Transplantation of derivative retinal organoids from chemically induced pluripotent stem cells restored visual function.

As an emerging type of pluripotent stem cells, chemically induced pluripotent stem cells (CiPSCs) avoid the risks of genomic disintegration by exogenous DNAs from viruses or plasmids, providing a safer stem cell source. To verify CiPSCs' capacity to differentiate into retinal organoids (ROs), we induced CiPSCs from mouse embryonic fibroblasts by defined small-molecule compounds and successfully differentiated the CiPSCs into three-dimensional ROs, in which all major retinal cell types and retinal genes were in concordance with those in vivo. We transplanted retinal photoreceptors from ROs into the subretinal space of retinal degeneration mouse models and the cells could integrate into the host retina, establish synaptic connections, and significantly improve the visual functions of the murine models.

Chromone-deferiprone hybrids as novel MAO-B inhibitors and iron chelators for the treatment of Alzheimer's disease.

A series of chromone-deferiprone hybrids were designed, synthesized, and evaluated as inhibitors of human monoamine oxidase B (MAO-B) with iron-chelating activity for the treatment of Alzheimer's disease (AD). The majority exhibited moderate inhibitory activity towards MAO-B and potent iron-chelating properties. Particularly, compound 25c demonstrated remarkable selectivity against MAO-B with an IC value of 1.

Effects of fluorescent protein tdTomato on mouse retina.

Fluorescent proteins (FPs) have been widely used to investigate cellular and molecular interactions and trace biological events in many applications. Some of the FPs have been demonstrated to cause undesirable cellular damage by light-induced ROS production in vivo or in vitro. However, it remains unknown if one of the most popular FPs, tdTomato, has similar effects in neuronal cells.

REG1A protects retinal photoreceptors from blue light damage.

With the increased use of artificial light and the prolonged use of optoelectronic products, light damage (LD) to the human retina has been identified as a global vision-threatening problem. While there is evidence of a significant correlation between light-induced retinal damage and age-related vision impairment in age-related macular degeneration, it is unclear how light-induced retinal degeneration manifests itself and whether there are agents capable of preventing the development of LD in the retina. This study investigated a mechanism by which blue light leads to photoreceptor death.

Mutation of SLC7A14 causes auditory neuropathy and retinitis pigmentosa mediated by lysosomal dysfunction.

Lysosomes contribute to cellular homeostasis via processes including macromolecule degradation, nutrient sensing, and autophagy. Defective proteins related to lysosomal macromolecule catabolism are known to cause a range of lysosomal storage diseases; however, it is unclear whether mutations in proteins involved in homeostatic nutrient sensing mechanisms cause syndromic sensory disease. Here, we show that SLC7A14, a transporter protein mediating lysosomal uptake of cationic amino acids, is evolutionarily conserved in vertebrate mechanosensory hair cells and highly expressed in lysosomes of mammalian cochlear inner hair cells (IHCs) and retinal photoreceptors.

Antioxidant and anti-tyrosinase activity of a novel stilbene analogue as an anti-browning agent.

Background: Tyrosinase inhibitors find potential application in food, cosmetic and medicinal products, but most of the identified tyrosinase inhibitors are not suitable for practical use because of safety regulations or other problems. For the purpose of development of novel tyrosinase inhibitors that meet the requirement for practical application, a novel stilbene analogue (SA) was designed.

Results: SA was found to possess a potent inhibitory effect against both mono- and diphenolase activities of mushroom tyrosinase, with IC values of 1.

Retinal Degeneration Caused by Ago2 Disruption.

Purpose: Argonaute proteins are key players in small RNA-guided gene silencing processes. Ago2 is the member of the Argonaute subfamily with slicer endonuclease activity and is critical for microRNA homeostasis and indispensable for biological development. However, the impact of Ago2 dysregulation in the retina remains to be fully explored.

Transplantation of GMP-grade human iPSC-derived retinal pigment epithelial cells in rodent model: the first pre-clinical study for safety and efficacy in China.

