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1.
Hum Brain Mapp ; 45(2): e26604, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38339890

RESUMEN

Disruptions of neural metabolism and function occur in parallel during Alzheimer's disease (AD). While many studies have shown diverse metabolic-functional relationships in specific brain regions, much less is known about how large-scale network-level functional activity is associated with the topology of metabolism in AD. In this study, we took the advantages of simultaneous PET/MRI and multivariate analyses to investigate the associations between AD-related stereotypical spatial patterns (topographies) of glucose metabolism, measured by fluorodeoxyglucose PET, and functional connectivity, measured by resting-state functional MRI. A total of 101 participants, including 37 patients with AD, 25 patients with mild cognitive impairment (MCI), and 39 cognitively normal controls, underwent PET/MRI scans and cognitive assessments. Three pairs of distinct but optimally correlated metabolic and functional topographies were identified, encompassing large-scale networks including the default-mode, executive and control, salience, attention, and subcortical networks. Importantly, the metabolic-functional associations were not only limited to one-to-one-corresponding regions, but also occur in remote and non-overlapping regions. Furthermore, both glucose metabolism and functional connectivity, as well as their linkages, exhibited various degrees of disruptions in patients with MCI and AD, and were correlated with cognitive decline. In conclusion, our results support distributed and heterogeneous topographic associations between metabolism and function, which are jeopardized by AD. Findings of this study may deepen our understanding of the pathological mechanism of AD through the perspectives of both local energy efficiency and long-term interactions between synaptic disruption and functional disconnection contributing to the clinical symptomatology in AD.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Encéfalo , Tomografía de Emisión de Positrones/métodos , Imagen por Resonancia Magnética/métodos , Glucosa/metabolismo
2.
Eur J Nucl Med Mol Imaging ; 51(2): 455-467, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37801139

RESUMEN

PURPOSE: Despite the revealed role of immunological dysfunctions in the development and progression of Alzheimer's disease (AD) through animal and postmortem investigations, direct evidence regarding the impact of genetic factors on microglia response and amyloid-ß (Aß) deposition in AD individuals is lacking. This study aims to elucidate this mechanism by integrating transcriptomics and TSPO, Aß PET imaging in clinical AD cohort. METHODS: We analyzed 85 patients with PET/MR imaging for microglial activation (TSPO, [18F]DPA-714) and Aß ([18F]AV-45) within the prospective Alzheimer's Disease Immunization and Microbiota Initiative Study Cohort (ADIMIC). Immune-related differentially expressed genes (IREDGs), identified based on AlzData, were screened and verified using blood samples from ADIMIC. Correlation and mediation analyses were applied to investigate the relationships between immune-related genes expression, TSPO and Aß PET imaging. RESULTS: TSPO uptake increased significantly both in aMCI (P < 0.05) and AD participants (P < 0.01) and showed a positive correlation with Aß deposition (r = 0.42, P < 0.001). Decreased expression of TGFBR3, FABP3, CXCR4 and CD200 was observed in AD group. CD200 expression was significantly negatively associated with TSPO PET uptake (r =-0.33, P = 0.013). Mediation analysis indicated that CD200 acted as a significant mediator between TSPO uptake and Aß deposition (total effect B = 1.92, P = 0.004) and MMSE score (total effect B =-54.01, P = 0.003). CONCLUSION: By integrating transcriptomics and TSPO PET imaging in the same clinical AD cohort, this study revealed CD200 played an important role in regulating neuroinflammation, Aß deposition and cognitive dysfunction.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Perfilación de la Expresión Génica , Enfermedades Neuroinflamatorias , Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Receptores de GABA/genética , Receptores de GABA/metabolismo
3.
Alzheimers Dement ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39073196

