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OBJECTIVE: To analyze the gene expression profiling characteristics of peripheral blood mononuclear cells (PBMCs) from patients with secondary syphilis, and gain an insight into the host molecular immune mechanisms involved in Treponema pallidum infection. METHODS: Using genome-based high-throughput Illumina sequencing technology, we comprehensively determined the transcriptional difference in PBMCs from 4 secondary syphilis patients and 4 healthy controls, followed by real time PCR to validate the results of Illumina sequencing. RESULTS: Totally, 78 differentially expressed genes were found in the PBMCs of the secondary syphilis patients, among which 16 were associated with the immune system. Significant upregulation was observed in the expressions of pro-inflammatory cytokines and related receptors, such as TNF receptor super-family member 17 (TNFRSF17), IL-17C, IL-21, IL-31 receptor A (IL-31RA), chemokine C-X-C motif ligand 10 (CXCL10), and chemokine (C-C motif) ligand 1 (CCL1), as well as the transcripts for the CD4+ T lymphocytes activation markers CD38, Fc-mediated phagocytosis receptors (FcγR1A, FcγR3B), and complement (C2, SERPING1). CONCLUSIONS: Systemic innate and adaptive immune effecter molecules are involved in the host clearance mechanism of secondary syphilis.
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Perfilación de la Expresión Génica , Leucocitos Mononucleares/metabolismo , Sífilis/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Humanos , Treponema pallidumRESUMEN
All in a sequence: An organocatalyzed Morita-Baylis-Hillman (MBH)/bromination/[3+2] annulation sequence for highly stereoselective syntheses of bis(spirooxindole)s featuring adjacent spiro-stereocenters is described. The key step is an unprecedented catalytic asymmetric [3+2] annulation of isatin-derived MBH adducts, containing a tetrasubstituted alkene moiety, with isatins.
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Indoles/química , Compuestos de Espiro/química , Catálisis , Estructura Molecular , Oxindoles , EstereoisomerismoRESUMEN
We report an efficient Au(I)-catalyzed formal allylation of diazo(thio)oxindoles using allyltrimethylsilane to give 3-allyl (thio)oxindoles, which are difficult to access by using traditional alkylation methods under basic conditions. The approach enables a highly stereoselective synthesis of quaternary (thio)oxindoles via a formal allylation-asymmetric Michael addition sequence. These adducts are versatile synthons for spirocyclic (thio)oxindoles. Initial biological studies reveal that chiral thiooxindoles show promising antiproliferation activity that is better than that of the corresponding oxindoles.
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We report an unprecedented sequential Au(i)/bifunctional tertiary amine catalysis, which enables a tandem C-H functionalization of weak nucleophiles (anisoles or thiophenes) and asymmetric Michael addition for the highly enantioselective synthesis of quaternary oxindoles from diazooxindoles and nitroenynes.
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An unprecedented sequential gold-catalyzed enone-formation and bifunctional tertiary amine mediated asymmetric cyanosilylation reaction is developed, allowing the highly enantioselective synthesis of 3-alkenyloxindoles from diazooxindoles, furans and trimethylsilyl cyanide (TMSCN).
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Multiple myeloma (MM) is a rare hematological malignancy, characterized by uncontrolled proliferation of plasma cells in the bone marrow. MM is usually confined to the bone marrow, however, it may occasionally infiltrate other tissues, which is known as extramedullary plasmacytoma (EMP). The majority of EMPs involve the head and neck region, although different anatomical sites, including the gastrointestinal tract, central nervous system, thyroid gland and breast may also be affected. The simultaneous presentation of EMP in the kidney and head is rare, presenting diagnostic challenges due to its unusual location and non-specific or absent symptoms. To the best of our knowledge, no case of extramedullary plasmacytoma presenting with simultaneous renal and intracranial infiltration has been reported in the literature thus far. However, the present study reports a case of primary renal and intracranial extramedullary plasmacytoma in a 76-year-old male patient. The patient presented with a swelling over the right side of the forehead, which had slowly increased in size prior to hospital admission. The swelling was associated with dizziness and weakness, without bone pain. Contrast magnetic resonance imaging suggested an osteolytic skull lesion with intracranial extension. Abdominal enhanced computed tomography scanning revealed a large tumor mass extending around and into the kidneys. Immunohistochemical examination of the renal tumor biopsy, and blood and serum samples, as well as immunoelectrophoresis of serum proteins, resulted in a diagnosis of EMP being proposed. Therefore, the patient was administered with two cycles of cyclophosphamide and thalidomide in combination with dexamethasone. Follow-up imaging performed 4 months later revealed almost complete disappearance of the intracranial tumor mass and renal infiltration. The current study also presented a review of the literature. This study revealed that EMPs may co-exist with MM or present as the main symptom of MM. The diagnosis of an EMP is complex and requires radiological, hematological, biochemical and histological investigation. At present, no guidelines for EMP treatment have been established and thus, treatment options include surgery, chemotherapy and radiotherapy, either alone or in combination. We hypothesize that combined treatment may provide the best patient outcome.
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A new cinchona alkaloid derived bifunctional tertiary amine-phosphoramide is identified as a highly enantioselective catalyst for Michael addition of both unprotected 3-arylthio- and 3-alkylthiooxindoles to nitroolefins. The phosphoramide moiety of plays an indispensable role in this reaction.
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Alquenos/química , Alcaloides de Cinchona/química , Indoles/química , Fosforamidas/química , Compuestos de Sulfhidrilo/química , Catálisis , EstereoisomerismoRESUMEN
CD47 is a ubiquitously expressed transmembrane glycoprotein on surface of many cells. Through its interaction with integrin, signal regulatory protein alpha (SIRPα) and thrombin sensitive protein-1 (TSP-1), it plays important roles in various immunological processes including inflammatory response, immune response and tumor immunity. Recently, it has been found that CD47 interacts with SIRPα expressed on phagocytic cells, which transfers a negative signal when being activated. By the mechanisms described above, CD47-SIRPα signal complex is involved in the pathogenesis of hematological diseases and might provide some informations for the therapy of patients. This review focuses on the structure and immunoregulatory functions of CD47, the mechanism of CD47 in tumor therapy, the CD47 and hematologic malignancies including acute leukemia, B-cell lymphoma and multiple myeloma, as well as CD47 and hematopoietic stem cell transplantation.