irak1

Hepatocellular carcinoma (HCC) is a prevalent and deadly form of cancer globally with typically unfavorable outcomes. Increasing research suggests that lactate serves as an important carbon contributor to cellular metabolism and holds a crucial part in the progression, sustenance, and treatment response of tumors. However, the contribution of lactate-related genes (LRGs) in HCC is still unclear. In this study, we analyzed TCGA datasets and screened 21 differentially expressed LRGs related to long-term survivals in HCC patients...

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joint synovium. The traditional Chinese medicine Xinfeng capsule (XFC) has a remarkable alleviating effect on inflammatory symptoms, such as joint pain and swelling, in patients with RA. However, the underlying mechanism of action remains to be elucidated. This study intended to conduct network pharmacology, animal experiments, data mining, and molecular docking to explore the molecular mechanism through which XFC can improve the inflammatory symptoms of RA...

Oxomollugin is a degraded product of mollugin and was found to be an active compound that inhibits LPS-induced NF-κB activation. In this study, we investigated the inhibitory activity of oxomollugin, focusing on TLR4 signaling pathway, resulting in NF-κB activation. Oxomollugin inhibited the LPS-induced association of essential factors for initial activation of TLR4 signaling, MyD88, IRAK4 and TRAF6. Furthermore, oxomollugin showed suppressive effects on LPS-induced modification of IRAK1, IRAK2 and TRAF6, LPS-induced association of TRAF6-TAK1/TAB2, and followed by IKKα/β phosphorylation, which critical in signal transduction leading to LPS-induced NF-κB activation...

Pathologic type I interferon (T1IFN) expression is a key feature in systemic lupus erythematosus (SLE) that associates with disease activity. When compared to adult-onset disease, juvenile-onset (j)SLE is characterized by increased disease activity and damage, which likely relates to increased genetic burden. To identify T1IFN-associated gene polymorphisms (TLR7, IRAK1, miR-3142/miR-146a, IRF5, IRF7, IFIH1, IRF8, TYK2, STAT4), identify long-range linkage disequilibrium and gene:gene interrelations, 319 jSLE patients were genotyped using panel sequencing...

Piperine, the major active substance in black pepper, has been shown to have anti-inflammatory and antioxidant effects in several ischemic diseases. However, the role of piperine in hepatic ischemia/reperfusion injury (HIRI) and its underlying mechanisms remain unclear. In this study, the mice were administered piperine (30 mg/kg) intragastric administration before surgery. After 24 h of hepatic ischemia-reperfusion, liver histopathological evaluation, serum transaminase measurements, and TUNEL analysis were performed...

OBJECTIVES: X chromosome has been considered as a risk factor for SLE, which is a prototype of autoimmune diseases with a significant sex difference (female:male ratio is around 9:1). Our study aimed at exploring the association of genetic variants in X chromosome and investigating the influence of trisomy X in the development of SLE. METHODS: X chromosome-wide association studies were conducted using data from both Thai (835 patients with SLE and 2995 controls) and Chinese populations (1604 patients with SLE and 3324 controls)...

Transcriptome sequencing has offered immense opportunities to study non-model organisms. Abalone is an important marine mollusk that encounters harsh environmental conditions in its natural habitat and under aquaculture conditions; hence, research that increases molecular information to understand abalone physiology and stress response is noteworthy. Accordingly, the study used transcriptome sequencing of the gill tissues of abalone exposed to low salinity stress. The aim is to explore some enriched pathways during salinity stress and the crosstalk and functions of the genes involved in the candidate biological processes for future further analysis of their expression patterns...

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Primary effusion lymphoma (PEL) and a form of multicentric Castleman's disease (MCD) are both caused by Kaposi sarcoma herpesvirus (KSHV). There is a critical need for improved therapies for these disorders. The IL-6/JAK/STAT3 pathway plays an important role in the pathogenesis of both PEL and KSHV-MCD. We explored the potential of JAK inhibitors for use in PEL and KSHV-MCD, and found that pacritinib was superior to others in inhibiting the growth of PEL cell lines. Pacritinib induced apoptosis in PEL cells and inhibited STAT3 and NF-κB activity as evidenced by reduced amount of phosphorylated moieties...

Activation of endosomal Toll-like receptor (TLR) 7, TLR9, and TLR11/12 is a key event in the resistance against the parasite Toxoplasma gondii. Endosomal TLR engagement leads to expression of interleukin (IL)-12 via the myddosome, a protein complex containing MyD88 and IL-1 receptor-associated kinase (IRAK) 4 in addition to IRAK1 or IRAK2. In murine macrophages, IRAK2 is essential for IL-12 production via endosomal TLRs but, surprisingly, Irak2-/- mice are only slightly susceptible to T. gondii infection, similar to Irak1-/- mice...