RESUMEN

INTRODUCTION: Altered neurometabolism, detectable via proton magnetic resonance spectroscopic imaging (1H-MRSI), is spatially heterogeneous and underpins cognitive impairments in Alzheimer's disease (AD). However, the spatial relationships between neurometabolic topography and cognitive impairment in AD remain unexplored due to technical limitations. METHODS: We used a novel whole-brain high-resolution 1H-MRSI technique, with simultaneously acquired 18F-florbetapir positron emission tomography (PET) imaging, to investigate the relationship between neurometabolic topography and cognitive functions in 117 participants, including 22 prodromal AD, 51 AD dementia, and 44 controls. RESULTS: Prodromal AD and AD dementia patients exhibited spatially distinct reductions in N-acetylaspartate, and increases in myo-inositol. Reduced N-acetylaspartate and increased myo-inositol were associated with worse global cognitive performance, and N-acetylaspartate correlated with five specific cognitive scores. Neurometabolic topography provides biological insights into diverse cognitive dysfunctions. DISCUSSION: Whole-brain high-resolution 1H-MRSI revealed spatially distinct neurometabolic topographies associated with cognitive decline in AD, suggesting potential for noninvasive brain metabolic imaging to track AD progression. HIGHLIGHTS: Whole-brain high-resolution 1H-MRSI unveils neurometabolic topography in AD. Spatially distinct reductions in NAA, and increases in mI, are demonstrated. NAA and mI topography correlates with global cognitive performance. NAA topography correlates with specific cognitive performance.

4.
Int Wound J ; 20(3): 699-705, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35922093

RESUMEN

To evaluate the efficacy and safety of wet dressing combined with chitosan wound dressing for deep II degree burn wounds, and provide the basis for clinical application. From October 2019 to October 2021, 80 patients with second-degree deep burn treated in the Department of burn and plastic surgery of our hospital were selected as the research objects. Patients were randomly divided into two groups. The control group (40n) was treated with wet compress, and the study group (40n) was treated with wet compress combined with chitosan wound dressing. The wound healing time, wound healing percentage and pain score were used as the effectiveness indexes, and the incidence of adverse events and serious adverse events and the detection rate of bacterial culture of wound exudates were used as the safety indexes. The efficacy and safety of the two groups were compared. The wound healing time of the study group (19.53 ± 2.74 days) was shorter than that of the control group (24.78 ± 4.86 days), the difference was significant (t = 3.571, P = 0.015). The percentage of wound healing at the 14th after treatment in the study group was higher than that in the control group (65.00% versus 37.50%) (X2  = 6.054, P = 0.014). There was no significant difference in pain scores between the two groups at each time point. The scar growth was observed 3 months after wound healing. The scar score of the study group (6.00 ± 0.98) was lower than that of the control group (8.77 ± 1.19) (t = 2.571, P = 0.031). The positive rate of wound secretion culture on the 7th and 14th day was statistically significant (X2  = 4.528, P = 0.033; X2  = 6.646, P = 0.010), and the study group was lower than the control group (29.03% versus 81.82%; 8.11% versus 42.86%). There was no significant difference in treatment cost between the study group and the control group (1258.7 ± 223.6 versus 1248.9 ± 182.3) (t = 1.571, P = 0.071). No adverse events or serious adverse events occurred in both groups. Chitosan wound dressing can significantly shorten the time of wound healing and reduce wound pain and wound infection in patients with deep second-degree burns. And it can effectively improve the situation of scar hyperplasia, which is worthy of clinical application.


Asunto(s)
Quemaduras , Quitosano , Humanos , Cicatriz , Quitosano/uso terapéutico , Estudios Prospectivos , Método Simple Ciego , Resultado del Tratamiento , Vendajes , Quemaduras/tratamiento farmacológico , Dolor
5.
J Biochem Mol Toxicol ; 36(6): e23038, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35307907

