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1.
Front Public Health ; 12: 1378257, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601510

RESUMO

Background: Hospital resilience is essential in responding to disasters, but current research focuses mainly on frameworks and models rather than the protection of resilience and analysis of risk factors during public health emergencies. This study aims to examine the development of resilience in Chinese frontline hospitals during the initial COVID-19 outbreak in 2020, providing insights for future disaster response efforts. Objectives: We conducted interviews with 26 hospital staff members who were involved in the initial response to the COVID-19 outbreak in China. We used a semi-structured interview approach and employed purposive sampling and snowball sampling techniques. The interview outline was guided by the 'Action Framework' proposed by the World Health Organization (WHO) for responding to infectious disease emergencies. This framework includes dimensions such as command, surveillance, risk communication, medical response, and public health response. We analyzed the collected data using Colaizzi's seven-step data analysis method and the template analysis method. Results: WHO's 'action framework' effectively highlights the factors that contribute to hospital resilience. While medical response, including the availability of materials and facilities, the use of information technology, and the capacity for infectious disease diagnosis and treatment, remains crucial, other important aspects include awareness and beliefs about infections, treatment experience, interdisciplinary collaboration, and more. Additionally, it is essential to establish an intelligent command system, foster trusting partnerships between teams, improve monitoring capabilities for infectious disease agents, enhance risk communication through information synchronization and transparency, strengthen infection control planning, and improve environmental disinfection capabilities for effective public health emergency response. These contradictions significantly impact the enhancement of hospital resilience in dealing with major infectious disease outbreaks. Conclusion: In responding to sudden major infectious diseases, hospitals play a vital role within the healthcare system. Enhancing hospital resilience involves more than just improving treatment capabilities. It also requires effective command coordination at the hospital level, infection control planning, and the deployment of intelligent equipment. Additionally, planning for effective communication and coordination between hospitals, communities, and the national healthcare system can further enhance hospital resilience.


Assuntos
COVID-19 , Doenças Transmissíveis , Desastres , Resiliência Psicológica , Humanos , Emergências , Hospitais , COVID-19/epidemiologia , COVID-19/prevenção & controle
2.
Plant J ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446797

RESUMO

Histone 2B ubiquitination (H2Bub) and trimethylation of H3 at lysine 4 (H3K4me3) are associated with transcription activation. However, the function of these modifications in transcription in plants remains largely unknown. Here, we report that coordination of H2Bub and H3K4me3 deposition with the binding of the RNA polymerase-associated factor VERNALIZATION INDEPENDENCE2 (VIP2) to FLOWERING LOCUS C (FLC) modulates flowering time in Arabidopsis. We found that RING domain protein HISTONE MONOUBIQUITINATION1 (HUB1) and HUB2 (we refer as HUB1/2), which are responsible for H2Bub, interact with ARABIDOPSIS TRITHORAX1 (ATX1), which is required for H3K4me3 deposition, to promote the transcription of FLC and repress the flowering time. The atx1-2 hub1-10 hub2-2 triple mutant in FRIGIDIA (FRI) background displayed early flowering like FRI hub1-10 hub2-2 and overexpression of ATX1 failed to rescue the early flowering phenotype of hub1-10 hub2-2. Mutations in HUB1 and HUB2 reduced the ATX1 enrichment at FLC, indicating that HUB1 and HUB2 are required for ATX1 recruitment and H3K4me3 deposition at FLC. We also found that the VIP2 directly binds to HUB1, HUB2, and ATX1 and that loss of VIP2 in FRI hub1-10 hub2-2 and FRI atx1-2 plants resulted in early flowering like that observed in FRI vip2-10. Loss of function of HUB2 and ATX1 impaired VIP2 enrichment at FLC, and reduced the transcription initiation and elongation of FLC. In addition, mutations in VIP2 reduced HUB1 and ATX1 enrichment and H2Bub and H3K4me3 levels at FLC. Together, our findings revealed that HUB1/2, ATX1, and VIP2 coordinately modulate H2Bub and H3K4me3 deposition, FLC transcription, and flowering time.

