Potential therapeutic effects of pigment epithelium-derived factor for treatment of diabetic retinopathy

Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves multiple molecular pathways and is characterized chronic neurovascular degeneration. Current approaches to prevent or to treat DR are still far from satisfactory. Therefore, it is important to develop new therapeutic strategies for the prevention and treatment to DR. Pigment epithelium-derived factor (PEDF), a 50-kDa secreted glycoprotein, has been described as a multi-functional protein. Some emerging evidences indicate that PEDF are able to target multiple pathways exerting neurotropic, neuroprotective, anti-angiogenic, antivasopermeability, anti-inflammation, anti-thrombogenic and anti-oxidative effects in DR. In this review, we addressed the functions of PEDF in different pathways, which could lead to potential therapeutics on the treatment to DR.

Energy metabolism in cancer stem cells

Normal cells mainly rely on oxidative phosphorylation as an effective energy source in the presence of oxygen.In contrast,most cancer cells use less efficient glycolysis to produce ATP and essential biomolecules.Cancer cells gain the characteristics of metabolic adaptation by reprogramming their metabolic mechanisms to meet the needs of rapid tumor growth.A subset of cancer cells with stem characteristics and the ability to regenerate exist throughout the tumor and are therefore called cancer stem cells(CSCs).New evidence indicates that CSCs have different metabolic phenotypes compared with differentiated cancer cells.CSCs can dynamically transform their metabolic state to favor glycolysis or oxidative metabolism.The mechanism of the metabolic plasticity of CSCs has not been fully elucidated,and existing evidence indicates that the metabolic phenotype of cancer cells is closely related to the tumor microenvironment.Targeting CSC metabolism may provide new and effective methods for the treatment of tumors.In this review,we summarize the metabolic characteristics of cancer cells and CSCs and the mechanisms of the metabolic interplay between the tumor microenvironment and CSCs,and discuss the clinical implications of targeting CSC metabolism.

Alcohol promotes epithelial mesenchymal transformation-mediated premetastatic niche formation of colorectal cancer by activating interaction between laminin-γ2 and integrin-β1

BACKGROUND Colorectal cancer(CRC) is a common malignant tumor. Alcohol consumption is positively correlated with CRC malignant metastasis;however, the mechanism is unclear. The interaction between laminin-γ2(LAMC2) and integrin-β1(ITGB1) plays a role in premetastatic niche signaling, which may induce epithelial mesenchymal transformation(EMT) and lead to metastasis.AIM To investigate the effects of alcohol on CRC metastasis from the molecular mechanism of the premetastatic niche.METHODS The interaction between LAMC2 and ITGB1 was measured by Duolink assay, and the expression levels of LAMC2, ITGB1 and focal adhesion kinase(FAK), snail, fibronectin, N-cadherin and special AT-rich sequence binding protein 1(SATB1) were measured by quantitative real-time polymerase chain reaction, immunohistochemistry and western blotting. Interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and IL-6 levels were measured via enzyme-linked immunosorbent assay, histopathological assessment via hematoxylin eosin staining, and determination of aberrant crypt foci via methylene blue.RESULTS The lymph node metastasis rate was higher in the alcohol group than non-alcohol group. There was a significant increase in interaction signals between LAMC2 and ITGB1, and an increase in phosphorylate-FAK/FAK, snail, fibronectin, N-cadherin and SATB1, whereas E-cadherin was reduced in the alcohol group compared to the non-alcohol group in both animal and clinical samples. Serum IL-1β, TNF-α and IL-6 were higher in alcohol group than in non-alcohol group. Alcohol may promote CRC metastasis by influencing the molecular mechanism of the premetastatic niche.CONCLUSION Our study suggests that alcohol promotes EMT-mediated premetastatic niche formation of CRC by activating the early interaction between LAMC2 and ITGB1 and lead to CRC metastasis.

