scholarly journals Short-term transplantation of isolated human ovarian follicles and cortical tissue into nude mice

Reproduction ◽  
2007 ◽  
Vol 134 (2) ◽  
pp. 253-262 ◽  
Author(s):  
Marie-Madeleine Dolmans ◽  
Belen Martinez-Madrid ◽  
Elodie Gadisseux ◽  
Yves Guiot ◽  
Wu Yuan Yuan ◽  
...  

This study was designed to evaluate follicular survival and growth after short-term transplantation of fresh isolated human follicles and ovarian cortical tissue to nude mice. Ovarian biopsies were obtained from nine women undergoing laparoscopy. Twelve nude mice were xenografted with an ovarian cortical fragment in the right ovarian bursa, and a clot containing isolated follicles in the left, for a period of 7 days. One ungrafted fragment was used as a control. Histological sections were analyzed to determine follicle number and stage. The proliferative status of follicular cells was assessed by Ki-67 immunostaining. A total of 659 follicles was analyzed by histology and 545 follicles by immunohistochemistry. The percentage of primordial follicles was found to be markedly reduced 1 week post-grafting when compared with ungrafted tissue, while the percentage of primary follicles had significantly increased. Only 8% of follicles showed Ki-67-positive granulosa cells before grafting, whereas 1 week after grafting, 71% of follicles in fragments and 67% of isolated follicles were Ki-67-positive (P<0.001). Moreover, the histological aspect of isolated follicle grafts was similar to that of grafted fragments: follicles were surrounded by vimentin-positive stroma-like tissue of human origin, as confirmed by fluorescent in situ hybridization with human-specific probes. Our results demonstrate, for the first time, that isolated human follicles are able to survive and grow after xenografting. This study also shows massive in vivo follicular activation after transplantation of grafted fragments and isolated follicles. One week after grafting, well-structured stroma-like tissue of human origin was observed around the isolated follicles. The potential origin of this stroma is discussed.

2006 ◽  
Vol 52 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Kazuhiro KIKUCHI ◽  
Hiroyuki KANEKO ◽  
Michiko NAKAI ◽  
Junko NOGUCHI ◽  
Manabu OZAWA ◽  
...  

2021 ◽  
pp. 194855062110530
Author(s):  
Daniel R. Berry ◽  
Catherine S. J. Wall ◽  
Justin D. Tubbs ◽  
Fadel Zeidan ◽  
Kirk Warren Brown

A randomized controlled trial tested whether mindfulness training would increase lab-based and in vivo spontaneous helping behaviors toward racial outgroup members. First, across conditions, those scoring higher in baseline trait mindfulness showed higher levels of preintervention lab-based and ecological momentary assessment (EMA)-based helping behavior. Next, short-term (4-day) training in mindfulness, relative to a well-matched sham meditation training, increased interracial helping behavior in a lab-based simulation. Finally, among people scoring lower in a basic form of trait mindfulness at baseline—that is, with greater room for improvement—mindfulness training predicted higher postintervention in vivo helping behavior reported via EMA. However, neither training condition alone attenuated preferential helping toward racial ingroup members. These findings indicate, for the first time, that mindfulness and its training fosters helping behavior toward strangers and acquaintances regardless of their racial ingroup or outgroup status, but preferential helping of racial ingroup members remains.


Nanomedicine ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. 1001-1018 ◽  
Author(s):  
Juliete Nathali Scholl ◽  
Amanda de Fraga Dias ◽  
Pauline Rafaela Pizzato ◽  
Daniela Vasconcelos Lopes ◽  
Cesar Eduardo Jacintho Moritz ◽  
...  

