• Par oncojornal02 dans Accueil le 5 Juin 2020 à 15:22

    Cardiac progenitors cellsfor vascular repair

     
    June 05, 2020
    Cardiac progenitors cellsfor vascular repair  

    The heart is the first functional organ to develop, and cardiomyocytes (cardiac muscle cells) are the essentialand specific-cell type that supports its function during the entire lifespan, being highly resistant to cell damage and aging. Cardiomyocytes occupy ≈ 80% of the volume of mammalian heart, however, they are relatively few in total number compared with non-myocyte cells (endothelial cells, smooth muscle cells, fibroblasts; ≈ 70% of total cardiac cells) [1]. Both myocytes and non-myocytes respond to physiological and pathological insults and their maladaptive responses are linked with the pathogenesis of the cardiac tissue. During the last decade, various studies have identified cardiac progenitor-like cells, including immature cardiomyocytes, that contribute to the low cardiomyocyte turnover (< 2% per year), decreasing their contribution in an age-dependent manner. While cardiac regenerative response is effective in embryo and neonatal period (until 7th day after birth), the regeneration is particularly limited from adolescence where ischemic injury lead to the formation of a fibrotic scar and to the reduction in the heart's pumping capacity in mice (reviewed in [2]). The majority of the research in the field of cardiac regeneration have been focused on limiting the death of cardiomyocytes and on looking for the source of de novo cardiomyocytes. Despite the remarkable exchange rate of endothelial cells in adult heart (>15% per year) and their essential functions, the cellular source of mature endothelial cells in homeostasis and after injury is not characterized. He et al. traced adult cardiac endothelial cells using a genetic lineage-tracing strategy based on fluorochrome expression. Lineage dilution analysis based on the presence or absence of fluorochrome-positive endothelial cells showed that preexisting endothelium (or endothelial-related cells) mediated the neovascularization after infarction [3]. It is important to note that these lineage-tracing experiments were realized based on one endothelial-related gene (cd31, cdh5) whose expression is not only restricted to mature endothelial cells. Therefore, it would be possible that cardiac progenitors which express endothelialrelated genes could mediate the neovascularization response to myocardial infarction. In this context, several studies have found cardiac progenitor cells located along cardiac vasculature such as Sca1+ adventitial and Gli1+ fibroblast-progenitor cells [4]. We recently identified a cell population with adult cardiac progenitor characteristics that expresses high level of BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) protein [5]. Polycomb complex BMI1 expression is widely linked to the regenerative capacity of adult tissues and identifies cells with progenitorrelated characteristics in several tissues. In the mammalian heart, Bmi1+ cardiac progenitors are a heterogeneous cell population (≈1x105 cells/ adult heart) located in perivascular position that contributes to the three main cardiac cell lineages in homeostasis, increasing this contribution after several types of injury [6, 7]. Surprisingly, genetic ablation of Bmi1+ cardiac progenitors in homeostasis did not provoke cardiac dysfunction or mice death, probably due to cell plasticity events as showed in other tissue adult stem cells. The role of Bmi1+ progenitor cells, however, became essential in the neovascularization process after myocardial infarction (from 15-days to 2-months), contributing up to 20% of new endothelial cells. Genetic ablation of Bmi1+ progenitors before infarction confirmed that they are necessary for cardiac physiological remodeling and their absence led to cardiac dysfunction and increased mice death [8]. Cardiac progenitors cellsfor vascular repair    Diego Herrero and  Antonio Bernad www.aging‐us.com                AGING 2019, Vol. 11, No. 5 Figure 1. Lineage‐specific cardiac progenitor cells. Overall, our results suggest that the aging and pathological damage of Bmi1+ cardiac progenitors could play an important role in heart aging, exacerbating certain pathological responses. Stimulation of endogenous Bmi1+ cardiac progenitor cells in the infarcted myocardium would help counteract the pathological remodeling by sustaining injury‐induced neovascularization. https://www.aging-us.com/issue/v11i5

    When public speak of contemporary medicine, accuracy plays one of the most significant roles and human lives are directly dependent on it. Likewise, any researches pertaining to medicine are required to comply with the top standards. The issue nowadays is that any results of researches can be published online and used as a reference without being properly verified and validated. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this challenge and attempted to create an alternative solution. That’s how a weekly oncology-focused research journal named “Oncotarget” has been founded back in 2010. The major principle of this journal is related to Altmetric scores that are used as a quality indicator. That helps both readers and authors to verify publications with Altmetric Article Reports that create “real-time feedback containing data summary related to a particular publication.” Oncotarget website has a complete publications list with respective scores above 100 as well as reports mentioned above. Mikhail (Misha) Blagosklonny proud to share his new approach and hopes it provides the required assistance to anybody, who has interest in oncology.
    “A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This article was released back in 2018 by Oncotarget and written by different experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and provides an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
    The article has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that majority of readers are aiming to comprehend the very meaning of it. Based on the Altmetric website, the score indicates “how many people have been exposed to and engaged with a scholarly output.” Hereby, the article about melanoma, was used for citations in different news articles 69 times. Moreover, it was quoted in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their report on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study 
    Another Oncotarget’s study with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This study has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a concise overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do receive helpful scientific facts. Oncotarget is proud to have the ability to share with online readers this highly appreciated and high-quality information, that is trustworthy and reliable.
     

