- One-Year Results of Fixed Aflibercept Treatment Regime in Type 3 Neovascularization. [Journal Article]
- OOphthalmologica 2019 May 23; :1-8
- CONCLUSIONS: Intravitreal aflibercept administered in a fixed treatment regime during the first year of therapy may be effective for the improvement and stabilization of BCVA in eyes with type 3 neovascularization. However, RPE atrophy and subretinal/intraretinal fibrosis can develop during the treatment.
- Liquiritigenin inhibits hepatic fibrogenesis and TGF-β1/Smad with Hippo/YAP signal. [Journal Article]
- PPhytomedicine 2018 Dec 10; 62:152780
- CONCLUSIONS: These results clearly show that LQ ameliorated experimental liver fibrosis by acting on the TGF-β1/Smad and Hippo/YAP pathways, indicating that LQ has the potential for effective treatment of liver fibrosis.
- Distinct histomorphological features are associated with IDH1 mutation in intrahepatic Cholangiocarcinoma. [Journal Article]
- HPHum Pathol 2019 May 20
- Intrahepatic cholangiocarcinoma has known histological heterogeneity. Mutations in IDH1 (mIDH1) define a molecular subclass of intrahepatic cholangiocarcinoma and IDH-targeted therapies are in develo…
Intrahepatic cholangiocarcinoma has known histological heterogeneity. Mutations in IDH1 (mIDH1) define a molecular subclass of intrahepatic cholangiocarcinoma and IDH-targeted therapies are in development. Characterizing mIDH1 ICC histomorphology is of clinical interest for efficient identification. Resected ICCs with targeted next generation sequencing by MSK-IMPACT were selected. Clinical data were obtained. By slide review, blinded to IDH status, data were collected for histology type, mucin production, necrosis, fibrosis, cytoplasm cell shape (low cuboidal, plump cuboidal/polygonal, and columnar), and architectural pattern (anastomosing, tubular, compact tubular, and solid). A tumor was considered architecturally heterogeneous if no dominant pattern represented ≥75% of the tumor. Parameters were compared between mIDH1and IDH wild type controls. In the examined cohort (113 ICC: 29 mIDH1 and 84 IDH wild type), all IDH1 mutant tumors were of small duct type histology, thus analysis was limited to 101 small duct type tumors. mIDH1cases were more likely to have plump cuboidal/ polygonal shape (P=.014) and geographic-type fibrosis (P=.005) while IDH1 wild type were more likely to have low cuboidal shape (P=.005). Both groups were predominantly architecturally heterogeneous with no significant difference in the distribution of architectural patterns. Plump cuboidal/polygonal cell shape and a geographic-type pattern of intra-tumoral fibrosis are more often seen in mIDH1compared to IDH wild type tumors, however IDH1 mutation is not associated with a distinct histoarchitectural pattern.
- Asarone and metformin delays experimentally induced hepatocellular carcinoma in diabetic milieu. [Journal Article]
- LSLife Sci 2019 May 20
- CONCLUSIONS: The STZ can be used to promote the DEN induced HCC. Treatment with (α)-and (β)-asarone attenuates the effect of STZ + DEN induced HCC akin to metformin.
- Liver Fibrosis and Metabolic Alterations in Adults with Alpha1 Antitrypsin Deficiency Caused by the Pi*ZZ Mutation. [Journal Article]
- GGastroenterology 2019 May 20
- CONCLUSIONS: In studies of AATD patients with the Pi*ZZ mutation, and of Pi*Z-overexpressing mice, we found evidence of liver steatosis and impaired lipid secretion. We identified factors associated with significant liver fibrosis in patients, which could facilitate hepatologic assessment and counseling of individuals who carry the Pi*ZZ mutation.
- Pigment epithelium-derived factor inhibits adipogenesis in 3T3-L1 adipocytes and protects against high-fat diet-induced obesity and metabolic disorders in mice. [Journal Article]
- TRTransl Res 2019 May 03
- Obesity is a major cause of metabolic syndrome and type II diabetes, and it presents with metabolic disorders, such as hyperglycemia, hyperlipidemia, and insulin resistance. Pigment epithelium-derive…
Obesity is a major cause of metabolic syndrome and type II diabetes, and it presents with metabolic disorders, such as hyperglycemia, hyperlipidemia, and insulin resistance. Pigment epithelium-derived factor (PEDF), a protein isolated from retinal pigment epithelial cells, has multiple functions, including neuronal protection, antineoplastic effects, and anti-inflammatory activity. The aim of this study is to investigate the antiobesity effects of PEDF. The antiobesity effects of PEDF on fat accumulation, inflammation, energy expenditure, insulin resistance, and obesity-related physiological parameters and protein levels were assessed in high-fat diet (HFD)-induced obese mice in vivo and in 3T3-L1 adipocytes, palmitate (PA)-treated HepG2 cells, and C2C12 myotubes in vitro. In an in vivo assay, PEDF effectively decreased body weight gain, white adipose tissue mass, and inflammation and improved insulin resistance, dyslipidemia, and hyperglycemia in HFD-induced mice. In liver tissue, PEDF decreased lipid accumulation and fibrosis. In an in vitro assay, PEDF diminished the differentiation of 3T3-L1 preadipocytes. We also determined that PEDF promoted lipolysis and prolonged cell cycle progression, through the mTOR-S6K pathway and downstream transcription factors, such as peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein α (CEBP-α), and CEBP-β. In addition, PEDF decreased reactive oxygen species production in PA-induced HepG2 cells and improved glucose uptake ability in PA-induced HepG2 cells and C2C12 myotubes. In the present study, PEDF protected against HFD-induced obesity and metabolic disorders in mice, inhibited adipogenesis, and improved insulin resistance. These results provide a new potential treatment for obesity in the future.
