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101.
Radhika Kapoor Christina Anna Stratopoulou Marie-Madeleine Dolmans 《International journal of molecular sciences》2021,22(21)
Endometriosis is a female reproductive disorder characterized by growth of uterine cells and tissue in distant sites. Around 2–10% of women experience this condition during reproductive age, 35–50% of whom encounter fertility issues or pain. To date, there are no established methods for its early diagnosis and treatment, other than surgical procedures and scans. It is difficult to identify the disease at its onset, unless symptoms such as infertility and/or pain are present. Determining the mechanisms involved in its pathogenesis is vital, not only to pave the way for early identification, but also for disease management and development of less invasive but successful treatment strategies. Endometriosis is characterized by cell proliferation, propagation, evasion of immunosurveillance, and invasive metastasis. This review reports the underlying mechanisms that are individually or collectively responsible for disease establishment and evolution. Treatment of endometriosis mainly involves hormone therapies, which may be undesirable or have their own repercussions. It is therefore important to devise alternative strategies that are both effective and cause fewer side effects. Use of phytochemicals may be one of them. This review focuses on pharmacological inhibitors that can be therapeutically investigated in terms of their effects on signaling pathways and/or mechanisms involved in the pathogenesis of endometriosis. 相似文献
102.
Sarah Meister Laura Hahn Susanne Beyer Corinna Paul Sophie Mitter Christina Kuhn Viktoria von Schnfeldt Stefanie Corradini Kritika Sudan Christian Schulz Theresa Maria Kolben Sven Mahner Udo Jeschke Thomas Kolben 《International journal of molecular sciences》2021,22(22)
The aim of this study was to analyze the expression of peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RxRα), a binding heterodimer playing a pivotal role in the successful trophoblast invasion, in the placental tissue of preeclamptic patients. Furthermore, we aimed to characterize a possible interaction between PPARγ and H3K4me3 (trimethylated lysine 4 of the histone H3), respectively H3K9ac (acetylated lysine 9 of the histone H3), to illuminate the role of histone modifications in a defective trophoblast invasion in preeclampsia (PE). Therefore, the expression of PPARγ and RxRα was analyzed in 26 PE and 25 control placentas by immunohistochemical peroxidase staining, as well as the co-expression with H3K4me3 and H3K9ac by double immunofluorescence staining. Further, the effect of a specific PPARγ-agonist (Ciglitazone) and PPARγ-antagonist (T0070907) on the histone modifications H3K9ac and H3K4me3 was analyzed in vitro. In PE placentas, we found a reduced expression of PPARγ and RxRα and a reduced co-expression with H3K4me3 and H3K9ac in the extravillous trophoblast (EVT). Furthermore, with the PPARγ-antagonist treated human villous trophoblast (HVT) cells and primary isolated EVT cells showed higher levels of the histone modification proteins whereas treatment with the PPARγ-agonist reduced respective histone modifications. Our results show that the stimulation of PPARγ-activity leads to a reduction of H3K4me3 and H3K9ac in trophoblast cells, but paradoxically decreases the nuclear PPARγ expression. As the importance of PPARγ, being involved in a successful trophoblast invasion has already been investigated, our results reveal a pathophysiologic connection between PPARγ and the epigenetic modulation via H3K4me3 and H3K9ac in PE. 相似文献
103.
Cardiomyopathies (CMPs) are a heterogeneous group of myocardial diseases accountable for the majority of cases of heart failure (HF) and/or sudden cardiac death (SCD) worldwide. With the recent advances in genomics, the original classification of CMPs on the basis of morphological and functional criteria (dilated (DCM), hypertrophic (HCM), restrictive (RCM), and arrhythmogenic ventricular cardiomyopathy (AVC)) was further refined into genetic (inherited or familial) and acquired (non-inherited or secondary) forms. Despite substantial progress in the identification of novel CMP-associated genetic variations, as well as improved clinical recognition diagnoses, the functional consequences of these mutations and the exact details of the signaling pathways leading to hypertrophy, dilation, and/or contractile impairment remain elusive. To date, global research has mainly focused on the genetic factors underlying CMP pathogenesis. However, growing evidence shows that alterations in molecular mediators associated with the diagnosis of CMPs are not always correlated with genetic mutations, suggesting that additional mechanisms, such as epigenetics, may play a role in the onset or progression of CMPs. This review summarizes published findings of inherited CMPs with a specific focus on the potential role of epigenetic mechanisms in regulating these cardiac disorders. 相似文献
104.
