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271.
Platinum-based chemotherapies, such as cisplatin, play a large role in cancer treatment. The development of resistance and treatment toxicity creates substantial barriers to disease control, yet. To enhance the therapeutic index of cisplatin-based chemotherapy, it is imperative to circumvent resistance and toxicity while optimizing tumor sensitization. One of the primary mechanisms by which cancer cells develop resistance to cisplatin is through upregulation of DNA repair pathways. In this review, we discuss the DNA damage response in the context of cisplatin-induced DNA damage. We describe the proteins involved in the pathways and their roles in resistance development. Common biomarkers for cisplatin resistance and their utilization to improve patient risk stratification and treatment personalization are addressed. Finally, we discuss some of the current treatments and future strategies to circumvent the development of cisplatin resistance. 相似文献
272.
Ccile Morin David Guenoun Irvin Sautet Valrie Faivre Zsolt Csaba Leslie Schwendimann Pierrette Young-Ten Juliette Van Steenwinckel Pierre Gressens Cindy Bokobza 《International journal of molecular sciences》2022,23(9)
Preterm birth (PTB) represents 15 million births every year worldwide and is frequently associated with maternal/fetal infections and inflammation, inducing neuroinflammation. This neuroinflammation is mediated by microglial cells, which are brain-resident macrophages that release cytotoxic molecules that block oligodendrocyte differentiation, leading to hypomyelination. Some preterm survivors can face lifetime motor and/or cognitive disabilities linked to periventricular white matter injuries (PWMIs). There is currently no recommendation concerning the mode of delivery in the case of PTB and its impact on brain development. Many animal models of induced-PTB based on LPS injections exist, but with a low survival rate. There is a lack of information regarding clinically used pharmacological substances to induce PTB and their consequences on brain development. Mifepristone (RU-486) is a drug used clinically to induce preterm labor. This study aims to elaborate and characterize a new model of induced-PTB and PWMIs by the gestational injection of RU-486 and the perinatal injection of pups with IL-1beta. A RU-486 single subcutaneous (s.c.) injection at embryonic day (E)18.5 induced PTB at E19.5 in pregnant OF1 mice. All pups were born alive and were adopted directly after birth. IL-1beta was injected intraperitoneally from postnatal day (P)1 to P5. Animals exposed to both RU-486 and IL-1beta demonstrated microglial reactivity and subsequent PWMIs. In conclusion, the s.c. administration of RU-486 induced labor within 24 h with a high survival rate for pups. In the context of perinatal inflammation, RU-486 labor induction significantly decreases microglial reactivity in vivo but did not prevent subsequent PWMIs. 相似文献
273.
Marcell rpd Kordovn Csaba Hegeds Katalin Czifrk Csilla Lakatos Ibolya Klmn-Szab Lajos Darczi Mikls Zsuga Sndor Kki 《International journal of molecular sciences》2022,23(14)
In this paper, the synthesis, characterization, and properties of crosslinked poly(ε-caprolactone)-based polyurethanes as potential tissue replacement materials are reported. The polyurethane prepolymers were prepared from poly(ε-caprolactone)diol (PCD), polyethylene glycol (PEG)/polylactic acid diol (PLAD), and 1,6-hexamethylene diisocyanate (HDI). In these segmented polyurethanes, the role of PEG/PLAD was to tune the hydrophobic/hydrophilic character of the resulting polymer while sucrose served as a crosslinking agent. PLAD was synthesized by the polycondensation reaction of D,L-lactic acid and investigated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and nuclear magnetic resonance spectroscopy (NMR). The crosslinked polyurethane samples (SUPURs) obtained were characterized by attenuated total reflectance Fourier-transform infrared spectroscopy (AT-FT-IR), swelling, and mechanical (uniaxial tensile tests) experiments. The thermo and thermomechanical behavior were studied by differential scanning calorimetry (DSC) and dynamical mechanical analysis (DMA). The viability of dental pulp stem cells was investigated in the case of polyurethanes composed of fully biocompatible elements. In our studies, none of our polymers showed toxicity to stem cells (DPSCs). 相似文献
274.
Anett Hudk Gareth Morgan Jaromir Bacovsky Roland Patai Tams F. Polgr Annamria Letoha Aladar Pettko-Szandtner Csaba Vizler Lszl Szilk Tams Letoha 《International journal of molecular sciences》2022,23(14)
Despite the growing list of identified SARS-CoV-2 receptors, the human angiotensin-converting enzyme 2 (ACE2) is still viewed as the main cell entry receptor mediating SARS-CoV-2 internalization. It has been reported that wild-type mice, like other rodent species of the Muridae family, cannot be infected with SARS-CoV-2 due to differences in their ACE2 receptors. On the other hand, the consensus heparin-binding motif of SARS-CoV-2’s spike protein, PRRAR, enables the attachment to rodent heparan sulfate proteoglycans (HSPGs), including syndecans, a transmembrane HSPG family with a well-established role in clathrin- and caveolin-independent endocytosis. As mammalian syndecans possess a relatively conserved structure, we analyzed the cellular uptake of inactivated SARS-CoV-2 particles in in vitro and in vivo mice models. Cellular studies revealed efficient uptake into murine cell lines with established syndecan-4 expression. After intravenous administration, inactivated SARS-CoV-2 was taken up by several organs in vivo and could also be detected in the brain. Internalized by various tissues, inactivated SARS-CoV-2 raised tissue TNF-α levels, especially in the heart, reflecting the onset of inflammation. Our studies on in vitro and in vivo mice models thus shed light on unknown details of SARS-CoV-2 internalization and help broaden the understanding of the molecular interactions of SARS-CoV-2. 相似文献
275.
