Hallmarks in colorectal cancer:Angiogenesis and cancer stem-like cells

Carcinogenesis is a multistep process that requires the accumulation of various genetic and epigenetic aberrations to drive the progressive malignant transformation of normal human cells.Two major hallmarks of carcinogenesis that have been described are angiogenesis and the stem cell characteristic of limitless replicative potential.These properties have been targeted over the past decade in the development of therapeutic treatments for colorectal cancer(CRC),one of the most commonly diagnosed and lethal cancers worldwide.The treatment of solid tumor cancers such as CRC has been challenging due to the heterogeneity of the tumor itself and the chemoresistance of the malignant cells.Furthermore,the same microenvironment that maintains the pool of intestinal stem cells that contribute to the continuous renewal of the intestinal epithelia also provides the necessary conditions for proliferative growth of cancer stem-like cells.These cancer stem-like cells are responsible for the resistance to therapy and cancer recurrence,though they represent less than 2.5%of the tumor mass.The stromal environment surrounding the tumor cells,referred to as the tumor niche,also supports angiogenesis,which supplies the oxygen and nutrients needed for tumor development.Anti-angiogenic therapy,such as with bevacizumab,a monoclonal antibody against vascular-endothelial growth factor,significantly prolongs the survival of metastatic CRC patients.However,such treatments are not completely curative,and a large proportion of patient tumors retain chemoresistance or show recurrence.This article reviews the current knowledge regarding the molecular phenotype of CRC cancer cells,as well as discusses the mechanisms contributing to their maintenance.Future personalized therapeutic approaches that are based on the interaction of the carcinogenic hallmarks,namely angiogenic and proliferative attributes,could improve survival and decrease adverse effects induced by unnecessary chemotherapy.

ITO Etched by Photolithography Used in the Fabrication of Flexible Organic Solar Cells with PET Substrates

In this study, the authors have shown the power conversion efficiency of flexible organic solar cells. The structure of the device is PET/ITO/PEDOT： PSS/P3HT： PCBM/AI. P3HT （poly-3-hexylthiophene）. It was used as an electron donor, PCBM （[6, 6]-phenyl C6 l-butyric acid methyl ester） as an electron acceptor and PEDOT： PSS used as a HIL （hole injection layer）. These materials were deposited by spin coating method on the flexible substrates. Photolithography method is used to etch ITO. The electrical parameters of the fabricated cells were investigated by means of J （V）, FF （fill factor）, the efficiency （r/）, photocurrent and IPCE measurement. It was observed that 45% of the absorbed photons are converted into current. The results obtained using etching technology by photolithography is better than that obtained in the clean room.

Iohexol plasma and urinary concentrations in cirrhotic patients:A pilot study

BACKGROUND Renal failure is an independent prognostic factor for survival in patients with cirrhosis.Equations to calculate serum creatinine significantly overestimate the glomerular filtration rate(GFR).Plasma clearance of direct biomarkers has been used to improve the accuracy of evaluations of GFR in this population,but no study has simultaneously measured plasma and urinary clearance,which is the gold standard.AIM To study calculated plasma and urinary concentrations of iohexol,based on the kinetics of samples collected over 24 h from cirrhotic patients with three different grades of ascites.METHODS One dose of iohexol(5 mL)was injected intravenously and plasma concentrations were measured 11 times over 24 h in nine cirrhotic patients.The urinary concentration of iohexol was also measured,in urine collected at 4,8,12 and 24 h.RESULTS The plasma and urinary curves of iohexol were similar;however,incomplete urinary excretion was detected at 24 h.Within the estimated GFR limits of our population(>30 and<120 mL/min/1.73 m^(2)),the median measured GFR(m GFR)was 63.7 mL/min/1.73 m^(2)(range:41.3–111.3 mL/min/1.73 m^(2)),which was an accurate reflection of the actual GFR.Creatinine-based formulas for estimatingGFR showed significant bias and imprecision,while the Brochner–Mortensen(BM)equation accurately estimated the m GFR(r=0.93).CONCLUSION Plasma clearance of iohexol seems useful for determining GFR regardless of the ascites grade.We will secondly devise a pharmacokinetics model requiring fewer samples andvalidate the BM equation.

Networks, Topology and Interaction Principle Implemented in the Kron＇s Method

This paper present electrical networks, with topological modelisations, generalized cross talked functions implemented in a Kron＇s formalism; Coupling functions are called chords and give a powerful extension to the method. Applied in electromagnetic compatibility, it has proven its efficiency in time computation and accuracy. The paper review the Kron＇s formalism, a mathematical modelisation of currents by tensorial analysis and topologie, the string principles, and an application, at the end, we propose power-chopper modeling.

