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BACKGROUND: Syntaxin6 (STX6) is a SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptors) protein complex located in the trans-Golgi network and endosomes, which is closely associated with a variety of intracellular membrane transport events. STX6 has been shown to be overexpressed in a variety of human malignant tumors such as esophageal, colorectal, and renal cell carcinomas, and participates in tumorigenesis and development. METHODS: Based on clinical public database and clinical liver samples analysis, the expression of STX6 in hepatocellular carcinoma (HCC) tissues was investigated. The effects of STX6 on proliferation, migration and invasion of HCC cell in vitro and in vivo were evaluated through gain- and loss-of-function studies. We further performed RNA-seq analysis and protein interactome analysis, to further decifer the detailed mechanisms of STX6 in the regulation of the JAK-STAT pathway in HCC. RESULTS: STX6 expression was upregulated in HCC tissues and its expression was highly correlated with the high histological grade of the tumor. STX6 promoted HCC cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, STX6 mediated tumor progression depending on promoting the activation of JAK-STAT signaling pathway. Receptor for activated protein kinase C (RACK1) as an essential adaptor protein mediating STX6 regulation of JAK-STAT pathway. Specifically, STX6 interacted with RACK1 and then recruited signal transducer and activator of transcription 3 (STAT3) to form a protein-binding complex and activates STAT3 transcriptional activity. CONCLUSIONS: This study provided a novel concept that STX6 exerted oncogenic effects by activating the STAT3 signaling pathway, and STX6 might be a promising therapeutic target for HCC.
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Type 2 diabetes (T2D), a global health concern, is closely associated with the gut microbiota. Restoration of a balanced microbiota and intestinal homeostasis benefit therapy of T2D. Some special phages may selectively alter the gut microbiota without causing dysbiosis, such as MS2 and P22. However, scarcely systematic analysis of cascading effects triggered by MS2 and P22 phages on the microbiota, as well as interactions between specific gut bacteria and systemic metabolism, seriously inhibit the development of positive interventions of phages. Based on multi-omic analysis, we analyzed the intrinsic correlations among specific microbiota, their bioactive metabolites, and key indicators of T2D. We found that gavage of the MS2-P22 phage cocktail could significantly alter the gut microbiome to attenuate dysbiosis of diabetic C57BL/6 mice caused by high-fat diets (HFDs) and streptozotocin (STZ), by affecting microbial compositions as well as their metabolic pathways and metabolites, especially increasing amounts of short-chain fatty acid-producing (SCFA-producing) bacteria (e.g., Blautia and Romboutsia) and short-chain fatty acids (SCFAs). Correspondingly, a noteworthy reduction in the number of several opportunistic pathogens occurred, e.g., Candidatus Saccharimonas, Aerococcus, Oscillibacter, Desulfovibrio, and Clostridium sensu stricto 1. Synchronously, the levels of proinflammatory cytokines and lipopolysaccharide (LPS) were reduced to recover gut barrier function in T2D mice. These findings might benefit the development of a new dietary intervention for T2D based on phage cocktails. KEY POINTS: ⢠Intestinal barrier integrity of T2D mice is improved by a phage cocktail ⢠Negative relationship between Muribaculaceae and Corynebacterium reshaped gut microbiota ⢠Acetate, propionate, and butyrate decreased the level of proinflammatory factors.
