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1.
J Am Chem Soc ; 146(25): 17517-17529, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38869959

RESUMEN

Despite the widespread use of hydrophilic building blocks to incorporate 18F and improve tracer pharmacokinetics, achieving effective leaving group-mediated nucleophilic 18F-fluorination in water (excluding 18F/19F-exchange) remains a formidable challenge. Here, we present a water-compatible SN2 leaving group-mediated 18F-fluorination method employing preconjugated "AquaF" (phosphonamidic fluorides) building blocks. Among 19 compact tetracoordinated pentavalent P(V)-F candidates, the "AquaF" building blocks exhibit superior water solubility, sufficient capacity for 18F-fluorination in water, and excellent in vivo metabolic properties. Two nitropyridinol leaving groups, identified from a pool of leaving group candidates that further enhance the precursor water solubility, enable 18F-fluorination in water with a 10-2 M-1 s-1 level reaction rate constant (surpassing the 18F/19F-exchange) at room temperature. With the exergonic concerted SN2 18F-fluorination mechanism confirmed, this 18F-fluorination method achieves ∼90% radiochemical conversions and reaches a molar activity of 175 ± 40 GBq/µmol (using 12.2 GBq initial activity) in saline for 12 "AquaF"-modified proof-of-concept functional substrates and small-molecule 18F-tracers. [18F]AquaF-Flurpiridaz demonstrates significantly improved radiochemical yield and molar activity compared to 18F-Flurpiridaz, alongside enhanced cardiac uptake and heart/liver ratio in targeted myocardial perfusion imaging, providing a comprehensive illustration of "AquaF" building blocks-assisted water-compatible SN2 18F-fluorination of small-molecule radiotracers.


Asunto(s)
Radioisótopos de Flúor , Halogenación , Agua , Radioisótopos de Flúor/química , Agua/química , Animales , Radiofármacos/química , Radiofármacos/síntesis química , Ratones , Tomografía de Emisión de Positrones , Solubilidad , Estructura Molecular , Trazadores Radiactivos
2.
Curr Issues Mol Biol ; 46(4): 3108-3121, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38666925

RESUMEN

Farnesyl pyrophosphate synthase (FPPS) catalyzes the synthesis of C15 farnesyl diphosphate (FPP) from C5 dimethylallyl diphosphate (DMAPP) and two or three C5 isopentenyl diphosphates (IPPs). FPP is an important precursor for the synthesis of isoprenoids and is involved in multiple metabolic pathways. Here, farnesyl pyrophosphate synthase from Sporobolomyces pararoseus NGR (SpFPPS) was isolated and expressed by the prokaryotic expression system. The SpFPPS full-length genomic DNA and cDNA are 1566 bp and 1053 bp, respectively. This gene encodes a 350-amino acid protein with a predicted molecular mass of 40.33 kDa and a molecular weight of 58.03 kDa (40.33 kDa + 17.7 kDa), as detected by SDS-PAGE. The function of SpFPPS was identified by induction, purification, protein concentration and in vitro enzymatic activity experiments. Structural analysis showed that Y90 was essential for chain termination and changing the substrate scope. Site-directed mutation of Y90 to the smaller side-chain amino acids alanine (A) and lysine (K) showed in vitro that wt-SpFPPS catalyzed the condensation of the substrate DMAPP or geranyl diphosphate (GPP) with IPP at apparent saturation to synthesize FPP as the sole product and that the mutant protein SpFPPS-Y90A synthesized FPP and C20 geranylgeranyl diphosphate (GGPP), while SpFPPS-Y90K hydrolyzed the substrate GGPP. Our results showed that FPPS in S. pararoseus encodes the SpFPPS protein and that the amino acid substitution at Y90 changed the distribution of SpFPPS-catalyzed products. This provides a baseline for potentially regulating SpFPPS downstream products and improving the carotenoid biosynthesis pathway.