Rita Brzsei Balzs Zoltn Zsid Mnika Blint Zsuzsanna Helyes Erika Pintr Csaba Hetnyi 《International journal of molecular sciences》2022,23(13)
Somatostatin (also named as growth hormone-inhibiting hormone or somatotropin release-inhibiting factor) is a regulatory peptide important for the proper functioning of the endocrine system, local inflammatory reactions, mood and motor coordination, and behavioral responses to stress. Somatostatin exerts its effects via binding to G-protein-coupled somatostatin receptors of which the fourth subtype (SSTR4) is a particularly important receptor mediating analgesic, anti-inflammatory, and anti-depressant effects without endocrine actions. Thus, SSTR4 agonists are promising drug candidates. Although the knowledge of the atomic resolution-binding modes of SST would be essential for drug development, experimental elucidation of the structures of SSTR4 and its complexes is still awaiting. In the present study, structures of the somatostatin–SSTR4 complex were produced using an unbiased, blind docking approach. Beyond the static structures, the binding mechanism of SST was also elucidated in the explicit water molecular dynamics (MD) calculations, and key binding modes (external, intermediate, and internal) were distinguished. The most important residues on both receptor and SST sides were identified. An energetic comparison of SST binding to SSTR4 and 2 offered a residue-level explanation of receptor subtype selectivity. The calculated structures show good agreement with available experimental results and indicate that somatostatin binding is realized via prerequisite binding modes and an induced fit mechanism. The identified binding modes and the corresponding key residues provide useful information for future drug design targeting SSTR4. 相似文献
276.
Katharina Holeczek Uwe Gbureck Tomasz Jungst Csaba Gergely Lisa Galaba Juliane C. Kade 《Advanced Engineering Materials》2023,25(8):2201330
Digital light processing (DLP) enables the fabrication of complex 3D structures based on a photopolymerizable resin usually containing a photo initiator and an UV or photo absorber. The resin and thus the final properties of the printed structures can be adjusted by adding fillers like bioceramic powders relevant for bone-regeneration applications. Herein, a water-based and biocompatible poly(ethylene glycol diacrylate) (PEGDA) resin containing the photo initiator lithium-phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) enables the production of 3D structures via DLP. The addition of calcium magnesium phosphate cement (CMPC) powder, acting as photo absorber, leads to higher accuracy of the final structures. After curing the printed construct in a diammonium–hydrogen phosphate (DAHP) bath for hardening, the resulting mechanical properties can be adjusted without post-process sintering. Solid loading of up to 40 wt% CMPC powder is possible, and the resins are investigated regarding their rheological behavior and printability. The resulting constructs are analyzed in respect to their surface morphology using scanning electron microscope (SEM), porosity, phase composition using X-ray diffraction (XRD) methods, as well as mechanical properties influenced by the hardening process using DAHP for different durations. 相似文献
277.
Csaba Somlai Levente Nyerges Botond Penke Pter Hegyes Wolfgang Voelter 《Advanced Synthesis \u0026amp; Catalysis》1994,336(5):429-433
Theoretical calculations on different xanthene derivatives and related structures were performed and as a result conclusions could be drawn for the acid-lability of substituted xanthenes. (9-Hydroxyxanthene-3-oxy)acetic- and valeric acid ( 6a and 6b ) were selected, synthesized in a six-step route, and 6b was tested for its applicabiliy as a handle for solid phase synthesis of peptides. 相似文献
278.
Katalin Balázsi Csaba Balázsi 《International Journal of Applied Ceramic Technology》2022,19(2):753-761
Titanium carbide-based thin films have been produced by DC magnetron sputtering. It was demonstrated that the same technology with changing of the deposition parameters, such as deposition temperature or power of Ti target, resulted in the preparation of TiC/a:C thin films with various structures. The structure of thin films and volume fraction of amorphous and crystal phases were precisely tailored by the control of deposition parameters. These ceramic nanocomposite TiC/a:C thin films according to their various structures, hence, their different mechanical, tribological, or wetting parameters can be used in wide range of applications. 相似文献
279.
Maroua H. Kaou Zsolt E. Horváth Katalin Balázsi Csaba Balázsi 《International Journal of Applied Ceramic Technology》2023,20(2):689-699
In this work, the preparation of calcium–silicate-based composites consisting of natural waste from calcium source as eggshell and silica gel from a desiccator as a silicon source both presenting alternative materials for cheap preparation of eco-friendly calcium–silicate bioceramics has been investigated. The effect of the CaO/SiO2 ratio on microstructural properties has also been studied. The pseudowollastonite formation has been observed in the case of 40 wt.% CaO and 60 wt.% SiO2 with lowest porosity and highest density 2.6 g/cm3. In the case of 50 wt.% CaO and 50 wt.% SiO2, the phase transformation from pseudowollastonite to wollastonite was observed. Increasing the calcium content caused higher apparent porosity with 19%. It was shown that the development of novel ceramics from reused waste, eggshell, or silica can be an optimal solution for the low-cost preparation of calcium silicates with potential applications in medicine or cement, food industry. 相似文献