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Bacteriófagos , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Camundongos , Animais , Diabetes Mellitus Tipo 2/terapia , Bacteriófagos/metabolismo , Citocinas , Disbiose/terapia , Camundongos Endogâmicos C57BL , Ácidos Graxos Voláteis/metabolismo , Bactérias/genética , Bactérias/metabolismoRESUMO
INTRODUCTION: There are some problems in the quality control of Epimedii Folium (leaves of Epimedium brevicornum Maxim.), such as the mixed use of Epimedii Folium from different harvesting periods and regions, incomplete quality evaluation, and time-consuming analysis methods. OBJECTIVE: Near-infrared (NIR) spectroscopy was conducted to establish a rapid overall quality evaluation method for Epimedii Folium. MATERIALS AND METHODS: Quantitative models of the total solid, moisture, total flavonoid, and flavonol glycoside (Epimedin A, Epimedin B, Epimedin C, Icariin) contents of Epimedii Folium were established by partial least squares regression (PLSR). The root mean square error (RMSE) and correlation coefficient (R) were used to evaluate the performance of models. The qualitative models of Epimedii Folium from different geographic origins and harvest periods were established based on K-nearest neighbor (KNN), back-propagation neural network (BPNN), and random forest (RF). Accuracy and Kappa values were used to evaluate the performance of models. A new multivariable signal conversion strategy was proposed, which combines NIR spectroscopy with the PLSR model to predict the absorbance values of retention time points in the high-performance liquid chromatography (HPLC) fingerprint to obtain the predicted HPLC fingerprint. The Pearson correlation coefficient and cosine coefficient were used to evaluate the similarity between real and predicted HPLC fingerprints. RESULTS: Qualitative models, quantitative models, and the similarity between real and predicted HPLC fingerprints are satisfactory. CONCLUSION: The method serves as a fast and green analytical quality evaluation method of Epimedii Folium and can replace traditional methods to achieve the overall quality evaluation of Epimedii Folium.
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Quimiometria , Epimedium , Flavonoides , Espectroscopia de Luz Próxima ao Infravermelho , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Epimedium/química , Flavonoides/análise , Análise dos Mínimos Quadrados , Quimiometria/métodos , Folhas de Planta/química , Controle de Qualidade , Cromatografia Líquida de Alta Pressão/métodosRESUMO
BACKGROUND AND AIMS: HCC is one of the main types of primary liver cancer, with high morbidity and mortality and poor treatment effect. Tripartite motif-containing protein 11 (TRIM11) has been shown to promote tumor formation in lung cancer, breast cancer, gastric cancer, and so on. However, the specific function and mechanism of TRIM11 in HCC remain open for study. APPROACH AND RESULTS: Through clinical analysis, we found that the expression of TRIM11 was up-regulated in HCC tissues and was associated with high tumor node metastasis (TNM) stages, advanced histological grade, and poor patient survival. Then, by gain- and loss-of-function investigations, we demonstrated that TRIM11 promoted cell proliferation, migration, and invasion in vitro and tumor growth in vivo. Mechanistically, RNA sequencing and mass spectrometry analysis showed that TRIM11 interacted with pleckstrin homology domain leucine-rich repeats protein phosphatase 1 (PHLPP1) and promoted K48-linked ubiquitination degradation of PHLPP1 and thus promoted activation of the protein kinase B (AKT) signaling pathway. Moreover, overexpression of PHLPP1 blocked the promotional effect of TRIM11 on HCC function. CONCLUSIONS: Our study confirmed that TRIM11 plays an oncogenic role in HCC through the PHLPP1/AKT signaling pathway, suggesting that targeting TRIM11 may be a promising target for the treatment of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinogênese/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Leucina , Neoplasias Hepáticas/patologia , Domínios de Homologia à Plecstrina , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteína Fosfatase 1/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina , Ubiquitina-Proteína Ligases/metabolismoRESUMO
METHODS: Using a retrospective 15-year cohort, stratified by age, this study aimed to analyze the effect of dialysis modality on mortality of ESRD patients in a city of China. Study data were from the medical insurance information system of Kunshan, Jiangsu Province of China, and 1484 patients with ESRD, enrolled from 1 January 2005 to 31 December 2019 were included in this study. The primary outcome event was all-cause mortality, which was calculated in months. Dialysis modalities included hemodialysis (HD) and peritoneal dialysis (PD). Survival analysis and competing-risk regression model were performed in this study. RESULTS: HD costs significantly higher medical expense than the PD treatment regimen. The mean survival time was 121.28 (SE = 3.020) months for HD patients, while that was 94.68 (SE = 3.534) months for the PD. Ten-year survival rates of the young, middle-aged, and elderly were 0.82, 0.56, and 0.26, respectively. For the young (SHR = 0.869, 95% CI: 0.525-1.436) and middle-aged (SHR = 0.715, 95% CI: 0.484-1.057) ESRD patients, different dialysis modalities exhibited no statistical significance on the survival, but for the elderly, HD had a lower risk of mortality than PD (SHR = 0.747, 95% CI: 0.581-0.961). CONCLUSION: Survival of the young and middle-aged ESRD patients was superior to that of the elderly. Considering both survival time and direct medical costs, we recommend that PD could be a better choice for young and middle-aged ESRD patients, while HD may be suitable for older patients.
