Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 616
Filtrar
2.
Org Lett ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851121

RESUMO

Transition-metal-catalyzed activations of carbon-carbons bonds of small strained rings have widespread applications in synthetic and medicinal chemistry. However, coupling reactions of cyclobutanols involving ß-carbon elimination to construct C(sp3)-C(sp3) bonds have scarcely been developed. Here, we demonstrate a highly enantioselective Pd-catalyzed intermolecular C(sp3)-C(sp3) coupling reaction of a broad range of cyclobutanol derivatives and unactivated alkenes, allowing convenient access to a series of chiral benzene-fused cyclic compounds in a highly regio-, chemo-, and enantioselective manner.

3.
Insect Sci ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723412

RESUMO

NADPH-cytochrome P450 reductase (CPR) is involved in the metabolism of endogenous and exogenous substances, and detoxification of insecticides. RNA interference (RNAi) of CPR in certain insects causes developmental defects and enhanced susceptibility to insecticides. However, the CPR of Acyrthosiphon pisum has not been characterized, and its function is still not understood. In this study, we investigated the biochemical functions of A. pisum CPR (ApCPR). ApCPR was found to be transcribed in all developmental stages and was abundant in the embryo stage, and in the gut, head, and abdominal cuticle. After optimizing the dose and silencing duration of RNAi for downregulating ApCPR, we found that ApCPR suppression resulted in a significant decrease in the production of cuticular and internal hydrocarbon contents, and of cuticular waxy coatings. Deficiency in cuticular hydrocarbons decreased the survival rate of A. pisum under desiccation stress, and increased its susceptibility to contact insecticides. Moreover, desiccation stress induced a significant increase in ApCPR mRNA levels. We further confirmed that ApCPR participates in cuticular hydrocarbon production. These results indicate that ApCPR modulates cuticular hydrocarbon production, desiccation tolerance, and insecticide susceptibility in A. pisum, and presents a novel target for pest control. This article is protected by copyright. All rights reserved.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34792639

RESUMO

Although tobacco leaves (TLs) contain abundant bacteria, how the geography and leaf position of TLs affect these bacteria is unclear. Here, TLs at different positions from Henan (HN, strong flavor style) and Yunnan (YN, fresh flavor style) provinces were collected, and the bacteria were characterized by Illumina sequencing at harvest and 1 year of storage. Bacterial communities were very different between TLs originating from different geographical areas and positions, and beta diversity analysis showed that leaf position was the most important factor for phyllospheric bacterial communities, followed by geographical area and storage time. At the genus level, Subdoligranulum, Thermus, and Acinetobacter were obviously more abundant in HN than in YN, while Blautia and Ruminococcus were significantly more abundant in YN. These differences in bacterial communities decreased after 1 year of storage, indicating that the microbiota tends to become similar during tobacco processing. Storage time also affected the phyllospheric bacteria of TLs, as the bacterial communities shifted significantly on both HN and YN TLs after 1 year of storage. Significant differences in the predicted genes were also observed between the different geographic locations and leaf positions. Potential human pathogens, including Acinetobacter, Methylobacterium, and Escherichia-Shigella, were greatly different between TLs originating from different areas and positions. These data suggested that geographic variations and positions were associated with phyllospheric bacterial communities on TLs, which may be related to not only the flavor style and quality of TLs but also the potential health risks to humans. KEY POINTS: • Tobacco leaf position and tobacco growth location affected bacterial communities. • Microbial communities of TLs shifted significantly after one year of storage. • Potential human pathogens differed at different leaf positions and growth locations.

