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1.
J Am Chem Soc ; 143(45): 19167-19177, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34738793

RESUMO

Organosilicon compounds and polymers have found wide applications as synthetic building blocks and functional materials. Hydrosilylation is a common strategy toward the synthesis of organosilicon compounds and polymers. Although transition-metal-catalyzed hydrosilylation has achieved great advances, the metal-free hydrosilylation polymerization of dienes and bis(silane)s, especially the one suitable for both electron-rich and electron-deficient dienes, is largely lacking. Herein, we report a visible-light-driven metal-free hydrosilylation polymerization of both electron-rich and electron-deficient dienes with bis(silane)s by using the organic photocatalyst and hydrogen atom transfer (HAT) catalyst. We achieved the well-controlled step-growth hydrosilylation polymerizations of the electron-rich diene and bis(silane) monomer due to the selective activation of Si-H bonds by the organic photocatalyst (4CzIPN) and the thiol polarity reversal reagent (HAT 1). For the electron-deficient dienes, hydrosilylation polymerization and self-polymerization occurred simultaneously in the presence of 4CzIPN and aceclidine (HAT 2), providing the opportunity to produce linear, hyperbranched, and network polymers by rationally tuning the concentration of electron-deficient dienes and the ratio of bis(silane)s and dienes to alter the proportion of the two polymerizations. A wide scope of bis(silane)s and dienes furnished polycarbosilanes with high molecular weight, excellent thermal stability, and tunable architectures.

2.
Biomacromolecules ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34775750

RESUMO

The adsorption-mediated transcytosis (AMT) induced by the electrostatic interaction between the positively charged surface of carriers and negatively charged cell membrane is a new paradigm enabling nanomedicine's tumor extravasation and infiltration. However, little is known about the correlation between the carrier's charge density and its AMT-induced tumor infiltration efficiency. Herein, we investigate the effect of the cationic polymer's charge on the AMT-induced tumor penetration ability using in vitro multilayer tumor spheroids (MTSs). A cationic polymer, polyethylenimine (PEI), is amidized with acetic anhydride to obtain acetylated PEIs (AcPEIs) with different cationic charge densities. As the amidization ratio increases, the AcPEIs' cytotoxicity, zeta potential, and cell-binding affinity significantly decrease. Notably, not only does the weak cell binding (AcPEIs with high acetylation degrees) lead to slow endocytosis and inefficient transcytosis, so does the strong cell-binding PEI. The PEI with 24% acetylation (AcPEI24%) is found to have the highest transcytosis efficiency because its balanced cell-binding affinity triggers fast adsorption-mediated endocytosis. The subsequent Golgi apparatus/endoplasmic reticulum-mediated exocytosis via extracellular vesicles leads to highly effective transcellular delivery and tumor penetration in MTSs. Therefore, the drug carrier's surface cationic charge density critically influences its AMT-induced tumor penetration efficiency. This study provides mechanistic insights into the design of drug-delivery systems with active transcytosis for improved tumor penetration and enhanced therapeutic efficiency.

3.
J Colloid Interface Sci ; 608(Pt 2): 2111-2119, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34752981

RESUMO

Three-dimensional (3D) plasmonic nano-arrays can provide high surface-enhanced Raman scattering (SERS) sensitivity, good spectral uniformity and excellent reproducibility. However, it is still a challenge to develop a simple and efficient method for fabrication of 3D plasmonic nano-arrays with high SERS performance. Here we report a facile approach to construct ordered arrays of silver (Ag) nanoparticles-assembled spherical micro-cavities using polystyrene (PS) sphere template-assisted electrodeposition and post-growth. The electrodeposited small Ag nanoparticles grow into bigger stable nanoparticles during the post-growth process, which could significantly improve the SERS sensitivity. The Ag nanoparticles-assembled 3D micro-cavity array provides much more hotspots in the excitation laser beam-covered volume than the two-dimensional counterpart. The relative standard deviation (RSD) of 612 cm-1 peak of rhodamine 6G (R6G) was calculated to be 8%, and the RSD of the characteristic peak taken from substrates of different batches was less than 10%. The detectable lower concentration as low as 1 fM was achieved for an aqueous solution of R6G. Such SERS substrate also showed high sensitivity to thiram (fungicide) and paraquat (herbicide) in water with limits of detection of 0.067 nM and 2.5 nM respectively. Furthermore, it also demonstrated that SERS detection of pesticide residues on fruits can be realized, showing a potential application in rapid monitoring food safety.

