Magnetic resonance imaging of extraocular rectus muscles abnormalities in acute acquired concomitant esotropia

AIM:To investigate the difference of medial rectus(MR)and lateral rectus(LR)between acute acquired concomitant esotropia(AACE)and the healthy controls(HCs)detected by magnetic resonance imaging(MRI).METHODS:A case-control study.Eighteen subjects with AACE and eighteen HCs were enrolled.MRI scanning data were conducted in target-controlled central gaze with a 3-Tesla magnetic resonance scanner.Extraocular muscles(EOMs)were scanned in contiguous image planes 2-mm thick spanning the EOM origins to the globe equator.To form posterior partial volumes(PPVs),the LR and MR cross-sections in the image planes 8,10,12,and 14 mm posterior to the globe were summed and multiplied by the 2-mm slice thickness.The data were classified according to the right eye,left eye,dominant eye,and non-dominant eye,and the differences in mean cross-sectional area,maximum cross-sectional area,and PPVs of the MR and LR muscle in the AACE group and HCs group were compared under the above classifications respectively.RESULTS:There were no significant differences between the two groups of demographic characteristics.The mean cross-sectional area of the LR muscle was significantly greater in the AACE group than that in the HCs group in the non-dominant eyes(P=0.028).The maximum cross-sectional area of the LR muscle both in the dominant and non-dominant eye of the AACE group was significantly greater than the HCs group(P=0.009,P=0.016).For the dominant eye,the PPVs of the LR muscle were significantly greater in the AACE than that in the HCs group(P=0.013),but not in the MR muscle(P=0.698).CONCLUSION:The size and volume of muscles dominant eyes of AACE subjects change significantly to overcome binocular diplopia.The LR muscle become larger to compensate for the enhanced convergence in the AACE.

Neonatal activation of Pxr results in persistent altered expression of DMEs in adult mice

OBJECTIVE To demonstrate the long-or short-term impacts of neonatal Pxr(pregnane X receptor) agonists exposureon DMEs(drug metabolism enzymes) expression in adulthood.METHODS C57 BL/6 mice(day 5,postnatal) were injected with different doses(0,50,100,150,200 mg·kg^(-1) ·d^(-1),constitutive 4 d) of PCN(pregnenolone-16 a-carbonitrile).Mice at different ages(day 5,10,15,25,postna.tal) were administrated with 200 mg·kg^(-1)·d^(-1) PCN in constitutive 4 d.All mice were sacrificed at day 60 after birth.Liver samples were collected for detecting the expression of Pxr target genes.RESULTS Compared with vehicle group,the significant inductions of Cyp2 b10,Cyp3a11 and Pxrwere observed in high dose groups(150,200 mg·kg^(-1) ·d^(-1),5-8 d after birth) both in male and female mice(n=4-9/group,P<0.05).Furthermore,high dose groups(200 mg·kg^(-1)·d^(-1),5-8 d after birth) were found to have higher mRNA expression levels of Cyp2a4,Ugt1a1,Abcc4,and Oatpla4 in female mice,while Papss2 in male mice compared with vehicle groups(n= 4-9/group,P<0.05).Interestingly,a decreased mRNA expression of Sult2a1 was identified in 200(5-8 d) groups(n=4-9/group,P<0.05).Consistent with these results,the protein expression of Cyp3a11 was only increased in 200(5-8 d) groups compared with the vehicle groups(n=3/group,P<0.05).Importantly,the persistent impacts on DMEs only occurred in day 5 and day 25 treatment groups,not day 10 and day 15 groups(n=4/group).CONCLUSION Neonatal Pxr activation has a long-term effect on the expression of DMEs in C57BL/6 mice.Dose and treatment exposure time are two key factors involved in this permanent alteration procedure.

Impacts of maternal LPS exposure on proinflammatory cytokines and DMEs expression in mouse offspring

OBJECTIVE To explore the effects of perinatal inflammation on the expression of proin.flammatory cytokines and DMEs(drug metabolism enzymes) in offspring mice.METHODS C57 BL/6 maternal mice were administrated with single dose 100 μg·kg^(-1) LPS(lipopolysaccharide) or saline(vehicle)during gestation(day 10 after fertilization).Offspring mice were sacrificed at 30 d after birth and liver samples were collected.Real-time PCR was adopted to test the mRNA expression of proinflammatory cytokines(Nrlp3 and IL-1β),nuclear receptors(Pxr and Car),and DMEs(Cyp3a11,2b10,1a2,and Ugt1a1).RESULTS Gender different expression of candidate genes was observed.The expression of Car,in the maternal injection of LPS groups,was significantly decreased in both female and male offspring(n=3-8/group,P<0.01).Concomitantly,a significantly lower expression of Cyp3a11 was found in both female and male offspring(P<0.01,P<0.05,respectively).Furthermore,the expression of Ugt1a1 was reduced in male offspring following maternal administration of LPS(P<0.01).In male offspring,Nrlp3 expression was specially decreased(P<0.05).Interestingly,there was an approximately 66% reduction in mRNA level of Cyp1a2 in female offspring(P<0.01),while in male offspring Cyp1a2 expression showed an increased trend(P>0.05) compared with vehicle group.The expression of Pxr,Cyp2b10,and IL-1β was no difference between LPS treatment group and vehicle group(P>0.05).CONCLUSION Maternal LPS administration affects the expression of proinflammatory cytokines,nuclear receptors and DMEs in mouse offspring.