     


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  • Par oncojornal02 dans Accueil le 5 Juin 2020 à 15:16

    Age-related changes in human sperm DNA integrity

     
    June 05, 2020

    Age-related changes in human sperm DNA integrity

    Abstract

    Abnormal standard semen characteristics and reduced sperm chromatin maturity can appear with increasing male age. However, the influence of paternal age on semen parameters is still controversial. Therefore, this study was designed to estimate the influence of paternal age not only on conventional semen characteristics but also on sperm DNA integrity. This research was carried out on ejaculated sperm cells obtained from men (n = 1124) aged ≥40 y and <40 y. Our data revealed a decreased semen volume and an increased percentage of DFI (sperm DNA fragmentation index) in older men compared to younger men in the entire study cohort, in men with normozoospermia and in men with abnormal semen parameters. Moreover, there was a higher incidence of sperm DNA damage (>10% DFI, low fertility potential) in the groups of men aged ≥40 y than in the groups of men aged <40 y. Older men had over twice the odds ratio for high sperm DNA damage as younger men. Our findings suggest a detrimental effect of advanced paternal age on sperm chromatin integrity. The data show that the evaluation of sperm DNA has greater clinical utility than standard semen analysis in case of male fertility potential assessment.

     

    Introduction

    Infertility has become a worldwide problem, affecting up to 20% of couples trying to conceive [1, 2]. In this context, a few important facts should be emphasized: 1) male factors (coexisting with female factors) contribute to infertility in up to 20–70% of cases, and one-third of these cases are due to male factors alone [1–3]; 2) an actual decline in semen quality over the past decades has been observed globally [4]; and 3) paternal age is rising, as an increasing number of men are decide to became a father at an older age [5, 6].

    It is known that the risk of poor reproductive outcomes can increase with a male age of >40 or even >35 y, commonly classified as advanced age. Age-dependent changes in male organism (e.g. vascular sufficiency, increase in incidence of systemic diseases and infections, disorders of histological structure of testes, decreased levels of sex hormones, oxidative stress, de novo mutations) are deleterious and the consequences of advanced paternal age include a prolonged waiting time to pregnancy, delayed embryo development in in vitro conditions, an increased incidence of embryo implantation failure and abortions, pregnancy problems and live birth outcome [7–9] (Figure 1). In addition, advanced paternal age also seems to affect children's health. There is a positive correlation between paternal age and the incidence of mental deprivation of offspring, such as those associated with the autism spectrum and diseases such as schizophrenia, especially when the paternal age is ≥40–50 y [10–13]. Furthermore, the frequency of genetic disorders, such as Klinefelter syndrome [14]; Down syndrome, when mother age is >35 y [15]; and autosomal dominant diseases such as Marfan syndrome (men >40 y), Pfeiffer and Crouzon syndrome (men >50 y), Apert syndrome (men >37 y), achondroplasia and neurofibromatosis type 1 rises in children of fathers >40 y. Unfortunately, the risk of central nervous system and breast cancers as well as leukaemia is growing [12]. More often, children with heart defects (e.g., ventricular septal defects, atrial septal defects, large vessel transposition), neural tube defects, anencephaly and tracheo-oesophageal fistula have been born to men >35, 40, and 45 y of age [13] (Figure 1) https://www.aging-us.com/article/102120/text


    When general population mention today’s medicine, precision plays one of the most significant roles and people’s lives are literally dependent on it. Likewise, any researches related to medicine are required to comply with the top standards. The challenge nowadays is that any recommendations of researches can be shared online and used as a reference without being adequately verified and approved. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this issue and tried to come up with an alternative solution. That’s how a weekly oncology-focused research journal called “Oncotarget” has been founded back in 2010. The main principle of this journal is based on Altmetric scores that are used as a quality measure. That allows both readers and authors to quality-check publications with Altmetric Article Reports that provide “real-time feedback containing data summary related to a particular publication.” Oncotarget website provides a full publications list with corresponding scores higher than 100 as well as reports mentioned above. Mikhail (Misha) Blagosklonny proud to share his new approach and hopes it creates the required assistance to anybody, who has interest in oncology.
    “A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This study was released back in 2018 by Oncotarget and written by various experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and provides an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
    The article has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that most of readers are willing to understand the very meaning of it. Based on the Altmetric website, the score indicates “how many people have been exposed to and engaged with a scholarly output.” Likewise, the article about melanoma, was utilized for citations in different news articles 69 times. In addition, it was quoted in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their news on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study 
    Another Oncotarget’s study with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This research has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a concise overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do receive helpful scientific facts. Oncotarget is glad to have the chance to share with online viewers this highly appreciated and top-quality information, that is trustworthy and reliable.