Background: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly due in large part to age-dependent atrophy of retinal pigment epithelium (RPE) cells. RPE cells form a monolayer located between the choroid and the outer segments of photoreceptors, playing multifarious roles in maintenance of visual function. Allogeneically induced pluripotent stem cell-derived RPE (iPSC-RPE or iRPE) has become a potential approach for providing an abundant source of donors for clinical cell products.

Human embryonic stem cell-derived organoid retinoblastoma reveals a cancerous origin.

Retinoblastoma (Rb) is the most prevalent intraocular malignancy in children, with a worldwide survival rate <30%. We have developed a cancerous model of Rb in retinal organoids derived from genetically engineered human embryonic stem cells (hESCs) with a biallelic mutagenesis of the gene. These organoid Rbs exhibit properties highly consistent with Rb tumorigenesis, transcriptome, and genome-wide methylation.

The road to restore vision with photoreceptor regeneration.

Neuroretinal diseases are the predominant cause of irreversible blindness worldwide, mainly due to photoreceptor loss. Currently, there are no radical treatments to fully reverse the degeneration or even stop the disease progression. Thus, it is urgent to develop new biological therapeutics for these diseases on the clinical side.

Generation of Nonhuman Primate Model of Cone Dysfunction through AAV-Mediated Ablation.

A major challenge to the development of therapies for human retinal degenerative diseases is the lack of an ideal preclinical model because of the physiological differences between humans and most model animals. Despite the successful generation of a primate model through germline knockout of a disease-causing gene, the major issues restricting modeling in nonhuman primates (NHPs) are their relatively long lifespan, lengthy gestation, and dominant pattern of singleton births. Herein, we generated three cynomolgus macaques with macular knockout by subretinal delivery of an adeno-associated virus (AAV)-mediated CRISPR-Cas9 system targeting , the gene responsible for achromatopsia.

Ablation of Mature miR-183 Leads to Retinal Dysfunction in Mice.

Purpose: The microRNA cluster miR-183C, which includes miR-183 and two other genes, is critical for multiple sensory systems. In mouse retina, removal of this cluster results in photoreceptor defects in polarization, phototransduction, and outer segment elongation. However, the individual roles of the three components of this cluster are not clearly known.

The Circular RNome of Developmental Retina in Mice.

Circular RNAs (circRNAs) represent a class of noncoding RNAs with a wide expression pattern, and they constitute an important layer of the genome regulatory network. To date, the expression pattern and regulatory potency of circRNAs in the retina, a key part of the central nervous system, are not yet well understood. In this study, RNAs from five stages (E18.

Serum Human Epididymis Protein 4 Combined with Carbohydrate Antigen 125 for Endometrial Carcinoma Diagnosis: A Meta-Analysis and Systematic Review.

To evaluate the overall diagnostic value of human epididymis protein 4 (HE4) combined with carbohydrate antigen 125 (CA125) in endometrial carcinoma (EC) based on a meta-analysis of all eligible studies. The PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP databases were searched by index words to identify eligible studies and also to search for relevant literature sources that had been published by January 2019. Eligible studies included prospective cohort studies or cross-sectional studies.

Deletion of miR-182 Leads to Retinal Dysfunction in Mice.

Purpose: MicroRNA-182 (miR-182) is abundantly expressed in mammalian retinas; however, the association between miR-182 and retinal function remains unclear. In this study, we explored whether miR-182 contributes to functional decline in retinas using a miR-182 depleted mouse.

Methods: Electroretinogram (ERG) amplitudes at different ages were measured in miR-182 knockout (KO) mice.

[Methyltransferase inhibitor BIX01294 promotes the migration and inhibits decidualization of mouse uterine stromal cells in vitro].

Objective: To investigate the effect of BIX01294 (BIX), a methyltransferase inhibitor, on the migration and decidualization of the stromal cells in mouse uterus.

Methods: Mouse endometrial stromal cells were isolated and cultured from the uterus of pregnant mice on day 3.5 of gestation.

miR-183/96 plays a pivotal regulatory role in mouse photoreceptor maturation and maintenance.

