Histone deacetylases in hearing loss: Current perspectives for therapy

Hearing loss is one of the most frequent health issues in industrialized countries. The pathogenesis and molecular mechanisms of hearing loss are still unclear. Histone deacetylases(HDACs) are emerging as key enzymes in many physiological processes, including chromatin remodeling,regulation of transcription, DNA repair, metabolism, genome stability and protein secretion. Recent studies indicated that HDACs are associated with the development and progression of hearing loss. Dysfunction of HDACs could promote the oxidative stress and aging in the inner ear. In light of considering the current stagnation in the development of therapeutic options, the need for new strategies in the treatment of hearing loss has never been so pressing. In this review, we will summarize the reported literatures for HDACs in hearing loss and discuss how HDAC family members show different performances for the possibility of process of diseases development. The possibility of pharmacological intervention on hearing loss opens a novel path in the treatment of hearing loss.

The potential application of formulation with pimelic acid as eye drops for corneal collagen cross-linking

Background and aim:Keratoconus is a slowly progressive and non-inflammatory disease of eye of unknown etiology characterized by significant structural degeneration,thinning and protrusion of cornea.Collagen cross linking using Riboflavin/ultraviolet A,paraformaldehyde and glutaraldehyde has been widely used to treat keratoconus,but these techniques have several clinical complications.This study aimed to develop a rapid,safer,less toxic and more effective method to increase the corneal stiffness hence treating keratoconus by using EDC/NHS coupling with pimelic acid(PA)as cross-linkers.Methods:The viability of corneal epithelial and endothelial cells was examined using Alamar blue.The corneal collagen and tissue integrity were evaluated with Masson and hematoxylin and eosin stains respectively.Uniaxial tensile testing was conducted to determine the tissue stiffness.We further assessed the effective penetration depth of cross-linking by fluorescence dye and confocal microscopy.TUNEL assay was performed to detect the damaged DNA fragments in the presence of PA.Results:The effect of PA solution on corneal cross-linking showed a significant increase in corneal rigidity without affecting the epithelium integrity under neutralized pH condition,while DEC/NHS alone did not induce the mechanical property.The penetration depth showed consistent results with increased stiffness,which could be affected by the parameters including pH condition,coupling with or without PA.In addition,PA significantly decreased the percentage of TUNEL-positive cells compared to that of EDC/NHS only condition.The cytotoxic effect to endothelium was considered minimal and protected in the presence of PA.Conclusions:We demonstrated PA as a potential alternative for cross-linking in the model of whole eye with intact epithelium and its protective role on endothelium.The administration of this chemical cross-linker stands as an extremely promising technique for the treatment of corneal keratoconus.

SOX10和GATA3在乳腺癌中的表达及意义

目的探讨SOX10和GATA3在乳腺癌中的表达特点及其联合应用的价值。方法收集深圳市人民医院病理科2018—2021年行SOX10免疫组织化学染色的乳腺癌标本360例, 其中同时行SOX10和GATA3染色的乳腺癌标本268例, 分析SOX10和GATA3在原发性及转移性乳腺癌中的表达, 并比较二者与乳腺癌分子分型、临床病理特征之间的相关性, 统计其在各分组间的分布差异。结果 SOX10和GATA3在乳腺癌中的总表达率分别为25.8%(93/360)、81.7%(219/268), 在三阴型乳腺癌(triple negative breast cancer, TNBC)中的总表达率分别为83.3%(80/96)、42.7%(32/75)。SOX10在TNBC中高表达(P<0.001), 而GATA3在luminal A型、luminal B型及HER2过表达型中高表达(P<0.001)。在TNBC中SOX10与GATA3的表达呈负相关, 二者联合应用在乳腺癌及TNBC中的表达率可分别高达97.8%(262/268)、94.7%(71/75)。此外, SOX10的表达与高组织学分级、高Ki-67阳性指数及淋巴结转移密切相关, 与雄激素受体(AR)呈负相关, GATA3的表达与低组织学分级及淋巴结转移密切相关, 与AR呈正相关, 差异有统计学意义。结论 SOX10是TNBC的灵敏标志物, 而GATA3在非三阴型乳腺癌中高表达, 二者互补, 联合应用SOX10及GATA3可提高乳腺癌尤其是TNBC的检出率。此外, SOX10与肿瘤恶性特征相关, 提示SOX10可作为乳腺癌预后评估及潜在治疗靶点。