MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages.

Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder in which macrophages play a critical role. Mammalian sterile-20-like kinase 4 (MST4), a member of the germinal-center kinase STE20 family, has been demonstrated to be a regulator of inflammation. Whether MST4 participates in the macrophage-dependent inflammation of ITP remains elusive.

Decreased cyclooxygenase-2 associated with impaired megakaryopoiesis and thrombopoiesis in primary immune thrombocytopenia.

Background: Cyclooxygenase (COX)-2 is a rate-limiting enzyme in the biosynthesis of prostanoids, which is mostly inducible by inflammatory cytokines. The participation of COX-2 in the maturation of megakaryocytes has been reported but barely studied in primary immune thrombocytopenia (ITP).

Methods: The expressions of COX-2 and Caspase-1, Caspase-3 and Caspase-3 p17 subunit in platelets from ITP patients and healthy controls (HC), and the expressions of COX-2 and CD41 in bone marrow (BM) of ITP patients were measured and analyzed for correlations.

Low-dose decitabine promotes M2 macrophage polarization in patients with primary immune thrombocytopenia via enhancing KLF4 binding to PPARγ promoter.

Background: The first-line therapy is effective for the treatment of primary immune thrombocytopenia (ITP); however, maintaining the long-term responses remains challenging. Low-dose decitabine (DAC) has been adopted to treat refractory ITP, while its role in macrophage polarization has not been fully understood. We aimed to investigate the mechanistic role of DAC in M2 macrophage polarization and evaluated its therapeutic effect in ITP.

Proinflammatory plasticity towards Th17 paradigm of regulatory T cells consistent with elevated prevalence of TGFBR2 variants in elderly patients with primary immune thrombocytopenia.

Background: Primary immune thrombocytopenia (ITP) is characterized for the skewed Th differentiation towards Th1 and Th17 cells as well as the impaired number and function of regulatory T cells (Tregs). Tregs are capable of co-expressing effector Th markers in different inflammatory milieu, which probably indicates Treg dysfunction and incompetence to counter over-activated immune responses.

Methods: Ninety-two primary ITP patients from March 2013 to December 2018 were included, and proinflammatory plasticity in different Treg compartments, age groups, and TGFBR2 variant carrier status were investigated.

Recombinant Thrombopoietin Effectively Shortens the Time to Response and Increases Platelet Counts in Elderly Patients with Severe Immune Thrombocytopenia.

Background: This study was conducted to investigate the short-term efficacy and safety of rhTPO for the management of severe ITP in the elderly as first-line treatment.

Methods: A total of 54 elderly patients with severe ITP were studied, including 39 patients treated with a combination regimen of rhTPO plus standard treatment (glucocorticoid; rhTPO group) and 15 patients treated with glucocorticoid treatment alone (control group). The response rate, time to initial response, peak platelet counts, and time to peak platelet counts were compared, and clinical characteristics correlated with the efficacy of rhTPO were analyzed.

TCR Sequencing as a Clue to Elucidate the Landscape of Dysimmunity in Patients with Primary Immune Thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder. The existence of autoreactive T cells has long been proposed in ITP. Yet the identification of autoreactive T cells has not been achieved, which is an important step to elucidate the pathogenesis of ITP.

Impaired mitochondria of Tregs decreases OXPHOS-derived ATP in primary immune thrombocytopenia with positive plasma pathogens detected by metagenomic sequencing.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune disease. Some ITP patients are associated with pathogen infection undetected with conventional technologies. Investigating the changes of T cells and potential metabolic mechanism are important for better understanding of ITP.

Exosomal circCARM1 from spheroids reprograms cell metabolism by regulating PFKFB2 in breast cancer.

Cancer stem cells (CSC) are the major obstacle for cancer therapy in clinic. Exosomes are one type of vesicles that containing circular RNA (circRNAs) involved in cell-cell communication. However, the roles of breast CSC (BCSC) exosomes are still unclear, and the purpose of the study was to investigate breast cancer cell metabolism reprogramming by circRNAs from BCSC exosomes.