MicroRNAs (miRNAs) are known to be essential for retinal maturation and functionality; however, the role of the most abundant miRNAs, the miR-183/96/182 cluster (miR-183 cluster), in photoreceptor cells remains unclear. Here we demonstrate that ablation of two components of the miR-183 cluster, miR-183 and miR-96, significantly affects photoreceptor maturation and maintenance in mice. Morphologically, early-onset dislocated cone nuclei, shortened outer segments and thinned outer nuclear layers are observed in the miR-183/96 double-knockout (DKO) mice.

[Expression of FABP7 in mouse placenta tissue and human trophoblast HTR-8/Svneo cells].

Objective: To detect the expression of FABP7 in the placenta of pregnant mice and in HTR-8/Svneo cells.

Methods: Real-time PCR and immunofluorescence were used to detect FABP7 mRNA and protein expressions in the uterine and placental tissue of pregnant mice at different days of gestation. FABP7 expression was also detected in cultured HTR-8/Svneo cells using immunofluorescence assay.

Protective Effects of Curcumin against Sodium Arsenite-induced Ovarian Oxidative Injury in a Mouse Model.

Background: Excessive reactive oxygen species (ROS) may lead to a number of reproductive diseases such as polycystic ovary syndrome. This study aimed to establish an animal model of ovarian oxidative stress and to assess the protective effect of curcumin against oxidative injury.

Methods: Ovarian oxidative stress was induced in female Kunming mice (n = 40) with intraperitoneal injection of 8 mg/kg sodium arsenite (As) once every other day for 16 days; meanwhile, they were, respectively, treated by intragastric administration of 0, 100, 150, or 200 mg/kg (n = 10/group) curcumin once per day for 21 days.

Toll-Like Receptor 3 Activation Initiates Photoreceptor Cell Death In Vivo and In Vitro.

Purpose: Accumulating evidence has demonstrated that excessive immunoreaction plays a prominent role in the pathogenesis of dry AMD. Toll-like receptor 3 (TLR3) can be activated by double-stranded (ds)RNA in retinal pigment epithelia and trigger an innate immunity-mediated inflammatory response. However, its role in photoreceptor cells, the effectors of AMD geographic atrophy, remains unclear.

Astilbin ameliorates experimental autoimmune myasthenia gravis by decreased Th17 cytokines and up-regulated T regulatory cells.

Astilbin, a major bioactive compound extracted from Rhizoma smilacis glabrae (RSG), has been reported to possess immunosuppressive properties. Our study first evaluated the effect of astilbin on experimental autoimmune myasthenia gravis (EAMG) in Lewis rats. The results showed that astilbin could attenuate the severity of EAMG by decreasing antigen-specific autoantibodies with up-regulation of regulatory T cells and down-regulation of Th17 cells.

Strong association of and gene variants with idiopathic male infertility in Han Chinese.

Male infertility is a multifactorial syndrome encompassing a wide variety of disorders. In recent years, several genome-wide single-nucleotide polymorphism (SNP) association studies (GWAS) have been performed on azoospermia and/or oligozoospermia in different populations including two GWAS on nonobstructive azoospermia in China; however, the association of SNPs with idiopathic male infertility, especially asthenozoospermia and oligozoospermia, and their correlation with semen parameters are still not clear. To investigate genetic variants associated with idiopathic male infertility (asthenozoospermia, oligozoospermia, and oligoasthenozoospermia) in Chinese Han people, 20 candidate SNPs were selected from GWAS results and genotyped using the Sequenom MassARRAY assay.

Twin delivery after IVF-ET with variable dose letrozole-FSH protocol of lower estradiol in a patient previously treated for breast cancer: a case report.

Objective: To present a case of twin pregnancy obtained by in vitro fertilization and embryo transfer (IVF-ET) with variable dose letrozole-FSH protocol of lower peak estradiol level, after treatment of carcinoma of the breast.

Materials And Methods: A 34-year-old patient diagnosed with mucinous breast carcinoma undergoing assisted fertilization treatment after breast cancer operation and treatment including controlled ovarian stimulation (COS), oocyte retrieval, IVF, and embryo culture and transfer.

Results: Four oocytes were obtained in three COS procedures in the three IVF cycle.