3.
ACS Appl Mater Interfaces ; 16(4): 4550-4560, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38232046

RESUMO

Understanding the complex solvent effects on the microstructures of ink and catalyst layer (CL) is crucial for the development of high-performance anion exchange membrane fuel cells (AEMFCs). Herein, we study the solvent effects within the binary solvent ink system composed of water, isopropyl alcohol (IPA), commercial anion exchange ionomer, and Pt/C catalyst. The results show that the Pt/C particles and ionomer tend to form large aggregates wrapped with a thick ionomer layer in IPA-rich ink and promote the formation of large mesopores within the CL. With the increase of the water content in the ink, Pt/C particles are more likely to bridge to each other through wrapped FAA to form a well-connected three-dimensional network. The CL fabricated using water-rich ink shows smaller pores, higher porosity, and a more homogeneous ionomer network without the formation of large aggregates. Based on these results, we propose that the properties of the solvent mixture, including dielectric constant (ε) and solubility parameter (δ), affect the coulomb interaction of charged particles and surface tension at interfaces, which in turn affects the microstructure of ink and CL. By leveraging the solvent effects, we optimize the CL microstructures and improve the performance of AEMFC. These results may guide the rational design and fabrication of AEMFCs.

4.
Adv Mater ; 36(5): e2304496, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37934652

RESUMO

Developing high-performance electrocatalysts for alkaline hydrogen oxidation reaction (HOR) is crucial for the commercialization of anion exchange membrane fuel cells (AEMFCs). Here, boron interstitially inserted ruthenium (B-Ru/C) is synthesized and used as an anode catalyst for AEMFC, achieving a peak power density of 1.37 W cm-2 , close to the state-of-the-art commercial PtRu catalyst. Unexpectedly, instead of the monotonous decline of HOR kinetics with pH as generally believed, an inflection point behavior in the pH-dependent HOR kinetics on B-Ru/C is observed, showing an anomalous behavior that the HOR activity under alkaline electrolyte surpasses acidic electrolyte. Experimental results and density functional theory calculations reveal that the upshifted d-band center of Ru after the intervention of interstitial boron can lead to enhanced adsorption ability of OH and H2 O, which together with the reduced energy barrier of water formation, contributes to the outstanding alkaline HOR performance with a mass activity of 1.716 mA µgPGM -1 , which is 13.4-fold and 5.2-fold higher than that of Ru/C and commercial Pt/C, respectively.

5.
Angew Chem Int Ed Engl ; 62(38): e202308089, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37551837

RESUMO

The development of heterogeneous asymmetric catalysts has attracted increasing interest in synthetic chemistry but mostly relies on the immobilization of homogeneous chiral catalysts. Herein, a series of chiral metal-organic frameworks (MOFs) have been fabricated by anchoring similar chiral hydroxylated molecules (catalytically inactive) with different lengths onto Zr-oxo clusters in achiral PCN-222(Cu). The resulting chiral MOFs exhibit regulated enantioselectivity up to 83 % ee in the asymmetric ring-opening of cyclohexene oxide. The chiral molecules furnished onto the catalytic Lewis sites in the MOF create multilevel microenvironment, including the hydrogen interaction between the substrate and the chiral -OH group, the steric hindrance endowed by the benzene ring on the chiral molecules, and the proximity between the catalytic sites and chiral molecules confined in the MOF pores, which play crucial roles and synergistically promote chiral catalysis. This work nicely achieves heterogeneous enantioselective catalysis by chiral microenvironment modulation around Lewis acid sites.

6.
Elife ; 122023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37458359

RESUMO

Decidualization is a process in which endometrial stromal fibroblasts differentiate into specialized secretory decidual cells and essential for the successful establishment of pregnancy. The underlying mechanism during decidualization still remains poorly defined. Because decidualization and fibroblast activation share similar characteristics, this study was to examine whether fibroblast activation is involved in decidualization. In our study, fibroblast activation-related markers are obviously detected in pregnant decidua and under in vitro decidualization. ACTIVIN A secreted under fibroblast activation promotes in vitro decidualization. We showed that arachidonic acid released from uterine luminal epithelium can induce fibroblast activation and decidualization through PGI2 and its nuclear receptor PPARδ. Based on the significant difference of fibroblast activation-related markers between pregnant and pseudopregnant mice, we found that embryo-derived TNF promotes CPLA2α phosphorylation and arachidonic acid release from luminal epithelium. Fibroblast activation is also detected under human in vitro decidualization. Similar arachidonic acid-PGI2-PPARδ-ACTIVIN A pathway is conserved in human endometrium. Collectively, our data indicate that embryo-derived TNF promotes CPLA2α phosphorylation and arachidonic acid release from luminal epithelium to induce fibroblast activation and decidualization.