- Silicosis and pulmonary tuberculosis in deceased female South African miners. [Journal Article]
- OMOccup Med (Lond) 2019 May 23
- CONCLUSIONS: It is important to report research findings by sex. Proportions of silicosis and PTB were comparable in women and men, suggesting similar exposures. Silicosis detection after short employment indicates inadequate dust control, particularly as most entered the industry after implementation of interventions to control silica dust in 2003.
- Does liver cirrhosis have any impact on patients with lung cancer after surgical resection? [Journal Article]
- ICInteract Cardiovasc Thorac Surg 2019 May 23
- A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: 'Does liver cirrhosis have any impact on patients with lung cancer after surgical…
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: 'Does liver cirrhosis have any impact on patients with lung cancer after surgical resection?' Altogether, 134 papers were found using the reported search, of which 6 cohort studies represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. Five of the cohort studies found that liver cirrhosis was correlated to higher postoperative mortality after lung cancer surgery, 4 also showed a correlation with higher postoperative morbidity and 2 of them found that patients with Child grade B or above experienced a higher risk of morbidity and mortality than those with Child grade A. Four of the cohort studies found that cirrhotic patients had poorer long-term survival, with 2 studies showing patients with Child grade B or above having a worse overall survival than those with Child grade A. Therefore, we conclude that liver cirrhosis (especially Child grade B or above) imposed a significant unfavourable impact on both short-term and long-term outcomes for patients intended for lung cancer surgery.
- Clonorchis sinensis excretory-secretory products increase malignant characteristics of cholangiocarcinoma cells in three-dimensional co-culture with biliary ductal plates. [Journal Article]
- PPPLoS Pathog 2019 May 23; 15(5):e1007818
- Clonorchis sinensis is a carcinogenic human liver fluke, prolonged infection which provokes chronic inflammation, epithelial hyperplasia, periductal fibrosis, and even cholangiocarcinoma (CCA). These…
Clonorchis sinensis is a carcinogenic human liver fluke, prolonged infection which provokes chronic inflammation, epithelial hyperplasia, periductal fibrosis, and even cholangiocarcinoma (CCA). These effects are driven by direct physical damage caused by the worms, as well as chemical irritation from their excretory-secretory products (ESPs) in the bile duct and surrounding liver tissues. We investigated the C. sinensis ESP-mediated malignant features of CCA cells (HuCCT1) in a three-dimensional microfluidic culture model that mimics an in vitro tumor microenvironment. This system consisted of a type I collagen extracellular matrix, applied ESPs, GFP-labeled HuCCT1 cells and quiescent biliary ductal plates formed by normal cholangiocytes (H69 cells). HuCCT1 cells were attracted by a gradient of ESPs in a concentration-dependent manner and migrated in the direction of the ESPs. Meanwhile, single cell invasion by HuCCT1 cells increased independently of the direction of the ESP gradient. ESP treatment resulted in elevated secretion of interleukin-6 (IL-6) and transforming growth factor-beta1 (TGF-β1) by H69 cells and a cadherin switch (decrease in E-cadherin/increase in N-cadherin expression) in HuCCT1 cells, indicating an increase in epithelial-mesenchymal transition-like changes by HuCCT1 cells. Our findings suggest that C. sinensis ESPs promote the progression of CCA in a tumor microenvironment via the interaction between normal cholangiocytes and CCA cells. These observations broaden our understanding of the progression of CCA caused by liver fluke infection and suggest a new approach for the development of chemotherapeutic for this infectious cancer.
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- Evaluation of model performance to predict survival after transjugular intrahepatic portosystemic shunt placement. [Journal Article]
- PlosPLoS One 2019; 14(5):e0217442
- CONCLUSIONS: MELD score best predicted 90-day mortality. Addition of sodium to the MELD score did not improve its performance, though mortality prediction was improved using Age-MELD for ascites and Hemoglobin-MELD for bleeding. An individualized risk stratification approach may be best when considering candidates for TIPS placement.