Publications by authors named "Zhaofa Xu"

RNA methylation of N6-methyladenosine (m6A) is emerging as a fundamental regulator of every aspect of RNA biology. RNA methylation directly impacts protein production to achieve quick modulation of dynamic biological processes. However, whether RNA methylation regulates mitochondrial function is not known, especially in neuronal cells which require a high energy supply and quick reactive responses.

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Spinal muscular atrophy (SMA), the top genetic cause of infant mortality, is characterized by motor neuron degeneration. Mechanisms underlying SMA pathogenesis remain largely unknown. Here, we report that the activity of cyclin-dependent kinase 5 (Cdk5) and the conversion of its activating subunit p35 to the more potent activator p25 are significantly up-regulated in mouse models and human induced pluripotent stem cell (iPSC) models of SMA.

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Oxidative stress response is a fundamental biological process mediated by conserved mechanisms. The identities and functions of some key regulators remain unknown. Here, we report a novel role of C.

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Centromeres are known to cluster around nucleoli in and mammalian cells, but the significance of the nucleoli-centromere interaction remains underexplored. To determine whether the interaction is dynamic under different physiological and pathological conditions, we examined nucleolar structure and centromeres at various differentiation stages using cell culture models and the results showed dynamic changes in nucleolar characteristics and nucleoli-centromere interactions through differentiation and in cancer cells. Embryonic stem cells usually have a single large nucleolus, which is clustered with a high percentage of centromeres.

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Manganese (Mn) can accumulate in the striatum through the blood-brain barrier and cause neurotoxicity. It is mainly due to the decrease of dopamine (DA) levels in the striatum, which leads to extrapyramidal dysfunction. Netrin-1, as an axon guidance factor, can regulate the normal transmission of DA.

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One of the major environmental factors that induce PD is Manganese (Mn). Cellular and molecular mechanism of parkinsonism caused by Mn has not been explored clearly. The results of in vivo and in vitro experiments showed that Mn exposure caused abnormal projection of dopaminergic neurons and decreased mRNA expression and protein levels of FTO.

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The GABA receptor (GABAR) plays important roles in the regulation of Mn-induced GnRH secretion in immature female rats. However, the underlying molecular mechanisms remain unknown. Here, we assessed whether FTO and its substrate mA are correlated with GABAR expression in GnRH neurons after treatment with Mn in vitro and in vivo.

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Human infertility has become the third largest serious disease in the world, seriously affecting the quality of human fertility. Studies have shown that manganese (Mn) can accumulate in the testis through the blood-testicular barrier and damage the male reproductive system. However, the mechanism has not been explored clearly.

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Eukaryotic messenger mRNAs contain many RNA methyl chemical modifications, in which N-methyladenosine (mA) plays a very important role. The modification process of RNA methylation is a dynamic reversible regulatory process that is mainly catalyzed by "Writer" mA methyltransferase, removed by "Eraser" mA demethylase, and recognized by the mA binding protein, thereby, linking mA modification with other mRNA pathways. At various stages of the life cycle, mA modification plays an extremely important role in regulating mRNA splicing, processing, translation, as well as degradation, and is associated with gametogenesis and fertility for both sexes.

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Epigenetics play an essential role in the occurrence and improvement of many diseases. Evidence shows that epigenetic modifications are crucial to the regulation of gene expression. DNA methylation is closely linked to embryonic development in mammalian.

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Di-(2-ethylhexyl) phthalate (DEHP) is a representative endocrine-disrupting chemical (EDC) that has reproductive, developmental, neurological and immune toxicity in humans and rodents, of which damage to the reproductive system is the most serious. However, exposure to DEHP at different stages of life may produce different symptoms. Studies on this substance are also controversial.

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Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by progressive memory decline and cognitive dysfunctions. Although the causes of AD have not yet been established, many mechanisms have been proposed. Axon-guidance molecules play the roles in the occurrence and development of AD by participating in different mechanisms.

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In December 2019, the 2019 novel coronavirus disease (COVID-19), which has been identified to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China and spread across the world. Higher plasma levels of cytokines, including interleukin (IL)-6, IL-2, IL-7, IL-10, and tumor necrosis factor-α, were found in patients with COVID-19, which implies the occurrence of a cytokine storm and its association with disease severity. Extracorporeal blood purification has been proven to effectively remove the released inflammatory cytokines.

