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71.
《Ceramics International》2021,47(21):30051-30060
Hydroxyapatite (HA) is a highly regarded synthetic bone graft material. Porous HA ceramics blocks are used to substitute harvested natural bone grafts. Being similar to bone mineral, HA material integrates with the host bone through surface osteointegration and slowly resorb along with the natural bone remodeling process. The blocks in use currently have random and tortuous pore structures. The present work explores the usefulness of cage-like HA ceramic design with end-to-end open pores, with the help of in vitro cell culture methods. Such a structure, on implantation, will take up the blood factors and cells and host the bone remodeling process inside the bulk of the cage, leading to early healing. In the study, HA samples with aligned through-pores were prepared and explored in vitro, with a focus on how the pores host the cells inside and to what level the cells maintain their activity. Human osteoblast-like cells (HOS) were used, at different seeding and culturing approaches. Cell seeding was done through (i) conventional large volume cell suspension, (ii) a confined mini chamber with a limited volume of cell suspension, and (iii) placing a concentrated drop of cell suspension directly on top of the scaffold. The third approach gave the best cell adhesion and proliferation, and hence used for further explorations. A dynamic culture system was designed in-house by bifurcating the cell culture wells using vertical inserts, holding the samples horizontally with their ends open to both sides, and making the media flow across using a rocker platform. The HOS cell adhesion, viability and proliferation were tested in the HA cages, in static and dynamic culture conditions, with conventional porous ceramics as the control. The cell infiltration was deeper and the cell viability over a period of 7 days was significantly higher in dynamic culture conditions in the test samples. 相似文献
72.
Alfonso Martín-Bernab Josep Tarrag-Celada Valrie Cunin Sylvie Michelland Roldn Corts Johann Poignant Cyril Boyault Walid Rachidi Sandrine Bourgoin-Voillard Marta Cascante Michel Seve 《International journal of molecular sciences》2021,22(7)
Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies. 相似文献
73.
《Ceramics International》2021,47(19):27177-27187
BaZrO3-based materials doped with a trivalent cation have excellent chemical stability and relatively high proton conductivity which makes them potential proton conducting oxide materials for various electrochemical device applications such as hydrogen processing, high-temperature electrolysis, and solid electrolyte in fuel cells. However, BaZrO3 showed poor sinterability, requiring high sintering temperatures (1700–2100 °C) with longtime sintering (20–100 h) to achieve the desired microstructure and grain growth. This sintering problem can be solved by slightly doping BaZrO3 with a sintering aid element. Therefore, in this study, two different zirconate proton conductors: BaZr0·9Y0·1O3-α (BZY) and BaZr0·955Y0·03Co0·015O3-α (BZYC) were sintered in an air atmosphere and an oxygen atmosphere for 20 h in the temperature range of 1500–1640 °C. The sinterability was evaluated by analyzing the XRD diffraction patterns, lattice constant, lattice strain, crystallite size, relative density, open porosity, closed porosity, surface morphology, grain size, and grain boundary distribution, using the XRD, SEM, EDX, and Archimedes density measurement methods. It is concluded that in an oxygen atmosphere, sintering aid Co not only improves the relative density but also produces highly dense fine particles with clear grain boundaries which are promising for electrochemical hydrogen device applications. 相似文献
74.
Myriam Gonzlez María Ovejero-Snchez Alba Vicente-Blzquez Raquel lvarez Ana B. Herrero Manuel Medarde Rogelio Gonzlez-Sarmiento Rafael Pelez 《International journal of molecular sciences》2021,22(4)
Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers. 相似文献
75.
Shamila Vibhushan Manuela Bratti Juan Eduardo Montero-Hernndez Alaa El Ghoneimi Marc Benhamou Nicolas Charles Eric Daugas Ulrich Blank 《International journal of molecular sciences》2021,22(1)
A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions. 相似文献
76.
Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models
Beata Filip-Psurska Mateusz Psurski Artur Anisiewicz Patrycja Libako Ewa Zbrojewicz Magdalena Maciejewska Micha Chodyski Andrzej Kutner Joanna Wietrzyk 《International journal of molecular sciences》2021,22(5)
1,25-Dihydroxycholecalciferol, the hormonally active vitamin D3 metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)2D3 analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR. 相似文献
77.