RESUMEN

Antioxidants may provide a complementary treatment for patients with chronic diseases. Nevertheless, studies that have measured the effects of antioxidant on diabetes complications have provided conflicting results. This study aimed to elucidate the association between antioxidant and diabetic complications and to develop robust evidence for clinical decisions by systematic reviews and meta-analysis. PubMed, Embase, The Cochrane Library, Web of Science, Scopus databases were searched to collect clinical studies related to the efficacy of antioxidants in the treatment of diabetes complications from inception to May 5, 2021. Statistical meta-analyses were performed using the RevMan 5.4 software. Stata16 software was used to detect publication bias. The data of diabetic nephropathy (DN), diabetic nonalcoholic fatty liver disease (NAFLD), and diabetic periodontitis were collected to analyze the effect of antioxidant on diabetes and the above three complications. The meta-analysis results showed that antioxidant treatment was associated with significantly changes in the fasting plasma glucose (FPG) (standardized mean difference [SMD]: - 0.21 [95% confidence interval [CI]: - 0.33, -0.10], p < 0.001), hemoglobin A1c (HbA1c) (MD: - 0.41 [95% CI: - 0.63, -0.18], p < 0.001), total antioxidant capacity (TAC) (SMD: 0.44 [95% CI: 0.24, 0.63], p < 0.001) and malondialdehyde (MDA) (SMD: - 0.82 [95% CI: - 1.24, -0.41], p < 0.001) than the control group. Antioxidant supplements have the potential to treat three complications of diabetes. In conclusion, the meta-analysis results indicate that antioxidant treatment is effective clinically for diabetes mellitus and its complications.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Antioxidantes/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Suplementos Dietéticos , Hemoglobina Glucada , Humanos
6.
Biochem Biophys Res Commun ; 505(3): 858-864, 2018 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-30301525

RESUMEN

Chronic myeloid leukemia (CML) responds well to BCR-ABL tyrosine kinase inhibitors (TKI), such as imatinib and dasatinib. However, these inhibitors have been less effective as single agents in the blast phase-CML. In this work, we show that anisomycin, a clinically available drug, targets CML cells at all stages of development and enhances BCR-ABL TKIs' efficacy. Anisomycin at nanomolar concentration inhibits proliferation and induces apoptosis in a panel of CML cell lines in a dose-dependent manner. It induces apoptosis CD34 stem/progenitor cells isolated from patients with blast phase CML. Using colony formation and serial replating assays, we further show that anisomycin inhibits CML CD34 cell differentiation, proliferation and self-renewal. Additionally, anisomycin is less effective in normal bone marrow (NBM) CD34 cells, suggesting the selective anti-leukemia activity of anisomycin. Combination of anisomycin with imatinib or dasatinib achieves significantly better efficacy than TKI alone in leukemia cell lines and patient samples while sparing normal counterparts. Mechanistically, we demonstrate that p38 MAPK/JNK activation is not required for anti-leukemia activities of anisomycin. Instead, anisomycin displays preferential inhibitory effects to Wnt/ß-catenin-mediated signaling in CML. Our work provides the preclinical evidence on the potent efficacy of anisomycin in leukemia and its mechanisms of action. Our work suggests that anisomycin is a potential drug to overcome resistance to BCR-ABL TKI treatment in blast phase CML.


Asunto(s)
Anisomicina/farmacología , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Antibacterianos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Crisis Blástica/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dasatinib , Resistencia a Antineoplásicos , Humanos , Mesilato de Imatinib , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Células Madre Neoplásicas , Inhibidores de Proteínas Quinasas , Vía de Señalización Wnt/efectos de los fármacos
7.
Curr Microbiol ; 74(4): 431-436, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28213661

RESUMEN

Rhodopseudomonas palustris was selected for the ability to grow in diglycosylated flavonoids-based media, exhibited deglycosylation activity. The present study aimed to investigate the ability of a crude enzyme from Rhodopseudomonas palustris to transform rutin. Our results showed the crude enzyme was found to transform rutin to quercetin via isoquercitrin. The maximum enzyme activities were observed at pH 7.0, 25 °C, and rutin concentration of 1.0 mg mL- 1. Under optimal conditions, 13.11 µM rutin was biotransformed into 6.86 µM isoquercitrin and 11.64 µM quercetin after 11 and 21 h, respectively. The study demonstrates an eco-friendly and potential economically viable 'green' conversion route to convert rutin to isoquercitrin and quercetin, which is of great interest, considering the therapeutic applications of isoquercitrin and quercetin. The specific biotransformation of rutin to isoquercitrin and quercetin, using the crude enzyme from Rhodopseudomonas palustris, may potentially serve as a new method for industrial production of isoquercitrin and quercetin.