3.
BMC Plant Biol ; 24(1): 731, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39085772

RESUMEN

BACKGROUND: In the field of ornamental horticulture, phenotypic mutations, particularly in leaf color, are of great interest due to their potential in developing new plant varieties. The introduction of variegated leaf traits in plants like Heliopsis helianthoides, a perennial herbaceous species with ecological adaptability, provides a rich resource for molecular breeding and research on pigment metabolism and photosynthesis. We aimed to explore the mechanism of leaf variegation of Heliopsis helianthoides (using HY2021F1-0915 variegated mutant named HY, and green-leaf control check named CK in 2020 April, May and June) by analyzing the transcriptome and metabolome. RESULTS: Leaf color and physiological parameters were found to be significantly different between HY and CK types. Chlorophyll content of HY was lower than that of CK samples. Combined with the result of Weighted Gene Co-expression Network Analysis (WGCNA), 26 consistently downregulated differentially expressed genes (DEGs) were screened in HY compared to CK subtypes. Among the DEGs, 9 genes were verified to be downregulated in HY than CK by qRT-PCR. The reduction of chlorophyll content in HY might be due to the downregulation of FSD2. Low expression level of PFE2, annotated as ferritin-4, might also contribute to the interveinal chlorosis of HY. Based on metabolome data, differential metabolites (DEMs) between HY and CK samples were significantly enriched on ABC transporters in three months. By integrating DEGs and DEMs, they were enriched on carotenoids pathway. Downregulation of four carotenoid pigments might be one of the reasons for HY's light color. CONCLUSION: FSD2 and PFE2 (ferritin-4) were identified as key genes which likely contribute to the reduced chlorophyll content and interveinal chlorosis observed in HY. The differential metabolites were significantly enriched in ABC transporters. Carotenoid biosynthesis pathway was highlighted with decreased pigments in HY individuals. These findings not only enhance our understanding of leaf variegation mechanisms but also offer valuable insights for future plant breeding strategies aimed at preserving and enhancing variegated-leaf traits in ornamental plants.


Asunto(s)
Metaboloma , Hojas de la Planta , Transcriptoma , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Clorofila/metabolismo , Regulación de la Expresión Génica de las Plantas , Perfilación de la Expresión Génica , Pigmentación/genética
4.
Small ; 20(11): e2305120, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37926783

RESUMEN

To reduce electromagnetic interference and noise pollution within communication base stations and servers, it is necessary for electromagnetic wave absorption (EWA) materials to transition from coating to multifunctional devices. Up to now, the stable and effective integration of multiple functions into one material by a simple method has remained a large challenge. Herein, a foam-type microwave absorption device assembled with multicomponent organic matter and graphite powder is synthesized by a universal combination process. Melamine and phenolic aldehyde amine work as the skeleton and cementing compound, respectively, in which graphite is embedded in the cementing compound interconnected into the mesoscopic 3D electric conductive and heat conductive network. Interestingly, the prepared flexible graphite/melamine foam (CMF) delivers a great EWA performance, with a great effective absorption bandwidth of 9.8 GHz, ultrathin thickness of 2.60 mm, and a strong absorption reflection loss of -41.7 dB. Moreover, the CMF possesses porosity and flexibility, endowing it with sound absorption ability. The CMF is unique in its integration of EWA, heat conduction, sound absorption, and mechanical robustness, as well as its cost-effective and scalable manufacturing. These attributes make CMF promising as a multifunctional device widely used in communication base stations, servers, and chips protection.

5.
J Org Chem ; 89(17): 11837-11863, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39173032

RESUMEN

Radioactive iodines and astatine, possessing distinct exploitable nuclear properties, play indispensable roles in the realms of nuclear imaging and therapy. Their analogous chemical characteristics shape the design, preparation, and substrate range for tracers labeled with these radiohalogens through interconnected radiosynthetic chemistry. This perspective systematically explores the labeling methods by types of halogenating reagents─nucleophilic and electrophilic─underpinning the rational design of such compounds. It delves into the rapidly evolving synthetic strategies and reactions in radioiodination and radioastatination over the past decade, comparing their intrinsic relationships and highlighting variations. This comparative analysis illuminates potential radiosynthetic methods for exploration. Moreover, stability concerns related to compounds labeled with radioactive iodines and astatine are addressed, offering valuable insights for radiochemists and physicians alike.

