THE CLINICAL EXPERIENCE AND EXPERIMENTAL FINDINGS IN UTERINE CONTRACTILITY IN PREGNANCY. STUDIES « IN VIVO » AND « IN VITRO »

1967 ◽  
Vol 5 (3) ◽  
pp. 171-189 ◽  
Author(s):  
Roberto Martin Pinto
Keyword(s):  
Clinical Experience ◽  
Uterine Contractility ◽  
Experimental Findings ◽  
In Pregnancy

scholarly journals STEM-29. THE HISTONE VARIANT macroH2A2 ORCHESTRATES AN ACTIONABLE CHROMATIN PROGRAM OF STEMNESS IN GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii202-ii202
Author(s):  
Ana Nikolic ◽  
Anna Bobyn ◽  
Katrina Ellestad ◽  
Xueqing Lun ◽  
Michael Johnston ◽  
...  
Keyword(s):  
Chromatin Accessibility ◽  
Histone Variant ◽  
Clinical Settings ◽  
Glioblastoma Cells ◽  
Self Renewal ◽  
Viral Mimicry ◽  
Experimental Findings ◽  
Preclinical Work

Abstract Glioblastoma cells with the crucial stemness property of self-renewal constitute therapy-resistant reservoirs that seed tumor relapse. Effective targeting of these cells in clinical settings has been hampered by their relative quiescence, which invalidates the cell replication bias of most current treatments. Furthermore, although their dependence on specific chromatin and transcriptional states for the maintenance of stemness programs has been proposed as a vulnerability, these nuclear programs have been challenging to target pharmaceutically. Therefore the identification of targetable chromatin paradigms regulating self-renewal would represent a significant advancement for this incurable malignancy. Here we report a new role for the histone variant macroH2A2 in modulating a targetable epigenetic network of stemness in glioblastoma. By integrating transcriptomic, bulk and single-cell epigenomic datasets we generated from patient-derived models and surgical specimens, we show that macroH2A2 represses a transcriptional network of stemness through direct regulation of chromatin accessibility at enhancer elements. Functional assays in vitro and in vivo further showcase that macroH2A2 antagonizes self-renewal and stemness in glioblastoma preclinical models. In agreement with our experimental findings, high expression of macroH2A2 is a positive prognostic factor in clinical glioblastoma cohorts. Reasoning that increasing macroH2A2 levels could be an effective strategy to repress stemness programs and ameliorate patient outcome, we embarked on a screen to identify compounds that could elevate macroH2A2 levels. We report that an inhibitor of the chromatin remodeler Menin increases macroH2A2 levels, which in turn repress self-renewal. Additionally, we provide evidence that Menin inhibition induces viral mimicry programs and the demise of glioblastoma cells. Menin inhibition is being tested in clinical trials for blood malignancies (NCT04067336). Our preclinical work therefore reveals a novel and central role for macroH2A2 in an epigenetic network of stemness and suggests new clinical approaches for glioblastoma.

scholarly journals Bioinformatic and experimental findings to indicate anti-cancer targets and mechanisms of calycosin against nasopharyngeal carcinoma

2020 ◽  
Author(s):  
Fangxian Liu ◽  
Qijin Pan ◽  
Liangliang Wang ◽  
Shijiang Yi ◽  
Peng Liu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Cell Number ◽  
Network Pharmacology ◽  
Tunel Staining ◽  
Pharmacological Targets ◽  
Experimental Findings