5.
Ecotoxicol Environ Saf ; 228: 112983, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34781135

RESUMO

BACKGROUND: Recently, both trivalent chromium Cr (III) and hexavalent chromium Cr (VI) have been reported to produce neurotoxicity. However, the underlying mechanisms of the neurotoxicity caused by different chemical valence of chromium remain unclear. OBJECTIVE: The purpose of this study was to investigate the mechanism of neurotoxicity induced by exposure to chromium with different valence states based on metabolic disturbance in zebrafish larvae. METHODS: Zebrafish embryos were exposed to 1 mg/L Cr (III) and 1 mg/L Cr (VI) for 120 hpf respectively. The related indexes of neural development were observed by stereoscope and behavior analysis system. 8OH-dG were detected using enzyme-linked immunosorbent assay. The generation of reactive oxygen species was detected using an oxidant-sensing probe 2',7'-dichlorodihydrofluorescein diacetate. AChE activity was determined by a colorimetric assay based on hydrolysis of acetylcholine. The expression levels of neurodevelopmental genes and methyltransferase genes in juvenile zebrafish was analyzed by real-time PCR. The methylation status of neurogenin1 and neurod1 genes was detected by bisulfite sequencing PCR. The binding of H3K27me3 was detected by chromatin immunoprecipitation-qPCR. Metabolic profiles and one carbon metabolic analysis were performed by UPLC-MS. RESULTS: There were no significant differences in survival rate, hatching rate and spontaneous movement of zebrafish in both Cr-exposed groups compared to the control. The malformation rate in Cr (VI) -exposed group was obviously increased compared to the control and Cr (III) -exposed group. At 48hpf and 72hpf of exposure, the embryonic heart rate in Cr (III)-exposed group was significantly higher than that of Cr (VI)-exposed group and the control. At 120hpf, zebrafish in both Cr-exposed groups exhibited decreasing changes in swimming distance and disturbance of sensitivity to light and dark. 8OH-dG in Cr (VI)-exposed group were significantly higher than that in the control. The generation of ROS in both Cr -exposed groups was significantly higher than that in the control. The activity of AchE was significantly decreased in both Cr-exposed groups compared to the control. Most of early neurogenesis related genes, such as α-tubulin, elavl3, gap43, sox19b, neurogenin1 and neurod1 in Cr-exposed groups were significantly up-regulated compared to those in the control. The expression of dnmt1 and dnmt3 genes was significantly down-regulated in both Cr-exposed groups. BSP-PCR results showed that genic sequences in the neurogenin1 and neurod1 genes have lower levels of DNA methylation in both Cr-exposed groups, especial in Cr (VI)-exposed group. ChIP analysis showed that there was a decrease in H3K27me3 binding within the corresponding region of neurogenin1 in both Cr-exposed groups and that of neurod1 in Cr (III)-exposed group. Untargeted metabolomic analysis showed that significant changes in metabolites induced by Cr exposure were associated with differences in primary bile acid biosynthesis, phospholipid biosynthesis (phosphatidylcholine biosynthesis and phosphatidylethanolamine biosynthesis), linoleic acid metabolism, arachidonic acid metabolism, amino acid metabolism, purine metabolism, betaine metabolism, spermidine and spermine biosynthesis, and folate metabolism, the last four of which are related to one carbon metabolism. Targeted analysis of one carbon metabolites (5-MT, Gly, Met, SAH and Hcy) related with folate cycle and methionine metabolism were significantly decreased upon Cr exposure. The elevated SAM to SAH ratio in both Cr- exposed group indicated the decreasing capacity for methylation reaction. CONCLUSION: Cr (III) and Cr (VI) can induce neurotoxicity by interfering with one carbon metabolism and affecting DNA methylation and histone methylation to regulate the expression of neuro-related genes. Cr exposure also influenced primary bile acid biosynthesis and phospholipid biosynthesis, which are associated with neuroprotective effects and need to be further validated.

6.
Inform Health Soc Care ; : 1-12, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34822311

RESUMO

As older adult populations rise in the United States, community-based telehealth programs are gaining momentum because of their ability to provide telehealth services for community-dwelling older adults at a lower cost compared to home-based telehealth services. The success of such community-based telehealth programs heavily depends on end-user engagement and acceptance; however, few studies to date have explored these issues. We conducted an interview study with 14 active and 3 inactive participants of a community-based Telehealth Intervention Program for Seniors (TIPS) to examine older individuals' perceived benefits and barriers to participating in community-based telehealth programs as well as strategies to improve those programs. We found that older adults had a positive experience toward the use of telehealth services in a community setting, including benefits like monitoring health status and enabling socialization. There were no perceived barriers about the telehealth program. Aspects that can be improved include facilitating the management and sharing of historical physiological data, providing additional assessments of cognitive and/or mental status, supporting self-education, and enabling more comprehensive health status tracking. We conclude this paper by discussing the implications of our results to the improvement of community-based telehealth programs for low-income, vulnerable aging populations.

