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1.
J Nanobiotechnology ; 21(1): 15, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36647056

RESUMO

BACKGROUND: Malaria remains a serious threat to global public health. With poor efficacies of vaccines and the emergence of drug resistance, novel strategies to control malaria are urgently needed. RESULTS: We developed erythrocyte membrane-camouflaged nanoparticles loaded with artemether based on the growth characteristics of Plasmodium. The nanoparticles could capture the merozoites to inhibit them from repeatedly infecting normal erythrocytes, owing to the interactions between merozoites and heparin-like molecules on the erythrocyte membrane. Modification with a phosphatidylserine-targeting peptide (CLIPPKF) improved the drug accumulation in infected red blood cells (iRBCs) from the externalized phosphatidylserine induced by Plasmodium infection. In Plasmodium berghei ANKA strain (pbANKA)-infected C57BL/6 mice, the nanoparticles significantly attenuated Plasmodium-induced inflammation, apoptosis, and anemia. We observed reduced weight variation and prolonged survival time in pbANKA-challenged mice, and the nanoparticles showed good biocompatibility and negligible cytotoxicity. CONCLUSION: Erythrocyte membrane-camouflaged nanoparticles loaded with artemether were shown to provide safe and effective protection against Plasmodium infection.


Assuntos
Malária , Merozoítos , Animais , Camundongos , Membrana Eritrocítica , Fosfatidilserinas , Biomimética , Camundongos Endogâmicos C57BL , Malária/tratamento farmacológico , Malária/prevenção & controle , Eritrócitos , Artemeter/farmacologia , Plasmodium berghei , Plasmodium falciparum
2.
Int J Mol Sci ; 24(2)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36674699

RESUMO

Retinoid X receptor alpha (RXRA) is a well-characterized factor that regulates lipid metabolism; however, the regulatory mechanism in muscle cells of poultry is still unknown. The overexpression and the knockdown of RXRA in myoblasts (CS2 cells), RT-PCR, and western blotting were used to detect the expression levels of genes and proteins related to PPAR-signaling pathways. Intracellular triglycerides (TGs), cholesterol (CHOL), and nonesterified free fatty acids (NEFAs) were detected by the Elisa kit. Fat droplets were stained with Oil Red O. The double-fluorescein reporter gene and chromatin immunoprecipitation (CHIP) were used to verify the relationship between RXRA and candidate target genes. The RXRA gene was highly expressed in duck breast muscle, and its mRNA and its protein were reduced during the differentiation of CS2 cells. The CS2 cells, with the overexpression of RXRA, showed reduced content in TGs, CHOL, NEFAs, and lipid droplets and upregulated the mRNA expression of CD36, ACSL1, and PPARG genes and the protein expression of CD36 and PPARG. The knockdown of RXRA expression in CS2 cells enhanced the content of TGs, CHOL, NEFAs, and lipid droplets and downregulated the mRNA and protein expression of CD36, ACLS1, ELOVL6, and PPARG. The overexpression of the RXRA gene, the activity of the double-luciferase reporter gene of the wild-type CD36 promoter was higher than that of the mutant type. RXRA bound to -860/-852 nt, -688/-680 nt, and -165/-157 nt at the promoter region of CD36. Moreover, the overexpression of CD36 in CS2 cells could suppress the content of TGs, CHOL, NEFAs, and lipid droplets, while the knockdown expression of CD36 increased the content of TGs, CHOL, NEFAs, and lipid droplets. In this study, the transcription factor, RXRA, inhibited the accumulation of TGs, CHOL, NEFAs, and fat droplets in CS2 cells by promoting CD36 expression.


Assuntos
Patos , Fatores de Transcrição , Animais , Fatores de Transcrição/metabolismo , Patos/genética , Receptor X Retinoide alfa/metabolismo , PPAR gama/metabolismo , Ácidos Graxos não Esterificados , Metabolismo dos Lipídeos/genética , Triglicerídeos/metabolismo , Colesterol , Mioblastos/metabolismo , RNA Mensageiro/metabolismo , Antígenos CD36/genética , Antígenos CD36/metabolismo
3.
Magn Reson Med ; 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36594439