Abstract Background: Calycosin is a naturally-occurring phytoestrogen that reportedly exerts anti- nasopharyngeal carcinoma (NPC) effects. Nevertheless, the molecular mechanisms for anti-NPC using calycosin remain unrevealed. Methods: Thus, a network pharmacology was used to uncover anti-NPC pharmacological targets and mechanisms of calycosin. Additionally, validated experiments were conducted to validate the bioinformatic findings of calycosin for treating NPC. Results: As results, bioinformatic assays showed that the predictive pharmacological targets of calycosin against NPC were TP53, MAPK14, CASP8, MAPK3, CASP3, RIPK1, JUN, ESR1, respectively. And the top 20 biological processes and pharmacological mechanisms of calycosin against NPC were identified accordingly. In clinical data, NPC samples showed positive expression of MAPK14, reduced TP53, CASP8 expressions. In studies in vitro and in vivo, calycosin-dosed NPC cells resulted in reduced cell proliferation, promoted cell apoptosis. In TUNEL staining, calycosin exhibited elevated apoptotic cell number. And immunostaining assays resulted in increased TP53, CASP8 positive cells, and reduced MAPK14 expressions in calycosin-dosed NPC cells and tumor-bearing nude mice. Conclusion: Altogether, these bioinformatic findings reveal optimal pharmacological targets and mechanisms of calycosin against NPC, following with representative identification of human and preclinical experiments. Notably, some of original biotargets may be potentially used to treat NPC.

scholarly journals Nanostructured Lipid Carrier Gel for the Dermal Application of Lidocaine: Comparison of Skin Penetration Testing Methods

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 310 ◽  
Author(s):  
Stella Zsikó ◽  
Kendra Cutcher ◽  
Anita Kovács ◽  
Mária Budai-Szűcs ◽  
Attila Gácsi ◽  
...  
Keyword(s):  
Drug Release ◽  
Human Skin ◽  
Ex Vivo ◽  
Study Drug ◽  
Skin Penetration ◽  
Human Epidermis ◽  
Nanostructured Lipid Carrier ◽  
Experimental Findings

The aim of this research was to investigate the stability of a lidocaine-loaded nanostructured lipid carrier dispersion at different temperatures, formulate a nanostructured lipid carrier gel, and test the penetration profile of lidocaine from the nanostructured lipid carrier gel using different skin penetration modeling methods. The formulations were characterized by laser diffraction, rheological measurements and microscopic examinations. Various in vitro methods were used to study drug release, diffusion and penetration. Two types of vertical Franz diffusion cells with three different membranes, including cellulose, Strat-M®, and heat separated human epidermis were used and compared to the Skin-parallel artificial membrane permeability assay (PAMPA) method. Results indicated that the nanostructured lipid carrier dispersion had to be gelified as soon as possible for proper stability. Both the Skin-PAMPA model and Strat-M® membranes correlated favorably with heat separated human epidermis in this research, with the Strat-M® membranes sharing the most similar drug permeability profile to an ex vivo human skin model. Our experimental findings suggest that even when the best available in vitro experiment is selected for modeling human skin penetration to study nanostructured lipid carrier gel systems, relevant in vitro/in vivo correlation should be made to calculate the drug release/permeation in vivo. Future investigations in this field are still needed to demonstrate the influence of membranes and equipment from other classes on other drug candidates.

The Permeability of Dialytic Membranes to Endotoxins: Clinical and Experimental Findings

1989 ◽  
Vol 12 (8) ◽  
pp. 505-508 ◽  
Author(s):  
G. Passavanti ◽  
E. Buongiorno ◽  
G. De Fino ◽  
D. Fumarola ◽  
P. Coratelli
Keyword(s):  
Active Component ◽  
Lipid A ◽  
In Vitro Study ◽  
The Body ◽  
Biologically Active ◽  
Limulus Amebocyte Lysate ◽  
Membrane Interaction ◽  
Experimental Findings

