A primate nigrostriatal atlas of neuronal vulnerability and resilience in a model of Parkinson's disease.

The degenerative process in Parkinson's disease (PD) causes a progressive loss of dopaminergic neurons (DaNs) in the nigrostriatal system. Resolving the differences in neuronal susceptibility warrants an amenable PD model that, in comparison to post-mortem human specimens, controls for environmental and genetic differences in PD pathogenesis. Here we generated high-quality profiles for 250,173 cells from the substantia nigra (SN) and putamen (PT) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian macaques and matched controls.

Neural cell isolation from adult macaques for high-throughput analyses and neurosphere cultures.

The low number of neural progenitor cells (NPCs) present in the adult and aged primate brains represents a challenge for generating high-yield and viable in vitro cultures of primary brain cells. Here we report a step-by-step approach for the fast and reproducible isolation of high-yield and viable primary brain cells, including mature neurons, immature cells and NPCs, from adult and aged macaques. We describe the anesthesia, transcardial perfusion and brain tissue preparation; the subsequent microdissection of the regions of interest and their enzymatic dissociation, leading to the separation of single cells.

Embryonic stem cell extracellular vesicles reverse the senescence of retinal pigment epithelial cells by the p38MAPK pathway.

Retinal pigment epithelial (RPE) cellular senescence is regarded as an initiator for age-related macular degeneration (AMD). We previously demonstrated that by the coculture way, embryonic stem cells (ESCs) can reverse the senescence of RPE cells, but xenograft cells can cause a plethora of adverse effects. Extracellular vesicles (EVs) derived from ESCs can act as messengers to mediate nearby cell activities and have the same potential as ESCs to reverse RPE senescence.

Defects and asymmetries in the visual pathway of non-human primates with natural strabismus and amblyopia.

Strabismus and amblyopia are common ophthalmologic developmental diseases caused by abnormal visual experiences. However, the underlying pathogenesis and visual defects are still not fully understood. Most studies have used experimental interference to establish disease-associated animal models, while ignoring the natural pathophysiological mechanisms.

Linking transcriptomes with morphological and functional phenotypes in mammalian retinal ganglion cells.

Retinal ganglion cells (RGCs) are the brain's gateway to the visual world. They can be classified into different types on the basis of their electrophysiological, transcriptomic, or morphological characteristics. Here, we characterize the transcriptomic, morphological, and functional features of 472 high-quality RGCs using Patch sequencing (Patch-seq), providing functional and morphological annotation of many transcriptomic-defined cell types of a previously established RGC atlas.

The embryonic stem cell microenvironment inhibits mouse glioma cell proliferation by regulating the PI3K/AKT pathway.

Background: Glioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system, accounting for 48.6% of malignant tumors. The current standard treatment plan includes the widest range of safe surgical resection, supplemented by local brain radiotherapy and temozolomide concurrent chemotherapy; this can cause serious side effects.

Tumor Microenvironmental Competitive Endogenous RNA Network and Immune Cells Act as Robust Prognostic Predictor of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is malignant hematologic tumors with frequent recurrence and cause high mortality. Its fate is determined by abnormal intracellular competitive endogenous RNA (ceRNA) network and extracellular tumor microenvironment (TME). This study aims to build a ceRNA network related to AML TME to explore new prognostic and therapeutic targets.

Therapeutic effects and perspective of stem cell extracellular vesicles in aging and cancer.

Senescent cells can secrete a plethora of cytokines which induce senescent phenotype of neighboring cells and was called senescence-associated secretory phenotype. Previously, it was believed that cancer was caused by the infinite division and uncontrolled proliferation of cells. Based on this, anticancer treatments were all aimed at killing cancer cells.

Immune Microenvironment Related Competitive Endogenous RNA Network as Powerful Predictors for Melanoma Prognosis Based on WGCNA Analysis.

Cutaneous melanoma is the most life-threatening skin malignant tumor due to its increasing metastasis and mortality rate. The abnormal competitive endogenous RNA network promotes the development of tumors and becomes biomarkers for the prognosis of various tumors. At the same time, the tumor immune microenvironment (TIME) is of great significance for tumor outcome and prognosis.

