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1.
Crit Rev Food Sci Nutr ; : 1-15, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38961829

RESUMEN

During the application of Whey proteins (WPs), they often have complex interactions with saccharides (Ss), another important biopolymer in food substrate. The texture and sensory qualities of foods containing WPs and Ss are largely influenced by the interactions of WPs-Ss. Moreover, the combination of WPs and Ss is possible to produce many excellent functional properties including emulsifying properties and thermal stability. However, the interactions between WPs-Ss are complex and susceptible to some processing conditions. In addition, with different interaction ways, they can be applied in different fields. Therefore, the non-covalent interaction mechanisms between WPs-Ss are firstly summarized in detail, including electrostatic interaction, hydrogen bond, hydrophobic interaction, van der Waals force. Furthermore, the existence modes of WPs-Ss are introduced, including complex coacervates, soluble complexes, segregation, and co-solubility. The covalent interactions of WPs-Ss in food applications are often formed by Maillard reaction (dry or wet heat reaction) and occasionally through enzyme induction. Then, two common influencing factors, pH and temperature, on non-covalent/covalent bonds are introduced. Finally, the applications of WPs-Ss complexes and conjugations in improving WP stability, delivery system, and emulsification are described. This review can improve our understanding of the interactions between WPs-Ss and further promote their wider application.

2.
BMC Med ; 22(1): 278, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956533

RESUMEN

BACKGROUND: APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs). METHODS: Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations. RESULTS: Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P < 0.05, P < 0.01 and P < 0.001 in 3, 1 and 3 cohort comparisons, respectively). Conversely, the DOC test was equivalent to APRI and FIB-4 when all tests showed moderate/adequate diagnostic performances (P > 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%). CONCLUSIONS: This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.


Asunto(s)
Biomarcadores , Ditiotreitol , Cirrosis Hepática , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/sangre , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Femenino , Adulto , Anciano , Oxidación-Reducción , Curva ROC , Estudios de Cohortes , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/sangre , Prueba de Estudio Conceptual
4.
J Mol Histol ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38869753

RESUMEN

BACKGROUND: Sorting nexin 14 (SNX14) is a member of the sorting junction protein family. Its specific roles in cancer development remain unclear. Therefore, in this study, we aimed to determine the effects and underlying mechanisms of SNX14 on autophagy of breast cancer cells to aid in the therapeutic treatment of breast cancer. METHODS: In this study, we performed in vitro experiments to determine the effect of SNX14 on breast cancer cell growth. Moreover, we used an MCF7 breast cancer tumor-bearing mouse model to confirm the effect of SNX14 on tumor cell growth in vivo. We also performed western blotting and quantitative polymerase chain reaction to identify the mechanism by which SNX14 affects breast cancer MCF7 cells. RESULTS: We found that SNX14 regulated the onset and progression of breast cancer by promoting the proliferation and inhibiting the autophagy of MCF7 breast cancer cells. In vivo experiments further confirmed that SNX14 knockdown inhibited the tumorigenicity and inhibited the growth of tumor cells in tumor tissues of nude mice. In addition, western blotting analysis revealed that SNX14 modulate the autophagy of MCF7 breast cancer cells via the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin kinase signaling pathway. CONCLUSION: Our findings indicate that SNX14 is an essential tumor-promoting factor in the development of breast cancer.

5.
ACS Omega ; 9(23): 24333-24345, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38882112

RESUMEN

At present, the identification of the main factors controlling low-production coalbed methane (CBM) wells and production enhancement measures does not consider geological and reservoir differences between individual wells and the CBM production effect of well groups simultaneously. In view of this, an evaluation index system suitable for use on inefficient well-blocks was established, which involves their geological resource potential, ground stress, coal structure, and comprehensive permeability under engineering influences from a systemic perspective. The main geological engineering types were determined by zoning superposition, and the corresponding stimulation measures were proposed. The evaluation results of the Shizhuang South Block in the Qinshui Basin show that the area of interest can be divided into Class I, II, and III potential areas, of which the Class II potential areas are subdivided into six blocks. In Zone I, the horizontal well infill method is preferred to increase the CBM production from well groups. At the current level of technology, it is difficult to gain economic benefits from Zone III. In Zone II, these stimulation measures such as the infilling method of staged fracturing horizontal wells, refracturing under supplementary injection holes, roof fracturing, the combined method of acidification and secondary fracturing or nitrogen injection and secondary fracturing, the combined method of acidification and controlled displacement secondary fracturing, and controlled displacement repetitive roof fracturing, among others, can be adopted.

