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1.
Fish Shellfish Immunol ; 147: 109437, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38360192

RESUMO

Antimicrobial peptides (AMPs), which are widely present in animals and plants, have a broad distribution, strong broad-spectrum antibacterial activity, low likelihood of developing drug resistance, high thermal stability and antiviral properties. The present study investigated the effects of adding AMPs from Hermetia illucens larvae on the growth performance, muscle composition, antioxidant capacity, immune response, gene expression, antibacterial ability and intestinal microbiota of Cherax quadricarinatus (red claw crayfish). Five experimental diets were prepared by adding 50 (M1), 100 (M2), 150 (M3) and 200 (M4) mg/kg of crude AMP extract from H. illucens larvae to the basal diet feed, which was also used as the control (M0). After an eight-week feeding experiment, it was discovered that the addition of 100-150 mg/kg of H. illucens larvae AMPs to the feed significantly improved the weight gain rate and specific growth rate of C. quadricarinatus. Furthermore, the addition of H. illucens larvae AMPs to the feed had no significant effect on the moisture content, crude protein, crude fat and ash content of the C. quadricarinatus muscle. The addition of 100-150 mg/kg of H. illucens larvae AMPs in the feed also increased the antioxidant capacity, nonspecific immune enzyme activity and related gene expression levels in C. quadricarinatus, thereby enhancing their antioxidant capacity and immune function. The H. illucens larvae AMPs improved the structure and composition of the intestinal microbiota of C. quadricarinatus, increasing the microbial community diversity of the crayfish gut. Finally, the addition of 100-150 mg/kg of H. illucens larvae AMPs in the feed enhanced the resistance of C. quadricarinatus against Aeromonas hydrophila, improving the survival rate of the crayfish. Based on the aforementioned findings, it is recommended that H. illucens larvae AMPs be incorporated into the C. quadricarinatus feed at a concentration of 100-150 mg/kg.


Assuntos
Dípteros , Microbioma Gastrointestinal , Animais , Larva/microbiologia , Astacoidea , Aeromonas hydrophila/genética , Peptídeos Antimicrobianos , Antioxidantes , Dieta , Expressão Gênica , Antibacterianos
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 309: 123822, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38176193

RESUMO

Fluoride ion is not only important for dental health, but also a contributing factor in a variety of diseases. At the same time, fluoride ions and cell viscosity are both important to the physiological environment of mitochondria. We developed a dual-response ratiometric fluorescent probe BDF based on Förster resonance energy transfer (FRET) and intramolecular charge transfer (ICT) mechanism for the detection of F- and viscosity. BDF has an outstanding intramolecular energy transfer efficiency of 97.7% and shows excellent performance for fluorine ion detection. In addition, when the system viscosity increases, the fluorescence emission intensity of BDF is greatly heightened, indicating the possibility of viscosity detection. Finally, based on the fluorescence properties of BDF, we used the probe to detect F- in the toothpaste sample and image exogenous fluoride ions in HeLa cells.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Fluoretos , Humanos , Transferência Ressonante de Energia de Fluorescência/métodos , Corantes Fluorescentes , Células HeLa , Flúor , Viscosidade
3.
Fish Shellfish Immunol ; 145: 109363, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38185392

RESUMO

Astaxanthin is one of the important immunopotentators in aquaculture. However, little is known about the physiological changes and stress resistance effects of astaxanthin in marine gastropods. In this study, the effects of different astaxanthin concentrations (0, 25, 50, 75, and 100 mg/kg) on the growth, muscle composition, immune function, and resistance to ammonia stress in Babylonia areolata were investigated after three months of rearing. With the increase in astaxanthin content, the weight gain rate (WGR), specific growth rate (SGR), and survival rate (SR) of B. areolata showed an increasing trend. The 75-100 mg/kg group was significantly higher than the control group (0 mg/kg). There was no significant difference in the flesh shell ratio (FSR), viscerosomatic index (VSI), and soft tissue index (STI) of the experimental groups. Astaxanthin (75 mg/kg) significantly increased muscle crude protein content and increased hepatopancreas alkaline phosphatase (AKP), superoxide dismutase (SOD), and catalase (CAT) activity. Astaxanthin (75-100 mg/kg) significantly increased the total antioxidant capacity (T-AOC) and acid phosphatase (ACP) of the hepatopancreas and decreased the malondialdehyde (MDA) content of B. areolata. Astaxanthin significantly induced the expression levels of functional genes, such as SOD, Cu/ZnSOD, ferritin, ACP, and CYC in hepatopancreas and increased the survival rate of B. areolata under ammonia stress. The addition of 75-100 mg/kg astaxanthin to the feed improved the growth performance, muscle composition, immune function, and resistance to ammonia stress of B. areolata.


