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  1. AU=Salles Thiago A.
  2. AU="Saremi, S"
  3. AU="Heller, Regine"
  4. AU="He, Dongyuan"
  5. AU=Beer Arno
  6. AU="Wirth, Steffen"
  7. AU="Renza, Louis A."
  8. AU="Maleckis, Matiss"
  9. AU="Sridhar, Nikitha"
  10. AU=Daley G Q
  11. AU=Kawasaki Hideya
  12. AU="Pape, Terry D"
  13. AU="Mungra, Neelakshi"
  14. AU="Gurgu, Mihai"
  15. AU=Duan Surong
  16. AU="Kasmi, Yassine"
  17. AU="Katori, Machiko"
  18. AU="Richter, Susanna"
  19. AU="Oladipo, Aishat T"
  20. AU="Arango, Alissa"
  21. AU=Manjili Rose H AU=Manjili Rose H
  22. AU=Chen Hongtao
  23. AU="Soto Alsar, Javier"
  24. AU="Eric Woode"
  25. AU="Zybina O"
  26. AU="Reynolds, Cecil R"
  27. AU="Shahidul Khan"
  28. AU="Vasisth, Rashi"
  29. AU="Raju Mandal"
  30. AU="Owen, Noel L"
  31. AU=Liu Xiaolei
  32. AU="Fırıncıoğluları, Ali"
  33. AU="Piepel, Christiane"
  34. AU="Saremi, Saeid"
  35. AU="Dunxian She"

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  1. Artikel: Association of women-specific health factors in the severity of Parkinson's disease.

    Rao, Shilpa C / Li, Yadi / Lapin, Brittany / Pattipati, Sreya / Ghosh Galvelis, Kamalini / Naito, Anna / Gutierrez, Nicolas / Leal, Thiago Peixoto / Salim, Amira / Salles, Philippe A / De Leon, Maria / Mata, Ignacio F

    NPJ Parkinson's disease

    2023  Band 9, Heft 1, Seite(n) 86

    Abstract: Parkinson's disease (PD) is an age-related neurological disorder known for the observational differences in its risk, progression, and severity between men and women. While estrogen has been considered to be a protective factor in the development of PD, ... ...

    Abstract Parkinson's disease (PD) is an age-related neurological disorder known for the observational differences in its risk, progression, and severity between men and women. While estrogen has been considered to be a protective factor in the development of PD, there is little known about the role that fluctuations in hormones and immune responses from sex-specific health experiences have in the disease's development and severity. We sought to identify women-specific health experiences associated with PD severity, after adjusting for known PD factors, by developing and distributing a women-specific questionnaire across the United States and creating multivariable models for PD severity. We created a questionnaire that addresses women's specific experiences and their PD clinical history and deployed it through The Parkinson's Foundation: PD Generation. To determine the association between women-specific health factors and PD severity, we constructed multivariable logistic regression models based on the MDS-UPDRS scale and the participants' questionnaire responses, genetics, and clinical data. For our initial launch in November 2021, we had 304 complete responses from PD GENEration. Univariate and multivariate logistic modeling found significant associations between major depressive disorder, perinatal depression, natural childbirth, LRRK2 genotype, B12 deficiency, total hysterectomy, and increased PD severity. This study is a nationally available questionnaire for women's health and PD. It shifts the paradigm in understanding PD etiology and acknowledging how sex-specific experiences may contribute to PD severity. In addition, the work in this study sets the foundation for future research to investigate the factors behind sex differences in PD.
    Sprache Englisch
    Erscheinungsdatum 2023-06-05
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2819218-7
    ISSN 2373-8057
    ISSN 2373-8057
    DOI 10.1038/s41531-023-00524-x
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Potentiation of combined p19Arf and interferon-beta cancer gene therapy through its association with doxorubicin chemotherapy.

    Medrano, Ruan F V / Salles, Thiago A / Dariolli, Rafael / Antunes, Fernanda / Feitosa, Valker A / Hunger, Aline / Catani, João P P / Mendonça, Samir A / Tamura, Rodrigo E / Lana, Marlous G / Rodrigues, Elaine G / Strauss, Bryan E

    Scientific reports

    2022  Band 12, Heft 1, Seite(n) 13636

    Abstract: Balancing safety and efficacy is a major consideration for cancer treatments, especially when combining cancer immunotherapy with other treatment modalities such as chemotherapy. Approaches that induce immunogenic cell death (ICD) are expected to ... ...

