Inhaled particulate matter 2.5 (PM2.5) can cause lung injury by inducing serious inflammation in lung tissue. Renin-angiotensin system (RAS) is involved in the pathogenesis of inflammatory lung diseases and regulates inflammatory response. Angiotensin-converting enzyme II (ACE2), which is produced through the angiotensin-converting enzyme (ACE)/angiotensin II (Ang II) axis, protects against lung disease. However, few studies have focused on the relationships between PM2.5 and ACE2. Therefore, we aimed to explore the role of ACE2 in PM2.5-induced acute lung injury (ALI). An animal model of PM2.5-induced ALI was established with wild type (C57BL/6, WT) and ACE2 gene knockout (ACE2 KO) mice. The mice were exposed to PM2.5 through intratracheal instillation once a day for 3 days (6.25 mg/kg/day) and then sacrificed at 2 days and 5 days after PM2.5 instillation. The results show that resting respiratory rate (RRR), levels of inflammatory cytokines, ACE and MMPs in the lungs of WT and ACE2 KO mice were significantly increased at 2 days postinstillation. At 5 days postinstillation, the PM2.5-induced ALI significantly recovered in the WT mice, but only partially recovered in the ACE2 KO mice. The results hint that PM2.5 could induce severe ALI through pulmonary inflammation, and the repair after acute PM2.5 postinstillation could be attenuated in the absence of ACE2. Additionally, our results show that PM2.5-induced ALI is associated with signaling p-ERK1/2 and p-STAT3 pathways and ACE2 knockdown could increase pulmonary p-STAT3 and p-ERK1/2 levels in the PM2.5-induced ALI.

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Angiogenesis plays a primary role in tumor growth and metastasis. Angiostatin, a proteolytic fragment containing the first four kringle domains of human plasminogen, can inhibit angiogenesis. The anti-angiogenic activities of kringle 1-5 (K(1-5)) and kringle 5 fragments of plasminogen are greater than angiostatin in inhibiting angiogenesis and angiogenesis-dependent tumor growth. To further optimize kringle fragment anti-angiogenic activities, mutations were created at the potential glycosylation sites Asn-289 and Thr-346 and the Lys binding site, Leu-532, at kringle 5, including K(1-5)N289A (replacing Asn by Ala at residue 289), K(1-5)T346A, K(1-5)L532R, K(1-5)N289A/T346A, K(1-5)T346A/L532R, K(1-5)N289A/L532R, and K(1-5)N289A/T346A/L532R. Wild-type and mutant K(1-5) proteins were expressed successfully by the Pichia pastoris expression system. Native K(1-5) from proteolytic cleavage and wild-type K(1-5) have similar activity in inhibiting basic fibroblast growth factor-induced endothelial cell proliferation. Among these mutated proteins, K(1-5)N289A/T346A/L532R exhibited the greatest effect in inhibiting endothelial cell proliferation and in inducing endothelial cell apoptosis. Integrin alpha(v)beta(3)-mediated adhesion of K(1-5)N289A/T346A/L532R to endothelial cells was more greatly enhanced when compared to wild type K(1-5). Furthermore, K(1-5)N289A/T346A/L532R was most potent in inhibiting basic fibroblast growth factor-induced angiogenesis in Matrigel assay in vivo. Angiogenesis-dependent tumor growth was inhibited by systemically injected K(1-5)N289A/T346A/L532R into mice. These results demonstrate that alteration of glycosylation and Lys binding properties could increase the anti-angiogenic action of K(1-5), possibly via enhanced interaction with integrin alpha(v)beta(3) in endothelial cells.

This essay argues that the idea of name-rectification (zheng ming 正名) in the Xunzi can be properly reconstructed as revealing a normative pragmatic semantic theme that linguistic contents embody, and are embedded in, the normative, justificatory network, or pattern, of dao li 道理 (proper routes/patterns of norm) which, in turn, is constituted and manifested by social inferential justificatory practices of bian shuo 辯說 (dialectical justification/explanation).