The Potential of Acorn Extract Treatment on PUFAs Oxidative Stability: A Case Study on Fish Cooking Wastewater.

Fish byproducts are valuable sources of Ω-3 polyunsaturated fatty acids (PUFAs). Their valorization potentially alleviates pressure on this sector. This study uses a circular economy approach to investigate the oil fraction from sardine cooking wastewater (SCW). Analysis of its fatty acid (FA) profile revealed promising PUFA levels. However, PUFAs are highly susceptible to oxidation, prompting the exploration of effective and natural strategies to replace synthetic antioxidants and mitigate their associated risks and concerns. An antioxidant extract from acorn shells was developed and evaluated for its efficacy in preventing oxidative degradation. The extract exhibited significant levels of total phenolic compounds (TPC: 49.94 and 22.99 mg TAE or GAE/g DW) and antioxidant activities (ABTS: 72.46; ORAC: 59.60; DPPH: 248.24 mg TE/g DW), with tannins comprising a significant portion of phenolics (20.61 mg TAE/g DW). LC-ESI-UHR-QqTOF-MS identified ellagic acid, epicatechin, procyanidin B2 and azelaic acid as the predominant phenolic compounds. The extract demonstrated the ability to significantly reduce the peroxide index and inhibit PUFA oxidation, including linoleic acid (LA), eicosapentaenoic (EPA), and docosahexaenoic acid (DHA). This approach holds promise for developing stable, functional ingredients rich in PUFAs. Future research will focus on refining oil extraction procedures and conducting stability tests towards the development of specific applications.

Features of the microalga Raphidocelis subcapitata: physiology and applications.

The microalga Raphidocelis subcapitata was isolated from the Nitelva River (Norway) and subsequently deposited in the collection of the Norwegian Institute of Water Research as "Selenastrum capricornutum Printz". This freshwater microalga, also known as Pseudokirchneriella subcapitata, acquired much of its notoriety due to its high sensitivity to different chemical species, which makes it recommended by different international organizations for the assessment of ecotoxicity. However, outside this scope, R. subcapitata continues to be little explored. This review aims to shed light on a microalga that, despite its popularity, continues to be an "illustrious" unknown in many ways. Therefore, R. subcapitata taxonomy, phylogeny, shape, size/biovolume, cell ultra-structure, and reproduction are reviewed. The nutritional and cultural conditions, chronological aging, and maintenance and preservation of the alga are summarized and critically discussed. Applications of R. subcapitata, such as its use in aquatic toxicology (ecotoxicity assessment and elucidation of adverse toxic outcome pathways) are presented. Furthermore, the latest advances in the use of this alga in biotechnology, namely in the bioremediation of effluents and the production of value-added biomolecules and biofuels, are highlighted. To end, a perspective regarding the future exploitation of R. subcapitata potentialities, in a modern concept of biorefinery, is outlined. KEY POINTS: • An overview of alga phylogeny and physiology is critically reviewed. • Advances in alga nutrition, cultural conditions, and chronological aging are presented. • Its use in aquatic toxicology and biotechnology is highlighted.

Lavandula pedunculata Polyphenol-Rich Extracts Obtained by Conventional, MAE and UAE Methods: Exploring the Bioactive Potential and Safety for Use a Medicine Plant as Food and Nutraceutical Ingredient.

Nowadays, plant-based bioactive compounds (BCs) are a key focus of research, supporting sustainable food production and favored by consumers for their perceived safety and health advantages over synthetic options. Lavandula pedunculata (LP) is a Portuguese, native species relevant to the bioeconomy that can be useful as a source of natural BCs, mainly phenolic compounds. This study compared LP polyphenol-rich extracts from conventional maceration extraction (CE), microwave and ultrasound-assisted extraction (MAE and UAE). As a result, rosmarinic acid (58.68-48.27 mg/g DE) and salvianolic acid B (43.19-40.09 mg/g DE) were the most representative phenolic compounds in the LP extracts. The three methods exhibited high antioxidant activity, highlighting the ORAC (1306.0 to 1765.5 mg Trolox equivalents (TE)/g DE) results. In addition, the extracts obtained with MAE and CE showed outstanding growth inhibition for B. cereus, S. aureus, E. coli, S. enterica and P. aeruginosa (>50%, at 10 mg/mL). The MAE extract showed the lowest IC50 (0.98 mg DE/mL) for angiotensin-converting enzyme inhibition and the best results for α-glucosidase and tyrosinase inhibition (at 5 mg/mL, the inhibition was 87 and 73%, respectively). The LP polyphenol-rich extracts were also safe on caco-2 intestinal cells, and no mutagenicity was detected. The UAE had lower efficiency in obtaining LP polyphenol-rich extracts. MAE equaled CE's efficiency, saving time and energy. LP shows potential as a sustainable raw material, allowing diverse extraction methods to safely develop health-promoting food and nutraceutical ingredients.

Anti-obesity potential of a yogurt functionalized with a CLNA-rich pomegranate oil.

