Oxidized galectin-1 in SLE fails to bind the inhibitory receptor VSTM1 and increases reactive oxygen species levels in neutrophils.

Inhibitory immune receptors set thresholds for immune cell activation, and their deficiency predisposes a person to autoimmune responses. However, the agonists of inhibitory immune receptors remain largely unknown, representing untapped sources of treatments for autoimmune diseases. Here, we show that V-set and transmembrane domain-containing 1 (VSTM1) is an inhibitory receptor and that its binding by the competent ligand soluble galectin-1 (Gal1) is essential for maintaining neutrophil viability mediated by downregulated reactive oxygen species production.

Proximity-enabled covalent binding of IL-2 to IL-2Rα selectively activates regulatory T cells and suppresses autoimmunity.

Interleukin-2 (IL-2) is a pleiotropic cytokine that orchestrates bidirectional immune responses via regulatory T cells (Tregs) and effector cells, leading to paradoxical consequences. Here, we report a strategy that exploited genetic code expansion-guided incorporation of the latent bioreactive artificial amino acid fluorosulfate-L-tyrosine (FSY) into IL-2 for proximity-enabled covalent binding to IL-2Rα to selectively promote Treg activation. We found that FSY-bearing IL-2 variants, such as L72-FSY, covalently bound to IL-2Rα via sulfur-fluoride exchange when in proximity, resulting in persistent recycling of IL-2 and selectively promoting the expansion of Tregs but not effector cells.

Study of Chloride Ion Diffusion in Coral Aggregate Seawater Concrete with Different Water-Cement Ratios under Load.

This study was conducted to investigate the chloride ion transport in coral aggregate seawater concrete (CASC) with varying water-cement ratios under different loads. The ultimate compressive strength was obtained by conducting compression testing of three groups of CASC with different water-cement ratios. Steady loads of 0%, 10%, and 20% of their respective ultimate compressive strengths were applied to the concrete specimens with different water-cement ratios.

Insights into the pathogenic role of neutrophils in systemic lupus erythematosus.

Purpose Of Review: Although dysregulated adaptive immune response has been considered as the main culprit for systemic lupus erythematosus (SLE), emerging studies have indicated that innate immunity, functioning upstream of adaptive immunity, acts as an important trigger of autoimmune diseases and promotes SLE development. Here, we have reviewed the most recent findings to highlight the influence of neutrophils on SLE pathogenesis.

Recent Findings: Neutrophils participate in SLE development mainly via promoting self-antigen exposure and autoantibody production, advocating the release of type I interferons (IFNs) and other pro-inflammatory cytokines, and mediating systemic tissue injury.

Systemic lupus erythematosus-complicating immune thrombocytopenia: From pathogenesis to treatment.

Immune thrombocytopenia (ITP) is a common hematological manifestation of systemic lupus erythematosus (SLE). The heterogeneity of its clinical characteristics and therapeutic responses reflects a complex pathogenesis. A better understanding of its pathophysiological mechanisms and employing an optimal treatment regimen is therefore important to improve the response rate and prognosis, and avoid unwanted outcomes.

Purification and properties of a novel trypsin inhibitor from ginkgo fruits and its antiproliferative effect in triple-negative breast cancer cells.

A novel low molecular mass ginkgo biloba trypsin inhibitor (GBTI) was isolated from ginkgo fruits (GF) by trypsin inhibitory activity-guided fractionation by using ammonium sulphate precipitation, followed by ultra-filtration, affinity chromatography and RP-HPLC. The molecular mass and amino acid sequence of GBTI was determined using ESI-MS and ESI-MS/MS, respectively. The structure of GBTI was identified as MKNLTVIPPICLKFPN, with a molecular mass of 1826 Da.

Intermittent fasting suppressed splenic CD205+ G-MDSC accumulation in a murine breast cancer model by attenuating cell trafficking and inducing apoptosis.

Immune-based interventions are the most promising approach for new cancer treatments to achieve long-term cancer-free survival. However, the expansion of myeloid-derived suppression cells (MDSCs) attenuates the therapeutic potential of immunotherapy. We recently showed that CD205+ granulocytic MDSCs (G-MDSCs), but not T cells, are sensitive to glucose deficiency.

CD205 polymorphonuclear myeloid-derived suppressor cells suppress antitumor immunity by overexpressing GLUT3.