Asunto(s)
Proteínas Bacterianas/metabolismo , Rhodopseudomonas/enzimología , Rhodopseudomonas/metabolismo , Rutina/metabolismo , Biotransformación , Quercetina/análogos & derivados , Quercetina/metabolismo
8.
Appl Radiat Isot ; 214: 111518, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39276637

RESUMEN

The TDCR (Triple-to-Double Coincidence Ratio) measurement technique is a primary standardization method used by metrology laboratories to accurately determine the activity of radioactive solutions, particularly for radionuclides unsuitable for traditional coincidence counting methods, such as pure beta emitters. The TDCR method leverages a liquid scintillation counter equipped with three photomultiplier tubes (PMTs). This paper introduces TDCRPy, a novel Python package developed by the BIPM, designed to calculate detection efficiency of liquid scintillation counters using Monte Carlo simulations and decay data evaluations from the Decay Data Evaluation Project (DDEP). The software simulates particle interactions within the liquid scintillation counter, utilizing pre-calculated probability distributions for energy deposition. Comparisons with the PENNUC/NUR code and tests with measurement from the BIPM.RI(II)-K1.Co-60 key comparison demonstrate the potential of TDCRPy. This open-source package is distributed at https://pypi.org/project/TDCRPy and available for collaborative development on GitHub https://github.com/RomainCoulon/TDCRPy, where detailed user documentation can be found.

9.
Medicine (Baltimore) ; 103(28): e38864, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38996161

RESUMEN

The main causative factors of diabetic nephropathy (DN), a common complication of diabetes mellitus, are metabolic abnormalities and hemodynamic changes. However, studies have shown that the immune-inflammatory response also plays an important role in DN pathogenesis. Therefore, in this study, we analyzed the causal relationship and immune infiltration between inflammatory factors and DN using Mendelian randomization (MR) and bioinformatics techniques. We analyzed the causal relationship between 91 inflammatory factors and DN using two-sample MR dominated by the results of inverse variance-weighted analysis. Based on the MR analysis, the immune mechanism of inflammatory factors in DN was further explored using immune cell infiltration analysis. MR analysis indicated a positive causal relationship between DN and IL1A, caspase 8 (CASP8), macrophage colony-stimulating factor 1, IL10, STAM-binding protein, and tumor necrosis factor ligand superfamily member 12 (TNFSF12) and a negative causal relationship between DN and cystatin D, fibroblast growth factor 19, neurturin, and TNFSF14. The pathogenic mechanism of CASP8 may involve the recruitment of CD4+ T cells and macrophages for DN infiltration. In this study, we found a causal relationship between DN and IL1A, CASP8, macrophage colony-stimulating factor 1, IL10, STAM-binding protein, TNFSF12, cystatin D, fibroblast growth factor 19, neurturin, and TNFSF14. Bioinformatic immune infiltration analysis further revealed that CASP8 regulates DN by influencing the infiltration of immune cells, such as T cells and macrophages.


Asunto(s)
Biología Computacional , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Análisis de la Aleatorización Mendeliana , Humanos , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/inmunología , Biología Computacional/métodos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Factores de Riesgo , Inflamación/genética , Inflamación/sangre , Caspasa 8/genética
10.
J Mater Chem B ; 12(3): 691-700, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38126510

RESUMEN

Herein, four haptens of niacin (Vitamin B3, VB3) were designed, and after a series of experiments, it was concluded that hapten D had the best immune effect. To avoid false positives in the detection of real samples, a monoclonal antibody (mAb) against VB3 was prepared by a matrix effect-enhanced mAb screening method. The concentration of the inhibition rate reaching 50% (IC50) was 603.41 ng mL-1 and the limit of detection (LOD) using an indirect enzyme-linked immunosorbent assay (ic-ELISA) was 54.89 ng mL-1. A lateral flow immunochromatographic assay (LFIA) based on gold nanoparticles was established to detect the concentration of VB3 in compound vitamin B tablets and infant formulas, with a visual LOD of 5 µg mL-1. Using a handheld reader, the quantitative LOD was calculated to be 0.60 µg mL-1. The contents of the compound vitamin B tablets and infant formulas were also verified by liquid chromatography. Therefore, the LFIA developed in this study can be applied to the specific identification and rapid detection of niacin in nutritional dietary supplements, thus meeting the market's demand for efficient niacin detection methods.