6.
Bioorg Med Chem Lett ; 109: 129818, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38823726

RESUMEN

Despite the availability of various 11C-labeled positron emission tomography (PET) tracers for assessing P-glycoprotein (P-gp) function, there are still limitations related to complex metabolism, high lipophilicity, and low baseline uptake. This study aimed to address these issues by exploring a series of customized dihydropyridines (DHPs) with enhanced stability and reduced lipophilicity as alternative PET tracers for P-gp dysfunction. Compared with verapamil and the rest DHPs, dimethyl 4-(4-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (1) exhibited superior cellular uptake differences between the human gastric cancer cell line SGC7901 and its drug-resistant counterpart. [18F]1 is successfully synthesized using a novel "hot-Hantzsch" approach in 22.1 ± 0.1 % radiochemical yields. MicroPET/CT imaging demonstrated that the uptake of [18F]1 in the brains of P-gp blocked mice increased by > 3 times compared to the control group. Additionally, [18F]1 displayed favorable lipophilicity (log D = 2.3) and excellent clearance characteristics, making it a promising tracer candidate with low background noise and high contrast.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Dihidropiridinas , Radioisótopos de Flúor , Tomografía de Emisión de Positrones , Dihidropiridinas/química , Dihidropiridinas/síntesis química , Dihidropiridinas/farmacología , Humanos , Animales , Radioisótopos de Flúor/química , Ratones , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Línea Celular Tumoral , Estructura Molecular , Radiofármacos/química , Radiofármacos/síntesis química , Radiofármacos/farmacología , Relación Estructura-Actividad , Distribución Tisular
7.
Ophthalmic Res ; : 1-20, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39231456

RESUMEN

INTRODUCTION: To compare various machine learning algorithms for constructing a diabetic retinopathy (DR) prediction model among type 2 diabetes mellitus (DM) patients and to develop a nomogram based on the best model. METHODS: This cross-sectional study included DM patients receiving routine DR screening. Patients were randomly divided into training (244) and validation (105) sets. Least absolute shrinkage and selection operator regression was used for the selection of clinical characteristics. Six machine learning algorithms were compared: decision tree (DT), k-nearest neighbours (KNN), logistic regression model (LM), random forest (RF), support vector machine (SVM), and XGBoost (XGB). Model performance was assessed via receiver operating characteristic (ROC), calibration, and decision curve analyses (DCAs). A nomogram was then developed on the basis of the best model. RESULTS: Compared with the five other machine learning algorithms (DT, KNN, RF, SVM, and XGB), the LM demonstrated the highest area under the ROC curve (AUC, 0.894) and recall (0.92) in the validation set. Additionally, the calibration curves and DCA results were relatively favourable. Disease duration, DPN, insulin dosage, urinary protein, and ALB were included in the LM. The nomogram exhibited robust discrimination (AUC: 0.856 in the training set and 0.868 in the validation set), calibration, and clinical applicability across the two datasets after 1,000 bootstraps. CONCLUSIONS: Among the six different machine learning algorithms, the LM algorithm demonstrated the best performance. A logistic regression-based nomogram for predicting DR in type-2 DM patients was established. This nomogram may serve as a valuable tool for DR detection, facilitating timely treatment.