7.
J Ethnopharmacol ; : 114845, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34800645

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sheng-ji Hua-yu (SJHY) formula is a Chinese herbal prescription for diabetic ulcers (DUs) treatment, which can accelerate wound reconstruction and shorten the healing time. However, its mechanism role maintains unclear. AIM OF THE STUDY: To elucidate the molecular mechanisms of SJHY application on DUs. MATERIALS AND METHODS: To begin with, transcriptome sequencing was adopted to identified differentially expression mRNAs among normal ulcers, DUs, and DUs + SJHY treatment in vivo. Liquid chromatography-tandem mass spectrometry was applied for the quality control of SJHY formula. GO and KEGG enrichment analysis were used to identify the mechanisms underlying the therapeutic effect of SJHY formula, and then gene set enrichment analysis and ingenuity pathway analysis were conducted for functional analysis. Further, qPCR detection was performed in vivo for validation. RESULTS: SJHY administration could regulate the glucose metabolic process, AMPK and HIF-1 pathway to accelerate healing processes of DUs. Besides, CRHR1, SHH, and GAL were identified as the critical targets, and SLC6A3, GRP, FGF23, and CYP27B1 were considered as the upstream genes of SJHY treatment. Combined with animal experiments, the prediction results were validated in DUs mice model. CONCLUSIONS: This study used modular pharmacology analysis to identify the biomarkers of SJHY formula and provide the potential therapeutic targets for DUs treatment as well.

8.
JCI Insight ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34784298

RESUMO

Synthetic immunosuppressive glucocorticoids (GCs) are widely used to control inflammatory bowel disease (IBD). However, the impact of GC signaling on intestinal tumorigenesis remains controversial. Here, we report that intestinal epithelial glucocorticoid receptor (GR), but not whole intestinal tissue GR, promotes chronic intestinal inflammation-associated colorectal cancer in both humans and mice. In colorectal cancer patients, GR is enriched in intestinal epithelial cells and high epithelial GR is associated with poor prognosis. Consistently, intestinal epithelium-specific deletion of GR (GR iKO) in mice increases macrophage infiltration, improves tissue recovery, and enhances anti-tumor response in a chronic inflammation-associated colorectal cancer model. Consequently, GR iKO mice develop fewer and less advanced tumors than control mice. Furthermore, oral GC administration in the early-phase of tissue injury delays recovery and accelerates the formation of aggressive colorectal cancers. Our study reveals that intestinal epithelial GR signaling represses acute colitis but promotes chronic inflammation-associated colorectal cancer, and suggests that colorectal epithelial GR could serve as a predictive marker for colorectal cancer risk and prognosis. Our findings further suggest that although synthetic glucocorticoid treatment for IBD should be used with caution, there is a therapeutic window for glucocorticoid therapy during colorectal cancer development in immunocompetent patients.

9.
Zhongguo Gu Shang ; 34(11): 1077-82, 2021 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-34812028

RESUMO

OBJECTIVE: To investigate the value of lumbar quantitative CT (QCT) in vertebroplasty for osteoporotic fracture combined with scoliosis. METHODS: The clinical data of 60 patients with osteoporotic fractures combined with different degrees of scoliosis treated by vertebroplasty from December 2017 to December 2019 were retrospectively analyzed. There were 18 males and 42 females, aged from 65 to 81 (72.63±3.34)years old. All patients were received QCT examination before surgery. According to the QCT value, the patients were divided into osteopenia group(QCT>80 g/L, 10 cases, 12 vertebrae), osteoporosis group(QCT 40-80 g/L, 35 cases, 48 vertebrae) and severe osteoporosis group(QCT<40 g/L, 15 cases, 22 vertebrae). The dispersion and leakage of bone cement in the injured vertebrae of patients with different degrees of QCT value were observed, and the QCT value in the selection of puncture point, correction of Cobb angle and recovery of vertebral height were analyzed in the patients. RESULTS: Among 60 cases of 82 vertebrae, 41 cases of 55 vertebrae were punctured by concave unilateral puncture, according for 67.07%. Among them, there were 2 cases with 2 vertebrae in osteopenia group, 26 cases with 35 vertebrae in osteoporosis group, and 13 cases with 18 vertebrae in severe osteoporosis group. There was significant difference in the number of cases with unilateral or bilateral puncture among the three groups (χ2=13.699, P=0.001); there was no significant difference in the number of cases with bone cement leakage among the three groups (χ2=1.403, P=0.496). The Cobb angle of scoliosis was significantly differentbetween preoperative and postoperative follow-up(P<0.05);the height of injured vertebral body was significantly different between preoperative and postoperative follow-up (P<0.05). CONCLUSION: For patients with osteoporotic fracture combined with scoliosis undergoing vertebroplasty, the severity of osteoporosis should be determined according to lumbar QCT detection, and the concave side of scoliosis should be selected for puncture, which is conducive to improving scoliosis, restoring spinal stability and improving surgical safety.