6.
Biochem Pharmacol ; 225: 116334, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38824967

RESUMEN

Alcoholic liver injury (ALI) stands as a prevalent affliction within the spectrum of complex liver diseases. Prolonged and excessive alcohol consumption can pave the way for liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Recent findings have unveiled the protective role of proline serine-threonine phosphatase interacting protein 2 (PSTPIP2) in combating liver ailments. However, the role of PSTPIP2 in ALI remains mostly unknown. This study aimed to determine the expression profile of PSTPIP2 in ALI and to uncover the mechanism through which PSTPIP2 affects the survival and apoptosis of hepatocytes in ALI, using both ethyl alcohol (EtOH)-fed mice and an EtOH-induced AML-12 cell model. We observed a consistent decrease in PSTPIP2 expression both in vivo and in vitro. Functionally, we assessed the impact of PSTPIP2 overexpression on ALI by administering adeno-associated virus 9 (AAV9)-PSTPIP2 into mice. The results demonstrated that augmenting PSTPIP2 expression significantly shielded against liver parenchymal distortion and curbed caspase-dependent hepatocyte apoptosis in EtOH-induced ALI mice. Furthermore, enforcing PSTPIP2 expression reduced hepatocyte apoptosis in a stable PSTPIP2-overexpressing AML-12 cell line established through lentivirus-PSTPIP2 transfection in vitro. Mechanistically, this study also identified signal transducer and activator of transcription 3 (STAT3) as a direct signaling pathway regulated by PSTPIP2 in ALI. In conclusion, our findings provide compelling evidence that PSTPIP2 has a regulatory role in hepatocyte apoptosis via the STAT3 pathway in ALI, suggesting PSTPIP2 as a promising therapeutic target for ALI.


Asunto(s)
Apoptosis , Ratones Endogámicos C57BL , Factor de Transcripción STAT3 , Animales , Apoptosis/fisiología , Apoptosis/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Ratones , Masculino , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/patología , Hepatopatías Alcohólicas/prevención & control , Etanol/toxicidad , Etanol/administración & dosificación , Hepatocitos/metabolismo , Hepatocitos/patología , Línea Celular , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética
7.
Nat Commun ; 15(1): 5193, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890366

RESUMEN

Multichannel meta-imaging, inspired by the parallel-processing capability of neuromorphic computing, offers considerable advancements in resolution enhancement and edge discrimination in imaging systems, extending even into the mid- to far-infrared spectrum. Currently typical multichannel infrared imaging systems consist of separating optical gratings or merging multi-cameras, which require complex circuit design and heavy power consumption, hindering the implementation of advanced human-eye-like imagers. Here, we present printable graphene plasmonic photodetector arrays driven by a ferroelectric superdomain for multichannel meta-infrared imaging with enhanced edge discrimination. The fabricated photodetectors exhibited multiple spectral responses with zero-bias operation by directly rescaling the ferroelectric superdomain instead of reconstructing the separated gratings. We also demonstrated enhanced and faster shape classification (98.1%) and edge detection (98.2%) using our multichannel infrared images compared with single-channel detectors. Our proof-of-concept photodetector arrays simplify multichannel infrared imaging systems and offer potential solutions in efficient edge detection in human-brain-type machine vision.

8.
Nanomicro Lett ; 16(1): 208, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38833205

RESUMEN

The structure of liquid water is primarily composed of three-dimensional networks of water clusters formed by hydrogen bonds, and dissolved oxygen is one of the most important indicators for assessing water quality. In this work, distilled water with different concentration of dissolved oxygen were prepared, and a clear negative correlation between the size of water clusters and dissolved oxygen concentration was observed. Besides, a phenomenon of rapid absorption and release of oxygen at the water interfaces was unveiled, suggesting that oxygen molecules predominantly exist at the interfaces of water clusters. Oxygen molecules can move rapidly through the interfaces among water clusters, allowing dissolved oxygen to quickly reach a saturation level at certain partial pressure of oxygen and temperature. Further exploration into the mechanism by molecular dynamics simulations of oxygen and water clusters found that oxygen molecules can only exist stably at the interfaces among water clusters. A semi-empirical formula relating the average number of water molecules in a cluster (n) to 17O NMR half-peak width (W) was summarized: n = 0.1 W + 0.85. These findings provide a foundation for exploring the structure and properties of water.

