Bacteroides Fragilis Exacerbates T2D Vascular Calcification by Secreting Extracellular Vesicles to Induce M2 Macrophages.

Vascular calcification (VC) in type 2 diabetes (T2D) poses a serious threat to the life and health of patients. However, its pathogenesis remains unclear, resulting in a lack of effective treatment for the root cause. It is found that both intestinal Bacteroides fragilis (BF) and peripheral M2 monocytes/macrophages are significantly elevated in patients with T2D VC.

Extracellular vesicles of Bacteroides fragilis regulated macrophage polarization through promoted Sema7a expression.

Abnormal activation of macrophage and gut Bacteroides fragilis (BF) are the important induction factors in the occurrence of type 2 diabetes (T2D) and vascular complications. However, it remains unknown whether BF involves in macrophage polarization. In this study, we found that BF extracellular vesicles (EV) can be uptaken by macrophage.

Emerging role of RNA acetylation modification ac4C in diseases: Current advances and future challenges.

The oldest known highly conserved modification of RNA, N4-acetylcytidine, is widely distributed from archaea to eukaryotes and acts as a posttranscriptional chemical modification of RNA, contributing to the correct reading of specific nucleotide sequences during translation, stabilising mRNA and improving transcription efficiency. Yeast Kre33 and human NAT10, the only known authors of ac4C, modify tRNA with the help of the Tan1/THUMPD1 adapter to stabilise its structure. Currently, the mRNA for N4-acetylcytidine (ac4C), catalysed by NAT10 (N-acetyltransferase 10), has been implicated in a variety of human diseases, particularly cancer.

Amnio acid substitution at position 298 of human glucose-6 phosphatase-α significantly impacts its stability in mammalian cells.

Glucose-6-phosphatase-α (G6Pase-α) catalyzes the hydrolysis of glucose-6-phosphate to glucose and functions as a key regulator in maintaining blood glucose homeostasis. Deficiency in G6Pase-α causes glycogen storage disease 1a (GSD1a), an inherited disorder characterized by life-threatening hypoglycemia and other long-term complications. We have developed a potential mRNA-based therapy for GSD1a and demonstrated that a human G6Pase-α (hG6Pase-α) variant harboring a single serine (S) to cysteine (C) substitution at the amino acid site 298 (S298C) had > twofold increase in protein expression, resulting in improved in vivo efficacy.

Extracellular vesicle miR-32 derived from macrophage promotes arterial calcification in mice with type 2 diabetes via inhibiting VSMC autophagy.

Background: The development of diabetes vascular calcification (VC) is tightly associated with the inhibition of vascular smooth muscle cell (VSMC) autophagy. Previously, our team found that miR-32-5p (miR-32) promotes macrophage activation, and miR-32 is expressed at higher level in the plasma of patients with coronary calcification. However, whether miR-32 mediates the function of macrophages in type 2 diabetes (T2D) VC is still unclear.

Tumor-associated macrophages: An important player in breast cancer progression.

Breast cancer is the most common form of malignant tumor in females, accounting for the second highest mortality among cancer patients. In the breast tumor microenvironment, tumor-associated macrophages (TAMs) are the most abundant immune cells, which regulate the progression of breast cancer. During breast cancer tumorigenesis and progression, TAMs support breast tumor growth by promoting angiogenesis and cancer cell metastasis, inducing cancer stemness, regulating energy metabolism, and supporting immune system suppression.

Preparation and application of modified three-dimensional cellulose microspheres for paclitaxel targeted separation.

In this article, we successfully prepared three-dimensional cellulose microspheres modified by molecularly imprinted polymer for paclitaxel recognition and separation (3D-CM &PTX&MIPs). The material was characterized by Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron Microscope (SEM), Thermogravimetric Analysis (TG) and diffraction of X-rays (XRD). Under the optimized adsorption conditions, the maximum adsorption capacity reached 65.

The roles of immune cells in atherosclerotic calcification.

Atherosclerosis is the leading cause of acute cardiovascular events, and vascular calcification is an important pathological phenomenon in atherosclerosis. Recently, many studies have shown that immune cells are closely associated with the development of atherosclerosis and calcification, but there are many conflicting viewpoints because of immune system complications, such as the pro-atherosclerotic and atheroprotective effects of regulatory B cells (Bregs), T helper type 2 (Th2) cells and T helper type 17 (Th17) cells. In this review, we summarize the studies on the roles of immune cells, especially lymphocytes and macrophages, in atherosclerotic calcification.

mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease.

Glycogen Storage Disease 1a (GSD1a) is a rare, inherited metabolic disorder caused by deficiency of glucose 6-phosphatase (G6Pase-α). G6Pase-α is critical for maintaining interprandial euglycemia. GSD1a patients exhibit life-threatening hypoglycemia and long-term liver complications including hepatocellular adenomas (HCAs) and carcinomas (HCCs).

A cellulose-based temperature sensitivity molecular imprinted hydrogel for specific recognition and enrichment of paclitaxel.

A microcrystalline cellulose-based temperature sensitivity paclitaxel molecular imprinted hydrogel (MCC-TSMIHs-PTX) was successfully prepared by temperature-sensitive monomer N-isopropylacrylamide, functional monomer 4-vinylpyridine, cross-linking agent N, N'-methylenebisacrylamide and microcrystalline cellulose. They showed imprinting effective responses to the temperature changes. The results of adsorption kinetics, adsorption equilibrium, thermodynamics, selectivity and reusability showed the successful formation of a grafting thermosensitivity hydrogel with higher adsorption capacity and specific recognition.

