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1.
Fish Shellfish Immunol ; 149: 109617, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38723876

RESUMO

Microbiome in the intestines of aquatic invertebrates plays pivotal roles in maintaining intestinal homeostasis, especially when the host is exposed to pathogen invasion. Decapod iridescent virus 1 (DIV1) is a devastating virus seriously affecting the productivity and success of crustacean aquaculture. In this study, a metagenomic analysis was conducted to investigate the genomic sequences, community structure and functional characteristics of the intestinal microbiome in the giant river prawn Macrobrachiumrosenbergii infected with DIV1. The results showed that DIV1 infection could significantly reduce the diversity and richness of intestinal microbiome. Proteobacteria represented the largest taxon at the phylum level, and at the species level, the abundance of Gonapodya prolifera and Solemya velum gill symbiont increased significantly following DIV1 infection. In the infected prawns, four metabolic pathways related to purine metabolism, pyrimidine metabolism, glycerophospholipid metabolism, and pentose phosphate pathway, and five pathways related to nucleotide excision repair, homologous recombination, mismatch repair, base excision repair, and DNA replication were significantly enriched. Moreover, several immune response related pathways, such as shigellosis, bacterial invasion of epithelial cells, Salmonella infection, and Vibrio cholerae infection were repressed, indicating that secondary infection in M. rosenbergii may be inhibited via the suppression of these immune related pathways. DIV1 infection led to the induction of microbial carbohydrate enzymes such as the glycoside hydrolases (GHs), and reduced the abundance and number of antibiotic-resistant ontologies (AROs). A variety of AROs were identified from the microbiota, and mdtF and lrfA appeared as the dominant genes in the detected AROs. In addition, antibiotic efflux, antibiotic inactivation, and antibiotic target alteration were the main antibiotic resistance mechanisms. Collectively, the data would enable a deeper understanding of the molecular response of intestinal microbiota to DIV1, and offer more insights into its roles in prawn resistance to DIVI infection.


Assuntos
Microbioma Gastrointestinal , Palaemonidae , Animais , Palaemonidae/imunologia , Palaemonidae/virologia , Palaemonidae/microbiologia , Palaemonidae/genética , Metagenômica , Metagenoma , Iridoviridae/fisiologia
2.
Bioorg Chem ; 152: 107742, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39186916

RESUMO

Human serum albumin (HSA) serves as a crucial indicator for therapeutic monitoring and biomedical diagnosis. In this study, a near infrared (NIR) fluorescent probe, termed BTPA, characterized a donor-π-acceptor (D-π-A) structure based on bridged triphenylamine (TPA) was developed. BTPA exhibited outstanding sensitivity and selectivity towards HSA among various analysts, with a remarkable 50-fold fluorescence enhancement with a significant Stokes shift (∼190 nm) and a wide linear detection range of 0-20 µM of HSA. Especially, BTPA displayed selectivity for discrimination of HSA from BSA. Job's Plot analysis suggested a 1:1 stoichiometry for the formation of the BTPA-HSA complex. Displacement assays and molecular docking demonstrated that BTPA binds to subdomain IB of HSA which could effectively avoid interference from most drugs. Besides, BTPA have good biocompatibility and could detect of exogenous HSA with a relatively low fluorescence background. For practical applications, BTPA was tested for detecting HSA levels in human urine without any pretreatment, showing detection capability in the range of 0-10 µM with a fast response (<30 s), a limit of detection (LOD) of 0.12 µM and good recoveries (81.7-92.9 %), highlighting the high performance of bridged triphenylamine-based probe BTPA.