BACKGROUND: Juvenile SLE (JSLE) is a complex autoimmune disorder that predominantly affects children and adolescents with several unique challenges, and microRNA-146a (miRNA-146a) might be an interesting anti-inflammatory molecule. Because exosomes in the blood might protect miRNAs, the association between circulating exosomal miRNA-146a and lupus proinflammatory genes, such as IRAK1 and TRAF6 , was studied in peripheral blood mononuclear cells from people with JSLE. METHODS: Blood samples from 12 patients were collected every 3 months until 1 year with the recorded disease activity, and quantitative real-time PCR was used to determine the circulating exosomal miRNA-146a and the gene expression ( IRAK1 and TRAF6 )...

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Accumulating evidence indicates that hypoxia and lactate metabolism play critical roles in tumor progression and therapeutic efficacy. This study aimed to construct a hypoxia- and lactate metabolism-related prognostic model (HLPM) to evaluate survival and treatment responses for HCC patients and develop a nomogram integrated with HLPM and clinical characteristics for prognosis prediction in HCC...

Transforming growth factor (TGF)-β and toll-like receptors (TLRs) have been shown to independently modulate the proliferation of hepatocellular carcinoma (HCC). Since a direct cross-talk between these two signalling pathways in HCC has not been clearly described before, we aimed here to explore the possibility of such interaction. A human HCC tissue array (n = 20 vs. four control samples), human HCC samples (n = 10) and steatohepatitis-driven murine HCC samples (control, NASH and HCC; n = 6/group) were immunostained for TGFβR1, pSMAD2, TRAF6, IRAK1 and PCNA...

Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and lymphomas have poor patient outcomes; novel therapies are needed. CD22 is an attractive target for antibody-drug conjugates (ADCs), being highly expressed in R/R B-ALL with rapid internalization kinetics. ADCT-602 is a novel CD22-targeting ADC, consisting of humanized monoclonal antibody hLL2-C220, site-specifically conjugated to the pyrrolobenzodiazepine dimer-based payload tesirine. In preclinical studies, ADCT-602 demonstrated potent, specific cytotoxicity in CD22-positive lymphomas and leukemias...

Spring viremia of carp virus (SVCV) is a globally distributed virus that causes severe clinical symptoms and high mortality in fish belonging to the families Cyprinidae and Siluridae. To protect the host against viral infection, understanding the relatedness between viral susceptibility and antiviral mechanisms must be crucial. Thus, we evaluated the viral suppression efficacy of ribavirin by measuring the transcription levels of viral and immune genes in vitro. The results showed that following ribavirin treatment after SVCV infection (MOI 0...

ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus elatus Lindl. was traditionally used for pain treatment and Gooderoside A (GA) was regarded as its principal constituent. AIM OF THE STUDY: To investigate whether GA can be responsible for the antinociceptive activity of A. elatus and explore its underlying mechanism. MATERIALS AND METHODS: Acetic acid-induced abdominal writhing and tail flick tests were employed to evaluate the antinociceptive activity of ethanolic extract of A...

Long-term alcohol misuse triggers cellular adaptions in susceptible regions of the human brain, resulting in neurodegeneration, neuroinflammation and altered gene expression. Previous studies have identified ∼35 miRNAs, including miR-146a-5p, which are up-regulated in the frontal cortex of males with alcohol use disorder (AUD), but the influence of liver cirrhosis and sex is unknown. The expression of miR-146a-5p, IRAK1, and TRAF6 was measured in the prefrontal cortex of controls and individuals with AUD with and without cirrhosis of the liver...

PURPOSE OF REVIEW: This review will discuss selected emerging molecular targets and associated potential therapeutic agents for rheumatoid arthritis (RA)-directed treatment. RECENT FINDINGS: Agents in active development for RA treatment include those targeted to CD40 and CD40 ligand, programmed death protein 1 (PD-1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Several other molecules with a strong theoretical role in RA pathogenesis and/or demonstrated efficacy in other autoimmune diseases are also being evaluated as potential drug targets in preclinical or translational studies in RA...

Alphaviruses are arthropod-borne, single-stranded positive-sense RNA viruses that are recognized as rapidly emerging pathogens. Despite being exquisitely sensitive to the effects of the innate immune response alphaviruses can readily replicate, disseminate, and induce pathogenesis in immunologically competent hosts. Nonetheless, how alphaviruses evade the induction of an innate immune response prior to viral gene expression, or in non-permissive infections, is unknown. Previously we reported the identification of a novel host/pathogen interaction between the viral Capsid (CP) protein and the host IRAK1 protein...

Acne is a chronic inflammatory skin disease, and the pathogenesis of acne induced by Cutibacterium acnes (C.acnes) is not well understood. Recently, circular RNAs (circRNAs) have attracted much attention because of its involvement in various diseases. However, the mechanisms by which circRNAs regulated acne have rarely been reported. We identified several differentially expressed circRNAs by sequencing patient-derived acne tissues. Among them, hsa_circ_0105040 was determined to be low expressed in acne tissues and localized in the cytoplasm of human primary keratinocytes...