4.
Comput Math Methods Med ; 2021: 5770228, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691238

RESUMO

Background: Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer. Treatment is dramatically difficult due to its high complexity and poor prognosis. Due to the disclosed dual functions of autophagy in cancer development, understanding autophagy-related genes devotes into novel biomarkers for HCC. Methods: Differential expression of genes in normal and tumor groups was analyzed to acquire autophagy-related genes in HCC. These genes were subjected to GO and KEGG pathway analyses. Genes were then screened by univariate regression analysis. The screened genes were subjected to multivariate Cox regression analysis to build a prognostic model. The model was validated by the ICGC validation set. Results: To sum up, 42 differential genes relevant to autophagy were screened by differential expression analysis. Enrichment analysis showed that they were mainly enriched in pathways including regulation of autophagy and cell apoptosis. Genes were screened by univariate analysis and multivariate Cox regression analysis to build a prognostic model. The model constituted 6 feature genes: EIF2S1, BIRC5, SQSTM1, ATG7, HDAC1, and FKBP1A. Validation confirmed the accuracy and independence of this model in predicting the HCC patient's prognosis. Conclusion: A total of 6 feature genes were identified to build a prognostic risk model. This model is conducive to investigating interplay between autophagy-related genes and HCC prognosis.

5.
ACS Appl Mater Interfaces ; 13(37): 44028-44040, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34499483

RESUMO

Polymeric nanocapsules hold considerable applications in cancer drug delivery, but the synthesis of well-defined nanocapsules with a tunable drug release property remains a significant challenge in fabrication. Herein, we demonstrate a supramolecular complexation strategy to assemble small molecular platinum (Pt) compounds into well-defined nanocapsules with high drug loading, acidity-sensitivity, and tunable Pt releasing profile. The design utilizes poly(ethylene glycol)-dendritic polylysine-G4/amides to complex with Pt compounds, forming stable nanocapsules with diameters approximately ∼20 nm and membrane thickness around several nanometers. The stability, drug content, and release profiles are tunable by tailoring the dendritic structure. The designated polymer-Pt nanocapsules, PEG-G4/MSA-Pt, showed sustained blood retention, preferential tumor accumulation, enhanced cellular uptake, lysosomal drug release, and nuclear delivery capability. PEG-G4/MSA-Pt showed enhanced antitumor efficacy compared to free cisplatin and other nanocapsules, which stopped the progression of both A549 cell xenografts and patient-derived xenografts (PDXs) of hepatocellular carcinoma on a mice tumor model. Thus, we believe this strategy is promising for developing Pt-based nanomedicine for cancer drug delivery.

6.
Cancer Lett ; 522: 93-104, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34536556

RESUMO

Obesity is a global public health issue. Obesity-related chronic low-grade inflammation (meta-inflammation) can lead to aberrant adipokine release and promote cardiometabolic diseases and obesity-related tumors. However, the mechanisms involved in the initiation of inflammatory responses in obesity and obesity-related tumors as well as metastasis are not fully understood. In this study, we found that the increased tumor necrosis factor-alpha (TNF-α) in adipocytes promoted the lung metastasis of MC38 colon cancer cells via Fas signaling. The release of TNF-α and interleukin (IL)-6 by Fas signaling in adipocytes was caused by the activation of the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways mediated by the interaction of Fas with Bmx, a non-receptor tyrosine kinase. Moreover, the Fas/Bmx complex is involved in the inflammation of adipocytes via Fas at the Tyr189 site and SH2 domain of Bmx. This is the first study to report the interaction between Fas and Bmx in adipocyte inflammation, which may provide clues for the development of potential new treatment strategies for obesity-related diseases.