Myeloid-derived suppressor cells (MDSCs) are responsible for antitumor immunodeficiency in tumor-bearing hosts. Primarily, MDSCs are classified into 2 groups: monocytic (M)-MDSCs and polymorphonuclear (PMN)-MDSCs. In most cancers, PMN-MDSCs (CD11b Ly6C Ly6G cells) represent the most abundant MDSC subpopulation.

Expression pattern analysis and drug differential sensitivity of cancer-associated fibroblasts in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) has the characteristics of a complex molecular landscape, aggressive or high proliferation leading to poor prognosis, and behavioral heterogeneity. The purpose of the present study was to determine the spatiotemporal expression of α-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs) at histological level in 4T1 tumors and to predict the sensitivity to 138 drugs in patients with TNBC according to α-SMA expression. The quantitative results of fibrosis showed that the volume of 4T1 tumors correlated positively with the area of tumor fibrosis.

A method for separation and purification of mouse splenocytes by density gradient centrifugation.

Spleen is an information-rich and easy-accessible peripheral lymphoid organ. It has complex cell composition because of the immunocytes maturity and settle down. Changes of the composition and function of these immunocytes are critical to body immune response.

Detection of microRNA expression levels based on microarray analysis for classification of idiopathic pulmonary fibrosis.

The etiology and pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) are yet to be fully elucidated; however, mining of disease-related microRNAs (miRNAs/miRs) has improved the understanding of the progression of IPF. The aim of the current study was to screen miRNAs associated with IPF using three mathematical algorithms: One-way ANOVA, least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). Using ANOVA, three miRNAs and two miRNAs were selected with opposite expression patterns in moderate and severe IPF, respectively.

Peptidomic analysis of pilose antler and its inhibitory effect on triple-negative breast cancer at multiple sites.

Pilose antler (PA) is a traditional Chinese functional food that has been reported to inhibit breast cancer; however, the specific substances that exert this effect and the underlying mechanisms remain unknown. This study aims to identify the specific proteins in PA water-soluble polypeptides (PAWPs) that are involved in cancer inhibition and determine the effects of PAWPs on triple-negative breast cancer in mice. In this study, peptidomic analysis of 105 varieties of polypeptides from PAWPs was carried out using LC-MS, 22 of which had functions that could potentially suppress tumors, including endopeptidase inhibitors, metal ion-binding proteins, angiogenesis inhibitors, intercellular adhesion proteins, and extracellular matrix repair proteins.

Anti-migration and anti-invasion effects of 2-hydroxy-6-tridecylbenzoic acid is associated with the enhancement of CYP1B1 expression through activating the AMPK signaling pathway in triple-negative breast cancer cells.

2-hydroxy-6-tridecylbenzoic acid is alkylsalicylic acid monomer compound, abundantly existed in the ginkgo biloba extracts, however, the underlying mechanism of its anti-migration and anti-invasion effects in triple-negative breast cancer (TNBC) is not clear. Here, 2-hydroxy-6 -tridecylbenzoic acid inhibited MDA-MB-231 and 4 T-1 cells growth without toxicity to MCF-10A normal breast cells. Meanwhile, 2-hydroxy-6-tridecylbenzoic acid inhibited cells migration and invasion as well as EMT with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, Vimentin, Snail, MMP-2 and MMP-9 expression.

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway.

Purpose: To explore the regulatory mechanism of miR-137 and transcription factor 4 (TCF4) in the progression of osteoarthritis (OA).

Patients And Methods: The expressions of miR-137 and TCF4 were detected in OA cartilage tissue, chondrocytes and OA rat cartilage tissue. miR-137 and TCF4 were up-regulated or down-regulated and transfected into chondrocytes and OA rat cartilage tissue.

Donkey milk inhibits triple-negative breast tumor progression and is associated with increased cleaved-caspase-3 expression.

Donkey milk is considered an ideal substitute for human milk and is considered a potential complementary dairy product for the treatment of a variety of human diseases, including cancer. The purpose of this study was to investigate the inhibitory effect of donkey colostrum (DC) and mature milk (DM) on 4T1 triple-negative breast cancer (TNBC) tumors in mice. Metabolomics analyses showed that a total of 476 possible metabolites were found in both types of milk.

Low-dose Roundup induces developmental toxicity in bovine preimplantation embryos in vitro.

Roundup is a widely used glyphosate-based herbicide worldwide. Roundup residues can be detected in the organs and urine of animals. However, its toxicity on mammalian preimplantation embryos has not been well investigated.

Exploration of the immune-related signature and immune infiltration analysis for breast ductal and lobular carcinoma.

