Ask about this productRelated genes to: MYD88 Blocking Peptide
- Gene:
- MYD88 NIH gene
- Name:
- MYD88 innate immune signal transduction adaptor
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 3p22.2
- Locus Type:
- gene with protein product
- Date approved:
- 1997-12-23
- Date modifiied:
- 2019-04-23
Related products to: MYD88 Blocking Peptide
Related articles to: MYD88 Blocking Peptide
- Erectile dysfunction (ED) is a highly prevalent and refractory complication of type 2 diabetes mellitus (T2DM), with penile cavernosal dysfunction, inflammation, apoptosis, and fibrosis as core pathological features. Here we identify gut microbiota dysbiosis and its downstream metabolite arachidonic acid (AA) as critical mediators of T2DM-associated erectile dysfunction (T2DM-ED) through a systemic gut-penis axis. Gut dysbiosis is sufficient to induce an ED phenotype, as demonstrated by fecal microbiota transplantation (FMT) from T2DM-ED rats into pseudo-germ-free recipients, which successfully transferred the erectile impairment with significantly decreased ICP/MAP ratios. Recipient rats showed impaired colonic barrier integrity, mucosal damage, goblet cell depletion, and downregulated tight junction proteins (Occludin, Claudin-4). Multi-omics integration of 16S rRNA sequencing and serum metabolomics identified AA as a key elevated metabolite that drives inflammatory signaling via the HIF-1α and NF-κB pathways. In penile corpus cavernosum tissue, ED-FMT rats displayed smooth muscle loss, fibrosis, increased apoptosis, and hyperactivation of the TLR4-MyD88-NF-κB-HIF-1α axis. In primary corpus cavernosum smooth muscle cells (CCSMCs), AA stimulation recapitulated pathological activation, including a pro-apoptotic shift in the Bax/Bcl-2 ratio, elevated Cleaved Caspase-3, reduced α-SMA, increased COX-2, stabilized HIF-1α, and excessive PGE production; these effects were abolished by pharmacological inhibition of NF-κB. Mechanistically, gut dysbiosis-induced systemic AA accumulation triggers inflammatory damage, apoptosis, and functional impairment in penile smooth muscle via the TLR4-MyD88-NF-κB/HIF-1α cascade. These findings define a gut-AA-NF-κB-penis axis that drives T2DM-ED pathogenesis, highlighting AA and its downstream signaling as promising therapeutic targets for diabetic erectile dysfunction. - Source: PubMed
Publication date: 2026/05/06
Cheng ChengZheng LeiBao XingjunWei LetianJiang HuiJiang Tao - Toll-like receptors (TLRs), as core pattern recognition receptors (PRRs), play pivotal roles in pathogen detection during innate immune defense and are critical for initiating immune responses. In this study, we investigated a novel member of the TLR1 subfamily, TLR18, in the economically significant species Scophthalmus maximus, aiming to elucidate its molecular mechanisms in antibacterial immunity and provide insights into innate immune regulation in fish. In our results, SmTLR18 (2652 bp) encoded an 883-amino-acid protein sharing high identity with Paralichthys olivaceus TLR14 (84.15%). SmTLR18 localizes to the cytoplasm and cell membrane and is ubiquitously expressed with the highest expression level in spleen and lowest expression level in the blood. In vitro, SmTLR18 was upregulated by PGN and LTA but downregulated by LPS. The extracellular domain of SmTLR18 bound all tested ligands and bacteria, exhibiting the highest affinity for Vibrio anguillarum, and immunohistochemical analysis revealed strong positive SmTLR18 signals within hyperplastic hemocytes. Molecular docking, co-localization, and co-immunoprecipitation assays revealed that SmTLR18 recruits MyD88 to activate downstream signaling. Transcriptomics following SmTLR18 overexpression suggested regulation of IRF, ZBTB, MYSM, STAT, and zf-C2H pathways, upregulating MyD88 and IL-1β while downregulating TNF-α. Conversely, knockdown increased TNF-α and downregulated MyD88 and IL-1β. Mechanistically, dual-luciferase assays demonstrated SmTLR18-mediated NF-κB activation. Results demonstrated SmTLR18 recognizes PAMPs, specifically Vibrio anguillarum, and recruits MyD88 to activate NF-κB and IRF pathways driving cytokine production. These findings underscore the critical role of SmTLR18 in turbot antibacterial immunity. - Source: PubMed