Assuntos
Amônia , Gastrópodes , Animais , Dieta , Antioxidantes/metabolismo , Gastrópodes/metabolismo , Imunidade Inata , Expressão Gênica , Músculos/metabolismo , Superóxido Dismutase/metabolismo , Ração Animal/análise , Suplementos Nutricionais , Xantofilas
4.
Fish Shellfish Immunol ; 145: 109288, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38104697

RESUMO

This study aimed to evaluate the potential benefits of chitosan oligosaccharide (COS) on red claw crayfish (Cherax quadricarinatus) and explore its underlying mechanisms. The crayfish were randomly divided into six groups, and the diets were supplemented with COS at levels of 0 (C0), 0.2 (C1), 0.4 (C2), 0.6 (C3), 0.8 (C4), and 1 (C5) g kg-1. Treatment with COS significantly improved the growth performance of the crayfish with a higher weight gain rate (WGR) and specific growth rate (SGR) in the C2 group compared to the C0 group. Additionally, the content of crude protein in the crayfish muscles in the C1 group was significantly higher than that of the C0 group. Regarding non-specific immunity, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and alkaline phosphatase (AKP), and the levels of expression of the genes related to immunity (SOD; anti-lipopolysaccharide factor [ALF]; thioredoxin1 [Trx1]; C-type lysozyme, [C-LZM]; and GSH-Px) in the hepatopancreas and hemolymph increased significantly (P < 0.05) after supplementation with 0.4 g kg-1 of COS, while the content of malondialdehyde (MDA) decreased (P < 0.05). The survival rate of C. quadricarinatus increased (P < 0.05) in the C2, C3, C4, and C5 groups after the challenge with Aeromonas hydrophila. This study found that COS has the potential to modulate the composition of the intestinal microbiota and significantly reduce the abundance of species of the phylum Proteobacteria and the genera Aeromonas and Vibrio in the gut of C. quadricarinatus, while the abundance of bacteria in the phylum Firmicutes and the genus Candidatus_Hepatoplasma improved significantly. This study suggests that the inclusion of COS in the diet of C. quadricarinatus can enhance growth, boost immunity, and increase resistance to infection with A. hydrophila, especially when supplemented at 0.4-0.8 g kg-1.


Assuntos
Quitosana , Microbioma Gastrointestinal , Animais , Astacoidea , Quitosana/farmacologia , Dieta , Suplementos Nutricionais/análise , Superóxido Dismutase/metabolismo , Oligossacarídeos/farmacologia , Imunidade Inata , Ração Animal/análise
5.
Talanta ; 256: 124302, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36708620

RESUMO

The intracellular viscosity is an important parameter of the microenvironment and SO2 is a vital gas signal molecule. At present, some dual-response fluorescence probes for simultaneous measurements of viscosity and SO2 derivatives (HSO3-/SO32-) possessed poor water solubility. In this work, we developed a water-soluble fluorescence probe CIJ (0.0864 g/100 mL of water at 20 °C) for simultaneous measurements of viscosity and SO2 derivatives. CIJ exhibited a sensitive fluorescence enhancement to environmental viscosity from 0.97 to 28.04 cP based on a twisted intramolecular charge transfer mechanism and was applied to effective measurement of viscosity in vitro and in vivo. CIJ could also respond to SO2 derivatives with a low detection limit (44 nM) and a fast response time (5 min) based on the nucleophilic addition reaction. Furthermore, CIJ was applied to monitor SO2 derivatives in ratiometric response manner in living cells.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes , Humanos , Solubilidade , Viscosidade , Sulfitos , Células HeLa , Água , Dióxido de Enxofre
6.
Fish Shellfish Immunol ; 132: 108505, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36581251