8.
Ecotoxicol Environ Saf ; 283: 116770, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39067077

RESUMEN

Isotope technology is an ideal tool for tracing the sources of certain pollutants or providing insights into environmental processes. In recent years, the advent of multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) has enabled the precise measurement of various metal stable isotopes. Due to the presence of "fingerprint" properties in various environmental samples, metal stable isotopes have been applied to distinguish the source of contaminants effectively and further understand the corresponding environmental processes. The environmental fate of metal elements is strongly controlled by adsorption, an essential process for the distribution of elements between the dissolved and particulate phases. The adsorption of metal elements on mineral and organic surfaces significantly affects their biogeochemical cycles in the environment. Therefore, it is crucial to elucidate the fractionation characteristics of stable metal isotopes during the adsorption process. In this review, three typical transitional metal elements were selected, considering Mo as the representative of anionic species and Fe and Zn as the representative of cationic species. For Mo, the heavier Mo isotope is preferentially adsorbed in the solution phase, pH has a more significant influence on isotope fractionation, and temperature and ionic strength are relatively insensitive. Differences in coordination environments between dissolved and adsorbed Mo during adsorption, i.e., attachment mode (inner- or outer-sphere) or molecular symmetry (e.g., coordination number and magnitude of distortion), are likely responsible for isotopic fractionation. For Fe, The study of equilibrium/kinetic Fe isotopic fractionation in aqueous Fe(II)-mineral is not simple. The interaction between aqueous Fe(II) and Fe (hydroxyl) oxides is complex and dynamic. The isotope effect is due to coupled electron and atom exchange between adsorbed Fe(II), aqueous Fe(II), and reactive Fe(III) on the surface of Fe (hydroxyl) oxide. For Zn, the heavier Fe isotope preferentially adsorbs on the solid phase, and pH and ionic strength are essential influencing factors. The difference in coordination environment may be the cause of isotope fractionation.


Asunto(s)
Fraccionamiento Químico , Isótopos , Metales , Adsorción , Fraccionamiento Químico/métodos , Metales/química , Metales/análisis , Monitoreo del Ambiente/métodos , Concentración de Iones de Hidrógeno , Contaminantes Ambientales/química , Contaminantes Ambientales/análisis
9.
BMC Microbiol ; 23(1): 170, 2023 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-37337195

RESUMEN

BACKGROUND: Phages play a pivotal role in the evolution of microbial populations. The interactions between phages and their hosts are complex and may vary in response to host physiology and environmental conditions. Here, we have selected the genomes of some representative Bacillus prophages and lysosomes from the NCBI database for evolutionary analysis. We explored their evolutionary relationships and analyzed the protein information encoded by hundreds of Bacillus phages. RESULTS: We obtained the following conclusions: First, Bacillus phages carried some known functional gene fragments and a large number of unknown functional gene fragments, which might have an important impact on Bacillus populations, such as the formation of spores and biofilms and the transmission of virulence factors. Secondly, the Bacillus phage genome showed diversity, with a clear genome boundary between Bacillus prophages and Bacillus lytic phages. Furthermore, genetic mutations, sequence losses, duplications, and host-switching have occurred during the evolution of the Bacillus phage, resulting in low genome similarity between the Bacillus phages. Finally, the lysis module played an important influence on the process of Bacillus phage cross-species infestation. CONCLUSIONS: This study systematically described their protein function, diversity, and genome evolution, and the results of this study provide a basis for evolutionary diversity, horizontal gene transfer and co-evolution with the host in Bacillus phages.


Asunto(s)
Fagos de Bacillus , Bacteriófagos , Fagos de Bacillus/genética , Genoma Viral , Bacteriófagos/genética , Profagos/genética , Mutación , Evolución Molecular
10.
Bioconjug Chem ; 34(1): 140-161, 2023 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-36594786

RESUMEN

18F-Labeling methods for the preparation of 18F-labeled molecular probes can be classified into electrophilic fluorination, nucleophilic fluorination, metal-F coordination, and 18F/19F isotope exchange. Isotope exchange-based 18F-labeling methods demonstrate mild conditions featuring water resistance and facile high-performance liquid chromatography-free purification in direct 18F-labeling of substrates. This paper systematically reviews isotope exchange-based 18F-labeling methods sorted by the adjacent atom bonding with F, i.e., carbon and noncarbon atoms (Si, B, P, S, Ga, Fe, etc.). The respective isotope exchange mechanism, radiolabeling condition, radiochemical yield, molar activity, and stability of the 18F-product are mainly discussed for each isotope exchange-based 18F-labeling method as well as the cutting-edge application of the corresponding 18F-labeled molecular probes.