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Exposure to manganese (Mn) can cause male reproductive damage and lead to abnormal secretion of sex hormones. Gonadotropin-releasing hormone (GnRH) plays an important role in the neuromodulation of vertebrate reproduction. Astrocytes can indirectly regulate the secretion of GnRH by binding paracrine prostaglandin E (PGE) specifically to the EP1 and EP2 receptors on GnRH neurons.

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Manganese (Mn) is an essential element required for many biological processes and systems in the human body. Mn intoxication increases brain glutamate (Glu) levels causing neuronal damage. Recent studies have reported that ephrin-A3 regulates this glutamate transporter.

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Glutamate (Glu) is the predominant excitatory neurotransmitter in the central nervous system (CNS). Glutamatergic transmission is critical for controlling neuronal activity. In presynaptic neurons, Glu is stored in synaptic vesicles and released by stimulation.

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Methylmercury (MeHg) is a potent neurotoxin,which leads to a wide range of intracellular effects. The molecular mechanismsassociated to MeHg-induced neurotoxicity have not been fully understood.Oxidative stress, as well as synaptic glutamate (Glu) dyshomeostasis have beenidentified as two critical mechanisms during MeHg-mediated cytotoxicity.

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Gamma-aminobutyric acid (GABA) plays a critical role in regulation of gonadotropin-releasing hormone (GnRH) through GABA receptor (GABAR). Nitric oxide (NO) production has correlation with GABA and regulates GnRH secretion. This study was performed to examine the mechanisms by which manganese (Mn) accelerate puberty onset involves GABAR/NO pathway in the preoptic area-anterior hypothalamus (POA-AH) in immature female rats.

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Epitranscriptomics, also known as "RNA epigenetics", is a chemical modification for RNA regulation. Ribonucleic acid (RNA) methylation is considered to be a major discovery following the deoxyribonucleic acid (DNA) and histone methylation. Messenger RNA (mRNA) methylation modification accounts for more than 60% of all RNA modifications and N6-methyladenosine (mA) is known as one of the most common type of eukaryotic mRNA methylation modifications in current.

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N-methyladenosine (mA) modification of mRNA is emerging as a vital mechanism regulating RNA function. Here, we show that fragile X mental retardation protein (FMRP) reads mA to promote nuclear export of methylated mRNA targets during neural differentiation. Fmr1 knockout (KO) mice show delayed neural progenitor cell cycle progression and extended maintenance of proliferating neural progenitors into postnatal stages, phenocopying methyltransferase Mettl14 conditional KO (cKO) mice that have no mA modification.

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There are limited studies focused on the precise mechanism of gonadotropin-releasing hormone (GnRH) secretion dysfunction after overexposure to manganese (Mn). The objective of the present study was to explore the mechanism of Mn disruption of GnRH synthesis via nuclear factor erythroid-2-related factor-2 (Nrf2)/metabotropic glutamate receptor-5 (mGluR5)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE) signaling pathway in vitro and in vivo. Primary astrocytes were cultured and treated with different doses of Mn, tert-butylhydroquinonet (tBHQ; Nrf2 agonists), 3-[(2-methyl-4-thaizolyl) ethynyl] pyridine (MTEP; mGluR5 inhibitor), and celecoxib (COX-2 inhibitor) to measure the levels of COX-2, mGluR5, Nrf2, and Nrf2 target genes.

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Overexposure to manganese (Mn) is an important environmental risk factor for Parkinsonian-like symptoms referred to as manganism. Alpha-synuclein (α-Syn) oligomerization is a major cause in Mn-induced neurotoxicity. Autophagy, as an adjust response to control intracellular protein homeostasis, is involved in the degradation of α-Syn monomers or oligomers.

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Synaptic vesicle fusion is mediated by an assembly of soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNAREs), composed of syntaxin 1, soluble NSF-attachment protein (SNAP)-25, and synaptobrevin-2/VAMP-2. Previous studies have suggested that over-exposure to manganese (Mn) could disrupt synaptic vesicle fusion by influencing SNARE complex formation, both in vitro and in vivo. However, the mechanisms underlying this effect remain unclear.

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