Synthetic human ABCB4 mRNA therapy rescues severe liver disease phenotype in a BALB/c.Abcb4 mouse model of PFIC3.

Background & Aims: Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare lethal autosomal recessive liver disorder caused by loss-of-function variations of the ABCB4 gene, encoding a phosphatidylcholine transporter (ABCB4/MDR3). Currently, no effective treatment exists for PFIC3 outside of liver transplantation.

Methods: We have produced and screened chemically and genetically modified mRNA variants encoding human ABCB4 (hABCB4 mRNA) encapsulated in lipid nanoparticles (LNPs).

A porous cellulose-based molecular imprinted polymer for specific recognition and enrichment of resveratrol.

A novel resveratrol molecularly imprinted polymer (p-CM@MPS@MIP-Res) was prepared on the surface of silanized porous cellulose microspheres (p-CM@MPS) for the first time, and was successfully applied for the efficient enrichment of targeted resveratrol in Polygonum cuspidatum. The adsorption kinetics and adsorption equilibrium of p-CM@MPS@MIP-Res were also studied in detail. Compared with non-molecularly imprinted polymer (p-CM@MPS@NIP), the prepared p-CM@MPS@MIP-Res showed high adsorption capacity for resveratrol, the adsorption capacity of the p-CM@MPS@MIP-Res could reach to 11.

miR32-5p promoted vascular smooth muscle cell calcification by upregulating TNFα in the microenvironment.

Background: Vascular calcification is often associated with chronic inflammation and is a risk factor for brain arterial stiffness. Our previous results showed that miR32-5p was positively correlated with vascular smooth muscle cells (VSMC) calcification, but it is unclear whether miR32-5p promoted VSMC calcification by regulating inflammatory factor production.

Results: In this study, bioinformatics analysis was used to select tumour necrosis factor α (TNFα) as a candidate inflammatory factor associated with calcification.

Identification of an activation-related protein in B cells in the ABO incompatible condition.

In ABO-incompatible (ABOi) kidney transplantation (KT), antibodies can mediate immunological accommodation or immune rejection, but the mechanism by which B cells are induced to produce antibodies with different functions is still unclear. Previous research established an ABOi kidney cell model and identified that haptoglobin (HP) is associated with the activation of lymphocytes. In the present study, the results of a flow cytometric assay demonstrated that HP was expressed by B cells.

mRNA Therapy Improves Metabolic and Behavioral Abnormalities in a Murine Model of Citrin Deficiency.

Citrin deficiency is an autosomal recessive disorder caused by loss-of-function mutations in SLC25A13, encoding the liver-specific mitochondrial aspartate/glutamate transporter. It has a broad spectrum of clinical phenotypes, including life-threatening neurological complications. Conventional protein replacement therapy is not an option for these patients because of drug delivery hurdles, and current gene therapy approaches (e.

Salinomycin triggers endoplasmic reticulum stress through ATP2A3 upregulation in PC-3 cells.

Background: Salinomycin is a monocarboxylic polyether antibiotic and is a potential chemotherapy drug. Our previous studies showed that salinomycin inhibited cell growth and targeted CSCs in prostate cancer. However, the precise target of salinomycin action is unclear.

Salinomycin-induced autophagy blocks apoptosis via the ATG3/AKT/mTOR signaling axis in PC-3 cells.

Aims: This study evaluated the mechanism by which salinomycin-induced autophagy blocks apoptosis in PC-3 prostate cancer cells.

Main Methods: The anti-cancer effects of salinomycin in PC-3 cells were confirmed by flow cytometry, JC-1 staining and western blotting. Then, the autophagic effects were measured by western blotting, GFP-LC3 puncta formation assay, immunofluorescence staining and electron microscopy.

Discovery of EBI-2511: A Highly Potent and Orally Active EZH2 Inhibitor for the Treatment of Non-Hodgkin's Lymphoma.

A novel series of benzofuran derived EZH2 inhibitors were discovered through a scaffold hopping approach based on the clinical compound of EPZ-6438. Further rational structure-activity relationship exploration and optimization led to the discovery of more potent EZH2 inhibitors with oral bioavailability in mice and rats. A lead compound (compound ) demonstrated excellent efficacy in Pfeiffer tumor Xenograft models in mouse and is under preclinical development for the treatment of cancers associated with EZH2 mutations.

The effects of hemocyanin on T cells cultured .

As a broad-spectrum antibiotic, gentamicin is used extensively in T cell culturing , but preliminary studies have identified that T cell activity is significantly affected by gentamicin. In the present study, the hemocyanin from () was selected as an additive for T cell cultures . Compared with those in the control group, the cell quantity exhibited no significant difference, and the formation rate of cell colony increased gradually with increases in the hemocyanin concentration.

Discovery of EBI-1051: A novel and orally efficacious MEK inhibitor with benzofuran scaffold.

A novel series of benzodihydrofuran derivatives was developed as potent MEK inhibitors through scaffold hopping based on known clinical compounds. Further SAR exploration and optimization led to another benzofuran series with good oral bioavailability in rats. One of the compounds EBI-1051 (28d) demonstrated excellent in vivo efficacy in colo-205 tumor xenograft models in mouse and is suitable for pre-clinical development studies for the treatment of melanoma and MEK associated cancers.

The influence of HK2 blood group antigen on human B cell activation for ABOi-KT conditions.

Background: It is well known that ABO blood group system incompatible kidney transplantation (ABOi-KT) is an effective strategy for end-stage renal disease. The main barrier for ABOi-KT is how to keep host B cell activation and blood group antibody titer in low levels. Moreover, the mechanism of B cell activation induced by blood group antigen was unclear in ABOi-KT.