Background
Long non-coding RNAs (lncRNAs) have been increasingly uncovered to participate in multiple human cancers, including pancreatic cancer (PC). However, the underlying mechanisms of most of ...the lncRNAs have not been fully understood yet.
Aims
In this study, we probed the role and latent mechanism of LINC01420 in PC.
Methods
Several online tools were applied. Gene expression was evaluated by qRT-PCR or Western blot. Both in vitro and in vivo assays were conducted to probe LINC01420 function in PC. ChIP, RIP, and luciferase reporter assays were performed to determine relationships between genes.
Results
The bioinformatics analyses revealed LINC01420 was highly expressed in PC tissues. Besides, LINC01420 was pronouncedly upregulated in PC cell lines and its depletion controlled PC cell proliferation and EMT in vitro and hindered tumor growth in vivo. Importantly, KRAS was proved to mediate LINC01420-facilitated PC cell proliferation. Further, we explained that KRAS transcription was regulated by MYC, while LINC01420 enhanced the binding of MYC to KRAS promoter in the nucleus of PC cells. Intriguingly, LINC01420 boosted MYC expression in the cytoplasm of PC cells by sponging miR-494-3p.
Conclusion
This study illustrated that LINC01420 accelerates PC progression through releasing miR-494-3p-silenced MYC in cytoplasm and upregulating MYC-activated KRAS in nucleus, unveiling LINC01420 as a latent therapeutic strategy for PC patients.
Gastric cancer is one of the most common cancers leading to tumor-related deaths worldwide. Chicoric acid (CA) exhibits a variety of protective effects in different diseases. However, its role in ...regulating tumor progression has not been reported. Autophagy, as a conserved catabolic process, sustains cellular homoeostasis responding to stress to modulate cell fate. In the study, the effects of CA on gastric cancer were investigated. The results indicated that CA treatment markedly reduced the cell viability and induced apoptosis in gastric cancer cells, and prevented tumor growth in an established xenograft gastric cancer model. Furthermore, CA exposure significantly induced autophagy both in gastric cancer cells and tumor samples, as evidenced by the up-regulated expression of LC3II. Moreover, phosphorylated AMP-activated protein kinase (AMPK) and p70S6 kinase (p70s6k) expression were obviously promoted by CA in vitro and in vivo. Importantly, blocking AMPK activation abrogated CA-induced expression of LC3II in gastric cancer cells. In addition, endoplasmic reticulum (ER) stress in tumor samples or cells was markedly induced by CA treatment through promoting the expression of associated signals such as Parkin, protein kinase RNA-like ER kinase (PERK), activating transcription factors 4 (ATF4) and ATF6. Importantly, these effects were abolished by the inhibition of AMPK signaling. Collectively, our findings indicated that CA prevents human gastric cancer progression by inducing autophagy partly through the activation of AMPK, and represents an effective therapeutic strategy against gastric cancer development.
This article presents investigation of the flavor profile on 5 different regional Chinese smoked chicken samples using gas chromatography−ion mobility spectrometry analysis methods. Five batches of ...samples were obtained over the course of 6 mo. A total of 34 flavor substances were identified in the 5 smoked chicken samples, including 10 aldehydes, 7 alcohols, 4 ketones, 2 hydrocarbons, 3 heterocyclic compounds, 4 esters, 2 ethers, and 2 phenolic compounds. The whole spectral fingerprint visually displayed flavor differences and relations in 5 types of smoked chicken with local characteristics. Moreover, the orthogonal projections to latent structures discriminant analysis model revealed that these samples could be separately classified into 5 groups. Multivariate statistical analysis showed that 20 chemicals with higher Variable Importance for the Projection values were the key contributors to the differences of flavor in these 5 kinds of smoked chicken. N-nonanal, heptanal, n-nonanal, heptanal, furfurol, and hexanal were the main common flavor compounds in the 5 types of Chinese smoked chicken, whereas linalool, alpha-terpineol, 1,8-cineole, and anethole were the main characteristic flavor compounds of Goubangzi chicken (No. 1); gamma-butyrolactone, 2-acetylfuran, 2-methoxyphenol, 2-acetylpyrrole, and limonene were determined as the key flavor compounds of Liaocheng chicken (No. 2); the concentration of octanal and n-nonanal was higher in Tangqiao chicken (No. 3); butyl acetate was the key contributor to the flavor compounds of Jinshan chicken (No. 4). 2-Heptanone and 2-pentylfuran had a high correlation with Zhuozishan chicken (No. 5). The different raw materials and ingredients used, especially the method of preparation and cultural differences, in different regions of the country in China were the main reasons leading to the similarities and differences of volatile compounds in the 5 kinds of Chinese traditional smoked chicken.