Assuntos
Decídua , PPAR delta , Gravidez , Feminino , Humanos , Animais , Camundongos , Decídua/metabolismo , PPAR delta/metabolismo , Ácido Araquidônico , Endométrio , Fibroblastos , Células Estromais/metabolismo
7.
Acta Pharm Sin B ; 13(7): 3153-3167, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37521875

RESUMO

Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies. Heat shock protein 90 (Hsp90) as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and resistance. Targeting Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and resistance. In this study, a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX, and a COA-modified 4-arm PEG polymer (4PSC) was synthesized. COA, an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression, was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory activity. Our results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic toxicity. By blocking the Hsp90 signaling pathway, 4PSC significantly enhanced the antitumor effect of PTX, inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in vitro. Remarkable results were further confirmed in vivo with two preclinical tumor models. These findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.

8.
J Cell Biol ; 222(9)2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37389657

RESUMO

Glutathionylation is a posttranslational modification involved in various molecular and cellular processes. However, it remains unknown whether and how glutathionylation regulates nervous system development. To identify critical regulators of synapse growth and development, we performed an RNAi screen and found that postsynaptic knockdown of glutathione transferase omega 1 (GstO1) caused significantly more synaptic boutons at the Drosophila neuromuscular junctions. Genetic and biochemical analysis revealed an increased level of glass boat bottom (Gbb), the Drosophila homolog of mammalian bone morphogenetic protein (BMP), in GstO1 mutants. Further experiments showed that GstO1 is a critical regulator of Gbb glutathionylation at cysteines 354 and 420, which promoted its degradation via the proteasome pathway. Moreover, the E3 ligase Ctrip negatively regulated the Gbb protein level by preferentially binding to glutathionylated Gbb. These results unveil a novel regulatory mechanism in which glutathionylation of Gbb facilitates its ubiquitin-mediated degradation. Taken together, our findings shed new light on the crosstalk between glutathionylation and ubiquitination of Gbb in synapse development.


Assuntos
Proteínas de Drosophila , Complexo de Endopeptidases do Proteassoma , Sinapses , Animais , Drosophila , Junção Neuromuscular , Complexo de Endopeptidases do Proteassoma/genética , Sinapses/fisiologia , Proteínas de Drosophila/genética
9.
J Mater Chem B ; 11(25): 5777-5785, 2023 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-37259766

RESUMO

A photoacoustic imaging (Au@PDA-WL NPs) probe was successfully prepared for monitoring the early degeneration of articular cartilage. WYRGRL immobilized on the surface of Au@PDA NPs could target the collagen II peptide, which is expressed on chondrocytes in vivo and in vitro, and the enrichment of this nano-probe on cartilage tissue further resulted in the localized plasmon resonance coupling effect, inducing an enhancement in photothermal conversion capacity after the formation of aggregates. Besides, the catechol structure in the PDA shell could eliminate ROS to effectively delay the development of osteoarthrosis.


Assuntos
Nanopartículas Metálicas , Osteoartrite , Técnicas Fotoacústicas , Humanos , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Técnicas Fotoacústicas/métodos , Osteoartrite/diagnóstico por imagem , Osteoartrite/terapia , Fototerapia , Diagnóstico Precoce
10.
Front Psychol ; 14: 1089608, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36777219

RESUMO

Background: Impulsivity has been defined as a tendency to respond with little forethought, often with disregard to the negative consequences to the impulsive individual or others. Problem gambling patients are characterized with impulse control and absent inhibition control, a tendency to react to stimuli in a rapid and unplanned fashion without complete processing of information. Method: Based on the information processing theory and the dual-systems model of self-control, 208 moderate-risk gambling were investigated by questionnaire to explore the moderating effect of self-control in the process of cognitive bias and cognitive style affecting the gambling impulse of moderate-risk gambling. Conclusion: Using hierarchical regression analysis, it is found that: (a) The gambling impulse of male moderate-risk gambling was stronger than female moderate-risk gambling. (b) Self-control negatively predicted trait impulsivity, and the stronger the individual self-control, the lower the level of trait impulsivity. (c) Cognitive bias positively predicted trait impulsivity, and high cognitive bias induced high-level trait impulsivity. Self-control played a moderating role between cognitive bias and trait impulsivity. (d) Compared with field-independent gambling, field-dependent gambling were more likely to have impulsive thoughts of gambling activities. Self-control played a moderating role between cognitive style and trait impulsivity.

