RNA interference (RNAi) is a natural process through which double‐stranded RNA molecules can silence the gene carrying the same code as the particular RNA of interest. In 2006, the discovery of RNAi ...was awarded the Nobel Prize in Medicine and its success has accumulated since. Gene silencing through RNAi has been used successfully in a broad range of diseases, and, more recently, this technique has gained interest in the field of organ transplantation. Here, genes related to ischemia‐reperfusion injury (IRI) or graft rejection may be silenced to improve organ quality after transplantation. Several strategies have been used to deliver siRNA, and pretransplant machine perfusion presents a unique opportunity to deliver siRNA to the target organ during ex situ preservation. In this review, the potential of RNAi in the field of organ transplantation will be discussed. A brief overview on the discovery of RNAi, its mechanism, and limitations are included. In addition, studies using RNAi to target genes related to IRI in liver, kidney, lung, and heart transplantation are discussed.
Gene silencing through RNA interference during organ preservation can improve outcomes after transplantation.
Bile secretion and composition reflects the functional status of hepatocytes and cholangiocytes. Bile composition can have a role in the assessment of donor grafts before implantation in the ...recipient. In addition, changes in bile composition after liver transplantation can serve as a diagnostic and prognostic tool to predict posttransplant complications, such as primary nonfunction, acute cellular rejection, or nonanastomotic biliary strictures. With the popularization of liver machine perfusion preservation in the clinical setting, there is a revisited interest in biliary biomarkers to assess graft viability before implantation. This review discusses current literature on biliary biomarkers that could predict or assess liver graft and bile duct viability. Bile composition offers an exciting and novel perspective in the search for reliable hepatocyte and cholangiocyte viability biomarkers.
The transplant community continues to be challenged by the disparity between the need for liver transplantation and the shortage of suitable donor organs. At the same time, the number of unused donor ...livers continues to increase, most likely attributed to the worsening quality of these organs. To date, there is no reliable marker of liver graft viability that can predict good posttransplant outcomes. Ex situ machine perfusion offers additional data to assess the viability of donor livers before transplantation. Hence, livers initially considered unsuitable for transplantation can be assessed during machine perfusion in terms of appearance and consistency, hemodynamics, and metabolic and excretory function. In addition, postoperative complications such as primary nonfunction or posttransplant cholangiopathy may be predicted and avoided. A variety of viability criteria have been used in machine perfusion, and to date there is no widely accepted composition of criteria for clinical use. This review discusses potential viability markers for hepatobiliary function during machine perfusion, describes current limitations, and provides future recommendations for the use of viability criteria in clinical liver transplantation.
Humans often respond to sensory impulses provided by aromas, and current trends have generated interest in natural sources of fragrances rather than the commonly used synthetic additives. For the ...first time, the resulting aroma of a selected culture of Thymus mastichina L. was studied as a potential food ingredient. In this context, dried (DR) and fresh (FR) samples were submitted to carbon dioxide (CO2) supercritical extraction (SFE) and hydrodistillation (HD) methods. The extracts were characterised according to their volatile composition by GC-MS, cytotoxicity against a non-tumour cell culture, and sensory attributes (odour threshold and olfactive descriptors). The most abundant aromas were quantified, and the analysis performed by GC-MS revealed an abundance of terpenoids such as thymol chemotype, followed by the precursors α-terpinene and p-cymene. DR and FR extracts (EX) obtained from SFE-CO2 show the highest content of thymol, achieving 52.7% and 72.5% of the isolated volatile fraction. The DR essential oil (EO) contained the highest amount of terpenoids, but it was also the most cytotoxic extract. In contrast, SFE-CO2 products showed the lowest cytotoxic potential. Regarding FR-OE, it had the lowest extraction yield and composition in aroma volatiles. Additionally, all samples were described as having green, fresh and floral sensory notes, with no significant statistical differences regarding the odour detection threshold (ODT) values. Finally, FR-EX of T. mastichina obtained by SFE-CO2 presented the most promising results regarding food application.
•Microencapsulation has numerous industrial applications.•The choice of the appropriate technique depends on several factors.•Coacervation is one of the preferable techniques to encapsulate essential ...oils.•Microencapsulation efficiency depends on several variables.•The release profile of essential oils can be explained by a diffusion mechanism.
Microencapsulation provides an important tool for cosmetic and/or pharmaceutical industry, enabling protection and controlled release of several active agents. The encapsulation of essential oils in core–shell or matrix particles has been investigated for various reasons, e.g., protection from oxidative decomposition and evaporation, odor masking or merely to act as support to ensure controlled release. A large number of microencapsulation methods have been developed in order to be adapted to different types of active agents and shell materials, generating particles with a variable range of sizes, shell thicknesses and permeability, providing a tool to modulate the release rate of the active principle.
With this work, an overview regarding properties and applications of essential oils and biodegradable polymers in the cosmetic field, focusing the use of polylactide as the base material to encapsulate thyme oil, as well as of microencapsulation processes with a particular emphasis on the coacervation, will be presented.
