Integrative molecular medicine最新文献

{"title":"The dynamic molecular landscape of malignant melanomas arising from congenital or common nevi","authors":"O. Harou, G. Tondeur, F. Descôtes, B. Balme, L. Depaepe, P. Bringuier, J. Caramel, L. Thomas, S. Dalle, Jonathan Lopez","doi":"10.15761/imm.1000370","DOIUrl":"https://doi.org/10.15761/imm.1000370","url":null,"abstract":"Background. Some cutaneous melanomas are arising from nevus, that can be either from the congenital or the common type. Objective: We aimed at comparing: i) the genomic landscape of small/medium congenital versus common nevi and ii) explore whether there is a different mutational pattern acquired during progression to melanoma between this two groups. Methods: We analysed BRAF, NRAS and TERT promoter status on micro-dissected melanocytic nevi and performed massively parallel sequencing on paired melanomas in 42 patients, half from the congenital and half from the common type. Results: Both common and small/medium congenital nevi mainly harboured BRAF V600E mutation at a similar rate. During melanoma progression, both groups acquired recurrent second hit TERT promoter mutations. Additional genomic alterations affecting oncogenic pathways also accumulated during progression, without a specific pattern. Conclusions: Small/medium congenital and common nevi shared the same mutational landscape and did not show any difference during progression to melanoma.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88351400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EC-SOD can prevent the chronic stages of pulmonary hypertension induced by hypoxia","authors":"Lopez Da Re JM, Zaghloul N, Kamesh A, R. A., Ochani K, Mansoor N, Miller Ej, A. M","doi":"10.15761/imm.1000389","DOIUrl":"https://doi.org/10.15761/imm.1000389","url":null,"abstract":"","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84233423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of a new genetic variant on FVII: C activity","authors":"Miolo Gianmaria, Caggiari Laura, De Zorzi Mariangela, Tedeschi Massimo, Tessitori Giovanni, Percesepe Antonio, Santeufemia Davide Adriano, V. Re, Steffan Agostino, Corona Giuseppe","doi":"10.15761/imm.1000381","DOIUrl":"https://doi.org/10.15761/imm.1000381","url":null,"abstract":"Background: The prediction of the phenotypic effect of a genetic variant represents a useful tool in genetic counseling. However, in coagulation factor VII (FVII) deficiency there is no straight correlation between genotype and phenotype since the residual FVII coagulant (FVII:C) activity associated with specific genetic variants does not always account for the observed clinical signs. Objective: to better describe the correlation between genotype and clinical phenotype of F7 gene we report a family case with a deficient FVII:C activity. Results and discussion: The case under investigation came to our attention during a genetic counseling attended by the proband, because she wanted to know, given the familiarity for breast cancer, her carrier probability for a BRCA1/2 pathogenetic variant. Pedigree analysis showed that besides cancer predisposition both the proband and her two sons suffered from recurrent spontaneous bleeding. Their coagulation pathway analysis was indicative of a FVII:C activity reduction with a pattern mimicking an autosomal dominant inheritance. Proband F7 sequencing showed the following heterozygous variants: c.1088C>A (p.Pro363His), c.-326_-325insCCTATATCC, c.-122T>C and c.1238G>A. The molecular analysis of her sons highlighted that c.1088C>A variant was in trans configuration. The occurrence of c.1088C>A variant alone was associated with 36% of FVII:C residual activity. Conversely, when this variant was in compound heterozygosity with c.-326_-325insCCTATATCC, c.-122T>C and c.1238G>A haplotype, the FVII:C residual activity further shrinked to 22%. c.1088C>A variant alone determined the most significant FVII:C activity reduction, however, when found in combination with c.-326_-325insCCTATATCC, c.122T>C and c.1238G>A haplotype an additive effect on the FVII:C activity phenotype was observed.