RESUMO

Red claw crayfish (Cherax quadricarinatus) is an important freshwater shrimp species worldwide with enormous economic value. Waterless transportation is an inherent feature of red claw crayfish transportation. However, the high mortality of red claw crayfish is a severe problem in the aquaculture of crayfish after waterless transportation. In this study, we investigated the responses of the hepatopancreas from the red claw crayfish undergoing air exposure stress and normal conditions on transcriptome levels. We used Illumina-based RNA sequencing (RNA-Seq) to perform a transcriptome analysis from the hepatopancreas of red claw crayfish challenged by air exposure. An average of 57,148,800 clean reads per library was obtained, and 33,567 unigenes could be predicted and classified according to their homology with matches in the National Center for Biotechnology Information (NCBI) non-redundant protein sequences (Nr), Gene Ontology (GO), a manually annotated and reviewed protein sequence database (Swiss-Prot), protein families (Pfam), Clusters of Orthologous Groups (COG) of proteins, and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. 690 and 3407 differentially expressed genes (DEGs) were identified between the two stress stages of the red claw crayfish. More DEGs were identified in 12 h, indicating that gene expressions were largely changed at 12 h. Some immune-related pathways and genes were identified according to KEGG and GO enrichment analysis. A total of 12 DEGs involved in immune response and trehalose mechanism were verified by quantitative real-time-polymerase chain reaction (qRT-PCR). The results indicated that the red claw crayfish might counteract the stress of air exposure at the transcriptomic level by increasing expression levels of antioxidant-, immune-, and trehalose metabolism-related genes. These transcriptome results from the hepatopancreas provide significant insights into the influence mechanism of air exposure to the trehalose mechanism and immune response in the red claw crayfish.


Assuntos
Astacoidea , Hepatopâncreas , Animais , Astacoidea/genética , Trealose/metabolismo , Perfilação da Expressão Gênica/veterinária , Transcriptoma
7.
Ying Yong Sheng Tai Xue Bao ; 33(9): 2347-2355, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36131649

RESUMO

We established 340-year chronologies of total ring width, early wood width, and late wood width with tree-ring samples of Pinus taiwanensis at high altitude collected from the western Tianmu Mountain in northern Zhejiang Province. According to the criterion that subsample signal strength (SSS) should be larger than 0.8, the reliable period was from 1810 to 2019. Through the correlation analysis between chronologies and climatic factors, we examined the responses of tree ring growth to climate. The results showed that radial growth of P. taiwanensis was more sensitive to temperature than to precipitation. Comprehensively considering the correlation analysis results for the raw and first-order difference series, early wood width was significantly correlated with the early growing season mean and maximum temperatures of the prior year, while late wood width with prior May and current September mean and maximum temperatures. The correlation pattern of total ring width was similar to that of early wood width, although at a low level. The optimal correlation was between early wood width and prior April-July mean temperature. Based on this relationship, April-July mean temperature of the Tianmu Mountain, East China was reconstructed for the period of 1809-2018 with an explained variance of 61.5%. Both the raw and first-order difference series passed the split sample calibration-verification test. The warm periods were 1809-1833 and 1965-2018, with a cold period in 1834-1964. Temperature had risen rapidly since the 1960s. From the standpoint of low frequency, it reached an unprecedented level since the 1980s over the past 210 years. Spatial correlation analysis showed that the reconstructed temperature series could represent temperature variations of East China, which had a good agreement with a reconstructed regional temperature series from East China. Our results showed that P. taiwanensis had a great potential for paleoclimate reconstruction in East China.