Asunto(s)
Nanopartículas del Metal , Niacina , Lactante , Humanos , Oro/química , Nanopartículas del Metal/química , Anticuerpos Monoclonales , Suplementos Dietéticos , Vitaminas
11.
Cancer Lett ; 588: 216765, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38408604

RESUMEN

Current immune checkpoint blockade (ICB) immunotherapeutics have revolutionized cancer treatment. However, many cancers especially the "immunologically cold" tumors, do not respond to ICB, prompting the search for additional strategies to achieve durable responses. The cGAS-STING pathway, as an essential immune response pathway, has been demonstrated for a potent target to sensitize ICB immunotherapy. However, the low efficiency of conventional STING agonists limits their clinical application. Recent studies have shown that DNA topoisomerase I (TOPI) inhibitor chemodrug SN38 can activate the cGAS-STING pathway and induce an immune response through DNA damage, while the traditional statins medication lovastatin was found to inhibit DNA damage repair, which may in turn upregulate the damaged DNA level. Herein, we have developed a liposomal carrier co-loaded with SN38 and lovastatin (SL@Lip), which can be accumulated in tumors and efficiently released SN38 and lovastatin, addressing the problem of weak solubility of these two drugs. Importantly, lovastatin can increase DNA damage and enhance the activation of cGAS-STING pathway, coordinating with SN38 chemotherapy and exhibiting the enhanced combinational immunotherapy of PD-1 antibody by remodeling the tumor microenvironment in mouse colorectal cancer of both subcutaneous and orthotopic xenograft models. Overall, this study demonstrates that lovastatin-assisted cGAS-STING stimulation mediated by liposomal delivery system significantly strengthened both chemotherapy and immunotherapy of colorectal cancer, providing a clinically translational strategy for combinational ICB therapy in the "immunologically cold" tumors.


Asunto(s)
Neoplasias del Colon , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Neoplasias , Humanos , Animales , Ratones , Lovastatina/farmacología , Inhibidores de Puntos de Control Inmunológico , Liposomas , Neoplasias del Colon/tratamiento farmacológico , Inmunoterapia , Microambiente Tumoral
12.
FEMS Microbiol Ecol ; 99(5)2023 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-36977576

RESUMEN

There is increasing evidence that microbes can help ameliorate plant growth under environmental stress. Still, it is largely unknown what microbes and potential functions are involved in sustaining turfgrass, the major component of urban/suburban landscapes, under drought. We examined microbial responses to water deficits in bulk soil, rhizosphere, and root endosphere of bermudagrass by applying evapotranspiration (ET)-based dynamic irrigation twice per week during the growing season to create six treatments (0%, 40%, 60%, 80%, 100%, and 120% ET) and respective drought-stressed soil conditions. Bacterial and fungal communities were analyzed via marker gene amplicon sequencing and thereafter drought-reshaped potential functions of the bacterial community were projected. Slight yet significant microbial responses to irrigation treatments were observed in all three microhabitats. The root endophytic bacterial community was most responsive to water stress. No-irrigation primarily increased the relative abundance of root endophytic Actinobacteria, especially the genus Streptomyces. Irrigation at ≤40% ET increased the relative abundances of PICRUSt2-predicted functional genes encoding 1-aminocyclopropane-1-carboxylic acid deaminase, superoxide dismutase, and chitinase in root endosphere. Our data suggest that the root endophytic Actinobacteria are likely the key players to improve bermudagrass fitness under drought by modulating phytohormone ethylene production, scavenging reactive oxygen species, or ameliorating nutrient acquisition.


