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In the field of microplastics (MPs) toxicity prediction, machine learning (ML) computer simulation techniques are showing great potential. In this study, six ML algorithms were utilized to predict the toxicity of MPs on BEAS-2B cells based on quantitative structure-activity relationship (QSAR) models. Comparing the models of different algorithms, the extreme gradient boosting model showed the best fit and prediction performance (R2tra = 0.9876, R2test = 0.9286). Additionally, Williams plot analysis showed that the six models developed were able to predict stably within their applicability domain, with few outliers. Finally, the three feature importance methods-Embedded Feature Importance (EFI), Recursive Feature Elimination (RFE), and SHapley Additive exPlanations (SHAP)-consistently identified particle size as the most critical feature affecting toxicity prediction. The proposed QSAR model can be utilized for preliminary environmental exposure assessments of MPs and to better understand the associated health risks.
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The main type of saponins occurring in the root of Platycodon grandiflorus (Jacq.) A. DC. are oleanolic acid glycosides. The CYP716 gene family plays a major role in catalyzing the conversion of ß-amyrin into oleanolic acid. However, studies on the CYP716 genes in P. grandiflorus are limited, and its evolutionary history remains poorly understood. In this study, 22 PgCYP716 genes were identified, distributed among seven subfamilies. Cis-acting elements of the PgCYP716 promoters were mainly involved in plant hormone regulation and responses to abiotic stresses. PgCYP716A264, PgCYP716A391, PgCYP716A291, and PgCYP716BWv3 genes were upregulated in the root and during saponin accumulation, as shown by RNA-seq analysis, suggesting that these four genes play an important role in saponin synthesis. The results of subcellular localization indicated that these four genes encoded membrane proteins. Furthermore, the catalytic activity of these four genes was proved in the yeast, which catalyzed the conversion of ß-amyrin into oleanolic acid. We found that the content of ß-amyrin, platycodin D, platycoside E, platycodin D3, and total saponins increased significantly when either of the four genes was over expressed in the transgenic hair root. In addition, the expression of PgSS, PgGPPS2, PgHMGS, and PgSE was also upregulated while these four genes were overexpressed. These data support that these four PgCYP716 enzymes oxidize ß-amyrin to produce oleanolic acid, ultimately promoting saponin accumulation by activating the expression of upstream pathway genes. Our results enhanced the understanding of the functional variation among the PgCYP716 gene family involved in triterpenoid biosynthesis and provided a theoretical foundation for improving saponin content and enriching the saponin biosynthetic pathway in P. grandiflorus.
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Polyvinyl chloride microplastics (PVC-MPs) are microplastic pollutants widely present in the environment, but their potential risks to human lung health and underlying toxicity mechanisms remain unknown. In this study, we systematically analyzed the effects of PVC-MPs on the transcriptome and metabolome of BEAS-2B cells using high-throughput RNA sequencing and untargeted metabolomics technologies. The results showed that exposure to PVC-MPs significantly reduced the viability of BEAS-2B cells, leading to the differential expression of 530 genes and 3768 metabolites. Further bioinformatics analyses showed that PVC-MP exposure influenced the expression of genes associated with fluid shear stress, the MAPK and TGF-ß signaling pathways, and the levels of metabolites associated with amino acid metabolism. In particular, integrated pathway analysis showed that lipid metabolic pathways (including glycerophospholipid metabolism, glycerolipid metabolism, and sphingolipid metabolism) were significantly perturbed in BEAS-2B cells following PVC-MPs exposure. This study provides new insights and targets for a deeper understanding of the toxicity mechanism of PVC-MPs and for the prevention and treatment of PVC-MP-associated lung diseases.
