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Tegillarca granosa can survive intermittent hypoxia for a long-term. We used the clam T. granosa as model to investigate the respiratory, antioxidant and metabolic responses to consecutive hypoxia-reoxygenation (H/R) stress at both physiological and transcriptional levels. The results showed that the clams were able to rapidly regulate oxygen consumption and ammonia excretion during H/R stress, and alleviate oxidative stress during the second-time challenge. The clams also efficiently balanced energy metabolism through the rapid conversion and decomposition of glycogen. According to the transcriptome profile, KEGG pathways of starch and sucrose metabolism, ECM-receptor interaction, and protein processing in endoplasmic reticulum were significantly enriched in H group (the second-time 24 h hypoxia exposure), while pathways associated with lipid metabolism were significantly enriched in h group (the first-time 24 h hypoxia exposure). DEGs including hspa5 , birc2 / 3 , and map3k5 might play important roles in alleviating endoplasmic reticulum stress, cpla2 and pla2g16 might mitigate oxidative stress by adjusting the composition of cellular membrane. In conclusions, our findings suggest that rapid adjustment of oxygen consumption, ammonia metabolism, glycogen metabolism, and the ability to adjust the composition of the membrane lipid may be critical for T. granosa in maintaining energy homeostasis and reducing oxidative damage during intermittent H/R exposure. This study preliminarily clarified the response of T. granosa to intermittent hypoxia stress on the physiological and molecular levels, offering insights into the hypoxia-tolerant mechanisms in this species and providing a reference for the following study on the other hypoxic-tolerant species. [Display omitted] • Tegillarca granosa rapidly adjusts glycometabolism to adapt to intermittent hypoxia. • ECM-receptor interaction mediates the transmission of hypoxia signaling. • CPLA2 might be crucial in alleviating oxidative damage. [ABSTRACT FROM AUTHOR]

Background: Recent studies have reported that receptor-interacting protein kinase 3 (RIPK3)-dependent necroptosis is related to the pathological process of intracerebral hemorrhage (ICH). Some studies support the view that inhibiting necroptosis is a key mechanism preventing inflammation. Inflammation is a crucial factor contributing to neurological injuries and unfavorable outcomes after ICH. The aim of this study was to clarify the association between necroptosis and monocyte chemoattractant protein-1 (MCP-1)-mediated inflammation and identify a new target for the treatment of ICH.Methods: An ICH model was established in C57BL/6 mice by injecting collagenase IV into the right basal ganglia. The RIPK3 inhibitor GSK872 was administered through intraventricular injection. Then, we assessed brain edema and neurobehavioral function. Western blotting was employed to detect changes in RIPK3, phospho-mixed lineage kinase domain-like protein (p-MLKL), MCP-1, phospho-c-Jun N-terminal kinase (p-JNK) and interleukin 6 (IL-6) levels in the brain tissue. The localization of RIPK3 and MCP-1 was observed using immunofluorescence staining. Co-immunoprecipitation was performed to determine the interaction between RIPK3 and MCP-1.Results: Compared with the sham group, the levels of RIPK3, p-MLKL, MCP-1, p-JNK and IL-6 were increased post-ICH. GSK872 pretreatment significantly reduced RIPK3, p-MLKL, MCP-1, p-JNK and IL-6 expression, accompanied by mitigated cerebral edema and neurobehavioral defects. RIPK3 and MCP-1 colocalized in the perinuclear region after ICH. We detected the formation of the RIPK3-MCP-1 complex in ICH brain tissue.Conclusions: There exerted an association between RIPK3 and MCP-1. The inhibition of RIPK3 alleviated MCP-1-mediated inflammation following ICH. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) remains one of the prevalent causes of cancer-related deaths globally. Long non-coding RNAs (lncRNAs) have been associated with different cancers. The polarization of macrophages towards the M2 (alternatively activated) phenotype promotes immunologic tolerance and can induce gastric tumorigenesis. Thus far, lncRNAs have been shown to modulate the differentiation of immune cells. Here, we investigated the biological effects of LINC00665 on the progression of GC and explored the mechanisms underlying its ability to mediate the polarization of macrophages towards the M2 phenotype. We report that the levels of LINC00665 were increased in GC tissues. Furthermore, this increase in LINC00665 expression could be associated with decreased overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS). Using cell-based macrophage polarization models, we demonstrated that LINC00665 upregulation in GC cells facilitated the polarization of macrophages towards the M2 but not M1 (classically activated) phenotype. Furthermore, the loss of LINC00665 prevented the M2 polarization of macrophages. Mechanically, we identified that Wnt1 was the downstream target of LINC00665. Additionally, LINC00665 could directly interact with the transcription factor BTB domain and CNC homology 1 (BACH1). The interaction between LINC00665 and BACH1 resulted in the activation and binding of BACH1 to the Wnt1 promoters. Furthermore, BACH1 silencing could inhibit GC progression, which highlighted a crucial role for BACH1 in LINC00665-mediated Wnt1 activation. In addition, genetic Wnt1 overexpression effectively abolished the repression of Wnt signaling after BACH1 depletion and mediated GC development by supporting M2 macrophage polarization. In conclusion, we report that LINC00665 modulates M2 macrophage polarization and suggest that it may facilitate macrophage-dependent GC progression. • LINC00665 level was increased in GC tissues. • M2 showed an increased expression of LINC00665 and LINC00665 contributed to M2-like polarization of macrophages. • LINC00665 binding to BACH1 increased its occupancy in Wnt1 promoter. [ABSTRACT FROM AUTHOR]