Asunto(s)
Actinobacteria , Cynodon , Deshidratación , Microbiota , Raíces de Plantas , Actinobacteria/efectos de los fármacos , Actinobacteria/genética , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Cynodon/microbiología , Microbiota/efectos de los fármacos , Microbiota/genética , Raíces de Plantas/microbiología , Rizosfera , Suelo/química , Microbiología del Suelo , Agua/farmacología , Biodiversidad , Genes Bacterianos/genética
13.
Transl Vis Sci Technol ; 12(4): 5, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-37017958

RESUMEN

Purpose: This study analyzed the biomechanical responses of different corneal cap thicknesses after small incision lenticule extraction (SMILE). Methods: Individual finite element models of myopic eyes were constructed based on the clinical data. Then, four types of corneal cap thicknesses after SMILE were included for each model. The biomechanical effects of material parameters and intraocular pressure on corneas with different cap thicknesses were analyzed. Results: When the cap thickness increased, the vertex displacements of the anterior and posterior corneal surfaces decreased slightly. The corneal stress distributions demonstrated little change. Regarding wave-front aberrations caused by the displacements of the anterior surface, the absolute defocus value decreased slightly, but the magnitude of primary spherical aberration increased slightly. The horizontal coma increased, and the levels of other low-order and high-order aberrations were small and demonstrated little change. The corneal vertex displacement and wave-front aberration were significantly affected by elastic modulus and intraocular pressure, whereas the corneal stress distribution was greatly affected by intraocular pressure. There were obvious individual differences in the biomechanical responses of human eyes. Conclusions: The biomechanical difference of different corneal cap thicknesses after SMILE was small. The effect of corneal cap thickness was significantly less than that resulting from material parameters and intraocular pressure. Translational Relevance: Individual models were constructed based on the clinical data. The elastic modulus was controlled by programming to simulate its heterogeneous distribution in the actual human eye. The simulation was improved to bridge the gap between basic research and clinical care.


Asunto(s)
Cirugía Laser de Córnea , Miopía , Humanos , Análisis de Elementos Finitos , Agudeza Visual , Cirugía Laser de Córnea/métodos , Córnea , Miopía/cirugía
14.
Pharmaceutics ; 15(12)2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38140054

RESUMEN

Gefitinib (GEF) is a clinical medication for the treatment of lung cancer targeting the epidermal growth factor receptor (EGFR). However, its efficacy is remarkably limited by low solubility and dissolution rates. In this study, two cocrystals of GEF with co-formers were successfully synthesized using the recrystallization method characterized via Powder X-ray Diffraction, Fourier Transform Infrared Spectroscopy, and 2D Nuclear Overhauser Effect Spectroscopy. The solubility and dissolution rates of cocrystals were found to be two times higher than those of free GEF. In vitro cytotoxicity studies revealed that the cocrystals enhanced the inhibition of cell proliferation and apoptosis in A549 and H1299 cells compared to free GEF. In mouse models, GEF@TSBO demonstrated targeted, safe, and effective antitumor activity with only one-dose administration. Mechanistically, the GEF cocrystals were shown to increase the cellular levels of damaged DNA, while potentially downregulating PARP, thereby impairing the DNA repair machinery and leading to an imbalance between DNA damage and restoration. These findings suggest that the cocrystallization of GEF could serve as a promising adjunct to significantly enhance the physicochemical and biopharmaceutical performance for lung cancer treatment, providing a facial strategy to improve GEF anticancer efficiency with high bioavailability that can be orally administrated with only one dose.

15.
Front Cell Infect Microbiol ; 13: 1169909, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37448775

RESUMEN

Background: To establish antibiotic preregimes and administration routes for studies on urinary microbiota. Methods and materials: Antibiotics for enteritis (Abx-enteritis) and UTIs (Abx-UTI) were administered via gavage and/or urinary catheterisation (UC) for 1 and/or 2 weeks. The effects of these Abx on the urinary microbiota of rats were examined via 16S rRNA sequencing and urine culture, including anaerobic and aerobic culture. Additionally, the safety of the Abx was examined. Results: Abx-enteritis/Abx-UTI (0.5 g/L and 1 g/L) administered via gavage did not alter the microbial community and bacterial diversity in the urine of rats (FDR > 0.05); however, Abx-UTI (1 g/L) administered via UC for 1 and 2 weeks altered the urinary microbial community (FDR < 0.05). Rats administered Abx-UTI (1 g/L) via UC for 1 week demonstrated a distinct urinary microbiota in culture. Abx-enteritis/Abx-UTI administered via gavage disrupted the microbial community and reduced bacterial diversity in the faeces of rats (FDR < 0.05), and Abx-UTI administered via UC for 2 weeks (FDR < 0.05) altered the fecal microbiota. Abx-UTI (1 g/L) administered via UC did not alter safety considerations. In addition, we noticed that UC did not induce infections and injuries to the bladder and kidney tissues. Conclusions: Administration of Abx-UTI via UC for 1 week can be considered a pre-treatment option while investigating the urinary microbiota.