RESUMO

PURPOSE: To combine a new two-stage N/2 ghost correction and an adapted L1-SPIRiT method for reconstruction of 7T highly accelerated whole-brain diffusion MRI (dMRI) using only autocalibration scans (ACS) without the need of additional single-band reference (SBref) scans. METHODS: The proposed ghost correction consisted of a 3-line reference approach in stage 1 and the reference-free entropy method in stage 2. The adapted L1-SPIRiT method was formulated within the 3D k-space framework. Its efficacy was examined by acquiring two dMRI data sets at 1.05-mm isotropic resolutions with a total acceleration of 6 or 9 (i.e., 2-fold or 3-fold slice and 3-fold in-plane acceleration). Diffusion analysis was performed to derive DTI metrics and estimate fiber orientation distribution functions (fODFs). The results were compared with those of 3D k-space GRAPPA using only ACS, all in reference to 3D k-space GRAPPA using both ACS and SBref (serving as a reference). RESULTS: The proposed ghost correction eliminated artifacts more robustly than conventional approaches. Our adapted L1-SPIRiT method outperformed 3D k-space GRAPPA when using only ACS, improving image quality to what was achievable with 3D k-space GRAPPA using both ACS and SBref scans. The improvement in image quality further resulted in an improvement in estimation performances for DTI and fODFs. CONCLUSION: The combination of our new ghost correction and adapted L1-SPIRiT method can reliably reconstruct 7T highly accelerated whole-brain dMRI without the need of SBref scans, increasing acquisition efficiency and reducing motion sensitivity.

4.
Nano Lett ; 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36459114

RESUMO

Strontium-containing agents have been demonstrated to elicit both bone anabolic and antiosteoporotic effects, showing great potential for the treatment of bone loss. However, an increased incidence of strontium-induced side effects restricts their clinical applications. Herein, oxidized carbon nitride nanosheets (CN) are delicately used to incorporate Sr2+ for the first time to achieve high osteogenic efficacy. The lamellar structure and enriched nitrogen species of CN provide them with a high surface area-to-volume ratio and abundant anchoring sites for Sr2+ incorporation. Importantly, Sr2+-incorporated CN (CNS) could synergistically promote osteoblast differentiation and bone regeneration at a single, very low Sr2+ dose. Mechanically, CNS could activate the FAK/RhoA signaling pathway to modulate the intracellular tension that stimulates osteoblasts differentiation. The present study will provide a new paradigm to enhance the efficacy of osteogenic metal ions by using lamellar nanocarriers.

5.
Foods ; 11(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36360081

RESUMO

The influence of surface substance production on the freeze-drying survival of Lactobacillus casei and methods to control the surface substances during fermentation were studied. The bacteria were treated with hypertonicity combined with ultrasound, and the survival rate was determined. The optimal conditions for removing surface substance without harming the bacteria were 81 w/18 min. The surface substances provided a protective effect on the lyophilization of the bacteria without protectants. However, in the presence of protectants, excessive surface substances reduced the protective effect of the optimum protectant alginate to 39.69 ± 1.27%. Finally, the amount of surface substances and lyophilized survival rate of collected bacteria were determined by adding EDTA during fermentation and regulating fermentation conditions, such as the carbon source, carbon-to-nitrogen ratio, and pH. The highest survival rate was 85.79 ± 3.29%, which was achieved when the amount of surface substances was (2.82 ± 0.55) × 10-11 mg/CFU. Therefore, the production of surface substances by the bacteria could be reduced by modifying the fermentation stage, which has significance in the improvement of the lyophilization survival rate of L. casei and the number of live bacteria per unit mass of L. casei in the lyophilized preparation.