Aim: To characterize a method to isolate glioma-derived extracellular vesicles (GEVs) and understand their role in immune system modulation and glioma progression. Materials & methods: GEVs were isolated by differential centrifugation from C6 cell supernatant and characterized by size and expression of CD9, HSP70, CD39 and CD73. The glioma model was performed by injecting C6 glioma cells into the right striatum of Wistar rats in the following groups: controls (C6 cells alone), coinjection (C6 cells + GEVs) and GEVs by intranasal administration followed by immune cells, tumor size and cells proliferation analyses. Results: GEVs presented uniform size (175 nm), expressed CD9, HSP70, CD39, CD73 and produced adenosine. In vivo, we observed a reduction in tumor size, in cell proliferation (Ki-67) and in a regulatory cell marker (FoxP3). Conclusion: GEVs, administered before or at tumor challenge, have antiproliferative properties and reduce regulatory cells in the glioma microenvironment.


1995 ◽  
Vol 311 (3) ◽  
pp. 1001-1007 ◽  
Author(s):  
C A Brearley ◽  
D E Hanke

Short-term 32P labelling and enzymic dissection of inositol phospholipids was used to study the turnover of 3-, 3,4-, 4-, and 4,5-phosphorylated phosphatidylinositols in the plant Spirodela polyrhiza L. Analysis of label in the whole headgroup reveals that phosphatidylinositol 3- and 4-monophosphates (PtdIns3P and PtdIns4P) and phosphatidylinositol 3,4- and 4,5-bisphosphates [PtdIns(3,4)P2 and PtdIns(4,5)P2] all turn over with a half-life of approximately 2-5 h. Analysis of the labelling of individual phosphomonoesters and phosphodiesters of these lipids indicates a rapid equilibration of label between the 4- and 5-monoester phosphates of PtdIns(4,5)P2 within 5 h and largely independent of changes of labelling in the diester. We observed substantially slower equilibration of label (within approximately 27 h) between the monoester and diester of PtdIns4P. These studies therefore indicate that PtdIns4P and PtdIns(4,5)P2 participate in substrate-cycling reactions, evidence for which has been described experimentally only in erythrocytes, and give confirmation in vivo of the previous detection of inositol phospholipid phosphomonoesterase activity. Similar analyses of label in PtdIns3P and PtdIns(3,4)P2 reveal the likely participation of these molecules in substrate cycles and hence for the first time the presence of PtdIns3P 3-phosphatase and PtdIns(3,4)P2 4-phosphatase activities in plants. PtdIns3P and PtdIns(3,4)P2 undergo turnover at rates similar to those of PtdIns4P and PtdIns(4,5)P2. Estimates are made of the relative sizes of the pools of phospholipid participating in the turnover process.


2009 ◽  
Vol 297 (5) ◽  
pp. E1078-E1088 ◽  
Author(s):  
Federica Barbieri ◽  
Alessandra Pattarozzi ◽  
Monica Gatti ◽  
Cinzia Aiello ◽  
Ana Quintero ◽  
...  

Somatostatin receptors (SSTR1–5) mediate antiproliferative effects. In C6 rat glioma cells, somatostatin is cytostatic in vitro via phosphotyrosine phosphatase-dependent inhibition of ERK1/2 activity mediated by SSTR1, -2, and -5. Here we analyzed the effects of SSTR activation on C6 glioma growth in vivo and the intracellular mechanisms involved, comparing somatostatin effects with selective agonists for SSTR1, -2, and -5 (BIM-23745, BIM-23120, BIM-23206) or receptor biselective compounds (SSTR1 and -2, BIM-23704; and SSTR2 and -5, BIM-23190). Nude mice subcutaneously xenografted with C6 cells were treated with somatostatin, SSTR agonists (50 μg, twice/day), or vehicle. Tumor growth was evaluated every 3 days for 19 days. The intracellular pathways responsible of SSTR effects in vivo were evaluated measuring Ki-67, phospho-ERK1/2, and p27kip1 expression by immunohistochemistry in sections from explanted tumors. Somatostatin and SSTR1, -2, and -5 agonists strongly inhibited in vivo C6 tumor growth, intratumoral neovessel formation, Ki-67 expression, and ERK1/2 phosphorylation and induced upregulation of p27Kip1, whereas only a modest activation of caspase-3 was observed. Somatostatin (acting on SSTR1, -2, and -5) displayed the highest efficacy; SSTR5 selective agonist showed a stronger effect than SSTR1 agonist, and SSTR2 agonist was less effective. On the other hand, SSTR1 and -2 agonists maximally reduced tumor neovascularization. The combined activation of SSTR1 and -2 showed a synergistic activity, reaching a higher efficacy than BIM-23206, whereas the simultaneous activation of SSTR2 and -5 resulted in a response resembling SSTR5 effects. Thus the simultaneous activation of different SSTRs inhibits glioma cell proliferation in vivo through both direct cytotostatic and antiangiogenic effects.