Identification of circRNA-lncRNA-miRNA-mRNA Competitive Endogenous RNA Network as Novel Prognostic Markers for Acute Myeloid Leukemia.

Background: Acute myeloid leukemia (AML) is one of the most common malignant and aggressive hematologic tumors, and its pathogenesis is associated with abnormal post-transcriptional regulation. Unbalanced competitive endogenous RNA (ceRNA) promotes tumorigenesis and progression, and greatly contributes to tumor risk classification and prognosis. However, the comprehensive analysis of the circular RNA (circRNA)-long non-coding RNA (lncRNA)-miRNA-mRNA ceRNA network in the prognosis of AML is still rarely reported.

Modifying the tumour microenvironment and reverting tumour cells: New strategies for treating malignant tumours.

The tumour microenvironment (TME) plays a pivotal role in tumour fate determination. The TME acts together with the genetic material of tumour cells to determine their initiation, metastasis and drug resistance. Stromal cells in the TME promote the growth and metastasis of tumour cells by secreting soluble molecules or exosomes.

Alternative Splicing Events as Indicators for the Prognosis of Uveal Melanoma.

Growing evidence has revealed that abnormal alternative splicing (AS) events are closely related to carcinogenic processes. However, the comprehensive study on the prognostic value of splicing events involved in uveal melanoma (UM) is still lacking. Therefore, splicing data of 80 UM patients were obtained from the Cancer Genome Atlas (TCGA) SpliceSeq and RNA sequence data of UM and patient clinical features were downloaded from the Cancer Genome Atlas (TCGA) database to identify survival related splicing events in UM.

Embryonic Stem Cells Modulate the Cancer-Permissive Microenvironment of Human Uveal Melanoma.

The currently used anti-cancer therapies work by killing cancer cells but result in adverse effects and resistance to treatment, which accelerates aging and causes damage to normal somatic cells. On one hand, chicken and zebrafish embryos can reprogram cancer cells towards a non-tumorigenic phenotype; however, they cannot be used in the clinical practice. On the other hand, embryonic stem cells (ESCs) mimic the early embryonic microenvironment and are easily available.

Autophagy Dysfunction, Cellular Senescence, and Abnormal Immune-Inflammatory Responses in AMD: From Mechanisms to Therapeutic Potential.

Age-related macular degeneration (AMD) is a blinding disease caused by multiple factors and is the primary cause of vision loss in the elderly. The morbidity of AMD increases every year. Currently, there is no effective treatment option for AMD.

Embryonic stem cell microenvironment suppresses the malignancy of cutaneous melanoma cells by down-regulating PI3K/AKT pathway.

Malignant cancer cells engage in a dynamic reciprocity with the tumor microenvironment (TME) that promotes tumor growth, development, and resistance to therapy. Early embryonic blastocyst microenvironments can reverse the tumorigenic phenotype of malignant cancer cells via ameliorating of TME. It is potential to apply embryonic stem cell (ESC) microenvironment to suppress the malignant behaviors of cancer cells.

Lipid layer thickness and tear meniscus height measurements for the differential diagnosis of evaporative dry eye subtypes.

Aim: To explore a new diagnostic index for differentiating the evaporative dry eye (EDE) subtypes by analysis of their respective clinical characteristics.

Methods: A cross-sectional study of 139 patients (139 eyes) with EDE who were enrolled and classified as obstructive meibomian gland dysfunction (MGD) (=81) and non-obstructive MGD (=58) EDE. All patients completed a Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire and were evaluated for average lipid layer thickness (LLT), tear meniscus height measurements (TMH), tear break-up time (TBUT), ocular surface staining score, Schirmer I test (SIT), lid margin abnormalities, and meibomian gland function and morphology.

Low concentration of sodium hyaluronate temporarily elevates the tear film lipid layer thickness in dry eye patients with lipid deficiency.

Aim: To investigate the effects of different concentrations of artificial tears on lipid layer thickness (LLT) and blink rate (BR) in dry eye patients.

Methods: This study included 106 eyes of 58 patients with dry eye. The lipid deficiency type was defined as the LLT baseline <75 nm.