简介：AbstractChronic obstructive pulmonary disease (COPD) has become the third-leading cause of death worldwide, which is a severe economic burden to the healthcare system. Chronic bronchitis is the most common condition that contributes to COPD, both locally and systemically. Neutrophilic inflammation predominates in the COPD airway wall and lumen. Logically, repression of neutrophilia is an essential fashion to COPD treatment. However, currently available anti-neutrophilic therapies provide little benefit in COPD patients and may have serious side effects. Thus, there is an urgent need to explore an effective and safe anti-neutrophilic approach that might delay progression of the disease. Sialic acid-binding immunoglobulin-like lectin (Siglec)-9 is a member of the Siglec cell surface immunoglobulin family. It is noteworthy that Siglec-9 is highly expressed on human neutrophils and monocytes. Ligation of Siglec-9 by chemical compounds or synthetic ligands induced apoptosis and autophagic-like cell death in human neutrophils. Furthermore, administration of antibody to Siglec-E, mouse functional ortholog of Siglec-9, restrained recruitment and activation of neutrophils in mouse models of airway inflammation in vivo. Given the critical role that neutrophils play in chronic bronchitis and emphysema, targeting Siglec-9 could be beneficial for the treatment of COPD, asthma, fibrosis, and related chronic inflammatory lung diseases.

简介：Astodeterminetheeffectofpost-remissiontherapyinprolongingsurvivalanddurationofremissionaftercompleteremission,50patientswithAPLIncompleteremissionInducedbyretinolcacid(RA)weredividedintothreegroupsrandomly:(A)30cases,treatedbyalternatechemotherapywithRA;(B)10cases,withRAalone;(C)10cases,onlywithchemotherapy.ThesurvivalcurvesshowedmatGroupAhadthesurvivaltimemorethan1yearIn87.4%,morethan2yearin80.7%.26/30casesweresurvivalandstillinremission,thesurvivalcurvetendtobeaplateauat16months.InGroupBmorethan1yearin45.7%.InGroupC,morethan1yearIn50%.(Keplan-Melerx2=8.93P<0.01).ThisresultshowedthatthealternatechemotherapywithRAforpost-InductionremissiontherapycouldbeusefultoImprovelong-termsurvivorsandtoprolongthedurationofremission.

简介：Inthepresentstudy,weaimedtodeterminethequalityofdifferentbrands(Test1–Test6)ofmefenamicacid,whicharecommerciallyavailableinlocalmarketofKarachi,Pakistan.Variousqualityevaluationtests,includingweightvariation,hardness,thickness,friability,disintegration,assayanddrugrelease,werecarriedout.Resultswerefoundtobeinacceptablelimits.Moreover,releaseprofileswerecomparedusingdifferentdissolutionmedia,suchasphosphatebufferpH6.8,7.4andbiorelevantmedia(FaSSGF,FaSSIF,FeSSIFandSCoF).ReleaseprofilesatpH6.8and7.4wereevaluatedbyone--wayANOVA,model-independentandmodel--dependentmethods.ResultsofANOVAshowedthatnosignificantdifferencewasfoundamongtesterandreferencebrands(Test1–Test6).Similarly,allthebrandswerefoundtobebestfittedwithWeibullmodel.

简介：无

简介：Oneofthechallengesinthefieldoftissueengineeringisthedevelopmentofbiomaterial/cellinteractions.Forthispurpose,theuseofbiologicalmaterialsintissueengineeringrequirestheapplicationofdifferentchemicalorphysicalproceduresforsurfacemodificationinordertoimprovethecellaffinityofbiomaterials.Wehavestudiedtheeffectsofonechemicaltreatmentandonephysicaltreatment:1-(3-dimethylaminopropyl)-3-ethylcarbodiimide(WSC)andentrapment.