The recovery of biomolecules from food industry by-products is of major relevance for a circular economy strategy. However, by-products' contamination with mycotoxins represents a drawback for their ...reliable valorization for food and feed, hampering their application range, especially as food ingredients. Mycotoxin contamination occurs even in dried matrices. There is a need for the implantation of monitoring programs, even for by-products used as animal feed, since very high levels can be reached. This systematic review aims to identify the food by-products that have been studied from 2000 until 2022 (22 years) concerning mycotoxins' contamination, distribution, and prevalence in those by-products. PRISMA ("Preferred Reporting Items for Systematic Reviews and MetaAnalyses") protocol was performed via two databases (PubMed and SCOPUS) to summarize the research findings. After the screening and selection process, the full texts of eligible articles (32 studies) were evaluated, and data from 16 studies were considered. A total of 6 by-products were assessed concerning mycotoxin content; these include distiller dried grain with solubles, brewer's spent grain, brewer's spent yeast, cocoa shell, grape pomace, and sugar beet pulp. Frequent mycotoxins in these by-products are AFB
, OTA, FBs, DON, and ZEA. The high prevalence of contaminated samples, which surpasses the limits established for human consumption, thus limiting their valorization as ingredients in the food industry. Co-contamination is frequent, which can cause synergistic interactions and amplify their toxicity.
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•A mouse model developed that recapitulates the progressive stages of human fatty liver disease.•The functional pathways of gene expression and immune abnormalities in this model ...closely resemble human disease.•The ease and reproducibility of this model makes it ideal to study disease pathogenesis and test new treatments.
Although the majority of patients with non-alcoholic fatty liver disease (NAFLD) have only steatosis without progression, a sizeable fraction develop non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis and hepatocellular carcinoma (HCC). Many established diet-induced mouse models for NASH require 24–52 weeks, which makes testing for drug response costly and time consuming.
We have sought to establish a murine NASH model with rapid progression of extensive fibrosis and HCC by using a western diet (WD), which is high-fat, high-fructose and high-cholesterol, combined with low weekly dose of intraperitoneal carbon tetrachloride (CCl4), which serves as an accelerator.
C57BL/6J mice were fed a normal chow diet ± CCl4 or WD ± CCl4 for 12 and 24 weeks. Addition of CCl4 exacerbated histological features of NASH, fibrosis, and tumor development induced by WD, which resulted in stage 3 fibrosis at 12 weeks and HCC development at 24 weeks. Furthermore, whole liver transcriptomic analysis indicated that dysregulated molecular pathways in WD/CCl4 mice and immunologic features were similar to those of human NASH.
Our mouse NASH model exhibits rapid progression of advanced fibrosis and HCC, and mimics histological, immunological and transcriptomic features of human NASH, suggesting that it will be a useful experimental tool for preclinical drug testing.
A carefully characterized model has been developed in mice that recapitulates the progressive stages of human fatty liver disease, from simple steatosis, to inflammation, fibrosis and cancer. The functional pathways of gene expression and immune abnormalities in this model closely resemble human disease. The ease and reproducibility of this model make it ideal to study disease pathogenesis and test new treatments.
Coffee is one of the world's most traded agricultural products. Modeling studies have predicted that climate change will have a strong impact on the suitability of current cultivation areas, but ...these studies have not anticipated possible mitigating effects of the elevated atmospheric CO2 because no information exists for the coffee plant. Potted plants from two genotypes of Coffea arabica and one of C. canephora were grown under controlled conditions of irradiance (800 μmol m(-2) s(-1)), RH (75%) and 380 or 700 μL CO2 L(-1) for 1 year, without water, nutrient or root development restrictions. In all genotypes, the high CO2 treatment promoted opposite trends for stomatal density and size, which decreased and increased, respectively. Regardless of the genotype or the growth CO2, the net rate of CO2 assimilation increased (34-49%) when measured at 700 than at 380 μL CO2 L(-1). This result, together with the almost unchanged stomatal conductance, led to an instantaneous water use efficiency increase. The results also showed a reinforcement of photosynthetic (and respiratory) components, namely thylakoid electron transport and the activities of RuBisCo, ribulose 5-phosphate kinase, malate dehydrogenase and pyruvate kinase, what may have contributed to the enhancements in the maximum rates of electron transport, carboxylation and photosynthetic capacity under elevated CO2, although these responses were genotype dependent. The photosystem II efficiency, energy driven to photochemical events, non-structural carbohydrates, photosynthetic pigment and membrane permeability did not respond to CO2 supply. Some alterations in total fatty acid content and the unsaturation level of the chloroplast membranes were noted but, apparently, did not affect photosynthetic functioning. Despite some differences among the genotypes, no clear species-dependent responses to elevated CO2 were observed. Overall, as no apparent sign of photosynthetic down-regulation was found, our data suggest that Coffea spp. plants may successfully cope with high CO2 under the present experimental conditions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cellular components of solid tumors including DNA are released into the bloodstream, but data on circulating-free DNA (cfDNA) in hepatocellular carcinoma (HCC) are still scarce. This study aimed at ...analyzing mutations in cfDNA and their correlation with tissue mutations in patients with HCC. We included 8 HCC patients treated with surgical resection for whom we collected paired tissue and plasma/serum samples. We analyzed 45 specimens, including multiregional tumor tissue sampling (n = 24), peripheral blood mononuclear cells (PMBC, n = 8), plasma (n = 8) and serum (n = 5). Ultra-deep sequencing (5500× coverage) of all exons was performed in a targeted panel of 58 genes, including frequent HCC driver genes and druggable mutations. Mutations detected in plasma included known HCC oncogenes and tumor suppressors (e.g., TERT promoter, TP53, and NTRK3) as well as a candidate druggable mutation (JAK1). This approach increased the detection rates previously reported for mutations in plasma of HCC patients. A thorough characterization of cis mutations found in plasma confirmed their tumoral origin, which provides definitive evidence of the release of HCC-derived DNA fragments into the bloodstream. This study demonstrates that ultra-deep sequencing of cfDNA is feasible and can confidently detect somatic mutations found in tissue; these data reinforce the role of plasma DNA as a promising minimally invasive tool to interrogate HCC genetics.
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