11.
Public Health Pract (Oxf) ; 4: 100320, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36186155

RESUMO

Objectives: Coronavirus disease (COVID-19) outbreaks occurred on ships during the global pandemic of COVID-19. Investigation of the management and outcomes of these outbreaks will help guide future prevention and control strategies for respiratory infectious diseases on ships. Study design: Non-systematic narrative review. Methods: PubMed and Embase databases were searched using the keywords "ship", "cargo ship", "fishing boat", "cruise ship", "yacht", "merchant ship", "port", "SARS-COV-2" and "COVID-19", connected by "OR" internally and "AND" between two keywords. After review of the titles and abstracts, and exclusion of irrelevant articles, the infection situation and details of the response measures were recorded. Cases were subsequently selected for this study based on the detailed information and records available on the COVID-19 outbreak prevention and control measures and experiences. Results: Three representative cases were selected; the outbreak timeline and infection situation for these cases were summarised. Infection prevention and control measures and experiences for the three outbreaks were investigated in detail, including analysis of epidemic reports, and isolation, detection, screening, treatment and transportation procedures. Conclusions: This study demonstrates that timely detection and intervention, exposure reduction, control of asymptomatic infections, treatment and transport of patients, preparation for prevention and control in advance, the communication and cooperation of various stakeholders, and the establishment of short-term and long-term response mechanisms are key elements to improve the efficiency of infection prevention and control on ships.

12.
J Int Med Res ; 50(9): 3000605221121958, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36127814

RESUMO

OBJECTIVE: Vasovagal reaction (VVR) is an adverse reaction to blood donation. Applied muscle tension (AMT) has been reported to reduce the probability of VVR during blood donation; however, the results have been controversial. We therefore conducted a meta-analysis to systematically evaluate the effect of AMT in reducing VVR. METHODS: We searched six major databases using "applied muscle tension" and "blood donation-related vasovagal response" as keywords. Relevant articles published in English or Chinese between 1 January 2000 and 30 June 2021 were included in the analysis. The quality of the included articles was evaluated and publication bias was assessed by forest and funnel plots and by Egger's test. RESULTS: Fifty-one articles were identified, of which six were included according to the pre-defined inclusion and exclusion criteria. A fixed-effects model was adopted for effect size combination and revealed a relative risk of 0.52 (95% confidence interval 0.40 to 0.67). The AMT group was superior to the control in terms of VVR prevention. A funnel plot and Egger's test suggested that the findings were accurate and reliable with low publication bias. CONCLUSION: AMT could effectively reduce VVR during blood donation. Further multicenter studies with large sample sizes are needed to confirm these results.


Assuntos
Doadores de Sangue , Síncope Vasovagal , Humanos , Tono Muscular , Viés de Publicação , Risco , Síncope Vasovagal/etiologia , Síncope Vasovagal/prevenção & controle
13.
Am J Health Behav ; 46(3): 337-346, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35794752

RESUMO

Objective: In this study, we explored the characteristics of moral disengagement in sport and its mediating role in athletes' goal orientations and their attitudes towards doping We enrolled 203 athletes in the study. Methods: The Task and Ego Orientation in Sports Questionnaire, Moral Disengagement in Sport Scale and Performance Enhancement Attitude Scale were used to assess athletes' goal orientations and attitudes toward doping. Results: Our findings revealed that: (1) male athletes' scores for moral disengagement were significantly higher than those of female athletes; and (2) moral disengagement completely mediated the relationship between ego orientation and attitude towards doping, and partially mediated the association between task orientation and attitude towards doping. Conclusions: Changing the moral cognition and lowering the level of moral disengagement in athletes may be important issues to include in anti-doping education.


Assuntos
Objetivos , Esportes , Atletas , Atitude , Feminino , Humanos , Masculino , Princípios Morais
14.
Am J Health Behav ; 46(3): 259-273, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35794759

RESUMO

Objectives: In this study, we explored the occurrence and process of gambling addiction among sports lottery players. Methods: We used a case study approach. Three gamblers participated in this study and completed in-depth interviews and questionnaires. Results: We found that the motivation of winning is the key factor throughout the whole procedure of sports lottery addiction. The occurrence of sports lottery addiction generally experiences 4 patterns: initial, continuous, struggling, and addictive. Through these 4 patterns, we found that the procedure of sports lottery addiction includes interaction of individual needs and external attractions, motivation of sport lottery, action of sports lottery, emotional change, self-control versus out of control, investment expansion and motivation of winning, overconfidence or regret, continuous joint action of investment expansion and motivation of winning, addiction of sports lottery, and negativity. Conclusion: With in-depth analysis of the transition procedure from normal gambling to addiction to sports lottery, our findings not only revealed the changes of each sports lottery addiction pattern, but also analyzed the core factors for each pattern, which provide theoretical support for further study of sports lottery addiction.