Assuntos
Corantes Fluorescentes , Albumina Sérica Humana , Humanos , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Albumina Sérica Humana/urina , Estrutura Molecular , Simulação de Acoplamento Molecular , Compostos de Anilina/química , Compostos de Anilina/síntese química , Espectrometria de Fluorescência
3.
Plant Dis ; 107(2): 281-287, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35971259

RESUMO

A bacterial pathogen strain was isolated from susceptible tissue of Hongyang variety kiwifruit in Zhongfeng Town, Ziyuan County, Guilin City, Guangxi, China. Due to the relatively single variety of kiwifruit in Guangxi, the control technology of fruit farmers is backward, and the climate is humid, which is suitable for the growth of pathogenic bacteria, resulting in frequent occurrence of diseases. In this study, the pathogen strain was identified based on morphological, physiological, and biochemical tests; 16S rRNA gene; PCR detection with specific primers; and Biolog analysis. The results showed that a tobacco allergic reaction could be induced by inoculation with the pathogenic bacteria. Additionally, brown necrotic plaques appeared on kiwifruit leaves, necrotic phloem lesions appeared, and wounds on kiwifruit branches turned brown. The characteristics identified by morphological, physiological, biochemical, and Biolog identification were similar to those caused by Pectobacterium sp. Through 16S rRNA gene sequence analysis and PCR identification with specific primers, bands with a size corresponding to target bands indicated that the pathogen was Pectobacterium carotovorum subsp. actinidiae. This is the first report of kiwifruit canker disease caused by P. carotovorum subsp. actinidiae in Guangxi, China. In addition, through this study, a preliminary understanding of the pathogen has been obtained, which will lay the foundation for the prevention and control of the disease in the future.


Assuntos
Actinidia , Pectobacterium , China , RNA Ribossômico 16S/genética , Frutas , Doenças das Plantas/microbiologia , Pectobacterium/genética , Actinidia/microbiologia
4.
Int J Mol Sci ; 24(13)2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37446199

RESUMO

ß-Carbonic anhydrase (ßCA) is very important for plant growth and development, but its function in immunity has also been examined. In this study, we found that the expression level of Solanum lycopersicum ßCA1 (SlßCA1) was significantly upregulated in plants treated with Xanthomonas euvesicatoria 85-10. The protein was localized in the nucleus, cell membrane and chloroplast. Using tomato plants silenced with SlßCA1, we demonstrated that SlßCA1 plays an active role in plant disease resistance. Moreover, we found that the elicitor PopW upregulated the expression of SlßCA1, while the microbe-associated molecular pattern response induced by PopW was inhibited in TRV-SlßCA1. The interaction between PopW and SlßCA1 was confirmed. Here, we found that SlßCA1 was positively regulated during PopW-induced resistance to Xanthomonas euvesicatoria 85-10. These data indicate the importance of SlßCA1 in plant basic immunity and its recognition by the Harpin protein PopW as a new target for elicitor recognition.


Assuntos
Solanum lycopersicum , Xanthomonas , Solanum lycopersicum/genética , Xanthomonas/fisiologia , Proteínas de Bactérias/metabolismo , Imunidade Vegetal/genética , Doenças das Plantas/genética
5.
Int J Mol Sci ; 23(22)2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36430908

RESUMO

Glycoside hydrolases from pathogens have often been reported as inducers of immune responses. However, the roles of glycoside hydrolase from plant-growth-promoting rhizobacteria (PGPR) in the resistance of plants against pathogens is not well studied. In this study, we identified a glycoside hydrolase 43 protein, H1AD43, produced by Bacillus licheniformis BL06 that can trigger defense responses, including cell death. Ion-exchange and size-exclusion chromatography were used for separation, and the amino acid sequence was identified by mass spectrometry. The recombinant protein generated by prokaryotic expression was able to elicit a hypersensitive response (HR) in Nicotiana benthamiana and trigger early defense responses, including reactive oxygen species (ROS) burst, callose accumulation, and the induction of defense genes. In addition, the protein could induce resistance in N. benthamiana, in which it inhibited infection by Phytophthora capsici Leonian and tobacco mosaic virus-green fluorescent protein (TMV-GFP) expression. H1AD43 thus represents a microbe-associated molecular pattern (MAMP) of PGPR that induces plant disease resistance and may provide a new method for the biological control of plant disease.