7.
Neurochem Res ; 46(12): 3264-3272, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34536195

RESUMO

Neurobrucellosis is a serious central nervous system (CNS) inflammatory disorder caused by Brucella, and outer membrane protein-31 (Omp31) plays an important role in Brucella infection. This study aims to determine whether Omp31 can induce autophagy in BV-2 microglia. Another goal of the study is to further examine the effect of autophagy on the nuclear transcription factor κB (NF-κB) p65 signaling pathway. We observed that Omp31 stimulated autophagy by increasing microtubule-associated protein 1 light chain 3B (LC3B-II) levels and inducing autophagosome formation at 6 h and 12 h. Concomitantly, Omp31 induced tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expression in a time-dependent manner but reduced the expression of TNF-α at 6 h. We utilized Omp31 with or without rapamycin or 3-methyladenine (3-MA) to treat BV-2 microglia, and it demonstrated further that Omp31 induced autophagy by promoting LC3B-II, Beclin-1 proteins expression and inhibiting the p62 protein levels. Furthermore, we explored the effects of autophagy on the NF-κB p65 pathway through western blot analysis, RT-qPCR assay, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence. The data suggest that Omp31 as well as rapamycin, the autophagy inducer, can decrease TNF-α levels through the inhibition of the NF-κB p65 signaling pathway. Taken together, Omp31 can function as a catalyst in both autophagy induction and NF-κB p65 signal inhibition. Furthermore, Omp31-induced autophagy may inhibit the expression of TNF-α by negatively regulating NF-κB p65 signaling pathway.

8.
Front Med (Lausanne) ; 8: 662340, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277655

RESUMO

Background: Mechanically ventilated patients in the intensive care unit (ICU) have high mortality rates. There are multiple prediction scores, such as the Simplified Acute Physiology Score II (SAPS II), Oxford Acute Severity of Illness Score (OASIS), and Sequential Organ Failure Assessment (SOFA), widely used in the general ICU population. We aimed to establish prediction scores on mechanically ventilated patients with the combination of these disease severity scores and other features available on the first day of admission. Methods: A retrospective administrative database study from the Medical Information Mart for Intensive Care (MIMIC-III) database was conducted. The exposures of interest consisted of the demographics, pre-ICU comorbidity, ICU diagnosis, disease severity scores, vital signs, and laboratory test results on the first day of ICU admission. Hospital mortality was used as the outcome. We used the machine learning methods of k-nearest neighbors (KNN), logistic regression, bagging, decision tree, random forest, Extreme Gradient Boosting (XGBoost), and neural network for model establishment. A sample of 70% of the cohort was used for the training set; the remaining 30% was applied for testing. Areas under the receiver operating characteristic curves (AUCs) and calibration plots would be constructed for the evaluation and comparison of the models' performance. The significance of the risk factors was identified through models and the top factors were reported. Results: A total of 28,530 subjects were enrolled through the screening of the MIMIC-III database. After data preprocessing, 25,659 adult patients with 66 predictors were included in the model analyses. With the training set, the models of KNN, logistic regression, decision tree, random forest, neural network, bagging, and XGBoost were established and the testing set obtained AUCs of 0.806, 0.818, 0.743, 0.819, 0.780, 0.803, and 0.821, respectively. The calibration curves of all the models, except for the neural network, performed well. The XGBoost model performed best among the seven models. The top five predictors were age, respiratory dysfunction, SAPS II score, maximum hemoglobin, and minimum lactate. Conclusion: The current study indicates that models with the risk of factors on the first day could be successfully established for predicting mortality in ventilated patients. The XGBoost model performs best among the seven machine learning models.

9.
Cancer Lett ; 520: 100-108, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34245853

RESUMO

Pancreatic cancer is a severe disease that threatens human health. The hypoxic tumor microenvironment in pancreatic cancer leads to resistance to conventional therapies and helps to maintain tumor malignancy. First-line drugs present the disadvantage of systemic side effects, and a synergistic method with sonodynamic therapy (SDT) has been established as an emerging approach. In this study, we produced hypoxia-alleviating nanoplatforms (denoted as PZGI NPs) with zeolitic imidazolate frameworks-90 (ZIF-90) nanoparticles nucleating on platinum (Pt) nanoparticles and co-loaded with gemcitabine and IR780. This platform can catalyze peroxide to oxygen with loaded Pt nanoparticles to alleviate tumor hypoxia. Moreover, the loaded drugs could be quickly released in the lysosome microenvironment, which has a low pH value and high ATP level microenvironment in the mitochondria. This strategy could enhance the sensitivity of cancer cells to chemotherapy. Further, under ultrasound exposure, it could transfer the produced oxygen into a highly cytotoxic singlet oxygen for the augmented sonodynamic effect. Therefore, this multifunctional hypoxia-alleviating nanoplatform offers a promising strategy for chemo-sonodynamic therapy against pancreatic cancer.