Assuntos
Pinus , Árvores , China , Clima , Temperatura
8.
Fish Shellfish Immunol ; 127: 280-294, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35752371

RESUMO

This study aimed to investigate the effects of Elephantopus scaber extract on the GIFT (genetic improvement of farmed tilapia) strain of Nile tilapia Oreochromis niloticus. A total of 800 tilapia with an initial body weight of 1.34 ± 0.09 g each were randomly divided into five groups. The tilapia in the control group (E0 group) were fed on a basal diet only. Meanwhile, tilapia in the four experimental groups were fed on a basal diet supplemented with 1 g/kg (E1 group), 3 g/kg (E2 group), 5 g/kg (E3 group), and 7 g/kg (E4 group) of E. scaber extract for 10 weeks. Results showed that the survival rate was higher in the experimental groups than in the control group. Compared with the control group, some growth parameters (FW, WGR, SGR, VSI, and HSI) were significantly improved in the E1 group and E2 group. The crude lipid content in the dorsal muscle and liver was lower in the E1 group than in the control group. After E. scaber extract supplementation, activities of immunity-related enzymes (ACP, AKP, T-AOC, SOD, CAT, GSH-Px and LZM) in plasma, liver, spleen and head kidney, and expressions of immunity-related genes (IL-1ß, IFN-γ, TNF-α, and CCL-3) in liver, spleen and head kidney showed various degrees of improvement, while MDA content and Hsp70 expression level were decreased. The survival rate of tilapia increased in all the supplementation groups after Streptococcus agalactiae treatment. E. scaber extract addition changed the species composition, abundance, and diversity of intestinal microbiota in tilapia. These results demonstrate that E. scaber extract supplementation in diet can improve the growth, immunity, and disease resistance of GIFT against S. agalactiae. E. scaber extract supplementation can also change intestinal microbiota and reduce crude lipid content in dorsal muscle and liver. The above indicators show that the optimal dose of E. scaber extract for GIFT is 1 g/kg.


Assuntos
Asteraceae , Ciclídeos , Doenças dos Peixes , Microbioma Gastrointestinal , Infecções Estreptocócicas , Tilápia , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Lipídeos , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae/fisiologia , Tilápia/metabolismo
9.
Fish Shellfish Immunol ; 119: 524-532, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34737131

RESUMO

This study was performed to investigate the effects of dietary trehalose on growth, muscle composition, non-specific immune responses, gene expression and desiccation resistance of juvenile red claw crayfish (Cherax quadricarinatus). A total of 540 (body weight of 0.41 ± 0.05) crayfish were randomly divided into six groups for a feeding experiment. Six diets with trehalose levels at 0 (Diet 1), 1 (Diet 2), 2 (Diet 3), 5 (Diet 4), 10 (Diet 5) and 15 (Diet 6) g kg-1 were prepared to feed juvenile red claw crayfish for 8 weeks. The results showed that the weight gain rate (WGR) and specific growth rate (SGR) of crayfish in Diet 4, Diet 5 and Diet 6 groups were significantly improved compared with the control group (Diet 1). Muscle crude protein contents of crayfish fed Diet 4, Diet 5 and Diet 6 were significantly higher than those of the control group. The activities of superoxide dismutase (SOD) and alkaline phosphatase (AKP) in hepatopancreas and hemolymph of crayfish for Diet 4, Diet 5, and Diet 6 groups were significantly increased while malondialdehyde (MDA) content was significantly reduced when compared with the control. The total antioxidant capacity (T-AOC), catalase (CAT) and glutathione peroxidase (GPx) activities in the hepatopancreas and hemolymph of crayfish fed Diet 5 and Diet 6 were significantly higher than those in the control group. However, acid phosphatase (ACP) activity was not significantly different among all experimental groups. The hepatopancreas and intestine trehalose contents of crayfish showed an upward trend with the increase of dietary trehalose levels. Compared with the control group, supplementation of 5-15 g kg-1 trehalose in the feed up-regulated the expression levels of GPx, C-type lysozyme (C-LZM), antilipolysacchride factor (ALF), facilitated trehalose transporter homolog isoform X2 (Tret1-2) and facilitated trehalose transporter isoform X4 (Tret1-4) mRNA. In addition, supplementation of 5-15 g kg-1 trehalose in the feed could improve the survival rate of red claw crayfish under desiccation stress. These results suggested that supplementation of 5-15 g kg-1 trehalose in feed could significantly improve the growth performance, muscle protein, non-specific immunity and desiccation resistance of juvenile red claw crayfish.


