A humanized anti-b7h3×4-1BB bispecific antibody exerts potent antitumour effects through the activation of innate and adaptive immunity.

Agonistic monoclonal antibodies targeting 4-1BB have shown much preclinical promise, but their clinical development has been limited by obvious toxicity or unremarkable efficacy. Here, we generated two humanized anti-B7H3 × 4-1BB bsAbs (HK056-001/002) by fusing an anti-4-1BB scFv to the C-terminus of an anti-B7H3 with an intact Fc fragment from human IgG1 or IgG4. The two bsAbs were able to stimulate the 4-1BB signaling pathway, which was strictly dependent on B7H3 expression.

A humanized anti-MSLN×4-1BB bispecific antibody exhibits potent antitumour activity through 4-1BB signaling activation and fc function without systemic toxicity.

Background: Agonistic monoclonal antibodies targeting 4-1BB/CD137 have shown preclinical promise, but their clinical development has been limited by severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy.

Methods: A novel anti-MSLN×4-1BB bispecific antibody (bsAb) was generated via antibody engineering, and its affinity and activity were detected via enzyme-linked immunosorbent assay (ELISA), flow cytometry, and T-cell activation and luciferase reporter assays.

Unveiling the metabolic landscape of pulmonary hypertension: insights from metabolomics.

Pulmonary hypertension (PH) is regarded as cardiovascular disease with an extremely poor prognosis, primarily due to irreversible vascular remodeling. Despite decades of research progress, the absence of definitive curative therapies remains a critical challenge, leading to high mortality rates. Recent studies have shown that serious metabolic disorders generally exist in PH animal models and patients of PH, which may be the cause or results of the disease.

Iron metabolism disorder regulated by BMP signaling in hypoxic pulmonary hypertension.

Backgrounds And Aims: Unexplained iron deficiency is associated with poorer survival in patients with pulmonary hypertension (PH). Bone morphogenetic protein (BMP) signaling and BMP protein type II receptor (BMPR2) expression are important in the pathogenesis of PH. BMP6 in hepatocytes is a central transcriptional regulator of the iron hormone hepcidin that controls systemic iron balance.

Inhibition of sphingosine 1-phosphate (S1P) receptor 1/2/3 ameliorates biological dysfunction in rheumatoid arthritis fibroblast-like synoviocyte MH7A cells through Gαi/Gαs rebalancing.

Sphingosine 1-phosphate (S1P) exerts its various physiological and pathological effects by interacting with G protein-coupled receptors. In addition, S1P can induce biological dysfunction in fibroblast-like synoviocytes (FLSs) in the development of rheumatoid arthritis (RA). However, the mechanism underlying this S1P-induced dysfunction remains unclear.

Anti-Inflammatory Effect of Geniposide on Regulating the Functions of Rheumatoid Arthritis Synovial Fibroblasts via Inhibiting Sphingosine-1-Phosphate Receptors1/3 Coupling Gαi/Gαs Conversion.

The activated Gα protein subunit (Gαs) and the inhibitory Gα protein subunit (Gαi) are involved in the signal transduction of G protein coupled receptors (GPCRs). Moreover, the conversion of Gαi/Gαs can couple with sphingosine-1-phosphate receptors (S1PRs) and have a critical role in rheumatoid arthritis (RA). Through binding to S1PRs, sphingosine-1-phosphate (S1P) leads to activation of the pro-inflammatory signaling in rheumatoid arthritis synovial fibroblasts (RASFs).

[Pharmacokinetics of Achyranthes bidentata on adjuvant arthritis rats by microdialysis and UHPLC-MS/MS].

To investigate the " drug-guide" effect of Achyranthes bidentata saponins( ABS) and geniposide( GE) in the treatment on adjuvant arthritis( AA) rats. A UHPLC-MS/MS method for the quantitative determination of GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa in rat blood and joint dialysate was established. After single or combined administration with ABS and GE was given to AA rat model,a microdialysis sampling method for rat joint cavity and jugular vein blood vessels was established to collect microdialysis samples.

UHPLC-MS/MS analysis of sphingosine 1-phosphate in joint cavity dialysate and hemodialysis solution of adjuvant arthritis rats: Application to geniposide pharmacodynamic study.

Geniposide (GE) is an iridoid glycoside compound with anti-inflammatory effect. The potential of sphingosine 1-phosphate (S1P) as a plasma marker in human diseases was suggested recently in the literature, which demonstrated that, in patients with inflammatory diseases, plasma S1P was elevated. It follows that the obstructive coronary artery disease can be predicted with serum S1P.

Novel anti-inflammatory target of geniposide: Inhibiting Itgβ1/Ras-Erk1/2 signal pathway via the miRNA-124a in rheumatoid arthritis synovial fibroblasts.

Geniposide (GE) is an active component isolated from the fruit of Gardenia jasminoides Ellis that has anti-inflammatory and other pharmacological effects; however, the underlying mechanism of GE action has not been elucidated in rheumatoid arthritis (RA). Previous studies have shown that GE plays a therapeutic role in RA via regulation of the integrin beta 1 (Itgβ1)-mediated Ras-Erk1/2 signalling pathway. However, the specific mechanism of GE action on Itgβ1 has not been clarified.

Immunosuppressive Effect of Geniposide on Mitogen-Activated Protein Kinase Signalling Pathway and Their Cross-Talk in Fibroblast-Like Synoviocytes of Adjuvant Arthritis Rats.

Geniposide (GE), an iridoid glycoside compound derived from fruit, is known to have anti-inflammatory and immunoregulatory activities. The aim of this study was to investigate the protective mechanism of GE in the regulation of the mitogen-activated protein kinase (MAPK) signalling pathway and the cross-talk among the MAPK signalling pathway in fibroblast-like synoviocytes (FLS) of adjuvant arthritis (AA) rats. AA was induced by injecting with Freund's complete adjuvant.

Vacuum metal deposition: visualisation of gold agglomerates using TEM imaging.

Vacuum metal deposition (VMD) is a well-established technique that can be used for the development of latent fingermarks on a range of polymer surfaces, including polyethylene (PE) bags exposed to harsh environmental conditions. The technique has also proved to be effective on difficult semi-porous surfaces such as the polymer banknotes in circulation in Australia and in an increasing number of other countries. VMD is a two-stage technique.