9.
Molecules ; 29(12)2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38930856

RESUMEN

The extract of Dendrobium huoshanense, a traditional Chinese medicinal and food homologous plant belonging to the family Orchidaceae, was previously reported to have hypoglycemic and antioxidant effects. In this study, the direct effects of polysaccharide (DHP) and non-polysaccharide (NDHP) components of D. huoshanense, as well as its water extract (DHWE) were compared with that of metformin (an antidiabetic drug) on the gut microbiota (collected from fecal flora) of rats with streptozotocin-induced type 1 diabetes (T1D) using an in vitro fermentation method. The results showed that DHWE, DHP, and NDHP reduced pH and increased bacterial proliferation and short-chain fatty acid (SCFA) content in fermentation broth. DHWE, DHP, NDHP and metformin promoted the production of acetic and propionic acid, acetic acid, propionic acid and butyric acid, and propionic acid, respectively. DHWE, DHP, and NDHP reduced the abundance of Proteobacteria (subdominant pathogenic bacteria) and increased the abundance of Firmicutes (dominant beneficial gut bacteria). NDHP also reduced the abundance of Bacteroidetes (beneficial and conditional pathogenic). Metformin increased the abundance of Proteobacteria and reduced the abundance of Firmicutes and Bacteroidetes. At the genus level, NDHP promoted the proliferation of Megamonas and Megasphaera and decreased harmful bacteria (e.g., Klebsiella), and DHP increased the abundance of Prevotellaceae (opportunistic and usually harmless). By contrast, metformin increased the abundance of harmful bacteria (e.g., Citrobacter) and reduced the abundance of beneficial bacteria (e.g., Oscillospira). Our study indicates that DHWE, DHP, and NDHP are potentially more beneficial than metformin on the gut microbiota of T1D rats in vitro.


Asunto(s)
Dendrobium , Diabetes Mellitus Tipo 1 , Ácidos Grasos Volátiles , Microbioma Gastrointestinal , Metformina , Polisacáridos , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Metformina/farmacología , Dendrobium/química , Polisacáridos/farmacología , Polisacáridos/química , Ratas , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/microbiología , Ácidos Grasos Volátiles/metabolismo , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Masculino , Diabetes Mellitus Experimental/tratamiento farmacológico
10.
Nat Commun ; 15(1): 3780, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38710714

RESUMEN

Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.


Asunto(s)
Neovascularización Coroidal , Dependovirus , Terapia Genética , Vectores Genéticos , Epitelio Pigmentado de la Retina , Animales , Dependovirus/genética , Vectores Genéticos/genética , Vectores Genéticos/administración & dosificación , Terapia Genética/métodos , Ratones , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/virología , Neovascularización Coroidal/terapia , Neovascularización Coroidal/genética , Conejos , Humanos , Técnicas de Transferencia de Gen , Degeneración Macular/terapia , Degeneración Macular/genética , Degeneración Macular/patología , Modelos Animales de Enfermedad , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Transducción Genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ratones Endogámicos C57BL , Retina/metabolismo , Retina/virología , Masculino , Células HEK293
11.
Angew Chem Int Ed Engl ; : e202407923, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38738617

RESUMEN

Although catenated cages have been widely constructed due to their unique and elegant topological structures, cyclic catenanes formed by the connection of multiple catenane units have been rarely reported. Herein, based on the orthogonal metal-coordination-driven self-assembly, we prepare a series of heterometallic [2]catenanes and cyclic bis[2]catenanes, whose structures are clearly evidenced by single-crystal X-ray analysis. Owing to the multiple positively charged nature, as well as the potential synergistic effect of the Cu(I) and Pt(II) metal ions, the cyclic bis[2]catenanes display broad-spectrum antibacterial activity. This work not only provides an efficient strategy for the construction of heterometallic [2]catenanes and cyclic bis[2]catenanes but also explores their applications as superior antibacterial agents, which will promote the construction of advanced supramolecular structures for biomedical applications.