Assuntos
Astacoidea , Trealose , Ração Animal/análise , Animais , Antioxidantes , Astacoidea/genética , Dessecação , Dieta/veterinária , Suplementos Nutricionais/análise , Expressão Gênica , Imunidade Inata/genética
11.
Mol Ther Oncolytics ; 18: 396-408, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32913889

RESUMO

Relapse of cancer is associated with multidirectional differentiation and unrestricted proliferative replication potential of cancer stem cells. Herein, we propose the plastic differentiation strategy for irreversible differentiation of cancer stem cells; further, salinomycin and its newly constructed functional liposomes are used to implement this strategy. Whole gene, cancer stem cell-related RNA, and protein expression analyses reveal that salinomycin induces the cancer stem cells into normal cells, dormant cells, and mature cancer cells. Besides, the results indicate that the gatekeeper is related to the inhibition of the protein kinase C (PKC) α signaling pathway. The differentiated normal or dormant cells are incorporated into normal tissue, whereas the rest are killed by chemotherapy. The findings would offer the evidence for plastic differentiation of cancer stem cells and propose a novel strategy for cancer therapy.

12.
Nanomaterials (Basel) ; 10(5)2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32429472

RESUMO

Regular chemotherapy cannot eliminate leukemic cells, due to the sparse distribution of cancer cells in leukemia patients. Here, we report a precise nanostructure of folate-overhung mitoxantrone DNA tetrahedron that enables the treatment of leukemic cells by targeted action. Folate is used as a targeting molecule and synthesized with DNA strand in forming the folate-overhang DNA complement, and the complement is then separately base-paired onto six sides of the fabricated DNA tetrahedron. Mitoxantrone is used as an anticancer agent and intercalated into the double strands of the folate-overhung DNA tetrahedron for drug loading. The evaluation studies are performed on leukemia BALL-1 and K562 cells. The results demonstrate that the folate-overhung mitoxantrone DNA tetrahedra (approximately 25 nm) are able to target leukemic cells, transport across the nuclei membrane, induce the apoptosis, and enhance the overall efficacy of treating leukemic cells in vitro and in leukemia-bearing mice. This study provides a potential drug-containing DNA nanostructure, to clean the sparsely distributed leukemic cells in patients.

13.
Ann Transl Med ; 7(20): 534, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31807516

RESUMO

BACKGROUND: The aim of the study was to evaluate whether the preemptive renal replacement therapy (RRT) might improve outcomes in post-cardiotomy cardiogenic shock (PCCS) patients. METHODS: In Period A (September 2014-April 2016), patients with PCCS received RRT, depending on conventional indications or bedside attendings. In Period B (May 2016-November 2017), the preemptive RRT strategy was implemented in all PCCS patients in our intensive care unit. The goal-directed RRT was applied for the RRT patients. The hospital mortality and renal recovery were compared between the two periods. RESULTS: A total of 155 patients (76 patients in Period A and 79 patients in Period B) were ultimately enrolled in this study. There were no significant differences in demographic characteristics and intraoperative and postoperative parameters between the two groups. The duration between surgery and RRT initiation was significantly shorter in Period B than in Period A [23 (17, 66) vs. 47 (20, 127) h, P<0.01]. The hospital mortality in Period B was significantly lower than that in Period A (38.0% vs. 59.2%, P<0.01). There were fewer patients with no renal recovery in Period B (4.1% vs. 19.4%, P=0.026). Patients in Period B displayed a significantly shorter time to completely renal recovery (12±15 vs. 25±15 d, P<0.05). CONCLUSIONS: Among PCCS patients, preemptive RRT compared with conventional initiation of RRT reduced mortality in hospital and also led to faster and more frequent recovery of renal function. Our preliminary study supposed that preemptive initiation of RRT might be an effective approach to PCCS with acute kidney injury (AKI).