Assuntos
Comportamento Aditivo , Jogo de Azar , Esportes , Comportamento Aditivo/epidemiologia , Comportamento Aditivo/psicologia , Jogo de Azar/epidemiologia , Humanos , Motivação , Esportes/psicologia , Inquéritos e Questionários
15.
ACS Appl Mater Interfaces ; 14(21): 24174-24186, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35604134

RESUMO

Preventing tumor recurrence is the most important target for cancer treatment. However, the current effective and advanced technology relies on the use of near-infrared region (NIR), and the equipment of NIR-I and NIR-II fluorescence imaging technique-based fluorescent-guided surgery is expensive and complicated to operate. Here, we report a safe and effective strategy of an organic-inorganic hybrid gold nanoparticle-based novel smart probe (Au@PDA-ss-PEGm NPs) which is appropriate for photoacoustic imaging (PAI) and plasmonic photothermal therapy (PPTT) of tumors in vivo. After intravenous injection, the probe would be transported to the tumor to penetrate the cellular membrane. Then the disulfide bond on the probe surface would be broken with the help of a high concentration of glutathione in the tumor cell. The remaining Au@PDA NPs would aggregate to form plasmonic nanoclusters and exhibit a notable plasmon coupling enhanced photothermal (PCEPT) effect. Besides, the results further proved its good biosafety and pharmacokinetic characteristics in vivo and, more important, a short time exposure under 808 nm laser after surgical removal of the tumor, which would be effective to prevent tumor recurrence and bring dawn to the high-efficiency treatment of tumors.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Técnicas Fotoacústicas , Linhagem Celular Tumoral , Glutationa , Ouro/química , Ouro/farmacologia , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Nanopartículas/química , Recidiva Local de Neoplasia , Técnicas Fotoacústicas/métodos , Fototerapia , Terapia Fototérmica , Nanomedicina Teranóstica/métodos
16.
Biosensors (Basel) ; 13(1)2022 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-36671856

RESUMO

As one of the most important parameters of biochemical analysis and detection, the pH value plays a very important role in cell function, food preservation and production, soil and water sources, and other applications. This makes it increasingly important to explore pH detection methods in depth. In this paper, a pH-responsive SERS probe based on the cyano Raman Tag was designed to realize pH sensing detection through the influence of the pH value of analytes on the displacement of the cyano Raman peak in the SERS probe. This cyano Raman tag exhibited not only excellent sensitivity in the liner range of pH 3.0-9.0 with a limit of detection (LOD) of pH 0.33, but also the anti-interference performance and stability (the relative standard deviation (RSD) was calculated to be 6.68%, n = 5). These results indicated that this pH SERS probe with the Raman cyano tag can provide new research ideas for future biological detection, bioimaging, and environmental detection.


Assuntos
Cianetos , Nanopartículas Metálicas , Análise Espectral Raman/métodos , Ouro , Limite de Detecção , Concentração de Íons de Hidrogênio
17.
J Am Chem Soc ; 143(32): 12499-12508, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34343431

RESUMO

Photoelectrochemical overall water splitting has been considered as a promising approach for producing chemical energy from solar energy. Although many photoelectrochemical cells have been developed for overall water splitting by coupling two semiconductor photoelectrodes, inefficient charge transfer between the light-harvesters and electron acceptor/donor severely restricts the solar energy conversion efficiency. Inspired by natural photosynthesis, we assembled a photoelectrochemical platform with multimediator modulation to achieve unassisted overall water splitting. Photogenerated electrons are transferred in order through multimediators driven by the electrochemical potential gradient, resulting in efficient charge separation and transportation with enhanced charge transfer rate and reduced charge recombination rate. The integrated system composed of inorganic oxide-based photoanode (BiVO4) and organic polymer-based photocathode (PBDB-T:ITIC:PC71BM) with complementary light absorption, exhibits a solar-to-hydrogen conversion efficiency as high as 4.3%. This work makes a rational design possible by constructing an efficient charge-transfer chain in artificial photosynthesis systems for solar fuel production.