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83054430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative proteomic analysis of the mouse ovary in response to GnIH and GnRH: An in vitro approach","authors":"Anushree Dave, Michael D. Powell, R. Sridaran, K. Tsutsui, A. Krishna","doi":"10.15761/IMM.1000358","DOIUrl":"https://doi.org/10.15761/IMM.1000358","url":null,"abstract":"The present study conducted proteomic analysis to identify ovarian proteins induced by GnRH/GnIH in comparison with untreated control mice. We used methods of 2-dimentional gel electrophoresis and LC-MS/MS for protein identification. Out of the 25 differentially expressed spots from each of the GnRH/GnIH treated ovaries we were randomly selected 18 protein spots identified by LC-MS/MS. The proteins 14-3-3, prohibitin and superoxide dismutase (SOD1) identified by LCMS/MS were further verified by Western blotting, which confirmed that GnRH/GnIH-induced changes in expression of 14-3-3, prohibitin and SOD1 were similar to the observations of proteomics. These selected proteins, 14-3-3, prohibitin and SOD1, were further have been the correlation with various ovarian activities, such as cell proliferation, survival or markers of apoptotic. Out of 18 identified GnRH-induced proteins, 9 showed up-regulations whereas other 9 showed down-regulations. This finding suggests that GnRH acts both by stimulating and inhibiting expression of protein. Interestingly, in the GnIH-induced ovary, 15 out of 18 proteins were significantly down-regulated suggesting that, GnIH acts mainly by inhibiting the expression of proteins involved in ongoing ovarian activities. Thus, the present study indicates many of the identified GnRH/GnIH-induced proteins are potentially linked to ovarian follicular development, atresia, steroidogenesis and cancer.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72604648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Ca2+/calmodulin kinase/AMP-activated protein kinase pathway regulates the lectin phaseolus vulgaris agglutinin induced NO production in human platelets","authors":"M. Signorello, G. Leoncini","doi":"10.15761/IMM.1000369","DOIUrl":"https://doi.org/10.15761/IMM.1000369","url":null,"abstract":"Previously it was shown that wheat germ agglutinin (WGA) and, at a minor extent, phaseolus vulgaris agglutinin (PHA), are able to induce platelet activation. Since the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO)/soluble guanylyl cyclase/cGMP/cGMP-dependent protein kinase (PKG) pathway is one of the major antiaggregating mechanism present in platelets, we tested the WGA or PHA effect on this pathway. It has been shown that platelets treated with WGA did not produce NO, while PHA stimulated NO production in a dose and time dependent manner. It has been found that the increased NO formation induced by PHA was dependent on eNOS phosphorylation/activation. The Ca2+/calmodulin-dependent kinase kinase/AMP activated protein kinase pathway seems to be greatly involved as STO-609 and Compound C, Ca2+/calmodulin protein kinase kinase/AMP kinase inhibitors respectively, cancelled eNOS phosphorylation induced by PHA. One crucial effect of NO and cGMP elevation is the activation of PKG, that can phosphorylate vasodilator-stimulated phosphoprotein (VASP). It was found that NO and cGMP elevation and VASP phosphorylation both on ser239 and thr278 were greatly stimulated by PHA and strongly inhibited by STO-609 and Compound C and by the eNOS inhibitor L-NAME. Thus, the CaMKK/AMPK pathway activated by PHA can regulate platelet activation stimulating the eNOS/NO/cGMP/ PKG signalling pathway. Abbreviations: ACC: acetylCoA carboxylase; AKT: protein kinase B; AMPK: AMP-activated protein kinase; CaMKK: Ca2+/calmodulin kinase kinase; eNOS: endothelial nitric oxide synthase; LKB1: liver kinase B1; NO: nitric oxide; PHA: phaseolus vulgaris agglutinin; PI3K: phosphatidylinositol 3 kinase; PKA: protein kinase A; PKG: protein kinase G; PLC: phospholipase C; VASP: vasodilator-stimulated phosphoprotein; WGA: wheat germ agglutinin. Introduction Platelet activation is involved in both haemostasis and thrombosis. When platelets encounter matrix proteins exposed by injury to the vessel wall, they stop on the exposed subendothelial surface, become activated showing morphological alterations, secrete the content of their granules and aggregate. Inhibition of platelet aggregation can be produced by the block of membrane receptors interaction with intracellular signalling pathways, by interfering with platelet-activating messengers or by potentiating the action of physiological platelet inhibitors such as endothelium derived PGI2 and nitric oxide (NO). These compounds activate adenylyl and guanylyl cyclases leading to cAMP and cGMP increase, respectively. The