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Diabetic retinopathy (DR) is a very serious diabetes complication. Changes in the O-linked N-acetylglucosamine (O-GlcNAc) modification are associated with many diseases. However, its role in DR is not fully understood. In this research, we explored the effect of O-GlcNAc modification regulation by activating AMP-activated protein kinase (AMPK) in DR, providing some evidence for clinical DR treatment in the future. Bioinformatics was used to make predictions from the database, which were validated using the serum samples of diabetic patients. As an in vivo model, diabetic mice were induced using streptozotocin (STZ) injection with/without an AMPK agonist (metformin) or an AMPK inhibitor (compound C) treatment. Electroretinogram (ERG) and H&E staining were used to evaluate the retinal functional and morphological changes. In vitro, 661 w cells were exposed to high-glucose conditions, with or without metformin treatment. Apoptosis was evaluated using TUNEL staining. The protein expression was detected using Western blot and immunofluorescence staining. The angiogenesis ability was detected using a tube formation assay. The levels of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) in the serum changed in the DR patients in the clinic. In the diabetic mice, the ERG wave amplitude and retinal thickness decreased. In vitro, the apoptotic cell percentage and Bax expression were increased, and Bcl2 expression was decreased in the 661 w cells under high-glucose conditions. The O-GlcNAc modification was increased in DR. In addition, the expression of GFAT/TXNIP O-GlcNAc was also increased in the 661 w cells after the high-glucose treatment. Additionally, the Co-immunoprecipitation(CO-IP) results show that TXNIP interacted with the O-GlcNAc modification. However, AMPK activation ameliorated this effect. We also found that silencing the AMPKα1 subunit reversed this process. In addition, the conditioned medium of the 661 w cells may have affected the tube formation in vitro. Taken together, O-GlcNAc modification was increased in DR with photoreceptor cell degeneration and neovascularization; however, it was reversed after activating AMPK. The underlying mechanism is linked to the GFAT/TXNIP-O-GlcNAc modification signaling axis. Therefore, the AMPKα1 subunit plays a vital role in the process.
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Proteínas Quinases Ativadas por AMP , Acetilglucosamina , Diabetes Mellitus Experimental , Retinopatia Diabética , N-Acetilglucosaminiltransferases , Retinopatia Diabética/metabolismo , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/patologia , Animais , Camundongos , Acetilglucosamina/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , N-Acetilglucosaminiltransferases/antagonistas & inibidores , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Masculino , Apoptose/efeitos dos fármacos , Metformina/farmacologia , beta-N-Acetil-Hexosaminidases/metabolismo , beta-N-Acetil-Hexosaminidases/antagonistas & inibidores , Retina/metabolismo , Retina/patologia , Retina/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Linhagem CelularRESUMO
Background: Several scholarly publications have thoroughly examined the significant role of autophagy in the pathogenesis, progression, and treatment of retinal diseases. This research utilized bibliometric analysis to identify the primary areas of focus and emerging trends within the discipline and offer a comprehensive summary. Methods: The research articles and reviews regarding autophagy and retinal diseases from 2009-01-01 to 2022-12-31 were from the Web of Science Core Collection (WOSCC). The software VOSviewer and CiteSpace were applied to analyze and visualize maps of countries, organizations, authors, journals, keyword networks, and citations in the field of autophagy in retinal diseases. Results: 854 qualified records (721 articles and 133 reviews) were retrieved in this research. The annual publication output of literature shows a growing trend. China is the most productive country, and the author with the most publications is Kai Kaarniranta. Journal Autophagy published the most articles in this field. Keywords analysis can effectively reflect the research hot spots and indicate that diabetic retinopathy and glaucoma have drawn more attention recently. Researchers have shifted the research emphasis on "AMPK", "angiogenesis", "mutation", and "inflammation". Conclusions: With the bibliometric analysis approach, we presented the number of publications, countries, regions, authors, institutions, keywords, and citations, which further helps researchers understand the hot spots and trends in the field of autophagy in retinal diseases and explore the issues in the rapidly developing area.