This study of 20 endotoxemic patients submitted to 70 hemodialyses (HD) found a reduction of the pre-HD limulus amebocyte lysate (LAL) positivity in 50 HD (71%), without appreciable differences in terms of effectiveness between cuprophan and AN 69 membranes. To define the mechanisms responsible for the reduction in LAL positivity during HD, the membranes were used in two in vitro studies, the first of which showed that the LAL positivity of blood containing lipopolysaccharide (LPS), submitted to hemofiltration (HF) for 300 min, remained unchanged and the ultrafiltrate remained constantly LAL negative. These results suggest that the reduction in LAL positivity observed in HD in vivo, an expression of reduced endotoxemia, cannot be attributed either to the filtration of the LPS as such or to its fragmentation following blood-membrane interaction into theoretically less filtrable molecules or to mechanisms of LPS adsorption on the membrane. The in vivo reduction of LAL positivity is more likely due to removal of the filtrable endotoxin fragments already released in the body, like lipid A, the biologically active component of LPS, known to react to LAL. This hypothesis was borne out by the second in vitro study, where the LAL positivity of blood containing lipid A, treated by HF for 80 min, gradually decreased, and dialytic permeability to lipid A was confirmed by the appearance of LAL positivity in the ultrafiltrate.

In vitro-produced horse embryos exhibit a very narrow window of acceptable recipient mare uterine synchrony compared with in vivo-derived embryos

2019 ◽  
Vol 31 (12) ◽  
pp. 1904 ◽  
Author(s):  
Juan Cuervo-Arango ◽  
Anthony N. Claes ◽  
Tom A. E. Stout
Keyword(s):  
Pregnancy Rate ◽  
Pregnancy Loss ◽  
Oestrous Cycle ◽  
Ongoing Pregnancy ◽  
Ongoing Pregnancy Rate ◽  
Wide Range ◽  
In Pregnancy

In recent years, the number of equine invitro-produced embryos (IVP) has increased markedly; as yet, there are few reports on what constitutes an ‘ideal’ recipient for an IVP embryo. This study retrospectively investigated the effects of recipient mare oestrous cycle characteristics on the likelihood of pregnancy after transfer of IVP (n=264) and invivo-derived embryos (n=262). IVP embryos tolerated only a narrow window of recipient mare ‘synchrony’, with transfer on Day 4 after ovulation resulting in a higher likelihood of ongoing pregnancy (69%) than transfer on Days 3, 5 or 6 (53.2%, 41.3% and 23.1% respectively; P=0.02). In contrast, Day 8 invivo-derived embryos tolerated a wide range of uterine (a)synchrony, with no difference in pregnancy or pregnancy loss for recipients that ovulated between Day 4 and Day 9 before transfer. However, transferring invivo-derived embryos to recipients that had a longer oestrus preceding transfer resulted in higher Day 12 and ongoing pregnancy rate (P<0.01). This effect was not significant in IVP embryos. In conclusion, Day 6–8 IVP blastocysts survive best after transfer to Day 4 recipient mares; Day 8 invivo-derived embryos survive equally well in Day 4–9 recipients, but do better in mares that have a long preceding oestrus.

Post-ovulation nutritional status in ewes does not influence early conceptus development in vivo or luteotrophic protein secretion in vitro.

1993 ◽  
Vol 1993 ◽  
pp. 58-58
Author(s):  
J.M. Wallace ◽  
R.P. Aitken ◽  
M.A. Cheyne
Keyword(s):  
Pregnancy Rate ◽  
Immunosuppressive Agents ◽  
Maternal Environment ◽  
Embryo Survival ◽  
Domestic Species ◽  
Progesterone Secretion ◽  
Conceptus Development ◽  
In Pregnancy

Overfeeding during early pregnancy compromises pregnancy establishment and /or embryo survival in a variety of domestic species including sheep, cattle and pigs (reviewed by Robinson, 1990). Embryo survival was reduced in recipient ewes receiving a high as opposed to a low plane of nutrition from embryo transfer on day 5 post-ovulation to day 60 of gestation (McKelvey & Robinson, 1988).Similarly high plane feeding for only 12 days starting on day 2 after mating significantly reduced pregnancy rates at day 60 ( Parr et al .,1987). Although not extensively monitored in either study, peripheral progesterone concentrations were inversely correlated with feed intake. Indeed, the reduction in pregnancy rate in high plane ewes in Parr's study was reversed by progesterone supplementation on days 8-14 after mating.The inhibition of luteolysis and maintenance of adequate progesterone secretion by the corpus luteum is central to the maternal recognition of pregnancy in sheep ( Bazer et al .,1991 ). Progesterone plays a major role in controlling maternal secretion of nutrients, growth factors , immunosuppressive agents .enzymes and steroids required for successful embryo development. It seems likely therefor that the mechanisms underlying nutritionally induced differences in pregnancy rate and embryo survival may operate via changes in progesterone levels which in turn alter the secretory dialogue between the conceptus and its maternal environment.