Ulrich Koller Stefan Hainzl Thomas Kocher Clemens Hüttner Alfred Klausegger Christina Gruber Elisabeth Mayr Verena Wally Johann W. Bauer Eva M. Murauer 《International journal of molecular sciences》2015,16(1):1179-1191
Spliceosome-mediated RNA trans-splicing has become an emergent tool for the repair of mutated pre-mRNAs in the treatment of genetic diseases. RNA trans-splicing molecules (RTMs) are designed to induce a specific trans-splicing reaction via a binding domain for a respective target pre-mRNA region. A previously established reporter-based screening system allows us to analyze the impact of various factors on the RTM trans-splicing efficiency in vitro. Using this system, we are further able to investigate the potential of antisense RNAs (AS RNAs), presuming to improve the trans-splicing efficiency of a selected RTM, specific for intron 102 of COL7A1. Mutations in the COL7A1 gene underlie the dystrophic subtype of the skin blistering disease epidermolysis bullosa (DEB). We have shown that co-transfections of the RTM and a selected AS RNA, interfering with competitive splicing elements on a COL7A1-minigene (COL7A1-MG), lead to a significant increase of the RNA trans-splicing efficiency. Thereby, accurate trans-splicing between the RTM and the COL7A1-MG is represented by the restoration of full-length green fluorescent protein GFP on mRNA and protein level. This mechanism can be crucial for the improvement of an RTM-mediated correction, especially in cases where a high trans-splicing efficiency is required. 相似文献
105.
Cover Picture: Discovery of MK‐8970: An Acetal Carbonate Prodrug of Raltegravir with Enhanced Colonic Absorption (ChemMedChem 2/2015) 下载免费PDF全文
Dr. Abbas M. Walji Dr. Rosa I. Sanchez Dr. Sophie‐Dorothee Clas Dr. Rebecca Nofsinger Dr. Manuel de Lera Ruiz Dr. Jing Li Dr. Amrithraj Bennet Christopher John Dr. David Jonathan Bennett Dr. John M. Sanders Christina N. Di Marco Somang Hope Kim Dr. Jaume Balsells Scott S. Ceglia Dr. Qun Dang Kimberly Manser Becky Nissley Dr. John S. Wai Dr. Michael Hafey Junying Wang Gene Chessen Dr. Allen Templeton Dr. John Higgins Dr. Ronald Smith Dr. Yunhui Wu Dr. Jay Grobler Dr. Paul J. Coleman 《ChemMedChem》2015,10(2):213-213
106.
Christina Siakati Alexios P. Douvalis Panagiotis Ziogas Arne Peys Yiannis Pontikes 《Journal of the American Ceramic Society》2020,103(3):2173-2184
Aiming to reduce the carbon dioxide emissions associated with cement production, alternative binders such as inorganic polymers currently receive substantial attention and slags from the non-ferrous metallurgy are promising precursors. However, studies that correlate their chemistry and crystallinity with the newly formed binder remain limited. In this work, the effect of three different solidification methods on glass formation and reactivity of FeOx–SiO2 slags, as well as on the molecular structure of the resultant Fe-rich inorganic polymers, was investigated. The inorganic polymers were synthesized by mixing the slags (approximate molar ratio FeO/SiO2 = 1.6) with an alkali silicate solution (molar ratios SiO2/Na2O = 1.6 and H2O/Na2O = 25). Results demonstrated that higher cooling rates promoted higher glass formation and faster reaction kinetics when the slags were activated. 57Fe Mössbauer spectroscopy indicated that all the slags consisted predominantly of Fe2+ ions with a minor amount of Fe3+ ions, regardless of the variability in glass content. The binder phase of all inorganic polymers consisted of iron in both Fe2+ and Fe3+ states, after 28 days of curing. After pulverizing the inorganic polymer pastes and exposing the powder to air for 28 additional days, the Fe2+ state in the binder transformed to Fe3+. The compressive strength evolution of the three slags showed that the 2-day strength was higher for the samples with a higher amorphous fraction, while after 28 days, this influence was less pronounced. 相似文献
107.
