METTL5 promotes gastric cancer progression via sphingomyelin metabolism

BACKGROUND The treatment of gastric cancer(GC)has caused an enormous social burden worldwide.Accumulating studies have reported that N6-methyladenosine(m6A)is closely related to tumor progression.METTL5 is a m6A methyltransferase that plays a pivotal role in maintaining the metabolic stability of cells.However,its aberrant regulation in GC has not been fully elucidated.AIM To excavate the role of METTL5 in the development of GC.METHODS METTL5 expression and clinicopathological characteristics were analyzed via The Cancer Genome Atlas dataset and further verified via immunohistochemistry,western blotting and real-time quantitative polymerase chain reaction in tissue microarrays and clinical samples.The tumor-promoting effect of METTL5 on HGC-27 and AGS cells was explored in vitro by Cell Counting Kit-8 assays,colony formation assays,scratch healing assays,transwell assays and flow cytometry.The tumor-promoting role of METTL5 in vivo was evaluated in a xenograft tumor model.The EpiQuik m6A RNA Methylation Quantification Kit was used for m6A quantification.Next,liquid chromatography-mass spectrometry was used to evaluate the association between METTL5 and sphingomyelin metabolism,which was confirmed by Enzyme-linked immunosorbent assay and rescue tests.In addition,we investigated whether METTL5 affects the sensitivity of GC cells to cisplatin via colony formation and transwell experiments.RESULTS Our research revealed substantial upregulation of METTL5,which suggested a poor prognosis of GC patients.Increased METTL5 expression indicated distant lymph node metastasis,advanced cancer stage and pathological grade.An increased level of METTL5 correlated with a high degree of m6A methylation.METTL5 markedly promotes the proliferation,migration,and invasion of GC cells in vitro.METTL5 also promotes the growth of GC in animal models.METTL5 knockdown resulted in significant changes in sphingomyelin metabolism,which implies that METTL5 may impact the development of GC via sphingomyelin metabolism.In addition,high METTL5 expression led to cisplatin resistance.CONCLUSION METTL5 was found to be an oncogenic driver of GC and may be a new target for therapy since it facilitates GC carcinogenesis through sphingomyelin metabolism and cisplatin resistance.

人工智能技术在消化内镜领域的研究现状

近年来,我国消化道肿瘤发病率、病死率居高不下。内镜检查作为诊疗消化道疾病的重要方法,尤其在肿瘤早期癌前病变的筛查阶段具有重要的应用价值。但是肿瘤早期癌前病变的内镜下发现率较低,提高内镜下早癌的诊断率对改善消化道肿瘤患者预后具有重要意义。随着计算机技术不断提高及大数据时代到来,人工智能技术辅助内镜下疾病诊断的相关研究也蓬勃发展。该文对人工智能技术的胃肠镜下疾病诊断结合国内外文献进行综述。

New Amides and Phenylpropanoid Glucosides from the Fruits of Piper retrofractum

Two new amides(E)-N-cinnamoyl-2-methoxypiperidine(1)and(R)-1-(2-oxopyrrolidin-3-yl)-5,6-dihydropyridin-2(1H)-one(2),four new amide glucosides,retrofractosides A-D(3-6),and two new phenylpropanoid glucosides,retrofractosides E(7)and F(8),together with 24 known compounds(9-32)were isolated from the fruits of Piper retrofractum.The chemical structures of these new compounds were elucidated based on extensive spectroscopic analysis.All of these isolates(1-32)were evaluated for inhibitory activity against mouse platelet aggregation induced by the peptide AYPGKF-NH2.(E)-N-(Tetrahydro-2H-pyran-2-yl)cinnamamide(9)showed a weak inhibitory efect,with an inhibition ratio of 52.0%at a concentration of 150μM.

Down-regulation of protein kinase C alpha/ezrin signals in light-induced phagocytic crisis of retinal pigment epithelium cells

AIM： To investigate the roles of PKC-α/ezrin signals in phagocytosis crisis of retinal pigment epithelium（RPE） cells in light damage model. METHODS： Light induced mice RPE injury model was established by continuously irradiating cool white light at different exposure time（0, 4, 8h light intensity： 4.18×10^-6 J/cm^2）. In vitro, human ARPE-19 cells treated with the doses and intensity（1.57×10^-6 J/cm^2） of laser irradiation. Histology analysis was evaluated by hematoxylin and eosin（HE） staining. In vivo RPE phagocytosis was quantified by measuring the accumulation of photoreceptor outer segments in the sub-retinal space. In vitro RPE phagocytosis was assessed by calculating the relative fluorescence intensity of FITC-labeled microspheres in ARPE-19 cells. To further investigate the molecular mechanism, the activation of PKC-α/ezrin signal was evaluated by Western blot in vivo and in vitro.RESULTS： HE staining revealed that the thickness of outer nuclear layer decreased significantly after 4 and 8h light exposure. By immunostaining with rhodopsin, a significant greater accumulation of photoreceptor outer segment was noticed after light injury. In vitro, light injuredRPE cells had less phagocytic activity in a dose dependent manner than that of the normal control（P〈0.01）. Western blot suggested the activation of PKC-α/ezrin signaling was down-regulated in a dose-dependent manner after light exposure. CONCLUSION： Our data suggest that light induced phagocytic crisis of RPE cells may result from the downregulation of PKC-α/ezrin signaling.

