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1.
Front Immunol ; 14: 1250920, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38077388

RESUMO

Introduction: Radiation pneumonitis is a critical complication that constrains the use of radiation therapy for thoracic malignancies, leading to substantial morbidity via respiratory distress and lung function impairment. The role of Natural killer (NK) cells in inflammatory diseases is well-documented; however, their involvement in radiation pneumonitis is not fully understood. Methods: To explore the involvement of NK cells in radiation pneumonitis, we analyzed tissue samples for NK cell presence and function. The study utilized immunofluorescence staining, western blotting, and immunoprecipitation to investigate CXCL10 and ROS levels, autophagy activity, and NKG2D receptor dynamics in NK cells derived from patients and animal models subjected to radiation. Result: In this study, we observed an augmented infiltration of NK cells in tissues affected by radiation pneumonitis, although their function was markedly diminished. In animal models, enhancing NK cell activity appeared to decelerate the disease progression. Concomitant with the disease course, there was a notable upsurge in CXCL10 and ROS levels. CXCL10 was found to facilitate NK cell migration through CXCR3 receptor activation. Furthermore, evidence of excessive autophagy in patient NK cells was linked to ROS accumulation, as indicated by immunofluorescence and Western blot analyses. The association between the NKG2D receptor and its adaptor proteins (AP2 subunits AP2A1 and AP2M1), LC3, and lysosomes was intensified after radiation exposure, as demonstrated by immunoprecipitation. This interaction led to NKG2D receptor endocytosis and subsequent lysosomal degradation. Conclusion: Our findings delineate a mechanism by which radiation-induced lung injury may suppress NK cell function through an autophagy-dependent pathway. The dysregulation observed suggests potential therapeutic targets; hence, modulating autophagy and enhancing NK cell activity could represent novel strategies for mitigating radiation pneumonitis.


Assuntos
Subfamília K de Receptores Semelhantes a Lectina de Células NK , Pneumonite por Radiação , Animais , Humanos , Autofagia , Células Matadoras Naturais/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Pneumonite por Radiação/metabolismo , Espécies Reativas de Oxigênio/metabolismo
2.
Prep Biochem Biotechnol ; 53(9): 1109-1119, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36785995

RESUMO

Prodigiosin (2-methyl-3-pentyl-6-methoxyprodiginine) is a valuable medicinal and edible natural pigment derived from Serratia marcescens. How prodigiosin synthesis is suppressed by environmental factors has not been investigated. Previous studies described a low level of prodigiosin production in the presence of yeast extracts. However, we have observed that S. marcescens SDSPY-136 did not synthesize prodigiosin in yeast extract culture. In this study, transcriptome sequencing of yeast extract cultures was used to estimate the metabolic control of the synthetic prodigiosin pathway in S. marcescens. Key phosphorylation enzymes in the glycolysis pathway, 6-phosphofructokinase, and glyceraldehyde 3-phosphate dehydrogenase, were downregulated by yeast extract and other carbon metabolism pathway genes were enhanced. Genes related to ribosomes, amino acid metabolism, and aminoacyl-tRNA biosynthesis were also highly up-regulated. The presence of metal ions in yeast extracts and the accumulation of fermentation metabolites alter the two-component signaling system, which regulated metabolism to various degrees. The results of metal ion testing suggested that prodigiosin inhibition could be caused by metal ions, such as zinc ion. The findings indicate that yeast extract may affect metabolism through multiple pathways in S. marcescens. This research sheds light on the mechanism of prodigiosin regulatory inhibition.


Assuntos
Prodigiosina , Serratia marcescens , Serratia marcescens/genética , Perfilação da Expressão Gênica , Íons/metabolismo
3.
Int J Biol Macromol ; 231: 123405, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36693608

RESUMO

Resistant glucan, a functional dietary fiber, has been shown to alleviate type 2 diabetes mellitus (T2DM) and its complications in clinical studies. However, the interactions between the special structure of resistant glucan and the metabolism-related pathways in T2DM have not yet been systematically studied. This study identified the structural differences between resistant glucans prepared by new and old methods. Oral gavage with two resistant glucans in T2DM mice, led to significant improvements in glucose and lipid metabolism as measured by related indicators (including gut microbiota, fecal metabolites, and physiological and biochemical indexes). According to these results, in addition to van der Waals forces, micelle formation, and hydrogen bonding, the branching structures of resistant glucans produced more hydroxyl, carbonyl, and keto groups that linked cholesterols, cholesterol esters, and low-density lipoprotein intermediates. Moreover, after lipid clearing, the metabolic environment was more conducive to the proliferation of specific gut microbiota (including Phascolarctobacterium, Prevotella, Butyricicoccus, Weissella, and Anaerostipes) with decreasing abundance ratios of Firmicutes and Bacteroides. This facilitated the synthesis of high-density lipoprotein, conversion of cholesterol into coprostanol, and production of short-chain fatty acids and bile acids. Our findings provide a foundation for comprehensive investigation of the structure of resistant glucan in the promotion and prevention of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Glucanos , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos Voláteis , Firmicutes , Colesterol
4.
Sensors (Basel) ; 22(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36080908

RESUMO

Automatic modulation classification (AMC) plays a fundamental role in common communication systems. Existing clustering models typically handle fewer modulation types with lower classification accuracies and more computational resources. This paper proposes a hierarchical self-organizing map (SOM) based on a feature space composed of high-order cumulants (HOC) and amplitude moment features. This SOM with two stacked layers can identify intrinsic differences among samples in the feature space without the need to set thresholds. This model can roughly cluster the multiple amplitude-shift keying (MASK), multiple phase-shift keying (MPSK), and multiple quadrature amplitude keying (MQAM) samples in the root layer and then finely distinguish the samples with different orders in the leaf layers. We creatively implement a discrete transformation method based on modified activation functions. This method causes MQAM samples to cluster in the leaf layer with more distinct boundaries between clusters and higher classification accuracies. The simulation results demonstrate the superior performance of the proposed hierarchical SOM on AMC problems when compared with other clustering models. Our proposed method can manage more categories of modulation signals and obtain higher classification accuracies while using fewer computational resources.


Assuntos
Algoritmos , Análise por Conglomerados , Simulação por Computador
5.
Int J Biol Macromol ; 219: 150-158, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-35905764

RESUMO

This study describes a new method for producing high-quality resistant glucan by characterizing the structural mechanism of indigestibility. The structures and properties of resistant glucans were characterized before and after in vitro simulated digestion. The results demonstrated that high-pressure processing (HPP) led to the complete disappearance of crystal peaks and increased the efficiency of the two enzymes (α-amylase and transglucosidase). Moreover, α-1,6 and ß-linkages were abundant in the connecting parts of the long and branching chains in the resulting resistant glucans, thus hindering the ability of digestive enzymes to hydrolyze short chains with a degree of polymerization (DP) ≤ 6. In addition, transglucosidase activity led to a higher proportion of short chains (DP 3-6), further promoting indigestibility. We demonstrated that, without rectification and decolorization, the dietary fiber content was >75 %, and the degree of branching increased to 50.9 %, indicating higher indigestibility than that resistant glucans produced by traditional methods.


Assuntos
Fibras na Dieta , Glucanos , Glucanos/química , Glucanos/farmacologia , alfa-Amilases
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