Ablation of Liver X receptor β in mice leads to overactive macrophages and death of spiral ganglion neurons.

Age-related hearing loss is the most common type of hearing impairment, and is typically characterized by the loss of spiral ganglion neurons (SGNs). The two Liver X receptors (LXRs) are oxysterol-activated nuclear receptors which in adults, regulate genes involved in cholesterol homeostasis and modulation of macrophage activity. LXRβ plays a key role in maintenance of health of dopaminergic neurons in the substantia nigra, large motor neurons in the spinal cord, and retinal ganglion cells in adult mice.

A phase I clinical trial of human embryonic stem cell-derived retinal pigment epithelial cells for early-stage Stargardt macular degeneration: 5-years' follow-up.

Objectives: To evaluate the long-term biosafety and efficacy of transplantation of human embryonic stem cells-derived retinal pigment epithelial (hESC-RPE) cells in early-stage of Stargardt macular degeneration (STGD1).

Materials And Methods: Seven patients participated in this prospective clinical study, where they underwent a single subretinal transplantation of 1 × 10 hESC-RPE cells in one eye, whereas the fellow eye served as control. These patients were reassessed for a 60-month follow-up through systemic and ophthalmic examinations.

LCT-3d Induces Oxidative Stress-Mediated Apoptosis by Upregulating Death Receptor 5 in Gastric Cancer Cells.

Gastric cancer is a global health problem. In this study, we investigate the role of a novel Indole derivative, named LCT-3d, in inhibiting the growth of gastric cancer cells by MTT assay. The Western blotting results showed that LCT-3d modulated the mitochondrial-related proteins and Cleaved-Caspases 3/9, to induce cell apoptosis.

Functional assessment of cryopreserved clinical grade hESC-RPE cells as a qualified cell source for stem cell therapy of retinal degenerative diseases.

The biosafety and efficiency of transplanting retinal pigment epithelial (RPE) cells derived from both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been evaluated in phase I and phase II clinical trials. For further large-scale application, cryopreserved RPE cells must be used; thus, it is highly important to investigate the influence of cryopreservation and thawing on the biological characteristics of hESC-RPE cells and their post-transplantation vision-restoring function. Here, via immunofluorescence, qPCR, transmission electron microscopy, transepithelial electrical resistance, and enzyme-linked immunosorbent assays (ELISAs), we showed that cryopreserved hESC-RPE cells retained the specific gene expression profile, morphology, ultrastructure, and maturity-related functions of induced RPE cells.

Biosafety of a 3D-printed intraocular lens made of a poly(acrylamide-co-sodium acrylate) hydrogel and .

Aim: To assess the biosafety of a poly(acrylamide-co-sodium acrylate) hydrogel (PAH) as a 3D-printed intraocular lens (IOL) material.

Methods: The biosafety of PAH was first evaluated using human lens epithelial cells (LECs) and the ARPE19 cell line, and a cell counting kit-8 (CCK-8) assay was performed to investigate alterations in cell proliferation. A thin film of PAH and a conventional IOL were intraocularly implanted into the eyes of New Zealand white rabbits respectively, and a sham surgery served as control group.

A low toxic CRM1 degrader: Synthesis and anti-proliferation on MGC803 and HGC27.

Chromosome region maintenance 1 (CRM1) is the sole nuclear exporter of several tumor suppressor, a growth regulatory protein as an attractive cancer drug target. In the present work, a novel CRM1 degrader was discovered from newly synthesized α, β-unsaturated-δ-lactone based on a natural product Goniothalamin. It induces apoptosis of both MGC803 and HGC27 cell lines via degrading CRM1.

Identification of 13 novel USH2A mutations in Chinese retinitis pigmentosa and Usher syndrome patients by targeted next-generation sequencing.

Background: The USH2A gene encodes usherin, a basement membrane protein that is involved in the development and homeostasis of the inner ear and retina. Mutations in USH2A are linked to Usher syndrome type II (USH II) and non-syndromic retinitis pigmentosa (RP). Molecular diagnosis can provide insight into the pathogenesis of these diseases, facilitate clinical diagnosis, and identify individuals who can most benefit from gene or cell replacement therapy.

