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Paraquat (PQ) poisoning can cause oxidative stress, acute lung injury (ALI), and fibrosis. Excess oxidative stress can induce mitophagy. However, whether PQ exposure can induce mitophagy, contributing to the development of ALI and pulmonary fibrosis in vivo has not been clarified. Here, we show that PQ exposure induces ALI and fiber accumulation in the lung of rats in a time-dependent manner, accompanied by upregulating fibronectin (FN) and Collagen I (COL-I) expression. PQ exposure increased mitophagosome formation and PINK1 and Parkin expression in the lungs of rats. Similarly, PQ exposure reduced the viability and mitochondrial membrane potential, but enhanced FN, COL-I, PINK1, and Parkin expression in A549 cells. In contrast, PINK1 silencing significantly mitigated the PQ-upregulated Parkin, FN, and COL-I expression in A549 cells. Hence, PQ exposure induced ALI and fibrosis in rats by enhancing the PINK1/Parkin signaling and profibrotic factor expression in the lungs. Therefore, our findings suggest that the PINK1/Parkin signaling may be new therapeutic targets and may provide new insights in the pathogenesis of PQ-related ALI in rats.

There are a lot of bacteria in the environment, and Gram-positive bacteria are the most common ones. Some Gram-positive bacteria are very harmful to the human body, so it is significant to predict Gram-positive bacterial protein subcellular location. And identification of Gram-positive bacterial protein subcellular location is important for developing effective drugs. In this paper, a new Gram-positive bacterial protein subcellular location dataset was established. The amino acid composition, the gene ontology annotation information, the hydropathy dipeptide composition information, the amino acid dipeptide composition information, and the autocovariance average chemical shift information were selected as characteristic parameters, then these parameters were combined. The locations of Gram-positive bacterial proteins were predicted by the Support Vector Machine (SVM) algorithm, and the overall accuracy (OA) reached 86.1% under the Jackknife test. The overall accuracy (OA) in our predictive model was higher than those in existing methods. This improved method may be helpful for protein function prediction.

Ventilator-induced lung injury aggravates the existing lung injury. This study investigated the effect of desflurane on VILI in a rat model of acute respiratory distress syndrome. Forty-eight rats were randomized into a sham (S) group, control (C) group, lipopolysaccharide/ventilation (LV) group, lipopolysaccharide/ventilation/desflurane (LVD) group, or lipopolysaccharide/low ventilation with and without desflurane (LLV and LLVD) groups. Rats in the S group received anesthesia only. Rats in the LV and LVD groups received lipopolysaccharide and were ventilated with a high tidal volume. Rats in LLV and LLVD groups were treated as the LV and LVD groups and ventilated with a low tidal volume. PaO2/FiO2, lung wet-to-dry weight ratios, concentrations of inflammatory factors in serum and BALF, histopathologic analysis of lung tissue, and levels of nuclear factor- (NF-) κB protein in lung tissue were investigated. PaO2/FiO2 was significantly increased by desflurane. Total cell count, macrophages, and neutrophils in BALF and proinflammatory factors in BALF and serum were significantly decreased by desflurane, while IL-10 was increased. The histopathological changes and levels of NF-κB protein in lung tissue were decreased by desflurane. The results indicated that desflurane ameliorated VILI in a rat model of acute respiratory distress syndrome.

Introduction. Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor of low malignant potential. The aim of this study was designed to evaluate the clinicopathologic feature, predictive factors of malignancy, and survival from experience of a single center. Methods. 53 consecutive patients who underwent surgery for a pathologically definitive SPN were retrospectively reviewed. Results. A total of 53 cases included 7 male cases and 46 female cases with the median age of 35.4 years (14–67). Abdominal pain and mass were the most common clinical presentations. The radiological presentations were consistent with solid and cystic pattern in 18 cases, solid pattern in 25 cases, and cystic pattern in 10 cases. The predominant location of tumor was pancreatic body and tail. The mean size of the tumors was 6.4 cm. Aggressive en bloc resection combined with organ-preserving should be indicated whenever feasible. Follow-up information was available for 48 patients with a median follow-up time of 48 months. The 5-year disease-specific survival was 95.7%. Incomplete capsule was not only the predictive factor of malignancy but also the significant predictor of disease-specific survival. Conclusion. Incomplete capsule may suggest a malignant SPN and a prognostic indicator of disease-specific survival. We recommend that surgeons consider a more radical resection with an incomplete capsule of tumor.

Ionizing radiation may cause irreversible ovarian failure, which, therefore, calls for an effective radioprotective reagent. The aim of the present study was to evaluate the potential radioprotective effect of N-acetylcysteine (NAC) on ionizing radiation induced ovarian failure and loss of ovarian reserve in mice. Kun-Ming mice were either exposed to X-irradiation (4 Gy), once, and/or treated with NAC (300 mg/kg), once daily for 7 days before X-irradiation. We examined the serum circulating hormone levels and the development of ovarian follicles as well as apoptosis, cell proliferation, and oxidative stress 24 hours after X-irradiation. In addition, morphological observations on the endometrial luminal epithelium and the fertility assessment were performed. We found that NAC successfully restored the ovarian and uterine function, enhanced the embryo implantation, improved the follicle development, and altered the abnormal hormone levels through reducing the oxidative stress and apoptosis level in granulosa cells while promoting the proliferation of granulosa cells. In conclusion, the radioprotective effect of NAC on mice ovary from X-irradiation was assessed, and our results suggested that NAC can be a potential radioprotector which is capable of preventing the ovarian failure occurrence and restoring the ovarian reserve.

