Treatment of a MyD88 inhibitor alleviates rejection and inflammation in xenotransplantation by inhibiting dendritic cells activation and trained immunity in macrophages.

Background: Acute vascular rejection (AVR) and systemic inflammation in xenograft recipients (SIXR) negatively impact the xenografts survival, and novel immunosuppressants are required to improve survival outcomes. We previously reported that TJ-M2010-5, a myeloid differentiation factor 88 (MyD88) inhibitor, exerts excellent anti-rejection effects in allogeneic transplantation. The aim of the present study was to evaluate the efficacy of TJ-M2010-5 in preventing AVR and SIXR and to investigate whether combined treatment of TJ-M2010-5 with anti-CD154 antibody (MR1) could prolong xenograft survival furthermore.

The role of pyroptosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the main histologic type of liver cancer. It accounts for the majority of all diagnoses and deaths due to liver cancer. The induction of tumor cell death is an effective strategy to control tumor development.

TJ-M2010-5, a novel CNS drug candidate, attenuates acute cerebral ischemia-reperfusion injury through the MyD88/NF-κB and ERK pathway.

Cerebral ischemia-reperfusion injury (CIRI) inevitably occurs after vascular recanalization treatment for ischemic stroke. The accompanying inflammatory cascades have a major impact on outcome and regeneration after ischemic stroke. Evidences have demonstrated that TLR/MyD88/NF-κB signaling contributes to CIRI.

The Novel MyD88 Inhibitor TJ-M2010-5 Protects Against Hepatic Ischemia-reperfusion Injury by Suppressing Pyroptosis in Mice.

Background: . With the development of medical technology and increased surgical experience, the number of patients receiving liver transplants has increased. However, restoration of liver function in patients is limited by the occurrence of hepatic ischemia-reperfusion injury (IRI).

Liraglutide attenuates intestinal ischemia/reperfusion injury via NF-κB and PI3K/Akt pathways in mice.

Aims: Previous studies have reported that glucagon-like peptide-1 (GLP-1) may play a critical role in the development of intestinal ischemia-reperfusion (I/R) injury. The present study aimed to investigate whether liraglutide (GLP-1 analog) protects against intestinal I/R injury and reveals the possible underlying mechanism.

Main Methods: Temporary superior mesenteric artery occlusion was performed to establish an intestinal I/R injury mouse model.

TJ-M2010-5 Attenuates Severe Myocardial Ischemia/Reperfusion Injury in Heart Transplantation by Inhibiting MyD88 Homodimerization In Vivo.

Survival of transplanted hearts is often limited by cold ischemia time. Here, we assessed the effects of the small molecular compound TJ-M2010-5 on graft preservation. In a cardiac cold ischemia/reperfusion model, TJ-M2010-5 ameliorated myocardial ischemia/reperfusion injury (MIRI) in histidine-tryptophan-ketoglutarate (HTK) organ preservation solution.

TJ-M2010-5, A self-developed MyD88 inhibitor, attenuates liver fibrosis by inhibiting the NF-κB pathway.

Liver fibrosis is the result of most chronic inflammatory liver damage and seriously endangers human health. However, no drugs have been approved to treat this disease. Previous studies showed that the Toll-like receptors (TLRs)/myeloid differentiation factor-88 (MyD88)/nuclear factor-κB (NF-κB) pathway plays a key role in liver fibrosis.

Inhibition of MyD88 by a novel inhibitor reverses two-thirds of the infarct area in myocardial ischemia and reperfusion injury.

Cardiomyocytes, macrophages, and fibroblasts play important roles in inflammation and repair during myocardial ischemia/reperfusion injury (MIRI). Myeloid differentiation primary response 88 (MyD88) is upregulated in immunocytes, cardiomyocytes, and fibroblasts during MIRI. MyD88 induces the secretion of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), while fibroblasts are recruited and activated to mediate cardiac remodeling.

The MyD88 inhibitor TJ-M2010-2 suppresses proliferation, migration and invasion of breast cancer cells by regulating MyD88/GSK-3β and MyD88/NF-κB signalling pathways.

MyD88 has been implicated in the tumourigenesis, metastasis and recurrence of breast cancer (BC). Here we utilized TJ-M2010-2 (TJ), an inhibitor of MyD88 homodimerimerization, and siMyD88 to suppress the function of MyD88 in MCF-7 and MDA-MB-231 cells. BC cells were treated in vitro and xenografted into nude mice to generate a model in vivo.

TJ-M2010-5, a novel MyD88 inhibitor, corrects R848-induced lupus-like immune disorders of B cells in vitro.

B cell hyperactivities are involved in the development of systemic lupus erythematosus (SLE). Toll-like receptor 7 (TLR7) in the B cells plays a pivotal role in the pathogenesis of SLE. Previous studies have focused on the intrinsic role of B cells in TLR7/MyD88 signaling and consequently on immune activation, autoantibody production, and systemic inflammation.

Human MiR-4660 regulates the expression of alanine-glyoxylate aminotransferase and may be a biomarker for idiopathic oxalosis.

Background: Dysfunction of oxalate synthesis can cause calcium oxalate stone disease and inherited primary hyperoxaluria (PH) disorders. PH type I (PH1) is one of the most severe hyperoxaluria disorders, which results in urolithiasis, nephrocalcinosis, and end-stage renal disease. Here, we sought to determine the role of microRNAs in regulating AGXT to contribute to the pathogenesis of mutation-negative idiopathic oxalosis.

Short-term use of MyD88 inhibitor TJ-M2010-5 prevents d-galactosamine/lipopolysaccharide-induced acute liver injury in mice.

Excessive activation of the TLR/MyD88 signaling pathway contributes to several inflammation-related diseases. Previously, our laboratory synthesized a novel thiazaol-aminoramification MyD88 inhibitor named TJ-M2010-5. In this study, we interrogated the role of MyD88, as well as the protective effect of TJ-M2010-5, in a d-gal/LPS-induced acute liver injury mouse model.

A Novel Inhibitor of Homodimerization Targeting MyD88 Ameliorates Renal Interstitial Fibrosis by Counteracting TGF-β1-Induced EMT in Vivo and in Vitro.

Background/aims: The TLR/MyD88/NF-κB signaling pathway has been successfully used to treat renal interstitial fibrosis (RIF). However, the exact therapeutic mechanism is still unknown. Here, we assessed the therapeutic efficacy of TJ-M2010-2, a small molecular compound that inhibits MyD88 homodimerization, in RIF induced by ischemia reperfusion injury (IRI).