Effects of endotoxin on endothelin receptor in hepatic and intestinal tissues after endotoxemia in rats

INTRODUCTIONEndothelins(ETs) has a potent and sustainedvasoconstrictive effect on a variety of blood vessels.The vascular smooth muscle cell (VSMC)is thetarget for ETs.VSMC of the whole body containsendothelin receptor (ETR).A great number ofexperiments have shown that three distinctcomplementary DNAs of ETR have been identifiedi.e.,endothelin A receptor(ET_A receptor),endothelin B receptor(ET_B receptor)

Inhibitory effect of caffeic acid phenethyl ester on the growth of SW480 colorectal tumor cells involvesβ-catenin associated signaling pathway down-regulation

AIM： To study the anti-tumor effect of caffeic acid phenethyl ester （CAPE） and the influence of CAPE on β-catenin associated signaling pathway in SW480 colorectal cancer （CRC） cells. METHODS： SW480 cells were treated with CAPE at serial concentrations. The proliferative status of cells was measured by methabenzthiazuron （MTT） assay. Cell cycle and cell apoptosis were analyzed using flow cytometry （FCM）. Western blotting assay was used to evaluate the protein level of β-catenin, c-myc and cyclinD1. β-catenin localization was determined by indirect immunofluorescence. RESULTS： CAPE displayed a strong inhibitory effect in a significant dose- and time-dependent manner on SW480 cell growth. FCM analysis showed that the ratio of G0/G1 phase cells increased, S phase ratio decreased and apoptosis rate increased after SW480 cells were exposed to CAPE for 24 h. Pretreatment of SW480 cells with CAPE significantly suppressed β-catenin, c-myc and cyclinD1 protein expression. CAPE treatment was associated with decreased accumulation of β-catenin protein in nucleus and cytoplasm, and concurrently increased its accumulation on the surface of cell membrane. CONCLUSION： CAPE can inhibit SW480 cell proliferation by inducing cell cycle arrest and apoptosis. Decreased β-catenin and the associated signaling pathway target gene expression may mediate the anti-tumor effects of CAPE.

Identification of differential proteins in colorectal cancer cells treated with caffeic acid phenethyl ester

AIM: To investigate the molecular mechanisms of the anti-cancer activity of caffeic acid phenethyl ester (CAPE).

The Contradictory Effects of Equol on Breast Cancer

Natural products and their derivatives provide an attractive source for novel preventive and therapeutic agents.Epidemiological studies have indicated that the low incidence of breast cancer in Asian women may be related to a high consumption of soy foods.Equol,a metabolite of the soybean isoflavone daidzein,has been suggested to have preventive and therapeutic activity for breast cancer.However,conflicting data have been reported.There are two optical isomers of equol,S-equol and R-equol,with S-equol appearing to be the clinically-relevant compound.While equol is considered to be a selective estrogen receptor modulator,the molecular mechanisms underlying the biological activities of equol have not been fully elucidated.In addition,only part of the population can metabolize daidzein into equol due to differences in gut flora.This article will help provide a better understanding of the molecular mechanisms underlying the anti-(or potentially pro-)cancer and invasion activities of this unique secondary metabolite of a natural product,and will provide a basis for the development of equol and/or its analogs as novel cancer preventive or therapeutic agents.

APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans

AIM: To study the association between four base excision repair gene polymorphisms and colorectal cancer risk in a Chinese population.

Expert consensus on prevention and control of COVID-19 in the neurological intensive care unit(first edition)

During the COVID-19 epidemic,the treatment of critically ill patients has been increasingly difficult and challenging.During the epidemic,some patients with neurological diseases also have COVID-19,which could be misdiagnosed and cause silent transmission and nosocomial infection.Such risk is high in a neurological intensive care unit(NCU).Therefore,prevention and control of epidemic in critically ill patients is of utmost importance.The principle of NCU care should include comprehensive screening and risk assessment,weighing risk against benefits and reducing the risk of COVID-19 transmission while treating patients as promptly as possible.

Establishment of trauma care system based on local conditions： Un imperative trend

Today the world is unstable with frequent incidence of local mil- itary conflicts, terrorist attacks, traffic accidents, and natural disasters, thus trauma has become one of the most important modern diseases threatening human health. Accompanying the proposed concept of golden 1 h and platinum 10 rain, trauma care has been closely con- cerned in the fields of disaster medicine, trauma medicine, and even modern medicine. Narrowly speaking, trauma care includes pre-hospital care and in-hospital care; but from the wide side trauma care should additionally cover the intensive care, functional rehabil- itation and psychological rehabilitation following trauma.

Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system

Chimeric antigen receptor(CAR)T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies.However,CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence,in addition to antigen-negative relapse and an immunosuppressive microenvironment.Various preclinical studies are exploring strategies to overcome the above challenges.Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors.In this review,we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies,especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response.We also explored the sensitizing effects of conventional treatment approaches,such as chemotherapy and radiotherapy,on CAR T cell therapy.Finally,we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.

Role of speckle tracking imaging in the assessment of myocardial regional ventricular function in experimental blunt cardiac injury

Purpose： To evaluate the usefulness and information collecting ability of speckle tracking imaging techniques in the assessment of myocardial regional ventricular contractility in a rabbit model with blunt cardiac injury. Methods： Fifteen healthy New Zealand rabbits weighing （2.70 ± 0.28） kg were anesthetized （3% pentobarbital sodium/i.v） and impacted using the BIM-II biological impact machine to induce myocardial contusion （MC）. Hemodynamic parameters, such as heart rate, systolic pressure, mean arterial pressure, diastolic pressure and central venous pressure, were determined before and after MC. Further, param- eters reflecting left ventricular functions, such as left ventricular end systolic pressure, left ventricular end diastolic pressure, isovolumic pressure （IP） and the maximal increasing/decreasing rate of left intraventricular pressure （±dp/dtmax）, were also determined before and after MC. Left ventricular functions were determined either by two dimensional transthoracic echocardiography or by speckle tracking imaging for segmental abnormal ventricular wall motions. Results： Heart rate, systolic pressure, diastolic pressure and mean arterial pressure decreased signifi- cantly but transiently, while central venous pressure markedly increased after MC. In contrast to significant changes in diastolic functions, there was no significant change in cardiac systolic functions after MC. The speckle tracking imaging demonstrated that strain values of different myocardial segment significantly decreased post impact, and that of the ventricular segment decreased from segment to segment. Conclusion： Speckle tracking imaging is useful and informative to assess myocardial regional dysfunctions post MC.

The Ap-2α/Elk-1 axis regulates Sirpα-dependent tumor phagocytosis by tumor-associated macrophages in colorectal cancer

The inhibitory receptor signal regulatory protein-α(Sirpα)is a myeloid-specific immune checkpoint that engages the“don’t eat me”signal CD47,which is expressed on tumor and normal tissue cells.However,the profile and regulatory mechanism of Sirpαexpression in tumor-associated macrophages(TAMs)are still not clear.Here,we found that the expression of Sirpαin TAMs increased dynamically with colorectal cancer(CRC)progression.Mechanistically,CRC cell-derived lactate induced the nuclear translocation of the transcription factor Ap-2αfrom the cytoplasm in TAMs.Ap-2αfunctioned as a transcription factor for Elk-1 by binding to the conserved element GCCTGC located at−1396/−1391 in the mouse Elk-1 promoter.Subsequently,the Elk-1 protein bound to two conserved sites,CTTCCTACA(located at−229/−221)and CTTCCTCTC(located at−190/−182),in the mouse Sirpαpromoter and promoted Sirpαexpression in TAMs.Functionally,the macrophage-specific knockout of Ap-2αnotably promoted the phagocytic activity of TAMs and suppressed CRC progression,whereas these effects were prevented by the transgenic macrophage-specific expression of Elk-1,which regulated TAM phagocytosis and CRC development in a Sirpα-dependent manner.Furthermore,we showed that Elk-1 expression was positively correlated with Sirpαexpression in TAMs and was associated with poor survival in CRC patients.Taken together,our findings revealed a novel mechanism through which CRC evades innate immune surveillance and provided potential targets for macrophage-based immunotherapy for CRC patients.

Three-Center Experience on Patients with Influenza-Associated Acute Respiratory Distress Syndrome in Chongqing, China

To the Editor：Influenza-associated acute respiratory distress syndrome （ARDS） remains a devastating clinical picture. From December 2017 to January 2018,ten patients with influenza-associated ARDS were admitted to three different hospital＇s Intensive Care Units （ICUs） in Chongqing,with all cases resulting in demise.The main documented reasons for their admission to the ICU were due to progressive dyspnea and worsening hypoxemia which lead to endotracheal intubation and mechanical ventilation in these patients.Identification of influenza viruses was achieved using nucleic-acid testing from venous blood.This study was approved by the Institutional Review Board of Daping Hospital,Army Medical University.