简介：高度病原的鸟的流行性感冒H5N1流行病是重要公共健康危险。有哺乳动物的传播活动的遗传上设计的H5N1病毒加亮人的流行性感冒H5N1的潜在的风险流行。响应流行性感冒H5N1病毒理解天生的免疫系统的内在的原则将导致这些潜在地致命的病毒的改进预防和控制。γ；δ；当第一对微生物引起的感染防卫排队并且帮助在病毒的感染的早阶段期间开始适应有免疫力的回答，T房间行动。在这研究，我们调查了γ的分子的机制；δ；响应流行性感冒H5N1病毒的感染的T房间。我们发现从流行性感冒H5N1病毒的三不同紧张导出的recombinant红血球凝聚素(rHA)得到了γ的激活；δ；在外部血mononuclear房间(PBMC)有教养的T房间。两CD69的房间表面表示，γ上的一个早激活标记；δ；interferon-γ的T房间，和生产；(IFN-γ；)显著地被增加。尤其是，rHA导致蛋白质的γ；δ；T房间激活没被TCRγ调停；δ；，NKG2D或模式识别受体(PRR)或NKp46受体。有sialic酸受体的rHA蛋白质的相互作用可以在γ起一个关键作用；δ；T房间激活。我们的数据可以提供卓见进位于γ下面的机制；δ；响应有H5N1病毒的感染的T房间激活。

简介：

简介：AbstractBackground:The effects of keto acid (KA) supplements on Chinese patients receiving maintenance hemodialysis (MHD) are unclear. This study aimed to evaluate the effects of KA supplementation on nutritional status, inflammatory markers, and bioelectric impedance analysis (BIA) parameters in a cohort of Chinese patients with MHD without malnutrition.Methods:This was a prospective, randomized, controlled, single-center clinical study conducted in 2011 till 2014. Twenty-nine patients with MHD were randomly assigned to a control (n = 14) or a KA (n = 15) group. The control group maintained a dietary protein intake of 0.9 g/kg/day. The KA group received additional KA supplement (0.1 g/kg/day). BIA was used to determine the lean tissue mass, adipose tissue mass, and body cell mass. The patients’ nutritional status, dialysis adequacy, and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test.Results:The daily total energy intake for both groups was about 28 kcal/kg/day. After 6 months, the Kt/V (where K is the dialyzer clearance of urea, t is the dialysis time, and V is the volume of the distribution of urea) was 1.33 ± 0.25 in KA group, and 1.34 ± 0.25 in the control group. The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group. In addition, the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group. There were no significant differences between the groups with respect to the anthropometry parameters, dialysis adequacy, serum calcium and phosphorus levels, inflammatory markers, and amino-acid profiles, or in relation to the parameters determined by BIA. Both groups achieved dialysis adequacy and maintained nutritional status during the study.Conclusions:In this cohort of Chinese patients with MHD, the patients in the control group whose dietary protein intake was 0.9 g/kg/day and total energy intake was 28 kcal/kg/day, maintained well nutritional status during study period. The KA supplement(0.1 g/kg/day) did not improve the essential amino acid/non-essential amino acid ratio, nor did it change the patients’ mineral metabolism, inflammatory parameters, or body compositions.

简介：瞄准：为了学习在老鼠期间使酶RALDH2和CYP26b1产生代射变化的retinoic酸的表示模式，在mRNA和蛋白质的出生后的睾丸开发铺平。方法：实时聚合酶链反应和西方的污点分析被执行在出生后的白天在mRNA和蛋白质层次决定RALDH2和CYP26b1的相对数量1，5，10，20，并且在成年老鼠(70个天睾丸)。RALDH2和CYP26b1的阴囊的本地化用免疫组织化学试金在老鼠产后发育期间被检验。结果：Aldhla2抄本和它的蛋白质RALDH2开始在出生后的白天增加了10，并且整个出生后的白天在高水平留下了20到成人生活。Cyp26b1抄本和CYP26b1蛋白质没在鼠标期间显著地变化出生后的睾丸开发。RALDH2在出生后的1，5和10个天睾丸使用免疫组织化学试金是无法发现的。在出生后的白天20它在粗线期spermatocytes被检测。RALDH2的柔韧的表示在成年老鼠睾丸在圆spermatids被限制。在发展和成年睾丸，CYP26b1蛋白质被限制到仙子管状的肌上皮房间。结论：我们的结果显示那后面的出生，在细精管的retinoic酸的水平可能开始在出生后的白天增加10，并且整个出生后的白天维持高水平20到成人生活。

