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1.
Oncol Rep ; 51(5)2024 May.
Article in English | MEDLINE | ID: mdl-38456515

ABSTRACT

After the publication of the article, an interested reader drew to the authors' attention that, in the western blots shown in Fig. 5C and D, a pair of data panels were inadvertently duplicated comparing between panels (C) and (D); in addition, the cell migration data shown in Fig. 7F on p. 1852 were selected incorrectly. The authors have examined their original data, and realize that these errors arose inadvertently as a consequence of their mishandling of their data. The revised versions of Figs. 5 and 7, featuring the corrected data for the caspase-8 experiment in Fig. 5C and alternative data for the cell migration assay experiments in Fig. 7F, are shown on the next two pages. The revised data shown for these Figures do not affect the overall conclusions reported in the paper. All the authors agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. Furthermore, the authors apologize to the readership for any inconvenience caused. [Oncology Reports 40: 1843-1854, 2018; DOI: 10.3892/or.2018.6593].

2.
Small ; : e2309194, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38039490

ABSTRACT

Hierarchical self-assembly of 2D metal-organic layers (MOLs) for the construction of advanced functional materials have witnessed considerable interest, due to the increasing atomic utilizations and well-defined atom-property relationship. However, the construction of atomically precise MOLs with mono-/few-layered thickness through hierarchical self-assembly process remains a challenge, mostly because the elaborate long-range order is difficult to control via conventional noncovalent interaction. Herein, a quadruple π-sticked metal-organic layer (πMOL) is reported with checkerboard-like lattice in ≈1.0 nanometre thickness, on which the catalytic selectivity can be manipulated for highly efficient CO2 reduction reaction (CO2 RR) and hydrogen evolution reaction (HER) over a single metal site. In saturated CO2 aqueous acetonitrile, Fe-πMOL achieves a highly effective CO2 RR with the yield of ≈3.98 mmol g-1  h-1 and 91.7% selectivity. In contrast, the isostructural Co-πMOL as well as mixed metallic FeCo-πMOL exhibits a high activity toward HER under similar conditions. DFT calculations reveal that single metal site exhibits the significant difference in CO2 adsorption energy and activation barrier, which triggers highly selective CO2 RR for Fe site and HER for Co site, respectively. This work highlights the potential of supramolecular π… π interaction for constructing monolayer MOL materials to uniformly distribute the single metal sites for artificial photosynthesis.

3.
PeerJ ; 11: e16631, 2023.
Article in English | MEDLINE | ID: mdl-38144182

ABSTRACT

Background: The heterogeneity of colorectal cancer (CRC) is the main cause of the disparity of drug sensitivity and the variability of prognosis. Pyroptosis is closely associated with the development and prognosis of various tumors, including CRC. Dividing CRC into distinct subgroups based on pyroptosis is a worthwhile topic for improving the precision treatment and prognosis prediction of CRC. Methods: We classified patients into two clusters using the consensus clustering based on the pyroptosis-related genes (PRGs). Next, the prognostic signature was developed with LASSO regression analysis using the screened genes from differentially expressed genes (DEGs) by univariate and multivariate Cox analyses. According to the pyroptosis-related score (PR score) calculated with the signature, patients belonged to two groups with distinct prognosis. Moreover, we assessed the immune profile to explore the relationship between the signature and immunological characteristics. Two single cell sequencing databases were adopted for further exploration of tumor immune microenvironment (TME). In addition, we applied our own cohort and Drugbank to explore the correlation of the signature and clinical therapies. We also studied the expression of key genes by immunohistochemistry. Results: The signature performed well in predicting the prognosis of CRC as the high area under curve (AUC) value demonstrated. Patients with a higher PR score had poorer prognosis and higher expression of immune checkpoints but more abundant infiltration of immune cells. Combining with the indicator of therapeutic analysis, they might benefit more from immune checkpoint blockade (ICB) and neo-adjuvant chemoradiotherapy (nCRT). Conclusion: In conclusion, our study is based on genomics and transcriptomics to investigate the role of PRGs in CRC. We have established a prognostic signature and integrated single-cell data to study the relationship between the signature with the TME in CRC. Its clinical application in reliable prediction of prognosis and personalized treatment was validated by public and own sequencing cohort. It provided a new insight for the personalized treatment of CRC.