    Abstract Balancing safety and efficacy is a major consideration for cancer treatments, especially when combining cancer immunotherapy with other treatment modalities such as chemotherapy. Approaches that induce immunogenic cell death (ICD) are expected to eliminate cancer cells by direct cell killing as well as activation of an antitumor immune response. We have developed a gene therapy approach based on p19Arf and interferon-β gene transfer that, similar to conventional inducers of ICD, results in the release of DAMPS and immune activation. Here, aiming to potentiate this response, we explore whether association between our approach and treatment with doxorubicin (Dox), a known inducer of ICD, could further potentiate treatment efficacy without inducing cardiotoxicity, a critical side effect of Dox. Using central composite rotational design analysis, we show that cooperation between gene transfer and chemotherapy killed MCA205 and B16F10 cells and permitted the application of reduced viral and drug doses. The treatments also cooperated to induce elevated levels of ICD markers in MCA205, which correlated with improved efficacy of immunotherapy in vivo. Treatment of subcutaneous MCA205 tumors associating gene transfer and low dose (10 mg/kg) chemotherapy resulted in inhibition of tumor progression. Moreover, the reduced dose did not cause cardiotoxicity as compared to the therapeutic dose of Dox (20 mg/kg). The association of p19Arf/interferon-β gene transfer and Dox chemotherapy potentiated antitumor response and minimized cardiotoxicity.
    Mesh-Begriff(e) Cardiotoxicity/drug therapy ; Cell Line, Tumor ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Genes, Neoplasm ; Humans ; Immunotherapy/methods ; Interferon-beta/genetics ; Neoplasms/drug therapy ; Neoplasms/genetics
    Chemische Substanzen Interferon-beta (77238-31-4) ; Doxorubicin (80168379AG)
    Sprache Englisch
    Erscheinungsdatum 2022-08-10
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-17775-y
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Association between pathogenic germline mutations in BRCA2 and ATM and tumor-infiltrating lymphocytes in primary prostate cancer.

    Kaur, Harsimar B / Vidotto, Thiago / Mendes, Adrianna A / Salles, Daniela C / Isaacs, William B / Antonarakis, Emmanuel S / Lotan, Tamara L

    Cancer immunology, immunotherapy : CII

    2021  Band 71, Heft 4, Seite(n) 943–951

    Abstract: Pathogenic mutations in homologous recombination (HR) DNA repair genes may be associated with increased tumor mutational burden and numbers of tumor-infiltrating lymphocytes (TIL). Though HR-deficient prostate tumors have been anecdotally associated with ...

    Abstract Pathogenic mutations in homologous recombination (HR) DNA repair genes may be associated with increased tumor mutational burden and numbers of tumor-infiltrating lymphocytes (TIL). Though HR-deficient prostate tumors have been anecdotally associated with improved responses to immunotherapy, it is unclear whether HR mutations or HR deficiency (HRD) scores predict for increased T-cell densities in this cancer. We evaluated 17 primary prostate tumors from patients with pathogenic germline BRCA2 mutations (gBRCA2) and 21 primary prostate tumors from patients with pathogenic germline ATM (gATM) mutations, which were compared to 19 control tumors lacking HR gene mutations, as well as the TCGA prostate cancer cohort. HRD score was estimated by targeted sequencing (gBRCA2 and gATM) or by SNP microarray (TCGA). Tumor-associated T-cell densities were assessed using validated automated digital image analysis of CD8 and FOXP3 immunostaining (gBRCA2 or gATM) or by methylCIBERSORT (TCGA). CD8 + and FOXP3 + T-cell densities were significantly correlated with each other in gBRCA2 and gATM cases. There was no significant difference between CD8 + or FOXP3 + TIL densities in gBRCA2 or gATM cases compared to controls. In the TCGA cohort, HRD score was associated with predicted CD8 + and FOXP3 + TILs. Associations were also seen for HRD score and TIL density among the germline-mutated cases. In contrast to mismatch repair-deficient primary prostate tumors, cancers from germline BRCA2 or ATM mutation carriers do not appear to be associated with elevated TIL density. However, measures of genomic scarring, such as HRD score, may be associated with increased tumor-infiltrating T-cells.
    Mesh-Begriff(e) Ataxia Telangiectasia Mutated Proteins/genetics ; BRCA2 Protein/genetics ; Biomarkers, Tumor/genetics ; Genes, BRCA2 ; Germ-Line Mutation ; Humans ; Lymphocytes, Tumor-Infiltrating ; Male ; Prostatic Neoplasms/genetics
    Chemische Substanzen BRCA2 Protein ; BRCA2 protein, human ; Biomarkers, Tumor ; ATM protein, human (EC 2.7.11.1) ; Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1)
    Sprache Englisch
    Erscheinungsdatum 2021-09-17
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s00262-021-03050-y
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  4. Artikel ; Online: An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss.