Rachana R. Borkute Sren Woelke Gang Pei Anca Dorhoi 《International journal of molecular sciences》2021,22(9)
Neutrophils readily infiltrate infection foci, phagocytose and usually destroy microbes. In tuberculosis (TB), a chronic pulmonary infection caused by Mycobacterium tuberculosis (Mtb), neutrophils harbor bacilli, are abundant in tissue lesions, and their abundances in blood correlate with poor disease outcomes in patients. The biology of these innate immune cells in TB is complex. Neutrophils have been assigned host-beneficial as well as deleterious roles. The short lifespan of neutrophils purified from blood poses challenges to cell biology studies, leaving intracellular biological processes and the precise consequences of Mtb–neutrophil interactions ill-defined. The phenotypic heterogeneity of neutrophils, and their propensity to engage in cellular cross-talk and to exert various functions during homeostasis and disease, have recently been reported, and such observations are newly emerging in TB. Here, we review the interactions of neutrophils with Mtb, including subcellular events and cell fate upon infection, and summarize the cross-talks between neutrophils and lung-residing and -recruited cells. We highlight the roles of neutrophils in TB pathophysiology, discussing recent findings from distinct models of pulmonary TB, and emphasize technical advances that could facilitate the discovery of novel neutrophil-related disease mechanisms and enrich our knowledge of TB pathogenesis. 相似文献
78.
Manjunatha S. Muttigi Byoung Ju Kim Bogyu Choi Inbo Han Hansoo Park Soo-Hong Lee 《International journal of molecular sciences》2020,21(23)
Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for articular cartilage repair and regeneration. However, the terminal hypertrophic differentiation of Ad-MSC-derived cartilage is a critical barrier during hyaline cartilage regeneration. In this study, we investigated the role of matrilin-3 in preventing Ad-MSC-derived chondrocyte hypertrophy in vitro and in an osteoarthritis (OA) destabilization of the medial meniscus (DMM) model. Methacrylated hyaluron (MAHA) (1%) was used to encapsulate and make scaffolds containing Ad-MSCs and matrilin-3. Subsequently, the encapsulated cells in the scaffolds were differentiated in chondrogenic medium (TGF-β, 1–14 days) and thyroid hormone hypertrophic medium (T3, 15–28 days). The presence of matrilin-3 with Ad-MSCs in the MAHA scaffold significantly increased the chondrogenic marker and decreased the hypertrophy marker mRNA and protein expression. Furthermore, matrilin-3 significantly modified the expression of TGF-β2, BMP-2, and BMP-4. Next, we prepared the OA model and transplanted Ad-MSCs primed with matrilin-3, either as a single-cell suspension or in spheroid form. Safranin-O staining and the OA score suggested that the regenerated cartilage morphology in the matrilin-3-primed Ad-MSC spheroids was similar to the positive control. Furthermore, matrilin-3-primed Ad-MSC spheroids prevented subchondral bone sclerosis in the mouse model. Here, we show that matrilin-3 plays a major role in modulating Ad-MSCs’ therapeutic effect on cartilage regeneration and hypertrophy suppression. 相似文献
79.
PROfound研究——前列腺癌精准治疗新希望 总被引:1,自引:0,他引:1
转移性去势抵抗性前列腺癌(metastatic castrate-resistant prostate cancer,mCRPC)是前列腺癌发展的终末阶段。患者生存预后很差。尽管不断地有新的治疗手段出现,比如新型内分泌治疗以及紫杉醇类化疗,mCRPC患者的生存期依然很有限。奥拉帕利是一款聚腺苷酸二磷酸核糖基聚合酶(poly ADP-ribose polymerase,PARP)抑制剂,PARP酶在DNA修复中扮演着重要的角色。奥拉帕利已经获批用于卵巢癌和乳腺癌的治疗。目前,奥拉帕利用于mCRPC治疗的III期临床研究PROfound的结果在2019年的欧洲肿瘤内科学会(ESMO)年会与2020年的美国临床肿瘤学会-泌尿生殖系统肿瘤研讨会(ASCO-GU)已经发布。本文将带来PROfound研究的结果以及最新的结果更新。 相似文献
80.
Breast cancer is the most frequently diagnosed cancer in women worldwide. The disease and its treatments exert profound effects on an individual’s physical and mental health. There are many factors that impact an individual’s risk of developing breast cancer, their response to treatments, and their risk of recurrence. The community of microorganisms inhabiting the gastrointestinal tract, the gut microbiota, affects human health through metabolic, neural, and endocrine signaling, and immune activity. It is through these mechanisms that the gut microbiota appears to influence breast cancer risk, response to treatment, and recurrence. A disrupted gut microbiota or state of ‘dysbiosis’ can contribute to a biological environment associated with higher risk for cancer development as well as contribute to negative treatment side-effects. Many cancer treatments have been shown to shift the gut microbiota toward dysbiosis; however, the microbiota can also be positively manipulated through diet, prebiotic and probiotic supplementation, and exercise. The objective of this review is to provide an overview of the current understanding of the relationship between the gut microbiota and breast cancer and to highlight potential strategies for modulation of the gut microbiota that could lead to improved clinical outcomes and overall health in this population. 相似文献