Subject(s)
Colorectal Neoplasms , Pyroptosis , Humans , Prognosis , Pyroptosis/genetics , Area Under Curve , Chemoradiotherapy, Adjuvant , Colorectal Neoplasms/genetics , Tumor Microenvironment/genetics
4.
Radiat Oncol ; 18(1): 175, 2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37891611

ABSTRACT

BACKGROUND: Accurate prediction of response to neoadjuvant chemoradiotherapy (nCRT) is very important for treatment plan decision in locally advanced rectal cancer (LARC). The aim of this study was to investigate whether self-attention mechanism based multi-sequence fusion strategy applied to multiparametric magnetic resonance imaging (MRI) based deep learning or hand-crafted radiomics model construction can improve prediction of response to nCRT in LARC. METHODS: This retrospective analysis enrolled 422 consecutive patients with LARC who received nCRT before surgery at two hospitals. All patients underwent multiparametric MRI scans with three imaging sequences. Tumor regression grade (TRG) was used to assess the response of nCRT based on the resected specimen. Patients were separated into 2 groups: poor responders (TRG 2, 3) versus good responders (TRG 0, 1). A self-attention mechanism, namely channel attention, was applied to fuse the three sequence information for deep learning and radiomics models construction. For comparison, other two models without channel attention were also constructed. All models were developed in the same hospital and validated in the other hospital. RESULTS: The deep learning model with channel attention mechanism achieved area under the curves (AUCs) of 0.898 in the internal validation cohort and 0.873 in the external validation cohort, which was the best performed model in all cohorts. More importantly, both the deep learning and radiomics model that applied channel attention mechanism performed better than those without channel attention mechanism. CONCLUSIONS: The self-attention mechanism based multi-sequence fusion strategy can improve prediction of response to nCRT in LARC.


Subject(s)
Multiparametric Magnetic Resonance Imaging , Rectal Neoplasms , Humans , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Retrospective Studies , Neoadjuvant Therapy/methods , Treatment Outcome , Chemoradiotherapy/methods
5.
Front Pharmacol ; 14: 1188215, 2023.
Article in English | MEDLINE | ID: mdl-37324450

ABSTRACT

Osteoarthritis (OA), a chronic joint cartilage disease, is characterized by the imbalanced homeostasis between anabolism and catabolism. Oxidative stress contributes to inflammatory responses, extracellular matrix (ECM) degradation, and chondrocyte apoptosis and promotes the pathogenesis of OA. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central regulator of intracellular redox homeostasis. Activation of the NRF2/ARE signaling may effectively suppress oxidative stress, attenuate ECM degradation, and inhibit chondrocyte apoptosis. Increasing evidence suggests that the NRF2/ARE signaling has become a potential target for the therapeutic management of OA. Natural compounds, such as polyphenols and terpenoids, have been explored to protect against OA cartilage degeneration by activating the NRF2/ARE pathway. Specifically, flavonoids may function as NRF2 activators and exhibit chondroprotective activity. In conclusion, natural compounds provide rich resources to explore the therapeutic management of OA by activating NRF2/ARE signaling.