10.
Phytomedicine ; 87: 153588, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34091148

RESUMO

BACKGROUND: Cholestasis is characterized by accumulation of bile components in liver and systemic circulation. Restoration of bile acid homeostasis via activating farnesoid x receptor (FXR) is a promising strategy for the treatment of cholestasis. FXR-SHP (small heterodimer partner) axis plays an important role in maintaining bile acid homeostasis. PURPOSE: To investigate the anti-cholestasis effect of Dolomiaea souliei (Franch.) C.Shih (D. souliei) and clarify its underlying mechanism against α-naphthylisothiocyanate (ANIT) induced acute intrahepatic cholestasis. METHODS: ANIT-induced Sprague-Dawley rats were employed to investigate the anti-cholestasis effect of D. souliei ethyl acetate extract (DSE). Ursodeoxycholic acid (UDCA) was used as positive control. Bile flow and blood biochemical parameters were measured. Liver histopathological examination was conducted via hematoxylin-eosin staining. Western blot analysis was carried out to evaluate the protein levels related to bile acids metabolism and inflammation. The interactions between FXR and costunolide or dehydrocostus lactone, were conducted by molecular docking experiments. The effect of costunolide and dehydrocostus lactone on aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and FXR expression were also evaluated using guggulsterone-induced L02 cells. RESULTS: DSE could promote bile excretions and protect against ANIT-induced liver damage in cholestasis rats. Protein levels of FXR, SHP, Na+/taurocholate cotransporter (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2) were increased and the expressions of cholesterol 7α-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1) were decreased by DSE. Meanwhile, the anti-inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) were also significantly increased, and the pro-inflammatory factor, interleukin-10 (IL-10), was significantly decreased in rats of DSE groups. Molecular docking revealed that costunolide and dehydrocostus lactone could be well docked into the FXR protein molecule, and hydrophobic interactions played the main function. Costunolide could reverse the increased AST and ALT levels and increase the FXR expression in guggulsterone-induced L02 cells. CONCLUSION: DSE had an anti-cholestasis effect by activating FXR-SHP axis, inhibiting synthesis of bile acid, and increasing bile secretion, together with inflammatory response and improving liver injury. Costunolide may be the main active component. This study provided a potential therapeutic mechanism for D. souliei as an anti-cholestasis medicine in the treatment of cholestasis liver diseases.


Assuntos
Asteraceae/química , Ácidos e Sais Biliares/metabolismo , Colestase Intra-Hepática/tratamento farmacológico , Extratos Vegetais/farmacologia , 1-Naftilisotiocianato/toxicidade , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/metabolismo , Acetatos/química , Alanina Transaminase/metabolismo , Animais , Colestase Intra-Hepática/induzido quimicamente , Colestase Intra-Hepática/metabolismo , Colestase Intra-Hepática/patologia , Lactonas/química , Masculino , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Ratos Sprague-Dawley , Receptores Citoplasmáticos e Nucleares/química , Receptores Citoplasmáticos e Nucleares/metabolismo , Sesquiterpenos/química
11.
BMC Genomics ; 22(1): 353, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34000984

RESUMO

BACKGROUND: Polygonum cuspidatum Sieb. et Zucc. is a well-known medicinal plant whose pharmacological effects derive mainly from its stilbenes, anthraquinones, and flavonoids. These compounds accumulate differentially in the root, stem, and leaf; however, the molecular basis of such tissue-specific accumulation remains poorly understood. Because tissue-specific accumulation of compounds is usually associated with tissue-specific expression of the related biosynthetic enzyme genes and regulators, we aimed to clarify and compare the transcripts expressed in different tissues of P. cuspidatum in this study. RESULTS: High-throughput RNA sequencing was performed using three different tissues (the leaf, stem, and root) of P. cuspidatum. In total, 80,981 unigenes were obtained, of which 40,729 were annotated, and 21,235 differentially expressed genes were identified. Fifty-four candidate synthetase genes and 12 transcription factors associated with stilbene, flavonoid, and anthraquinone biosynthetic pathways were identified, and their expression levels in the three different tissues were analyzed. Phylogenetic analysis of polyketide synthase gene families revealed two novel CHS genes in P. cuspidatum. Most phenylpropanoid pathway genes were predominantly expressed in the root and stem, while methylerythritol 4-phosphate and isochorismate pathways for anthraquinone biosynthesis were dominant in the leaf. The expression patterns of synthase genes were almost in accordance with metabolite profiling in different tissues of P. cuspidatum as measured by high-performance liquid chromatography or ultraviolet spectrophotometry. All predicted transcription factors associated with regulation of the phenylpropanoid pathway were expressed at lower levels in the stem than in the leaf and root, but no consistent trend in their expression was observed between the leaf and the root. CONCLUSIONS: The molecular knowledge of key genes involved in the biosynthesis of P. cuspidatum stilbenes, flavonoids, and anthraquinones is poor. This study offers some novel insights into the biosynthetic regulation of bioactive compounds in different P. cuspidatum tissues and provides valuable resources for the potential metabolic engineering of this important medicinal plant.


