Project description:PPARgamma null (PpargΔ/Δ) mice and AZIP mice present a generalized lipodystrophy, accompanied by strong hyperlipidemia and hyperglycemia. Both mouse model develop progressive nephropathy. To shed ligh on the molecular mechanisms underlying the early kidney damage induced by lipodystrophy, we used microarrays to detail the global program of gene expression in whole kidney of PpargΔ/Δ mice and AZIP mice with their respective control mice at 3 weeks of age.
Project description:Keratins 5 and 14 are critical for cytoskeletal integrity, as shown by missense mutations in these genes, which cause the severe skin fragility disorder epidermolysis bullosa simplex (EBS). The complexity of the pathomechanisms in EBS is not fully understood and no effective management exists. In addition to fragility, EBS keratinocytes are characterized by aggregates of misfolded keratin. Here, we tested the chemical chaperone 4-phenylbutyrate (4-PBA) as a putative novel therapy, using keratinocytes from patients with severe generalized EBS due to distinct KRT5 and KRT14 mutations.
Project description:Congenital generalized lipodystrophy (CGL) is an autosomal recessive disorder characterized by defective adipose tissue, extreme insulin resistance, and early onset of diabetes. There are four types of congenital generalized lipodystrophy based on the causative genetic alterations. The symptoms and the degrees of disease progression are varied among all affected individuals, which might be due to unknown genetic modifiers. To identify potential predictive biomarkers associated with the disease progressions, we recruited 7 patients (cgl2_p1,cgl2_p2,cgl2_p3,cgl2_p4,cgl2_p5,cgl2_p6,cgl2_p7),as well as gender/aged-matched controls (cgl2_c1,cgl2_c2,cgl2_c3,cgl2_c4,cgl2_c5,cgl2_c6,cgl2_c7).The total RNA samples were extracted from the participants' peripheral blood mononuclear cells, followed by RNA-Seq. To find the molecular signatures that might be associated with disease progression, patients were further categorized into sub-groups based on the results of biochemical analysis and their clinical symptoms (e.g. diabetes, metabolic syndrome and metal retardation). DEGs were identified for each sub-groups of patients, and pathway analysis was performed to explore the underlying dysregulated mechanisms.
Project description:Background: The outbreak of coronavirus disease 2019 (COVID-19) poses a considerable health threat to humanity, with potential implications for the ovarian microenvironment remaining uncertain. Methods: Transcriptomic and proteomic analyses of ovarian granulosa cells, along with metabolomic and lipidomic profiling of follicular fluid, were conducted on 17 non-COVID-19 cases and 9 COVID-19 cases. This study received approval from the ethics committee (KYLL-2022-581). Generalized estimating equations model was performed to identify oocyte competency biomarkers. Additionally, cell proliferation, apoptosis, and altered pathways were examined following lentivirus transfection. Methods: Transcriptomic and proteomic analyses of ovarian granulosa cells, along with metabolomic and lipidomic profiling of follicular fluid, were conducted on 17 non-COVID-19 cases and 9 COVID-19 cases. This study received approval from the ethics committee (KYLL-2022-581). Generalized estimating equations model was performed to identify oocyte competency biomarkers. Additionally, cell proliferation, apoptosis, and altered pathways were examined following lentivirus transfection. Conclusions: By integrating untargeted metabolomic and lipidomic features, we identified biomarkers indicative of oocyte competency influenced by COVID-19.
Project description:Global efforts against COVID-19 have vaccinated a significant portion of the world population in recent years. Combating the COVID-19 pandemic with mRNA vaccines playinged a pivotal role in global immunization effort. However, individual responses to these vaccines vary, leading to diverse vaccination efficacy. Despite significant progress, full understanding of the molecular mechanisms driving the personalized immune response to COVID-19 vaccine remains elusive. To address this gap, we combined a novel nanoparticle-based proteomic workflow with tandem mass tag (TMT) labeling, to quantitatively assess the proteomic changes in a cohort of 12 volunteers following two doses of the Pfizer-BioNTech mRNA COVID-19 vaccine. This optimized protocol seamlessly integrates comprehensive proteome analysis with enhanced throughput by leveraging the enrichment of low-abundant plasma proteins by engineered nanoparticles. Our data demonstrate the ability of this nanoparticle-based workflow to quantify over 3,000 proteins from 48 human plasma samples, providing the deepest view into COVID-19 vaccine-related plasma proteome study. We identified 69 proteins exhibiting a boosted response to the vaccine after the second dose. Additionally, 74 proteins were differentially regulated between seven volunteers, who contracted COVID-19 despite receiving two doses of the vaccine, and the ones who did not contract COVID-19. These findings offer valuable insights into individual variability in response to vaccination, demonstrating the potential of personalized medicine approaches in vaccine development.
Project description:This is a cross-sectional case-control study. Study subjects of generalized myopic patients in preparation for small incision lenticule extraction (SMILE) surgery were recruited and divided into low and high myopia subgroups.
Project description:This study aims to under the characteristics and diversitification of Dengue speicific immunoglobulin repertoires after different immunization strategies in mouse. We propose two different immunization strategies in dengue vaccine development, one is repeated strategy, which DENV1 virus and administrated three times. The other one is epitope-decreased sequential strategy, which sequetially administrated DENV1 virus, DENV1 E protein and DENV1 E protein domain III subunit.