Asunto(s)
Halogenación , Agua , Sondas Moleculares , Marcaje Isotópico/métodos , Radioisótopos de Flúor/química , Radiofármacos/química
11.
Microvasc Res ; 150: 104586, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37451332

RESUMEN

PURPOSE: To compare long-term real-world outcomes of retinal microvasculature changes in proliferative diabetic retinopathy (PDR) treated with panretinal photocoagulation (PRP) vs. intravitreal conbercept (IVC) and to explore the potential factors affecting these changes. METHODS: This study retrospectively included 96 treatment-naïve PDR eyes of 96 type 2 diabetes mellitus patients [59 PRP and 37 IVC]. Baseline characteristics and treatment details were collected. Optical coherence tomography angiography (OCTA) data of macular vessel density (VD) and optic disc capillary density (CD) at baseline and at the last follow-up were compared between groups. The differences between the baseline and the last follow-up OCTA data in each group were also tested for significance. The correlation between the change in each OCTA parameter from baseline and each baseline characteristic/treatment parameter was investigated in each group. RESULTS: During a mean follow-up of two years, greater superficial (SCP) (p = 0.004) and deep capillary plexus (DCP) VD (p < 0.001) were observed in the foveal area in the PRP than in the IVC. Compared to the baseline, SCP VD in the foveal area increased in the PRP (p = 0.012), while an increased SCP VD in some sectors in the parafoveal and perifoveal areas (p < 0.05), rather than the foveal area (p = 0.908), was seen in the IVC. For both groups, eyes with a higher VD/CD at baseline tended to develop capillary dropout more intensively (all p < 0.05). In the IVC group, foveal avascular zone (FAZ) area change showed a negative correlation with baseline FAZ area (p = 0.020), and complementary PRP exerted a negative influence on FAZ area change (p = 0.002). In the PRP group, SCP VD change was positively correlated with follow-up frequency, and was negatively correlated with diastolic blood pressure (all p < 0.05); DCP VD change showed a positive correlation with PRP shot number (p = 0.019). CONCLUSION: The aforementioned microvasculature changes should be considered when PRP or IVC is adopted in PDR long-term management.


Asunto(s)
Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Humanos , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/terapia , Vasos Retinianos/diagnóstico por imagen , Angiografía con Fluoresceína/métodos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Estudios Retrospectivos , Retina , Tomografía de Coherencia Óptica/métodos , Microvasos/diagnóstico por imagen , Fotocoagulación
12.
Chemistry ; 29(37): e202300248, 2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37102671

RESUMEN

18 F-Labeled molecular tracers and subsequent positron emission tomography are indispensable molecular imaging tools in medical diagnosis and research. The preparation of 18 F-labeled molecular tracers involves critical steps such as the 18 F-labeling reaction, work-up, and 18 F-product purification, which are governed by 18 F-labeling chemistry. Since direct incorporation of 18 F in aqueous media exhibits many advantages in practice, this Review summarizes the existing 18 F-labeling methods in aqueous media, which are sorted by atoms forming chemical covalent bonds with F. The Review is focused on the respective reaction mechanism, the water effect and the applications of these methods for the development of 18 F-radiopharmaceuticals. The research progress on aqueous nucleophilic labeling methods using [18 F]F- as the 18 F source has been mainly discussed.

13.
Langmuir ; 39(26): 9007-9016, 2023 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-37329319

RESUMEN

Radiochemical yields (RCYs) of isotope exchange-based 18F-fluorination of non-carbon-centered substrates in water are rationally enhanced by adding surfactants, which increases both the rate constant k and local reactant concentrations. Among 12 surfactants, the cationic surfactant cetrimonium bromide (CTAB) and two nonionic surfactants (Tween 20 and Tween 80) were selected for their superior catalytic effects, namely, electrostatic effects or solubilization effects. For a model substrate, bis(4-methoxyphenyl)phosphinic fluoride, the 18F-fluorination rate constant (k) increased up to 7-fold, while its saturation concentration rose up to 15-fold due to micelle formation, encapsulating 70-94% of the substrate. With 30.0 mmol/L CTAB, the required 18F-labeling temperature of a typical organofluorosilicon prosthesis ([18F]SiFA) decreased from 95 °C to room temperature, achieving an RCY of 22%. For an E[c(RGDyK)]2-derived peptide tracer with an organofluorophosphine prosthesis, the RCY in water at 90 °C achieved 25%, correspondingly increasing the molar activity (Am). After high-performance liquid chromatography (HPLC) or solid-phase purification, the residual selected surfactant concentrations in the tracer injections were well below the FDA DII (Inactive Ingredient Database) limits or the LD50 in mice.