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Objective: A comprehensive strategy for microbial identification and contamination investigation during sterile drug manufacturing was innovatively established in this study, mainly based on MALDI-TOF MS for the identification and complemented by sequencing technology on strain typing. Methods: It was implemented to monitor the bacterial contamination of a sterile drug manufacturing facility, including its bacterial distribution features and patterns. In three months, two hundred ninety-two samples were collected covering multiple critical components of raw materials, personnel, environment, and production water. Results: Based on our strategy, the bacterial profile across the production process was determined: 241/292 bacterial identities were obtained, and Staphylococcus spp. (40.25%), Micrococcus spp.(11.20%), Bacillus spp. (8.30%), Actinobacteria (5.81%), and Paenibacillus spp. (4.56%) are shown to be the most dominant microbial contaminants. With 75.8% species-level and 95.4% genus-level identification capability, MALDI-TOF MS was promising to be a first-line tool for environmental monitoring routine. Furthermore, to determine the source of the most frequently occurring Staphylococcus cohnii, which evidenced a widespread presence in the entire process, a more discriminating S. cohnii whole-genome SNP typing method was developed to track the transmission routes. Phylogenetic analysis based on SNP results indicated critical environment contamination is highly relevant to personnel flow in this case. The strain typing results provide robust and accurate information for the following risk assessment step and support effective preventive and corrective measures. Conclusion: In general, the strategy presented in this research will facilitate the development of improved production and environmental control processes for the pharmaceutical industry, and give insights about how to provide more sound and reliable evidence for the optimization of its control program.
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Actinobacillus pleuropneumoniae (APP) is an important pathogen of the porcine respiratory disease complex, which leads to huge economic losses worldwide. We previously demonstrated that Pichia pastoris-producing bovine neutrophil ß-defensin-5 (B5) could resist the infection by the bovine intracellular pathogen Mycobacterium bovis. In this study, the roles of synthetic B5 in regulating mucosal innate immune response and protecting against extracellular APP infection were further investigated using a mouse model. Results showed that B5 promoted the production of tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, and interferon (IFN)-ß in macrophages as well as dendritic cells (DC) and enhanced DC maturation in vitro. Importantly, intranasal B5 was safe and conferred effective protection against APP via reducing the bacterial load in lungs and alleviating pulmonary inflammatory damage. Furthermore, in the early stage of APP infection, we found that intranasal B5 up-regulated the secretion of TNF-α, IL-1ß, IL-17, and IL-22; enhanced the rapid recruitment of macrophages, neutrophils, and DC; and facilitated the generation of group 3 innate lymphoid cells in lungs. In addition, B5 activated signalling pathways associated with cellular response to IFN-ß and activation of innate immune response in APP-challenged lungs. Collectively, B5 via the intranasal route can effectively ameliorate the immune suppression caused by early APP infection and provide protection against APP. The immunization strategy may be applied to animals or human respiratory bacterial infectious diseases. Our findings highlight the potential importance of B5, enhancing mucosal defence against intracellular bacteria like APP which causes early-phase immune suppression.
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Actinobacillus pleuropneumoniae , Imunidade Inata , Humanos , Suínos , Animais , Bovinos , Actinobacillus pleuropneumoniae/metabolismo , Linfócitos , Pulmão/microbiologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Terapia de ImunossupressãoRESUMO
A series of furan-based poly(ester amide)s, namely poly(butylene 2,5-furanoate)-co-(hexamethylene furanamide) (PBAsF), were synthesized by partially substituting 1,4-butanediol (BDO) with linear hexamethylene diamine (HMDA). The introduction of amide bonding units enhances the intermolecular hydrogen bonding and intermolecular interaction forces, while the incorporation of flexible fragments results in a significant improvement in the thermal stability and mechanical properties of PBAsF. PBA20F exhibited an almost 50% increase in glass transition temperature, a mild improvement in tensile modulus of elasticity and tensile strength, and a tolerable decrease in elongation at break. Notably, the increased absorption in the UV wavelength range of PBAsF is enhanced due to the increase in amide bonding, which increases UV degradability. Additionally, the discovery of treatment methods with excellent performance in dye rejection is another important aspect.
