulation of several cellular immune factors, in which CTL11 has been suggested to be involved in both spore recognition and immune signal transduction. Microarray and real-time PCR analysis indicated the activation of silkworm Toll and JAK/STAT pathways. The notable up-regulation of antimicrobial peptides, including gloverins, lebocins and moricins, strongly indicated that antimicrobial peptide defense mechanisms were triggered to resist the invasive microsporidia. An analysis of N. bombycis-specific response factors suggested their important roles in anti-microsporidia defense. Overall, this study primarily provides insight into the potential molecular mechanisms for the host-parasite interaction between B. mori and N. bombycis and may provide a foundation for further work on host-parasite interaction between insects and microsporidia.     

Characterization of Lignins Isolated with Alkaline Ethanol from the Hydrothermal Pretreated Tamarix ramosissima

The objective of this study was to characterize the changes in lignin structure during hydrothermal pretreatment of shrub Tamarix ramosissima. Lignins in residual wood meal were isolated with alkaline ethanol solution and recovered with acid precipitation. A comparison between the recovered lignin fractions with milled wood lignin has been made in terms of yield, purity, gel permeation chromatography, Fourier transform infrared spectroscopy, pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS), 1D ¹³C and 2D heteronuclear single quantum coherence nuclear magnetic resonance (HSQC NMR) spectroscopic techniques. Semiquantitative HSQC NMR showed that the relative amounts of β-O-4′ (around 76 % side chains) and resinol type substructures (16 %) of lignins were significantly modified during hydrothermal pretreatment. Py-GC/MS analyses brought direct evidences of these lignin samples with high S/G ratios ranging from 1.7 to 2.6. Moreover, the results indicated that an increase in the severity of the hydrothermal pretreatment enhanced the degradation of lignin unit side chains and the condensation of lignin and decreased the molecular weight of the recovered lignin fractions. This study demonstrated that the combination of autohydrolysis and alkaline ethanol process could potentially turn the recovered lignin fractions into value added products being in accordance with the “biorefinery” concept.     

Developability studies before initiation of process development

Monoclonal antibodies constitute a robust class of therapeutic proteins. Their stability, resistance to stress conditions and high solubility have allowed the successful development and commercialization of over 40 antibody-based drugs. Although mAbs enjoy a relatively high probability of success compared with other therapeutic proteins, examples of projects that are suspended due to the instability of the molecule are not uncommon. Developability assessment studies have therefore been devised to identify early during process development problems associated with stability, solubility that is insufficient to meet expected dosing or sensitivity to stress. This set of experiments includes short-term stability studies at 2−8 þC, 25 þC and 40 þC, freeze-thaw studies, limited forced degradation studies and determination of the viscosity of high concentration samples. We present here three case studies reflecting three typical outcomes: (1) no major or unexpected degradation is found and the study results are used to inform early identification of degradation pathways and potential critical quality attributes within the Quality by Design framework defined by US Food and Drug Administration guidance documents; (2) identification of specific degradation pathway(s) that do not affect potency of the molecule, with subsequent definition of proper process control and formulation strategies; and (3) identification of degradation that affects potency, resulting in program termination and reallocation of resources.