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Falência Renal Crônica , Diálise Peritoneal , Idoso , Pessoa de Meia-Idade , Humanos , Diálise Renal/efeitos adversos , Estudos de Coortes , Estudos Retrospectivos , Falência Renal Crônica/terapia , Diálise Peritoneal/efeitos adversosRESUMO
Metformin, a traditional first-line pharmacological treatment for type 2 diabetes, has recently been shown to have anti-cancer effects on hepatocellular carcinoma (HCC). However, the molecular mechanism underlying the anti-tumor activity of metformin remains unclear. The Sonic hedgehog (Shh) signaling pathway is closely associated with the initiation and progression of HCC. Therefore, the aim of the current study was to investigate the effects of metformin on the biological behavior of HCC and the underlying functional mechanism of metformin in the Shh pathway. HCC was induced in HepG2 cells using recombinant human Shh (rhShh). The effects of metformin on proliferation and metastasis were evaluated using in vitro proliferation, wound healing, and invasion assays. The mRNA and protein expression levels of proteins related to the Shh pathway were measured using western blotting, quantitative PCR, and immunofluorescence staining. Metformin inhibited rhShh-induced proliferation and metastasis. Furthermore, metformin decreased the mRNA and protein expression of Shh pathway components, including Shh, Ptch, Smo, and Gli-1. Silencing of AMPK in the presence of metformin revealed that metformin exerted its inhibitory effects via AMPK. Our findings demonstrate that metformin suppresses the migration and invasion of HepG2 cells via AMPK-mediated inhibition of the Shh pathway.
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Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Metformina , Proteínas Quinases Ativadas por AMP/metabolismo , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Metformina/farmacologia , Transdução de Sinais , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína GLI1 em Dedos de Zinco/farmacologiaRESUMO
BACKGROUND: Glioma is the most common brain malignant tumor, with a high morbidity rate and a mortality rate of more than three percent, which seriously endangers human health. The main method of acquiring brain tumors in the clinic is MRI. Segmentation of brain tumor regions from multi-modal MRI scan images is helpful for treatment inspection, post-diagnosis monitoring, and effect evaluation of patients. However, the common operation in clinical brain tumor segmentation is still manual segmentation, lead to its time-consuming and large performance difference between different operators, a consistent and accurate automatic segmentation method is urgently needed. With the continuous development of deep learning, researchers have designed many automatic segmentation algorithms; however, there are still some problems: (1) The research of segmentation algorithm mostly stays on the 2D plane, this will reduce the accuracy of 3D image feature extraction to a certain extent. (2) MRI images have gray-scale offset fields that make it difficult to divide the contours accurately. METHODS: To meet the above challenges, we propose an automatic brain tumor MRI data segmentation framework which is called AGSE-VNet. In our study, the Squeeze and Excite (SE) module is added to each encoder, the Attention Guide Filter (AG) module is added to each decoder, using the channel relationship to automatically enhance the useful information in the channel to suppress the useless information, and use the attention mechanism to guide the edge information and remove the influence of irrelevant information such as noise. RESULTS: We used the BraTS2020 challenge online verification tool to evaluate our approach. The focus of verification is that the Dice scores of the whole tumor, tumor core and enhanced tumor are 0.68, 0.85 and 0.70, respectively. CONCLUSION: Although MRI images have different intensities, AGSE-VNet is not affected by the size of the tumor, and can more accurately extract the features of the three regions, it has achieved impressive results and made outstanding contributions to the clinical diagnosis and treatment of brain tumor patients.
