Objectives: Many complex mechanisms responsible for the pathogenesis of pressure ulcers (PUs) currently remain poorly understood. The objective of this study was to discover the major roles for inflammatory cytokines, growth factors and several apoptosis-related signal molecules in chronic PU wound. Methods: We investigated expression of inflammatory cytokines, growth factors and their corresponding receptors, and the apoptosis signal of caspase-3 in chronic stage III/IV chronic PU wound, acute wounds as well as normal skin controls. Tissues were stained by hematoxylin and eosin (HE) for histopathology and Masson's trichrome for collagen. Vascular endothelial growth factor (VEGF), fibroblast growth factors 2 (bFGF) and caspase-3 were detected by immunohistochemical analysis. Expression of mRNAs for interleukin (IL)-1b, tumor necrosis factor-a (TNF-a), VEGF, KDR, bFGF and FGFR1 was determined by real-time reverse transcription PCR. Results: Stage III and IV chronic PUs stained had increased inflammatory cell infiltration and decreased collagen compared with controls. Levels of mRNAs for inflammatory cytokines IL-1b and TNF-a were elevated in PUs compared with acute wounds and normal skin. VEGF and bFGF, together with their receptors KDR and FGFR1, respectively, were significantly decreased compared with controls. However, the expression levels of caspase-3 were elevated in the PUs. Conclusion: Our series of studies have shown that chronic PUs displayed high levels of inflammation and disruption of the collagen matrix, along with increased indications of apoptosis and decreased levels of growth factors and their receptors. These characteristics can be used to comprehensively evaluate the etiology and treatment of chronic PUs.

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Glioma is the most aggressive tumor of the central nervous system. Long non-coding RNAs (lncRNAs) may be involved in modulating tumor generation. The present study analyzed an lncRNA microarray of glioma and selected long intergenic non-protein coding RNA 665 ( LINC00665 ) as the research object. The mode of expression and biological function of LINC00665 in glioma were assessed using lncRNA microarray and RT-qPCR analyses. Gain-of-function assays and/or loss-of-function assays were implemented to explore the role of LINC00665 in the progression of glioma. Dual-luciferase reporter and RNA immunoprecipitation assays explored the downstream molecular mechanism of LINC00665 . The function of the molecular pathway in progression of glioma was analyzed using rescue assays. High expression of LINC00665 was marked in glioma tissues and cells, which correlated with an unsatisfactory prognosis. Upregulation of LINC00665 significantly promoted the proliferation and invasion of glioma cells. LINC00665 acted as a competing endogenous RNA by sponging miR-34a-5p to upregulate angiotensin II receptor type 1 (AGTR1). LINC00665 promoted the progression of glioma by acting as a competitive endogenous RNA to competitively bind to miR-34a-5p and mediate AGTR1 expression.

Nitric oxide (NO) is an important vascular modulator in the development of pulmonary hypertension. NO exerts its regulatory effect mainly by activating soluble guanylate cyclase (sGC) to synthesize cyclic guanosine monophosphate (cGMP). Exposure to hypoxia causes pulmonary hypertension. But in lung disease, hypoxia is commonly accompanied by hypercapnia. The aim of this study was to examine the changes of sGC enzyme activity and cGMP content in lung tissue, as well as the expression of inducible nitric oxide synthase (iNOS) and sGC in rat pulmonary artery after exposure to hypoxia and hypercapnia, and assess the role of iNOS-sGC-cGMP signal pathway in the development of hypoxic and hypercapnic pulmonary hypertension. Male Sprague-Dawley rats were exposed to hypoxia and hypercapnia for 4 weeks to establish model of chronic pulmonary hypertension. Weight-matched rats exposed to normoxia served as control. After exposure to hypoxia and hypercapnia, mean pulmonary artery pressure, the ratio of right ventricle/left ventricle+septum, and the ratio of right ventricle/body weight were significantly increased. iNOS mRNA and protein levels were significantly increased, but sGC α(1) mRNA and protein levels were significantly decreased in small pulmonary arteries of hypoxic and hypercapnic exposed rat. In addition, basal and stimulated sGC enzyme activity and cGMP content in lung tissue were significantly lower after exposure to hypoxia and hypercapnia. These results demonstrate that hypoxia and hypercapnia lead to the upregulation of iNOS expression, downregulation of sGC expression and activity, which then contribute to the development of pulmonary hypertension.

Cerebrovascular smooth muscle cell proliferation and migration contribute to hyperplasia in case of cerebrovascular remodeling and stroke. In the present study, we investigated the effects of acetylshikonin, the main ingredient of a Chinese traditional medicine Zicao, on human brain vascular smooth muscle cell (HBVSMCs) proliferation and migration induced by angiotensin II (AngII), and the underlying mechanisms. We found that acetylshikonin treatment significantly inhibited AngII-induced HBVSMCs proliferation and cell cycle transition from G1 to S phase. Wound-healing assay and Transwell assay showed that AngII-induced cell migration and invasion were markedly attenuated by acetylshikonin. In addition, AngII challenge significantly induced Wnt/β-catenin signaling activation, as evidenced by increased β-catenin phosphorylation and nuclear translocation and GSK-3β phosphorylation. However, acetylshikonin treatment inhibited the activation of Wnt/β-catenin signaling. Consequently, western blotting analysis revealed that acetylshikonin effectively reduced the expression of downstream target genes in AngII-treated cells, including c-myc, survivin and cyclin D1, which contributed to the inhibitory effect of acetylshikonin on HBVSMCs proliferation. Further, stimulation with recombinant Wnt3a dramatically reversed acetylshikonin-mediated inhibition of proliferation and cell cycle transition in HBVSMCs. Our study demonstrates that acetylshikonin prevents AngII-induced cerebrovascular smooth muscle cells proliferation and migration through inhibition of Wnt/β-catenin pathway, indicating that acetylshikonin may present a potential option for the treatment of cerebrovascular remodeling.