Food-grade emulsion gels and oleogels prepared by all-natural dual nanofibril system from citrus fiber and glycyrrhizic acid.

The natural dual nanofibril system consisting of the rigid semicrystalline nanofibrils disintegrated from citrus fiber (CF) and soft semiflexible nanofibrils self-assembled from glycyrrhizic acid (GA) has been recently shown to be effective structural building blocks for fabrication of emulsion gels. In this work, the effect of the CF nanofibrils prepared by different mechanical disintegration approaches (i.e., high-pressure microfluidization and hydrodynamic cavitation) on the interfibrillar CF-GA interactions and the subsequent formation and properties of emulsion gels were investigated, with the aim of evaluating the potential of the dual nanofibril-stabilized emulsion gels as templates for synthesizing all-natural edible oleogels. The obtained results demonstrate that compared to the cavitation, the high-pressure microfluidization is more capable of generating CF nanofibrils with a higher degree of nanofibrillation and individualization, thus forming a denser CF-GA gel network with higher viscoelasticity and structural stability due to the stronger multiple intrafibrillar and interfibrillar interactions. The emulsion gels stabilized by the dual nanofibril system are demonstrated to be an efficient template to fabricate solid-like oleogels, and the structural properties of the oleogels can be well tuned by the mechanical disintegration of CF and the GA nanofibril concentration. The prepared oleogels possess high oil loading capacity, dense network microstructure, superior rheological and large deformation compression performances, and satisfactory thermal stability, which is attributed to the compact and ordered CF-GA dual nanofibrillar network via multiple hydrogen-bonding interactions in the continuous phase as well as at the droplet surface. This study highlights the unique use of all-natural dual nanofibrils to develop oil structured soft materials for sustainable applications.

Exosomes derived from periodontitis induce hepatic steatosis through the SCD-1/AMPK signaling pathway.

AIM: To investigate the impact of exosomes released by Porphyromonas gingivalis-Lipopolysaccharide activated THP-1 macrophages and human periodontal ligament fibroblasts on hepatocyte fat metabolism. RESULTS: The liver of rats with experimental periodontitis showed obvious steatosis and inflammation compared with control rats. The culture supernatant of macrophages and human periodontal ligament fibroblasts (hPDLFs), when stimulated with Pg-LPS, induced lipogenesis in HepG2 cells. Furthermore, the lipid-promoting effect was effectively inhibited by the addition of the exosome inhibitor GW4869. Subsequently, we isolated exosomes from cells associated with periodontitis. Exosomes released by Pg-LPS-stimulated macrophages and hPDLFs are taken up by hepatocytes, causing mRNA expression related to fat synthesis, promoting triglyceride synthesis, and aggravating NAFLD progression. Finally, two sets of exosomes were injected into mice through the tail vein. In vivo experiments have also demonstrated that periodontitis-associated exosomes promote the development of hepatic injury and steatosis, upregulate SCD-1 expression and inhibit the AMPK signaling pathway. CONCLUSIONS: In conclusion, we found that exosomes associated with periodontitis promote hepatocyte adipogenesis by increasing the expression of SCD-1 and suppressing the AMPK pathway, which indicates that close monitoring of the progression of stomatopathy associated extra-oral disorders is important and establishes a theoretical foundation for the prevention and management of fatty liver disease linked to periodontitis.

[Screening for Characteristic Genes of Different Traditional Chinese Medicine Syndromes of Psoriasis Vulgaris: A Study Based on Bioinformatics and Machine Learning]. / ç”Ÿç‰©ä¿¡æ¯å­¦å’Œæœºå™¨å­¦ä¹ ç­›é€‰é“¶å±‘ç— ä¸­åŒ»è¯åž‹ç‰¹å¾åŸºå› .