Assuntos
Bacillus licheniformis , Vírus do Mosaico do Tabaco , Bacillus licheniformis/genética , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Nicotiana/metabolismo , Doenças das Plantas/microbiologia
6.
Biomacromolecules ; 22(6): 2451-2459, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34024108

RESUMO

The present study aimed to purify, structurally characterize, and evaluate the anti-inflammatory activity of the polysaccharide extracted from Typha angustifolia. Two purified polysaccharides (PTA-1 and PTA-2) were obtained via DEAE-52 cellulose chromatography. Their structural characterizations and antioxidant activity were in vitro analyzed. To evaluate the anti-inflammatory activity of PTA-2, the levels of inflammatory cytokines, intracellular ROS production, and the inhibitory effects of the transcriptional activation of the nuclear factor kappa B (NF-κB) signaling pathway were determined. PTA-1 comprises glucose (100%) with α-(1 → 3) glycosidic bonds, and PTA-2 comprises glucose (66.7%) and rhamnose (33.3%) formed by ß-(1 → 3) glycosidic bonds. PTA-1 and PTA-2 showed strong antioxidant activity in vitro. Moreover, PTA-2 intervention (50, 100, and 200 µg/mL) suppressed the production of inflammatory cytokines, the activation of NF-κB signaling, and reactive oxygen species production significantly. The results identified PTA-2 as a natural product that could be applied in anti-inflammatory drugs.


Assuntos
Typhaceae , Anti-Inflamatórios/farmacologia , Citocinas , Lipopolissacarídeos/farmacologia , NF-kappa B/genética , NF-kappa B/metabolismo , Polissacarídeos/farmacologia , Espécies Reativas de Oxigênio , Transdução de Sinais , Typhaceae/metabolismo
7.
Med Res Rev ; 39(2): 561-578, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30136283

RESUMO

Kidney diseases have become a global public health problem. The application of kidney-targeted drug-delivery systems in the management of kidney diseases has profound transformative potential. Kidney-targeted drug delivery can reduce the undesired side effects of often potent drugs and enhance drug efficacy in alleviating the kidney disease. Here, we review the literature on the potential strategies for targeting drugs to the kidneys. Specifically, we provide a broad overview of the targeting vectors and targeting pathways for renal tubules and glomeruli, as well as how the unique structural features of the glomerulus and the receptor-mediated internalization pathways of the tubules allows for drug targeting. Finally, we summarized the literature examples of drug delivery to the kidneys and elaborated strategies suitable for renal targeting to provide new therapeutic approaches for kidney diseases.


Assuntos
Sistemas de Liberação de Medicamentos , Nefropatias/tratamento farmacológico , Glomérulos Renais/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Rim/efeitos dos fármacos , Animais , Anticorpos/química , Taxa de Filtração Glomerular , Humanos , Células-Tronco Mesenquimais/citologia , Nanomedicina , Nanopartículas , Podócitos/citologia , Polímeros/química , Pró-Fármacos
8.
Int J Mol Sci ; 20(13)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261843

RESUMO

The antioxidant effect of salidroside has been proven, but its role in liver injury is poorly understood. In this study, we aimed to evaluate the protective effects and mechanism of salidroside on liver injury induced by carbon tetrachloride (CCl4) in vivo. Mice were pretreated with salidroside (60 mg/kg, intraperitoneally injected, i.p.) once per day for 14 consecutive days and then administered with CCl4 (15.95 g/kg, i.p.) for 24 h to produce a liver injury model. Salidroside attenuated hepatic transaminase elevation in serum and ameliorated liver steatosis and necrosis, thereby suggesting its protective effect on the liver. Salidroside antagonized CCl4-induced toxicity by equilibrating antioxidation system, thereby inhibiting reactive oxygen species accumulation, and restoring mitochondrial structure and function. Salidroside exerts antioxidant and liver-protective effects by selectively inhibiting the activation of genes, including growth arrest and DNA -damage-inducible 45 α (Gadd45a), mitogen-activated protein kinase 7 (Mapk7), and related RAS viral oncogene homolog 2 (Rras2), which induce oxidative stress in the mitogen-activated protein kinase pathway. These results revealed that salidroside can protect the liver from CCl4-induced injury by resisting oxidative stress and protecting mitochondrial function.