Assuntos
Fallopia japonica , Plantas Medicinais , Estilbenos , Antraquinonas , Fallopia japonica/genética , Flavonoides , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Humanos , Filogenia , Transcriptoma
12.
Nanoscale Res Lett ; 16(1): 98, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34052936

RESUMO

The InAs/GaSb superlattice infrared detector has been developed with tremendous effort. However, the performance of it, especially long-wavelength infrared detectors (LWIR), is still limited by the electrical performance and optical quantum efficiency (QE). Forcing the active region to be p-type through proper doping can highly improve QE, and the gating technique can be employed to greatly enhance electrical performance. However, the saturation bias voltage is too high. Reducing the saturation bias voltage has broad prospects for the future application of gate voltage control devices. In this paper, we report that the gated P+-π-M-N+ InAs/GaSb superlattice long-wavelength infrared detectors exhibit different π region doping levels that have a reduced minimum saturation bias at - 10 V with a 200-nm SiO2 layer after a simple and effective anodic vulcanization pretreatment. The saturation gate bias voltage is much lower than - 40 V that reported with the same thickness of a 200-nm SiO2 passivation layer and similar structure. The optical and electrical characterization indicates that the electrical and optical performance of the device would be weakened by excessive doping concentration. At 77 K, the 50% cutoff wavelength of the device is about 8 µm, the 100% cutoff wavelength is 10 µm, the maximum quantum efficiency is 62.4%, the maximum of responsivity is 2.26 A/W at 5 µm, and the maximum RA of the device is 1259.4 Ω cm2. Besides, the specific detectivity of Be 780 °C-doped detector without gate electrode exhibits a peak of 5.6 × 1010 cm Hz1/2/W at 5 µm with a 70-mv reverse bias voltage, which is more than three times that of Be 820 °C-doped detector. Moreover, the peak specific detectivity could be further increased to 1.3 × 1011 cm Hz1/2/W at 5 µm with a 10-mv reserve bias voltage that has the bias of - 10 V at the gate electrode.

13.
Phytomedicine ; 85: 153548, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33831690

RESUMO

BACKGROUND: Pterocephalus hookeri (C. B. Clarke) Höeck, a Tibetan medicine widely used for treatment of rheumatoid arthritis, was recorded in Chinese Pharmacopoeia (2020 version) with slight toxicity. The liver injury was observed in mice with administration of n-butanol extract (BUE) in our previously study. However, the toxic components and the mechanism were still unrevealed. PURPOSE: The present study was aimed to isolate and structural elucidate of the toxic compound pterocephin A (PA), as well as evaluate its liver toxicity and investigate its mechanism. METHODS: PA was isolated from the BUE of P. hookeri. Its structure was determined by analysis of HRMS, NMR and ECD data. L-02 cellular viability, LDH, ALT, AST, ROS, intracellular Ca2+ and the fluidity of cell membrane were assessed by multifunctional microplate reader. The PI staining, cell membrane permeability assessment, and mitochondrial fluorescence staining analysis were determined through the fluorescence microscope. Liver samples for mice were assessed by pathological and immunohistochemistry analysis. Expression levels of indicated proteins were measured by western blotting assays. RESULTS: PA was determined as a previously undescribed oleanolane-type triterpenoid saponin. In vitro study revealed PA significantly induced hepatotoxicity by inhibition of L-02 cell growth, abnormally elevation of ALT and AST. Mechanically, PA induced the damage of cell membrane, fragmentation of mitochondria, and subsequently increase of intracellular Ca2+ and ROS levels, which trigged by necroptosis with the activation of RIP1 and NF-κB signaling pathways. In vivo study confirmed PA could induce liver injury in mice with observation of the body weight loss, increasing of serum ALT and AST, and the histopathological changes in liver tissues. CONCLUSION: Our present study indicated that PA was an undescribed toxic constituent in P. hookeri to induce liver injury in mice by activation of necroptosis and inflammation. And the findings are of great significance for the clinical use safely of this herb.