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  • Par oncojornal02 dans Accueil le 5 Juin 2020 à 15:12

    Accumulation of hypoxia-inducible factor-1α is limited by transcription-dependent depletion

     
    June 05, 2020

    Accumulation of hypoxia-inducible factor-1α is limited by transcription-dependent depletion

    http://vivo.med.cornell.edu/display/person484997

    abstract

    • In the presence of oxygen and iron, hypoxia-inducible factor (HIF-1alpha) is rapidly degraded via the prolyl hydroxylases (PHD)/VHL pathways. Given striking similarities between p53 and HIF-1alpha regulation, we previously suggested that HIF-1 transcriptionally initiates its own degradation and therefore inhibitors of transcription must induce HIF-1alpha. Under normoxia, while inducing p53, inhibitors of transcription did not induce HIF-1alpha. Under hypoxia or low iron (DFX), inhibitors of transcription dramatically super-induced HIF-1alpha. Removal of inhibitors resulted in outburst of the HIF-1-dependent transcription followed by depletion of HIF-1alpha. Although hypoxia/DFX induced PHD3, we excluded the PHD/VHL pathway in the regulation of HIF-1alpha under hypoxia/DFX. The transcription-dependent degradation of HIF-1alpha under hypoxia occurs via the proteasome and is accelerated by protein acetylation. Thus, HIF-1alpha is regulated by two distinct mechanisms. Under normoxia, HIF-1alpha is degraded via the classic PHD/VHL pathway, is expressed at low levels and therefore does not activate the feedback loop. But under hypoxia, HIF-1alpha accumulates and transcriptionally activates its own degradation that is independent from the PHD/VHL pathway.

    authors

    publication date

    • июля 14, 2005

    published in

    RESEARCH

    keywords

    • Academic Article

    IDENTITY

    Language

    • eng

    Digital Object Identifier (DOI)

    • 10.1038/sj.onc.1208636

    PubMed ID

    • 15897903
    When public mention contemporary medicine, accuracy plays one of the most crucial roles and human lives are directly dependent on it. Hence, any researches pertaining to medicine are necessary to meet the top standards. The problem nowadays is that any outcomes of researches can be posted online and used as a reference without being adequately checked and approved. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this problem and attempted to create an alternative solution. That’s how a weekly oncology-focused research journal named “Oncotarget” has been established back in 2010. The main principle of this journal is related to Altmetric scores that are used as a quality measure. That helps both readers and authors to validate publications with Altmetric Article Reports that generate “real-time feedback containing data summary related to a particular publication.” Oncotarget website has a complete publications list with corresponding scores above 100 as well as reports mentioned previously. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it provides the necessary help to anyone, who has interest in oncology.
    https://medium.com/@OncotargetImpact/ride-for-roswell-connects-us-all-in-making-a-difference-and-finding-a-cure-for-cancer-says-49471b50c657
    “A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This paper was released back in 2018 by Oncotarget and written by diversified experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
    The article has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that most of readers are willing to understand the very meaning of it. Based on the Altmetric website, the score indicates “how many people have been exposed to and engaged with a scholarly output.” Likewise, the publication about melanoma, was used for citations in various news articles 69 times. In addition, it was mentioned in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their report on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study
    Another Oncotarget’s research with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This research has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a short overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get useful scientific facts. Oncotarget is glad to have the chance to share with online customers this highly appreciated and high-quality information, that is trustworthy and reliable.
    https://twitter.com/blagosklonny?lang=en
     

     


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  • Par oncojornal02 dans Accueil le 5 Juin 2020 à 15:09