Assuntos
Antioxidantes , Doença Hepática Induzida por Substâncias e Drogas , Glucosídeos , Mitocôndrias Hepáticas , Estresse Oxidativo , Fenóis , Animais , Masculino , Camundongos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Tetracloreto de Carbono/toxicidade , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Sistema de Sinalização das MAP Quinases , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Proteínas Monoméricas de Ligação ao GTP/genética , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Fenóis/farmacologia , Fenóis/uso terapêutico
9.
Pharm Biol ; 57(1): 710-716, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31622118

RESUMO

Context: Methicillin-resistant Staphylococcus aureus (MRSA) is a very harmful bacterium. Oridonin, a component in Rabdosia rubescens (Hemsl.) Hara (Lamiaceae), is widely used against bacterial infections in China. Objective: We evaluated oridonin effects on MRSA cell membrane and wall, protein metabolism, lactate dehydrogenase (LDH), DNA and microscopic structure. Materials and methods: Broth microdilution and flat colony counting methods were used to measure oridonin minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against USA300 strain. Electrical conductivity and DNA exosmosis were analysed to study oridonin effects (128 µg/mL) on cell membrane and wall for 0, 1, 2, 4 and 6 h. Sodium dodecyl sulphate polyacrylamide gel electrophoresis was used to detect effects on soluble protein synthesis after 6, 10 and 16 h. LDH activity was examined with an enzyme-linked immunosorbent assay. Effects of oridonin on USA300 DNA were investigated with DAPI staining. Morphological changes in MRSA following oridonin treatment were determined with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: Oridonin MIC and MBC values against USA300 were 64 and 512 µg/mL, respectively. The conductivity and DNA exosmosis level of oridonin-treated USA300 improved by 3.20±0.84% and increased by 58.63 ± 1.78 µg/mL, respectively. LDH and soluble protein levels decreased by 30.85±7.69% and 27.51 ± 1.39%, respectively. A decrease in fluorescence intensity was reported with time. Oridonin affected the morphology of USA300. Conclusions: Oridonin antibacterial mechanism was related to changes in cell membrane and cell wall permeability, disturbance in protein and DNA metabolism, and influence on bacterial morphology. Thus, oridonin may help in treating MRSA infection.


Assuntos
Antibacterianos/farmacologia , Membrana Celular/efeitos dos fármacos , Diterpenos do Tipo Caurano/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/administração & dosagem , Parede Celular/efeitos dos fármacos , DNA Bacteriano/metabolismo , Diterpenos do Tipo Caurano/administração & dosagem , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Fatores de Tempo
10.
Biochem Biophys Res Commun ; 495(2): 1702-1707, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29225170

RESUMO

The success of all-trans retinoic acid (ATRA) in differentiation therapy for patients with acute promyelocytic leukemia (APL) highly encourages researches to apply a new combination therapy based on ATRA. Therefore, research strategies to further sensitize cells to retinoids are urgently needed. In this study, we showed that Dihydromyricetin (DMY), a 2,3-dihydroflavonol compound, exhibited a strong synergy with ATRA to promote APL NB4 cell differentiation. We observed that DMY sensitized the NB4 cells to ATRA-induced cell growth inhibition, CD11b expression, NBT reduction and myeloid regulator expression. PML-RARα might not be essential for DMY-enhanced differentiation when combined with ATRA, while the enhanced differentiation was dependent on the activation of p38-STAT1 signaling pathway. Taken together, our study is the first to evaluate the synergy of DMY and ATRA in NB4 cell differentiation and to assess new opportunities for the combination of DMY and ATRA as a promising approach for future differentiation therapy.


