VISTA antibody-loaded FeO@TiO nanoparticles for sonodynamic therapy-synergistic immune checkpoint therapy of pancreatic cancer.

Breaking the poor permeability of immune checkpoint inhibitors (ICIs) caused by the stromal barrier and reversing the immunosuppressive microenvironment are significant challenges in pancreatic cancer immunotherapy. In this study, we synthesized core-shell FeO@TiO nanoparticles to act as carriers for loading VISTA monoclonal antibodies to form FeO@TiO@VISTAmAb (FTV). The nanoparticles are designed to target the overexpressed ICIs VISTA in pancreatic cancer, aiming to improve magnetic resonance imaging-guided sonodynamic therapy (SDT)-facilitated immunotherapy.

Cathepsin B/NLRP3/GSDMD axis-mediated macrophage pyroptosis induces inflammation and fibrosis in systemic sclerosis.

Background: Pyroptosis is a newly discovered type of programmed cell death associated with inflammatory and fibrotic diseases. Macrophages play an important role in inducing early immune inflammation in systemic sclerosis (SSc).

Objective: To investigate the effect of macrophages pyroptosis on fibrosis of SSc.

Inhibition of JAK1/STAT3 pathway by 2-methoxyestradiol ameliorates psoriatic features in vitro and in an imiquimod-induced psoriasis-like mouse model.

Psoriasis is characterized by hyperproliferative keratinocytes, dilated capillaries and leukocyte infiltration. 2-Methoxyestradiol (2-ME) has shown significant inhibition on proliferation, angiogenesis and inflammation. To evaluate the anti-psoriatic potential of 2-ME, psoriasis-like dermatitis was induced by topical application of imiquimod (IMQ) on the dorsal skin of C57BL/6 mice for seven consecutive days, followed by treatment of vehicle or 2-ME ointment from Day 4 on.

DNA from macrophages induces fibrosis and vasculopathy through POLR3A/STING/type I interferon axis in systemic sclerosis.

Objective: To clarify the role of RNA polymerase III A (POLR3A)/type I IFN in the pathogenesis of SSc.

Methods: Cytosolic DNA and stimulator of IFN genes (STING) pathway in skin or serum of SSc patients were detected by immunofluorescence, immunohistochemistry and western blotting. DNA from human macrophages was transfected to SSc fibroblasts or human umbilical vein endothelial cells (HUVECs) and then markers of POLR3A/STING pathway were detected by real-time qPCR, western blotting and confocal microscopy.

Palmar erythema and palmar papules as predictors for dermatomyositis-related acute/subacute interstitial lung disease: a retrospective study.

Objectives: DM-related acute/subacute interstitial lung disease (A/S-ILD) remains a big therapeutic challenge due to its insidious onset and rapid development. In the present study, we aimed to investigate the association between clinical features of DM and ILD.

Methods: We retrospectively assessed skin manifestations, muscle damage, laboratory tests, concurrent ILD and malignancy in 207 patients with DM and analysed the high-risk factors for ILD.

Autophagy mediates 2-methoxyestradiol-inhibited scleroderma collagen synthesis and endothelial-to-mesenchymal transition induced by hypoxia.

Objectives: To investigate whether autophagy mediates 2-methoxyestradiol (2-ME)-inhibited hypoxia-induced fibrosis and endothelial-to-mesenchymal transition (endoMT) in SSc.

Methods: Autophagy in the skin of SSc patients was assessed by transmission electron microscopy. SSc skin fibroblasts and human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic (1% O2) conditions with 2-ME or autophagy inhibitor.

2-Methoxyestradiol inhibits hypoxia-induced scleroderma fibroblast collagen synthesis by phosphatidylinositol 3-kinase/Akt/mTOR signalling.

Objectives: To investigate the mechanism of 2-methoxyestradiol (2-ME) in inhibiting hypoxia-induced collagen synthesis of fibroblasts in SSc.

Methods: The expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and connective tissue growth factor (CTGF) in skin specimens derived from SSc patients and healthy volunteers were examined by immunohistochemistry. HIF-1α was knocked down by lentiviral transduction, and SSc dermal fibroblasts cultured under normoxic (21% O2) or hypoxic (1% O2) condition were treated with PI3K inhibitor LY294002, rapamycin or 2-ME (25 μM).

Interferon-gamma Inhibits Melanogenesis and Induces Apoptosis in Melanocytes: A Pivotal Role of CD8+ Cytotoxic T Lymphocytes in Vitiligo.

Increased expression of the cytokine interferon (IFN)-γ plays a pivotal role in vitiligo-induced depigmentation. However, the major source of IFN-γ in vitiligo patients and the mechanisms underlying melanocyte destruction are unknown. In this study, a large number of skin infiltrating IFN-γ+ cells and CD8+ T cells were detected in progressive vitiligo.

2-Methoxyestradiol inhibits bleomycin-induced systemic sclerosis through suppression of fibroblast activation.

Background: The most dominant feature of systemic sclerosis (SSc) is fibrosis, which is caused by overproduction of collagen by fibroblasts. 2-Methoxyestradiol (2-ME) has exhibited disease-modifying activity in animal models of rheumatoid arthritis and autoimmune encephalomyelitis and inhibitory effect in cell proliferation and collagen synthesis. Therefore, we hypothesized that 2-ME may exhibit antifibrotic effect in SSc.

IL-17A induces endothelial inflammation in systemic sclerosis via the ERK signaling pathway.

Recent reports have demonstrated that endothelial cells are involved in vascular inflammatory injury in systemic sclerosis (SSc) and interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of SSC. However, little is known about the effects of IL-17A on endothelial cell inflammation in SSC. The aim of our study was to investigate the role of IL-17A in endothelial inflammation.

Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice.

Objective: To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice.

Methods: Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 μM).

Th17 and natural Treg cell population dynamics in systemic lupus erythematosus.

Objective: To investigate the relative abundance and activities of Th17 cells and natural Treg cells in systemic lupus erythematosus (SLE).

Methods: Blood samples were collected from 50 adult patients with SLE. Samples were processed to detect Th17 cells and natural Treg cells by flow cytometry, and related gene expression was assessed by real-time reverse transcription-polymerase chain reaction.