6.
Mol Omics ; 18(8): 716-730, 2022 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-35960011

RESUMO

BACKGROUND: cerebral malaria (CM) is an important complication of malaria with a high mortality rate. Artesunate is recommended as the first-line artemisinin compound treatment for severe malaria. Due to the difficulty of obtaining brain tissue samples clinically, the use of animals to research host responses to CM parasite infections is necessary. Rodent malaria models allow for detailed time series studies of host responses in multiple organs. To date, studies on the transcriptome of severe malaria are only limited to the parasites in the peripheral blood of patients, and there is little data on the transcriptional changes in brain tissue in mice with CM treated with artesunate. METHOD AND RESULT: in this study, fresh tissue samples (three biological replicates per mouse) from the same area of the brain in each animal were collected from the uninfected, Plasmodium berghei ANKA-infected and artesunate-treated C57BL/6 mice, and then transcriptome research was performed by the RNA-seq technique. Differentially expressed genes (DEGs) included Il-21, Tnf, Il-6, Il-1ß, Il-10, Ifng, and Icam-1. Among which, Il-6, Il-10, Tnf-α and Il-1ß were further verified and validated via qRT-PCR and ELISA. This revealed that Il-1ß (p < 0.0001), Il-10 (p < 0.05) and Tnf-α (p < 0.05) were significantly up-regulated in the Pb ANKA-infected versus uninfected group, while Il-1ß (p < 0.0001) and Tnf-α (p < 0.05) were significantly down-regulated after artesunate treatment. All DEGs were closely related to the top 3 artesunate treatment pathways, including the JAK-STAT signaling pathway, apoptosis, and Toll-like receptor signaling pathway. CONCLUSION: the mechanism of improving the prognosis of cerebral malaria by artesunate may not only involve the killing of plasmodium but also the inhibition of a cytokine storm in the host. This study provides new insights into the molecular mechanism by which artesunate improves the prognosis of cerebral malaria.


Assuntos
Antimaláricos , Artemisininas , Malária Cerebral , Animais , Anti-Inflamatórios/uso terapêutico , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Artesunato/farmacologia , Artesunato/uso terapêutico , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Molécula 1 de Adesão Intercelular/uso terapêutico , Interleucina-10/uso terapêutico , Interleucina-6/uso terapêutico , Chumbo/uso terapêutico , Malária Cerebral/tratamento farmacológico , Malária Cerebral/genética , Malária Cerebral/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA-Seq , Receptores Toll-Like/uso terapêutico , Fator de Necrose Tumoral alfa/uso terapêutico
7.
Magn Reson Med ; 88(3): 1303-1313, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35657055

RESUMO

PURPOSE: To develop a 2D multi-echo passband balanced SSFP (bSSFP) sequence using an echo-train readout with a sequential phase-encoding order (sequential multi-echo bSSFP), and evaluate its performance in fast functional brain imaging at 7 T. METHODS: As images of sequential multi-echo bSSFP exhibit multiple ghosts due to periodic k-space modulations, a GRAPPA-based reconstruction method was proposed to eliminate ghosting artifacts. MRI experiments were performed to compare the image quality of multi-echo bSSFP and conventional single-echo bSSFP. Submillimeter-resolution fMRI using a checkerboard visual stimulus was conducted to compare the activation characteristics of multi-echo bSSFP, conventional single-echo bSSFP and standard gradient-echo EPI (GE-EPI). RESULTS: A higher mean structural similarity index was found between images of single-echo bSSFP and multi-echo bSSFP with a shorter echo train length (ETL). Multi-echo bSSFP (ETL = 3) showed higher temporal SNR (tSNR) values than GRAPPA-accelerated single-echo bSSFP (R = 2). In submillimeter-resolution fMRI experiments, multi-echo bSSFP (ETL = 3) approached the imaging speed of GRAPPA-accelerated single-echo bSSFP (R = 2), but without tSNR penalty and reduced activation due to acceleration. The median t-value and the number of significantly activated voxels were comparable between GE-EPI and multi-echo bSSFP (ETL = 3) that provides virtually distortion-free functional images and inherits the activation patterns of conventional bSSFP. CONCLUSION: Sequential multi-echo bSSFP (ETL = 3) is suitable for fast fMRI with submillimeter in-plane resolution, and offers an option to accelerate bSSFP imaging without tSNR penalty like parallel imaging.