Assuntos
Caprifoliaceae/química , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Necroptose , Saponinas/efeitos adversos , Triterpenos/efeitos adversos , Animais , Linhagem Celular , Feminino , Humanos , Inflamação , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Medicina Tradicional Tibetana , Camundongos , Estrutura Molecular , NF-kappa B/metabolismo , Compostos Fitoquímicos/efeitos adversos , Extratos Vegetais/efeitos adversos
14.
Nat Commun ; 12(1): 2425, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893275

RESUMO

Anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) antibodies are currently used in the clinic to interupt the PD-1/PD-L1 immune checkpoint, which reverses T cell dysfunction/exhaustion and shows success in treating cancer. Here, we report a histone demethylase inhibitor, 5-carboxy-8-hydroxyquinoline (IOX1), which inhibits tumour histone demethylase Jumonji domain-containing 1A (JMJD1A) and thus downregulates its downstream ß-catenin and subsequent PD-L1, providing an antibody-independent paradigm interrupting the PD-1/PD-L1 checkpoint. Synergistically, IOX1 inhibits cancer cells' P-glycoproteins (P-gp) through the JMJD1A/ß-catenin/P-gp pathway and greatly enhances doxorubicin (DOX)-induced immune-stimulatory immunogenic cell death. As a result, the IOX1 and DOX combination greatly promotes T cell infiltration and activity and significantly reduces tumour immunosuppressive factors. Their liposomal combination reduces the growth of various murine tumours, including subcutaneous, orthotopic, and lung metastasis tumours, and offers a long-term immunological memory function against tumour rechallenging. This work provides a small molecule-based potent cancer chemo-immunotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/farmacologia , Hidroxiquinolinas/farmacologia , Imunoterapia/métodos , Neoplasias/terapia , Linfócitos T/efeitos dos fármacos , Animais , Anticorpos/imunologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Doxorrubicina/administração & dosagem , Células HCT116 , Humanos , Hidroxiquinolinas/administração & dosagem , Hidroxiquinolinas/química , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células NIH 3T3 , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/imunologia
15.
Nat Biomed Eng ; 5(9): 1019-1037, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33859387

RESUMO

Effective anticancer nanomedicines need to exhibit prolonged circulation in blood, to extravasate and accumulate in tumours, and to be taken up by tumour cells. These contrasting criteria for persistent circulation and cell-membrane affinity have often led to complex nanoparticle designs with hampered clinical translatability. Here, we show that conjugates of small-molecule anticancer drugs with the polyzwitterion poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate) have long blood-circulation half-lives and bind reversibly to cell membranes, owing to the negligible interaction of the polyzwitterion with proteins and its weak interaction with phospholipids. Adsorption of the polyzwitterion-drug conjugates to tumour endothelial cells and then to cancer cells favoured their transcytosis-mediated extravasation into tumour interstitium and infiltration into tumours, and led to the eradication of large tumours and patient-derived tumour xenografts in mice. The simplicity and potency of the polyzwitterion-drug conjugates should facilitate the design of translational anticancer nanomedicines.