Assuntos
Fraturas por Compressão , Fraturas por Osteoporose , Escoliose , Fraturas da Coluna Vertebral , Vertebroplastia , Idoso , Cimentos Ósseos , Feminino , Humanos , Masculino , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/lesões , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
10.
Transl Pediatr ; 10(10): 2459-2466, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34765469

RESUMO

Background: Childhood neuromyelitis optica spectrum disorders (NMOSDs) may cause visual impairment and brain or spinal cord damage, and the effects may be permanent if left untreated. Since the incidence of NMOSD cases in children is relatively low, the understanding of NMOSD among children is inadequate. Methods: This investigation examined the clinical and neuroimaging characteristics of childhood NMOSD. We retrospectively analyzed the clinical information of 11 NMOSD patients admitted to our centre from 2012 to 2021. The disease status was assessed by the Expanded Disability Status Scale (EDSS) score. Results: The two major symptoms observed in the study cohort were optic neuritis (ON) (9/11) and encephalopathy (7/11). Antibody tests were performed on 8 children, 2 of whom showed serum aquaporin 4 (AQP4) antibody positivity, and another 2 presented with serum myelin oligodendrocyte glycoprotein (MOG) antibody positivity. All patients showed white matter hyperintensity on magnetic resonance imaging (MRI) scans. Interestingly, a rare radiological sign, enlarged perivascular space (PVS), which is more commonly observed in the elderly or adults, was found in 4 participants with more severe clinical manifestations. Conclusions: While NMOSD in children is less commonly diagnosed through clinical evaluations, the symptoms of ON and encephalopathy should raise the possibility of the disease. As the diagnosis of NMOSD in children is relatively difficult, enlarged PVS may represent a promising biomarker for the diagnosis and evaluation of NMOSD.

12.
JMIR Hum Factors ; 8(4): e26017, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34842529

RESUMO

BACKGROUND: Personal clinical data, such as laboratory test results, are increasingly being made available to patients via patient portals. However, laboratory test results are presented in a way that is difficult for patients to interpret and use. Furthermore, the indications of laboratory test results may vary among patients with different characteristics and from different medical contexts. To date, little is known about how to design patient-centered technology to facilitate the interpretation of laboratory test results. OBJECTIVE: The aim of this study is to explore design considerations for supporting patient-centered communication and comprehension of laboratory test results, as well as discussions between patients and health care providers. METHODS: We conducted a user-centered, multicomponent design research consisting of user studies, an iterative prototype design, and pilot user evaluations, to explore design concepts and considerations that are useful for supporting patients in not only viewing but also interpreting and acting upon laboratory test results. RESULTS: The user study results informed the iterative design of a system prototype, which had several interactive features: using graphical representations and clear takeaway messages to convey the concerning nature of the results; enabling users to annotate laboratory test reports; clarifying medical jargon using nontechnical verbiage and allowing users to interact with the medical terms (eg, saving, favoriting, or sorting); and providing pertinent and reliable information to help patients comprehend test results within their medical context. The results of a pilot user evaluation with 8 patients showed that the new patient-facing system was perceived as useful in not only presenting laboratory test results to patients in a meaningful way but also facilitating in situ patient-provider interactions. CONCLUSIONS: We draw on our findings to discuss design implications for supporting patient-centered communication of laboratory test results and how to make technology support informative, trustworthy, and empathetic.