12.
Neural Netw ; 176: 106349, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38723310

RESUMEN

Generalized Person Re-Identification (GReID) aims to develop a model capable of robust generalization across unseen target domains, even with training on a limited set of observed domains. Recently, methods based on the Attack-Defense mechanism are emerging as a prevailing technology to this issue, which treats domain transformation as a type of attack and enhances the model's generalization performance on the target domain by equipping it with a defense module. However, a significant limitation of most existing approaches is their inability to effectively model complex domain transformations, largely due to the separation of attack and defense components. To overcome this limitation, we introduce an innovative Interactive Attack-Defense (IAD) mechanism for GReID. The core of IAD is the interactive learning of two models: an attack model and a defense model. The attack model dynamically generates directional attack information responsive to the current state of the defense model, while the defense model is designed to derive generalizable representations by utilizing a variety of attack samples. The training approach involves a dual process: for the attack model, the aim is to increase the challenge for the defense model in countering the attack; conversely, for the defense model, the focus is on minimizing the effects instigated by the attack model. This interactive framework allows for mutual learning between attack and defense, creating a synergistic learning environment. Our diverse experiments across datasets confirm IAD's effectiveness, consistently surpassing current state-of-the-art methods, and using MSMT17 as the target domain in different protocols resulted in a notable 13.4% improvement in GReID task average Rank-1 accuracy. Code is available at: https://github.com/lhf12278/IAD.


Asunto(s)
Redes Neurales de la Computación , Humanos , Algoritmos , Seguridad Computacional
13.
Autophagy ; : 1-17, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38705725

RESUMEN

Macroautophagy/autophagy is a catabolic process crucial for degrading cytosolic components and damaged organelles to maintain cellular homeostasis, enabling cells to survive in extreme extracellular environments. ENAH/MENA, a member of the Ena/VASP protein family, functions as a highly efficient actin elongation factor. In this study, our objective was to explore the role of ENAH in the autophagy process. Initially, we demonstrated that depleting ENAH in cancer cells inhibits autophagosome formation. Subsequently, we observed ENAH's colocalization with MAP1LC3/LC3 during tumor cell starvation, dependent on actin cytoskeleton polymerization and the interaction between ENAH and BECN1 (beclin 1). Additionally, mammalian ATG9A formed a ring-like structure around ENAH-LC3 puncta during starvation, relying on actin cytoskeleton polymerization. Furthermore, ENAH's EVH1 and EVH2 domains were found to be indispensable for its colocalization with LC3 and BECN1, while the PRD domain played a crucial role in the formation of the ATG9A ring. Finally, our study revealed ENAH-led actin comet tails in autophagosome trafficking. In conclusion, our findings provide initial insights into the regulatory role of the mammalian actin elongation factor ENAH in autophagy.Abbreviations: 3-MA 3-methyladenine; ABPs actin-binding proteins; ATG autophagy related; ATG9A autophagy related 9A; Baf A1 bafilomycin A1; CM complete medium; CytERM endoplasmic reticulum signal-anchor membrane protein; Cyto D cytochalasin D; EBSS Earl's balanced salt solution; ENAH/MENA ENAH actin regulator; EVH1 Ena/VASP homology 1 domain; EVH2 Ena/VASP homology 2 domain; GAPDH glyceraldehyde-3-phosphate dehydrogenase; Lat B latrunculin B; LC3-I unlipidated form of LC3; LC3-II phosphatidylethanolamine-conjugated form of LC3; MAP1LC3/LC3 microtubule associated protein 1 light chain 3; mEGFP monomeric enhanced green fluorescent protein; mTagBFP2 monomeric Tag blue fluorescent protein 2; OSER organized smooth endoplasmic reticulum; PRD proline-rich domain; PtdIns3K class III phosphatidylinositol 3-kinase; WM wortmannin.