Assuntos
Flavonóis/administração & dosagem , Leucemia Promielocítica Aguda/tratamento farmacológico , Fator de Transcrição STAT1/metabolismo , Tretinoína/administração & dosagem , Antineoplásicos/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas de Fusão Oncogênica/metabolismo , Proteólise/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
11.
J Sep Sci ; 40(22): 4329-4337, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28898533

RESUMO

The purpose of this study was to optimize the extraction process of phloridzin from Lithocarpus polystachyus Rehd. leaves using response surface methodology and to determine the antioxidant capacity of the extract. A Box-Behnken design was used to analyze the effects of ethanol concentration, liquid-solid ratio, soak time and extraction time on the extraction yield of phloridzin. The content of phloridzin was determined by high-performance liquid chromatography. To assess the antioxidant capacity of the extract, three in vitro test systems were used (1,1-,diphenyl-2-picrylhydrazyl, hydroxyl radical scavenging test and reduction force). The optimal parameters obtained by response surface methodology were a volume fraction of ethanol of 64%, a liquid-solid ratio of 37:1, a soaking time of 35 h and a sonication time of 38 min. The proportion of the extraction of phloridzin from L. polystachyus under these industrial process conditions was 3.83%. According to the obtained results, response surface methodology could be suggested as an adequate model for optimizing the extraction process of phloridzin from L. polystachyus. Ultrasound extraction significantly increased the extraction rate of phloridzin, which could be used as an antioxidant in pharmaceutical and food products.


Assuntos
Antioxidantes/isolamento & purificação , Fagaceae/química , Florizina/isolamento & purificação , Extratos Vegetais/química , Folhas de Planta/química , Ultrassom
12.
Molecules ; 22(1)2016 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-28035986

RESUMO

The goal of this research was to evaluate the anti-hepatitis B virus (HBV) activities of three compounds extracted and purified from Herpetospermum seeds (HS) on HepG2.2.15 cells. Herpetin (HPT), herpetone (HPO), and herpetfluorenone (HPF) were isolated from HS and identified using HR-ESI-MS and NMR. Different concentrations of the drugs were added to the HepG2.2.15 cells. Cell toxicity was observed with an MTT assay, cell culture supernatants were collected, and HBsAg and HBeAg were detected by ELISA. The content of HBV DNA was determined via quantitative polymerase chain reaction (PCR) with fluorescent probes. The 50% toxicity concentration (TC50) of HPF was 531.48 µg/mL, suggesting that this species is less toxic than HPT and HPO. HPT and HPF showed more potent antiviral activities than HPO. The 50% inhibition concentration (IC50) values of HPF on HBsAg and HBeAg were 176.99 and 134.53 µg/mL, respectively, and the corresponding therapeutic index (TI) values were 2.66 and 3.49, respectively. HPT and HPF were shown to significantly reduce the level of HBV DNA in the HepG2.2.15 culture medium compared to the negative control. This initial investigation of the anti-HBV constituents of HS yielded three compounds that revealed a synergistic effect of multiple components in the ethnopharmacological use of HS.


Assuntos
Antivirais/farmacologia , Benzofuranos/farmacologia , Fluorenos/farmacologia , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B/metabolismo , Vírus da Hepatite B/efeitos dos fármacos , Lignanas/farmacologia , Linhagem Celular Tumoral , Cucurbitaceae/química , DNA Viral/genética , Medicamentos de Ervas Chinesas/química , Ensaio de Imunoadsorção Enzimática , Células Hep G2 , Hepatite B/tratamento farmacológico , Vírus da Hepatite B/genética , Humanos , Ressonância Magnética Nuclear Biomolecular , Extratos Vegetais/farmacologia , Sementes/química , Espectrometria de Massas por Ionização por Electrospray , Replicação Viral/efeitos dos fármacos
13.
Pharmazie ; 70(11): 745-52, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26790192