Assuntos
Imagem Ecoplanar , Imageamento por Ressonância Magnética , Artefatos , Encéfalo/diagnóstico por imagem , Imagem Ecoplanar/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos
8.
Front Physiol ; 13: 890520, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574439

RESUMO

This study was done to evaluate the effects of heat stress (HS) on production performance, redox status, small intestinal barrier-related parameters, cecal microbiota, and metabolome of indigenous broilers. A total of forty female indigenous broilers (56-day-old) were randomly and equally divided into normal treatment group (NT group, 21.3 ± 1.2°C, 24 h/day) and HS group (32.5 ± 1.4°C, 8 h/day) with five replicates of each for 4 weeks feeding trial. The results showed that the body weight gain (BWG) of broilers in HS group was lower than those in NT group during 3-4 weeks and 1-4 weeks (p < 0.05). The HS exposure increased the abdominal fat rate (p < 0.05) but decreased the thigh muscle rate (p < 0.01). Besides, broilers in HS group had higher drip loss of breast muscle than NT group (p < 0.01). Broilers exposed to HS had lower total antioxidant capacity (T-AOC) in serum and jejunum, activities of total superoxide dismutase (T-SOD) in the jejunum, glutathione peroxidase (GSH-Px) in the thigh muscle, duodenum, and jejunum; and catalase (CAT) in breast muscle, duodenum, and jejunum (p < 0.05). Whereas the malondialdehyde (MDA) contents in breast muscle, duodenum, and jejunum was elevated by HS exposure (p < 0.05). Moreover, the relative mRNA expression of Occludin and ZO-1 in the duodenum, Occludin, Claudin-1, Claudin-4, ZO-1, Mucin-2 in the jejunum, and the Claudin-4 and Mucin-2 in the ileum was down-regulated by HS exposure (p < 0.05). The 16S rRNA sequencing results showed that the HS group increased the relative abundance of Anaerovorax in the cecum at the genus level (p < 0.05). Cecal metabolomics analysis indicated 19 differential metabolites between the two groups (p < 0.10, VIP >1). The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the differential metabolites mainly enriched in 10 signaling pathways such as the Citrate cycle (TCA cycle) (p < 0.01). In summary, chronic HS exposure caused a decline of production performance, reduced antioxidant capacity, disrupted intestinal barrier function, and negatively affected cecal microbiota and metabolome in indigenous broilers.

9.
Sci Rep ; 11(1): 7623, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33828164

RESUMO

MicroRNAs (miRNAs) are mRNA suppressors that regulate a variety of cellular and physiological processes, including cell proliferation, apoptosis, triglyceride synthesis, fat formation, and lipolysis, by post-transcriptional processing. In previous studies, we isolated and sequenced miRNAs from mammary epithelial cells from Chinese Holstein cows with high and low milk fat percentages. MiR-485 was one of the significantly differentially expressed miRNAs that were identified. In the present study, the relationship between the candidate target gene DTX4 and miR-485 was validated by bioinformatics and real-time fluorescent quantitative PCR (qRT-PCR) and Western blot (WB) analyses in bovine mammary epithelial cells (bMECs). The results indicated that miR-485 negatively regulated the mRNA expression of the target gene DTX4. Furthermore, an shRNA interference vector for the target gene DTX4 was constructed successfully, and it increased the triglyceride content and reduced the cholesterol content of transfected cells. These results suggest that miR-485 may affect the contents of triglycerides (TGs) and cholesterol (CHOL) by targeting the DTX4 gene. This study indicates that miR-485 has a role in regulating milk fat synthesis and that miR-485 targets the DTX4 gene to regulate lipid metabolism in bMECs. These findings contribute to the understanding of the functional significance of miR-485 in milk fat synthesis.


Assuntos
Glicolipídeos/biossíntese , Glicoproteínas/biossíntese , MicroRNAs/genética , Ubiquitina-Proteína Ligases/genética , Animais , Bovinos , China , Colesterol/metabolismo , Biologia Computacional , Células Epiteliais/metabolismo , Feminino , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Glicolipídeos/genética , Glicoproteínas/genética , Lactação/genética , Gotículas Lipídicas , Metabolismo dos Lipídeos/genética , Glândulas Mamárias Animais/metabolismo , Leite/metabolismo , RNA Mensageiro/metabolismo , Triglicerídeos/metabolismo
10.
Adv Healthc Mater ; 10(23): e2101586, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34601825

RESUMO

Pathological mineralization (PTM) often occurs under inflammation and affects the prognosis of diseases, such as atherosclerosis and cancers. However, how the PTM impacts inflammation has not been well explored. Herein, poly lactic-co-glycolic acid (PLGA)/gelatin/hydroxyapatite (HA) electrospun nanofibers are rationally designed as an ideal PTM microenvironment biomimetic system for unraveling the role of PTM on inflammation. The results demonstrate that the inflammatory response decreases continuously during the process of mineralization. When mature macromineralization forms, the inflammation almost completely disappears. Mechanistically, the PTM formation is mediated by matrix proteins, local high calcium, and cell debris (nuclei), or actively regulated by the lysosomal/plasma membrane components secreted by macrophages. These inflammatory inducible factors (calcium, cell debris, etc.) can be "buried" through PTM process, resulting in reduced immune responses. Overall, the present study demonstrates that PTM is an innate mechanism of inflammation subsidence, providing valuable insight into understanding the action of mineralization on inflammation.