14.
AAPS PharmSciTech ; 21(1): 6, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754916

RESUMO

The aim of the study is to investigate the feasibility of fabricating FDM 3D-printed gastric floating tablets with low infill percentages and the effect of infill percentage on the properties of gastric floating tablets in vitro. Propranolol hydrochloride was selected as a model drug, and drug-loaded polyvinyl alcohol (PVA) filaments were produced by hot melt extrusion (HME). Ellipsoid-shaped gastric floating tablets with low infill percentage of 15% and 25% (namely E-15 and E-25) were then prepared respectively by feeding the extruded filaments to FDM 3D printer. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) were employed to characterize the filaments and 3D-printed tablets, and a series of evaluations were performed to the 3D-printed tablets, including the weight variation, drug content, hardness, in vitro floating behavior, and drug release of the tablets. The SEM results showed that the drug-loaded filaments and 3D-printed tablets appeared intact without defects, and the printed tablets were composed of filaments deposited uniformly layer by layer. The model drug and the excipients were thermally stable under the process temperature of extruding and printing, with a small amount of drug crystals dispersing in the drug-loaded filaments and 3D-printed tablets. Both E-15 and E-25 could float on artificial gastric fluids without any lag time and released in a sustained manner. Compared with E-15, the E-25 presented less weight variation, higher tablet hardness, shorter floating time, and longer drug release time.


Assuntos
Portadores de Fármacos/síntese química , Excipientes/síntese química , Impressão Tridimensional , Comprimidos/síntese química , Tecnologia Farmacêutica/métodos , Varredura Diferencial de Calorimetria/métodos , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Excipientes/farmacocinética , Álcool de Polivinil/síntese química , Álcool de Polivinil/farmacocinética , Propranolol/síntese química , Propranolol/farmacocinética , Comprimidos/farmacocinética , Difração de Raios X/métodos
15.
Int J Nanomedicine ; 14: 3645-3667, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190817

RESUMO

Background: Neo-adjuvant chemotherapy is an effective strategy for improving treatment of breast cancers. However, the efficacy of this treatment strategy is limited for treatment of triple negative breast cancer (TNBC). Gene therapy may be a more effective strategy for improving the prognosis of TNBC. Methods: A novel 25 nucleotide sense strand of miRNA was designed to treat TNBC by silencing the Slug gene, and encapsulated into DSPE-PEG2000-tLyp-1 peptide-modified functional liposomes. The efficacy of miRNA liposomes was evaluated on invasive TNBC cells and TNBC cancer-bearing nude mice. Furthermore, functional vinorelbine liposomes were constructed to investigate the anticancer effects of combined treatment. Results: The functional miRNA liposomes had a round shape and were nanosized (120 nm). Functional miRNA liposomes were effectively captured by TNBC cells in vitro and were target to mitochondria. Treatment with functional liposomes silenced the expression of Slug and Slug protein, inhibited the TGF-ß1/Smad pathway, and inhibited invasiveness and growth of TNBC cells. In TNBC cancer-bearing mice, functional miRNA liposomes exerted a stronger anticancer effect than functional vinorelbine liposomes, and combination therapy with these two formulations resulted in nearly complete inhibition of tumor growth. Preliminary safety evaluations indicated that the functional miRNA liposomes did not affect body weight or cause damage to any major organs. Furthermore, the functional liposomes significantly increased the half-life of the drug in the blood of cancer-bearing nude mice, and increased drug accumulation in breast cancer tissues. Conclusion: In this study, we constructed novel functional miRNA liposomes. These liposomes silenced Slug expression and inhibited the TGF-ß1/Smad pathway in TNBC cells, and enhanced anticancer efficacy in mice using combined chemotherapy. Hence, the present study demonstrated a promising strategy for gene therapy of invasive breast cancer.


Assuntos
Inativação Gênica , MicroRNAs/metabolismo , Nanopartículas/química , Tamanho da Partícula , Fatores de Transcrição da Família Snail/genética , Neoplasias de Mama Triplo Negativas/terapia , Animais , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Lipossomos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
16.
Int J Mol Sci ; 20(9)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060324