14.
Antonie Van Leeuwenhoek ; 117(1): 74, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691182

RESUMEN

A Gram-stain positive, aerobic, alkalitolerant and halotolerant bacterium, designated HH7-29 T, was isolated from the confluence of the Fenhe River and the Yellow River in Shanxi Province, PR China. Growth occurred at pH 6.0-12.0 (optimum, pH 8.0-8.5) and 15-40℃ (optimum, 32℃) with 0.5-24% NaCl (optimum, 2-9%). The predominant fatty acids (> 10.0%) were iso-C15:0 and anteiso-C15:0. The major menaquinones were MK-7 and MK-8. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol and two unidentified phospholipids. Phylogenetic analyses based on the 16S rRNA gene sequence revealed that strain HH7-29 T was a member of the genus Jeotgalibacillus, exhibiting high sequence similarity to the 16S rRNA gene sequences of Jeotgalibacillus alkaliphilus JC303T (98.4%), Jeotgalibacillus salarius ASL-1 T (98.1%) and Jeotgalibacillus alimentarius YKJ-13 T (98.1%). The genomic DNA G + C content was 43.0%. Gene annotation showed that strain HH7-29 T had lower protein isoelectric points (pIs) and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt and alkali. The average nucleotide identity, digital DNA-DNA hybridization values, amino acid identity values, and percentage of conserved proteins values between strain HH7-29 T and its related species were 71.1-83.8%, 19.5-27.4%, 66.5-88.4% and 59.8-76.6%, respectively. Based on the analyses of phenotypic, chemotaxonomic, phylogenetic and genomic features, strain HH7-29 T represents a novel species of the genus Jeotgalibacillus, for which the name Jeotgalibacillus haloalkalitolerans sp. nov. is proposed. The type strain is HH7-29 T (= KCTC 43417 T = MCCC 1K07541T).


Asunto(s)
Composición de Base , ADN Bacteriano , Ácidos Grasos , Filogenia , ARN Ribosómico 16S , Ríos , ARN Ribosómico 16S/genética , China , Ríos/microbiología , ADN Bacteriano/genética , Ácidos Grasos/análisis , Cloruro de Sodio/metabolismo , Técnicas de Tipificación Bacteriana , Fosfolípidos/análisis , Análisis de Secuencia de ADN , Hibridación de Ácido Nucleico
15.
Biomed Pharmacother ; 174: 116507, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38565059

RESUMEN

Thioredoxin reductase 1 (TrxR1) has emerged as a promising target for cancer therapy. In our previous research, we discovered several new TrxR1 inhibitors and found that they all have excellent anti-tumor activity. At the same time, we found these TrxR1 inhibitors all lead to an increase in AKT phosphorylation in cancer cells, but the detailed role of AKT phosphorylation in TrxR1 inhibitor-mediated cell death remains unclear. In this study, we identified the combination of AKT and TrxR1 inhibitor displayed a strong synergistic effect in colon cancer cells. Furthermore, we demonstrated that the synergistic effect of auranofin (TrxR1 inhibitor) and MK-2206 (AKT inhibitor) was caused by ROS accumulation. Importantly, we found that ATM inhibitor KU-55933 can block the increase of AKT phosphorylation caused by auranofin, and exhibited a synergistic effect with auranofin. Taken together, our study demonstrated that the activation of ATM/AKT pathway is a compensatory mechanism to cope with ROS accumulation induced by TrxR1 inhibitor, and synergistic targeting of TrxR1 and ATM/AKT pathway is a promising strategy for treating colon cancer.


Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada , Auranofina , Neoplasias del Colon , Sinergismo Farmacológico , Compuestos Heterocíclicos con 3 Anillos , Proteínas Proto-Oncogénicas c-akt , Pironas , Especies Reactivas de Oxígeno , Transducción de Señal , Tiorredoxina Reductasa 1 , Humanos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Neoplasias del Colon/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Tiorredoxina Reductasa 1/metabolismo , Tiorredoxina Reductasa 1/antagonistas & inhibidores , Auranofina/farmacología , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos/farmacología , Línea Celular Tumoral , Fosforilación/efectos de los fármacos , Morfolinas/farmacología , Células HCT116
16.
Brain Behav ; 14(4): e3479, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38648388