Assuntos
Nanofibras , Durapatita , Gelatina , Humanos , Inflamação , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
11.
J Neurosci Methods ; 348: 108986, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33141036

RESUMO

BACKGROUND: Diffusion magnetic resonance imaging (dMRI) is a popular non-invasive imaging technique applied for the study of nerve fibers in vivo, with diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI) as the commonly used dMRI methods. However, DTI cannot resolve complex fiber orientations in a local area and HARDI lacks a solid physical basis. NEW METHOD: We introduce a diffusion coefficient orientation distribution function (DCODF). It has a clear physical meaning to represent the orientation distribution of diffusion coefficients for Gaussian and non-Gaussian diffusion. Based on DCODF, we then propose a new HARDI method, termed as diffusion coefficient orientation distribution transform (DCODT), to estimate the orientation distribution of nerve fibers in voxels. RESULTS: The method is verified on the simulated data, ISMRM-2015-Tracto-challenge data, and HCP datasets. The results show the superior capability of DCODT in resolving the complex distribution of multiple fiber bundles effectively. COMPARISON WITH EXISTING METHOD(S): The method is compared to other common model-free HARDI estimators. In the numerical simulations, DCODT achieves a better trade-off between the resolution and accuracy than the counterparts for high b-values. In the comparisons based on the challenge data, the improvement of DCODT is significant in scoring. The results on the HCP datasets show that DCODT provides fewer spurious lobes in the glyphs, resulting in more coherent fiber orientations. CONCLUSIONS: We conclude that DCODT may be a reliable method to extract accurate information about fiber orientations from dMRI data and promising for the study of neural architecture.


Assuntos
Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Algoritmos , Encéfalo/diagnóstico por imagem , Difusão , Fibras Nervosas
12.
Front Pharmacol ; 11: 596697, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343367

RESUMO

Objective: The purpose of this meta-analysis of longitudinal studies is to determine the safety and efficacy of artesunate combined with other forms of adjunctive therapies for severe malaria. Methods: Following the PRISMA guidelines, we searched multiple databases with the search terms "artesunate" and "adjunctive therapy" and "severe malaria" in July 2020. If the search showed a randomized controlled trial, the study was included in this meta-analysis. The random-effects model was used to calculate the combined incidence rate and relative risk or risk difference. Results: This meta-analysis included nine longitudinal studies with 724 participants. We found that the mortality rates in the artesunate monotherapy group and the artesunate + adjuvant therapy group are similar (RD = -0.02, 95% confidence interval: -0.06-0.02). The incidence of adverse reactions in the artesunate monotherapy group and the artesunate + adjuvant therapy group was also similar. Conclusion: No significant differences in safety and efficacy were observed between the artesunate monotherapy group and the artesunate + adjuvant therapy group. Higher quality and rigorously designed randomized controlled studies are needed to validate our findings.