18.
Front Oncol ; 11: 654995, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34094948

RESUMO

Lung cancer is the most frequently diagnosed cancer and the main cause of cancer death in the world. X-box binding protein 1 (XBP1), which is an important transcription factor involved in regulating the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress, might act as a potent oncogenic protein in the processes of tumorigenesis, tumor proliferation and metastasis in various cancers. However, the clinical significance and pathological role of XBP1 in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the expression of XBP1s protein in the 104 NSCLC tumor tissues and matched adjacent normal lung tissues (ANLT) by Immunohistochemical (IHC), and we found overexpressed XBP1s protein was associated with NSCLC TNM stages, lymph node metastasis and poor prognosis. The further gain-and loss-of-function experiments indicated overexpression of XBP1s protein promoted cell invasion, migration and metastasis both in vitro and in vivo. Further study showed XBP1s protein could upregulate insulin-like growth factor binding protein-3 (IGFBP3) expression, and regulated NSCLC cells invasion and metastasis by regulating IGFBP3. Taken together, XBP1s protein is markedly overexpressed in NSCLC and serves as an oncogene that play a critical role in NSCLC tumorigenesis and development. Importantly, XBP1s protein might not only be a potential biomarker for metastasis and prognosis but also a potential therapeutic target in NSCLC.

19.
J Nanobiotechnology ; 19(1): 152, 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022909

RESUMO

BACKGROUND: Mitochondria play a role in the occurrence, development, drug resistance, metastasis, and other functions of cancer and thus are a drug target. An acid-activated mitochondria-targeting drug nanocarrier with redox-responsive function was constructed in the present study. However, whether this vector can precisely delivery paclitaxel (PTX) to enhance therapeutic efficacy in drug-resistant lung cancer is unknown. RESULTS: Acid-cleavable dimethylmaleic anhydride (DA) was used to modify pluronic P85-conjugated mitochondria-targeting triphenylphosphonium (TPP) using disulfide bonds as intermediate linkers (DA-P85-SS-TPP and DA-P-SS-T). The constructed nanocarriers demonstrated enhanced cellular uptake and selective mitochondrial targeting at extracellular pH characteristic for a tumor (6.5) and were characterized by extended circulation in the blood. TPP promoted the targeting of the DA-P-SS-T/PTX nanomicelles to the mitochondrial outer membrane to decrease the membrane potential and ATP level, resulting in inhibition of P-glycoprotein and suppression of drug resistance and cancer metastasis. PTX was also rapidly released in the presence of high glutathione (GSH) levels and directly diffused into the mitochondria, resulting in apoptosis of drug-resistant lung cancer cells. CONCLUSIONS: These promising results indicated that acid-activated mitochondria-targeting and redox-responsive nanomicelles potentially represent a significant advancement in cancer treatment. GRAPHIC ABSTARCT.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Micelas , Mitocôndrias/metabolismo , Nanopartículas/química , Paclitaxel/metabolismo , Células A549 , Apoptose , Sistemas de Liberação de Medicamentos/métodos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Mitocôndrias/efeitos dos fármacos , Membranas Mitocondriais/efeitos dos fármacos , Nanopartículas/uso terapêutico , Oxirredução , Paclitaxel/química , Poloxaleno
20.
Molecules ; 26(5)2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33668340

RESUMO

Sigma-1 (σ-1) receptor agonists are considered as potential treatment for stroke. TS-157 is an alkoxyisoxazole-based σ-1 receptor agonist previously discovered in our group. The present study describes TS-157 profile in a battery of tests for cerebral ischemia. Initial evaluation demonstrated the compound's safety profile and blood-brain barrier permeability, as well as its ability to induce neurite outgrowth in vitro. The neurite outgrowth was shown to be mediated via σ-1 receptor agonism and involves upregulation of ERK phosphorylation (pERK). In particular, TS-157 also significantly accelerated the recovery of motor function in rats with transient middle cerebral artery occlusion (tMCAO). Overall, the results herein support the notion that σ-1 receptor agonists are potential therapeutics for stroke and further animal efficacy studies are warranted.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , Crescimento Neuronal/efeitos dos fármacos , Oxazóis/farmacologia , Receptores sigma/agonistas , Recuperação de Função Fisiológica/efeitos dos fármacos , Animais , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Estrutura Molecular , Oxazóis/síntese química , Oxazóis/química , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
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