GSK-3β inhibition induces cardioprotection via attenuating activation of NLRP3 inflammasome after acute myocardial infarction in rats

OBJECTIVE To observe the effects of glycogen synthase 3β(GSK-3β) in the regula.tion of NLRP3 inflammasome activation after acute myocardial infarction(MI) in Sprague Dawley(SD)rats.METHODS Ligation of the left anterior descending(LAD) in SD rats was used to establish an acute myocardial infarction model.SD rats were randomly divided into 3 groups(n=10,each group):sham group,MI group,and MI+SB group:the GSK-3β inhibitor(SB216763) was given 1 h by intrave.nous injection(0.6 mg·kg^(-1)·d-1) before surgery.The serum and heart tissue were collected to measure lactate dehydrogenase(LDH) and IL-1β content and mRNA and protein levels of NLRP3,ASC,Cas.pase-1,IL-1β and GSK-3β after 2 days and 7 days operation,respectively.RESULTS The serum levels of LDH and IL-1β in the MI group were significantly higher than those in the sham group(P<0.01),and the MI+SB group was obviously lower than the MI group(P<0.01).In addition,mRNA and protein levels of NNLRP3,ASC,Caspase-1,IL-1β and GSK-3β expressions in MI group were clearly increased(P<0.01) compared with those in sham group.These indicators were significantly decreased in SB + MI group(P<0.01).Interestingly,the indicators were all higher at 7 days than 2 days.CONCLUSION GSK-3β inhibition induces cardioprotection via attenuating the activation of NLRP3 inflammasome after the acute myocardial infarction in rats.

Engineering Multifunctional Thylakoid as an Oxygen Self-Supplying Photosensitizer for Esophageal Squamous Cell Carcinoma-Targeted Photodynamic Therapy

Photodynamic therapy(PDT)has emerged as an alternative treatment strategy for esophageal squamous cell carcinoma(ESCC).However,the clinical therapeutic efficiency of PDT is severely limited by poorly targeted photosensitizer delivery,insufficient oxygen supply,and neutralization by excessive glutathione(GSH)in tumor tissue.Herein,an engineered multifunctional thylakoid nanostructure,TMEM@PLGA@GA(abbreviated as TEPG),composed of a thylakoid membrane(TM)and ESCC cell membrane(EM)-fused biomembrane(TM-EM)shell and gambogic acid(GA)-loaded poly(lactic-co-glycolic acid)nanocore,was designed for enhanced PDT for ESCC.When fused with EM,TM-EM exhibits a tumor targeting advantage due to the homologous affinity of tumor membrane camouflage.The catalase present on TM-EM catalytically decomposes endogenous hydrogen peroxide into oxygen to alleviate hypoxia in the tumor tissue.Moreover,when TEPG was selectively internalized by ESCC cells,GA was released to consume the excessive intracellular GSH.Under infrared irradiation,the PDT effects were enhanced by the self-oxygen supply and GSH scavenging ability provided by TEPG.An in vivo study showed that TEPG effectively induced ESCC tumor cell apoptosis and greatly inhibited the growth of ESCC tumors under infrared irradiation.This study constructed an engineered multifunctional thylakoid-based nanomedicine as an integrated solution to enhance PDT for ESCC.

Skp2 is a novel regulator of LSD1 expression and function in gastric cancer

S-phase kinase-associated protein 2(Skp2)is a well-characterized oncoprotein localized mainly in the nucleus and cytoplasm.It is an integral component of SCFskp2 E3 ubiquitin ligase complex which confers substrate selectivity to the ligase by specifically targeting a distinct set of proteins destined for proteasomal degradation such as p21,p27,cyclin E,and c-Myc.1 Skp2 is crucial in a multitude of cellular processes including cell cycle,cell proliferation,apoptosis,differentiation,and survival.However,despite its immense and well-established role in ubiquitin-proteasome system-mediated protein turnover,much is unknown about the function of Skp2 independent of the ubiquitination pathway.Previously,Skp2 has been reported to regulate RhoA gene transcription and the p300 signaling pathway in an E3 ligase-independent manner.2Moreover,Skp2 also acts as a cofactor for c-Myc-regulated gene expression.

Additive effects of warming and grazing on fine-root decomposition and loss of nutrients in an alpine meadow

Fine-root decomposition is a critical process regulating ecosystem carbon cycles and affecting nutrient cycling and soil fertility.However,whether interaction between warming and grazing affects fine-root decomposition is still under-researched in natural grasslands.A two-factorial experiment with asymmetric warming(i.e.daytime vs.nighttime and growing season vs.nongrowing season)and moderate grazing(i.e.about average 50%forage utilization rate)was conducted to explore whether warming and grazing affect fine-root decomposition and loss of nutrients during a 2-year decomposition period in an alpine meadow on the Tibetan Plateau.Both warming and grazing facilitated carbon cycling through increase in fine-root decomposition,and influenced element cycling which varies among elements.The effects of warming and grazing on fine-root decomposition and loss of nutrients were additive.Both warming and grazing significantly increased cumulative percentage mass loss and total organic carbon loss of fine roots during the 2-year experiment.Only warming with grazing treatment reduced percentage nitrogen loss,whereas warming,regardless of grazing,decreased percentage phosphorus loss.Warming and grazing alone increased percentage loss of potassium,sodium,calcium and magnesium compared with control.There were no interactions between warming and grazing on fine-root decomposition and loss of nutrients.There was greater temperature sensitivity of decreased phosphorus loss than that of decreased nitrogen loss.Different temperature sensitivities of percentage loss of nutrients from fine-root decomposition would alter ratios of the available nutrients in soils,and may further affect ecosystem structure and functions in future warming.