Purinergic signaling has emerged as an important player in cancer progression and is regulated by a series of nucleotidases. Among the enzyme cascade, CD73, which catelyzes AMP breakdown to adenosine, has been found to be overexpressed in many types of cancer. Various factors and mechanisms are employed to regulate expression of CD73. Accumulating studies have shown that CD73 is a key regulatory molecule of cancer cells proliferation, migration and invasionin vitro, tumor angiogenesis, and tumor immune escapein vivo. With such important roles in cancer, CD73 has become an appealing therapy target. Recent evidences in mice models demonstrated that targeted blockade of CD73 could be a favorable therapeutic approach for cancer patients in the future. In this review, we will summarize the multiple roles of CD73 in cancer development, including its clinical significance, its promotive effects on tumor growth, metastasis, and angiogenesis, and its suppressive effects on immune response, regulatory mechanisms of CD73 expression, and current situation of anti-CD73 cancer therapy.

Downregulation of E-cadherin in solid tumors with regional migration and systematic metastasis is well recognized. In view of its significance in tumorigenesis and solid cancer progression, studies on the regulatory mechanisms are important for the development of target treatment and prediction of clinical behavior for cancer patients. The vertebrate zinc finger E-box binding homeobox (ZEB) protein family comprises 2 major members: ZEB1 and ZEB2. Both contain the motif for specific binding to multiple enhancer boxes (E-boxes) located within the short-range transcription regulatory regions of the E-cadherin gene. Binding of ZEB1 and ZEB2 to the spaced E-cadherin E-boxes has been implicated in the regulation of E-cadherin expression in multiple human cancers. The widespread functions of ZEB proteins in human malignancies indicate their significance. Given the significance of E-cadherin in the solid tumors, a deeper understanding of the functional role of ZEB proteins in solid tumors could provide insights in the design of target therapy against the migratory nature of solid cancers.

Background. Recent studies suggested that non-protein-coding genes are implicated in the tumorigenic process of nasopharyngeal carcinoma (NPC). In the present study, we aimed to identify the differentially expressed long noncoding RNA (lncRNA) using data available in the public domain. Methods. Microarray data set GSE12452 was reannotated with ncFANs. Real-time quantitative PCR was used to quantify and validate the identified lncRNAs in NPC. Results. In primary NPC, upregulation of lnc-C22orf32-1, lnc-AL355149.1-1, and lnc-ZNF674-1 was observed. High levels of lnc-C22orf32-1 and lnc-AL355149.1-1 were significantly associated with the male patients. In addition, increased expression of lnc-C22orf32-1 and lnc-ZNF674-1 was associated with advanced tumor stages. Recurrent NPC displayed a distinctive lncRNA expression pattern. lnc-BCL2L11-3 was significantly increased in the recurrent NPC tissues. In addition, significant reduction of lnc-AL355149.1-1 and lnc-ZNF674-1 was observed in the recurrent NPC tissues. Conclusions. Our results demonstrated that it is feasible to identify the differentially expressed lncRNA in the microarray dataset by functional reannotation. The association of lncRNA with gender and tumor size implicated that lncRNA possibly plays a part in the pathogenesis of primary NPC. Further, the distinctive lncRNA identified in the recurrent NPC may reveal a distinctive development mechanism underlying tumor recurrence. © 2014 Wei Gao et al., published_or_final_version

Recent studies have suggested that endogenous angiogenesis inhibitor endostatin/collagen XVIII might play an important role in the secondary brain injury following traumatic brain injury (TBI). In this study, we measured endostatin/collagen XVIII concentrations serially for 1 week after hospitalization by using the enzyme-linked immunosorbent assay method in the cerebrospinal fluid (CSF) of 30 patients with TBI and a Glasgow Coma Scale (GCS) score of 8 or less on admission. There was a significant trend toward increased CSF levels of endostatin after TBI versus control from 72 h after injury. In patients with GCS score of 3–5, CSF endostatin concentration was substantially higher at 72 h after injury than that in patients with GCS score of 6–8 (P<0.05) and peaked rapidly at day 5 after injury, but decreased thereafter. The CSF endostatin concentration in 12 patients with an unfavorable outcome was significantly higher than that in 18 patients with a favorable outcome at day 5 (P=0.043) and day 7 (P=0.005) after trauma. Receiver operating characteristic curve analysis suggested a reliable operating point for the 7-day CSF endostatin concentration predicting poor prognosis to be 67.29 pg/mL. Our preliminary findings provide new evidence that endostatin/collagen XVIII concentration in the CSF increases substantially in patients with sTBI. Its dynamic change may have some clinical significance on the judgment of brain injury severity and the assessment of prognosis. This trial is registered with the ClinicalTrials.gov Identifier:NCT01846546.