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Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Neoplasias Encefálicas/patologia , Aprendizado Profundo , Glioma/patologia , HumanosRESUMO
Foodborne pathogens and microbial toxins are the main causes of foodborne illness. However, trace pathogens and toxins in foods are difficult to detect. Thus, techniques for their rapid and sensitive identification and quantification are urgently needed. Phages can specifically recognize and adhere to certain species of microbes or toxins due to molecular complementation between capsid proteins of phages and receptors on the host cell wall or toxins, and thus they have been successfully developed into a detection platform for pathogens and toxins. This review presents an update on phage-based luminescent detection technologies as well as their working principles and characteristics. Based on phage display techniques of temperate phages, reporter gene detection assays have been designed to sensitively detect trace pathogens by luminous intensity. By the host-specific lytic effects of virulent phages, enzyme-catalyzed chemiluminescent detection technologies for pathogens have been exploited. Notably, these phage-based luminescent detection technologies can discriminate viable versus dead microbes. Further, highly selective and sensitive immune-based assays have been developed to detect trace toxins qualitatively and quantitatively via antibody analogs displayed by phages, such as phage-ELISA (enzyme-linked immunosorbent assay) and phage-IPCR (immuno-polymerase chain reaction). This literature research may lead to novel and innocuous phage-based rapid detection technologies to ensure food safety.
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Bacteriófagos , Bacteriófagos/genéticaRESUMO
The liver has multiple functions that preserve homeostasis. Liver diseases are debilitating, costly and often result in death. Elucidating the developmental mechanisms that establish the liver's architecture or generate the cellular diversity of this organ should help advance the prevention, diagnosis and treatment of hepatic diseases. We previously reported that migration of early hepatic precursors away from the gut epithelium requires the activity of the homeobox gene Prox1. Here, we show that Prox1 is a novel regulator of cell differentiation and morphogenesis during hepatogenesis. Prox1 ablation in bipotent hepatoblasts dramatically reduced the expression of multiple hepatocyte genes and led to very defective hepatocyte morphogenesis. As a result, abnormal epithelial structures expressing hepatocyte and cholangiocyte markers or resembling ectopic bile ducts developed in the Prox1-deficient liver parenchyma. By contrast, excessive commitment of hepatoblasts into cholangiocytes, premature intrahepatic bile duct morphogenesis, and biliary hyperplasia occurred in periportal areas of Prox1-deficient livers. Together, these abnormalities indicate that Prox1 activity is necessary to correctly allocate cell fates in liver precursors. These results increase our understanding of differentiation anomalies in pathological conditions and will contribute to improving stem cell protocols in which differentiation is directed towards hepatocytes and cholangiocytes.