Objective: To screen for the key characteristic genes of the psoriasis vulgaris (PV) patients with different Traditional Chinese Medicine (TCM) syndromes, including blood-heat syndrome (BHS), blood stasis syndrome (BSS), and blood-dryness syndrome (BDS), through bioinformatics and machine learning and to provide a scientific basis for the clinical diagnosis and treatment of PV of different TCM syndrome types. Methods: The GSE192867 dataset was downloaded from Gene Expression Omnibus (GEO). The limma package was used to screen for the differentially expressed genes (DEGs) of PV, BHS, BSS, and BDS in PV patients and healthy populations. In addition, KEGG (Kyoto Encyclopedia of Genes and Genes) pathway enrichment analysis was performed. The DEGs associated with PV, BHS, BSS, and BDS were identified in the screening and were intersected separately to obtain differentially characterized genes. Out of two algorithms, the support vector machine (SVM) and random forest (RF), the one that produced the optimal performance was used to analyze the characteristic genes and the top 5 genes were identified as the key characteristic genes. The receiver operating characteristic (ROC) curves of the key characteristic genes were plotted by using the pROC package, the area under curve (AUC) was calculated, and the diagnostic performance was evaluated, accordingly. Results: The numbers of DEGs associated with PV, BHS, BSS, and BDS were 7699, 7291, 7654, and 6578, respectively. KEGG enrichment analysis was focused on Janus kinase (JAK)/signal transducer and activator of transcription (STAT), cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), apoptosis, and other pathways. A total of 13 key characteristic genes were identified in the screening by machine learning. Among the 13 key characteristic genes, malectin (MLEC), TUB like protein 3 (TULP3), SET domain containing 9 (SETD9), nuclear envelope integral membrane protein 2 (NEMP2), and BTG anti-proliferation factor 3 (BTG3) were the key characteristic genes of BHS; phosphatase 15 (DUSP15), C1q and tumor necrosis factor related protein 7 (C1QTNF7), solute carrier family 12 member 5 (SLC12A5), tripartite motif containing 63 (TRIM63), and ubiquitin associated protein 1 like (UBAP1L) were the key characteristic genes of BSS; recombinant mouse protein (RRNAD1), GTPase-activating protein ASAP3 Protein (ASAP3), and human myomesin 2 (MYOM2) were the key characteristic genes of BDS. Moreover, all of them showed high diagnostic efficacy. Conclusion: There are significant differences in the characteristic genes of different PV syndromes and they may be potential biomarkers for diagnosing TCM syndromes of PV.

Multiple neuroendocrine tumors in the stomach, duodenum and pancreas of a MEN1 patient.

Gastrinoma, a common type of GEP-NENs, is often sporadic, rarely manifested as multiple endocrine neoplasia type 1 (MEN1). We described a rare case of MEN1-related gastrinomas in the stomach, duodenum and pancreas along with lymph node metastases. The female patient had a long history of recurrent abdominal pain and diarrhea. G1 neuroendocrine tumors were diagnosed by endoscopic biopsy in the pylorus, duodenal bulb and the neck of the pancreas successively. Her symptoms lessened and serum gastrin level decreased after surgery. This case will help us learn more about MEN1-associated patients who are confirmed with multiple neuroendocrine tumors.

Evaluation of Taraxacum mongolicum flavonoids in diets for Channa argus based on growth performance, immune responses, apoptosis and antioxidant defense system under lipopolysaccharide stress.

