Metabolic reprogramming induced by DCA enhances cisplatin sensitivity through increasing mitochondrial oxidative stress in cholangiocarcinoma

Background: Cholangiocarcinoma has obvious primary multidrug resistance and is generally resistant to cisplatin and other chemotherapy drugs and high glycolytic levels may be associated with chemotherapy resistance of cholangiocarcinoma cells. Dichloroacetate (DCA) is a specific inhibitor of PDK, which can promote mitochondrial aerobic oxidation process by activating PDH. In the past few years, there have been an increasing number of studies supporting the action of DCA against cancer, which also provided evidence for targeting metabolism to enhance the efficacy of cholangiocarcinoma chemotherapy.Methods: Glucose uptake and lactic acid secretion were used to detect cell metabolism level. Cell apoptosis and cell cycle were detected to confirm cell fate induced by cisplatin combined with DCA. Mito-TEMPO was used to inhibit mtROS to explore the relationship between oxidative stress and cell cycle arrest induced by DCA under cisplatin stress. Finally, PCR array and autophagy inhibitor CQ were used to explore the potential protective mechanism under cell stress.Results: DCA changed the metabolic model from glycolysis to aerobic oxidation in cholangiocarcinoma cells under cisplatin stress. This metabolic reprogramming increased mitochondrial reactive oxygen species (mtROS) levels, which promoted cell cycle arrest, increased the expression of antioxidant genes and activated autophagy. Inhibition of autophagy further increased the synergistic effect of DCA and cisplatin.Conclusion: DCA increased cisplatin sensitivity in cholangiocarcinoma cells via increasing the mitochondria oxidative stress and cell growth inhibition. Synergistic effects of DCA and CQ were observed in cholangiocarcinoma cells, which further increased the cisplatin sensitivity via both metabolic reprogramming and inhibition of the stress response autophagy

Mitochondrial stress response and myogenic differentiation

Regeneration and repair are prerequisites for maintaining effective function of skeletal muscle under high energy demands, and myogenic differentiation is one of the key steps in the regeneration and repair process. A striking feature of the process of myogenic differentiation is the alteration of mitochondria in number and function. Mitochondrial dysfunction can activate a number of transcriptional, translational and post-translational programmes and pathways to maintain cellular homeostasis under different types and degrees of stress, either through its own signaling or through constant signaling interactions with the nucleus and cytoplasm, a process known as the mitochondrial stress responses (MSRs). It is now believed that mitochondrial dysfunction is closely associated with a variety of muscle diseases caused by reduced levels of myogenic differentiation, suggesting the possibility that MSRs are involved in messaging during myogenic differentiation. Also, MSRs may be involved in myogenesis by promoting bioenergetic remodeling and assisting myoblast survival during myogenic differentiation. In this review, we will take MSRs as an entry point to explore its concrete regulatory mechanisms during myogenic differentiation, with a perspective to provide a theoretical basis for the treatment and repair of related muscle diseases

The Performance Analysis for Embedded Systems using Statistics Methods

Performance comparison for the computer system under different hardware platform & system structure is of vital importance in the study of the performance evaluation. The Performance Analysis for Embedded Systems by using statistics methods based on the randomized complete block designs was proposed. Using the randomized block design, the differences between conditions can be separated from the difference in the processing, and be separated from the experimental bias. A case study of automatic gate machines used in the automatic fare collection system of Shanghai Metro is presented. The obtained assessment results show that our approach is helpful and effective. DOI: http://dx.doi.org/10.11591/telkomnika.v11i7.2864

The Evaluation of Pneumonectomy and Bronchoplasty Lobectomy in the Treatment of Non-small Cell Lung Cancer: A Report of 64 Cases