16.
Sci Total Environ ; 784: 147227, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-33905930

RESUMO

A high-efficiency Z-scheme Bi2MoO6/AgI heterojunction was designed and fabricated via in situ growth of AgI on Bi2MoO6. Its photocatalytic activity was investigated with the degradation of malachite green (MG). After 40 min of visible light irradiation, near complete degradation of MG (20 mg/L) occurred when BA11 (Bi2MoO6:AgI = 1:1, 2.0 g/L) was present, while only 29.0% and 49.7% of the MG could be degraded in the presence of Bi2MoO6 and AgI, respectively. The excellent photocatalytic activity of BA11 results from strong visible light absorption and the low recombination efficiency of photogenerated electron-hole pairs induced by the formation of heterojunction. Density function theory (DFT) calculations revealed that the formation of built-in electric field at the interface between Bi2MoO6 and AgI facilitates the effective separation and transfer of photogenerated charge carriers. Results of reuse experiments indicated that the heterostructured photocatalyst has excellent stability. Radical scavenging experiments and electron spin resonance spectra showed that superoxide radicals (O2-) and hydroxyl radicals (OH) were the major reactive oxygen species in the photocatalytic system. The photocatalytic degradation pathway of MG was proposed based on the organic degradation intermediates detected. These findings demonstrate that the mediator-free Z-scheme Bi2MoO6/AgI heterojunction could serve as a promising photocatalyst in photocatalytic treatment of organic pollutants.

17.
Nat Prod Res ; : 1-8, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33719777

RESUMO

Two new neolignans, dolominol A (1) and dolominol B (2), together with 12 known lignans, erythro-(7S,8R)-guaiacyl-glycerol-ß-O-4'-dihydroconiferyl ether (3), threo-(7R,​8R)-1-​(4-​hydroxy-​3-​methoxyphenyl)​-​2-{4-[(E)-​3-​hydroxy-​1-​propen​yl)​]-​2-​methoxyphenoxy}-1,​3-​propanediol (4), (-)-dihydrodehydrodiconiferyl alcohol (5), (-)-massoniresinol (6), vladinol D (7), syringaresinol (8), prinsepiol (9), medioresinol (10), (+)-pinoresinol (11), 2α-guaicyl-4-oxo-6α-catechyl-3,7-dioxabicyclo [3.3.0]octane (12), cycloolivil (13), isolariciresinol (14) were isolated from Dolomiaea souliei (Franch.) C.Shih. Their structures were determined by UV, CD, HR-ESI-TOFMS, 1 D and 2 D NMR experiments. Their hepatoprotective effect against LPS-induced L-02 cells injury was also studied. Result revealed that compound 4 showed best protective effect on LPS-induced L-02 cells.

18.
Fitoterapia ; 151: 104886, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33757847

RESUMO

Two undescribed sesamin-type sesquilignans ptehoosines A (1) and B (2), together with 4 known lignans (3-6), were isolated from Pterocephalus hookeri (C.B. Clarke) Höeck which was widely used as traditional Tibetan medicine for treatment of rheumatoid arthritis. Their structures were determined by HR-ESI-MS, NMR analysis and CD experiment. The in vitro antiangiogenic effect of all isolated compounds against human umbilical vein endothelial cells (HUVECs) were evaluated by CCK-8 assay. Among them, compound 1 exhibited significant proliferative inhibition on HUVECs with IC50 value of 32.82 ± 0.99 µM. Further in vitro study indicated 1 could arrest cell cycle at G0/G1 phase and reduce the migration of HUVECs. In vivo experiment exhibited 1 could inhibit tail vessels plexus in zebrafish. The above finding suggested that 1 was a promising lead compound against RA by inhibiting of angiogenesis.


Assuntos
Inibidores da Angiogênese/farmacologia , Caprifoliaceae/química , Dioxóis/farmacologia , Lignanas/farmacologia , Inibidores da Angiogênese/isolamento & purificação , Animais , Pontos de Checagem do Ciclo Celular , Dioxóis/isolamento & purificação , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Lignanas/isolamento & purificação , Medicina Tradicional Tibetana , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Tibet , Peixe-Zebra
20.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(1): 96-99, 2021 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-33522186

RESUMO

In this study, cytometric beads array(CBA) was used to determine the immunoglobulin content in humoral immunity evaluation of biomedical materials. The bovine-derived acellular dermal matrix was selected as a test sample and implanted into Balb/C mice subcutaneously to 4 weeks according to the high, medium and low dose groups. Four weeks later, IgG1, IgG2a, IgG2b, IgG3, IgA, and IgM were measured by CBA. The data of the test group and the control group were analyzed statistically. The results showed that compared with the negative control group, there was no significant difference in the IgG3, IgA content in the positive control group, while the IgG1, IgG2a, IgG2b, and IgM contents were significantly higher than the negative control group; no significant differences were seen in the sample groups. The results show that the method is suitable for analysis of immunoglobulin content in humoral immunity evaluation of biomedical materials.


Assuntos
Imunidade Humoral , Animais , Bovinos , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA
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