Decreased levels of immune-regulatory cytokines in patients with immune thrombocytopenia and long-lasting overexpression of these cytokines in the splenectomized patients.

Immune thrombocytopenia (ITP) is an autoimmune-mediated disease characterized by decreased platelet counts. Cytokines play important roles in modulating the immune response and are involved in the pathogenesis of many autoimmune diseases. This study aimed at exploring the serum levels of a core set of cytokines that exert immune-regulatory functions in newly diagnosed ITP patients (both before and after treatment) and splenectomized ITP patients.

Cytokine Consistency Between Bone Marrow and Peripheral Blood in Patients With Philadelphia-Negative Myeloproliferative Neoplasms.

Inflammation might play a critical role in the pathogenesis and progression of Philadelphia-negative myeloproliferative neoplasms (PhMPNs) with elevated inflammatory cytokines in peripheral blood (PB). However, the inflammatory status inside the bone marrow (BM), which is the place of malignancy origin and important microenvironment of neoplasm evolution, has not yet been elucidated. Inflammatory cytokine profiles in PB and BM of 24 Ph-MPNs patients were measured by a multiplex quantitative inflammation array.

Carcinoma associated fibroblasts small extracellular vesicles with low miR-7641 promotes breast cancer stemness and glycolysis by HIF-1α.

Fibroblasts play an important role in cancer development and progression. Small extracellular vesicles (sEVs) are one type of extracellular vesicles, which mediate the interaction between cancer-associated fibroblasts and cancer cells by transferring their contents. However, the roles of sEVs from cancer-associated fibroblasts on breast cancer stem cell properties are largely unraveled.

Interleukin (IL)-1 family cytokines could differentiate primary immune thrombocytopenia from systemic lupus erythematosus-associated thrombocytopenia.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune-mediated disorder characterized by a decreased platelet count. Systemic lupus erythematosus (SLE) is also an autoimmune disease in which thrombocytopenia is a common hematologic manifestation. Interleukin (IL)-1 family cytokines are major proinflammatory and immunoregulatory mediators.

Circulating CX3CR1CD163 M2 monocytes markedly elevated and correlated with cardiac markers in patients with acute myocardial infarction.

Background: Vulnerable plaques have been generally recognized to play a role in the pathogenesis of acute myocardial infarction (AMI), however, the role of circulating CX3CR1CD163 M2 monocytes has not been studied properly. We aim to evaluate the features of CX3CR1CD163 M2 monocytes and its relationship with cardiac specific markers in AMI patients.

Methods: The circulating M2 monocytes were identified in AMI patients (n=35) and healthy controls (HCs, n=10) by flow cytometry using two staining methods: CD68CD163 (cytoplasmic staining) and CX3CR1CD163 (surface staining).

Intestinal microbiota dysbiosis play a role in pathogenesis of patients with primary immune thrombocytopenia.

Background: The intestinal microbiota is essential for the maintenance of the physiology of immune homeostasis. Dysbiosis has been described in some autoimmune diseases, however its role is still elusive in primary immune thrombocytopenia (ITP), which is one kind of autoimmune diseases. This study aimed to characterize the phylogenetic diversity of the fecal microbiota and its relationship with the platelet activation status in patients with ITP.

Transcription Factor IRF4 Dysfunction Affects the Immunosuppressive Function of Treg Cells in Patients with Primary Immune Thrombocytopenia.

Background: Th17/Treg balance skews towards Th17 in ITP patient. IRF4 has been highlighted for its close relationship to the immunosuppressive function of Treg cells and the IL-17 synthesis in CD4 T cells. This study was aimed at examining the effects of IRF4 to the Th17/Treg cells in patients with ITP.