To ascertain the effects of Taraxacum mongolicum flavonoids (TMF) on the growth performance, digestive enzyme activity, immune indices, inflammatory response and antioxidant capacity of Channa argus, 400 C. argus with an average body weight of (8.08 ± 0.21) g were selected and divided randomly into four groups. They were fed with four experimental diets supplemented with TMF of 0 (control), 25, 50 and 100 mg/kg for 56 d, and then challenged with lipopolysaccharide (LPS) for 96 h, afterwards indices were detected. The results manifested that the addition of TMF above 50 mg/kg in the dietary could significantly improve the final body weight, WGR, SGR and PER of C. argus, while decreased FCR (P < 0.05). Similarly, the 50 mg/kg group had the highest activity of digestive enzymes (protease, lipase, amylase) in intestine and hepatopancreas, which were notably higher than those in the control group (P < 0.05). Nevertheless, 100 mg/kg group could effectively inhibit the liver and gut injury caused by LPS and reduce the contents of ALT and AST, LPS and LBP in serum. In the immune (LY, AKP, ACP, IgM, C3) and antioxidant (T-AOC, SOD, CAT, GSH-PX, GR, ASA, MDA) systems, 100 mg/kg groups were the optimal group, which were remarkably higher than those of the control group (P < 0.05). Additionally, the expression of genes revealed that 100 mg/kg group could noteworthy restrain the expression of pro-inflammatory factors (tnf-α, il-1ß, il-8) and pro-apoptosis (cas-3,8,9, p53, bax, bcl-2) related genes, up-regulate the expression of anti-inflammatory (il-10, tgf-ß) factors, antioxidant-related (nrf2, gpx, gst, cat) genes and heat shock proteins (hsp70, hsp90). Simultaneously, the survival rate of C. argus in the 100 mg/kg TMF-supplemented group was the highest after LPS challenge. Our results elucidate that dietary supplementation TMF protects C. argus from LPS-induced inflammatory injury, to ameliorate digestion, immune response, antioxidant status and apoptosis, implying that TMF could be regarded as an anti-inflammatory and antioxidant agent adding to aquatic animal feed.

Convergence between germline and somatic mutations in pancreatic neuroendocrine tumors.

Objectives: The pancreatic neuroendocrine tumors (PanNETs) are a group of clinically heterogeneous neoplasms. Although previous studies illustrated the somatic mutation pattern for PanNETs, the germline mutation pattern is still unclear. Here, we comprehensively screened the underlying germline mutations in a cohort of multiple endocrine neoplasia type 1 (MEN1)-related and sporadic PanNETs to reveal the characteristics of germline mutation in PanNET patients. Methods: Patients diagnosed with PanNETs by biopsy or surgical pathology were enrolled in this study. Peripheral blood samples were used for genomic DNA purification and subsequent sequencing. The following sequencing techniques were used and compared for validation: (1) targeted gene capture with a customized panel; (2) whole exome sequencing data from previous study. Results: A total of 184 PanNET patients were enrolled, including 20 MEN1-related and 164 sporadic cases. In this study, MEN1 mutation rate in MEN1-related PanNETs was 60% (12/20), of which 50% were novel mutation sites. For sporadic PanNETs, the overall germline mutation rate was very low. Besides the rare MEN1 mutation, previously unreported germline variant in DAXX was found in one non-functional PanNET. Conclusions: This study revealed distinctive germline mutation rates between MEN1-related and sporadic PanNETs. The novel MEN1 mutations contribute to revealing the spectrum of MEN1 mutations in PanNETs. The newly discovered germline variant of DAXX in sporadic PanNET implies a tendency of convergence between germline and somatic mutation genes.

Tailoring structure and properties of long-lived emulsion foams stabilized by a natural saponin glycyrrhizic acid: Role of oil phase.

Novel supramolecular nanofibrils assembled from food-grade saponin glycyrrhizic acid (GA) are effective building blocks to make complex multiphase systems, e.g., emulsion foams. In this work, the effects of different oil phases (castor oil, sunflower oil, dodecane, and limonene) on the formation, stability and structural properties of long-lived emulsion foams prepared by GA nanofibrils (GNs) were investigated. The obtained results showed that soft-solid emulsion foams (4 wt% GNs) can be fabricated, independently of oil phase, and their structural properties, viscoelasticity, and tribological properties can be well tuned by oil phase polarity. Compared to the GNs aqueous foams, the presence of jammed emulsion droplets in the liquid channels and at the surfaces of bubbles can provide a higher bubble stability for emulsion foams. For more polar oil phase (castor oil), GNs showed a higher affinity to the oil-water interface with a lower interfacial tension, thus forming smaller oil droplets and bubbles, which leads to the higher mechanical strength, denser network microstructures, and lower friction coefficients of emulsion foams. However, the limonene foam exhibited weak storage stability and rheological properties, as well as the relatively low lubrication, which may be related to the formation of oil droplet aggregates and clusters induced by the volatility of limonene. GN-based emulsion foams are thermoresponsive, independently of oils, and the temperature-switchable process for the destabilization and regeneration of foams can be controlled and repeated. These emulsion foams based on natural saponin nanofibrils with tunable properties have potential sustainable applications in foods, pharmaceuticals, and personal care products.