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Ductos Biliares/patologia , Linhagem da Célula , Deleção de Genes , Hepatócitos/metabolismo , Hepatócitos/patologia , Células-Tronco/metabolismo , Proteínas Supressoras de Tumor/deficiência , Envelhecimento/metabolismo , Animais , Animais Recém-Nascidos , Contagem de Células , Linhagem da Célula/genética , Coristoma/patologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Fator 4 Nuclear de Hepatócito/metabolismo , Proteínas de Homeodomínio/metabolismo , Fígado/embriologia , Fígado/metabolismo , Camundongos , Fatores de Transcrição SOX9/metabolismo , Transdução de Sinais/genética , Células-Tronco/patologia , Fator de Crescimento Transformador beta/metabolismo , Proteínas Supressoras de Tumor/metabolismoRESUMO
AIM: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are implicated in many fibrotic diseases, including renal fibrosis. Whether Ginsenoside-Rg1 (G-Rg1) could attenuate renal fibrosis via suppression of ER stress and UPR has not been reported. The aim of this study was to explore the effect of G-Rg1 on ER stress and UPR-induced apoptosis in kidneys with unilateral ureteral obstruction (UUO) rat model. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into control group, model group and G-Rg1 treatment group. G-Rg1 was administered to rats by intraperitoneal injection. Renal interstitial fibrosis in the model group was developed by UUO in rats. Renal function was estimated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). Renal pathological damage was evaluated by hematoxylin and eosin (HE) and Masson's trichrome staining. The ER stress was assessed with glucose-regulated protein (GRP) 78 expression, and the proapoptotic response was detected with CCAAT/enhancer-binding protein homologous protein (CHOP) and caspase-12 expressions by Western Blot. The number of apoptotic cells was determined by Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling (TUNEL) analysis. RESULTS: UUO for 14 days aggravated renal function, renal damage and renal interstitial fibrosis, activated ER stress response (induction of GRP78 protein), enhanced the proapoptotic response (increase in CHOP and caspase-12 proteins) and increased the number of apoptotic cells (shown by the TUNEL assay). Treatment with G-Rg1 significantly ameliorates the renal pathological lesions and decreases expressions of ER stress-associated proteins and the level of apoptotic cells in kidneys. CONCLUSION: G-Rg1 suppresses renal cell apoptotic and fibrotic process partly through inhibition of ERS- and UPR-related apoptotic pathway in the kidneys after UUO.
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Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fibrose/tratamento farmacológico , Ginsenosídeos/administração & dosagem , Rim/patologia , Obstrução Ureteral/patologia , Animais , Nitrogênio da Ureia Sanguínea , Caspase 12/genética , Creatinina/sangue , Proteínas de Choque Térmico/genética , Marcação In Situ das Extremidades Cortadas/métodos , Masculino , Ratos , Ratos Sprague-Dawley , Fator de Transcrição CHOP/genéticaRESUMO
Based on variation of Pinus massoniana families, heritablility and correlation analysis, the contents of shikimic acid and procyanidine (heritability 0.90, 0.70), dry weight of single branch (heritability 0.60) and and leaf length (heritability 0.46) were screened out as quality, yield and harvest cost traits of Folium Pini, respectively. For the different medicinal application of Folium Pini, varied methods were chosen to estimate weight and construct index equation. Weight adjustment based.on equal emphasis were used as economic weight determining method to select the best families, and the index (accuracy 0. 936 4 and heritability 0. 881 6) obtained was a little better than that obtained by equal emphasis, and much better than that by restricted index. The superior families selected with adjustment weight and equal emphasis were No. 46, 43 and 28. Partial regression were used as economic weight determining method to select the best families,and the index obtained had the highest accuracy (0.941 5) , index heritability (0. 889 9) and the genetic gain of shikimic acid content. The superior families selected with this method were No. 46, 27 and 47. No. 46 was the best families with maximal economic benefit. Our study indicated that suitable method for estimate weight and construct index equation can be applied for better accuracy of superior families selection of P. massoniana.
