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1.
J Adv Res ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945295

RESUMO

INTRODUCTION: The postharvest physiological disorder known as 'black spot' in radish roots (Raphanus sativus) poses a significant challenge to quality maintenance during storage, particularly under summer conditions. The cause of this disorder, however, is poorly understood. OBJECTIVES: Characterize the underlying causes of 'black spot' disorder in radish roots and identify strategies to delay its onset. METHODS: Radish roots were placed in either polyvinyl chloride (PVC) or oriented polypropylene (OPP) packaging and stored for 4 days at 30 °C. Appearance and physiological parameters were assessed and transcriptomic and metabolomic analyses were conducted to identify the key molecular and biochemical factors contributing to the disorder and strategies for delaying its onset and development. RESULTS: OPP packaging effectively delayed the onset of 'black spot' in radishes, potentially due to changes in phenolic and lipid metabolism. Regarding phenolic metabolism, POD and PPO activity decreased, RsCCR and RsPOD expression was downregulated, genes involved in phenols and flavonoids synthesis were upregulated and their content increased, preventing the oxidative browning of phenols and generally enhancing stress tolerance. Regarding lipid metabolism, the level of alpha-linolenic acid increased, and genes regulating cutin and wax synthesis were upregulated. Notably, high flavonoid and low ROS levels collectively inhibited RsPLA2G expression, which reduced the production of arachidonic acid, pro-inflammatory compounds (LTA4 and PGG2), and ROS, alleviating the inflammatory response and oxidative stress in radish epidermal tissues. CONCLUSION: PVC packaging enhanced the postharvest onset of 'black spot' in radishes, while OPP packaging delayed both its onset and development. Our study provides insights into the response of radishes to different packaging materials during storage, and the causes and host responses that either enhance or delay 'black spot' disorder onset. Further studies will be conducted to confirm the molecular and biochemical processes responsible for the onset and development of 'black spot' in radishes.

2.
Adv Mater ; 36(23): e2312153, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38444205

RESUMO

The presence of bacteria in tumor results in chemotherapeutic drug resistance and weakens the immune response in colorectal cancer. To overcome bacterium-induced chemotherapeutic drug resistance and potentiate antitumor immunity, herein a novel molecule Biotin-Lys(SA-Cip-OH)-Lys(SA-CPT)-Phe-Phe-Nap (Biotin-Cip-CPT-Nap) is rationally designed containing four functional motifs (i.e., a biotin motif for targeting, Phe-Phe(-Nap) motif for self-assembly, ciprofloxacin derivative (Cip-OH) motif for antibacterial effect, and camptothecin (CPT) motif for chemotherapy). Using the designed molecule, a novel strategy of intracellular enzymatic nanofiber formation and synergistic antibacterium-enhanced chemotherapy and immunotherapy is achieved. Under endocytosis mediated by highly expressed biotin receptor in colorectal cancer cell membrane and the catalysis of highly expressed carboxylesterase in the cytoplasm, this novel molecule can be transformed into Biotin-Nap, which self-assembled into nanofibers. Meanwhile, antibiotic Cip-OH and chemotherapeutic drug CPT are released, overcoming bacterium-induced drug resistance and enhancing the therapeutic efficacy of immunotherapy towards colorectal cancer. This work offers a feasible strategy for the design of novel multifunctional prodrugs to improve the efficiency of colorectal cancer treatment.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Pró-Fármacos , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Imunoterapia , Peptídeos/química , Peptídeos/farmacologia , Camptotecina/farmacologia , Camptotecina/química , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Nanofibras/química , Ciprofloxacina/farmacologia , Ciprofloxacina/química , Liberação Controlada de Fármacos , Biotina/química
3.
Antioxidants (Basel) ; 12(10)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37891958

RESUMO

Tea tree oil (TTO) is an essential plant oil with diverse antibacterial and antioxidant properties; however, whether the role played by TTO in low fish meal (LF) diets induced the observed effects in the farmed crustaceans remains unclear. Therefore, this study used Macrobrachium rosenbergii as the model crustacean, and an 8-week feeding experiment with NF (normal fish meal), LF (soybean meal replacing 40% fish meal), and LFT (LF with 200 mg/kg TTO) diets was conducted to evaluate the positive effects of TTO under the LF diet. Compared to the NF diet, the LF diet reduced hemolymph antioxidant capacity and non-specific immunity, and induced hepatopancreas apoptosis and damage. However, in comparison with LF, LTF significantly ameliorated morphological impairment in the hepatopancreas, improved hepatopancreas energy metabolism by upregulating the Bcl-2/Bax and Akt/mTOR pathways, and enhanced antioxidant and non-specific immune capacity by activating the NF-κB/NO pathway. In addition, LFT repaired intestinal barrier injury and the imbalance of intestinal microbiota induced by the LF diet. Moreover, the Pearson correlation revealed the variations of the above indicators, which were related to the abundance changes of Klebsiella, Clostridium sensu stricto 12, Thermobifida, Bifidobacterium, and Alistipes, indicating that these microbes might serve as prospective targets for the intestine-hepatopancreas axis to affect hepatopancreas apoptosis, metabolism, and non-specific immunity. In summary, 200 mg/kg TTO supplementation mediated gut microbiota and positively improved energy metabolism and non-specific immunity, thereby alleviating hepatopancreas dysplasia and damage induced by the LF diet in M. rosenbergii.