6.
bioRxiv ; 2023 May 04.
Article in English | MEDLINE | ID: mdl-37205371

ABSTRACT

NLR family, apoptosis inhibitory proteins (NAIPs) detect bacterial flagellin and structurally related components of bacterial type III secretion systems (T3SS), and recruit NLR family, CARD domain containing protein 4 (NLRC4) and caspase-1 into an inflammasome complex that induces pyroptosis. NAIP/NLRC4 inflammasome assembly is initiated by the binding of a single NAIP to its cognate ligand, but a subset of bacterial flagellins or T3SS structural proteins are thought to evade NAIP/NLRC4 inflammasome sensing by not binding to their cognate NAIPs. Unlike other inflammasome components such as NLRP3, AIM2, or some NAIPs, NLRC4 is constitutively present in resting macrophages, and not thought to be regulated by inflammatory signals. Here, we demonstrate that Toll-like receptor (TLR) stimulation upregulates NLRC4 transcription and protein expression in murine macrophages, which licenses NAIP detection of evasive ligands. TLR-induced NLRC4 upregulation and NAIP detection of evasive ligands required p38 MAPK signaling. In contrast, TLR priming in human macrophages did not upregulate NLRC4 expression, and human macrophages remained unable to detect NAIP-evasive ligands even following priming. Critically, ectopic expression of either murine or human NLRC4 was sufficient to induce pyroptosis in response to immunoevasive NAIP ligands, indicating that increased levels of NLRC4 enable the NAIP/NLRC4 inflammasome to detect these normally evasive ligands. Altogether, our data reveal that TLR priming tunes the threshold for NAIP/NLRC4 inflammasome activation and enables inflammasome responses against immunoevasive or suboptimal NAIP ligands.

7.
Carbohydr Polym ; 310: 120713, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-36925260

ABSTRACT

Carboxymethyl cellulose (CMC)/polyvinyl alcohol (PVA) hydrogels loaded with soybean peptide (SPE) were fabricated via a freeze-thaw method. These hydrogels conquer barriers in simulated gastric fluid (SGF), and then release SPE in simulated intestinal fluid (SIF). The results of in vitro SPE release from these hydrogels showed that in SGF only a little of the SPE released, but in SIF the SPE was completely released. The released SPE had scavenging rates for DPPH and ABTS free radicals of 41.68 and 31.43 %. The pharmacokinetic model of SPE release from the hydrogels in SIF was studied. When the hydrogels are moved from SGF to SIF, the sorption of the shrinkage hydrogel network is entirely controlled by stress-induced relaxations. There are swollen and shrunken regions during SPE release. For SPE release into the SIF, SPE has to be freed from the weak bonds in the swollen regions by changes in the conformation of CMC and PVA. The release rate of SPE was found to be governed by the diffusion and swelling rate of the shrinkage hydrogel network. The Korsmeyer-Peppas equation diffusion exponents (n) for SPE release from the hydrogels are >2.063, indicating a super case II transport. These data demonstrate CMC/PVA hydrogels have potential applications in oral peptide delivery.


Subject(s)
Drug Delivery Systems , Polyvinyl Alcohol , Drug Delivery Systems/methods , Polyvinyl Alcohol/chemistry , Carboxymethylcellulose Sodium , Glycine max , Hydrogen-Ion Concentration , Peptides , Hydrogels/chemistry
8.
Angew Chem Int Ed Engl ; 62(18): e202301925, 2023 Apr 24.
Article in English | MEDLINE | ID: mdl-36866977

ABSTRACT

Spin manipulation of transition-metal catalysts has great potential in mimicking enzyme electronic structures to improve activity and/or selectivity. However, it remains a great challenge to manipulate room-temperature spin state of catalytic centers. Herein, we report a mechanical exfoliation strategy to in situ induce partial spin crossover from high-spin (s=5/2) to low-spin (s=1/2) of the ferric center. Due to spin transition of catalytic center, mixed-spin catalyst exhibits a high CO yield of 19.7 mmol g-1 with selectivity of 91.6 %, much superior to that of high-spin bulk counterpart (50 % selectivity). Density functional theory calculations reveal that low-spin 3d-orbital electronic configuration performs a key function in promoting CO2 adsorption and reducing activation barrier. Hence, the spin manipulation highlights a new insight into designing highly efficient biomimetic catalysts via optimizing spin state.