Mutant Kras co-opts a proto-oncogenic enhancer network in inflammation-induced metaplastic progenitor cells to initiate pancreatic cancer.

Kras-activating mutations display the highest incidence in pancreatic ductal adenocarcinoma. Pancreatic inflammation accelerates mutant Kras-driven tumorigenesis in mice, suggesting high selectivity in the cells that oncogenic Kras transforms, although the mechanisms dictating this specificity are poorly understood. Here we show that pancreatic inflammation is coupled to the emergence of a transient progenitor cell population that is readily transformed in the presence of mutant KrasG12D. These progenitors harbor a proto-oncogenic transcriptional program driven by a transient enhancer network. KrasG12D mutations lock this enhancer network in place, providing a sustained Kras-dependent oncogenic program that drives tumors throughout progression. Enhancer co-option occurs through functional interactions between the Kras-activated transcription factors Junb and Fosl1 and pancreatic lineage transcription factors, potentially accounting for inter-tissue specificity of oncogene transformation. The pancreatic ductal adenocarcinoma cell of origin thus provides an oncogenic transcriptional program that fuels tumor progression beyond initiation, accounting for the intra-tissue selectivity of Kras transformation.

Novel technologies in cfDNA analysis and potential utility in clinic.

The profiling of plasma cell-free DNA (cfDNA) is becoming a valuable tool rapidly for tumor diagnosis, monitoring and prognosis. Diverse plasma cfDNA technologies have been in routine or emerging use, including analyses of mutations, copy number alterations, gene fusions and DNA methylation. Recently, new technologies in cfDNA analysis have been developed in laboratories, and potentially reflect the status of epigenetic modification, the immune microenvironment and the microbiome in tumor tissues. In this review, the authors discuss the principles, methods and effects of the current cfDNA assays and provide an overview of studies that may inform clinical applications in the near future.

Synthesis of imidazo[1,2-c]thiazoles through Pd-catalyzed bicyclization of tert-butyl isonitrile with thioamides.

Building new biological molecules is challenging. Herein, imidazo[1,2-c]thiazoles were synthesized as a new class of heterobicyclic analogs through Pd-catalyzed cascade bicyclization from isonitriles with thioamides. The bicyclic scaffolds were constructed by inserting three molecules of isonitrile into two molecules of thioamide and then cyclizing them in a one-pot procedure. In vitro antitumor studies of these new compounds were conducted by using the MTT assay, and compound 3c showed excellent inhibitory effects against HepG2 at 7.06 ± 0.68 µM.

Functions of pancreatic stellate cell-derived soluble factors in the microenvironment of pancreatic ductal carcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer with poor prognosis because it is highly resistant to traditional chemotherapy and radiotherapy and it has a low rate of surgical resection eligibility. Pancreatic stellate cells (PSC) have become a research hotspot in recent years, and play a vital role in PDAC microenvironment by secreting soluble factors such as transforming growth factor ß, interleukin-6, stromal cell-derived factor-1, hepatocyte growth factor and galectin-1. These PSC-derived cytokines and proteins contribute to PSC activation, participating in PDAC cell proliferation, migration, fibrosis, angiogenesis, immunosuppression, epithelial-mesenchymal transition, and chemoradiation resistance, leading to malignant outcome. Consequently, targeting these cytokines and proteins or their downstream signaling pathways is promising for treating PDAC.