Permanent neonatal diabetes mellitus (PNDM) can be caused by insulin mutations. We generated induced pluripotent stem cells from fibroblasts of a patient with PNDM and undetectable insulin at birth ...due to a homozygous mutation in the translation start site of the insulin gene. Differentiation of mutant cells resulted in insulin-negative endocrine stem cells expressing MAFA, NKX6.1, and chromogranin A. Correction of the mutation in stem cells and differentiation to pancreatic endocrine cells restored insulin production and insulin secretion to levels comparable to those of wild-type cells. Grafting of corrected cells into mice, followed by ablating mouse β cells using streptozotocin, resulted in normal glucose homeostasis, including at night, and the stem cell-derived grafts adapted insulin secretion to metabolic changes. Our study provides proof of principle for the generation of genetically corrected cells autologous to a patient with non-autoimmune insulin-dependent diabetes. These cases should be readily amenable to autologous cell therapy.
•Neonatal diabetes due to homozygous mutation in the start codon of the insulin gene•iPSCs with INSATG>ATA mutation give rise to hormone-negative endocrine cells•Gene correction restores insulin production•Insulin-producing cells protect mice from diabetes
Stem cells from a subject with diabetes due to a mutation in the insulin locus can be corrected and insulin secretion restored. Grafted cells protect a mouse model from diabetes. This is a proof of principle for cell replacement for an insulin-dependent form of diabetes. Due to absence of autoimmunity such cases may be suitable for autologous cell therapy.
In this paper, the volatile compounds and profile of sugar-smoked chicken thighs were studied, which were proceed by using dividual smoking materials such as sucrose, maltose, glucose, fructose and ...xylose. A total of 33 volatile compounds in sugar-smoked samples were identified and quantitated by gas chromatography/mass spectrometry (GC/MS). The furfural, 5-methylfurfural, 1-octene-3-ol, hexanal, heptanal and nonanal were the most important volatile compounds with odour activity values (OAVs) greater than 1, among which furfural and 5-methylfurfural contributed mainly to the smoky aroma. The sucrose, glucose and fructose pyrolysis all produced high yield of furans, such as furfural (FF) and 5-hydroxymethylfurfural (5-HMF) based on pyrolysis mass spectrometry and gas chromatography/mass spectrometry (Py-GC/MS). During the smoking process, then the 5-HMF pyrolyzed into 5-methylfurfural. The sucrose was the good carbohydrate to form furans with smoky aroma.
7-Met, a derivative of soybean isoflavone, is a natural flavonoid compound that has been reported to have multiple signaling pathways regulation effects. This study investigated the therapeutic ...effects of 7-Met on mice with atopic dermatitis induced by fluorescein isothiocyanate (FITC), or oxazolone (OXZ). 7-Met ameliorated FITC or OXZ-induced atopic dermatitis symptoms by decreasing ear thickness, spleen index, mast cell activation, neutrophil infiltration and serum IgE levels in female BALB/c mice. In FITC-induced atopic dermatitis mice, 7-Met reduced Th1 cytokines production and regulated Th1/Th2 balance by downregulating the secretion of thymic stromal lymphopoietin (TSLP) via inactivation of the NF-κB pathway. In OXZ-induced atopic dermatitis, 7-Met functioned through the reduction of Th17 cytokine production. Our study showed that 7-Methoxyisoflavone alleviated atopic dermatitis by regulating multiple signaling pathways and downregulating chemokine production.