scholarly journals CHARACTERIZATION OF A HUMAN ACUTE PHASE PROTEIN FOUND IN ASSOCIATION WITH RUBELLA VIRUS INFECTION

1974 ◽  
Vol 139 (3) ◽  
pp. 497-511 ◽  
Author(s):  
Roger Cappel ◽  
Ann Schluederberg ◽  
Robert H. Gifford ◽  
Dorothy M. Horstmann
Keyword(s):  
Rheumatoid Arthritis ◽  
Virus Infection ◽  
Acute Phase ◽  
Rubella Virus ◽  
Acute Phase Protein ◽  
Phase Protein ◽  
Rubella Virus Infection ◽  
In Pregnancy

A precipitating antigen, rho, was first detected in the blood of persons with rubella and in rubella virus-infected cell culture fluids (1). Partially purified antigens from both sources were examined and shown to have similar properties, although antigen from serum sedimented more heterogeneously, with estimated coefficients from 15 to 21 S, while that from culture fluids sedimented in the 11–14 S region. In each case, antigen was located in the ß-1 zone after electrophoresis in agarose, and at a density of 1.305 g/ml after centrifugation in CsCl. Stability characteristics were typical of protein antigens. Immunofluorescent microscopy revealed that rubella virus induced the appearance of rho antigen scattered throughout the cytoplasm of infected cells. When cells containing antigen were exposed for 24 h to 5 µg/ml actinomycin D rho was no longer detectable, indicating the probable cellular origin of the antigen. Also, titers in medium of infected cultures showed a reduction after actinomycin treatment, but levels of the virus-specified antigen, iota, were relatively unaffected. Rho appears to be a protein common to man and many animals. In vitro, it was induced by rubella virus and by adenovirus. In vivo, rho titers were shown to be elevated after rubella virus infection and, to a lesser extent, after infection with certain other viruses. High titers were also demonstrated in women late in pregnancy and in patients with rheumatoid arthritis. In man and the chimpanzee, the appearance and decline of rho in the blood after rubella virus infection were temporally similar to the patterns of CRP, although rho seemed to be a more sensitive indicator of infection. The data presented indicate that rho is a newly recognized acute phase protein inducible by certain virus infections and by other unidentified stimuli present prominently in pregnancy and rheumatoid arthritis.

scholarly journals Quercetin-Based Nanocomposites as a Tool to Improve Dental Disease Management

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 504
Author(s):  
Giuseppe Angellotti ◽  
Denise Murgia ◽  
Giuseppina Campisi ◽  
Viviana De Caro
Keyword(s):  
Dental Implants ◽  
Antibacterial Activities ◽  
Missing Teeth ◽  
Positive Effects ◽  
Functionalized Surfaces ◽  
Osteoblast Activity ◽  
Experimental Findings

The restoration and prosthetic rehabilitation of missing teeth are commonly performed using dental implants, which are extremely effective and long-lasting techniques due to their osteointegration ability with the preimplant tissues. Quercetin is a phytoestrogen-like flavonoid well known for its several positive effects on human health, mostly linked to the anti-inflammatory, antioxidant, and antibacterial activities against both Gram-positive and Gram-negative bacteria. Moreover, many studies in dentistry and the maxillofacial fields have highlighted the positive effects of quercetin on osteogenesis, acting on osteoblast activity and angiogenetic process, and promoting soft and hard tissue regeneration. This review focuses on the role of quercetin on the healing and restoration of bony defects, considering the experimental findings of its application both in vitro and in vivo as a mere compound or in association with scaffolds and dental implants having functionalized surfaces.

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