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Medicamentos de Ervas Chinesas/análise , Pinus/química , Plantas Medicinais/química , Cruzamento , Pinus/classificação , Pinus/genética , Pinus/crescimento & desenvolvimento , Folhas de Planta/química , Plantas Medicinais/classificação , Plantas Medicinais/genética , Plantas Medicinais/crescimento & desenvolvimentoRESUMO
STAT (signal transducer and activator of the transcription) proteins, are a group of highly conserved transcription factors and fundamental components of the JAK-STAT signaling pathway. They play crucial roles in a variety of biological processes, such as immunity, proliferation, differentiation, and growth. However, little information is known regarding their role in gonad development and sex determination in mollusks. In this study, we identified 3 STAT genes in Pacific Oyster Crassostrea gigas. Phylogenetic analysis showed that STATs from mollusks were highly conserved, and most of them had four identical motif regions, except for the STAT1 and STAT3 predicted sequences from Crassostrea hongkongensis. Tissue expression analysis indicated CgSTAT1 had a high expression level in most tissues, while CgSTAT3 had a low expression level in most tissues. Expression analysis of early developmental stages showed CgSTAT1 had a higher expression level from egg to D shaped larva and a lower expression level in subsequent stages. In contrast CgSTAT1, CgSTAT2 had a reverse expression pattern. Expression analysis of different developmental stages of diploid gonads indicated that CgSTAT1 had a higher expression level at the S1 and S3 stages relative to the S2 stage in females, while in males the S3 stage had a higher expression than than the S2 stage. The expression level of CgSTAT1 between diploids and triploids in females differed significantly, but there were no significant differences in males. Expression of CgSTAT2 differed significantly between diploid and triploid males. These data suggest an important role for STATs in sex differentiation in diploid and triploid oysters. Our study is the first to explore the role of STATs in sex differentiation and gonadal development in oysters, and will help us better understand the molecular mechanisms of sex differentiation in shellfish.
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Crassostrea , Feminino , Masculino , Animais , Crassostrea/genética , Crassostrea/metabolismo , Triploidia , Filogenia , Gônadas/metabolismo , GenomaRESUMO
T2D and its complications are significant threats to human health and are among the most concerning metabolic diseases worldwide. Previous studies have revealed that Glycyrrhiza uralensis polysaccharide extract (GUP) exhibits remarkable antioxidant capabilities and inhibits alpha-glucosidase activity. However, whether GUP improves glycemic control in T2D is unknown. This study aims to investigate the effects of GUP on glucose and lipid metabolism as well as the intestinal microbiota in HFD/STZ-induced T2D. The results demonstrated that GUP could significantly ameliorate hyperglycemia, insulin resistance, oxidative stress, and reduce liver lipid levels in T2D mice. Furthermore, it also enhanced the integrity of the intestinal barrier in T2D mice by reducing the levels of pro-inflammatory cytokines and serum LPS levels. Interestingly, GUP treatment significantly lowered serum creatinine and urea nitrogen levels, mitigating renal function deterioration and interstitial fibrosis. Additionally, GUP intervention increased the α diversity of gut microbiota, promoting beneficial species like Akkermansia, Lactobacillus, Romboutsia and Faecalibaculum, while decreasing harmful ones such as Bacteroides, Escherichia-Shigella, and Clostridium sensu stricto 1 in T2D mice. Overall, this study highlights the potential of GUP in alleviating complications and enhancing intestinal health in T2D mice, providing valuable insights into dietary strategies for diabetes control and overall health improvement.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Glycyrrhiza uralensis , Camundongos , Humanos , Animais , Glycyrrhiza uralensis/química , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Camundongos Endogâmicos C57BLRESUMO
The endocytosis, intracellular transport, and exocytosis of different-sized nanoparticles were reported to greatly affect their efficacy and biosafety. The quantitation of endocytosis and exocytosis as well as subcellular distribution of nanoparticles might be an effective approach based on transport pathway flux analysis. Thus, the key parameters that could present the effects of three different-sized ultrasmall iron oxide nanoparticles (USIONPs) were systematically investigated in RAW264.7 cells. The endocytosis and exocytosis of USIONPs were related to their sizes; 15.4 nm of S2 could be quickly and more internalized and excreted in comparison to S1 (7.8 nm) and S3 (30.7 nm). In RAW264.7 cells, USIONPs were observed in endosomes, lysosomes, the Golgi apparatus, and autophagosomes via a transmission electron microscope. Based on flux analysis of intracellular transport pathways of USIONPs, it was found that 43% of S1, 40% of S2, and 44% of S3 were individually transported extracellularly through the Golgi apparatus-involved middle-fast pathway, while 24% of S1, 23% of S2, and 26% of S3 were transported through the fast recycling endosomal pathway, and the residues were transported through the slower speed lysosomal pathway. USIONPs might be transported via size-related endocytosis and exocytosis pathways. The pathway flux could be calculated on the basis of disturbance analysis of special transporters as well as their coding genes. Because there were rate differences among these transport pathways, this pathway flux could anticipate the intracellular remaining time and distribution of different-sized nanoparticles, the function exertion, and side effects of nanomaterials. The size of the nanomaterials could be optimized for improving functions and safety.