9.
Inorg Chem ; 62(7): 3170-3177, 2023 Feb 20.
Article in English | MEDLINE | ID: mdl-36744794

ABSTRACT

The peak photoluminescence (PL) of conventional fluorophores is independent of the excitation wavelength (called Kasha's rule), while the search of metal-organic framework materials with the so-called anti-Kasha's rule emission remains very limited. Herein, we report the observation of anti-Kasha's rule emission in a multicomponent PL three-dimensional nanotubular metal-organic framework (abbr. MOF-NT), [Zn(µ-L)(µ-bix)]n·0.33nH2O [H2L = biphenyl-3,5-dicarboxylic acid; bix = 1,4-bis(imidazole-1-ylmethyl)benzene]. The MOF-NT crystalline sample represents a notable example of strong excitation-dependent fluorescence from the ultraviolet to the visible spectral region. Moreover, by virtue of electronic flexibility and high PL efficiency, MOF-NT shows a discriminative PL response between isomeric nitroaromatic compounds. The work demonstrated the intrinsic anti-Kasha's rule emission in the crystalline-state MOF materials, providing new visions for the development of advanced solid-state emissive materials.

10.
J Biomater Appl ; 37(7): 1195-1204, 2023 02.
Article in English | MEDLINE | ID: mdl-36633217

ABSTRACT

Dopamine has been widely used for surface modification of cardiovascular medical devices as it forms films on most substrates that provide functional groups for surface chemical modification. However, under oxidative stress, the phenolic hydroxyl group on dopamine can undergo reversible transformation into phenol-semiquinone-quinone, which can cause cytotoxicity and immunotoxicity. In this study, we measured the effects of semiquinone on the behavior of vascular wall cells and inflammatory cells under oxidative stress via ultraviolet irradiation with a hydrogen peroxide diluent. Na2S2O3 was used as a stabilizer to obtain a semiquinone-rich poly-dopamine film, then phenol-semiquinone-quinone ratio on its surface was evaluated at three irradiation-oxidation time points. We found that the poly-dopamine film with ultraviolet irradiation in hydrogen peroxide solution for 15 min had the highest semiquinone occupancy of 19.18%. In the experimental group irradiated for 15 min, endothelial cells were cultured statically for 3 days and the number of surface adherent endothelial cells in the group with added semiquinone stabilizer was reduced to 73% of that in the group without stabilizer, indicating that semiquinone rich surface inhibits adhesion and proliferation of endothelial cells; Smooth muscle cells were cultured statically for 3 days, and the number of adherent smooth muscle on surfaces without stabilizer was reduced to 75% of that on surfaces with stabilizer added, indicating that semiquinone rich surfaces promote smooth muscle proliferation. These results demonstrate that semiquinone can adversely affect the repair effect after implantation of cardiovascular materials. Therefore, our study provides a reference for the application and optimization of dopamine in cardiovascular implant materials.


Subject(s)
Dopamine , Endothelial Cells , Dopamine/pharmacology , Hydrogen Peroxide , Oxidation-Reduction , Quinones
11.
Colloids Surf B Biointerfaces ; 223: 113141, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36682296

ABSTRACT

Dopamine is a small molecule inspired by the dopamine motif of mussel foot proteins, and PDA is formed by the self-polymerization of dopamine. Under the UV-irradiation,PDA would be oxidized by reactive oxygen species (ROS) which were produced by photocatalytic reactions on TiO2 surfaces,thus regulating the adhesion behavior of endothelial cells (ECs) TiO2 inhibited platelet (Plt) adhesion after UV exposure. Polydopamine (PDA)-TiO2 micropatterns (P-PDA-TiO2) were prepared by magnetron sputtering and photolithography. This micropatterns successfully achieves selective adhesion of Plt and ECs. The selective adhesion of ECs disappears after vacuum reduction. In contrast to conventional cell patterning strategies, P-PDA-TiO2 can easily achieve pattern separation of ECs and Plts and provide a new concept for building complex blood-contacting devices.


Subject(s)
Dopamine , Endothelial Cells , Polymers/pharmacology
12.
Chem Commun (Camb) ; 59(9): 1229-1232, 2023 Jan 26.
Article in English | MEDLINE | ID: mdl-36629868

ABSTRACT

High-temperature negative thermal quenching (NTQ) phosphors are crucial to high-performance light-emitting devices. Herein, we report the high-temperature NTQ effect in deep-red to near-infrared (NIR) emitting copper iodide cluster-based coordination polymers as unconventional phosphors, whose NTQ operating temperature can reach as high as 500 K, the highest temperature reached by NTQ molecular-based materials.