RESUMO

OBJECTIVE: The aims of this study were to demonstrate the hepatoprotective activity of herpetin (HPT) and the enhanced hepatoprotective efficiency of liposomal herpetin against carbon tetrachloride-induced liver injury in mice. METHODS: Herpetin was isolated from Herpetospermum seed and identified by ESI-MS and NMR. To enhance liver targeting and improve solubility of HPT, liposomal HPT was prepared with optimal formulation. The intravenous injection safety of the liposomes was then evaluated. Further, the hepatoprotective effects of liposomal HPT on model mice were investigated by the comparison of different liver marker enzymes and histopathological examination. RESULTS: The prepared HPT liposome showed spherical or ellipsoidal vesicles with the entrapment efficiency of 94.50 ± 2.15% and particle size of 119.2 ± 10.7 nm. After 4 days intravenous administration of liposomal herpetin, no obvious damage could be observed at the injection site of each group. The liposomal HPT has no destructive effect on erythrocytes and little influence on whole blood clotting time. Free HPT exhibited only a weak protective function to model mice, whereas an enhanced hepatoprotective activity was observed using liposomal herpetin for treatment. CONCLUSION: The hepatoprotective efficiency of herpetin is able to be promoted through pharmaceutical application of liposome and liposomal herpetin is a promising new medicine for hepatoprotection.


Assuntos
Benzofuranos/farmacologia , Intoxicação por Tetracloreto de Carbono/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cucurbitaceae/química , Substâncias Protetoras/farmacologia , Animais , Benzofuranos/efeitos adversos , Tempo de Circulação Sanguínea , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Eritrócitos/efeitos dos fármacos , Injeções Intravenosas , Lipossomos , Testes de Função Hepática , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos ICR , Tamanho da Partícula , Substâncias Protetoras/efeitos adversos , Sementes/química , Espectrometria de Massas por Ionização por Electrospray
14.
Colloids Surf B Biointerfaces ; 244: 114130, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39121570

RESUMO

The complexity and compensatory evolution of tumors weaken the effectiveness of single antitumor therapies. Therefore, multimodal combination therapies hold great promise in defeating tumors. Herein, we constructed a multi-level regulatory co-delivery system based on chemotherapy, phototherapy, and immunotherapy. Briefly, curcumin (Cur) was prepared as nanoparticles and coated with polydopamine (PDA) to form PCur-NPs, which along with an immune checkpoint inhibitor (indoximod, IND) were then loaded into a thermosensitive Pluronic F127 (F127) hydrogel to form a multifunctional nanocomposite hydrogel (PCur/IND@Gel). The in situ-formed hydrogel exhibited excellent photothermal conversion efficiency and sustained drug release behavior both in vitro and in vivo. In addition, PCur-NPs showed enhanced cellular uptake and cytotoxicity under NIR laser irradiation and induced potent immunogenic cell death (ICD). After intratumoral injection of PCur/IND@Gel, significant apoptosis in 4T1 tumors was induced, dendritic cells in lymph nodes were highly activated, potent CD8+ and CD4+ antitumor immune responses were elicited and regulative T cells in tumors were significantly reduced, which notably inhibited the tumor growth and prolonged the survive time of 4T1 tumor-bearing mice. Therefore, this injectable nanocomposite hydrogel is a promising drug co-delivery platform for chemo-photothermal-immunotherapy of breast tumors.


Assuntos
Neoplasias da Mama , Curcumina , Hidrogéis , Imunoterapia , Indóis , Nanopartículas , Polímeros , Indóis/química , Indóis/farmacologia , Curcumina/química , Curcumina/farmacologia , Polímeros/química , Polímeros/farmacologia , Animais , Nanopartículas/química , Camundongos , Hidrogéis/química , Hidrogéis/farmacologia , Feminino , Imunoterapia/métodos , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Camundongos Endogâmicos BALB C , Antineoplásicos/farmacologia , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Fototerapia , Terapia Combinada , Terapia Fototérmica , Tamanho da Partícula , Poloxâmero/química , Ensaios de Seleção de Medicamentos Antitumorais , Sobrevivência Celular/efeitos dos fármacos , Propriedades de Superfície , Linhagem Celular Tumoral , Humanos
15.
Artigo em Inglês | MEDLINE | ID: mdl-39126882

