Disruption of Thyroid Hormone Receptor Thrab Leads to Female Infertility in Zebrafish.

Thyroid hormones (THs) T4 and T3 are vital for development, growth, and metabolism. Thyroid dysfunction can also cause problems in fertility, suggesting involvement of THs in reproduction. In zebrafish, there exist 2 forms of TH receptor alpha gene (thraa and thrab).

Design of an automated robotic microinjection system for batch injection of zebrafish embryos and larvae.

This paper presents the design of a vision-based automated robotic microinjection system for batch injection of both zebrafish embryos and larvae. A novel visual recognition algorithm based on an automatic threshold and excessive dilatation is introduced to accurately identify the center of zebrafish embryos and larval yolks. A corresponding software system is developed using the producer-consumer model as the framework structure, and a friendly user interface is designed to allow operators to choose from a range of desired functions according to their different needs.

Genetic evidence for differential functions of figla and nobox in zebrafish ovarian differentiation and folliculogenesis.

FIGLA and NOBOX are important oocyte-specific transcription factors. Both figla-/- and nobox-/- mutants showed all-male phenotype in zebrafish due to increased dominance of the male-promoting pathway. The early diversion towards males in these mutants has precluded analysis of their roles in folliculogenesis.

Genetic and Epigenetic Evidence for Nonestrogenic Disruption of Otolith Development by Bisphenol A in Zebrafish.

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical (EDC) that has estrogenic activities. In addition to disrupting reproductive development and function via estrogenic signaling pathways, BPA can also interfere with nonreproductive functions through nonestrogenic pathways; however, the mechanisms underlying such nonestrogenic activities are not well understood. In this study, we demonstrated that BPA could disrupt otolith formation during the early development of zebrafish with long-lasting ethological effects.

Rescue of bmp15 deficiency in zebrafish by mutation of inha reveals mechanisms of BMP15 regulation of folliculogenesis.

As an oocyte-specific growth factor, bone morphogenetic protein 15 (BMP15) plays a critical role in controlling folliculogenesis. However, the mechanism of BMP15 action remains elusive. Using zebrafish as the model, we created a bmp15 mutant using CRISPR/Cas9 and demonstrated that bmp15 deficiency caused a significant delay in follicle activation and puberty onset followed by a complete arrest of follicle development at previtellogenic (PV) stage without yolk accumulation.

Azoramide prevents MPP-induced dopaminergic neuronal death via upregulating ER chaperone BiP expression.

Progressive death of dopaminergic (DA) neurons is the main cause of Parkinson's disease (PD). The discovery of drug candidates to prevent DA neuronal death is required to address the pathological aspects and alter the process of PD. Azoramide is a new small molecule compound targeting ER stress, which was originally developed for the treatment of diabetes.

Fighting drug-resistant lung cancer by induction of NAD(P)H:quinone oxidoreductase 1 (NQO1)-mediated ferroptosis.

Drug resistance is a major challenge in cancer treatment. The substrates of NAD(P)H:quinone oxidoreductase 1 (NQO1) show a promising anticancer effect in clinical trials. We previously identified a natural NQO1 substrate 2-methoxy-6-acetyl-7-methyljuglone (MAM) with a potent anticancer effect.

Crowded environments tune the fold-switching in metamorphic proteins.

Metamorphic proteins such as circadian clock protein KaiB and human chemokine XCL1 play vital roles in regulating biological processes, including gene expression, circadian clock and innate immune responses, and perform distinct functions in living cell by switching different structures in response to cellular environment stimuli. However, it is unclear how complex and crowded intracellular environments affect conformational rearrangement of metamorphic proteins. Here, the kinetics and thermodynamics of two well-characterized metamorphic proteins, circadian clock protein KaiB and human chemokine XCL1, were quantified in physiologically relevant environments by using NMR spectroscopy, indicating that crowded agents shift equilibrium towards the inactive form (ground-state KaiB and Ltn10-like state XCL1) without disturbing the corresponding structures, and crowded agents have predominantly impact on the exchange rate of XCL1 that switches folds on timescales of seconds, but have slightly impact on the exchange rate of KaiB that switches folds on timescales of hours.

Nitrovin (difurazone), an antibacterial growth promoter, induces ROS-mediated paraptosis-like cell death by targeting thioredoxin reductase 1 (TrxR1).

Glioblastoma multiforme (GBM) is one of the most lethal malignant tumors in the human brain, with only a few chemotherapeutic drugs available after surgery. Nitrovin (difurazone) is widely used as an antibacterial growth promoter in livestock. Here, we reported that nitrovin might be a potential anticancer lead.

Protein Kinase C Modulation Determines the Mesoderm/Extraembryonic Fate Under BMP4 Induction From Human Pluripotent Stem Cells.

The interplay among mitogenic signaling pathways is crucial for proper embryogenesis. These pathways collaboratively act through intracellular master regulators to determine specific cell fates. Identifying the master regulators is critical to understanding embryogenesis and to developing new applications of pluripotent stem cells.

Genetic analysis of activin/inhibin β subunits in zebrafish development and reproduction.