RESUMEN

OBJECTIVE: To explore the changes in the cerebral microstructure of patients with noise-induced hearing loss (NIHL) using diffusion tensor imaging (DTI). METHOD: Overall, 122 patients with NIHL (mild [MP, n = 79], relatively severe patients [including moderate and severe; RSP, n = 32], and undetermined [lost to follow-up, n = 11]) and 84 healthy controls (HCs) were enrolled. All clinical data, including age, education level, hearing threshold, occupation type, noise exposure time, and some scale scores (including the Mini-Mental State Examination [MMSE], tinnitus handicap inventory [THI], and Hamilton Anxiety Scale [HAMA]), were collected and analyzed. All participants underwent T1WI3DFSPGR and DTI, and tract-based spatial statistics and region of interest (ROI) analysis were used for assessment. RESULTS: The final sample included 71 MP, 28 RSP, and 75 HCs. The HAMA scores of the three groups were significantly different (p < .05). The noise exposure times, hearing thresholds, and HAMA scores of the MP and RSP were significantly different (p < .05). The noise exposure time was positively correlated with the hearing threshold and negatively correlated with the HAMA scores (p < .05), whereas the THI scores were positively correlated with the hearing threshold (p < .05). DTI analysis showed that all DTI parameters (fractional anisotropy [FA], axial diffusivity [AD], mean diffusivity [MD], and radial diffusivity [RD]) were significantly different in the left inferior longitudinal fasciculus (ILF) and left inferior fronto-occipital fasciculus (IFOF) for the three groups (p < .05). In addition, the FA values were significantly lower in the bilateral corticospinal tract (CST), right fronto-pontine tract (FPT), right forceps major, left superior longitudinal fasciculus (temporal part) (SLF), and left cingulum (hippocampus) (C-H) of the MP and RSP than in those of the HCs (p < .05); the AD values showed diverse changes in the bilateral CST, left IFOF, right anterior thalamic radiation, right external capsule (EC), right SLF, and right superior cerebellar peduncle (SCP) of the MP and RSP relative to those of the HC (p < .05). However, there were no significant differences among the bilateral auditory cortex ROIs of the three groups (p > .05). There was a significant negative correlation between the FA and HAMA scores for the left IFOF/ILF, right FPT, left SLF, and left C-H for the three groups (p < .05). There was a significant positive correlation between the AD and HAMA scores for the left IFOF/ILF and right EC of the three groups (p < .05). There were significantly positive correlations between the RD/MD and HAMA scores in the left IFOF/ILF of the three groups (p < .05). There was a significant negative correlation between the AD in the right SCP and noise exposure time of the MP and RSP groups (p < .05). The AD, MD, and RD in the left ROI were significantly positively correlated with hearing threshold in the MP and RSP groups (p < .05), whereas FA in the right ROI was significantly positively correlated with the HAMA scores for the three groups (p < .05). CONCLUSION: The changes in the white matter (WM) microstructure may be related to hearing loss caused by noise exposure, and the WM structural abnormalities in patients with NIHL were mainly located in the syndesmotic fibers of the temporooccipital region, which affected the auditory and language pathways. This confirmed that the auditory pathways have abnormal structural connectivity in patients with NIHL.


Asunto(s)
Imagen de Difusión Tensora , Pérdida Auditiva Provocada por Ruido , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Pérdida Auditiva Provocada por Ruido/patología , Pérdida Auditiva Provocada por Ruido/diagnóstico por imagen , Pérdida Auditiva Provocada por Ruido/fisiopatología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Sustancia Blanca/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiopatología
17.
Artículo en Inglés | MEDLINE | ID: mdl-38591775

RESUMEN

A Gram-stain-negative, aerobic, rod-shaped and halotolerant bacterium, designated as strain ASW11-75T, was isolated from intertidal sediments in Qingdao, PR China, and identified using a polyphasic taxonomic approach. Growth of strain ASW11-75T occurred at 10-45 °C (optimum, 37 °C), pH 6.5-9.0 (optimum, pH 8.0) and 0.5-18.0 % NaCl concentrations (optimum, 2.5 %). Phylogenetic analyses based on 16S rRNA gene sequences and 1179 single-copy orthologous clusters indicated that strain ASW11-75T is affiliated with the genus Marinobacter. Strain ASW11-75T showed highest 16S rRNA gene sequence similarity to 'Marinobacter arenosus' CAU 1620T (98.5 %). The digital DNA-DNA hybridization and average nucleotide identity values between strain ASW11-75T and its closely related strains (Marinobacter salarius R9SW1T, Marinobacter similis A3d10T, 'Marinobacter arenosus' CAU 1620T, Marinobacter sediminum R65T, Marinobacter salinus Hb8T, Marinobacter alexandrii LZ-8T and Marinobacter nauticus ATCC 49840T) were 19.8-24.5 % and 76.6-80.7 %, respectively. The predominant cellular fatty acids were C16 : 0, C18 : 1 ω9c and C16 : 0 N alcohol. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminophospholipid and two unidentified lipids. The major isoprenoid quinone was ubiquinone-9. The genomic DNA G+C content was 62.2 mol%. Based on genomic and gene function analysis, strain ASW11-75T had lower protein isoelectric points with higher ratios of acidic residues to basic residues and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt. The results of polyphasic characterization indicated strain ASW11-75T represents a novel Marinobacter species, for which the name Marinobacter qingdaonensis sp. nov. with the type strain ASW11-75T is proposed. The type strain is ASW11-75T (=KCTC 82497T=MCCC 1K05587T).