RESUMO

N6-methyladenosine (m6A) methylation is the most prevalent post-transcriptional RNA modification in eukaryotic organisms, but its roles in the regulation of physiological resistance of marine crustaceans to heavy metal pollutants are poorly understood. In this study, the transcriptome-wide m6A RNA methylation profiles and dynamic m6A changes induced by acute Cd2+ exposure in the the pacific whiteleg shrimp Litopenaeus vannamei were comprehensively analyzed. Cd2+ toxicity caused a significant reduction in global RNA m6A methylation level, with major m6A regulators including the m6A methyltransferase METTL3 and the m6A binding protein YTHDF2 showing declined expression. Totally, 11,467 m6A methylation peaks from 6415 genes and 17,291 peaks within 7855 genes were identified from the Cd2+ exposure group and the control group, respectively. These m6A peaks were predominantly enriched in the 3' untranslated region (UTR) and around the start codon region of the transcripts. 7132 differentially expressed genes (DEGs) and 7382 differentially m6A-methylated genes (DMGs) were identified. 3186 genes showed significant changes in both gene expression and m6A methylation levels upon cadmium exposure, and they were related to a variety of biological processes and gene pathways. Notably, an array of genes associated with antioxidation homeostasis, transmembrane transporter activity and intracellular detoxification processes were significantly enriched, demonstrating that m6A modification may mediate the physiological responses of shrimp to cadmium toxicity via regulating ROS balance, Cd2+ transport and toxicity mitigation. The study would contribute to a deeper understanding of the evolutionary and functional significance of m6A methylation to the physiological resilience of decapod crustaceans to heavy metal toxicants.

16.
Molecules ; 18(5): 5142-54, 2013 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-23644979

RESUMO

An efficient synthesis of novel dispirooxindoles has been achieved through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ by the decarboxylative condensation of isatin and an α-amino acid with the dipolarophile 5-benzylideneimidazolidine-2,4-dione. The improved procedure features mild reaction conditions, high yields, high diastereoselectivities, a one-pot procedure and operational simplicity.


Assuntos
Compostos Azo/química , Compostos Heterocíclicos com 1 Anel/química , Compostos Heterocíclicos com 1 Anel/síntese química , Isatina/química , Tiossemicarbazonas/química , Estrutura Molecular
17.
Colloids Surf B Biointerfaces ; 226: 113328, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37156026

RESUMO

Nanoparticles (NPs) can be incorporated into hydrogels to obtain multifunctional hybrid systems to meet the delivery needs of different drugs. However, the stability of NPs in hydrogels is rarely revealed. In this article, we tried to explore the underlying mechanism of an interesting phenomenon that poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PNPs) could flocculate and deposit in Pluronic F127 (F127) hydrogels at 4 °C. The results showed that this flocculation was relevant to the type of emulsifier formulated in PNPs, the particle materials and the F127 concentration, but independent of PLGA polymer end groups. Exactly, PNPs containing polyvinyl alcohol (PVA) as the emulsifier flocculated in F127 solution with a concentration above 15 %. The flocculated PNPs possessed increased particle size, decreased zeta potential, reduced hydrophobicity and an obvious coating layer, and these characteristics could be restored almost to the original state after two washes of flocculated PNPs with water. Moreover, the flocculation had no impact on the long-term size stability and drug-loading capacity of PNPs, and F127-treated PNPs showed improved cellular uptake than untreated PNPs. These results provide the evidence that adsorption of high concentrations of F127 on the surface of PNPs/PVA may lead to flocculation, and the flocculation is reversible by simply washing the flocs with water. To the best of our knowledge, this is the first study to scientifically explore the stability of PNPs in F127 hydrogels, providing theoretical and experimental support for the rational design and further development of nanoparticle-hydrogel composite.