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Atmospheric drag is an important influencing factor in precise orbit determination and the prediction of low-orbit space debris. It has received widespread attention. Currently, calculating atmospheric drag mainly relies on different atmospheric density models. This experiment was designed to explore the impact of different atmospheric density models on the orbit prediction of space debris. In the experiment, satellite laser ranging data published by the ILRS (International Laser Ranging Service) were used as the basis for the precise orbit determination for space debris. The prediction error of space debris orbits at different orbital heights using different atmospheric density models was used as a criterion to evaluate the impact of atmospheric density models on the determination of space-target orbits. Eight atmospheric density models, DTM78, DTM94, DTM2000, J71, RJ71, JB2006, MSIS86, and NRLMSISE00, were compared in the experiment. The experimental results indicated that the DTM2000 atmospheric density model is best for determining and predicting the orbits of LEO (low-Earth-orbit) targets.
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Objective: To mine specific proteins and their protein-coding genes as suitable molecular biomarkers for the Burkholderia cepacia Complex (BCC) bacteria detection based on mega analysis of microbial proteomic and genomic data comparisons and to develop a real-time recombinase polymerase amplification (rt-RPA) assay for rapid isothermal screening for pharmaceutical and personal care products. Methods: We constructed an automatic screening framework based on Python to compare the microbial proteomes of 78 BCC strains and 263 non-BCC strains to identify BCC-specific protein sequences. In addition, the specific protein-coding gene and its core DNA sequence were validated in silico with a self-built genome database containing 158 thousand bacteria. The appropriate methodology for BCC detection using rt-RPA was evaluated by 58 strains in pure culture and 33 batches of artificially contaminated pharmaceutical and personal care products. Results: We identified the protein SecY and its protein-coding gene secY through the automatic comparison framework. The virtual evaluation of the conserved region of the secY gene showed more than 99.8% specificity from the genome database, and it can distinguish all known BCC species from other bacteria by phylogenetic analysis. Furthermore, the detection limit of the rt-RPA assay targeting the secY gene was 5.6 × 102 CFU of BCC bacteria in pure culture or 1.2 pg of BCC bacteria genomic DNA within 30 min. It was validated to detect <1 CFU/portion of BCC bacteria from artificially contaminated samples after a pre-enrichment process. The relative trueness and sensitivity of the rt-RPA assay were 100% in practice compared to the reference methods. Conclusion: The automatic comparison framework for molecular biomarker mining is straightforward, universal, applicable, and efficient. Based on recognizing the BCC-specific protein SecY and its gene, we successfully established the rt-RPA assay for rapid detection in pharmaceutical and personal care products.
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Atmospheric drag is an important factor affecting orbit determination and prediction of low-orbit space debris. To obtain accurate ballistic coefficients of space debris, we propose a calculation method based on measured optical angles. Angle measurements of space debris with a perigee height below 1400 km acquired from a photoelectric array were used for orbit determination. Perturbation equations of atmospheric drag were used to calculate the semi-major-axis variation. The ballistic coefficients of space debris were estimated and compared with those published by the North American Aerospace Defense Command in terms of orbit prediction error. The 48 h orbit prediction error of the ballistic coefficients obtained from the proposed method is reduced by 18.65% compared with the published error. Hence, our method seems suitable for calculating space debris ballistic coefficients and supporting related practical applications.