elevation of these two platelet cyclic nucleotides interferes with platelet activatory signalling pathways such as the intracellular Ca2+ elevation and the reorganization of the cytoskeleton. In human platelets NO formation depends on endothelial nitric oxide synthase (eNOS) activation. Platelet eNOS is now largely considered a Ca2+-independent enzyme and the phosphorylation/ dephosphorylation of ser1177 and/or thr4","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78856301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantum chemistry-based verification of antioxidative action of iodide in mitochondria","authors":"S. Yanagida, A. Kaname, Nobuyuki Murakami","doi":"10.15761/imm.1000388","DOIUrl":"https://doi.org/10.15761/imm.1000388","url":null,"abstract":"Background: In view of the well-known health-care qualities of aqueous potassium iodide (KI), quantum chemistry-based molecular modeling, i.e., density functional theory-based molecular modeling (DFT/MM) is undertaken to understand how iodide ion (I-) shows antioxidative properties on aqueous phosphorylation process in mitochondria (mt) of alive cells. Materials and methods: We perform DFT/MM equivalent to the quantum mechanics/molecular mechanics (QM/MM) method, by using the B3LYP exchangecorrelation function and the 6–31G(d) basis set with Spartan’18 (Wavefunction, Inc. Irvine, CA). Results: Iodide ion (I-) is in equilibrium with hydrogen iodide (HI), being oxidized to hypoiodous acid (HOI) by ground state oxygen (O2) or by hydrogen peroxide (HOOH) in aqueous systems. DFT/MM also verifies that van der Waals force (vdW) induces van der Waal (vdW) aggregation of hypoiodous acid (HOI) with phenylalanine, resulting in giving tyrosine, and that vdW works strongly on aggregation of tyrosine with HOI, leading to formation of 2,6-diiodotyrosine via 2-iodotyrosine. 2,6-Diiodotyrosine as homolog of thyroid hormones T4 is validated to show antioxidative action to evil active oxygen in mt, i.e., HOOH and hydroxyl radical.","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"493 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86795833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypertensive heart failure: A review of clinical status and meta-analyses of prognostic value of echocardiography and antihypertensive medication","authors":"Aref Albakri","doi":"10.15761/imm.1000349","DOIUrl":"https://doi.org/10.15761/imm.1000349","url":null,"abstract":"","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81117099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Thalassemia and renal complications. A narrative review of pathophysiologic mechanisms","authors":"C. Demosthenous, P. Eleftheriou, C. Apostolou, P. Sarafidis, V. Perifanis, E. Vlachaki","doi":"10.15761/IMM.1000340","DOIUrl":"https://doi.org/10.15761/IMM.1000340","url":null,"abstract":"","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"104 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80674025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An interesting case report of a giant bladder calculi in China","authors":"C. Hui, H. Maping, Huang Tianhai, Yang Xiaoyi, Nicholl Jj, L. Qingqing, L. Qiuling, J. Chonghe, X. Ke-ji","doi":"10.15761/IMM.1000345","DOIUrl":"https://doi.org/10.15761/IMM.1000345","url":null,"abstract":"Case Report In February 2018, a 52‐year‐old man was admitted to hospital due to a complaint of intermittent, painful voiding, terminal hematuria and interruption of the urinary stream. The patient's medical history revealed that some of these typical worsening discomforts had been observed twenty years prior to the present study. Due to the lack of sufficient medical and health conditions in the countryside, he only received the Chinese traditional treatment and did not seek any urologic treatments for more than 20 years. Abstract","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83153138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a novel compound that protects beta cells and islets from dysfunction associated with inflammatory cytokines","authors":"W. Grzesik, J. Weaver, Lindsey M. Glenn, Kaiwen Ma, J. Nadler, D. Taylor-Fishwick","doi":"10.15761/IMM.1000329","DOIUrl":"https://doi.org/10.15761/IMM.1000329","url":null,"abstract":"","PeriodicalId":94322,"journal":{"name":"Integrative molecular medicine","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83217385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}