Assuntos
Nanopartículas , Poloxâmero , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ácido Poliglicólico , Ácido Láctico , Floculação , Álcool de Polivinil , Hidrogéis , Tamanho da Partícula
18.
J Hazard Mater ; 458: 131996, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37423135

RESUMO

Despite the versatility of RNA m6A methylation in regulating various biological processes, its involvement in the physiological response to ammonia nitrogen toxicity in decapod crustaceans like shrimp remains enigmatic. Here, we provided the first characterization of dynamic RNA m6A methylation landscapes induced by toxic ammonia exposure in the Pacific whiteleg shrimp Litopenaeus vannamei. The global m6A methylation level showed significant decrease following ammonia exposure, and most of the m6A methyltransferases and m6A binding proteins were significantly repressed. Distinct from many well-studied model organisms, m6A methylated peaks in the transcriptome of L. vannamei were enriched not only near the termination codon and in the 3' untranslated region (UTR), but also around the start codon and in the 5' UTR. Upon ammonia exposure, 11,430 m6A peaks corresponding to 6113 genes were hypo-methylated, and 5660 m6A peaks from 3912 genes were hyper-methylated. The differentially methylated genes showing significant changes in expression were over-represented by genes associated with metabolism, cellular immune defense and apoptotic signaling pathways. Notably, the m6A-modified ammonia-responsive genes encompassed a subset of genes related to glutamine synthesis, purine conversion and urea production, implying that m6A methylation may modulate shrimp ammonia stress responses partly through these ammonia metabolic processes.


Assuntos
Penaeidae , Transcriptoma , Animais , Amônia/toxicidade , Metilação , Nitrogênio , Estresse Fisiológico , Penaeidae/genética , RNA
19.
Pharmaceutics ; 15(7)2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37514197

RESUMO

With their seemingly limitless capacity for self-improvement, stem cells have a wide range of potential uses in the medical field. Stem-cell-secreted extracellular vesicles (EVs), as paracrine components of stem cells, are natural nanoscale particles that transport a variety of biological molecules and facilitate cell-to-cell communication which have been also widely used for targeted drug delivery. These nanocarriers exhibit inherent advantages, such as strong cell or tissue targeting and low immunogenicity, which synthetic nanocarriers lack. However, despite the tremendous therapeutic potential of stem cells and EVs, their further clinical application is still limited by low yield and a lack of standardized isolation and purification protocols. In recent years, inspired by the concept of biomimetics, a new approach to biomimetic nanocarriers for drug delivery has been developed through combining nanotechnology and bioengineering. This article reviews the application of biomimetic nanocarriers derived from stem cells and their EVs in targeted drug delivery and discusses their advantages and challenges in order to stimulate future research.

20.
Int J Nanomedicine ; 17: 1757-1781, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35469174

RESUMO

Inflammation is a beneficial and physiological process, but there are a number of inflammatory diseases which have detrimental effects on the body. In addition, the drugs used to treat inflammation have toxic side effects when used over a long period of time. Mesenchymal stem cells (MSCs) are pluripotent stem cells that can be isolated from a variety of tissues and can be differentiate into diverse cell types under appropriate conditions. They also exhibit noteworthy anti-inflammatory properties, providing new options for the treatment of inflammatory diseases. The therapeutic potential of MSCs is currently being investigated for various inflammatory diseases, such as kidney injury, lung injury, osteoarthritis (OA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). MSCs can perform multiple functions, including immunomodulation, homing, and differentiation, to enable damaged tissues to form a balanced inflammatory and regenerative microenvironment under severe inflammatory conditions. In addition, accumulated evidence indicates that exosomes from extracellular vesicles of MSCs (MSC-Exos) play an extraordinary role, mainly by transferring their components to recipient cells. In this review, we summarize the mechanism and clinical trials of MSCs and MSC-Exos in various inflammatory diseases in detail, with a view to contributing to the treatment of MSCs and MSC-Exos in inflammatory diseases.


Assuntos
Exossomos , Vesículas Extracelulares , Células-Tronco Mesenquimais , Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Imunomodulação , Inflamação/metabolismo , Inflamação/terapia
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