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Nanomaterials have been widely applied and developed due to its unique physicochemical characteristics, such as their small size. The environmental and biological effects caused by nanomaterials have raised concerns. In particular, some nanometal oxides have obvious biological toxicity and pose a major safety problem. The prediction model established by combining the expression levels of key genes with quantitative structure-activity relationship (QSAR) studies can predict the biotoxicity of nanomaterials by relying on both structural information and gene regulation information. This model can fill the gap of missing mechanisms in QSAR studies. In this study, we exposed A549 cells and BEAS-2B cells to 21 nanometal oxides for 24 h. Cell viability was assessed by measuring absorbance values using the CCK8 assay, and the expression levels of the Dlk1-Dio3 gene cluster were measured. By using the theoretical basis of the nano-QSAR model and the improved principles of the SMILES-based descriptors to combine specific gene expression and structural factors, new models were constructed using Monte Carlo partial least squares (MC-PLS) for the biotoxicity of the nanometal oxides on two different lung cells. The overall quality of the nano-QSAR models constructed by combining specific gene expression and structural parameters for A549 and BEAS-2B cells was better than that of the models constructed based on structural parameters only. The coefficient of determination (R2) of the A549 cell model increased from 0.9044 to 0.9969, and the Root Mean Square Error (RMSE) decreased from 0.1922 to 0.0348. The R2 of the BEAS-2B cell model increased from 0.9355 to 0.9705, and the RMSE decreased from 0.1206 to 0.0874. The model validation proved the proposed models have a good prediction, generalization ability and model stability. This study offers a new research perspective for the toxicity assessment of nanometal oxides, contributing to a more systematic safety evaluation of nanomaterials.
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Nanoestruturas , Nanoestruturas/toxicidade , Linhagem Celular , Óxidos/toxicidade , Sobrevivência Celular , Expressão Gênica , Relação Quantitativa Estrutura-AtividadeRESUMO
BACKGROUND: Surface polysaccharides (SPs), such as lipopolysaccharide (O antigen) and capsular polysaccharide (K antigen), play a key role in the pathogenicity of Escherichia coli (E. coli). Gene cluster for polysaccharide antigen biosynthesis encodes various glycosyltransferases (GTs), which drive the process of SP synthesis and determine the serotype. RESULTS: In this study, a total of 7,741 E. coli genomic sequences were chosen for systemic data mining. The monosaccharides in both O and K antigens were dominated by D-hexopyranose, and the SPs in 70-80% of the strains consisted of only the five most common hexoses (or some of them). The linkages between the two monosaccharides were mostly α-1,3 (23.15%) and ß-1,3 (20.49%) bonds. Uridine diphosphate activated more than 50% of monosaccharides for glycosyltransferase reactions. These results suggest that the most common pathways could be integrated into chassis cells to promote glycan biosynthesis. We constructed a database (EcoSP, http://ecosp.dmicrobe.cn/ ) for browse this information, such as monosaccharide synthesis pathways. It can also be used for serotype analysis and GT annotation of known or novel E. coli sequences, thus facilitating the diagnosis and typing. CONCLUSIONS: Summarizing and analyzing the properties of these polysaccharide antigens and GTs are of great significance for designing glycan-based vaccines and the synthetic glycobiology.
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Escherichia coli , Polissacarídeos , Escherichia coli/genética , Escherichia coli/metabolismo , Polissacarídeos/metabolismo , Lipopolissacarídeos , Antígenos O , Monossacarídeos/metabolismo , Família Multigênica , Biologia Computacional , Polissacarídeos Bacterianos/genéticaRESUMO
AIMS: To examine the longitudinal association between transportation noise exposure (road traffic, aircraft, and railway noise) and T2D in a meta-analysis. MATERIALS AND METHODS: We systematically searched PubMed, Embase, Scopus, Cochrane, and Web of Science published up to February 2022. The GRADE approach was used to evaluate the study quality, and the pooled effect estimate was calculated by the fixed-effects model or the random-effects model. RESULTS: We included 10 prospective studies with a total of 4,994,171 participants and 417,332 T2D cases in the meta-analysis. According to the Navigation guide, 8 studies out of 10 were rated as having a probably high or high risk of bias. For road noise, the pooled relative risk (RR) per 10 dB higher Lden for developing T2D was 1.06 (95% CI:1.03, 1.09) with high heterogeneity (I2 = 90.1%, p < 0.001). Similar associations were also observed in aircraft and railway noise: the pooled RR were separately were: 1.01 (1.00, 1.01) and 1.02 (1.01, 1.03) separately. A 'dose-response' analysis found a similar linear association between road noise exposure and the risk of T2D. CONCLUSIONS: An overall 6% increase in the risk of T2D per 10 dB increase in road exposure was observed. Further studies are needed to confirm our findings, especially for aircraft and railway noise, and to identify the mechanisms involved.