14.
BMC Musculoskelet Disord ; 22(1): 870, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641845

RESUMO

BACKGROUND: Matrix Gla (γ-carboxyglutamate) protein (MGP) is considered a strong inhibitor of ectopic calcification, and it has been associated with OA severity, although not conclusively. We utilized male Dunkin-Hartley (DH) guinea pigs to investigate the expression of MGP throughout aging and disease pathogenesis in a spontaneous model. METHOD: Twenty-five male DH guinea pigs were obtained and nurtured to several timepoints, and then randomly and equally divided by age into five subgroups (1-, 3-, 6-, 9-, and 12-months, with the 1-month group as the reference group). DH guinea pigs in each group were euthanized at the designated month-age and the left or right medial tibial plateaus cartilages were randomly excised. OA severity was described by modified Mankin Score (MMS) at microscopy (Safranin O/Fast Green stain). Proteomic evaluation using isobaric tags for relative and absolute quantification (iTRAQ) was performed to validate the age-related changes in the MGP profiles, and immunohistochemistry (IHC) methods were applied for semi-quantitative determination of MGP expression in articular cartilage. RESULTS: The histopathologic findings validated the increasing severity of cartilage degeneration with age in the DH guinea pigs. The MMS showed significant, stepwise (every adjacent comparison P < 0.05) disease progression with month-age. The iTRAQ indicated that MGP levels increased significantly with advancing age (P < 0.05), as supported by the IHC result (P < 0.05). CONCLUSION: Increased expression of MGP in male DH guinea pigs was present throughout aging and disease progression and may be link to increased OA severity. Further studies are needed to investigate and confirm the association between MGP levels and OA severity.


Assuntos
Cartilagem Articular , Osteoartrite , Animais , Proteínas de Ligação ao Cálcio , Proteínas da Matriz Extracelular , Cobaias , Masculino , Proteômica
15.
J Insect Sci ; 21(5)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34655291

RESUMO

Crop resistance plays a role in preventing aphid damage, benefiting food production industries, but its effects are limited due to aphid adaptation and phenotypic plasticity. Therefore, furthering understanding of aphid-crop interactions will improve our ability to protect crops from aphids. To determine how aphids adapt to resistant varieties of wheat, Triticum aestivum L. over time, we performed a laboratory experiment to assess the multi-generational effects of three wheat varieties, Batis, Ww2730, and Xiaoyan22, with different resistance levels on the fitness of Sitobion avenae (Fab.) (Hemiptera: Aphididae). The results showed that Ww2730 and Xiaoyan22 were more resistant than Batis to S. avenae, regardless of whether the aphids were newly introduced or had been acclimated before being introduced to the three wheat varieties. However, the effect of resistance on aphid life-history traits was time dependent. Aphid weigh gain increased and they development faster of the acclimated generation compared to the newly introduced generation on all three varieties. And the fecundity on the three varieties and net reproduction rates on Batis and Xiaoyan22 significantly decreased. Aphid fitness in terms of individual life-history parameters improved, whereas aphid fitness in terms of reproductive decreased, and a convergence effect, the difference gaps and standard errors of all life-history traits among the three acclimated populations had narrowed and were less than those in the three first-generation populations, was observed during the 3-mo experimental period. We suggested that S. avenae could rapidly respond to wheat resistance through life-history plasticity.


Assuntos
Afídeos , Controle de Insetos , Triticum , Animais , Afídeos/crescimento & desenvolvimento , Afídeos/fisiologia , Produtos Agrícolas , Fertilidade , Traços de História de Vida , Defesa das Plantas contra Herbivoria , Folhas de Planta , Reprodução
17.
Chem Commun (Camb) ; 57(87): 11473-11476, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34652356

RESUMO

Photothermal therapy (PTT) achieves substantive therapeutic progress in certain tumor types without exogenous agents but is hampered by the over-activated inflammatory response or tumor recurrence in some cases. Herein, we technically developed the metal-polyphenolic nanosystem with precise NIR-II fluorescence-imaging guidance for combining hafnium (Hf)-sensitized radiotherapy with PTT to regress tumor growth.