简介：AbstractObjective:To investigate the effects of rosmarinic acid (RA) on the DNA integrity and methylation levels of the H19 differentially methylated region (DMR) of freeze-dried human sperm after 1 week and 6 months of storage at 4℃.Methods:Semen samples from 15 healthy normospermic donors were used in this study. The samples were divided into five groups, including the control group with fresh sperm and four experimental groups with freeze-dried sperm (1-week storage with EGTA buffer solution, Group A; 1-week storage with EGTA buffer solution containing 105 μmol/L RA, Group B; 6-month storage with EGTA buffer solution, Group C; and 6-month storage with EGTA buffer solution containing 105 μmol/L RA, Group D). DNA integrity was evaluated using the sperm chromatin dispersion test. H19 DMR methylation levels were detected by bisulfite sequencing polymerase chain reaction.Results:After 1 week of storage, no differences in sperm DNA integrity were observed among Groups A, B, and controls (P > 0.05). After 6 months of storage, the sperm DNA integrity of Group D did not change significantly compared with that of the control group (P > 0.05), whereas that of Group C decreased significantly (P < 0.05). There were no differences in H19 DMR methylation levels among the five groups (P > 0.05).Conclusions:The DNA integrity of freeze-dried human sperm can be effectively protected by adding RA within 6 months, and the H19 DMR methylation level of human sperm can be maintained for 6 months after freeze-drying.

简介：Thestudyaimstoconfirmtheneuroregenerativeeffectsofbacterialmelanin(BM)oncentralnervoussysteminjuryusingaspecialstainingmethodbasedonthedetectionofCa~(2+)-dependentacidphosphataseactivity.Twenty-fourratswererandomlyassignedtoundergoeitherunilateraldestructionofsensorimotorcortex(groupI;n=12)orunilateralrubrospinaltracttransectionatthecervicallevel(C3–4)(groupⅡ;n=12).Ineachgroup,sixratswererandomlyselectedaftersurgerytoundergointramuscularinjectionofBMsolution(BMsubgroup)andtheremainingsixratswereintramuscularlyinjectedwithsaline(salinesubgroup).NeurologicaltestingconfirmedthatBMacceleratedtherecoveryofmotorfunctioninratsfrombothBMandsalinesubgroups.Twomonthsaftersurgery,Ca~(2+)-dependentacidphosphataseactivitydetectionincombinationwithChilingarian'scalciumadenosidetriphosphatemethodrevealedthatBMstimulatedthesproutingoffibersanddilatedthecapillariesinthebrainandspinalcord.TheseresultssuggestthatBMcanpromotetherecoveryofmotorfunctionofratswithcentralnervoussysteminjury;anddetectionofCa~(2+)-dependentacidphosphataseactivityisafastandeasymethodusedtostudytheregeneration-promotingeffectsofBMontheinjuredcentralnervoussystem.