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Diabetes Mellitus Tipo 2 , Ruído dos Transportes , Humanos , Ruído dos Transportes/efeitos adversos , Estudos Prospectivos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Exposição Ambiental/efeitos adversos , RiscoRESUMO
Modules consisting of antibiotic resistance genes (ARGs) flanked by inverted repeat Xer-specific recombination sites were thought to be mobile genetic elements that promote horizontal transmission. Less frequently, the presence of mobile modules in plasmids, which facilitate a pdif-mediated ARGs transfer, has been reported. Here, numerous ARGs and toxin-antitoxin genes have been found in pdif site pairs. However, the mechanisms underlying this apparent genetic mobility is currently not understood, and the studies relating to pdif-mediated ARGs transfer onto most bacterial genera are lacking. We developed the web server pdifFinder based on an algorithm called PdifSM that allows the prediction of diverse pdif-ARGs modules in bacterial genomes. Using test set consisting of almost 32 thousand plasmids from 717 species, PdifSM identified 481 plasmids from various bacteria containing pdif sites with ARGs. We found 28-bp-long elements from different genera with clear base preferences. The data we obtained indicate that XerCD-dif site-specific recombination mechanism may have evolutionary adapted to facilitate the pdif-mediated ARGs transfer. Through multiple sequence alignment and evolutionary analyses of duplicated pdif-ARGs modules, we discovered that pdif sites allow an interspecies transfer of ARGs but also across different genera. Mutations in pdif sites generate diverse arrays of modules which mediate multidrug-resistance, as these contain variable numbers of diverse ARGs, insertion sequences and other functional genes. The identification of pdif-ARGs modules and studies focused on the mechanism of ARGs co-transfer will help us to understand and possibly allow controlling the spread of MDR bacteria in clinical settings. The pdifFinder code, standalone software package and description with tutorials are available at https://github.com/mjshao06/pdifFinder.
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Antibacterianos , Bactérias , Antibacterianos/farmacologia , Bactérias/genética , Resistência Microbiana a Medicamentos/genética , Plasmídeos/genética , Genoma Bacteriano , Genes BacterianosRESUMO
To improve the viability of Lactobacillus plantarum (P) during digestion and storage, the probiotics were encapsulated by alginate (ALG) and alginate-gelatin (ALG-GE) hydrogels beads. ALG-P-GE showed much better physicochemical properties than ALG-P. The scanning electron microscopy (SEM) results validated the incorporation of bacterial cells into the beads. ALG-P-GE exhibited good encapsulation efficiency of 97.7 %, and the storage and thermal stability of probiotic were increased by 15 % and 8 %, respectively, when comparing with ALG-P. ALG-P-GE beads could protect the probiotics from inactivation in simulated gastric fluid and then release it in simulated intestinal fluid. The protective mechanism of ALG-GE for probiotics was further studied by fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and found that ALG and GE can form gel network through hydrogen bonding and electrostatic interactions. In the mimic beverage systems, ALG-P-GE beads could protect the encapsulated probiotics and increase its viability. The storage, thermal, and digestion stability of encapsulated probiotic were significantly increased and showed high viability in the mimic beverage systems. ALG-P-GE beads have great potential for the protection and delivery of probiotics in food systems.