13.
Acta Biomater ; 157: 655-669, 2023 02.
Article in English | MEDLINE | ID: mdl-36436757

ABSTRACT

In-stent restenosis (ISR) and late thrombosis, usually caused by excessive smooth muscle cell (SMC) proliferation and delayed endothelial layer repair, respectively, are the main risks for the failure of vascular stent implantation. For years, modification of stents with biomolecules that could selectively inhibit SMC proliferation and support endothelial cell (EC) growth had drawn extensive attention. However, the modulatory effect of these biomolecules faces the impact of oxidative stress, inflammation, and hyperlipidemia of the pathological vascular microenvironment, which is caused by the stent implantation injury and atherosclerosis lesions. Here, we modified stents with a natural and multi-functional flavonoid, baicalin (BCL), using poly-dopamine (PDA) coating technology to combat the harmful impact of the pathological microenvironment. Stent with an appropriate BCL immobilization density (approximately 2.03 µg/cm2) successfully supported ECs growth while inhibited SMC proliferation. Furthermore, baicalin-modified surfaces regulated the oxidative stress, inflammation, and high-lipid of the pathological microenvironment to inhibit endothelial dysfunction and the oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cells formation. In vivo results showed that baicalin-modified stents exhibited significant anti-ISR, anti-inflammatory, and endothelialization-promoting functions. Our study suggests that the multi-functional baicalin with pathological microenvironment-regulation (PMR) effect has potential use in the surface engineering of cardiovascular devices. STATEMENT OF SIGNIFICANCE: Empowering vascular stents with selective modulation of smooth muscle cells and endothelial cells by surface technology has become an important research direction for stent surface engineering. However, stent coatings that can furthermodulate the pathological microenvironment of blood vessels have been rarely reported. In this study, we constructed a multifunctional coating based on a flavonoid, baicalin, which can selectively modulate vascular wall cells and improve the pathological microenvironment. This study may provide a reference for developing advanced vascular stents.


Subject(s)
Endothelial Cells , Thrombosis , Humans , Stents , Endothelium , Cell Proliferation , Flavonoids/pharmacology
14.
Inorg Chem ; 61(46): 18779-18788, 2022 Nov 21.
Article in English | MEDLINE | ID: mdl-36346405

ABSTRACT

Phosphor-converted white light-emitting diodes (pc-wLEDs) are promising candidates for next-generation solid-state lighting and display technologies. However, most of the conventional phosphors in pc-wLED devices suffer from serious thermal quenching (TQ) at high temperatures. Herein, we investigate an unconventional high-efficiency metal-halide cluster-based phosphor with dynamic Cu-Cu interactions that can resist the TQ effect of photoluminescence. The temperature-dependent structure and solid-state and in situ NMR spectroscopy reveal that the weakening of the Cu-Cu interaction in such a phosphor system enables the electronic structural transition from a bonding to a nonbonding state and hence sustains the PL efficiency at high temperatures (up to 100 °C). The pc-wLEDs incorporating the zero-TQ phosphor show a rapid brightness rise even at a high bias current (1000 mA) with a color rendering index as high as 90, comparable to the commercial phosphor-based prototype LEDs (e.g., YAG:Ce3+). This work establishes a novel prototype of a cluster-based phosphor featuring dynamic intermetallic interactions, which paves the way for the exploration of pc-wLEDs against thermal quenching.

