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Duly characterization of isolated PDT-resistant glioblastoma revealed that the resistance to PDT might be a consequence of several mechanisms, including higher repair efficiency of oxidative DNA damage and repair of DNA breaks. Higher activity of APE1 endonuclease and increased expression and activation of DNA damage kinase ATM was demonstrated in the U-87 MGR cell line, suggesting and proving that they are good targets for sensitization of resistant cells to PDT.Kisspeptins (KISSs) and RFamide-related peptide-3 (RFRP-3) affect the synthesis and secretion of luteinizing hormone (LH) and modulate female reproductive processes. The presence of KISS and RFRP-3 in the porcine pituitary gland and their contribution to the regulation of follicle-stimulating hormone (FSH) synthesis and secretion is unknown. This study analyzed the presence of KISS and RFRP-3 in the pituitary of estrous-cyclic pigs on days 2 to 3, 10 to 11, 12 to 13, 15 to 16 and 19 to 20 and early pregnant pigs on days 10 to 11, 12 to 13 and 15 to 16, and evaluated the effect of KISS and RFRP-3 on β-Fsh mRNA expression and FSH secretion in vitro by pituitary cells collected on selected days of the estrous cycle. The cells were cultured in vitro and treated with KISS (10-6 M, 10-7 M) and RFRP-3 (10-6 M, 10-7 M) or gonadotropin-releasing hormone (GnRH; 100 ng/mL) alone and in combinations (4 h or 24 h). The relative abundance of Kiss and Rfrp-3 and their receptor mRNA transcripts, as well as the KISS and RFRP-3 proteins, were found in the pituitaries of estrous-cyclic and early pregnant pigs. KISS after 4 h increased the secretion of FSH in estrous cyclic pigs mostly during the early-luteal phase and luteolysis. RFRP-3 inhibited the synthesis and secretion of FSH in estrous-cyclic pigs on days 19 to 20 and the secretion of FSH on days 2 to 3 and 10 to 12 of the estrous cycle compared with GnRH-treated cells. KISS in co-treatment with GnRH after 24 h enhanced FSH release on days 2 to 3 and 15 to 16 of the estrous cycle. In conclusion, KISS and RFRP-3 systems are present in the pituitary of estrous-cyclic and pregnant pigs. In estrous-cyclic pigs, KISS and RFRP-3 may affect the synthesis and secretion of FSH by pituitary cells.Bacterial infection and oxidative stress remain critical problems for wound closure because they frequently trigger severe complications and delay wound healing. In addition, maintaining a moist microenvironment can promote skin regeneration. In this study, a bilayer hydrogel modified with tannic acid (TA) was constructed to accelerate wound repair. The bilayer hydrogel, composed of a layer with large pores to absorb the fluids and allow gas exchange and small pores to maintain the wound moist and prevent bacterial invasion, was initially developed. Thereafter, TA was introduced into the hydrogel to form a dual crosslinked network and endowed the hydrogel with adhesiveness, antibacterial, and oxidation resistance. In addition, the TA@bilayer hydrogel exhibited shape memory behaviour and self-healing ability due to the hydrogen bonds formed between TA and the bilayer hydrogel. this website As a result, the TA@bilayer hydrogel significantly promoted wound closure by accelerating collagen deposition, reducing tumour necrosis factor-α (TNF-α) levels, and facilitating the expression of vascular endothelial growth factor (VEGF).Constructing highly efficient and multifunctional nanoparticles to overcome the multiple challenges of targeted drug delivery is a new strategy urgently needed in tumor therapy. Here, we synthesized pH-responsive prodrug (PEG2K-NH-N-DOX), GSH-responsive prodrug (PEG2K-S-S-CPT), folate-receptor targeting polymers (FA-PEG2K-L8, FA-PEG2K-TOS) and T1-enhanced magnetic resonance imaging contrast agents (Gd-DTPA-N16-16), used to encapsulate combrestatinA4 (CA4) to prepare multifunctional nanoparticles (FTDCAG NPs). Unlike other nanoparticles, FTDCAG NPs contains three drugs with the ability to control the release in time and space, which can maximize the effectiveness of precise cancer chemotherapy. We first confirmed that specific binding between FTDCAG NPs and overexpressed folate-receptor cells by flow cytometry and confocal laser scanning microscopy. We then investigated the spatiotemporally controlled release ability of FTDCAG NPs loaded with doxorubicin (DOX), CA4 and camptothecin (CPT). Relative to pH = 7.4, the release efficiency of CA4 in the pH = 6.5 increased by 63.4 %. The first released CA4 is able to destroy the angiogenesis and help tumor cells to be exposed to the remaining FTDCG NPs. After being internalized into the tumor cells, FTDCG NPs is disassembled and the CPT and DOX were released due to the increase of intracellular GSH concentration and the decrease of pH value. Besides, the relaxation time of FTDCAG NPs is 3.86 times that of clinical Gd-DTPA, and the in vitro and vivo T1-weighted imaging is brighter, which can be used to trace the nanoparticles by MRI. Therefore, FTDCAG NPs provide an efficient strategy for the design of multifunctional drug delivery systems for enhancing antitumor efficacy.In this work, sulfur and nitrogen co-doped carbon quantum dots (S,N-CQDs) were prepared via one-pot hydrothermal treatment of EDTA disodium and sodium sulfide. The prepared S,N-CQDs were characterized by TEM, XRD, FT-IR, XPS, UV-vis absorption and fluorescence spectra to characterize their morphology, crystal structure, functional groups, elemental composition, and optical properties. It was found that S and N elements were successfully doped into the CQDs and the morphology was approximately spherical with an average particle size of 2.16 nm, in which the excitation/emission wavelengths were 350 and 420 nm, respectively. Compared with single element doped CQDs, double element doped CQDs have a higher quantum yield and excellent optical stability. Cell experiments showed that S,N-CQDs had good biocompatibility because they had no obvious toxicity on both normal cell lines and cancer cell lines. More importantly, based on the synergy of static quenching and dynamic quenching, the S,N-CQDs were used as effective fluorescent probes for sensitive detection of DA, with high anti-interference and low limit of detection. Based on the good biocompatibility of S,N-CQDs, the detection of dopamine in actual serum samples were carried out and the results showed an excellent recovery rate. Therefore, this work provides a dopamine sensor with a practical application prospect.
Homepage: https://www.selleckchem.com/Proteasome.html
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