13.
Front Pharmacol ; 11: 562363, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013398

RESUMO

OBJECTIVE: The World Health Organization recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria to improve the therapeutic efficacy and limit the choice of drug-resistant parasites. This systematic review and meta-analysis aimed to evaluate the comparative efficacy and safety of artemisinin-piperaquine (AP) in the treatment of uncomplicated malaria relative to other commonly used ACTs. METHODS: As per the PRISMA guidelines, the EMBASE, MEDLINE, the Google Scholar Library, and Cochrane library databases were systematically searched from inception until July 2020 with the following terms: "artemisinin-piperaquine" or "AP." Only randomized controlled trials (RCTs) were included. The competing interventions included dihydroartemisinin-piperaquine (DHA-PPQ), artemether-lumefantrine (AL, Coartem), artesunate-melfloquine (ASAM) and artesunate-amodiaquine (ASAQ, Artekin). Single-arm clinical trial on AP was also assessed. The reported outcomes, including the overall response, cure rate, fever and parasite clearance time, hematology, biochemistry, electrocardiogram (ECG), adverse events, recurrence rate, and sensitivity analyses, were systematically investigated. All data were analyzed using the Review Manager 5.3. RESULTS: A total of seven studies were reviewed, including five RCTs and two single-arm studies. A pooled analysis of 5 RCTs (n = 772) revealed a comparable efficacy on polymerase chain reaction (PCR)-confirmed cure rate between AP and competing interventions in treating uncomplicated malaria. As for the fever and parasite clearance time, due to the lack of complete data in some studies, only 3 studies' data could be used. The patients showed good tolerance to all drugs, and some side-effects (such as headache, anoxia, vomiting, nausea, and dizziness) were reported for every group, but they were self-limited and showed no significant difference. CONCLUSIONS: AP appeared to show similar efficacy and safety, with a simpler mode of administration and easier compliance when compared with other ACTs used in the treatment of uncomplicated malaria. Considering that the potential evolution of drug resistance is of a great concern, additional RCTs with high-quality and more rigorous design are warranted to substantiate the efficacy and safety in different populations and epidemiological regions.

14.
Front Pharmacol ; 11: 784, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581785

RESUMO

BACKGROUND: Malaria is a major public health concern in Togo. The Est-Mono district of Togo has a population of 150,000. Accordingly, the Guangzhou University of Chinese Medicine, China and the Ministry of Health and Social Security, Togo launched a nationwide Mass Drug Administration Project with artemisinin-piperaquine (AP) in Est-Mono. Before launching this project, the sensitivity test of AP was conducted in a general clinic in Elawagnon, Togo. With this background, we evaluated the efficacy and safety of AP for the treatment of uncomplicated falciparum malaria in children under the age of 5 years. METHODS: Children aged 6-59 months with uncomplicated falciparum malaria were enrolled in this study. The selected patients were treated with a combination regime of artemisinin-piperaquine. The patients were followed up for 28 days, during which signs of the following were observed for: the duration for fever clearance, parasitemia density, gametophyte generation, cure rate, hemoglobin level, and merozoite surface protein-2 (msp-2) polymorphism. The primary end point was a 28-day cure rate and polymerase chain reaction (PCR)-corrected reinfection and recrudescence. This research followed the standardized World Health Organization (WHO) protocol for the assessment of the efficacy of antimalarial drugs. RESULTS: A total of 91 children with uncomplicated falciparum malaria were enrolled in this study. Adequate clinical and parasitological responses (ACPRs) before and after PCR-correction were 66 (73%) and 90 (99%), respectively. The average hemoglobin level in the patient increased by 0.05 g/dl per day (p < 0.0001) after the treatment. The gametophyte generation did not decline at the beginning of the treatment; however, after 14 days, it declined (day 21: p < 0.05; day 28: p < 0.01). In the msp-2 polymorphism study of 24 children treated for parasite infection, one case of msp-2 with 3D7 haplotype and FC27 haplotype was noted, indicating its recrudescence, with a frequency of 4%. The remaining 23 cases could have been of reinfection, with a frequency of 96%. No serious adverse reactions occurred, and AP was well-tolerated by all patients. CONCLUSION: Artemisinin-piperaquine was found to be an effective combination for treating uncomplicated falciparum malaria in children aged <5 years in Togo, and the drugs were well-tolerated. In Togo, Plasmodium falciparum remains sensitive to artemisinin-piperaquine, necessitating its trial in this region. CLINICAL TRIAL REGISTRATION: Trial registration: ECGPHCM No. B2017-054-01; MHSST AVIS N° 0001/2016/CBRS du 07 janvier 2016. Registered 17 March 2014, http://www.chinadrugtrials.org.cn/eap/main.