18.
ACS Appl Mater Interfaces ; 13(43): 51205-51217, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34693713

RESUMO

Much recent attention has focused on the voltage-driven reversible topotactic transformation between the ferromagnetic metallic perovskite (P) SrCoO3-δ and oxygen-vacancy-ordered antiferromagnetic insulating brownmillerite (BM) SrCoO2.5. This is emerging as a paradigmatic example of the power of electrochemical gating (using, e.g., ionic liquids/gels), the wide modulation of electronic, magnetic, and optical properties generating clear application potential. SrCoO3 films are challenging with respect to stability, however, and there has been little exploration of alternate compositions. Here, we present the first study of ion-gel-gating-induced P → BM transformations across almost the entire La1-xSrxCoO3 phase diagram (0 ≤ x ≤ 0.70), under both tensile and compressive epitaxial strain. Electronic transport, magnetometry, and operando synchrotron X-ray diffraction establish that voltage-induced P → BM transformations are possible at essentially all x, including x ≤ 0.50, where both P and BM phases are highly stable. Under small compressive strain, the transformation threshold voltage decreases from approximately +2.7 V at x = 0 to negligible at x = 0.70. Both larger compressive strain and tensile strain induce further threshold voltage lowering, particularly at low x. The P → BM threshold voltage is thus tunable, via both composition and strain. At x = 0.50, voltage-controlled ferromagnetism, transport, and optical transmittance are then demonstrated, achieving Curie temperature and resistivity modulations of ∼220 K and at least 5 orders of magnitude, respectively, and enabling estimation of the voltage-dependent Co valence. The results are analyzed in the context of doping- and strain-dependent oxygen vacancy formation energies and diffusion coefficients, establishing that it is thermodynamic factors, not kinetics, that underpin the decrease in the threshold voltage with x, that is, with increasing formal Co valence. These findings substantially advance the practical and mechanistic understanding of this voltage-driven transformation, with fundamental and technological implications.

19.
Nat Commun ; 12(1): 5733, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593794

RESUMO

In addition to increasing the expression of programmed death-ligand 1 (PD-L1), tumor cells can also secrete exosomal PD-L1 to suppress T cell activity. Emerging evidence has revealed that exosomal PD-L1 resists immune checkpoint blockade, and may contribute to resistance to therapy. In this scenario, suppressing the secretion of tumor-derived exosomes may aid therapy. Here, we develop an assembly of exosome inhibitor (GW4869) and ferroptosis inducer (Fe3+) via amphiphilic hyaluronic acid. Cooperation between the two active components in the constructed nanounit induces an anti-tumor immunoresponse to B16F10 melanoma cells and stimulates cytotoxic T lymphocytes and immunological memory. The nanounit enhances the response to PD-L1 checkpoint blockade and may represent a therapeutic strategy for enhancing the response to this therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Portadores de Fármacos/química , Exossomos/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Melanoma Experimental/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Compostos de Benzilideno/farmacologia , Compostos de Benzilideno/uso terapêutico , Linhagem Celular Tumoral/transplante , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/imunologia , Exossomos/imunologia , Exossomos/metabolismo , Feminino , Ferroptose/imunologia , Humanos , Ácido Hialurônico/química , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Memória Imunológica , Ativação Linfocitária/efeitos dos fármacos , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Evasão Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
20.
ACS Nano ; 15(10): 16934-16945, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34661387

RESUMO

Nanomedicine has revolutionized cancer therapeutic strategies but has not completely changed the outcomes of tricky tumors that evolve a sophisticated immunosuppressive tumor microenvironment (TME) such as acidification. Here, a metal-phenolic network-based nanocomplex embedded with lactate oxidase (LOX) and a mitochondrial respiration inhibitor atovaquone (ATO) was constructed for immunosuppressive TME remodeling and sonodynamic therapy (SDT). In this nanocomplex, the sonosensitizer chlorin e6-conjugated polyphenol derivative can induce the generation of tumor lethal reactive oxygen species upon ultrasound irradiation. LOX served as a catalyst for intracellular lactic acid exhaustion, and ATO led to mitochondrial dysfunction to decrease oxygen consumption. This nanocomplex reversed the tumor immunosuppressive status by alleviating tumor hypoxia and acidic TME, achieving the characteristic enhancement of SDT and the inhibition of tumor proliferation and metastasis.


Assuntos
Microambiente Tumoral , Terapia por Ultrassom , Linhagem Celular Tumoral , Ácido Láctico , Espécies Reativas de Oxigênio , Hipóxia Tumoral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...