14.
Appl Microbiol Biotechnol ; 107(22): 6761-6773, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37698607

RESUMEN

Pullulan is a polymer produced by Aureobasidium spp. The yield of pullulan production can be impacted by the cellular differentiation of Aureobasidium spp., which changes with alterations in the growth environment. To improve pullulan yield, identifying key factors that regulate cellular differentiation is crucial. In this study, the main form of pullulan synthesis in Aureobasidium pullulans NG was through swollen cells (SC). The results showed that citric acid (CA) can regulate the cellular differentiation of Aureobasidium pullulans NG by accumulating higher levels of CA in the cells to maintain growth in SC form and increase pullulan production. The addition of 1.0% CA to Aureobasidium pullulans NG for 96 h resulted in a significant increase in pullulan production, producing 18.32 g/l compared to the control group which produced 10.23 g/l. Our findings suggest that controlling cellular differentiation using CA is a promising approach for enhancing pullulan production in Aureobasidium pullulans. KEY POINTS: • The regulation of cell differentiation in Aureobasidium pullulans NG is demonstrated to be influenced by citric acid. • Intracellular citric acid levels in Aureobasidium pullulans NG have been shown to support the growth of swollen cells. • Citric acid has been found to increase pullulan production in Aureobasidium pullulans NG.

15.
BMC Ophthalmol ; 23(1): 28, 2023 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-36690959

RESUMEN

OBJECTIVE: To develop and validate a nomogram model for predicting chronic ocular graft-versus-host disease (coGVHD) in patients after allogenic haematopoietic stem cell transplantation (allo-HSCT). METHODS: This study included 61 patients who survived at least 100 days after allo-HSCT. Risk factors for coGVHD were screened using LASSO regression, then the variables selected were subjected to logistic regression. Nomogram was established to further confirm the risk factors for coGVHD. Receiver operating characteristic (ROC) curves were constructed to assess the performance of the predictive model with the training and test sets. Odds ratios and 95% confidence intervals (95% CIs) were calculated by using logistic regression analysis. RESULTS: Among the 61 patients, 38 were diagnosed with coGVHD. We selected five texture features: lymphocytes (LYM) (OR = 2.26), plasma thromboplastin antecedent (PTA) (OR = 1.19), CD3 + CD25 + cells (OR = 1.38), CD3 + HLA-DR + cells (OR = 0.95), and the ocular surface disease index (OSDI) (OR = 1.44). The areas under the ROC curve (AUCs) of the nomogram with the training and test sets were 0.979 (95% CI, 0.895-1.000) and 0.969 (95% CI, 0.846-1.000), respectively.And the Hosmer-Lemeshow test was nonsignificant with the training (p = 0.9949) and test sets (p = 0.9691). CONCLUSION: We constructed a nomogram that can assess the risk of coGVHD in patients after allo-HSCT and help minimize the irreversible loss of vision caused by the disease in high-risk populations.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Nomogramas , Trasplante Homólogo/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Factores de Riesgo
16.
Int J Mol Sci ; 24(3)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36769154