2020 ◽  
Author(s):  
Giulia Comunale ◽  
Paolo Peruzzo ◽  
Biagio Castaldi ◽  
Renato Razzolini ◽  
Giovanni Di Salvo ◽  
...  

Abstract The role played by the right ventricular (RV) dysfunction has long been underestimated in clinical practice. Recent findings are progressively confirming that when the RV efficiency deteriorates both the right and the left circulation is (significantly) affected, but studies dedicated to a detailed description of RV hemodynamic role still lack. In response to such a gap in knowledge, this work proposes a numerical model that for the first time evaluates the effect of isolated RV dysfunction on the whole circulation. Lumped parameter modelling was applied to represent the physio-pathological hemodynamics. Different grades of impairment were simulated for three dysfunctions i.e., systolic, diastolic, and combined systolic and diastolic. Hemodynamic alterations (i.e., of blood pressure, flow, global hemodynamic parameters), arising from the dysfunctions, are calculated and analysed. Results well accord with clinical observations, showing that RV dysfunction significantly affects both the pulmonary and systemic hemodynamics. Successful validation against in vivo data proved the clinical potentiality of the model i.e., the capability of identifying the degree of RV impairment for given hemodynamic conditions. This study aims at contributing to the improvement of RV dysfunction recognition and treatment, and to the development of tools for the clinical management of pathologies involving the right heart.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhong-Kun Xia ◽  
Wei Wang ◽  
Jian-Ge Qiu ◽  
Xi-Nan Shi ◽  
Hong-Jian Li ◽  
...  

Background: Hepatocellular carcinoma (HCC) is a lethal malignancy lacking effective treatment. The Cyclin-dependent kinases 4/6 (CDK4/6) and PI3K/AKT signal pathways play pivotal roles in carcinogenesis and are promising therapeutic targets for HCC. Here we identified a new CDK4/6 and PI3K/AKT multi-kinase inhibitor for the treatment of HCC.Methods: Using a repurposing and ensemble docking methodology, we screened a library of worldwide approved drugs to identify candidate CDK4/6 inhibitors. By MTT, apoptosis, and flow cytometry analysis, we investigated the effects of candidate drug in reducing cell-viability,inducing apoptosis, and causing cell-cycle arrest. The drug combination and thermal proteomic profiling (TPP) method were used to investigate whether the candidate drug produced antagonistic effect. The in vivo anti-cancer effect was performed in BALB/C nude mice subcutaneously xenografted with Huh7 cells.Results: We demonstrated for the first time that the anti-plasmodium drug aminoquinol is a new CDK4/6 and PI3K/AKT inhibitor. Aminoquinol significantly decreased cell viability, induced apoptosis, increased the percentage of cells in G1 phase. Drug combination screening indicated that aminoquinol could produce antagonistic effect with the PI3K inhibitor LY294002. TPP analysis confirmed that aminoquinol significantly stabilized CDK4, CDK6, PI3K and AKT proteins. Finally, in vivo study in Huh7 cells xenografted nude mice demonstrated that aminoquinol exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil with the combination treatment showed the highest therapeutic effect.Conclusion: The present study indicates for the first time the discovery of a new CDK4/6 and PI3K/AKT multi-kinase inhibitor aminoquinol. It could be used alone or as a combination therapeutic strategy for the treatment of HCC.