4.
Eur J Pharmacol ; 897: 173951, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33607105

RESUMO

The conventional anti-caries agents exhibit many shortcomings such as poor stability, low efficacy or short residence time in the oral environment, it is urgent to develop efficacy treatments to prevent dental caries. As the most active polyphenols from tea, Epigallocatechin gallate (EGCG) shows remarkable anti-cariogenic bioactivity. However, the poor stability and low bioavailability of EGCG limit its potential application. This study aimed to fabricate nanovesicles in-situ gel based on EGCG phospholipid complex in order to increase its stability and efficacy. The formation of EGCG phospholipid complex was characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The ethanol injection method was used to prepare the EGCG-loaded nanovesicles, an optimal ratio of Poloxamer407 (P407) and Poloxamer188 (P188) as in-situ gel matrix was selected to fabricate oral nanovesicles in-situ gel. EGCG-loaded nanovesicle in-situ gel based on the phospholipid complex had uniform spherical shape without any agglomeration. The discrete nanoparticle with a size (131.44 ± 4.24 nm) and a negative zeta potential value at -30.7 ± 0.5 mV possessed good physical stability and high entrapment efficiency (83.66 ± 3.2%). The formulation exhibited a strong antibacterial activity on S. mutans, which could reduce acid production and tooth surface adhesion. In addition, EGCG formulation could inhibit the formation of glucan and biofilm from S. mutans by suppressing the activity of glycosyltransferase enzymes (GTF). In conclusion, the EGCG-loaded nanovesicle in-situ gel holds great promise as an efficient anti-cariogenic formulation for topical oral delivery.


Assuntos
Antibacterianos/farmacologia , Cariostáticos/farmacologia , Catequina/análogos & derivados , Cárie Dentária/prevenção & controle , Portadores de Fármacos , Nanopartículas , Fosfolipídeos/química , Staphylococcus aureus/efeitos dos fármacos , Administração Oral , Antibacterianos/administração & dosagem , Antibacterianos/química , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Cariostáticos/administração & dosagem , Cariostáticos/química , Catequina/administração & dosagem , Catequina/química , Catequina/farmacologia , Cárie Dentária/microbiologia , Composição de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Géis , Cinética , Staphylococcus aureus/crescimento & desenvolvimento
5.
Nanotechnology ; 31(36): 365101, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32434167

RESUMO

Chemotherapy-induced immunogenic cell death (ICD) may offer a strategy to improve the effect of the therapeutic treatment of triple-negative breast cancer (TNBC) by eliciting broad antitumor immunity. However, chemotherapy shows a limited therapeutic effect because of multi-drug resistance and the immunosuppressive tumor microenvironment (TME) of TNBC. The unique pharmacological actions of sunitinib (SUN) indicate its possible synergies with paclitaxel (PTX) to enhance chemo-immunotherapy for TNBC. Here, we prepared a co-delivery platform composed of poly(styrene-co-maleic anhydride) (SMA) via a self-assembly process for a combination of PTX and SUN, which was able to induce a higher synergistic ICD. The nanomicellar delivery of PTX and SUN loaded at an optimal ratio of 1:5 (PTX:SUN) presented the characteristics of an appropriate particle size, long-term stability, and time sequence release which synergistically promoted the apoptosis of MDA-MB-231 tumor cells. Moreover, we demonstrated that the combination of PTX and SUN could significantly induce a synergistic effect because it promoted an ICD response, improved tumor immunogenicity, and regulated immunosuppressive factors in the TME. Overall, PTX and SUN with synergistic effects entrapped in a self-assembly nano-delivery system could offer the potential for clinical applicationof a combination chemo-immunotherapy strategy to improve the effect of the therapeutic treatment of TNBC.


Assuntos
Antineoplásicos/administração & dosagem , Paclitaxel/administração & dosagem , Sunitinibe/administração & dosagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Estabilidade de Medicamentos , Sinergismo Farmacológico , Feminino , Humanos , Morte Celular Imunogênica , Maleatos/química , Camundongos , Micelas , Paclitaxel/química , Paclitaxel/farmacologia , Tamanho da Partícula , Poliestirenos/química , Sunitinibe/química , Sunitinibe/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Int J Nanomedicine ; 14: 3361-3373, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190797

RESUMO

Purpose: To fabricate multifunctional nanocapsule via Pickering emulsion route to facilitate tumor-targeted delivery. Methods: Poly(N-isopropylacrylamide-co-acrylic acid) nanoparticles (PNA) stabilized nanocapsules were fabricated by Pickering emulsion (PE) technology. For controllable drug-release and enhancing targeted antitumor effects, the nanocapsules were crosslinked with cystamine and coupled on cell-surface molecule markers (cRGDfK) to achieve on-demand drug release and targeted delivery. Results: The fabricated PE and nanocapsules with average particle sizes (250 and 150 nm) were obtained. Encapsulation efficiency of hydrophobic anticancer drug (DOX) was determined as >90%. Release kinetic profiles for encapsulated nanocapsules displayed circulation stability and redox-sensitive releasing behavior with the supposed increase bioavailability. Both cytotoxicity assay, cellular uptake analysis and anticancer efficacy in B16F10 murine model demonstrated these redox-responsive drug-release and active targeted delivery. Conclusion: The results clearly demonstrated nanocapsule via PE route as promising candidate to provide an effective platform for incorporating hydrophobic drug for targeted cancer chemotherapy.


Assuntos
Sistemas de Liberação de Medicamentos , Emulsões/química , Nanocápsulas/química , Neoplasias/tratamento farmacológico , Peptídeos Cíclicos/química , Resinas Acrílicas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Morte Celular , Reagentes de Ligações Cruzadas/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Feminino , Células HeLa , Humanos , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Nanocápsulas/ultraestrutura , Nanogéis , Oxirredução , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoimina/química
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