RESUMEN

In the traditional method of the bio-fabrication of zinc oxide nanoparticles (ZnONPs), bacterial strains face metal toxicity and antimicrobial action. In the current study, an alkalescent nucleoside antibiotic was mixed with zinc hexanitrate to fabricate the ZnONPs. An integrated approach of DIAION HP-20 macroporous resin and sephadex LH-20 column chromatography was adopted to separate and purify alkalescent nucleoside AN03 from Streptomyces koyanogensis. Alkalescent nucleoside was confirmed by the Doskochilova solvent system. The bio-fabricated ZnONPs were characterized by using Fourier transform infrared (FTIR), X-ray diffraction (XRD), and transmission electron microscopy (TEM) analyses. The XRD spectrum and the TEM images confirmed the crystallinity and the spherical shape of the ZnONPs with an average size of 22 nm. FTIR analysis showed the presence of functional groups, which confirmed the bio-fabrication of ZnONPs from alkalescent nucleoside ANO3. In-vitro studies showed that 75 µg/mL of ZnONPs had a strong inhibitory zone (28.39 mm) against the Magnaporthe grisea and significantly suppressed the spore germination. SEM and TEM observations respectively revealed that ZnONPs caused breakage in hyphae and could damage the cells of M. grisea. Greenhouse experiments revealed that the foliar spray of ZnONPs could control the rice blast disease by 98%. Results also revealed that ZnONPs had positive effects on the growth of the rice plant. The present study suggested that ZnONPs could be fabricated from microbe-derived nucleoside antibiotics without facing the problems of metal toxicity and antimicrobial action, thus overcoming the problem of pathogen resistance. This could be a potent biocontrol agent in rice blast disease management.


Asunto(s)
Magnaporthe , Nanopartículas , Oryza , Óxido de Zinc , Antibacterianos/farmacología , Antibacterianos/química , Óxido de Zinc/química , Nucleósidos/farmacología , Pyricularia grisea , Nanopartículas/química , Oryza/microbiología
17.
Int J Mol Sci ; 24(21)2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37958506

RESUMEN

Nicotine-induced endoplasmic reticulum (ER) stress in retinal pigment epithelium (RPE) cells is thought to be one pathological mechanism underlying age-related macular degeneration (AMD). ERp29 attenuates tobacco extract-induced ER stress and mitigates tight junction damage in RPE cells. Herein, we aimed to further investigate the role of ERp29 in nicotine-induced ER stress and choroidal neovascularization (CNV). We found that the expression of ERp29 and GRP78 in ARPE-19 cells was increased in response to nicotine exposure. Overexpression of ERp29 decreased the levels of GRP78 and the C/EBP homologous protein (CHOP). Knockdown of ERp29 increased the levels of GRP78 and CHOP while reducing the viability of ARPE-19 cells under nicotine exposure conditions. In the ARPE-19 cell/macrophage coculture system, overexpression of ERp29 decreased the levels of M2 markers and increased the levels of M1 markers. The viability, migration and tube formation of human umbilical vein endothelial cells (HUVECs) were inhibited by conditioned medium from the ERp29-overexpressing group. Moreover, overexpression of ERp29 inhibits the activity and growth of CNV in mice exposed to nicotine in vivo. Taken together, our results revealed that ERp29 attenuated nicotine-induced ER stress, regulated macrophage polarization and inhibited CNV.


Asunto(s)
Neovascularización Coroidal , Nicotina , Animales , Humanos , Ratones , Neovascularización Coroidal/genética , Neovascularización Coroidal/metabolismo , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Células Endoteliales de la Vena Umbilical Humana/patología , Nicotina/farmacología , Epitelio Pigmentado de la Retina/metabolismo , Proteínas de Choque Térmico/metabolismo
18.
Molecules ; 28(7)2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37050023

RESUMEN

The common mycotoxins in polluted grains are aflatoxin B1(AFB1), zearalenone (ZEN) and deoxynivalenol (DON). Because of the potential threat to humans and animals, it is necessary to detect mycotoxin contaminants rapidly. At present, later flow immunoassay (LFIA) is one of the most frequently used methods for rapid analysis. However, multistep sample pretreatment processes and organic solvents are also required to extract mycotoxins from grains. In this study, we developed a one-step and "green" sample pretreatment method without using organic solvents. By combining with LFIA test strips and a handheld detection device, an on-site method for the rapid detection of AFB1, ZEN and DON was developed. The LODs for AFB1, ZEN and DON in corn are 0.90 µg/kg, 7.11 µg/kg and 10.6 µg/kg, respectively, and the working ranges are from 1.25 µg/kg to 40 µg/kg, 20 µg/kg to 2000 µg/kg and 35 µg/kg to 1500 µg/kg, respectively. This method has been successfully applied to the detection of AFB1, ZEN and DON in corn, rice and peanut, with recoveries of 89 ± 3%-106 ± 3%, 86 ± 2%-108 ± 7% and 90 ± 2%-106 ± 10%, respectively. The detection results for the AFB1, ZEN and DON residues in certified reference materials by this method were in good agreement with their certificate values.


