Deletion of soluble epoxide hydrolase attenuates mice Hyperoxic acute lung injury.

BACKGROUND: Recent studies reported that soluble epoxide hydrolase (sEH) plays an important role in lung diseases. However, the role of sEH in hyperoxia-induced ALI is unclear. METHODS: ALI was induced by exposure to 100% oxygen in an airtight cage for 72 h in wild-type (WT) and sEH gene deletion (EPHX2-/-) mice. ALI was assessed by the lung dry/wet ratio, alveolar capillary protein leak, and the infiltration of inflammatory cells in the lung. RESULTS: Hyperoxia elevated sEH activity in WT mice. Simultaneously, epoxyeicosatrienoic acids (EETs) levels were decreased in WT mice exposed to hyperoxia. However, the level of EETs was increased in EPHX2-/- mice exposed to hyperoxia. Hyperoxia induced pulmonary edema and inflammation were dampened in EPHX2-/- mice compared with WT mice. Decreased expression of Kelch-like ECH-associated protein 1 (Keap1) was found in EPHX2-/- mice exposed to hyperoxia. Hyperoxia-induced the expression of nuclear-factor erythroid 2-related factor 2 (Nrf2) was enhanced in EPHX2-/- mice compared with WT mice. Simultaneously, the activities of heme oxygenase-1 and superoxide dismutase were elevated in EPHX2-/- mice. The levels of reactive oxygen species were inhibited in EPHX2-/- mice compared with WT mice exposed to hyperoxia. CONCLUSIONS: sEH is a harmful factor for hyperoxic ALI. The beneficial effect of sEH gene deletion is associated with the elevation of EETs and regulation of Nrf2/Keap1 signal pathway.

Treatment of a patient with severe lactic acidosis and multiple organ failure due to mitochondrial myopathy: A case report.

BACKGROUND: Mitochondrial myopathy is a rare genetic disease with maternal inheritance that may involve multiple organ systems. Due to the lack of typical characteristics, its clinical diagnosis is difficult, and it is often misdiagnosed or even missed. CASE SUMMARY: The patient was a young college student. When he presented at the hospital, he had severe lactic acidosis, respiratory failure, and shock with multiple organ dysfunction syndrome (MODS). He was treated by mechanical ventilation, veno-arterial extracorporeal membrane oxygenation, and other organ support. However, his condition continued to worsen. After a thorough and detailed medical and family history was taken, a mitochondrial crisis was suspected. A muscle biopsy was taken. Further genetic testing confirmed a mitochondrial gene mutation (TRNL1 3243A>G). The final diagnosis of mitochondrial myopathy was made. Although there is no known specific treatment, intravenous methylprednisone and intravenous immunoglobulin were started. The patient's shock eventually improved. The further course was complicated by severe infection in multiple sites, severe muscle weakness, and recurrent MODS. After 2 mo of multidisciplinary management and intensive rehabilitation, the patient could walk with assistance 4 mo after admission and walk independently 6 mo after admission. CONCLUSION: More attention should be paid to mitochondrial myopathy to avoid missed diagnosis and misdiagnosis.

Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression.

Correction to "Liu LP, Sheng XP, Shuai TK, Zhao YX, Li B, Li YM. Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression. World J Gastroenterol 2018; 24: 4565-4577 [PMID: 30386106 DOI: 10.3748/wjg.v24.i40.4565]." In this article, we have identified some of the images in Figure 2A, C, E, G, and I are identical to the images in Figures 1B, 2A, 3B, 3E, and 3G of another paper entitled "Liu L, Zhao Y, Fan G, Shuai T, Li B, Li Y. Helicobacter pylori infection enhances heparanase leading to cell proliferation via mitogenactivated protein kinase signalling in human gastric cancer cells.", which was published by us in the Molecular Medicine Reports in December, 2018 [PMID: 30320396 DOI: 10.3892/mmr.2018.9558]. The reason why we asked to replace the pictures was that when we were simultaneously preparing to submit our two different articles to the World Journal of Gastroenterology (WJG) and Molecular Medicine Reports, we uploaded the wrong pictures to the WJG, which were same as those submitted to the Molecular Medicine Reports. We apologize for this negligence and any inconvenience that this may cause. We would be grateful if you could replace the wrong pictures with the correct ones attached.

lncRNA TRMP-S directs dual mechanisms to regulate p27-mediated cellular senescence.

Long noncoding RNAs (lncRNAs) undergo extensive alternative splicing, but little is known about isoform functions. A prior investigation of lncRNA RP11-369C8.1 reported that its splice variant TRMP suppressed p27 translation through PTBP1. Here we characterize a second major splice variant, TRMP-S (short variant), whose enforced loss promotes cancer cell-cycle arrest and p27-dependent entry into cellular senescence. Remarkably, despite sharing a single common exon with TRMP, TRMP-S restrains p27 expression through distinct mechanisms. First, TRMP-S stabilizes UHRF1 protein levels, an epigenetic inhibitor of p27, by promoting interactions between UHRF1 and its deubiquitinating enzyme USP7. Alternatively, binding interactions between TRMP-S and FUBP3 prevent p53 mRNA interactions with RPL26 ribosomal protein, the latter essential for promoting p53 translation with ensuing suppression of p53 translation limiting p27 expression. Significantly, as TRMP-S is itself transactivated by p53, this identifies negative feedback regulation between p53 and TRMP-S. Different splicing variants of the RP11-369C8.1 gene thereby exert distinct roles that converge on the homeostatic control of p27 expression, providing an important precedent for understanding the actions of alternatively spliced lncRNAs.

Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression.

AIM: To detect the mechanisms of Helicobacter pylori (H. pylori) infection in the invasion and metastasis of gastric cancer (GC). METHODS: Specimens from 99 patients with GC were collected. The correlation among H. pylori infection, heparanase (HPA) and mitogen-activated protein kinase (MAPK) expression, which was determined by immunohistochemistry, and the clinical features of GC was analysed using SPSS 22.0. Overall survival (OS) and relapse-free survival (RFS) of GC patients were estimated by the Kaplan-Meier method. Independent and multiple factors of HPA and MAPK with prognosis were determined with COX proportional hazards models. HPA and MAPK expression in MKN-45 cells infected with H. pylori was analysed using Western blot. RESULTS: H. pylori infection was observed in 70 of 99 patients with GC (70.7%), which was significantly higher than that in healthy controls. H. pylori infection was related to lymph metastasis and expression of HPA and MAPK (P < 0.05); HPA expression was relevant to MAPK expression (P = 0.024). HPA and MAPK expression in MKN-45 cells was significantly upregulated following H. pylori infection and peaked at 24 h and 60 min, before decreasing (P < 0.05). SB203580, an inhibitor of MAPK, significantly decreased HPA expression. HPA was related to lymph metastasis and invasive depth. HPA positive GC cases and H. pylori positive GC cases showed poorer prognosis than HPA negative cases (P < 0.05). COX models showed that the prognosis of GC was connected with HPA expression, lymph metastasis, tissue differentiation, and invasive depth. CONCLUSION: H. pylori may promote the invasion and metastasis of GC by increasing HPA expression that may associate with MAPK activation, thus causing a poorer prognosis of GC.