15.
ACS Appl Mater Interfaces ; 12(23): 26405-26412, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32403921

RESUMO

Emerging moisture sensitive devices require robust encapsulation strategies to inhibit water ingress and prevent premature failure. A scalable, open-air plasma process has been developed to deposit alternating layers of conformal organosilicate and dense SiO2 thin-film barriers to prevent moisture ingress. The in situ low-temperature process is suitable for direct deposition on thermally sensitive devices and is compatible with flexible polymeric substrates. Using optical calcium testing, low water vapor transmission rates on the order of 10-3 g/m2/day at an accelerated aging condition of 38 °C and 90% relative humidity (RH) are achieved. Using moisture-sensitive perovskite devices as a representative moisture-susceptible device, devices retain over 80% of their initial performance for over 660 h in a 50 °C 50% RH accelerated aging environment. The ability of the multilayer barrier to enable device resistance to humid environments is crucial toward realizing longer operating lifetimes.

16.
Poult Sci ; 99(4): 2100-2107, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241495

RESUMO

The present study was conducted to evaluate the effects of dietary marine-derived polysaccharides (MDP) from seaweed Enteromorpha on productive performance, egg quality, antioxidant capacity, and jejunal morphology in late-phase laying hens. A total of 240 Lohmann white laying hens (62 wk of age) were assigned to 4 dietary treatments that included MDP at concentrations of 0, 1,000, 2,500, and 5,000 mg/kg for 6 wk. Each treatment had 6 replicates with 5 cages (2 birds/cage). The results showed that dietary MDP quadratically improved egg production (P < 0.05) during 5 to 6 wk and 1 to 6 wk. There was a linear reduction in cracked egg rate (P < 0.05) with dietary MDP levels increased during 3 to 4 wk and 1 to 6 wk. After 4 wk of feeding trial, the egg shell thickness, yolk color, and Haugh unit showed a linear increase (P < 0.05) in response to increasing dietary MDP levels. Besides, the egg shell breaking strength, egg shell thickness, yolk color, and Haugh unit were improved linearly (P < 0.05) by dietary MDP at the end of the experiment. Moreover, dietary MDP showed a linear and quadratic reduction in serum malondialdehyde (MDA) content (P < 0.05) at the end of third week. At the end of experiment, the activity of total superoxide dismutase in serum was increased quadratically (P < 0.05) by dietary MDP, and dietary MDP quadratically improved the liver catalase (CAT) activity (P < 0.05) and linearly enhanced jejunal CAT activity (P < 0.05), whereas linearly decreased jejunal MDA concentration (P < 0.05). Furthermore, supplemental MDP linearly improved the villus height (P < 0.05) and quadratically increased villus height/crypt depth ratio (P < 0.05) of jejunum. However, dietary MDP had no effect on jejunal trypsin, amylase, and protease activity (P > 0.10). Taken together, these findings provided new insights into the role of MDP in improving the productive performance, egg quality, antioxidant capacity, and jejunal morphology of late-phase laying hens.


Assuntos
Antioxidantes/metabolismo , Galinhas/fisiologia , Clorófitas/química , Carboidratos da Dieta/metabolismo , Jejuno/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Polissacarídeos/metabolismo , Ração Animal/análise , Animais , Galinhas/anatomia & histologia , Dieta/veterinária , Carboidratos da Dieta/administração & dosagem , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Feminino , Jejuno/anatomia & histologia , Óvulo/fisiologia , Polissacarídeos/administração & dosagem , Distribuição Aleatória
17.
Eur Radiol ; 30(4): 1876-1884, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31822971