    Asrani, Kaushal / Woo, Juhyung / Mendes, Adrianna A / Schaffer, Ethan / Vidotto, Thiago / Villanueva, Clarence Rachel / Feng, Kewen / Oliveira, Lia / Murali, Sanjana / Liu, Hans B / Salles, Daniela C / Lam, Brandon / Argani, Pedram / Lotan, Tamara L

    Nature communications

    2022  Band 13, Heft 1, Seite(n) 6808

    Abstract: The mechanistic target of rapamycin complex 1 (mTORC1) integrates inputs from growth factors and nutrients, but how mTORC1 autoregulates its activity remains unclear. The MiT/TFE transcription factors are phosphorylated and inactivated by mTORC1 ... ...

    Abstract The mechanistic target of rapamycin complex 1 (mTORC1) integrates inputs from growth factors and nutrients, but how mTORC1 autoregulates its activity remains unclear. The MiT/TFE transcription factors are phosphorylated and inactivated by mTORC1 following lysosomal recruitment by RagC/D GTPases in response to amino acid stimulation. We find that starvation-induced lysosomal localization of the RagC/D GAP complex, FLCN:FNIP2, is markedly impaired in a mTORC1-sensitive manner in renal cells with TSC2 loss, resulting in unexpected TFEB hypophosphorylation and activation upon feeding. TFEB phosphorylation in TSC2-null renal cells is partially restored by destabilization of the lysosomal folliculin complex (LFC) induced by FLCN mutants and is fully rescued by forced lysosomal localization of the FLCN:FNIP2 dimer. Our data indicate that a negative feedback loop constrains amino acid-induced, FLCN:FNIP2-mediated RagC activity in renal cells with constitutive mTORC1 signaling, and the resulting MiT/TFE hyperactivation may drive oncogenesis with loss of the TSC2 tumor suppressor.
    Mesh-Begriff(e) Amino Acids/metabolism ; Feedback ; Lysosomes/metabolism ; Mechanistic Target of Rapamycin Complex 1/genetics ; Mechanistic Target of Rapamycin Complex 1/metabolism
    Chemische Substanzen Amino Acids ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1)
    Sprache Englisch
    Erscheinungsdatum 2022-11-10
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-34617-7
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Unraveling the interplay between dipeptidyl peptidase 4 and the renin-angiotensin system in heart failure.

    Arruda-Junior, Daniel F / Salles, Thiago A / Martins, Flavia L / Antonio, Ednei L / Tucci, Paulo J F / Gowdak, Luís Henrique W / Tavares, Caio A M / Girardi, Adriana C

    Life sciences

    2022  Band 305, Seite(n) 120757

    Abstract: Aims: Emerging evidence suggests the existence of a crosstalk between dipeptidyl peptidase 4 (DPP4) and the renin-angiotensin system (RAS). Therefore, combined inhibition of DPP4 and RAS may produce similar pharmacological effects rather than being ... ...