Chemical constituents from heartwoods of Caesalpinia sappan with antiplatelet aggregation activities

Objective:To clarify the active constituents of the heartwoods of Caesalpinia sappan,a traditional Chinese medicine with the functions of promoting blood circulation(Huoxue in Chinese)and removing blood stasis(Quyu in Chinese).Methods:The chemical constituents were isolated and purified by combination of silica gel and Sephadex LH-20 column chromatography,along with semipreparative HPLC.Their chemical structures were established by multiple spectroscopic methods and comparison with literature data.The in vitro antiplatelet aggregation activities were evaluated using mouse platelet induced by AYPGKF-NH2,a gold agonist of protease-activated receptor 4(PAR4).Results:Two new phenols,methyl 2-(4,4’,5’-trihydroxy-2’-(methoxymethyl)biphenyl-2-yloxy)acetate(1)and 1’-methylcaesalpin J(2),together with 24 known compounds(3-26),were isolated from the heartwoods of C.sappan.Among them,sappanchalcone(16)and brazilin(20)showed inhibitory activities against mouse platelet aggregation with IC50 values of 114.8μmol/L and 100.8μmol/L,respectively.Conclusion:Antiplatelet compounds from C.sappan targeting at PAR4 are reported for the first time.

INCREASED SPHERULITIC GROWTH RATES OF SEMICRYSTALLINE POLYMER DUE TO ENHANCED LIMITED LOCAL CHAIN SEGMENTAL MOBILITY AT THE INTERFACE OF DOUBLE-LAYER THIN FILMS

In this work the nucleation and growth of spherulites for the below polylactide （PLA） layer in poly（ε- caprolactone）/polylactide （PCL/PLA） double-layer films during isothermal crystallization at various temperatures above the melting point of PCL have been investigated by using polarized optical microscopy （POM）. It is revealed that two types of spherulitic morphologies are observed in PCL/PLA double-layer films. One is the well defined highly birefringent spherulites, and the other one is the coarse spherulites. It is interesting to find that the spherulitic growth rate of the coarse spherulites is higher than that of the well defined spherulites. It is thought that the coarse spherulites nucleate and grow with the assistance of the interfaces between the PCL and PLA layers, and the well defined highly birefringent spherulites only nucleate and grow in the PLA layer.

针刺结合西药治疗糖尿病性周围神经病变临床研究

Objective:To compare the clinical effect differences between western medication,acupuncture,and acupuncture combine with western medication in the treatment of diabetic peripheral neuropathy.Methods:Ninety-three patients were randomized into western medication group,acupuncture group,and combination group,with 31 cases in each.The patients in western medication group were treated with lipoic acid injection and mecobalamin injection/tablets.The patients in acupuncture group were treated with acupuncture,and the acupoints were selected according to the symptoms.The needles were retained for 30 min,once a day.The patients in combination group were treated with both western medication and acupuncture,specific methods as the above.The treatments were for 18 days in succession in all of three group.The motor nerve conduction velocity(MNCV) and sensory nerve conduction velocity(SNCV) of median nerve and common peroneal nerve,as well as the changes of symptoms and signs of patients were observed before and after treatment.The clinical effect was evaluated.Results:After treatment,the median nerve MNCV in the three groups,the median nerve SNCV and common peroneal nerve MNCV in acupuncture group and combination groups,and the common peroneal nerve SNCV in acupuncture group were all higher than those of before treatment,with significantly statistical differences(all P<0.05).After treatment,the MNCV and SNCV of median nerve and common peroneal nerve in combination group were higher than those in western medication group and acupuncture group,with significantly statistical differences(all P<0.05).After treatment,the number of patients in the three groups with the symptoms and signs was lower than that of before treatment.The effective rate in combination group was 96.8%(30/31),higher than those of western medication group,74.2%(23/31),and acupuncture group,83.8%(26/31),with significantly statistical differences(both P<0.05).Conclusion:Acupuncture combined with western medication in the treatment of diabetic peripheral neuropathy can improve the nerve conduction velocity and improve the symptoms and signs of diabetic patients,with a better effect than those of western medication and simple acupuncture.