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The ultrasonically processed Eugenol (EU) and Carvacrol (CAR) nanoemulsions (NE) were successfully optimized via response surface methodology (RSM) to achieve broad spectrum antimicrobial efficacy. These NE were prepared using 2 % (w/w) purity gum ultra (i.e., succinylated starch), 10 % (v/v) oil phase, 80 % (800 W) sonication power, and 10 min of processing time as determined via RSM. The second order Polynomial method was suitable to RSM with a co-efficient of determination >0.90 and a narrow polydispersity index (PDI) ranging 0.12-0.19. NE had small droplet sizes (135.5-160 nm) and low volatility at high temperatures. The EU & CAR entrapment and heat stability (300 °C) confirmed by Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). Further, the volatility of EU & CAR NE was 18.18 ± 0.13 % and 12.29 ± 0.11 % respectively, being lower than that of bulk/unencapsulated EU & CAR (i.e., 23.48 ± 0.38 % and 19.11 ± 0.08 %) after 2 h at 90 °C. Interestingly, both EU & CAR NE showed sustained release behaviour till 48 h. Their digest could inhibit Salmonella typhimurium (S. typhimurium) via membrane disruption and access to cellular machinery as evident from SEM images. Furthermore, in-vivo bio-accessibility of EU & CAR in mice serum was up to 80 %. These cost-effective and short-processed EU/CAR NE have the potential as green preservatives for food industry.
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Anti-Infecciosos , Cimenos , Eugenol , Animais , Camundongos , Eugenol/farmacologia , Eugenol/química , Salmonella typhimurium , Amido/química , Anti-Infecciosos/farmacologia , EmulsõesRESUMO
Gap junctions, formed by gap junction proteins (GJ), play crucial roles in cell signaling and immune responses. The structure and function of the GJ from vertebrates (called connexins) have been extensively studied. However, little is known about the proteins forming gap junctions in invertebrates (called innexins). In this study, 14 GJ genes of Chlamys nobilis were identified. GJ proteins are mainly distributed on the plasma membrane, and all proteins are hydrophilic Phylogenetic tree analysis showed that the GJ proteins in C. nobilis were distantly related to those in vertebrates but closely related to those in invertebrates. Conserved motifs analysis of these GJ proteins in C. nobilis identified to have 10 conserved motifs, similar to gap junction proteins in other bivalves. Moreover, expression profiles of CnGJ genes under chronic and acute low temperature stress were also investigated. Results showed that chronic low temperature stress had a significant effect on the expression levels of CnGJ genes, and the expression profiles of CnGJ genes showed significantly variation under acute low temperature stress. All these results indicated that CnGJ genes play important roles in environmental adaptation in scallops. The present study initially elucidated the function of gap junction genes in noble scallop C. nobilis, which provides new insights into the GJ genes in mollusks and will help us better understand their roles in environmental stress in scallops.
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Mitogen-activated protein kinase kinase (MKK), the key element of the Mitogen-activated protein kinase (MAPK) signaling pathway, is crucial for the immune response to adverse environments in aquatic animals. Nevertheless, there is limited information regarding the role of the MKK gene family in mollusks. In our study, genome data and transcriptome were used to identify four MKK genes (CnMKK4, CnMKK5, CnMKK6, and CnMKK7) in the noble scallop. The result of the gene structure, motif analysis, and phylogenetic tree revealed that MKK genes are relatively conserved in bivalves. Moreover, four CnMKK genes were significantly highly expressed in immune-related tissues, suggesting that CnMKKs may related to bivalve immunity. Furthermore, CnMKK6 and CgMKK4 were significantly differentially expressed (P < 0.05) under 24 h of temperature stress, and all CnMKKs were significantly differentially expressed (P < 0.05) under 24 h of Vibrio parahaemolyticus infection. These results showed that the CnMKKs may have a significant impact under biotic and abiotic stresses. In conclusion, the result of the CnMKKs provides valuable insights into comprehending the function of MKK genes in mollusks.