RESUMO

Antigen peptides and adjuvants have been extensively investigated for cancer immunotherapy, and they are expected to elicit specific immune responses for cancer treatment. However, the anti-cancer efficacy of antigen peptide and adjuvant-based cancer vaccines has been limited due to the inefficient delivery to draining lymph nodes after administration. Therefore, it is necessary to develop a suitable delivery system to transport antigen peptides and adjuvants. Here, we report a novel type of nanostructured lipovaccines for the treatment of melanoma by delivering antigen peptide (SL9) and oligodeoxynucleotide adjuvant (CpG) to the lymphatic vessels and to the draining lymph node. The SL9-CpG lipovaccines were characterized using dynamic laser scattering (DLS) and transmission electron microscopy (TEM). The lymph uptake, immune response elicitation and treatment effects were evaluated on melanoma-bearing C57BL/6 mice using flow cytometry (FCM), enzyme-linked immunosorbent assay (ELISA) and tumor inhibitory efficacy. The SL9-CpG lipovaccines were uniform with a nanoscale size (~70 nm), had high encapsulation efficiency, and exhibited effective lymph uptake, resulting in activation of specific cytotoxic CD8+ T cells, and release of IFN-γ, and a robust inhibition of tumor growth. Therefore, the nanostructured SL9-CpG lipovaccines offer a promising strategy for melanoma treatment.


Assuntos
Vacinas Anticâncer/imunologia , Glicina/análogos & derivados , Imunomodulação , Melanoma/imunologia , Melanoma/terapia , Peptídeos/imunologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Glicina/química , Glicina/imunologia , Humanos , Imunoterapia , Linfonodos/imunologia , Melanoma/metabolismo , Camundongos , Peptídeos/química , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Nanomaterials (Basel) ; 8(10)2018 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-30304783

RESUMO

The heterogeneity of breast cancer and the development of drug resistance are the relapse reasons of disease after chemotherapy. To address this issue, a combined therapeutic strategy was developed by building the nanostructured dihydroartemisinin plus epirubicin liposomes. Investigations were performed on human breast cancer cells in vitro and xenografts in nude mice. The results indicated that dihydroartemisinin could significantly enhance the efficacy of epirubicin in killing different breast cancer cells in vitro and in vivo. We found that the combined use of dihydroartemisinin with epirubicin could efficiently inhibit the activity of Bcl-2, facilitate release of Beclin 1, and further activate Bax. Besides, Bax activated apoptosis which led to the type I programmed death of breast cancer cells while Beclin 1 initiated the excessive autophagy that resulted in the type II programmed death of breast cancer cells. In addition, the nanostructured dihydroartemisinin plus epirubicin liposomes prolonged circulation of drugs, and were beneficial for simultaneously delivering drugs into breast cancer tissues. Hence, the nanostructured dihydroartemisinin plus epirubicin liposomes could provide a new therapeutic strategy for treatment of breast cancer.

18.
Ther Clin Risk Manag ; 13: 1499-1505, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29184415

RESUMO

OBJECTIVE: To evaluate the impact of the renal dysfunction (RD) type and change of postoperative cardiac function on the risk of developing acute kidney injury (AKI) in patients who underwent cardiac valve surgery. METHOD: Reversible renal dysfunction (RRD) was defined as preoperative RD in patients who had not been initially diagnosed with chronic kidney disease (CKD). Cardiac function improvement (CFI) was defined as postoperative left ventricular ejection function - preoperative left ventricular ejection function (ΔEF) >0%, and cardiac function not improved (CFNI) as ΔEF ≤0%. RESULTS: Of the 4,805 (94%) cardiac valve surgery patients, 301 (6%) were RD cases. The AKI incidence in the RRD group (n=252) was significantly lower than in the CKD group (n=49) (36.5% vs 63.3%, P=0.018). The AKI and renal replacement therapy incidences in the CFI group (n=174) were significantly lower than in the CFNI group (n=127) (33.9% vs 50.4%, P=0.004; 6.3% vs 13.4%, P=0.037). After adjustment for age, gender, and other confounding factors, CKD and CKD + CFNI were identified as independent risk factors for AKI in all patients after cardiac valve surgery. Multivariate logistic regression analysis showed that the risk factors for postoperative AKI in preoperative RD patients were age, gender (male), hypertension, diabetes, chronic heart failure, cardiopulmonary bypass time (every 1 min added), and intraoperative hypotension, while CFI after surgery could reduce the risk. CONCLUSION: For cardiac valve surgery patients, preoperative CKD was an independent risk factor for postoperative AKI, but RRD did not add to the risk. Improved postoperative cardiac function can significantly reduce the risk of postoperative AKI.

