Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults.However,the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment.Ferropto...Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults.However,the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment.Ferroptosis is a recently discovered form of iron-dependent cell death that may have excellent prospect as chemosensitizer.The utilization of ferropotosis inducer Erastin could significantly mediate chemotherapy sensitization of Temozolomide and exert anti-tumor effects in glioblastoma.In this study,a combination of hydrogel-liposome nanoplatform encapsulatedwith Temozolomide and ferroptosis inducer Erastin was constructed.Theαvβ3 integrin-binding peptide cyclic RGD was utilized to modify codelivery system to achieve glioblastoma targeting strategy.As biocompatible drug reservoirs,cross-linked GelMA(gelatin methacrylamide)hydrogel and cRGD-coated liposome realized the sustained release of internal contents.In the modified intracranial tumor resection model,GelMA-liposome system achieved slow release of Temozolomide and Erastin in situ for more than 14 d.The results indicated that nanoplatform(T+E@LPs-cRGD+GelMA)improved glioblastoma sensitivity to chemotherapeutic temozolomide and exerted satisfactory anti-tumor effects.It was demonstrated that the induction of ferroptosis could be utilized as a therapeutic strategy to overcome drug resistance.Furthermore,transcriptome sequencing was conducted to reveal the underlying mechanism that the nanoplatform(T+E@LPs-cRGD+GelMA)implicated in.It is suggested that GelMA-liposome system participated in the immune response and immunomodulation of glioblastoma via interferon/PD-L1 pathway.Collectively,this study proposed a potential combinatory therapeutic strategy for glioblastoma treatment.展开更多
Psoriasis(Ps)and psoriatic arthritis(Ps A)are genetically complex diseases with strong genetic evidence.Recently,susceptibility genes for Ps and Ps A have been identified within the late cornified envelop(LCE)gene clu...Psoriasis(Ps)and psoriatic arthritis(Ps A)are genetically complex diseases with strong genetic evidence.Recently,susceptibility genes for Ps and Ps A have been identified within the late cornified envelop(LCE)gene cluster,especially the cluster 3(LCE3)genes.It is noteworthy that the deletion of LCE3B and LCE3C(LCE3C_LCE3B-del)is significantly associated with these two diseases.Gene-gene interactions between LCE3 genes and other genes are associated with Ps and Ps A.LCE3 genes also have pleiotropic effect on some autoimmune diseases,such as rheumatoid arthritis,atopic dermatitis and systemic lupus erythematosus.Further studies need to focus on the potential function of LCE3 genes in the pathogenesis of Ps and Ps A in the future.展开更多
Human height is a highly heritable trait in which multiple genes are involved. Recent genome-wide association studies(GWASs) have identified that COL11A1 is an important susceptibility gene for human height. To determ...Human height is a highly heritable trait in which multiple genes are involved. Recent genome-wide association studies(GWASs) have identified that COL11A1 is an important susceptibility gene for human height. To determine whether the variants of COL11A1 are associated with adult and children height,we analyzed splicing and coding single-nucleotide variants across COL11A1 through exome-targeted sequencing and two validation stages with a total 20,426 Chinese Han samples. A total of 105 variants were identified by exome-targeted sequencing, of which 30 SNPs were located in coding region. The strongest association signal was chr1_103380393 with P value of 4.8 * 10^(-7). Chr1_103380393 also showed nominal significance in the validation stage(P = 1.21 * 10^(-6)). Combined analysis of 16,738 samples strengthened the original association of chr1_103380393 with adult height(P_(combined)= 3.1 * 10^(-8)), with an increased height of 0.292sd(standard deviation) per G allele(95% CI:0.19-0.40). There was no evidence(P = 0.843) showing that chr1_103380393 altered child height in 3688 child samples. Only the group of 12-15 years showed slight significance with P value of 0.0258.This study firstly shows that genetic variants of COL11A1 contribute to adult height in Chinese Han population but not to children height, which expand our knowledge of the genetic factors underlying height variation and the biological regulation of human height.展开更多