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Hypericum perforatum L. (HPL), also known as St. John's wort, is one of the extensively researched domestically and internationally as a medicinal plant. In this study, non-targeted metabolomics combined with machine learning methods were used to identify reasonable quality indicators for the holistic quality control of HPL. First, the high-resolution MS data from different samples of HPL were collected, and visualized the chemical compounds through the MS molecular network. A total of 122 compounds were identified. Then, the orthogonal partial least squares-discriminant analysis (OPLS-DA) model was established for comparing the differences in metabolite expression between flower, leaf, and branches. A total of 46 differential metabolites were screened out. Subsequently, analyzing the pharmacological activities of these differential metabolites based on protein-protein interaction (PPI) network. A total of 25 compounds associated with 473 gene targets were retrieved. Among them, 13 highly active compounds were selected as potential quality markers, and five compounds were ultimately selected as quality control markers for HPL. Finally, three different classifiers (support vector machine (SVM), random forest (RF), and K-nearest neighbor (KNN)) were used to validate whether the selected quality control markers are qualified. When the feature count is set to 122 and 46, the RF model demonstrates optimal performance. As the number of variables decreases, the performance of the RF model degrades. The KNN model and the SVM model also exhibit a decrease in performance but still manage to satisfy the intended requirements. The strategy can be applied to the quality control of HPL and can provide a reference for the quality control of other herbal medicines.
Assuntos
Hypericum , Aprendizado de Máquina , Metabolômica , Controle de Qualidade , Espectrometria de Massas em Tandem , Hypericum/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Metabolômica/métodos , Máquina de Vetores de Suporte , Extratos Vegetais/química , Extratos Vegetais/análise , Análise dos Mínimos Quadrados , Mapas de Interação de Proteínas/efeitos dos fármacos , Análise Discriminante , Plantas Medicinais/químicaRESUMO
Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis. Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness. Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated. Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.
RESUMO
BACKGROUND: This study sought to compare the clinical outcomes of upper versus whole-neck prophylactic irradiation in the treatment of patients with node-negative nasopharyngeal carcinoma (NPC). METHODS: Between November 2005 and June 2012, 301 patients with node-negative NPC were randomly assigned to receive primary plus prophylactic upper neck irradiation (UNI, 153 patients) or primary plus whole-neck irradiation (WNI, 148 patients). Patients in both groups received irradiation to the primary tumor and the upper neck nodal regions, and patients in the WNI group also received irradiation to the lower neck. The main endpoint of the study was to compare the lower neck control rate between the 2 groups. RESULTS: With a median follow-up period of 39 months (range, 6-84 months), no patient in either group had a cervical node relapse. The overall survival at 3 years was 89.5% (95% confidence interval [CI] = 84.1%-95.0%) in the UNI group and 87.4% (95% CI = 81.4%-93.5%) in the WNI group (hazard ratio [HR] = 0.866, 95% CI = 0.41-1.82; P = .70). The 3-year relapse-free survival rate was 89.8% and 89.3% (95% CI = 84.2%-95.3% and 83.7%-94.8%, HR = 0.914, 95% CI = 0.42-2.00; P = .82), and the 3-year metastasis-free survival rate was 91.7% and 90.9% (95% CI = 87.0%-96.5% and 85.7%-96.1%) for the UNI and WNI groups, respectively (HR = 1.007, 95% CI = 0.44-2.32; P = .99). CONCLUSIONS: Prophylactic upper neck irradiation is sufficient for patients with node-negative NPC.