19.
BMJ Open ; 7(10): e014171, 2017 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-29061597

RESUMO

OBJECTIVE: The purpose of this study was to perform a systematic review and meta-analysis to evaluate the effect of high-dose versus low-dose haemofiltration on the survival of critically ill patients with acute kidney injury (AKI). We hypothesised that high-dose treatments are not associated with a higher risk of mortality. DESIGN: Meta-analysis. SETTING: Randomised controlled trials and two-arm prospective and retrospective studies were included. PARTICIPANTS: Critically ill patients with AKI. INTERVENTIONS: Continuous renal replacement therapy. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes: 90-day mortality, intensive care unit (ICU) mortality, hospital mortality; secondary outcomes: length of ICU and hospital stay. RESULT: Eight studies including 2970 patients were included in the analysis. Pooled results showed no significant difference in the 90-mortality rate between patients treated with high-dose or low-dose haemofiltration (pooled OR=0.90, 95% CI 0.73 to 1.11, p=0.32). Findings were similar for ICU (pooled OR=1.12, 95% CI 0.94 to 1.34, p=0.21) and hospital mortality (pooled OR=1.03, 95% CI 0.81 to 1.30, p=0.84). Length of ICU and hospital stay were similar between high-dose and low-dose groups. Pooled results are not overly influenced by any one study, different cut-off points of prescribed dose or different cut-off points of delivered dose. Meta-regression analysis indicated that the results were not affected by the percentage of patients with sepsis or septic shock. CONCLUSION: High-dose and low-dose haemofiltration produce similar outcomes with respect to mortality and length of ICU and hospital stay in critically ill patients with AKI.This study was not registered at the time the data were collected and analysed. It has since been registered on 17 February 2017 at http://www.researchregistry.com/, registration number: reviewregistry211.


Assuntos
Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Hemofiltração/métodos , Choque Séptico/complicações , Estado Terminal/terapia , Mortalidade Hospitalar , Humanos , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia de Substituição Renal
20.
Ann Med ; 49(4): 343-351, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27936959

RESUMO

PURPOSE: Goal-directed hemodynamic therapy (GDT) is used to prevent hypoperfusion resulting from surgery. The objective of this study was to analyze the efficacy and importance of perioperative GDT. METHODS: PUBMED, MEDLINE, CENTRAL, and Google Scholar databases were searched until 17 June 2016 using the search terms: cardiac output, cardiac surgical procedures, hemodynamics, goal-directed therapy, and intraoperative. Randomized-controlled trials with pre-emptive hemodynamic intervention for cardiac surgical population versus standard hemodynamic therapy were included. RESULTS: Nine studies were included with a total of 1148 patients. The overall analysis revealed no significant difference in the all-cause mortality (pooled peto OR =0.58, 95%CI =0.27-1.525, p = 0.164), duration of mechanical ventilation (pooled difference in mean= -1.48, 95%CI= -3.24 to 0.28, p = 0.099), or length of intensive care unit (ICU) stay (pooled difference in mean= -9.10, 95%CI= -20.14 to 1.93, p = 0.106) between patients in the GDT and control groups. Patients in the GDP group were associated with shorter hospital stay than those in the control group (pooled difference in mean= -1.52, 95%CI= -2.31 to -0.73, p < 0.001). CONCLUSION: GDT reduces the length of hospital stay compared with the standard of care. Further studies are necessary to continually assess the benefit of GDT following major surgery. Key Messages The results of this analysis revealed no significant difference between cardiac surgery patients receiving goal-directed hemodynamic therapy (GDT) or conventional fluid therapy in terms of the all-cause mortality, duration of mechanical intervention, and length of ICU-stay. The length of hospital stay was significantly reduced in patients treated with GDT compare to conventional fluid therapy. GDT may have limited benefit in reducing mortality; however, the association to shorter length of hospital stay may suggest that better hemodynamic balance can facilitate postoperative recovery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Idoso , Débito Cardíaco , Cuidados Críticos , Hemodinâmica , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Ensaios Clínicos Controlados Aleatórios como Assunto
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