简介：AbstractBackground:Coronavirus disease 2019 (Covid-19) remains a serious health threat worldwide. We aimed to investigate whether low molecular weight heparin (LMWH) can promote organ function recovery in moderate Covid-19 pneumonia patients.Methods:We initiated an LMWH protocol in Covid-19 patients with increased D-dimer, body mass index >30 kg/m2 or a history of diabetes from January 18, 2020 at Shanghai Public Health Clinical Center. In this retrospective study, we assigned moderate Covid-19 pneumonia patients admitted between January 18th and April 18, 2020 receiving the LMWH protocol to the LMWH group. Moderate patients who met the inclusion criteria but did not receive LMWH protocol were included in the control group by 1:2 propensity score matching. General clinical information, indicators for renal function, arterial blood gas analyses, arterial blood lactic acid content (mmol/L), and coagulation indexes at 0 day, 3 days, 7 days, and 11 days after admission were recorded and compared between the two groups.Results:There were 41 patients in the LMWH group and 82 patients in the control group. General information in both groups were similar. Compared to the control group, the arterial blood lactic acid content (mmol/L) at day 11 (1.3 [1.1, 1.7] vs. 1.2 [0.9, 1.3], P = 0.016) was reduced in the LMWH group. The estimated glomerular filtration rate (eGFR) in the LMWH group was higher than that in the control group at day 7 (108.54 [89.11, 128.17] vs. 116.85 [103.39, 133.47], P= 0.039) and day 11 (113.74 [94.49, 126.34] vs. 128.31 [112.75, 144.12], P = 0.003). The serum creatinine levels (Scr) in the LMWH group were lower than that in the control group at day 7 (62.13 [51.47, 77.64] vs. 55.49 [49.50, 65.75], P= 0.038) and day 11 (63.35 [50.17, 75.73] vs. 51.62 [44.62, 61.24], P = 0.005).Conclusions:LMWH treatment can reduce arterial blood lactic acid levels and improve eGFR in moderate Covid-19 pneumonia patients. Randomized controlled trials are warranted to further investigate this issue.Trial registration:ChiCTR.org.cn, ChiCTR2000034796.

简介：SpinaldorsalhornN-Methyl-D-asparticacidreceptor2B(NR2B)overexpressionplaysanimportantroleintheproductionandmaintenanceofneuropathicpain.BecausesmallinterferingRNA(siRNA)caninhibitNR2Bexpression,siRNAmayprovideanovelapproachtotreatneuropathicpainandpossiblynerveinjury.However,anefficientandsafevectorforNR2BsiRNAhasnotbeendiscov-ered.Thisstudyshowsthatawatersolublelipopolymer(WSLP)comprisedoflowmolecularweightpolyethyleneimine(PEI)andcholesterolcandeliversiRNAtargetingNR2Bforthetreatmentofneuropathicpain.ResultsshowthatintrathecalinjectionofWSLP/siRNAcomplexesfor3daysin-hibitNR2BgeneexpressionwithreductionsinmRNAandproteinlevelsby59%and54%,respec-tively,comparedwithcontrolrats(P<0.01).InjectionofWSLPcomplexedwithscrambledsiRNA,orPEIwithsiRNAdidnotshowthisinhibitoryeffect.Moreover,injectionofWSLP/siRNAcomplexessignificantlyrelievedneuropathicpainat3,7,12,and21days,whileinjectionofWSLPwithscrambledsiRNAorPEIwithsiRNAdidnot.TheseresultsdemonstratethatWSLPcanefficientlydeliversiRNAtargetingNR2Binvivoandrelieveneuropathicpain.

