Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
New strategies in vaccine development are urgently needed to combat emerging influenza viruses and to reduce the risk of pandemic disease surfacing. Being conserved, the M2 e protein, is a potential candidate for univ...New strategies in vaccine development are urgently needed to combat emerging influenza viruses and to reduce the risk of pandemic disease surfacing. Being conserved, the M2 e protein, is a potential candidate for universal vaccine development against influenza A viruses. Mycobacterium tuberculosis Hsp70(mHsp70) is known to cultivate the function of immunogenic antigen-presenting cells, stimulate a strong cytotoxic T lymphocyte(CTL) response, and stop the induction of tolerance. Thus, in this study, a recombinant protein from the extracellular domain of influenza A virus matrix protein 2(M2e), was fused to the C-terminus of Mycobacterium tuberculosis Hsp70(Hsp70c), to generate a vaccine candidate. Humoral immune responses, IFN-γ-producing lymphocyte, and strong CTL activity were all induced to confirm the immunogenicity of M2 e.Hsp70c(Hsp70359–610). And challenge tests showed protection against H1N1 and H9N2 strains in vaccinated groups. Finally these results demonstrates M2 e.Hsp70c fusion protein can be a candidate for a universal influenza A vaccine.展开更多
Aim: To evaluate in vitro the effectiveness of several anti-infective agents alone or in combination against Mycobacterium smegmatis. Method: A convenient stratified sampling method was used to obtain selected anti-in...Aim: To evaluate in vitro the effectiveness of several anti-infective agents alone or in combination against Mycobacterium smegmatis. Method: A convenient stratified sampling method was used to obtain selected anti-infective agents. For individual drug samples, Minimum Inhibitory Concentrations (MIC) were obtained using the agar-well plate diffusion technique. Fractional Inhibitory Concentration Indices (FICI) were calculated for drug combinations using their MIC as obtained from the broth dilution method. Results: Of the thirty (30) anti-infective agents analyzed, ten (10) had MIC equivalent to or better than rifampicin (reference TB drug). Seven (7) drugs had MIC higher than rifampicin, while twelve (12) showed no growth inhibition of M. smegmatis. Analysis of the effect of drug combinations on M. smegmatis indicated that four (4) combinations, including rifampicin/ethambutol showed synergism. One (1) was additive, two (2) were indifferent and one (1) combination showed antagonism. Conclusion: Notable in the results obtained was the high effectiveness of the carbapenems in inhibiting the growth of M. smegmatis. Carbapenems, though not indicated for TB treatment, has a potential of playing a significant role in the treatment of tuberculosis. Also the drug combinations which showed synergism, especially those that involved the macrolide antibiotics, should further be investigated. These results have to be confirmed by in vivo clinical studies to define their roles in tuberculosis treatment.展开更多
目的:探讨不同浓度重组Canstatin蛋白对碱烧伤后小鼠角膜基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)及其组织抑制剂-2(tissue inhibitor of metalloproteinase-2,TIMP-2)表达的影响及其调节作用。方法:BALB/c小鼠60只随机分...目的:探讨不同浓度重组Canstatin蛋白对碱烧伤后小鼠角膜基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)及其组织抑制剂-2(tissue inhibitor of metalloproteinase-2,TIMP-2)表达的影响及其调节作用。方法:BALB/c小鼠60只随机分为实验组A、实验B及对照组C,每组20只。采用1mol/L氢氧化钠溶液烧伤小鼠右眼角膜,建立炎症性角膜碱烧伤动物模型,分别予以A组、B组重组Canstatin蛋白3μg/mL、5μg/mL点右眼,4次/d,对照组C组予以生理眼水点右眼。在碱烧伤后第1、3、7、14d以形态学分析评价角膜上皮损伤面积及新生血管生长的情况,并于碱烧伤后第1、3、7、14d应用Western-blot检测角膜MMP-2和TIMP-2的表达,增强化学发光法(ECL)对结果进行分析。结果:形态学分析显示,A组和B组小鼠在碱烧伤后第3d起各时间点角膜上皮缺损面积均小于对照组(P<0.01),角膜新生血管均得到抑制,CNV面积明显小于对照组(P<0.01)。Western-blot结果显示,碱烧伤后各时间点MMP-2的表达,A组和B组均明显低于对照组(P<0.01),TIMP-2的表达高于对照组(P<0.01),且A组和B组间MMP-2的表达在第14d比较差异有统计学意义(P<0.05),TIMP-2的表达在第7d及第14d比较差异有统计学意义(P<0.05)。结论:重组Canstatin蛋白可通过抑制角膜细胞及浸润的炎性细胞产生MMP-2,促进TIMP-2表达,从而抑制和延迟碱烧伤后角膜融解的发生和发展,对碱烧伤后角膜的重塑起着重要作用。展开更多