Asunto(s)
Micotoxinas , Oryza , Zearalenona , Animales , Humanos , Arachis , Aflatoxina B1 , Zea mays , Micotoxinas/análisis , Contaminación de Alimentos/análisis
19.
Environ Geochem Health ; 45(8): 6177-6198, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37269417

RESUMEN

Metal mineral mining results in releases of large amounts of heavy metals into the environment, and it is necessary to better understand the response of rhizosphere microbial communities to simultaneous stress from multiple heavy metals (HMs), which directly impacts plant growth and human health. In this study, by adding different concentrations of cadmium (Cd) to a soil with high background concentrations of vanadium (V) and chromium (Cr), the growth of maize during the jointing stage was explored under limiting conditions. High-throughput sequencing was used to explore the response and survival strategies of rhizosphere soil microbial communities to complex HM stress. The results showed that complex HMs inhibited the growth of maize at the jointing stage, and the diversity and abundance of maize rhizosphere soil microorganisms were significantly different at different metal enrichment levels. In addition, according to the different stress levels, the maize rhizosphere attracted many tolerant colonizing bacteria, and cooccurrence network analysis showed that these bacteria interacted very closely. The effects of residual heavy metals on beneficial microorganisms (such as Xanthomonas, Sphingomonas, and lysozyme) were significantly stronger than those of bioavailable metals and soil physical and chemical properties. PICRUSt analysis revealed that the different forms of V and Cd had significantly greater effects on microbial metabolic pathways than all forms of Cr. Cr mainly affected the two major metabolic pathways: microbial cell growth and division and environmental information transmission. In addition, significant differences in rhizosphere microbial metabolism under different concentrations were found, and this can serve as a reference for subsequent metagenomic analysis. This study is helpful for exploring the threshold for the growth of crops in toxic HM soils in mining areas and achieving further biological remediation.


Asunto(s)
Metales Pesados , Microbiota , Contaminantes del Suelo , Humanos , Cadmio/análisis , Rizosfera , Metales Pesados/análisis , Suelo/química , Zea mays/metabolismo , Contaminantes del Suelo/análisis , Microbiología del Suelo
20.
J Neurochem ; 163(4): 310-326, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35775994

RESUMEN

GABAergic network activity has been established to be involved in numerous physiological processes and pathological conditions. Extensive studies have corroborated that GABAergic network activity regulates excitatory synaptic networks by activating presynaptic GABAB receptors (GABAB Rs). It is well documented that astrocytes express GABAB Rs and respond to GABAergic network activity. However, little is known about whether astrocytic GABAB Rs regulate excitatory synaptic transmission mediated by GABAergic network activity. To address this issue, we combined whole-cell recordings, optogenetics, calcium imaging, and pharmacological approaches to specifically activate hippocampal somatostatin-expressing interneurons (SOM-INs), a type of interneuron that targets pyramidal cell dendrites, while monitoring excitatory synaptic transmission in CA1 pyramidal cells. We found that optogenetic stimulation of SOM-INs increases astrocyte Ca2+ signaling via the activation of astrocytic GABAB Rs and GAT-3. SOM-INs depress excitatory neurotransmission by activating presynaptic GABAB Rs and astrocytic GABAB Rs, the latter inducing the release of ATP/adenosine. In turn, adenosine inhibits excitatory synaptic transmission by activating presynaptic adenosine A1 receptors (A1 Rs). Overall, our results reveal a novel mechanism that SOM-INs activation-induced synaptic depression is partially mediated by the activation of astrocytic GABAB Rs.


Asunto(s)
Astrocitos , Interneuronas , Astrocitos/metabolismo , Interneuronas/metabolismo , Hipocampo/metabolismo , Transmisión Sináptica/fisiología , Somatostatina , Receptores de GABA-B/fisiología , Receptores Purinérgicos P1/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Adenosina/metabolismo
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