The whey protein β-lactoglobulin (BLG) is a major milk allergen which is absent in human milk. Here, we for the first time generated DNA-free BLG bi-allelic knockout cow by zinc-finger nuclease ...(ZFNs) mRNA and produced BLG-free milk. According to the allergenicity evaluation of BLG-free milk, we found it can trigger lower allergic reaction of Balb/c mice including the rectal temperature drop and the allergen-specific immunoglobulin IgE production; BLG free-milk was easily digested by pepsin at 2 min, while BLG in control milk was still not completely digested after 60 min, and the binding of IgE from cow's milk allergy (CMA) patients to BLG free-milk was significantly lower than that to the control milk. Meanwhile, the genome sequencing revealed that our animal is free of off-target events. Importantly, editing animal genomes without introducing foreign DNA into cells may alleviate regulatory concerns related to foods produced by genome edited animals. Finally, the ZFNs-mediated targeting in cow could be transmitted through the germline by breeding. These findings will open up unlimited possibilities of modifying milk composition to make it more suitable for human health and also improve the functional properties of milk.
Transposon-associated ribonucleoprotein TnpB is known to be the ancestry endonuclease of diverse Cas12 effector proteins from type-V CRISPR system. Given its small size (408 aa), it is of interest to ...examine whether engineered TnpB could be used for efficient mammalian genome editing. Here, we showed that the gene editing activity of native TnpB from Deinococcus radiodurans (ISDra2 TnpB) in mouse embryos was already higher than previously identified small-sized Cas12f1. Further stepwise engineering of noncoding RNA (ωRNA or reRNA) component of TnpB significantly elevated the nuclease activity of TnpB. Notably, an optimized TnpB-ωRNA system could be efficiently delivered in vivo with single adeno-associated virus (AAV) and corrected the disease phenotype in a tyrosinaemia mouse model. Thus, the engineered miniature TnpB system represents a new addition to the current genome editing toolbox, with the unique feature of the smallest effector size that facilitate efficient AAV delivery for editing of cells and tissues.
In this paper, an Ag nanoparticles (AgNPs) modified multimode fiber (MMF) SERS probe prepared based on sol self-assembly method is proposed and fabricated. Different fiber SERS probes (AgNPs-MMF-x, x ...is the self-assembly time) are obtained by adjusting the self-assembly time. Using rhodamine 6G (R6G) solution as the probe molecule, the far-end performances of the prepared fiber SERS probe are studied, and the AgNPs-MMF-30 probe with obvious advantages in SERS performance is obtained. The limit of detection (LOD) for R6G is as low as 10 −9 M, demonstrating the high sensitivity of AgNPs-MMF-30 probe. The enhancement factor (EF) of AgNPs-MMF-30 probe to 10 −7 M R6G is about 1.36 × 10 8 . In addition, the AgNPs-MMF-30 probe has an outstanding reproducibility across the entire area with the maximum value of relative standard deviation (RSD) of less than 10.94%. The AgNPs-MMF-30 probe exhibit a long-term stability regarding Raman enhancement of up to 35 days. Importantly, the high-performance AgNPs-MMF-30 probe is further applied as a highly sensitive SERS platform for the trace detection of antibiotic in milk. The fiber SERS probe has the characteristics of fast, effective, remote real-time detection and so on, so it has great potential application in biochemical sensing and food security.
This study was intended to characterize six types of commercial smoked chicken products in China by using gas chromatography-mass spectrometry (GC-MS), odor-activity values (OAVs), and sensory ...evaluation. Results demonstrated that a total of 89 components were identified in all samples, and 34 were considered as odor-active compounds because their OAVs were greater than one. Liaocheng Chicken that smoked with fruit tree sawdust had more phenols, which contributed to the smoky aroma. Jinshan and Goubangzi Chicken that smoked with sugar had more furans which contributed the overall odor with sweety and caramel aroma. Zhuozishan and Laoting Chicken that smoked with sugar and wood chips had similar flavor and volatile compounds. Tengqiao Chicken that smoked with sugar, tea and rice had significant difference with other chicken in smoky, bittern and caramel aroma (P< .05). The diversity of these smoked chicken flavors was mainly due to the cooking culture differences.
PDF