The prediction value of Treg cell subtype alterations for glucocorticoid treatment in newly diagnosed primary immune thrombocytopenia patients.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder of which Treg cells are numerically or functionally deficient. It is known that human FoxP3CD4 T cells were composed of 3 phenotypically and functionally distinct subpopulations (resting Treg, rTreg; activated Treg, aTreg; and non-suppressive Treg, n-sTreg). The current study was aimed to determine whether these Treg subtypes are altered in ITP patients and the related potential clinical applications.

Clinical Significance of Platelet Volume and Other Platelet Parameters in Acute Myocardial Infarction and Stable Coronary Artery Disease.

Background: Platelets are important in the initiation of thrombosis, and their morphological and functional changes are closely related with the occurrence and development of coronary artery thrombosis. Platelet parameters might be valuable in distinguishing between acute myocardial infarction (AMI) and stable coronary artery disease (SCAD).

Objective: This study was designed to detect and compare changes in platelet parameters, such as mean platelet volume (MPV) in patients with acute myocardial infarction (AMI) and stable coronary artery disease (SCAD) and to investigate their roles in these diseases.

[Reactivated Expression of MicroRNA-124 in Patients with Myelodysplastic Syndromes after Demethylating Therapy].

Objective: To explore the role of microRNA-124(miR-124) in the pathogenesis of myelodysplastic syndromes(MDS) through detecting the expression level of miR-124 in bone marrow mononuclear cells(MNC) of MDS patients before and after demethylating therapy with decitabine.

Methods: The expression levels of miR-124 in the MNC of 35 MDS patients and 10 healthy donors were detected with stem-loop quantitative real time polymerase chain reaction assay.

Results: The expression level of miR-124 was lower in MDS patients than that in healthy donors.

Factors associated with the effect of open splenectomy for immune thrombocytopenic purpura.

Objective: To assess the effect and complications of open splenectomy (OS) for immune thrombocytopenic purpura (ITP) and determine preoperative factors associated with surgical effect.

Methods: This was a retrospective analysis of ITP patients who failed medical therapy and were treated with OS between 1997 and 2014 at the Jinshan Hospital, China. Follow-up was 60 months.

The expression profile of toll-like receptor signaling molecules in CD19(+) B cells from patients with primary immune thrombocytopenia.

Background: B cells play a critical role in the pathogenesis of immune thrombocytopenia (ITP), and toll-like receptor (TLR) signaling is essential for the activation of autoreactive B cells. The objective of this study was to investigate the expression profile of TLR signaling molecules in circulating and splenic CD19(+) B cells isolated from ITP patients.

Methods: CD19(+) B cells were magnetically isolated from peripheral blood and splenocytes.

Insufficient secretion of IL-10 by Tregs compromised its control on over-activated CD4+ T effector cells in newly diagnosed adult immune thrombocytopenia patients.

Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder. Excessive activated CD4(+) T effector cells (Teffs) and compromised regulatory T cells (Tregs) were reported in ITP patients, yet little is known about the mechanisms. Interleukin-10 (IL-10) is an important regulatory cytokine of Tregs in inflammatory condition.

Aberrant frequency of IL-10-producing B cells and its association with Treg/Th17 in adult primary immune thrombocytopenia patients.

Background: Regulatory B cells (Breg) are a distinct B cell subset with immunoregulatory properties. Pivotal to Breg function is interleukin-10. This study was to investigate the role of IL-10-producing B cell (B10) and its association with Treg and Th17 subsets in immune thrombocytopenia (ITP) patients.

High-dose dexamethasone modulates serum cytokine profile in patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder which is characterized by decreased platelet count. Serum cytokines play an important role in the pathogenesis of ITP by initiating and perpetuating various cellular and humoral autoimmune processes. To investigate a broad spectrum of cytokines in ITP patients and the effects of high-dose dexamethasone (HD-DXM) regimen on serum cytokines profile, a multiplex cytokine assay was used to measure the serum levels of 20 circulating cytokines simultaneously in 22 patients before and after oral administration of 40mg/day DXM for 4 consecutive days.