Asunto(s)
Microbiota , Infecciones Urinarias , Animales , Ratas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , ARN Ribosómico 16S/genética , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Vejiga Urinaria/microbiología
16.
Front Microbiol ; 13: 1078836, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36713160

RESUMEN

The plant breeding program has developed many cultivars of tall fescue (Festuca arundinacea) with low maintenance and stress tolerance. While the root-associated microbial community helps confer stress tolerance in the host plant, it is still largely unknown how the microbiota varies with plant cultivars under water stress. The study aimed to characterize drought-responsive bacteria and fungi in the roots and rhizosphere of different tall fescue cultivars. Intact grass-soil cores were collected from six cultivars grown in a field trial under no-irrigation for 3 years. Tall fescue under irrigation was also sampled from an adjacent area as the contrast. Bacterial and fungal communities in roots, rhizosphere, and bulk soil were examined for abundance, diversity, and composition using quantitative-PCR and high-throughput amplicon sequencing of 16S rRNA gene and ITS regions, respectively. Differences in microbial community composition and structure between non-irrigated and irrigated samples were statistically significant in all three microhabitats. No-irrigation enriched Actinobacteria in all three microhabitats, but mainly enriched Basidiomycota in the root endosphere and only Glomeromycota in bulk soil. Tall fescue cultivars slightly yet significantly modified endophytic microbial communities. Cultivars showing better adaptability to drought encompassed more relatively abundant Actinobacteria, Basidiomycota, or Glomeromycota in roots and the rhizosphere. PICRUSt2-based predictions revealed that the relative abundance of functional genes in roots related to phytohormones, antioxidant enzymes, and nutrient acquisition was enhanced under no-irrigation. Significant associations between Streptomyces and putative drought-ameliorating genes underscore possible mechanics for microbes to confer tall fescue with water stress tolerance. This work sheds important insight into the potential use of endophytic microbes for screening drought-adaptive genotypes and cultivars.

17.
Clin Cosmet Investig Dermatol ; 15: 1021-1027, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35669088

RESUMEN

Objective: To explore the clinical effect of wound edge microgranular skin grafting in the treatment of various small wounds. Methods: From September 2018 to September 2021, Yueqing people's Hospital of Wenzhou City, Zhejiang Province collected and recorded the data of 12 patients with chronic wounds and third degree burns. The method of skin grafting with particles at the edge of the wound was used to graft skin on the wound. Scar evaluation scale was used to evaluate the wound. The patients were followed up for 12 months. The preoperative and postoperative data, scar index and patient satisfaction after healing were recorded and statistically analyzed. Results: All patients in this group were followed up for 3-12 months, and the results showed that SCAR Scale score decreased gradually over time, with patient satisfaction ranging from 80% to 96%. The patient gradually healed, scar hyperplasia gradually improved, functional activities gradually returned to normal, clinical effect is satisfactory. Conclusion: Microparticle skin grafting at the edge of wound avoids skin grafting at different skin donor sites. It has the characteristics of simple anesthesia, small trauma and convenient operation. This method can be considered when treating patients with chronic wounds and burns who need skin grafting.