Effect of Chinese medicine prescriptions of warming-Yang or cooling-heat combined with Gefitinib on H1650 cell line

Purpose The warming-Yang or cooling-heat is the principle rules of traditional Chinese medicine theory. The purpose of this study is to identify the effect of warming-Yang or cooling-heat Chinese medicine prescriptions combining with Gefitinib on lung cancer H1650 cell line. Materials and Methods： The typical warming-Yang prescription, Shen-fu （SF） Injection, and cooling-heat prescription, Qing-kai-ling （QKL） Injection was combined with Gefitinib respectively to treat H1650 cells. Cell viability was measured by MTT assay and Annexin V/PI method. Epidermal growth factor receptor （EGFR） pathway proteins were detected by Western blot. Results： QKL combined with Gefitinib significantly suppressed cell proliferation and induced apoptosis in H1650 cell line compared with single drug （P 〈 0.05）. On the contrary, SF and Gefitinib had significant antagonism effects on both cell viability inhibition and apoptosis （48h： 0.85 〈 Q 〈 1.15, 72h： Q 〈 0.85）. Although higher EGFR protein level was observed in Gefitinib group, which was significantly reduced in QKL ＋ Gefitinib group, no significant differences were observed in the levels of p-EGFR （P 〉 0.05）, downstream AKT/p-AKT （P 〉 0.05）, or ERK/p-ERK （P 〉 0.05） among Gefitinib, Gefitinib ＋ SF, and Gefitinib ＋ QKL groups. Conclusion： QKL Injection may reduce the level of EGFR and then improve the resistance of H1650 cells to EGFR-TKIs, which may be the mechanism of synergism effect of QKL Injection and Gefitinib. The principle rules of warming-Yang or cooling-heat should be further elucidated, and more research are required to explore the combined effect of Chinese medicine with opposite principle and Gefitinib.

Unveiling Defect-Mediated Carrier Dynamics in Few-Layer MoS2 Prepared by Ion Exchange Method via Ultrafast Vis-NIR-MIR Spectroscopy

Defect-mediated processes in two-dimensional transition metal dichalcogenides have a significant influence on their carrier dynamics and transport properties,however,the detailed mechanisms remain poorly understood.Here,we present a comprehensive ultrafast study on defect-mediated carrier dynamics in ion exchange prepared few-layer MoS2 by femtosecond time-resolved Vis-NIR-MIR spectroscopy.The broadband photobleaching feature observed in the near-infrared transient spectrum discloses that the mid-gap defect states are widely distributed in few-layer MoS2 nanosheets.The processes of fast trapping of carriers by defect states and the following nonradiative recombination of trapped carriers are clearly revealed,demonstrating the mid-gap defect states play a significant role in the photoinduced carrier dynamics.The positive to negative crossover of the signal observed in the mid-infrared transient spectrum further uncovers some occupied shallow defect states distributed at less than0.24 e V below the conduction band minimum.These defect states can act as effective carrier trap centers to assist the nonradiative recombination of photo-induced carriers in few-layer MoS2 on the picosecond time scale.

Severe Sturge-Weber syndrome in a 9-year-old boy: a great challenge

Dear Editor,We present a severe Sturge-Weber syndrome(SWS)in a boy with Mongolian spot,congenital glaucoma,seizures,and intelligent disability.During the hospital,the boy was admitted Pediatrics Department and Ophthalmology Department to control the seizure of episode and glaucoma respectively.

Rare right congenital diaphragmatic hernia with ileum and colon hernia ted into thoracic cavity in an 18-year-old adult

To the Editor: Congenital diaphragmatic hernia is a congenital anomaly, rarely found in adults. Delayed presentation of congenital diaphragmatic hernia in adults can cause diagnostic dilemma. Immediate laparoscopic repair is recommended for these patients. Here, we presented a case of an 18-year-old man with complaints of chest pain and abdominal discomfort. X-ray and computed tomography (CT) scan revealed a right-sided pleuro-per让oneal hiatus hernia, which is located at postero-lateral diaphragm, also known as Bochdalek hernia.