Background and objective Pneumonectomy was the initial successful surgery to treat lung cancer, but there has been being a lot of controversy since its inception. The aim of this study is to evaluate its potential role in the treatment of lung cancer through analyzing the survival for 64 cases underwent pneumonectomy or bronchoplasty lobectomy out of 804 cases underwent lung resection. Methods Eight hundred and four cases of lung cancer underwent pulmonary surgery. We retrospectively reviewed the clinical data, especially foucused on the survival of 64 pneumonectomies or bronchoplasty lobectomies. Results Of the 64 patients, 25 underwent pneumonectomy (6 right, 19 left) due to involvement of ipsilateral pulmonary artery trunk. Owning to involving ipsilateral main bronchus with the distance of tumor from carina <2 cm, 4 pneumonectomies, 19 right upper bronchoplasty lobectomies, 1 left upper sleeve lobectomy and 1 left lower sleeve lobectomy were performed. Due to the ipsilateral main bronchus involvement with the distance of tumor from carina ≥2 cm, 13 cases underwent main bronchus bronchoplasty. One performed right sleeve pneumonectomy because of carina involvement. Overall 1-, 3- and 5-year survival rates of 64 pneumonectomies or bronchoplasty lobectomies were 93.6%, 69.0% and 45.1%, respectively, and that of 489 standard lobectomies done by the same surgery team in the same period were 92.5%, 77.3% and 56.9%, respectively. There was no significant difference in 5-year cumulative survival rates between the two groups (P=0.226). Conclusion Although standard lobectomy remains the main type of surgery, pneumonectomy or bronchoplasty lobectomy is still one of option for the highly selective patients combining the support of induction chemotherapy

Analysis of A Remote Rainstorm in the Yangtze River Delta Region Caused by Typhoon Mangkhut (2018)

An extraordinary heavy rain event caused by Typhoon Mangkhut occurred in the Yangtze River Delta region on 16 September 2018, with the maximum of 24-h accumulated rainfall at a single station reaching 297 mm. However, numerical models and subjective forecast failed to predict this typhoon remote rainstorm accurately. In this study, multiple observational data, an analysis dataset, and a trajectory model are used to analyze the causes of this severe rainstorm. The results show that the circulation situation provides a favorable large-scale background condition for the generation of the rainstorm. The coupling of the upper-level westerly jet and the low-level southerly jet is beneficial to the development of strong convections. In the rainstorm area there is a positive vorticity center connected to the main body of the typhoon. The cooling and humidifying effect of dry-cold air saturates the formerly unsaturated wet air, leading to the increase of precipitation. Besides, there is a lower-tropospheric moisture transport path connecting the typhoon and the rainstorm area, providing abundant moisture for the development of rainstorms. The backward trajectory simulation shows that the moisture mainly originates from the lower troposphere over the Philippine Sea, the southern South China Sea, and the sea south of the Philippines

Application of 18F-FDG PET/CT in Pulmonary Disease: A Report of 419 Cases

Background and objective The application and the value of PET/CT in lung cancer are on the way to development. The aim of this study is to summarize the data from 419 patients with pulmonary tumor or tumor-like disease and to explore the appliance of PET/CT. Methods From Dec 2007 to Aug 2011, 594 patients with pulmonary tumor or tumor-like disease underwent PET/CT examination during the different course of treatment, which were treated by single surgery team from Peking University Cancer Hospital. Of these patients, 419 cases diagnosed pathologically were included into study. The clinicapathological and follow-up data were collected to analyze the value of PET/CT in diagnosis, TNM staging, therapy response evaluation and posttherapy monitoring. Results Four hundred and nineteen cases comprised of 63 benign and 356 malignant, of which, 338 were primary lung cancer, and 18 were metastases. The SUVmax cutoff was defined as 2.5 to differentiate the benign and malignant disease. PET/CT obtained the role of diagnosis with sensitivity as 85.0%, specificity as 52.4%, accuracy rate as 79.2%, positive predictive value as 89.2% and negative predictive value as 42.9%, respectively. Of 338 primary cases, 275 underwent PET/CT at initial diagnosis, in which, 46 (16.7%) distant metastasis were found, including 8 additional metastasis not found by conventional utilities. Six of 43 recurrences were found by PET/CT following conventional examination. In T staging, SUVmax is positively correlated with diameter of tumors (P<0.05). In N staging, 610 stations of lymph nodes were resected from 168 cases, with 37 stations predicted as positive by PET/CT and 102 stations pathologically proven positive, therefore, calculating the sensitivity as 36.3%, specificity as 93.9%, accuracy rate as 84.3%, positive predictive value as 54.4% and negative predictive value as 88.0%, respectively. Ten patients underwent PET/CT scan for chemotherapy response evaluation, with SUVmax changing following T downstaging. Conclusion PET/CT is one optional method for diagnosis of pulmonary tumors. In TNM staging, PET/CT showed the superiority than conventional utilities in M staging, but possesses the high specificity but inferior sensitivity in N staging. Therefore, PET/CT should be used as routine examination for postoperation follow-up. Furthermore, PET/CT performed the outstanding role in chemotherapy response evaluation

Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells

Abstract Peritoneal fibrosis (PS) determines the long-term outcome of peritoneal dialysis (PD). We previous confirmed that hydrogen sulfide (H2S) inhibited PS, but its cellular mechanism was not fully elucidated. Epithelial-mesenchymal transition (EMT) of mesothelial cells (MCs) is an important cellular event of PS, we therefore investigated whether EMT can be affected by H2S in MCs. Rats were treated with 4.25% -glucose PD fluids plus lipopolysaccharide for 28 days to produce PS, and NaHS (56 μg/kg.d) was given simultaneously. NaHS (56 μg/kg.d) reduced the deposition of collagen in the submesothelial zone compared with the PS group. In primarily cultured rat MCs, 4.25% -glucose PD fluid induced EMT in MCs featured as loss of ZO-1 and Cytokeratin, and increase of α-SMA, plasminogen activator inhibitor 1, fibronectin and TGF-β1 proteins. PD fluid also increased IL-6 and monocyte chemotactic protein-1 mRNA expressions as well as the phosphorylation of Smad2/3 and Smad3. NaHS (50–300 μmol/L) reversed the above alterations with the optimal dose at 100 μmol/L. Thus, exogenous H2S improves PS by inhibiting EMT in MCs. The anti-EMT effect of H2S is associated with the inhibition of inflammation and TGF-β1-Smad signal pathway

The Current Immunohistochemistry Markers in the Resected Tissues of Non-small Cell Lung Cancer Could Not Predict Prognosis

Background and objective It has been drawn much attention to identify the molecular markers by immunohistochemistry (IHC) for evaluating the prognosis of non-small cell lung cancer (NSCLC) following resection. The aim of this study is to retrospectively associate ever tested IHC markers and prognosis of NSCLC after resection. Methods A total of 722 NSCLC patients underwent surgery by single surgeon team from 2008 to 2013. Twelve molecular markers had been examined by IHC and the staining signals was re-scored with unified standard. Survival analysis by univariate and multivariate was carried out to assess the significance of these markers in prognosis of NSCLC in our prospective database with strict follow-up. Results The following twelve IHC markers had been tested between 2008 and 2013, including platelet-derived growth factor receptor (PDGFR)(n=124), excision repair cross complementing 1 (ERCC1)(n=124), epithelial growth factor receptor (EGFR)(n=131), vascular endothelial growth factor receptor 3 (VEGFR3)(n=142), NM23 (n=129), MRP (n=109), P170 (n=104), TS (n=143), Tubulin (n=133), ribonucleotide reductase M1 (RRM1)(n=131), ribonucleotide reductase M1 (COX2)(n=138), and TOPII (n=127). Only VEGFR3 expression was correlated with prognosis of the patients by univariate analysis, with 5-yrs survival rate being 77.6% and 65.0% (positive vs. negative) respectively (P=0.042). However, VEGFR3 was not an independent prognostic factor for this series of NSCLC patients in multivariate analysis. Conclusion These twelve IHC markers could not predict prognosis of NSCLC patients after surgery in our series