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Biomedical subjects

Yafei Wang

Publications and source records attributed to Yafei Wang.

6 recordsLinked to original sources

Omics Profiling of Patients with Obstructive Sleep Apnoea Reveals Risks of Diabetes Mellitus and Cardiovascular Diseases.

Obstructive sleep apnoea (OSA) constitutes a multisystemic disorder often associated with cardiovascular and metabolic disorders. Thus, far, the underlying pathophysiological processes are not fully understood. In total, 142 plasma samples were acquired: 50 from controls (CON), 45 from mild/moderate OSA (M-OSA) patients, and 47 from severe OSA (S-OSA) patients. Proteomic and metabolic signatures significantly differed among S-OSA, M-OSA, and CON samples. A novel plasma biomarker panel including two proteins (ACTR2 and ENO1) and three metabolites (2-aminobicyclo[2 2·1], heptane-2-carboxylic acid, 1-O-[2r-hydroxy-hexadecyl]-sn-glycerol, and 1-pentadecene) was developed to identify S-OSA (AUC: 1.000) and distinguish severe cases from nonsevere cases (AUC: 0.813). An independent cohort was used to validate the model by distinguishing S-OSA samples from M-OSA (AUC: 0.729) and CON (AUC: 0.990) samples. Glycolysis pathway activation was identified as a characteristic of OSA; it may contribute to diabetes mellitus onset in OSA patients. Dyslipidaemia, foamy macrophage formation, platelet activation, and actin cytoskeleton might collectively play a key role in vascular damage in OSA patients, contributing to the development of atherosclerosis. These findings reveal molecular bases for OSA-related cardiometabolic complications and provide new diagnostic biomarkers for OSA and the identification of severe cases.

Humans↗

Thymocytes induced by antigen injection into the anterior chamber activate splenic CD8+ suppressor cells and enhance the antigen-induced production of immunoglobulin G1 antibodies.

Injection of antigen into the ocular anterior chamber (AC) of a mouse eye (an immunologically privileged site) induces the activation of immunoregulatory NK1.1+, CD4- CD8-, T-cell receptor (TCR) alphabeta+ thymocytes. These thymocytes transfer the suppression of delayed-type hypersensitivity (DTH) when injected into mice sensitized to the same antigen but do not effect the suppression of DTH. On the other hand, the immunized recipients of these transferred thymocytes produce splenic CD8+ T cells that effect the suppression of DTH. However, it is unclear whether the thymocytes transferred from the AC-injected donor differentiate into and/or activate CD8+ T-splenic suppressor cells. We therefore sought to determine the origin of splenic suppressor cells produced in the recipients of immunoregulatory thymocytes transferred from donors that receive an injection of antigen into the AC. CD45.1+ thymocytes from mice that received an AC injection of 2,4,6-trinitrobenzene sulphonic acid (TNP)-bovine serum albumin (BSA) were transferred to congenic CD45.2+ TNP-BSA-immune recipients. Spleen cells from the recipients were then sorted based on anti-CD45.1 or -CD45.2 antibody binding and assayed for suppressor cells. This was done by the injection of separated spleen cells into the footpad of TNP-BSA-immunized mice, concurrent with the induction of footpad swelling (contact sensitivity) of the footpad elicited by an epicutaneous application of picryl chloride. The systemic distribution of antigen after the injection of antigen into the AC was demonstrated by the injection of fluorescein or 125I-labelled TNP-BSA into the AC. The results demonstrate that (i) splenic CD8+ T-suppressor cells produced in the immunized recipients of immunoregulatory thymocytes are derived from the CD45.2 recipient of the CD45.1+ thymocytes; (ii) the induction of recipient splenic suppressor T cells by the transferred immunoregulatory thymocytes requires that the recipient be immunized to the same antigen as that used to induce immunoregulatory thymocytes; (iii) antigen is introduced to the thymus after an injection of antigen into the AC; (iv) although the transfer of the suppression of DTH by regulatory thymocytes was not dependent on interleukin-4 (IL-4), CD4+ NK1.1- regulatory thymocytes from AC-injected donors enhanced the production of immunoglobulin G1 antibodies to TNP-BSA by an IL-4-dependent mechanism. These observations suggest that the adult thymus plays an active role in the induction and maintenance of anterior chamber-associated immune deviation as manifested by the generation of the suppression of cell-mediated immunity to exogenous antigen and the antigen-induced production of IgG1 antibodies.

Adoptive Transfer↗

Splenic T cells from mice receiving intracameral antigen suppress in-vitro antigen-induced proliferation and interferon-gamma production by sensitized lymph node cells.