RESUMO

OBJECTIVES: To qualitatively and quantitatively compare the image quality between single-shot echo-planar (SS-EPI) and multi-shot echo-planar (IMS-EPI) diffusion-weighted imaging (DWI) in female pelvis METHODS: This was a prospective study involving 80 females who underwent 3.0T pelvic magnetic resonance imaging (MRI). SS-EPI and IMS-EPI DWI were acquired with 3 b values (0, 400, 800 s/mm2). Two independent reviewers assessed the overall image quality, artifacts, sharpness, and lesion conspicuity based on a 5-point Likert scale. Regions of interest (ROI) were placed on the endometrium and the gluteus muscles to quantify the signal intensities and apparent diffusion coefficient (ADC). Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and geometric distortion were quantified on both sequences. Inter-rater agreement was assessed using κ statistics and Kendall test. Qualitative scores were compared using Wilcoxon signed-rank test and quantitative parameters were compared with paired t test and Bland-Altman analysis. RESULTS: IMS-EPI demonstrated better image quality than SS-EPI for all aspects evaluated (SS-EPI vs. IMS-EPI: overall quality 3.04 vs. 4.17, artifacts 3.09 vs. 3.99, sharpness 2.40 vs. 4.32, lesion conspicuity 3.20 vs. 4.25; p < 0.001). Good agreement and correlation were observed between two reviewers (SS-EPI κ 0.699, r 0.742; IMS-EPI κ 0.702, r 0.789). IMS-EPI showed lower geometric distortion, SNR, and CNR than SS-EPI (p < 0.050). There was no significant difference in the mean ADC between the two sequences. CONCLUSION: IMS-EPI showed better image quality with lower geometric distortion without affecting the quantification of ADC, though the SNR and CNR decreased due to post-processing limitations. KEY POINTS: • IMS-EPI showed better image quality than SS-EPI. • IMS-EPI showed lower geometric distortion without affecting ADC compared with SS-EPI. • The SNR and CNR of IMS-EPI decreased due to post-processing limitations.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodos , Doenças dos Genitais Femininos/diagnóstico por imagem , Neoplasias dos Genitais Femininos/diagnóstico por imagem , Pelve/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Artefatos , Endométrio/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Pessoa de Meia-Idade , Estudos Prospectivos , Razão Sinal-Ruído , Adulto Jovem
18.
Artif Cells Nanomed Biotechnol ; 47(1): 1823-1832, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31066304

RESUMO

Poly(lactic-co-glycolic acid) (PLGA) based biomaterials have many advantages and potential applications in bone tissue engineering. Whereas, a significant problem which could not be ignored was that the acidic by-products generated during its degradation induced severe inflammatory reactions and negatively regulated bone regeneration. In this research, feasibility of using dexamethasone (Dex) to improve the biocompatibility of PLGA is investigated in detail. Hereby, various contents of PLGA/hydroxyapatite (PH) nanofibers loaded with Dex were synthesized by electrospinning technique. It was shown that 0.5% (wt) Dex in PH scaffolds was the minimum content which was required for anti-inflammatory effect. Admittedly, Dex to some extent had cytotoxic effect on osteoblasts and an inhibitory effect on ALP activity in this study; nevertheless, the relatively low Dex (<2% [wt]) had no inhibitory effects on osteoblasts maturation and mineralization. By this token, Dex is a good candidate for improving biocompatibility of PLGA based biomaterials. Moreover, the cytotoxic effects of Dex should be concerned. This study will provide a rationale for optimizing biocompatibility of PLGA based biomaterials by using Dex.


Assuntos
Dexametasona/química , Portadores de Fármacos/química , Durapatita/química , Nanofibras/química , Osteogênese/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Células 3T3 , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Liberação Controlada de Fármacos , Teste de Materiais , Camundongos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Ratos , Solventes/química
19.
Immunity ; 39(2): 272-85, 2013 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-23973223

RESUMO

Regulatory T (Treg) cells suppress inflammatory immune responses and autoimmunity caused by self-reactive T cells. The key Treg cell transcription factor Foxp3 is downregulated during inflammation to allow for the acquisition of effector T cell-like functions. Here, we demonstrate that stress signals elicited by proinflammatory cytokines and lipopolysaccharides lead to the degradation of Foxp3 through the action of the E3 ubiquitin ligase Stub1. Stub1 interacted with Foxp3 to promote its K48-linked polyubiquitination in an Hsp70-dependent manner. Knockdown of endogenous Stub1 or Hsp70 prevented Foxp3 degradation. Furthermore, the overexpression of Stub1 in Treg cells abrogated their ability to suppress inflammatory immune responses in vitro and in vivo and conferred a T-helper-1-cell-like phenotype. Our results demonstrate the critical role of the stress-activated Stub1-Hsp70 complex in promoting Treg cell inactivation, thus providing a potential therapeutic target for the intervention against autoimmune disease, infection, and cancer.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Células Cultivadas , Citocinas/metabolismo , Inibidores Enzimáticos , Células HEK293 , Proteínas de Choque Térmico HSP70/genética , Humanos , Imidazóis , Inflamação/genética , Inflamação/imunologia , Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fenótipo , Piridinas , Interferência de RNA , RNA Interferente Pequeno , Linfócitos T Auxiliares-Indutores/imunologia , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
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