Background: In this study, we aimed to explore the tumour associated immune signature of breast cancer (BC) and conduct integrative analyses with immune infiltrates in BC.

Methods: We downloaded the transcriptome profiling and clinical data of BC from The Cancer Genome Atlas (TCGA) database. The list of immune-related signatures was from the Innate database.

B Cell Dysfunction Associated With Aging and Autoimmune Diseases.

Impaired humoral responses, as well as an increased propensity for autoimmunity, play an important role in the development of immune system dysfunction associated with aging. Accumulation of a subset of atypical B cells, termed age-associated B cells (ABCs), is one of the key age-related changes in B cell compartments. ABCs are characterized by their distinct phenotypes, gene expression profiles, special survival requirements, variations in B cell receptor repertoires, and unique functions.

Development of a high efficient promoter finding method based on transient transfection.

In metazoan genome, the mechanism of gene expression regulation between transcriptional regulatory elements and their target gene is spatiotemporal. Active promoters possess many specific chromosomal features, such as hypersensitive to DNaseI and enrichment of specific histone modifications. In this article, we proposed a novel method which possesses a high efficiency to find promoters .

Development of a high efficient promoter finding method based on transient transfection.

In metazoan genome, the mechanism of gene expression regulation between transcriptional regulatory elements and their target gene is spatiotemporal. Active promoters possess many specific chromosomal features, such as hypersensitive to DNaseI and enrichment of specific histone modifications. In this article, we proposed a novel method which possesses a high efficiency to find promoters in vitro.

Antiproliferative effect of 2-Hydroxy-6-tridecylbenzoic acid from ginkgo biloba sarcotestas through the aryl hydrocarbon receptor pathway in triple-negative breast cancer cells.

This study aims to isolate the potential antiproliferative and cytotoxic compounds from ginkgo biloba sarcotestas (GBS) and investigates the underlying mechanism in human MDA-MB-231 and mouse 4T-1 triple-negative breast cancer cells. Our results showed that 2-Hydroxy-6-tridecylbenzoic acid was isolated by cytotoxicity-guided fractionation where different fractions were assessed using MTT assay against MDA-MB-231 and 4T-1 cells. Colony formation assay showed that 2-Hydroxy-6-tridecylbenzoic acid significantly inhibited cell proliferation.

[Blood extracts from pilose antler changes the proportion of immune cells in mammary tumor-bearing mice and inhibit the growth of transplanted tumor].

Objective To study the influence of blood extracts from pilose antler on the immune system in healthy mice and tumor-bearing mice. Methods A mouse mammary tumor transplantation model was established and both the healthy and the tumor-bearing mice were gavaged with the blood extracts of pilose antler. The percentages of mouse peripheral blood CD3 T cells, CD4 T cells, CD8 T cells, B220 B cells and myeloid-derived suppressor cells (MDSCs) in the healthy and tumor-bearing mice were analyzed by flow cytometry.

Asymmetric distribution of CRUMBS polarity complex proteins from compacted 8-cell to blastocyst stage during mouse preimplantation development.

During mouse preimplantation development, blastomeres are equipotent until polarity establishment at compacted 8-cell stage. The intrinsic nature of polarity is the asymmetric distribution of polarity proteins between inside and outside blastomeres along the direction of apical-basal axis. This study investigated the early developmental temporal and spatial expression of the main CRUMBS polarity complex proteins in the mouse preimplantation embryo.

Antiproliferative effect of the extract is associated with the enhancement of cytochrome P450 1B1 expression in estrogen receptor-negative breast cancer cells.

is a dioecious tree and its extract is a complex mixture that has been used for thousands of years to treat a variety of ailments in traditional Chinese medicine. The aim of this study was to present our observations on the inhibitory effects of different extracts on human breast cancer cell proliferation and growth. Our results demonstrated that treatment of MCF-7 and MDA-MB-231 human breast cancer cells with leaves and ginkgo fruit extract inhibited cell proliferation.

The cell cycle distribution should be given more consideration in cell-based in vitro toxicological studies.

In this study, to discuss the importance of the cell cycle distribution in cell-based in vitro toxicity mechanism studies, diethyl sulfate (DES) was selected as a model chemical that induced the alteration of the cell cycle distribution in human bronchial epithelial cell line 16HBE 14o- (HBE) cells. Cells were treated with various concentrations of DES, cell proliferation and apoptosis were then determined. The results showed that DES concentration-dependently inhibited HBE cells proliferation and induced apoptosis.