Discovery and synthesis of novel indole derivatives-containing 3-methylenedihydrofuran-2(3H)-one as irreversible LSD1 inhibitors.

Lysine-specific demethylase 1 (LSD1), demethylase against mono- and di - methylated histone3 lysine 4, has emerged as a promising target in oncology. More specifically, it has been demonstrated as a key promoter in acute myeloid leukemia (AML), and several LSD1 inhibitors have already entered into clinical trials for the treatment of AML. In this paper, a series of new indole derivatives were designed and synthesized based on a lead compound obtained by a high-throughput screening with our in-house compound library.

CT-based Morphometric Analysis of Approach of Percutaneous Transforaminal Endoscopic Lumbar Interbody Fusion.

Objectives: A radiographic study was designed to measure the relationship of the exiting nerve root and its surroundings to the corresponding intervertebral disc for percutaneous transforaminal endoscopic lumbar interbody fusion to better understand the regional anatomy and to improve clinical applications.

Methods: A retrospective study from January 2017 to October 2017 was conducted at Tianjin Hospital. CT images were obtained from patients presenting low back pain (110 patients), and analysis was performed bilaterally from L to L S .

Human embryonic stem cell-derived retinal pigment epithelium transplants as a potential treatment for wet age-related macular degeneration.

Stem cell therapy may provide a safe and promising treatment for retinal diseases. Wet age-related macular degeneration (wet-AMD) is a leading cause of blindness in China. We developed a clinical-grade human embryonic stem cell (hESC) line, Q-CTS-hESC-2, under xeno-free conditions that differentiated into retinal pigment epithelial cells (Q-CTS-hESC-2-RPE).

Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients.

Background: Retinitis pigmentosa is a common genetic disease that causes retinal degeneration and blindness for which there is currently no curable treatment available. Vision preservation was observed in retinitis pigmentosa animal models after retinal stem cell transplantation. However, long-term safety studies and visual assessment have not been thoroughly tested in retinitis pigmentosa patients.

Thoracic Endoscopic-Assisted Mini-Open Surgery for Thoracic and Thoracolumbar Spinal Cord Compression.

Intervertebral disc herniation is a common cause of spinal cord compression, especially for the thoracic and thoracolumbar spinal cord, which has limited buffer space in the spinal canal. Spinal cord compression usually causes decreased sensation and paralysis of limbs below the level of compression, urinary and fecal incontinence, and/or urinary retention, which brings great suffering to the patients and usually requires surgical intervention. Thoracotomy or abdominothoracic surgery is usually performed for the thoracolumbar cord compression caused by hard intervertebral disc herniation.

Promotion of axon regeneration and inhibition of astrocyte activation by alpha A-crystallin on crushed optic nerve.

Aim: To explore the effects of αA-crystallin in astrocyte gliosis after optic nerve crush (ONC) and the mechanism of α-crystallin in neuroprotection and axon regeneration.

Methods: ONC was established on the Sprague-Dawley rat model and αA-crystallin (10(-4) g/L, 4 µL) was intravitreously injected into the rat model. Flash-visual evoked potential (F-VEP) was examined 14d after ONC, and the glial fibrillary acidic protein (GFAP) levels in the retina and crush site were analyzed 1, 3, 5, 7 and 14d after ONC by immunohistochemistry (IHC) and Western blot respectively.

Intervertebral Fusion with Mobile Microendoscopic Discectomy for Lumbar Degenerative Disc Disease.

The aim of this article is to introduce a technique for lumbar intervertebral fusion that incorporates mobile microendoscopic discectomy (MMED) for lumbar degenerative disc disease. Minimally invasive transforaminal lumbar interbody fusion is frequently performed to treat degenerative diseases of the lumbar spine; however, the scope of such surgery and vision is limited by what the naked eye can see through the expanding channel system. To expand the visual scope and reduce trauma, we perform lumbar intervertebral fusion with the aid of a MMED system that provides a wide field through freely tilting the surgical instrument and canals.