    GSK-3 as potential target for therapeutic intervention in cancer

     
    June 05, 2020

    GSK-3 as potential target for therapeutic intervention in cancer

    Issue 1-2, January 2015

    ABSTRACT

    The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified and studied in the regulation of glycogen synthesis. GSK-3 functions in a wide range of cellular processes. Aberrant activity of GSK-3 has been implicated in many human pathologies including: bipolar depression, Alzheimer’s disease, Parkinson’s disease, cancer, non-insulin-dependent diabetes mellitus (NIDDM) and others. In some cases, suppression of GSK-3 activity by phosphorylation by Akt and other kinases has been associated with cancer progression. In these cases, GSK-3 has tumor suppressor functions. In other cases, GSK-3 has been associated with tumor progression by stabilizing components of the beta-catenin complex. In these situations, GSK-3 has oncogenic properties. While many inhibitors to GSK-3 have been developed, their use remains controversial because of the ambiguous role of GSK-3 in cancer development. In this review, we will focus on the diverse roles that GSK-3 plays in various human cancers, in particular in solid tumors. Recently, GSK-3 has also been implicated in the generation of cancer stem cells in various cell types. We will also discuss how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTORC1, Ras/Raf/MEK/ERK, Wnt/beta-catenin, Hedgehog, Notch and others.https://www.oncotarget.com/article/2037/


    When general population mention modern medicine, precision plays one of the most important roles and human lives are literally dependent on it. Likewise, any researches pertaining to medicine are required to meet the top standards. The issue today is that any conclusions of researches can be posted online and used as a reference without being properly verified and validated. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this issue and tried to develop an alternative solution. That’s how a weekly oncology-focused research journal named “Oncotarget” has been established back in 2010. The key principle of this journal is based on Altmetric scores that are used as a quality indicator. That helps both readers and authors to quality-check publications with Altmetric Article Reports that create “real-time feedback containing data summary related to a particular publication.” Oncotarget website demonstrates a complete publications list with respective scores above 100 as well as reports mentioned previously. Mikhail (Misha) Blagosklonny proud to share his new approach and hopes it provides the required assistance to anybody, who has interest in oncology.
    “A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This paper was published back in 2018 by Oncotarget and completed by several experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study mentions that “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
    The article has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that most of readers are willing to comprehend the very meaning of it. Based on the Altmetric website, the score relates to “how many people have been exposed to and engaged with a scholarly output.” Likewise, the paper about melanoma, was utilized for citations in different news articles 69 times. Besides that, it was referred to in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their report on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study 
    Another Oncotarget’s research with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This article has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a brief overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do receive helpful scientific facts. Oncotarget is glad to have the chance to share with online customers this highly appreciated and high-quality information, that is trustworthy and reliable.

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  • Par oncojornal02 dans Accueil le 5 Juin 2020 à 15:01

    Rapamycin decelerates cellular senescence

     
    June 05, 2020

    Rapamycin decelerates cellular senescence

     
     

    Abstract

    When the cell cycle is arrested but cellular growth is not, then cells senesce, permanently losing proliferative potential. Here we demonstrated that the duration of cell cycle arrest determines a progressive loss of proliferative capacity.  In human and rodent cell lines, rapamycin (an inhibitor of mTOR) dramatically decelerated loss of proliferative potential caused by ectopic p21, p16 and sodium butyrate-induced p21. Thus, when the cell cycle was arrested by these factors in the presence of rapamycin, cells retained the capacity to resume proliferation, once p21, p16 or sodium butyrate were removed. While rapamycin prevented the permanent loss of proliferative potential in arrested cells, it did not force the arrested cells into proliferation. During cell cycle arrest, rapamycin transformed the irreversible arrest into a reversible condition. Our data demonstrate that senescence can be pharmacologically suppressed.https://www.tandfonline.com/doi/abs/10.4161/cc.8.12.8606


    When people refer to modern medicine, accuracy plays one of the most important roles and human lives are literally dependent on it. Likewise, any researches related to medicine are necessary to meet the highest standards. The problem nowadays is that any conclusions of researches can be posted online and used as a reference without being thoroughly checked and approved. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this issue and tried to generate an alternative solution. That’s how a weekly oncology-focused research journal named “Oncotarget” has been established back in 2010. The key principle of this journal is related to Altmetric scores that are used as a quality measure. That assists both readers and authors to verify publications with Altmetric Article Reports that generate “real-time feedback containing data summary related to a particular publication.” Oncotarget website provides a complete publications list with respective scores higher than 100 as well as reports discussed previously. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it provides the necessary assistance to anybody, who has interest in oncology.
    “A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This article was released back in 2018 by Oncotarget and written by diversified experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
    The paper has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that majority of readers are aiming to comprehend the very meaning of it. Based on the Altmetric website, the score indicates “how many people have been exposed to and engaged with a scholarly output.” Hereby, the paper about melanoma, was utilized for citations in various news articles 69 times. Besides that, it was mentioned in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their report on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study 
    Another Oncotarget’s study with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This research has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a concise overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get useful scientific facts. Oncotarget is glad to have the ability to share with online customers this highly appreciated and top-quality information, that is trustworthy and reliable.
     

     


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