Publication date: 2026/05/06
Li HonghongWang ZhongyiLi YangLi ChaoYang Ning - Cryptococcus neoformans (C. neoformans), an opportunistic fungal pathogen with a worldwide distribution, is responsible for fatal meningitis in immunocompromised and immunocompetent populations. Extracellular vesicles (EVs) derived from C. neoformans embody bioactivities that contribute to fungal interaction and survival. In the present study, we demonstrated that EVs from the encapsulated strain H99 increased CD44 expression while decreasing occludin expression. In contrast, EVs from acapsular strains were ineffective in CD44 and occludin expression. Furthermore, we discovered that H99 EVs could induce the formation of neutrophil extracellular traps (NETs). Mechanistically, the inhibition of PAD4 and p65 and the use of an NADPH inhibitor reduced the formation of NETs induced by H99 EVs. However, Δcap59 EVs and Δcap67 EVs failed to induce NETs. Moreover, NETs induced by H99 EVs disrupted tight junctions (TJs) in brain endothelial cells (bEnd.3), leading to a reduction in the expression of claudin-5 and occludin. This disruption was accompanied by the activation of STAT3, NF-κB, and MyD88-MAPK (p38/JNK) signaling pathways. Consequently, using an in vitro blood‒brain-barrier (BBB) model, we demonstrated that H99-derived EVs and H99 EVs-induced NETs contributed to the adhesion to and penetration of brain endothelial cells by C. neoformans. In summary, we have revealed that EVs derived from C. neoformans induce the formation of NETs, potentially facilitating fungal infection by disrupting tight junctions in brain endothelial cells. - Source: PubMed
Publication date: 2026/05/06
Cai ZhenmingWu TianhaoXu QingZhang EnruiTao YuanWang TingLi YuweiYang YonglinRen DenghuaZhang Mingshun - Waldenström macroglobulinemia (WM) is a subset of lymphoplasmacytic lymphoma characterized by bone marrow infiltration of tumor cells and IgM monoclonal gammopathy. MYD88 mutations are found in more than 90% of WM patients and CXCR4 mutations in approximately 30-40%. For this reason, MYD88 mutation analysis is particularly important for the definitive diagnosis of WM. Furthermore, the CXCR4 S338* mutation is clinically significant for treatment selection in WM patients, as Bruton's tyrosine kinase inhibitors have been reported to be less effective in patients harboring both MYD88 and CXCR4 mutations. However, there are currently no simple methods available for the simultaneous detection of MYD88 and CXCR4 mutations. - Source: PubMed
Publication date: 2026/05/06
Kunimune YukiNishioka MitsuakiNamba HarukaTodaka KimikaFujii TomohiroKiso NayuNakahara YukikoShinkawa KanaeKumano YumikoKodama MasakiEbisui TomoyaNishimoto RyogaOkayama NaokoSuehiro YutakaYamasaki TakahiroYujiri Toshiaki - Aortic dissection (AD) is a fatal cardiovascular emergency for which effective pharmacological treatments are lacking. Increasing evidence suggests that spicy diets exert beneficial effects on cardiovascular diseases. However, whether a spicy diet can attenuate AD, and the mechanisms by which it might do so, remain unclear. - Source: PubMed
Publication date: 2026/05/03
Lan WanqiYang HengLiu WuLi CongcongLuo ChaoShi YonggangYang JueshengXiang HaiyanLi YongqinYi YuqiWei JingTang YanhuaChen Tingtao