Construction Strategy and Progress of Whole Intervertebral Disc Tissue Engineering.

Degenerative disc disease (DDD) is the major cause of low back pain, which usually leads to work absenteeism, medical visits and hospitalization. Because the current conservative procedures and surgical approaches to treatment of DDD only aim to relieve the symptoms of disease but not to regenerate the diseased disc, their long-term efficiency is limited. With the rapid developments in medical science, tissue engineering techniques have progressed markedly in recent years, providing a novel regenerative strategy for managing intervertebral disc disease.

Novel compound heterozygous mutation in the CNGA1 gene underlie autosomal recessive retinitis pigmentosa in a Chinese family.

Retinitis pigmentosa (RP) describes a group of inherited retinopathies that are characterized by the progressive degeneration of photoreceptor neurons, which causes night blindness, a reduction in the peripheral visual field and decreased visual acuity. More than 50 RP-related genes have been identified. In the present study, we analysed a Chinese family with autosomal recessive RP.

Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits.

Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression.

Base-promoted transannulation of heterocyclic enamines and 2,3-epoxypropan-1-ones: regio- and stereoselective synthesis of fused pyridines and pyrroles.

Base-promoted transannulation of heterocyclic enamines and 2,3-epoxypropan-1-ones has been successfully achieved, providing a new access to structurally diverse fused pyridines and pyrroles with excellent regio- and stereoselectivity. Treatment with N-aryl 4-aminofuran-2(5H)-ones and 2,3-epoxypropan-1-ones under microwave heating resulted in functional furo[3,2-b]pyridines in good yields. The N-aryl 4-aminopyrrol-2(5H)-ones bearing an electron-withdrawing group engaged in the reaction afforded pyrrolo[3,2-b]pyridines, whereas their counterparts with an electron-neutral or an electron-donating group underwent a different reaction pathway to form pyrrolo[3,2-b]pyrroles through C-C bond cleavage.

Identification of novel CYP4V2 gene mutations in 92 Chinese families with Bietti's crystalline corneoretinal dystrophy.

Purpose: To characterize the spectrum of CYP4V2 gene mutations in 92 unrelated Chinese probands with Bietti's crystalline dystrophy (BCD) and to describe the molecular and clinical characteristics of four novel CYP4V2 mutations associated with BCD.

Methods: All study participants underwent a complete ophthalmological examination. Mutational screening of CYP4V2 coding regions and flanking intron sequences was examined via directional Sanger sequencing, with allele separation confirmed by screening other family members.

Detecting novel genetic mutations in Chinese Usher syndrome families using next-generation sequencing technology.

Usher syndrome (USH) is the most common cause of combined blindness and deafness inherited in an autosomal recessive mode. Molecular diagnosis is of great significance in revealing the molecular pathogenesis and aiding the clinical diagnosis of this disease. However, molecular diagnosis remains a challenge due to high phenotypic and genetic heterogeneity in USH.

Detecting genetic variations in hereditary retinal dystrophies with next-generation sequencing technology.

Purpose: To identify pathogenic mutations responsible for retinal dystrophies (RDs) in three unrelated Chinese families.

Methods: Three probands from unrelated families with RDs were recruited. Genomic DNA prepared from leukocytes was analyzed using gene chip-based next-generation sequencing (NGS) to capture and sequence all of the exons of 100 known RD-associated genes.

Effect of optogenetic stimulus on the proliferation and cell cycle progression of neural stem cells.

Modulation of stem cell proliferation is a crucial aspect of neural developmental biology and regenerative medicine. To investigate the effect of optical stimulation on neural stem cell proliferation, cells transduced with channelrhodopsin-2 (ChR2) were used to analyze changes in cell proliferation and cell cycle distribution after light stimulation. Blue light significantly inhibited cell proliferation and affected the cell cycle, which increased the percentage of cells in G1 phase and reduced the percentage in S phase.