    Abstract Aims: Emerging evidence suggests the existence of a crosstalk between dipeptidyl peptidase 4 (DPP4) and the renin-angiotensin system (RAS). Therefore, combined inhibition of DPP4 and RAS may produce similar pharmacological effects rather than being additive. This study tested the hypothesis that combining an inhibitor of DPP4 with an angiotensin II (Ang II) receptor blocker does not provide additional cardioprotection compared to monotherapy in heart failure (HF) rats.
    Main methods: Male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were assigned into four groups and received vehicle (water), vildagliptin, valsartan, or both drugs, for four weeks by oral gavage.
    Key findings: Vildagliptin and valsartan in monotherapy reduced LV hypertrophy, alleviated cardiac interstitial fibrosis, and improved systolic and diastolic function in HF rats, with no additional effect of combination treatment. HF rats displayed higher cardiac and serum DPP4 activity and abundance than sham. Surprisingly, not only vildagliptin but also valsartan in monotherapy downregulated the catalytic function and expression levels of systemic and cardiac DPP4. Moreover, vildagliptin and valsartan alone or in combination comparably upregulate the components of the cardiac ACE2/Ang-(1-7)/MasR while downregulating the ACE/Ang II/AT1R axis.
    Significance: Vildagliptin or valsartan alone is as effective as combined to treat cardiac dysfunction and remodeling in experimental HF. DPP4 inhibition downregulates classic RAS components, and pharmacological RAS blockade downregulates DPP4 in the heart and serum of HF rats. This interplay between DPP4 and RAS may affect HF progression and pharmacotherapy.
    Mesh-Begriff(e) Animals ; Dipeptidyl Peptidase 4/metabolism ; Heart Failure/drug therapy ; Male ; Rats ; Rats, Wistar ; Renin-Angiotensin System ; Valsartan/pharmacology ; Valsartan/therapeutic use ; Vildagliptin/pharmacology ; Vildagliptin/therapeutic use
    Chemische Substanzen Valsartan (80M03YXJ7I) ; Dipeptidyl Peptidase 4 (EC 3.4.14.5) ; Vildagliptin (I6B4B2U96P)
    Sprache Englisch
    Erscheinungsdatum 2022-06-30
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2022.120757
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: An mTORC1-mediated negative feedback loop constrains amino acid-induced FLCN-Rag activation in renal cells with TSC2 loss

    Kaushal Asrani / Juhyung Woo / Adrianna A. Mendes / Ethan Schaffer / Thiago Vidotto / Clarence Rachel Villanueva / Kewen Feng / Lia Oliveira / Sanjana Murali / Hans B. Liu / Daniela C. Salles / Brandon Lam / Pedram Argani / Tamara L. Lotan

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Band 15

    Abstract: The MiT/TFE transcription factors are phosphorylated and inactivated by mTORC1. Here, authors demonstrate that TFEB is paradoxically hypophosphorylated and activated in cells with TSC2 loss due to impaired lysosomal recruitment of the FLCN:FNIP2 complex ... ...

    Abstract The MiT/TFE transcription factors are phosphorylated and inactivated by mTORC1. Here, authors demonstrate that TFEB is paradoxically hypophosphorylated and activated in cells with TSC2 loss due to impaired lysosomal recruitment of the FLCN:FNIP2 complex in renal cells.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2022-11-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Potentiation of combined p19Arf and interferon-beta cancer gene therapy through its association with doxorubicin chemotherapy

    Ruan F. V. Medrano / Thiago A. Salles / Rafael Dariolli / Fernanda Antunes / Valker A. Feitosa / Aline Hunger / João P. P. Catani / Samir A. Mendonça / Rodrigo E. Tamura / Marlous G. Lana / Elaine G. Rodrigues / Bryan E. Strauss

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Band 14

    Abstract: Abstract Balancing safety and efficacy is a major consideration for cancer treatments, especially when combining cancer immunotherapy with other treatment modalities such as chemotherapy. Approaches that induce immunogenic cell death (ICD) are expected ... ...

    Abstract Abstract Balancing safety and efficacy is a major consideration for cancer treatments, especially when combining cancer immunotherapy with other treatment modalities such as chemotherapy. Approaches that induce immunogenic cell death (ICD) are expected to eliminate cancer cells by direct cell killing as well as activation of an antitumor immune response. We have developed a gene therapy approach based on p19Arf and interferon-β gene transfer that, similar to conventional inducers of ICD, results in the release of DAMPS and immune activation. Here, aiming to potentiate this response, we explore whether association between our approach and treatment with doxorubicin (Dox), a known inducer of ICD, could further potentiate treatment efficacy without inducing cardiotoxicity, a critical side effect of Dox. Using central composite rotational design analysis, we show that cooperation between gene transfer and chemotherapy killed MCA205 and B16F10 cells and permitted the application of reduced viral and drug doses. The treatments also cooperated to induce elevated levels of ICD markers in MCA205, which correlated with improved efficacy of immunotherapy in vivo. Treatment of subcutaneous MCA205 tumors associating gene transfer and low dose (10 mg/kg) chemotherapy resulted in inhibition of tumor progression. Moreover, the reduced dose did not cause cardiotoxicity as compared to the therapeutic dose of Dox (20 mg/kg). The association of p19Arf/interferon-β gene transfer and Dox chemotherapy potentiated antitumor response and minimized cardiotoxicity.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2022-08-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: A presumptive association between obsessive compulsions and asymmetric temporal lobe atrophy: a case report.