18.
PeerJ ; 10: e13874, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35979477

RESUMEN

Soil microbial transformation of nitrogen (N) in nutrient-limited native C4 grasslands can be affected by N fertilization rate and C4 grass species. Here, we report in situ dynamics of the population size (gene copy abundances) and activity (transcript copy abundances) of five functional genes involved in soil N cycling (nifH, bacterial amoA, nirK, nirS, and nosZ) in a field experiment with two C4 grass species (switchgrass (Panicum virgatum) and big bluestem (Andropogon gerardii)) under three N fertilization rates (0, 67, and 202 kg N ha-1). Diazotroph (nifH) abundance and activity were not affected by N fertilization rate nor grass species. However, moderate and high N fertilization promoted population size and activity of ammonia oxidizing bacteria (AOB, quantified via amoA genes and transcripts) and nitrification potential. Moderate N fertilization increased abundances of nitrite-reducing bacterial genes (nirK and nirS) under switchgrass but decreased these genes under big bluestem. The activity of nitrous oxide reducing bacteria (nosZ transcripts) was also promoted by moderate N fertilization. In general, high N fertilization had a negative effect on N-cycling populations compared to moderate N addition. Compared to big bluestem, the soils planted with switchgrass had a greater population size of AOB and nitrite reducers. The significant interaction effects of sampling season, grass species, and N fertilization rate on N-cycling microbial community at genetic-level rather than transcriptional-level suggested the activity of N-cycling microbial communities may be driven by more complex environmental factors in native C4 grass systems, such as climatic and edaphic factors.


Asunto(s)
Pradera , Urea , Poaceae , Nitritos , Bacterias/genética , Suelo , Nitrógeno/farmacología , Fertilización
19.
Front Bioeng Biotechnol ; 10: 1053653, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36532565

RESUMEN

Nanomedicine has been extensively studied for its versatility and broad-spectrum applications of theranostics in the research of respiratory disease. However, to the best of our knowledge, a scientometrics study based on the scientific knowledge assay of the overall situation on nanomedicine applied in the research of respiratory disease has not been reported so far, which would be of major importance to relevant researchers. To explore and exhibit the research status and developing trend of nanomedicines deployed in basic or clinical research in respiratory disease, the research ecosystem and exciting subareas were profiled based on the massive data mining and visualization from the relevant works reported from 2006 to 2021. Data were collected from the Web of Science database. Data statistics software and bibliometric analysis software were employed to visualize the research trend and the relationship between respiratory diseases and nanomedicines in each representative direction. The cluster analysis and burst detections indicated that the improvement of drug delivery and vaccine developments are the up-to-date key directions in nanomedicines for respiratory disease research and treatments. Furthermore, we emphatically studied four branch areas in this field including COVID-19, nanotube, respiratory syncytial virus, and mRNA vaccine those are selected for in-depth mining and bibliometric coupling analysis. Research trends signify the future focuses will center on preventing respiratory diseases with mRNA vaccines using nanoparticle-based approaches. We anticipate our study will enable researchers to have the panorama and deep insights in this area, thus inspiriting further exploitations especially the nanobiomaterial-based systems for theranostic applications in respiratory disease treatment.

20.
Pharmaceutics ; 14(7)2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35890373

RESUMEN

5-aminolevulinic acid (5-ALA) has been extensively studied for its sustainability and broad-spectrum applications in medical research and theranostics, as well as other areas. It's a precursor of protoporphyrin IX (PpIX), a sustainable endogenous and naturally-existing photosensitizer. However, to the best of our knowledge, a scientometrics study based on the scientific knowledge assay of the overall situation on 5-ALA research has not been reported so far, which would be of major importance to the relevant researchers. In this study, we collected all the research articles published in the last two decades from the Web of Science Core Collection database and employed bibliometric methods to comprehensively analyze the dataset from different perspectives using CiteSpace. A total of 1595 articles were identified. The analysis results showed that China published the largest number of articles, and SBI Pharmaceuticals Co., Ltd. was the most productive institution that sponsored several of the most productive authors. The cluster analysis and burst detections indicated that the improvement of photodynamic efficacy theranostics is the up-to-date key direction in 5-ALA research. Furthermore, we emphatically studied nanotechnology involvement in 5-ALA delivery and theranostics research. We envision that our results will be beneficial for researchers to have a panorama of and deep insights into this area, thus inspiring further exploitations, especially of the nanomaterial-based systems for 5-ALA delivery and theranostic applications.

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