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
文摘New strategies in vaccine development are urgently needed to combat emerging influenza viruses and to reduce the risk of pandemic disease surfacing. Being conserved, the M2 e protein, is a potential candidate for universal vaccine development against influenza A viruses. Mycobacterium tuberculosis Hsp70(mHsp70) is known to cultivate the function of immunogenic antigen-presenting cells, stimulate a strong cytotoxic T lymphocyte(CTL) response, and stop the induction of tolerance. Thus, in this study, a recombinant protein from the extracellular domain of influenza A virus matrix protein 2(M2e), was fused to the C-terminus of Mycobacterium tuberculosis Hsp70(Hsp70c), to generate a vaccine candidate. Humoral immune responses, IFN-γ-producing lymphocyte, and strong CTL activity were all induced to confirm the immunogenicity of M2 e.Hsp70c(Hsp70359–610). And challenge tests showed protection against H1N1 and H9N2 strains in vaccinated groups. Finally these results demonstrates M2 e.Hsp70c fusion protein can be a candidate for a universal influenza A vaccine.
文摘Aim: To evaluate in vitro the effectiveness of several anti-infective agents alone or in combination against Mycobacterium smegmatis. Method: A convenient stratified sampling method was used to obtain selected anti-infective agents. For individual drug samples, Minimum Inhibitory Concentrations (MIC) were obtained using the agar-well plate diffusion technique. Fractional Inhibitory Concentration Indices (FICI) were calculated for drug combinations using their MIC as obtained from the broth dilution method. Results: Of the thirty (30) anti-infective agents analyzed, ten (10) had MIC equivalent to or better than rifampicin (reference TB drug). Seven (7) drugs had MIC higher than rifampicin, while twelve (12) showed no growth inhibition of M. smegmatis. Analysis of the effect of drug combinations on M. smegmatis indicated that four (4) combinations, including rifampicin/ethambutol showed synergism. One (1) was additive, two (2) were indifferent and one (1) combination showed antagonism. Conclusion: Notable in the results obtained was the high effectiveness of the carbapenems in inhibiting the growth of M. smegmatis. Carbapenems, though not indicated for TB treatment, has a potential of playing a significant role in the treatment of tuberculosis. Also the drug combinations which showed synergism, especially those that involved the macrolide antibiotics, should further be investigated. These results have to be confirmed by in vivo clinical studies to define their roles in tuberculosis treatment.
文摘目的:探讨不同浓度重组Canstatin蛋白对碱烧伤后小鼠角膜基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)及其组织抑制剂-2(tissue inhibitor of metalloproteinase-2,TIMP-2)表达的影响及其调节作用。方法:BALB/c小鼠60只随机分为实验组A、实验B及对照组C,每组20只。采用1mol/L氢氧化钠溶液烧伤小鼠右眼角膜,建立炎症性角膜碱烧伤动物模型,分别予以A组、B组重组Canstatin蛋白3μg/mL、5μg/mL点右眼,4次/d,对照组C组予以生理眼水点右眼。在碱烧伤后第1、3、7、14d以形态学分析评价角膜上皮损伤面积及新生血管生长的情况,并于碱烧伤后第1、3、7、14d应用Western-blot检测角膜MMP-2和TIMP-2的表达,增强化学发光法(ECL)对结果进行分析。结果:形态学分析显示,A组和B组小鼠在碱烧伤后第3d起各时间点角膜上皮缺损面积均小于对照组(P<0.01),角膜新生血管均得到抑制,CNV面积明显小于对照组(P<0.01)。Western-blot结果显示,碱烧伤后各时间点MMP-2的表达,A组和B组均明显低于对照组(P<0.01),TIMP-2的表达高于对照组(P<0.01),且A组和B组间MMP-2的表达在第14d比较差异有统计学意义(P<0.05),TIMP-2的表达在第7d及第14d比较差异有统计学意义(P<0.05)。结论:重组Canstatin蛋白可通过抑制角膜细胞及浸润的炎性细胞产生MMP-2,促进TIMP-2表达,从而抑制和延迟碱烧伤后角膜融解的发生和发展,对碱烧伤后角膜的重塑起着重要作用。