基金supported by Natural Science Foundation of China(Grant NO.81972340,82173140,81871196)Shandong Provincial Natural Science Foundation,China(Grant No.ZR202010300086)Academic promotion program of Shandong First Medical University(Grant NO.2019LJ005)。
文摘Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults.However,the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment.Ferroptosis is a recently discovered form of iron-dependent cell death that may have excellent prospect as chemosensitizer.The utilization of ferropotosis inducer Erastin could significantly mediate chemotherapy sensitization of Temozolomide and exert anti-tumor effects in glioblastoma.In this study,a combination of hydrogel-liposome nanoplatform encapsulatedwith Temozolomide and ferroptosis inducer Erastin was constructed.Theαvβ3 integrin-binding peptide cyclic RGD was utilized to modify codelivery system to achieve glioblastoma targeting strategy.As biocompatible drug reservoirs,cross-linked GelMA(gelatin methacrylamide)hydrogel and cRGD-coated liposome realized the sustained release of internal contents.In the modified intracranial tumor resection model,GelMA-liposome system achieved slow release of Temozolomide and Erastin in situ for more than 14 d.The results indicated that nanoplatform(T+E@LPs-cRGD+GelMA)improved glioblastoma sensitivity to chemotherapeutic temozolomide and exerted satisfactory anti-tumor effects.It was demonstrated that the induction of ferroptosis could be utilized as a therapeutic strategy to overcome drug resistance.Furthermore,transcriptome sequencing was conducted to reveal the underlying mechanism that the nanoplatform(T+E@LPs-cRGD+GelMA)implicated in.It is suggested that GelMA-liposome system participated in the immune response and immunomodulation of glioblastoma via interferon/PD-L1 pathway.Collectively,this study proposed a potential combinatory therapeutic strategy for glioblastoma treatment.
文摘Psoriasis(Ps)and psoriatic arthritis(Ps A)are genetically complex diseases with strong genetic evidence.Recently,susceptibility genes for Ps and Ps A have been identified within the late cornified envelop(LCE)gene cluster,especially the cluster 3(LCE3)genes.It is noteworthy that the deletion of LCE3B and LCE3C(LCE3C_LCE3B-del)is significantly associated with these two diseases.Gene-gene interactions between LCE3 genes and other genes are associated with Ps and Ps A.LCE3 genes also have pleiotropic effect on some autoimmune diseases,such as rheumatoid arthritis,atopic dermatitis and systemic lupus erythematosus.Further studies need to focus on the potential function of LCE3 genes in the pathogenesis of Ps and Ps A in the future.
基金supported by the grant from the Youth National Science Foundation of China (No.31100908)
文摘Human height is a highly heritable trait in which multiple genes are involved. Recent genome-wide association studies(GWASs) have identified that COL11A1 is an important susceptibility gene for human height. To determine whether the variants of COL11A1 are associated with adult and children height,we analyzed splicing and coding single-nucleotide variants across COL11A1 through exome-targeted sequencing and two validation stages with a total 20,426 Chinese Han samples. A total of 105 variants were identified by exome-targeted sequencing, of which 30 SNPs were located in coding region. The strongest association signal was chr1_103380393 with P value of 4.8 * 10^(-7). Chr1_103380393 also showed nominal significance in the validation stage(P = 1.21 * 10^(-6)). Combined analysis of 16,738 samples strengthened the original association of chr1_103380393 with adult height(P_(combined)= 3.1 * 10^(-8)), with an increased height of 0.292sd(standard deviation) per G allele(95% CI:0.19-0.40). There was no evidence(P = 0.843) showing that chr1_103380393 altered child height in 3688 child samples. Only the group of 12-15 years showed slight significance with P value of 0.0258.This study firstly shows that genetic variants of COL11A1 contribute to adult height in Chinese Han population but not to children height, which expand our knowledge of the genetic factors underlying height variation and the biological regulation of human height.
