Coeval records of ocean, atmosphere, and terrestrial change are crucial to understanding the pattern and causes of global mass extinction across the Permian-Triassic boundary (PTB). However, relationships among changes in different settings remain largely unclear, primarily due to the challenges associated with the correlation among disparate records. Here we compare marine carbon isotopic records with marine and terrestrial environmental and biotic events recorded in sediments from the Meishan PTB section of south China. Timescaled carbonate carbon isotopes exhibit two gradual major shifts across the PTB at Meishan, and these are duplicable elsewhere around the Tethys Ocean. The two shifts are associated with two episodes of enhanced terrestrial weathering indicated by an increased abundance of 13 C-enriched moretanes relative to hopanes and an elevated abundance of black carbon fragments. Key marine events previously reported for the PTB, including photic zone euxinia, faunal mass extinction, and cyanobacterial expansion, also occur as two episodes, coinciding with both of the progressive shifts to negative δ 13 C values and enhanced weathering. The temporal sequence of the duplicable events suggests that the biotic crisis was a consequence of prolonged and episodic changes in the marine and continental systems, and argues against an extraterrestrial impact as the main cause.
Background: Calycosin and genistein are the two main components of isoflavones. Previously, we reported that these compounds display antitumor activities in the breast cancer cell lines MCF-7 and T47D. In the present study, we investigated the mechanism of action of calycosin and genistein, and their respective efficacies as potential therapies for the treatment of breast carcinoma in the clinic. Methods: MCF-7 cells were treated with calycosin or genistein. Cell proliferation and apoptosis were measured using CCK8 assay and Hoechst 33258. The expression level of phosphorylated Akt protein was determined by western blotting. Expression level of HOTAIR was quantified by real-time PCR. Results: Both calycosin and genistein inhibited proliferation and induced apoptosis in MCF-7 breast cancer cells, especially after treatment with calycosin. Treatment of MCF-7 cells with calycosin or genistein resulted in decreased phosphorylation of Akt, and decreased expression of its downstream target, HOTAIR. Conclusion: Calycosin is more effective in inhibiting breast cancer growth in comparison with genistein, through its regulation of Akt signaling pathways and HOTAIR expression.
Hydroxysafflor yellow A (HSYA) is the major active chemical component of the flower of the safflower plant, Carthamus tinctorius L. Previously, its neuroprotection against cerebral ischemia-reperfusion (I/R) injury was reported by anti-oxidant action and suppression of thrombin generation. Here, we investigate the role of HSYA in cerebral I/R-mediated apoptosis and possible signaling pathways. Male Wistar rats were subjected to transient middle cerebral artery occlusion for 2 h, followed by 24 h reperfusion. HSYA was administered via tail-vein injection just 15 min after occlusion. The number of apoptotic cells was measured by TUNEL assay, apoptosis-related proteins Bcl-2, Bax and the phosphorylation levels of Akt and GSK3β in ischemic penumbra were assayed by western blot. The results showed that administration of HSYA at the doses of 4 and 8 mg/kg significantly inhibited the apoptosis by decreasing the number of apoptotic cells and increasing the Bcl-2/Bax ratio in rats subjected to I/R injury. Simultaneously, HSYA treatment markedly increased the phosphorylations of Akt and GSK3β. Blockade of PI3K activity by wortmannin dramatically abolished its anti-apoptotic effect and lowered both Akt and GSK3β phosphorylation levels. Taken together, these results suggest that HSYA protects against cerebral I/R injury partly by reducing apoptosis via PI3K/Akt/GSK3β signaling pathway.
Background: Increasing evidences suggest that innate immunity is involved in cerebral ischemia-reperfusion (I/R) injury, but the liable innate immune receptors have not been completely elucidated. Here, we explored the role of the nucleotide-binding oligomerization domain (NOD)2, a member of the cytosolic NOD-like receptor family, in acute focal cerebral I/R injury.Methods: An in vivo middle cerebral artery occlusion (MCAO) model that in wild type (WT) and NOD2 deficient (NOD2-/-) mice and in vitro model of oxygen glucose deprivation and reoxygenation (OGD/R) in cultured primary microglia and astrocytes were used to investigate the expression of NOD2 and explore the roles of NOD2 in ischemic stroke.Results: Our results showed that NOD2 expression was significantly increased in microglia and astrocytes in response to the I/R insult. Pretreatment with muramyl dipeptide, an extrinsic ligand of NOD2, significantly increased the infarct volume and neurological dysfunction in mice subjected to MCAO. Genetic ablation of the NOD2 gene significantly improved stroke outcomes and reduced inflammation, as evidenced by a lower expression of the pro-inflammatory cytokines IL-1β, IL-6 and TNFα in conjunction with attenuated activation of nuclear factor κB (NF-κB), p38 mitogen activated protein kinases (MAPK) and JNK. Moreover, NOD2 deficiency prevented the upregulation of the NADPH oxidase (NOX) 2 and ROS generation induced by I/R. Mechanistically, NOD2-induced production of IL-6 in primary cultured microglia was mediated through activation of NOX2.Conclusions: This study showed the contribution of NOD2 to inflammatory response and provided direct evidence that NOX2-mediated oxidative stress as an important target molecule linked NOD2 to inflammatory damage in ischemic stroke. Pharmacological targeting of NOD2-mediated inflammatory response at multiple levels may help design a new approach to develop therapeutic strategies for prevention of deterioration of cerebral function and for the treatment of stroke.
G protein–coupled receptor 120 (GPR120) has been shown to negatively regulate inflammation and apoptosis, but its role in cerebral ischemic injury remains unclear. Using an in vivo model of middle cerebral artery occlusion (MCAO) and an in vitro model of oxygen-glucose deprivation (OGD), we investigated the potential role and molecular mechanisms of GPR120 in focal cerebral ischemic injury. Increased GPR120 expression was observed in microglia and neurons following MCAO-induced ischemia in wild type C57BL/6 mice. Treatment with docosahexaenoic acid (DHA) inhibited OGD-induced inflammatory response in primary microglia and murine microglial BV2 cells, whereas silencing of GPR120 strongly exacerbated the inflammation induced by OGD and abolished the anti-inflammatory effects of DHA. Mechanistically, DHA inhibited OGD-induced inflammation through GPR120 interacting with β-arrestin2. In addition to its anti-inflammatory function, GPR120 also played a role in apoptosis as its knockdown impaired the antiapoptotic effect of DHA in OGD-induced rat pheochromocytoma (PC12) cells. Finally, using MCAO mouse model, we demonstrated that GPR120 activation protected against focal cerebral ischemic injury by preventing inflammation and apoptosis. Our study indicated that pharmacological targeting of GPR120 may provide a novel approach for the treatment of patients with ischemic stroke.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.