Project description:Blood platelets destined for transfusion release panoply of molecules during preparation and storage. The leukoreduction process made the transfusion safer but did not completely abolish the adverse events. The rationale is to study the proteome profile of platelet components PPC (platelet pellets) involved in transfusion adverse events.
Project description:Blood platelets destined for transfusion release panoply of molecules during preparation and storage. The leukoreduction process made the transfusion safer but did not completely abolish the adverse events. The rationale is to study the proteome profile of platelet components SDA-PC (platelet pellets) involved in transfusion adverse events.
Project description:The Mongolian horse has the characteristics of cold resistance, rough feeding resistance, good endurance, strong disease resistance and strong gregariousness. The normal production of sperm in male mammals is the basis of reproduction, and spermatogenesis includes a mitosis, meiosis twice and metamorphosis of sperm cells. The MEI1 gene is involved in the meiosis cycle and is required for normal meiosis chromosome association. Previous studies have shown that alternative splicing of MEI1 gene can promote spermatogenesis in Mongolian horses. In this study, the expression of MEI1 gene was determined by immunofluorescence in the third generation Mongolian horse testicular sertoli cells. Two overexpressed lentiviral vectors with MXE and SE events of MEI1 gene were constructed and successfully infected into sertoli cells. CCK-8 was used to detect the proliferation and activity of infected cells, transcripomics and metabolomics were used to screen and annotate differential genes and differential metabolites in the two sertoli cells with MXE and SE events. After 72 h of virus infection, 193 differentially expressed genes and 11360 differentially expressed metabolites were screened, 109 up-regulated genes including MEI1 and 84 down-regulated genes, 7494 up-regulated metabolites and 3866 down-regulated metabolites. Differential genes and differential metabolites were mainly enriched in several pathways related to spermatogenesis. Differential genes such as IL31RA, ATP2B3, CASQ2 were highly expressed in SE events, IL11, PRLR, CCR7 were highly expressed in MXE events. Metabolites such as folic acid and spermine were highly expressed in SE events, citric acid and glutathione were highly expressed in MXE events. This suggested that both MXE and SE events of MEI1 gene can promote the activity of spermatogenesis signaling pathway, and the gene influences spermatogenesis by regulating the expression of metabolites. In summary, MXE and SE events of MEI1 gene can promote the expression of spermatogen-related genes and metabolites, and genes affect spermatogenesis by regulating the expression of metabolites. The results of this study laid a theoretical foundation for exploring the regulatory mechanism of different alternative splicing events on spermatogenesis in Mongolian horse.
Project description:This mass spectroscopy was conducted by exploring NTP binding molecules. NTP is novel cell penetrating peptide. We resarched how the NTP was transport to nucleus by molecules which binds NTP.
Project description:Synapse loss is an early feature of prion disease, yet the underlying drivers are poorly understood. We recently found evidence of neuronal hyperactivity and synaptic loss in prion-infected mice. Herein we identified increased Arc/Arg3.1 in patients with prion disease, suggesting heightened neuronal activity also occurs in human prion-affected brain. To determine the signaling events initiated by prion aggregates (PrPSc), we developed a disease model in which human iPSC-derived excitatory neurons are stimulated with a PrPSc-mimetic antibody that binds cellular prion protein (PrPC). Within two hours, we detected an Arc/Arg3.1 response together with transcriptomic changes previously reported in prion-infected mice. We identified altered phosphorylation of PLC-γ1, ERK1/2, and EGFR as PrPC-triggered cell signaling events that accompany the Arc/Arg3.1. These results suggest that PrPC ligands, including PrPSc, trigger rapid signaling events linked to neuronal hyperactivity in human neurons, and indicate PLC-γ1 as a potential therapeutic target.
Project description:Urinary bladder wound healing is today pooorly chracterized. MicroRNAs are small non-coding RNA molecules with regulatory functions. In this study we aimed at identifying microRNAs expressed during bladder wound healing. We performed Affymetrix microRNA profiling of the rodent urinary bladder during healing of a surgically created wound.
Project description:Gut microbiota has been associated with carcinogenesis and immune regulation. While there is evidence supporting its influence on immunotherapy response in melanoma, its impact on BRAF/MEK-targeted therapy remains unexplored. This study assessed gut microbiota composition and immune-associated genes in melanoma, to generate hypothesis on prognostic and predictive biomarkers for BRAF/MEK inhibitor therapy. We hypothesize that GM composition may influence responses to treatment or toxicity in patients receiving iBRAF/MEK therapy. Specific microorganisms may serve as prognostic or predictive biomarkers of response, as well as of treatment-related adverse events. Additionally, genes associated with immune activation could further refine prognostic and predictive models. By identifying biomarkers for early prediction of response and microorganisms linked to treatment efficacy and toxicity, our findings aim to contribute to the development of microbiota-modulation strategies that could enhance therapeutic outcomes in specific contexts.
Project description:The immediate early gene product activity-regulated cytoskeleton-associate protein (Arc or Arg3.1) is a major regulator long-term synaptic plasticity with critical roles in postnatal cortical development and memory formation. However, the molecular basis of Arc function is not defined. Arc is a hub protein with interaction partners in the postsynaptic neuronal compartment and nucleus. In vitro biochemical and biophysical analysis of purified recombinant Arc show formation of low-order oligomers and larger particles including retrovirus-like capsids. Here, we provide evidence for naturally occurring Arc oligomers in mammalian brain. Using in situ protein crosslinking to trap weak Arc-Arc interactions, we identified in various preparations a prominent Arc immunoreactive band on SDS-PAGE of molecular mass corresponding to a dimer. While heavier Arc species or putative trimers and tetramers were detected, they were of lower abundance. In the dentate gyrus (DG) of adult anesthetized rats, induction of long-term potentiation (LTP) by high-frequency stimulation (HFS) of medial perforant synapses or by brief intrahippocampal infusion of BDNF led to a massive increase in Arc dimer expression. Arc immunoprecipitation of crosslinked DG tissue showed enhanced expression of dimer during four hours of LTP maintenance. Mass spectrometric proteomic analysis of immunoprecipitated, gel-excised bands corroborated detection of Arc dimer. Furthermore, Arc dimer was constitutively expressed in naïve cortical, hippocampal and DG tissue, with lowest levels in the DG. Taken together the results implicate Arc dimers as the predominant low-oligomeric form in mammalian brain, exhibiting regional differences in its constitutive expression and pronounced enhanced expression during DG LTP.