Dr. Tom Baladi Dr. Nedra Hamouda-Tekaya Dr. Leticia Christina Pires Gonçalves Dr. Stéphane Rocchi Dr. Cyril Ronco Dr. Rachid Benhida 《ChemMedChem》2020,15(13):1113-1117
Sulfonylguanidines are interesting bioactive compounds with a broad range of applications in the treatment of different pathologies. 2-Aminobenzazole-based structures are well employed in the development of new anticancer drugs. Two series of novel N-benzazol-2-yl-N′-sulfonyl guanidine derivatives were synthesized with the sulfonylguanidine in either an extra- or intracyclic frame. They were evaluated for their antiproliferative activity against malignant melanoma tumor cells, thus allowing structure-activity relationships to be defined. Additionally, NCI-60 screening was performed for the best analogue to study its efficiency against a panel of other cancer cell lines. The stability profile of this promising compound was then validated. During the synthetic process, an unexpected new deamidination of the sulfonylguanidine towards sulfonamide function was also identified. 相似文献
108.
Anna Lfdahl Gran Tornling Jenny Wign Anna-Karin Larsson-Callerfelt Christina Wengln Gunilla Westergren-Thorsson 《International journal of molecular sciences》2021,22(1)
Interstitial lung disease (ILD) encompasses a heterogeneous group of more than 200 conditions, of which primarily idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia, hypersensitivity pneumonitis, ILD associated with autoimmune diseases and sarcoidosis may present a progressive fibrosing (PF) phenotype. Despite different aetiology and histopathological patterns, the PF-ILDs have similarities regarding disease mechanisms with self-sustaining fibrosis, which suggests that the diseases may share common pathogenetic pathways. Previous studies show an enhanced activation of serotonergic signaling in pulmonary fibrosis, and the serotonin (5-HT)2 receptors have been implicated to have important roles in observed profibrotic actions. Our research findings in support by others, demonstrate antifibrotic effects with 5-HT2B receptor antagonists, alleviating several key events common for the fibrotic diseases such as myofibroblast differentiation and connective tissue deposition. In this review, we will address the potential role of 5-HT and in particular the 5-HT2B receptors in three PF-ILDs: ILD associated with systemic sclerosis (SSc-ILD), ILD associated with rheumatoid arthritis (RA-ILD) and IPF. Highlighting the converging pathways in these diseases discloses the 5-HT2B receptor as a potential disease target for PF-ILDs, which today have an urgent unmet need for therapeutic strategies. 相似文献
109.
Metastasis to the bone is a common feature of many cancers including those of the breast, prostate, lung, thyroid and kidney. Once tumors metastasize to the bone, they are essentially incurable. Bone metastasis is a complex process involving not only intravasation of tumor cells from the primary tumor into circulation, but extravasation from circulation into the bone where they meet an environment that is generally suppressive of their growth. The bone microenvironment can inhibit the growth of disseminated tumor cells (DTC) by inducing dormancy of the DTC directly and later on following formation of a micrometastatic tumour mass by inhibiting metastatic processes including angiogenesis, bone remodeling and immunosuppressive cell functions. In this review we will highlight some of the mechanisms mediating DTC dormancy and the complex relationships which occur between tumor cells and bone resident cells in the bone metastatic microenvironment. These inter-cellular interactions may be important targets to consider for development of novel effective therapies for the prevention or treatment of bone metastases. 相似文献
110.
Davidson Oranit B.; Eden Dov; Westman Mina; Cohen-Charash Yochi; Hammer Leslie B.; Kluger Avraham N.; Krausz Moshe; Maslach Christina; O'Driscoll Michael; Perrewé Pamela L.; Quick James Campbell; Rosenblatt Zehava; Spector Paul E. 《Canadian Metallurgical Quarterly》2010,95(5):953
A rigorous quasi-experiment tested the ameliorative effects of a sabbatical leave, a special case of respite from routine work. We hypothesized that (a) respite increases resource level and well-being and (b) individual differences and respite features moderate respite effects. A sample of 129 faculty members on sabbatical and 129 matched controls completed measures of resource gain, resource loss, and well-being before, during, and after the sabbatical. Among the sabbatees, resource loss declined and resource gain and well-being rose during the sabbatical. The comparison group showed no change. Moderation analysis revealed that those who reported higher respite self-efficacy and greater control, were more detached, had a more positive sabbatical experience, and spent their sabbatical outside their home country enjoyed more enhanced well-being than others. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献