Asunto(s)
Ácidos Grasos , Marinobacter , Ácidos Grasos/química , Fosfolípidos/química , Agua de Mar/microbiología , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Composición de Base , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana
18.
World J Hepatol ; 16(3): 405-417, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38577530

RESUMEN

BACKGROUND: Models for predicting hepatitis B e antigen (HBeAg) seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) after nucleos(t)ide analog treatment are rare. AIM: To establish a simple scoring model based on a response-guided therapy (RGT) strategy for predicting HBeAg seroconversion and hepatitis B surface antigen (HBsAg) clearance. METHODS: In this study, 75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa (PEG-IFNα) treatment and a 24-wk follow-up. Logistic regression analysis was used to assess parameters at baseline, week 12, and week 24 to predict HBeAg seroconversion at 24 wk post-treatment. The two best predictors at each time point were used to establish a prediction model for PEG-IFNα therapy efficacy. Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0. RESULTS: The two most meaningful predictors were HBsAg ≤ 1000 IU/mL and HBeAg ≤ 3 S/CO at baseline, HBsAg ≤ 600 IU/mL and HBeAg ≤ 3 S/CO at week 12, and HBsAg ≤ 300 IU/mL and HBeAg ≤ 2 S/CO at week 24. With a total score of 0 vs 2 at baseline, week 12, and week 24, the response rates were 23.8%, 15.2%, and 11.1% vs 81.8%, 80.0%, and 82.4%, respectively, and the HBsAg clearance rates were 2.4%, 3.0%, and 0.0%, vs 54.5%, 40.0%, and 41.2%, respectively. CONCLUSION: We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNα therapy.

19.
Int J Biol Macromol ; 265(Pt 1): 130897, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38490376

RESUMEN

Although iron in meat is an important trace element for human diet, its presence also induces postprandial oxidative stress and aggravates the condition of patients with iron overload. To overcome this situation, a type of new tunable Fe-absorption bioactive materials was constructed in this study. First, four phenolic acids (Caffeic acid, Gallic acid, Protocatechuic acid, Chlorogenic acid) were grafted onto chitosan. Then, the copolymers were prepared into micron-level microspheres by emulsification method, which were characterized in adsorption isotherms (Langmuir model), swelling behavior and digestion characteristics. In order to verify the practical application effect of microspheres, Protocatechuic acid grafted chitosan microspheres as the representative were used in sirloin powder to observe their effects in vitro digestion and rat experiment. In the present study, microspheres were innovatively applied in meat consumption, which significantly inhibited the oxidation of meat in the process of digestion and effectively controlled the iron absorption. These results are expected to play an important role in promoting the healthy consumption of meat around the world, improving gastrointestinal redox status through dietary assistance, and treating diseases related to iron overload.


Asunto(s)
Quitosano , Hidroxibenzoatos , Sobrecarga de Hierro , Humanos , Ratas , Animales , Microesferas , Oxidación-Reducción , Carne , Hierro , Digestión
20.
Bioresour Technol ; 398: 130530, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38447619

RESUMEN

Bio-photoelectrochemical cell (BPEC) is an emerging technology that can convert the solar energy into electricity or chemicals. However, traditional BPEC depending on abiotic electrodes is challenging for microbial/enzymatic catalysis because of the inefficient electron exchange. Here, electroactive bacteria (Shewanella loihica PV-4) were used to reduce graphene oxide (rGO) nanosheets and produce co-assembled rGO/Shewanella biohydrogel as a basic electrode. By adsorbing chlorophyll contained thylakoid membrane, this biohydrogel was fabricated as a photoanode that delivered maximum photocurrent 126 µA/cm3 under visible light. Impressively, the biohydrogel could be served as a cathode in BPEC by forming coculture system with genetically edited Clostridium ljungdahlii. Under illumination, the BPEC with above photoanode and cathode yielded âˆ¼ 5.4 mM butyrate from CO2 reduction, 169 % increase compared to dark process. This work provided a new strategy (nanotechnology combined with synthetic biology) to achieve efficient bioelectricity and valuable chemical production in PBEC.


Asunto(s)
Fuentes de Energía Bioeléctrica , Dióxido de Carbono , Grafito , Dióxido de Carbono/metabolismo , Butiratos , Hidrogeles , Electricidad , Luz , Electrodos
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