PURPOSE: To characterize the immunoregulatory mechanisms in vitro of spleen cells that are activated by intracameral injection of antigen (AC-spleen cells). METHODS: AC-spleen cell regulation of in-vitro antigen-induced proliferation and interferon-gamma production by lymph node cells from TNP-BSA-immunized mice was quantified by co-culture of the lymph node cells with TNP-BSA and AC-spleen cells induced by intracameral TNP-BSA. Cytokine production was quantified by ELISA. RESULTS: AC-spleen cells produced significantly more IL-4 and IL-10 than spleen cells from TNP-BSA-immunized mice or naive spleen cells; unlike spleen cells from immunized mice, AC-spleen cells did not produce IFN-gamma. AC-splenic CD4(+), CD8(+), CD4(-)/CD8( -) (DN) T cells differentially suppressed antigen-induced proliferation and IFN-gamma production by immunized lymph node cells by a mechanism dependent on IL-10 and antigen. Cultures of lymph node cells, antigen, and AC-splenic T cells contained increased amounts of IL-10 and/or TGFbeta2. CONCLUSIONS: The differential, cytokine-dependent immunoregulatory effects of CD4( +) and CD8(+) AC-spleen cells observed in vitro parallel their effects in vivo. We suggest that the suppression of antigen-induced lymphocyte proliferation and IFN-gamma production by AC-spleen cells provides a useful in-vitro assay of the immunoregulatory activity of cell populations that are induced by the injection of antigen into the anterior chamber.

Animals↗

Storage and release of tissue plasminogen activator by sympathetic axons in resistance vessel walls.

We studied the immunolocalization of tissue plasminogen activator (t-PA) in rat precapillary arteries, arterioles, and terminal arterioles. Lack of information about the precise location of t-PA within small vessel walls has contributed to uncertainty about its cellular source. The presumed origin has been an endothelial phenotype largely restricted to certain small vessels. However, vessel wall sympathetic axons were recently also shown to store significant amounts of a neuron-generated t-PA in secretory vesicles. Using immunolocalizations we determined the extension of t-PA-bearing axons into the resistance vasculature. Light and confocal images revealed the persistence of t-PA-bearing sympathetic nerve filaments down to the level of 15-microm-diameter terminal arterioles in vasa vasora and the choroidal microvasculature. Immunoelectron localizations confirmed the confinement of t-PA within individual nerve filaments in the deep adventitia. A complete plasminogen activator system (t-PA, plasminogen, and plasmin) was localized in the arteriolar wall matrix. Isolated iris-choroid and mesenteric artery explants from sympathectomized animals released 65 and 43% less t-PA, respectively, than controls. These data support the hypothesis that resistance vessel sympathetic axons release neural t-PA into the wall matrix and the microvascular plasma.

Animals↗

Tissue plasminogen activator is released into cultured medium by cultured human uveal melanocytes.

Melanoma cells produce tissue plasminogen activator (t-PA) that plays an important role in tumor invasion and metastasis. The production of t-PA by normal human uveal melanocytes has not been reported previously. In order to explore this possibility, we studied the production of t-PA by cultured human uveal melanocytes and compared that with the production by cultured human uveal melanoma cells and epidermal melanocytes. Human adult uveal melanocytes were isolated and cultured from donor eyes. The cells were cultured in serum-free medium for 48 h and the conditioned medium then collected for the plasminogen activator (PA) activity assay. Free PA activity was tested in an amidolytic assay using a t-PA standard curve. PA type was identified by fibrinography and antihuman t-PA and urokinase plasminogen activator (u-PA) blocking antibodies. Free PA activity was found in the conditioned medium of normal melanocytes and melanoma cells. The predominant PA activity was t-PA. Normal uveal melanocytes produced more t-PA (3.23 +/- 0.73 IU/105 cells/24 h) than that of epidermal melanocytes (1.25 IU/105 cells/24 h) but much less than uveal melanoma cells (11.0 +/- 3.39 IU/105 cells/24 h). Western blot analysis revealed that most t-PA in conditioned media were one-chain t-PA with molecular weight of 69 kDa. Our study indicates that uveal melanocytes may contribute to the free t-PA activity previously found in aqueous humor and choroidal eye cup superfusions. Therefore, this function of uveal melanocytes may play a role in intraocular matrix remodeling, fibrinolysis and aqueous humor outflow.

Blotting, Western↗

Compact bulb pipette simplifies paracentesis.

Anterior chamber paracentesis is typically done using a tuberculin syringe, hypodermic needle, fixation forceps, and lid speculum. A compact suction pipette design simplifies the tap by eliminating unneeded instrumentation and minimizing needle dead space. The short (1/4-inch) 30-gauge needle tip eases limbal penetration. The soft plastic suction bulb provides a prompt and controlled aspiration of small volumes. Compared with syringe-needle methods, the pipette refines paracentesis by reducing the complexity and duration of aqueous withdrawal.

Animals↗