Activin and inhibin are both dimeric proteins sharing the same β subunits that belong to the TGF-β superfamily. They are well known for stimulating and inhibiting pituitary FSH secretion, respectively, in mammals. In addition, activin also acts as a mesoderm-inducing factor in frogs.

Exogenous iron impairs the anti-cancer effect of ascorbic acid both in vitro and in vivo.

Introduction: The anti-cancer effect of high concentrations of ascorbic acid (AA) has been well established while its underlying mechanisms remain unclear. The association between iron and AA has attracted great attention but was still controversial due to the complicated roles of iron in tumors.

Objectives: Our study aims to explore the anti-cancer mechanisms of AA and the interaction between AA and iron in cancer.

An Fluorescence Resonance Energy Transfer-Based Imaging Platform for Targeted Drug Discovery and Cancer Therapy.

In the present study, an efficient drug screening platform is established based on FRET technique. We transfected cancer cells with FRET-based caspase-3 (C3) sensor and validated the cell lines by detecting the change in FRET signal caused by the drug-induced cell apoptosis. Furthermore, the C3 expressing cancer cells were then injected into zebrafish embryos and nude mice to establish the corresponding xenograft models.

Leptin and Its Signaling Are Not Involved in Zebrafish Puberty Onset.

Leptin is a peptide hormone secreted from the adipose tissues and its signaling plays a central role in metabolic regulation of growth, especially on fat mass. In addition, leptin is also involved in regulating reproduction in mammals. In teleosts, there are two leptin ligands (lepa and lepb) and one cognate leptin receptor (lepr); however, their functions are still elusive.

Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells.

Nicotinamide, the amide form of Vitamin B3, is a common nutrient supplement that plays important role in human fetal development. Nicotinamide has been widely used in clinical treatments, including the treatment of diseases during pregnancy. However, its impacts during embryogenesis have not been fully understood.

Accelerating precision anti-cancer therapy by time-lapse and label-free 3D tumor slice culture platform.

The feasibility of personalized medicine for cancer treatment is largely hampered by costly, labor-intensive and time-consuming models for drug discovery. Herein, establishing new pre-clinical models to tackle these issues for personalized medicine is urgently demanded. We established a three-dimensional tumor slice culture (3D-TSC) platform incorporating label-free techniques for time-course experiments to predict anti-cancer drug efficacy and validated the 3D-TSC model by multiphoton fluorescence microscopy, RNA sequence analysis, histochemical and histological analysis.

Nannocystin ax, an eEF1A inhibitor, induces G1 cell cycle arrest and caspase-independent apoptosis through cyclin D1 downregulation in colon cancer in vivo.

Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide. Nannocystin ax (NAN), a 21-membered cyclodepsipeptide initially isolated from myxobacteria of the Nannocystis genus, was found to target the eukaryotic elongation factor 1A (eEF1A). The current study was designed to evaluate the anticancer effect and underlying mechanisms of NAN with in vitro and in vivo models.

A novel bioengineered fragment peptide of Vasostatin-1 exerts smooth muscle pharmacological activities and anti-angiogenic effects via blocking VEGFR signalling pathway.

Chromogranin A (CgA) is a hydrophilic glycoprotein released by post-ganglionic sympathetic neurons. CgA consists of a single peptide chain containing numerous paired basic residues, which are typical cleavage sites in prohormones to generate bioactive peptides. It is recognized as a diagnostic and prognostic serum marker for neuroendocrine tumours.

Separation of Oocyte and Follicle Layer for Gene Expression Analysis in Zebrafish.

Zebrafish ovarian follicles are mainly composed of the oocyte and a thin layer of follicle cells. Recent studies have demonstrated extensive cell-cell interactions between the oocyte and surrounding follicle layer and that the two compartments communicate mostly through paracrine factors. To understand the paracrine communication within the follicle, it is essential to know the spatial expression patterns of genes in the two compartments.

A novel strategy for glioblastoma treatment by induction of noptosis, an NQO1-dependent necrosis.

Glioblastoma (GBM) is one of the most prevalent malignant primary tumors in the human brain. Temozolomide (TMZ), the chemotherapeutic drug for GBM treatment, induces apoptosis. Unfortunately, apoptosis-resistance to TMZ results in treatment failure.

2-Methoxy-6-acetyl-7-methyljuglone (MAM) induced programmed necrosis in glioblastoma by targeting NAD(P)H: Quinone oxidoreductase 1 (NQO1).

Glioblastoma (GBM) are the most malignant brain tumors in humans and have a very poor prognosis. Temozolomide (TMZ), the only chemotherapeutic drug for GBM treatment, induced apoptosis but frequently developed resistance. Non-apoptotic cell death offers an alternative strategy to fight cancers.

Endogenous IGF Signaling Directs Heterogeneous Mesoderm Differentiation in Human Embryonic Stem Cells.

During embryogenesis, various cell types emerge simultaneously from their common progenitors under the influence of intrinsic signals. Human embryonic stem cells can differentiate to diverse cell types of three embryonic lineages, making them an excellent system for understanding the regulatory mechanism that maintains the balance of different cell types in embryogenesis. In this report, we demonstrate that insulin-like growth factor (IGF) proteins are endogenously expressed during differentiation, and their temporal expression contributes to the cell fate diversity in mesoderm differentiation.