15.
Mater Today Bio ; 17: 100494, 2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36425925

ABSTRACT

Endowing materials with catalytic activities analogous to those of the natural endothelium to thus enhance their biological performance has become an option for constructing advanced blood-contact materials. The electron transfer between Cu2+ and Cu+ in the porphyrin center can catalyze the reaction of GSH and GSNO to generate NO, and this electron transfer can also catalyze the decomposition of ROS. Based on this, we created a dual-catalytic surface possessing NO-generating and ROS-scavenging activities to better mimic the versatile catalytic abilities of the endothelium. Copper tetraphenylporphyrin/titanium dioxide nanoparticles (CuTPP/TiO2-NPs) exhibiting excellent NO-generating and ROS-scavenging activities were synthesized and immobilized on the material surface to form a dual-catalytic film (CuTPP/TiO2-film) with the help of the catechol chemistry technique. Unlike most single catalytic surfaces, the dual-catalytic CuTPP/TiO2-film effectively regulated the microenvironment surrounding the implanted device by releasing NO signaling molecules and scavenging harmful ROS. This dual-catalytic film exhibited excellent biosafety and biocompatibility with anti-thrombosis, vascular wall cells (ECs and SMCs) modulation, and anti-inflammatory properties. We envision that this dual-catalytic endothelial bionic strategy may provide a promising solution to the clinical problems plaguing blood-contact devices and provide a novel basis for the further development of surface catalytic-engineered biomaterials.

16.
Psychiatry Res ; 317: 114904, 2022 11.
Article in English | MEDLINE | ID: mdl-36265196

ABSTRACT

Methamphetamine abuse is escalating worldwide. Its strong and irreversible neurotoxicity generally causes structural and functional changes in the brain. Repetitive transcranial magnetic stimulation (rTMS) as a non-invasive tool can be used to modulate neuronal activity, cortical excitability, and dopaminergic neurotransmission. This study aims to explore the efficacy of high-frequency rTMS in reducing drug craving and increasing decision-making ability for methamphetamine use disorder patients. Sixty-four methamphetamine use disorder patients were randomized to sham rTMS group and 10-Hz rTMS group. Visual analog scale (VAS) and Iowa game test (IGT) were used to evaluate drug craving and cognitive decision-making ability before and after treatment. Before the treatment, the two groups had no differences in the scores of VAS and IGT. After the intervention, VAS scores of 10-Hz rTMS group were significantly lower than that of sham rTMS group. In addition, the two groups had significant differences in the net score of IGT on block 4 and block 5, which favoured the 10-Hz rTMS group. Taken together, the present results suggest that High-frequency rTMS can be used to reduce drug craving and improve decision-making function for methamphetamine use disorder.


Subject(s)
Craving , Methamphetamine , Humans , Craving/physiology , Dorsolateral Prefrontal Cortex , Methamphetamine/adverse effects , Prefrontal Cortex , Transcranial Magnetic Stimulation/methods , Treatment Outcome
17.
Front Pharmacol ; 13: 1016981, 2022.
Article in English | MEDLINE | ID: mdl-36160403

ABSTRACT

Genistein, a natural isoflavone rich in soybean and leguminous plants, has been shown various biological effects, such as anti-inflammation, anti-oxidation, anti-cancer, and bone/cartilage protection. Due to the structural similarity to estrogen, genistein exhibits estrogen-like activity in protecting against osteoporosis and osteoarthritis. Furthermore, genistein has been considered as an inhibitor of tyrosine kinase, which has been found to be dysregulated in the pathological development of osteoporosis, osteoarthritis, and intervertebral disc degeneration (IDD). Many signaling pathways, such as MAPK, NF-κB, and NRF2/HO-1, are involved in the regulatory activity of genistein in protecting against bone and cartilage diseases. The potential molecular mechanisms of genistein in therapeutic management of bone and cartilage diseases have been investigated, but remain to be fully understood. In this article, we mainly discuss the current knowledge of genistein in protecting against bone and cartilage diseases, such as osteoporosis, osteoarthritis, rheumatoid arthritis (RA), and IDD.