2021 ◽  
pp. 1-7
Author(s):  
Rachelle Isidro ◽  
Iacopo Cioffi

The tendon-aponeurosis complex (TAC) of the temporalis dissipates forces produced during function. Abnormally reduced temporalis TACs have been found in individuals with chronic muscular temporomandibular disorders – a painful musculoskeletal condition that is more frequent in women than men. Whether there are sex differences in the temporalis TAC in healthy individuals is currently unknown. Here, we characterized and measured the temporalis TAC in healthy male and female young individuals between 5 and 15 years old to determine whether the volume of the temporalis TAC and the TAC-to-muscle ratio are different between males and females. We collected MRI studies from 90 healthy individuals, including equal numbers (15 M and 15 F) of young children (ages 5–7), children (9–11), and adolescents (13–15) and segmented the right temporalis and its TAC using software. Using general linear models, we tested the effect of sex, age, and their interaction on the volumes of the temporalis and its TAC, and the TAC-to-muscle ratio. The volumes of the temporalis and its TAC increased with age (both <i>p</i> &#x3c; 0.001) and were not affected by sex (<i>p</i> = 0.252 and <i>p</i> = 0.179) or by the interaction sex-by-age (<i>p</i> = 0.079 and <i>p</i> = 0.095, respectively). The TAC-to-muscle ratio did not change significantly with age (<i>p</i> = 0.655) and was not affected by sex (0.438) or by the interaction sex-by-age (0.524). We provide, for the first time, volumetric data of the temporalis TAC in children and adolescents. The volumes of the temporalis TAC and the TAC-to-muscle ratio are not different between male and female individuals until the age of 15.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Youn-Mook Lim ◽  
Bo Hae Kim ◽  
Hee-Bok Kim ◽  
EunJi Park ◽  
Seok-Won Park ◽  
...  

This study explored a novel strategy to restore the vocal gap by using cross-linkedβ-glucan hydrogel byγ-irradiation. An aqueous solution of 5 wt%β-glucan was prepared and cross-linked using60Coγirradiation. Ten nude mice were injected with 0.8 mL of irradiatedβ-glucan on the left back and the same volume of nonirradiatedβ-glucan on the right back for comparison. The mice were sacrificed at 1 and 2 weeks after injection and histological evaluations were performed. Irradiatedβ-glucan demonstrated a significantly larger volume than nonirradiatedβ-glucan in the back of nude mice with less inflammatory reaction. After unilateral recurrent laryngeal nerve section in New Zealand White rabbits, irradiated and nonirradiatedβ-glucan were injected into paralyzed vocal folds. Irradiatedβ-glucan remained at the paralyzed vocal fold without definite inflammatory signs on endoscopy. High-speed recordings of vocal fold vibration showed decreased vocal gap in irradiated group compared to nonirradiated group. Histologically, the laryngeal epithelium and lamina propria remained intact, without inflammatory cell infiltration. Our newly developed injection material, irradiatedβ-glucan, showed excellent biocompatibility and remained longer than nonirradiatedβ-glucanin vivo, suggesting irradiated hydrogels as a new therapeutic approach that may be useful for the long-term treatment of vocal fold palsy.


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yunli Zhou ◽  
Mi Zhang ◽  
Dan He ◽  
Xueyuan Hu ◽  
Huarong Xiong ◽  
...  

Abstract Enzyme therapy is an effective strategy to treat diseases. Three strategies were pursued to provide the favorable microenvironments for uricase (UCU) to eventually improve its features: using the right type of buffer to constitute the liquid media where catalyze reactions take place; entrapping UCU inside the selectively permeable lipid vesicle membranes; and entrapping catalase together with UCU inside the membranes. The nanosized alkaline enzymosomes containing UCU/(UCU and catalase) (ESU/ESUC) in bicine buffer had better thermal, hypothermal, acid-base and proteolytic stabilities, in vitro and in vivo kinetic characteristics, and uric acid lowering effects. The favorable microenvironments were conducive to the establishment of the enzymosomes with superior properties. It was the first time that two therapeutic enzymes were simultaneously entrapped into one enzymosome having the right type of buffer to achieve added treatment efficacy. The development of ESU/ESUC in bicine buffer provides valuable tactics in hypouricemic therapy and enzymosomal application.


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