    Paranhos, Thiago / Lucas, Tiago / de Salles, Antonio / Moll, Jorge / de Oliveira-Souza, Ricardo

    Journal of medical case reports

    2022  Band 16, Heft 1, Seite(n) 21

    Abstract: Background: The relatively isolated atrophy of the temporal lobes leads to a clinical radiological pattern, referred to as the temporal variant of frontotemporal dementia. While semantic dementia and behavioral variant frontotemporal dementia are ... ...

    Abstract Background: The relatively isolated atrophy of the temporal lobes leads to a clinical radiological pattern, referred to as the temporal variant of frontotemporal dementia. While semantic dementia and behavioral variant frontotemporal dementia are classically related to this syndrome, the logopenic variant of primary progressive aphasia has been less commonly reported. This case report aims to give a pictorial description of a case in which a patient with asymmetric temporal lobe atrophy presented with the logopenic variant of primary progressive aphasia and complex rituals of cleanliness.
    Case presentation: We report on the case of a 68-year-old, right-handed White woman with complex rituals and progressive speech impairment. The obsessive-compulsive rituals represented an exacerbation of lifelong preoccupations with cleanliness and orderliness that were praised by her relatives. Neuropsychological assessment revealed a striking impairment of language and memory, with relative sparing of tool-use praxis and visuospatial skills. Magnetic resonance imaging and
    Conclusions: This report gives a pictorial description of a temporal variant of frontotemporal dementia in a patient who presented with worsening of a lifelong obsessive-compulsive disorder and logopenic variant of primary progressive aphasia.
    Mesh-Begriff(e) Aged ; Aphasia, Primary Progressive ; Atrophy/pathology ; Female ; Frontotemporal Dementia ; Humans ; Magnetic Resonance Imaging ; Temporal Lobe/diagnostic imaging ; Temporal Lobe/pathology
    Sprache Englisch
    Erscheinungsdatum 2022-01-20
    Erscheinungsland England
    Dokumenttyp Case Reports ; Journal Article
    ZDB-ID 2269805-X
    ISSN 1752-1947 ; 1752-1947
    ISSN (online) 1752-1947
    ISSN 1752-1947
    DOI 10.1186/s13256-021-03228-z
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel: Unraveling the interplay between dipeptidyl peptidase 4 and the renin-angiotensin system in heart failure

    Arruda-Junior, Daniel F. / Salles, Thiago A. / Martins, Flavia L. / Antonio, Ednei L. / Tucci, Paulo J.F. / Gowdak, Luís Henrique W. / Tavares, Caio A.M. / Girardi, Adriana C.

    Life sciences. 2022 Sept. 15, v. 305

    2022  

    Abstract: Emerging evidence suggests the existence of a crosstalk between dipeptidyl peptidase 4 (DPP4) and the renin-angiotensin system (RAS). Therefore, combined inhibition of DPP4 and RAS may produce similar pharmacological effects rather than being additive. ... ...