简介：AristolochiaeFructus,aChineseherbalmedicinederivedfromthefruitofAristolochiacontortaBge.,containsnephrotoxicaristolochicacidanalogues(AAAs).Accordingtoancientmedicaltexts,variousmedicinalpartsofthefruitofA.contortawereeverused.Inordertorevealwhichpartcouldbesafelyandeffectivelyused,itisnecessarytoanalyzethechemicalprofilesofdifferentmedicinalparts.HereinwecomparedthechemicalcompositionsanddeterminedaristolochicacidI(AA-I)andaristolochicacidII(AA-II)inthefourpartsviz.outerpericarp,innerpericarp,septum,andseed.Ultra-highperformanceliquidchromatographyequippedwithquadrupoletime-of-flightmassspectrometry(UHPLC-QTOF-MS)wasappliedforchemicalprofiling.Ultra-highperformanceliquidcoupledwithtriplequadrupolemassspectrometry(UHPLC-QqQ-MS)wasemployedtoquantifyAA-IandAA-IIindifferentparts.Itwasfoundthatthechemicalcompositionsofthefourpartsvariedbothqualitativelyandquantitatively.Atotalof10AAAs,including5aristolochicacidsand5aristolactams,togetherwith3alkaloids,wereunambiguouslyortentativelyidentifiedbyUHPLC-QTOF-MS.ThequantitativelyanalyticalresultsobtainedbyUHPLC-QqQ-MSshowedthatAA-IandAA-IIexclusivelyaccumulateintheseedsofA.contorta.Thesefindingsprovidesupportingdatafortherationalselectionofmedicinalparts.

简介：AbstractBackground:Mounting evidence, consistent with our previous study, showed that γ-aminobutyric acid type A receptor (GABAAR) played an indispensable role in airway inflammation and mucus hypersecretion in asthma. Monocyte chemotactic protein-inducing protein 1 (MCPIP1) was a key negative regulator of inflammation. Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases. However, the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied. This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells, and its potential mechanism.Methods:In vivo, mice were sensitized and challenged by ovalbumin (OVA) to induce asthma. Airway inflammation and mucus secretion were analyzed. In vitro, BEAS-2B cells were chosen. Interleukin (IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells. MCPIP1 Lentiviral vector (LA-MCPIP1) and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells, respectively. MCP-1, thymic stromal lymphopoietin (TSLP), mucin 5AC (MUC5AC), MCPIP1, and GABAARβ2 expressions were measured in both lung and BEAS-2B cells. Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells.Results:MCPIP1 was up-regulated by LA-MCPIP1 (P < 0.001) and plasmid-MCPIP1 (P < 0.001) in lung and cells, respectively. OVA-induced airway inflammation and mucus hypersecretion, OVA-enhanced MCP-1, TSLP, MUC5AC, and GABAARβ2 expressions, and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice (all P < 0.001). IL-13-enhanced MCP-1, TSLP, MUC5AC, and GABAARβ2 expressions, and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells (all P < 0.001).Conclusion:The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells, involving GABAAR signaling pathway.

简介：AbstractBackground:Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib, are widely used to treat non-small cell lung cancer (NSCLC). However, acquired resistance is unavoidable, impairing the anti-tumor effects of EGFR-TKIs. It is reported that histone deacetylase (HDAC) inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy. However, whether the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) can overcome erlotinib-acquired resistance is not fully clear.Methods:An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures. NSCLC cells were co-cultured with SAHA, erlotinib, or their combination, and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting. Finally, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was assessed by western blotting.Results:The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line. PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells, and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells. Furthermore, treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone.Conclusions:PTEN deletion is closely related to acquired resistance to EGFR-TKIs, and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy. SAHA enhances the suppressive effects of erlotinib in lung cancer cells, increasing cellular apoptosis and PTEN expression. SAHA can be a potential adjuvant to erlotinib treatment, and thus, can improve the efficacy of NSCLC therapy.

简介：RecombinanthumanGABAAreceptorswereinvestigatedinvitrobycoexpressionofcDNAscodingforα1,β2andγ2subunitsinthebaculovirus/Sf-9insectcellsystem,Asingleaminoacidexchangeα1(asparaticacid151toasparaginorα1(threonine149toglutamine)intheN-terminal,extracellularpartoftheα1subunitinducedabout10folddecreaseinanantagonistpitrazepineaffinity.OtherGABAAreceptorligandshadlittledifferenceintheiraffinity.Itwaslikelythat151and149aminoacidresidueswereessentialforthebindingaffinityandefficacyofpitrazepinetoGABAAreceptorcombinationscontainiαααααααααnganα1subunit.