Ectoplasmic specialization: a friend or a foe of spermatogenesis?

The ectoplasmic specialization (ES) is a testis-specific, actin-based hybrid anchoring and tight junction. It is confined to the interface between Sertoli cells at the blood-testis barrier, known as the basal ES, as well as between Sertoli cells and developing spermatids designated the apical ES. The ES shares features of adherens junctions, tight junctions and focal contacts. By adopting the best features of each junction type, this hybrid nature of ES facilitates the extensive junction-restructuring events in the seminiferous epithelium during spermatogenesis. For instance, the alpha6beta1-integrin-laminin 333 complex, which is usually limited to the cell-matrix interface in other epithelia to facilitate cell movement, is a putative apical ES constituent. Furthermore, JAM-C and CAR, two tight junction integral membrane proteins, are also components of apical ES involving in spermatid orientation. We discuss herein the mechanisms that maintain the cross-talk between ES and blood-testis barrier to facilitate cell movement and orientation in the seminiferous epithelium.     

The S100 proteins for screening and prognostic grading of bladder cancer

The S100 gene family, which is composed of at least 24 members carrying the Ca2+ binding EF-hand motif, has been implicated in both intracellular and extracellular functions, including enzyme activities, immune responses, cytoskeleton dynamics, Ca2+ homeostasis, cell growth and cell differentiation. Altered S100 protein levels are associated with a broad range of diseases, including cardiomyopathy, inflammatory and immune disorders, neurodegenerative disorders and cancer. Although the precise role of S100 protein in carcinogenesis is poorly understood, it seems that formation of homo- and hetero-dimers, binding of Ca2+ and interaction with effector molecules are essential for the development and progression of many cancers. Several studies have suggested that S100 proteins promote cancer progression and metastasis through cell survival and apoptosis pathways. In animal models of bladder cancer, several S100 proteins are differentially expressed in bladder tumors relative to normal urothelium. In human bladder cancer, overexpression of S100A4, S100A8 or S100A11 are associated with stage progression, invasion, metastasis and poor survival. This review summarizes these findings and evaluates their implications for human bladder cancer management.     

LYVE-1和D2—40在检测早期宫颈鳞状细胞癌和癌前病变微淋巴管中的研究

目的对比分析两种常用的淋巴内皮细胞标记分子LYVE-1和D2—40在检测宫颈癌癌前病变和早期宫颈鳞状细胞癌（简称鳞癌）组织中微淋巴管的异同,结合临床资料分析其与宫颈鳞癌的临床分期,淋巴转移和病理特点之间的关系。方法采用SP法检测抗人淋巴管内皮透明质酸受体-1（1ymphatic Vesselendothelial HAreceptor-1,LYVE-1）多克隆抗体和D2—40单克隆抗体免疫组织化学染色分别检测22例宫颈癌癌前病变和36例早期宫颈鳞癌组织中的淋巴管密度（lympatie vessel density,LVD）,图像分析系统统计LVD的水平。结果 1.两种标记分子检测均发现在宫颈癌前病变和早期鳞癌中LVD随着疾病的进展而显著增加（P〈0．001）,同时均发现LVD与盆腔淋巴结状态密切相关。2．对比两种分子染色效果,两种标记分子各有优劣,联合起来使用更为可靠。结论 LYVE-1和D2-40结合使用能更准确反应宫颈淋巴管的情况,宫颈癌前病变和早期宫颈癌组织中高淋巴管分布与淋巴转移和肿瘤分期有关。     

Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury

Toll-like receptors (TLRs) play an essential role in innate immune responses and in the initiation of adaptive immune responses. Microglia, the resident innate immune cells in the CNS, express TLRs. In this study, we show that TLR3 is crucial for spinal cord glial activation and tactile allodynia after peripheral nerve injury. Intrathecal administration of TLR3 antisense oligodeoxynucleotide suppressed nerve injury-induced tactile allodynia, and decreased the phosphorylation of p38 mitogen-activated protein kinase, but not extracellular signal-regulated protein kinases 1/2, in spinal glial cells. Antisense knockdown of TLR3 also attenuated the activation of spinal microglia, but not astrocytes, caused by nerve injury. Furthermore, down-regulation of TLR3 inhibited nerve injury-induced up-regulation of spinal pro-inflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. Conversely, intrathecal injection of the TLR3 agonist polyinosine–polycytidylic acid induced behavioral, morphological, and biochemical changes similar to those observed after nerve injury. Indeed, TLR3-deficient mice did not develop tactile allodynia after nerve injury or polyinosine–polycytidylic acid injection. Our results indicate that TLR3 has a substantial role in the activation of spinal glial cells and the development of tactile allodynia after nerve injury. Thus, blocking TLR3 in the spinal glial cells might provide a fruitful strategy for treating neuropathic pain.     

Characterization of the in vivo and in vitro metabolic profile of PAC-1 using liquid chromatography-mass spectrometry

In the present study, the metabolic profile of PAC-1, a potential anticancer drug, was investigated using liquid chromatography-mass spectrometric (LC/MS) techniques. Two different types of mass spectrometers--a quadrupole time-of-flight (Q-TOF) mass spectrometer and an ion trap (IT) mass spectrometer--were employed to acquire structural information on PAC-1 metabolites. A gradient liquid chromatographic system composed of 0.2% formic acid in methanol and 0.2% formic acid in water was used for metabolite separation on an Agilent TC-C(18) column. A total of 16 metabolites were detected. The corresponding product ion spectra were acquired and interpreted, and structures were proposed. Accurate mass measurement using LC-Q-TOF was used to determine the elemental composition of metabolites thereby confirming the proposed structures of these metabolites. Phase I metabolic changes were predominantly observed, including debenzylation, dihydrodiol formation, hydroxylation, and dihydroxylation. The detected phase II metabolites included PAC-1 and hydroxylated PAC-1 glucuronide conjugates. Based on metabolite analysis, several PAC-1 metabolic pathways in rat were proposed.     

Association of single-nucleotide polymorphisms in RHOB and TXNDC3 with knee osteoarthritis susceptibility: two case-control studies in East Asian populations and a meta-analysis

Introduction

Conflicting findings on the association of single nucleotide polymorphisms (SNPs) in RHOB and TXNDC3 with susceptibility to knee osteoarthritis (OA) have been reported in European Caucasians. To examine the associations of these SNPs with OA in East Asian populations and to evaluate their global significance, we conducted two case-control studies in 955 Chinese and 750 Japanese patients.

Methods

We genotyped the previously implicated SNPs rs585017 (in RHOB) and rs4720262 (in TXNDC3) in patients with primary symptomatic knee OA with radiographic confirmation and in matched control individuals, and analyzed their associations. We further conducted a meta-analysis of the study findings together with those of previously reported European studies using the DerSimonian-Laird procedure.

Results

A significant association of RHOB with knee OA was observed in male Chinese patients (P = 0.02). No significant associations were found for RHOB in any other comparisons in the East Asian populations. The association of TXNDC3 was replicated in Chinese female (P = 0.04) and Japanese (P = 0.03) patients, although none of these associations persisted after Bonferroni correction. Significant association (P = 0.02 for the allelic frequency) with nonsignificant heterogeneity was found in the East Asian replication study. No significant association was found in any comparison in the meta-analysis for all studies.

Conclusion

Our study replicates the association, previously reported in European Caucasians, of TXNDC3 with knee OA susceptibility in an East Asian population.