    Abstract Emerging evidence suggests the existence of a crosstalk between dipeptidyl peptidase 4 (DPP4) and the renin-angiotensin system (RAS). Therefore, combined inhibition of DPP4 and RAS may produce similar pharmacological effects rather than being additive. This study tested the hypothesis that combining an inhibitor of DPP4 with an angiotensin II (Ang II) receptor blocker does not provide additional cardioprotection compared to monotherapy in heart failure (HF) rats. Male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were assigned into four groups and received vehicle (water), vildagliptin, valsartan, or both drugs, for four weeks by oral gavage. Vildagliptin and valsartan in monotherapy reduced LV hypertrophy, alleviated cardiac interstitial fibrosis, and improved systolic and diastolic function in HF rats, with no additional effect of combination treatment. HF rats displayed higher cardiac and serum DPP4 activity and abundance than sham. Surprisingly, not only vildagliptin but also valsartan in monotherapy downregulated the catalytic function and expression levels of systemic and cardiac DPP4. Moreover, vildagliptin and valsartan alone or in combination comparably upregulate the components of the cardiac ACE2/Ang-(1-7)/MasR while downregulating the ACE/Ang II/AT1R axis. Vildagliptin or valsartan alone is as effective as combined to treat cardiac dysfunction and remodeling in experimental HF. DPP4 inhibition downregulates classic RAS components, and pharmacological RAS blockade downregulates DPP4 in the heart and serum of HF rats. This interplay between DPP4 and RAS may affect HF progression and pharmacotherapy.
    Schlagwörter blood serum ; cardioprotective effect ; drug therapy ; fibrosis ; heart ; heart failure ; hypertrophy ; males ; radio waves ; renin-angiotensin system ; surgery
    Sprache Englisch
    Erscheinungsverlauf 2022-0915
    Erscheinungsort Elsevier Inc.
    Dokumenttyp Artikel
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2022.120757
    Datenquelle NAL Katalog (AGRICOLA)

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  10. Artikel ; Online: Assessment of MYC/PTEN Status by Gene-Protein Assay in Grade Group 2 Prostate Biopsies.

    Salles, Daniela C / Vidotto, Thiago / Faisal, Farzana A / Tosoian, Jeffrey J / Guedes, Liana B / Muranyi, Andrea / Bai, Isaac / Singh, Shalini / Yan, Dongyao / Shanmugam, Kandavel / Lotan, Tamara L

    The Journal of molecular diagnostics : JMD

    2021  Band 23, Heft 8, Seite(n) 1030–1041

    Abstract: This study leveraged a gene-protein assay to assess MYC and PTEN status at prostate cancer biopsy and examined the association with adverse outcomes after surgery. MYC gain and PTEN loss were simultaneously assessed by chromogenic in situ hybridization ... ...

    Abstract This study leveraged a gene-protein assay to assess MYC and PTEN status at prostate cancer biopsy and examined the association with adverse outcomes after surgery. MYC gain and PTEN loss were simultaneously assessed by chromogenic in situ hybridization and immunohistochemistry, respectively, using 277 Grade Group 2 needle biopsies that were followed by prostatectomy. The maximal size of cribriform Gleason pattern 4 carcinoma (CRIB), the presence of intraductal carcinoma (IDC), and percentage of Gleason pattern 4 carcinoma at biopsy were also annotated. MYC gain or PTEN loss was present in 19% and 18% of biopsies, respectively, whereas both alterations were present in 9% of biopsies. Tumors with one or both alterations were significantly more likely to have non-organ-confined disease (NOCD) at radical prostatectomy. In logistic regression models, including clinical stage, tumor volume on biopsy, and presence of CRIB/IDC, cases with MYC gain and PTEN loss remained at higher risk for NOCD (odds ratio, 6.23; 95% CI, 1.74-24.55; P = 0.005). The area under the curve for a baseline model using CAPRA variables (age, prostate-specific antigen, percentage of core involvement, clinical stage) was increased from 0.68 to 0.69 with inclusion of CRIB/IDC status and to 0.75 with MYC/PTEN status. Dual MYC/PTEN status can be assessed in a single slide and is independently associated with increased risk of NOCD for Grade Group 2 biopsies.
    Mesh-Begriff(e) Adult ; Aged ; Biomarkers, Tumor ; Humans ; Immunohistochemistry/methods ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Molecular Diagnostic Techniques/methods ; Molecular Diagnostic Techniques/standards ; Neoplasm Grading ; Neoplasm Staging ; PTEN Phosphohydrolase/genetics ; PTEN Phosphohydrolase/metabolism ; Prognosis ; Prostate/metabolism ; Prostate/pathology ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/mortality ; Protein Binding ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; Reproducibility of Results
    Chemische Substanzen Biomarkers, Tumor ; Proto-Oncogene Proteins c-myc ; PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67)
    Sprache Englisch
    Erscheinungsdatum 2021-05-29
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2000060-1
    ISSN 1943-7811 ; 1525-1578
    ISSN (online) 1943-7811
    ISSN 1525-1578
    DOI 10.1016/j.jmoldx.2021.05.006
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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