18.
Molecules ; 27(14)2022 Jul 11.
Article in English | MEDLINE | ID: mdl-35889315

ABSTRACT

Solid-state lighting technology, where light-emitting diodes (LEDs) are used for energy conversion from electricity to light, is considered a next-generation lighting technology. One of the significant challenges in the field is the synthesis of high-efficiency phosphors for designing phosphor-converted white LEDs under high flux operating currents. Here, we reported the synthesis, structure, and photophysical properties of a tetranuclear Cu(I)-halide cluster phosphor, [bppmCu2I2]2 (bppm = bisdiphenylphosphinemethane), for the fabrication of high-performance white LEDs. The PL investigations demonstrated that the red emission exhibits a near-unity photoluminescence quantum yield at room temperature and unusual spectral broadening with increasing temperature in the crystalline state. Considering the excellent photophysical properties, the crystalline sample of [bppmCu2I2]2 was successfully applied for the fabrication of phosphor-converted white LEDs. The prototype white LED device exhibited a continuous rise in brightness in the range of a high bias current (100-1000 mA) with CRI as high as 84 and CCT of 5828 K, implying great potential for high-quality white LEDs.

19.
Cell Death Discov ; 8(1): 217, 2022 Apr 21.
Article in English | MEDLINE | ID: mdl-35449198

ABSTRACT

Otitis media (OM) is a common disease that can cause hearing loss in children. Currently, the main clinical treatment for OM is antibiotics, but the overuse of antibiotics might lead to bacterial resistance, which is a worldwide public health challenge. Studying the pathogenesis of OM will help us develop new effective treatments. Ferroptosis is one type of programmed cell death characterized by the occurrence of lipid peroxidation driven by iron ions. Many studies have shown that ferroptosis is associated with infectious diseases. It is presently unclear whether ferroptosis is involved in the pathogenesis of OM. In this study, we explored the relationship between ferroptosis and OM by PGPS-induced OM in C57BL/6 mice and treating the induced OM with ferroptosis inhibitors deferoxamine (DFO), Ferrostatin-1 (Fer-1), and Liperoxstatin-1 (Lip-1). We examined the expression of ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) and prostaglandin-endoperoxide synthase 2 (Cox2), glutathione peroxidase 4 (GPX4) protein as well as lipid peroxidation markers 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). The results showed that in PGPS-induced OM model mice, several ferroptosis-related proteins including ACSL4 and Cox2 were up-regulated compared to mice treated with saline. Meanwhile, a ferroptosis-related protein GPX4 was down-regulated upon PGPS treatment. The DFO treatment in PGPS-inoculated mice effectively inhibited the development of OM. The inhibitors treatment caused a significant decrease in the expression of ACSL4, Cox2, 4 HNE, MDA, reduction in free iron. Meanwhile, the ferroptosis inhibitors treatment caused increase in the expression of inflammation-related factors tumor necrosis factor-α (TNF-α) and antioxidant protein GPX4. Our results suggest that there is a crosstalk between ferroptosis signaling pathway and the pathogenesis of OM. Ferroptosis inhibition can alleviate PGPS-induced OM.

20.
Front Bioeng Biotechnol ; 10: 855471, 2022.
Article in English | MEDLINE | ID: mdl-35252160

ABSTRACT

Silver nanoparticles (AgNPs) are widely used because of their excellent antimicrobial properties. However, the poor hemocompatibility limits the application of AgNPs in blood contact materials. General approaches to improve the hemocompatibility of AgNPs-containing surfaces are to construct barrier layers or co-immobilize anticoagulant biomolecules. But such modification strategies are often cumbersome to prepare and have limited applications. Therefore, this study proposes a simple UV-photo-functionalization strategy to improve the hemocompatibility of AgNPs. We loaded AgNPs onto titanium dioxide (TiO2) nanoparticles to form a composite nanoparticles (Ag@TiO2NPs). Then, UV treatment was performed to the Ag@TiO2NPs, utilizing the diffusible photo-induced anticoagulant properties of TiO2 nanoparticles to enhance the hemocompatibility of AgNPs. After being deposited onto the PU surface, the photo-functionalized Ag@TiO2NPs coating showed excellent antibacterial properties against both Gram-positive/Gram-negative bacteria. Besides, In vitro and ex-vivo experiments demonstrated that the photo-functionalized Ag@TiO2NPs coating had desirable hemocompatibility. This modification strategy can provide a new solution idea to improve the hemocompatibility of metal nanoparticles.

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