Elevated plasma interleukin-8 as a risk factor for mortality in children presenting with cerebral malaria

Background Cerebral malaria(CM)is a neuropathology which remains one of the deadliest forms of malaria among African children.The kinetics of the pathophysiological mechanisms leading to neuroinflammation and the death or survival of patients during CM are still poorly understood.The increasing production of cytokines,chemokines and other actors of the inflammatory and oxidative response by various local actors in response to neuroinflammation plays a major role during CM,participating in both the amplification of the neuroinflammation phenomenon and its resolution.In this study,we aimed to identify risk factors for CM death among specific variables of inflammatory and oxidative responses to improve our understanding of CM pathogenesis.Methods Children presenting with CM(n=70)due to P.falciparum infection were included in southern Benin and divided according to the clinical outcome into 50 children who survived and 20 who died.Clinical examination was complemented by fundoscopic examination and extensive blood biochemical analysis associated with molecular diagnosis by multiplex PCR targeting 14 pathogens in the patients'cerebrospinal fluid to rule out coinfections.Luminex technology and enzyme immunoassay kits were used to measure 17 plasma and 7 urinary biomarker levels,respectively.Data were analysed by univariate analysis using the nonparametric Mann-Whitney U test and Pearson’s Chi2 test.Adjusted and multivariate analyses were conducted separately for plasma and urinary biomarkers to identify CM mortality risk factors.Results Univariate analysis revealed higher plasma levels of tumour necrosis factor(TNF),interleukin-1beta(IL-1β),IL-10,IL-8,C-X-C motif chemokine ligand 9(CXCL9),granzyme B,and angiopoietin-2 and lower urinary levels of prostanglandine E2 metabolite(PGEM)in children who died compared to those who survived CM(Mann-Whitney U-test,P-values between 0.03 and<0.0001).The multivariate logistic analysis highlighted elevated plasma levels of IL-8 as the main risk factor for death during CM(adjusted odd ratio=14.2,P-value=0.002).Values obtained during follow-up at D3 and D30 revealed immune factors associated with disease resolution,including plasma CXCL5,C-C motif chemokine ligand 17(CCL17),CCL22,and urinary 15-F2t-isoprostane.Conclusions The main risk factor of death during CM was thus elevated plasma levels of IL-8 at inclusion.Follow-up of patients until D30 revealed marker profiles of disease aggravation and resolution for markers implicated in neutrophil activation,endothelium activation and damage,inflammatory and oxidative response.These results provide important insight into our understanding of CM pathogenesis and clinical outcome and may have important therapeutic implications.

High-throughput sequencing reveals similar molecular signatures for class switch recombination junctions for theγandαisotypes

INTRODUCTION After encountering an antigen,B cells undergo class switch recombination(CSR),which substitutes the Cμgene with Cγ,Cε,or Cαto generate IgG,IgE,and IgA antibodies with the same antigenic specificity but new effector functions.1 The DNAediting enzyme activation-induced deaminase(AID)is essential for CSR by targeting switch(S)regions preceding Cμ(namely,the Sμdonor region)and the Cγ,Cε,and Cαgenes(namely,the Sγ,ε,αacceptor regions).1 Cis-and trans-controlled DNA double strand beaks are generated during this process.2–6 Recruitment of DNA repair factors that facilitate the end-joining process is a crucial step of class switch recombination.Two pathways are implicated in this end joining.The classical non-homogenous end joining(c-NHEJ)pathway ligates DNA ends with no or little homology.By contrast,the alternative end joining(A-EJ)pathways is used to ligate DNA ends that have microhomology.

Non-traumatic coma in young children in Benin:are viral and bacterial infections gaining ground on cerebral malaria?

Background:While malaria morbidity and mortality have declined since 2000,viral central nervous system infections appear to be an important,underestimated cause of coma in malaria-endemic Eastern Africa.We aimed to describe the etiology of non-traumatic comas in young children in Benin,as well as their management and early outcomes,and to identify factors associated with death.Methods:From March to November 2018,we enrolled all HIV-negative children aged between 2 and 6 years,with a Blantyre Coma Score≤2,in this prospective observational study.Children were screened for malaria severity signs and assessed using a systematic diagnostic protocol,including blood cultures,malaria diagnostics,and cerebrospinal fluid analysis using multiplex PCR.To determine factors associated with death,univariate and multivariate analyses were performed.Results:From 3244 admissions,84 children were included:malaria was diagnosed in 78,eight of whom had a viral or bacterial co-infection.Six children had a non-malarial infection or no identified cause.The mortality rate was 29.8%(25/84),with 20 children dying in the first 24 h.Co-infected children appeared to have a poorer prognosis.Of the 76 children who consulted a healthcare professional before admission,only 5 were prescribed adequate antimalarial oral therapy.Predictors of early death were jaundice or increased bilirubin[odd ratio(OR)=8.6;95% confidential interval(CI):2.03-36.1]and lactate>5 mmol/L(OR=5.1;95%CI:1.49-17.30).Antibiotic use before admission(OR=0.1;95%CI:0.02-0.85)and vaccination against yellow fever(OR=0.2,95%CI:0.05-0.79)protected against mortality.Conclusions:Infections were found in all children who died,and cerebral malaria was by far the most common cause of non-traumatic coma.Missed opportunities to receive early effective antimalarial treatment were common.Other central nervous system infections must be considered in their management.Some factors that proved to be protective against early death were unexpected.