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Lactobacillus plantarum , Probióticos , Lactobacillus plantarum/fisiologia , Gelatina , Alginatos/química , Hidrogéis/química , Bebidas , Probióticos/química , Digestão , Viabilidade MicrobianaRESUMO
Probiotics are sensitive to external conditions, resulting in low survival rates after being ingested or during food production, transportation and storage. In order to improve the survival rate of Lactobacillus plantarum (LP) during gastrointestinal digestion, storage, and freeze-drying, alginate-whey protein isolate (ALG-WPI) and alginate-pectin-whey protein isolate (ALG-PEC-WPI) composites were employed to encapsulate LP. The encapsulation efficiency of ALG-WPI-LP and ALG-PEC-WPI-LP beads both reached more than 99 %. Scanning electron microscopy (SEM) indicated that dense and rough aggregates were formed on the surface of both composites, and attached LP cells could be observed inside the beads. The ALG-WPI and ALG-PEC-WPI composites can protect the viability of LP in simulated gastric fluid (SGF) and release the probiotics in simulated intestinal fluid (SIF). The storage stability of LP at 4 °C was improved by about 15 % in comparison with bare LP and the survival rates of LP in ALG-WPI-LP and ALG-PEC-WPI-LP powders after freeze-drying were increased by 65.37 % and 72.06 %, respectively. The formation mechanism of ALG-WPI and ALG-PEC-WPI composites was further explored by fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The ALG-WPI and ALG-PEC-WPI composites have great potential to protect and deliver probiotics in food systems.
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Lactobacillus plantarum , Probióticos , Alginatos/química , Lactobacillus plantarum/química , Pectinas/química , Probióticos/química , Proteínas do Soro do Leite/químicaRESUMO
Diabetic retinopathy (DR) is a common complication of diabetes mellitus and has been considered a microvascular disease for a long time. However, recent evidence suggests that diabetic retinal neurodegeneration (DRN), which manifests as neuronal apoptosis, a decrease in optic nerve axons, and reactive gliosis, occurs prior to retinal microvascular alterations. Thioredoxin-interacting protein (TXNIP) is an endogenous inhibitor of thioredoxin (Trx), and it acts by inhibiting its reducing capacity, thereby promoting cellular oxidative stress. In addition, it participates in regulating multiple signaling pathways as a member of the α-arrestin family of proteins. Accumulating evidence suggests that TXNIP is upregulated in diabetes and plays a pivotal role in the pathophysiological process of DR. In this review, we summarized the role of TXNIP in DRN, aiming to provide evidence for DR treatment in the future.
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Diabetic retinopathy (DR) is a leading complication in type 1 and type 2 diabetes and has emerged as a significant health problem. Currently, there are no effective therapeutic strategies owing to its inconspicuous early lesions and complex pathological mechanisms. Therefore, the mechanism of molecular pathogenesis requires further elucidation to identify potential targets that can aid in the prevention of DR. As a type of protein translational modification, O-linked ß-N-acetylglucosamine (O-GlcNAc) modification is involved in many diseases, and increasing evidence suggests that dysregulated O-GlcNAc modification is associated with DR. The present review discusses O-GlcNAc modification and its molecular mechanisms involved in DR. O-GlcNAc modification might represent a novel alternative therapeutic target for DR in the future.
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Epigallocatechin gallate (EGCG) has many excellent qualities such as its antitumor, antiradiation and anti-oxidation properties, but its application is limited because its oral bioavailability is low and stability is poor. In this paper, zein and gum arabic (GA) were used as wall materials to prepare Zein-GA complex nanoparticles for encapsulating and protecting the EGCG. The particle size of Zein-GA-EGCG complex nanoparticles ranged from 128.03-221.23 nm, and the EGCG encapsulation efficiency reached a maximum of 75.23% when the mass ratio of zein to GA was 1:1. The FTIR and XRD results illustrated that the components of the Zein-GA-EGCG complex nanoparticles interacted by electrostatic, hydrogen bonding, and hydrophobic interactions. The EGCG release rate of Zein-GA-EGCG nanoparticles (16.42%) was lower than that of Zein-EGCG (25.52%) during gastric digestion, and a large amount of EGCG was released during intestinal digestion, suggesting that the Zein-GA-EGCG nanoparticles could achieve the sustained release of EGCG during in vitro digestion. Hence, using Zein-GA complexes to encapsulate EGCG effectively increased the encapsulation efficiency of EGCG and realized the purpose of sustained release during simulated gastrointestinal digestion.