Pomegranate oil is rich in conjugated linolenic acids, compounds which have attracted attention due to their potential applicability in obesity management as they are capable of modulating leptin and adiponectin secretion and regulate fatty acids storage and glucose metabolism. Among the possible bioactive foodstuffs capable of delivering these bioactive compounds yogurts have shown potential. Thus, the purpose of this work was to develop functional yogurts through the addition of pomegranate oil either in its free or encapsulated (used as a protective strategy against oxidation and gastrointestinal tract passage) forms. To that end, the pomegranate oil (free and encapsulated) was incorporated in yogurt and the functional yogurt capacity to modulate hepatic lipid accumulation, adipocyte metabolism (in terms of lipolysis, and adipokines secretion) and immune response was evaluated. The results obtained showed that the pomegranate oil's incorporation led to an improvement in the yogurts' nutritional values, with a reduction in its atherogenic and thrombogenic indexes (more than 78% for atherogenic and 76% for thrombogenic index) and an enhancement of its hypocholesterolemic/hypercholesterolemic ratio (more than 62%) when compared to the control yogurt. Furthermore, data also showed for the first time how these functional yogurts promoted modulation of metabolic processes post GIT as they were capable of reducing by 40% triglycerides accumulation in steatosis-induced Hep G2 cells and by 30 % in differentiated adipocytes. Moreover, samples also showed a capacity to modulate the leptin and adiponectin secretion (56 % of increase in adiponectin) and reduce the IL-6 secretion (ca 44%) and TNF-α (ca 12%) in LPS-stimulated cells. Thus, the CLNA-rich yogurt here developed showed potential as a viable nutraceutical alternative for obesity management.

Palmelloid-like phenotype in the alga Raphidocelis subcapitata exposed to pollutants: A generalized adaptive strategy to stress or a specific cellular response?

This work focuses on the formation of palmelloid-like phenotype in the freshwater alga Raphidocelis subcapitata (formerly known as Pseudokirchneriella subcapitata and Selenastrum capricornutum), when exposed to adverse conditions generated by the presence of organic [the antibiotic erythromycin (ERY) and the herbicide metolachlor (MET)] or inorganic [the heavy metals, cadmium (Cd) and zinc (Zn)] pollutants, at environmentally relevant concentrations. This alga in absence of stress or when exposed to ERY or Zn, up to 200 µg/L, essentially showed a single-nucleus state, although algal growth was reduced or stopped. R. subcapitata "switched" to a multinucleated state (palmelloid-like morphology) and accumulated energy-reserve compounds (neutral lipids) when stressed by 100-200 µg/L MET or 200 µg/L Cd; at these concentrations of pollutants, growth was arrested, however, the majority of the algal population (≥83 %) was alive. The formation of palmelloid-like phenotype, at sub-lethal concentrations of pollutants, was dependent on the pollutant, its concentration and exposure time. The multinucleated structure is a transitory phenotype since R. subcapitata population was able to revert to a single-nucleus state, with normal cell size, within 24-96 h (depending on the impact of the toxic in the alga), after being transferred to fresh OECD medium, without pollutants. The obtained results indicate that the formation of a palmelloid-like phenotype in R. subcapitata is dependent on the mode of action of toxics and their concentration, not constituting a generalized defense mechanism against stress. The observations here shown contribute to understanding the different strategies used by the unicellular alga R. subcapitata to cope with severe stress imposed by organic and inorganic pollutants.

Modification of Acorn Starch Structure and Properties by High Hydrostatic Pressure.

Despite being rich in starch, over half of acorn production is undervalued. High hydrostatic pressure was used to modify the properties of Q. pyrenaica (0.1 and 460 MPa for 20 min) and Q. robur (0.1 and 333 MPa for 17.4 min) acorn starches to obtain high-valued ingredients. Pressure significantly altered the span distribution and heterogeneity of the acorn starch granules depending on the species, but their morphology was unaffected. Pressurization increased the amylose/amylopectin ratio and damaged starch contents, but the effect was more prominent in Q. pyrenaica than in Q. robur. However, the polymorphism, relative crystallinity, gelatinization temperatures, and enthalpies were preserved. The pressure effect on the starch properties depended on the property and species. The solubility, swelling power, and acorn gels' resistance towards deformation for both species decreased after pressurization. For Q. pyrenaica starch, the in vitro digestibility increased, but the pseudoplastic behavior decreased after pressurization. No differences were seen for Q. robur. Regarding the commercial starch, acorn starches had lower gelatinization temperatures and enthalpies, lower in vitro digestibility, lower resistance towards deformation, superior pseudoplastic behavior, and overall higher solubility and swelling power until 80 °C. This encourages the usage of acorn starches as a new food ingredient.

Are Antimicrobial Peptides a 21st-Century Solution for Atopic Dermatitis?

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that is the result of various environmental, bacterial and genetic stimuli, which culminate in the disruption of the skin's barrier function. Characterized by highly pruritic skin lesions, xerosis and an array of comorbidities among which skin infections are the most common, this condition results in both a significant loss of quality of life and in the need for life-long treatments (e.g., corticosteroids, monoclonal antibodies and regular antibiotic intake), all of which may have harmful secondary effects. This, in conjunction with AD's rising prevalence, made the development of alternative treatment strategies the focus of both the scientific community and the pharmaceutical industry. Given their potential to both manage the skin microbiome, fight infections and even modulate the local immune response, the use of antimicrobial peptides (AMPs) from more diverse origins has become one of the most promising alternative solutions for AD management, with some being already used with some success towards this end. However, their production and use also exhibit some limitations. The current work seeks to compile the available information and provide a better understanding of the state of the art in the understanding of AMPs' true potential in addressing AD.

Understanding the Anti-Obesity Potential of an Avocado Oil-Rich Cheese through an In Vitro Co-Culture Intestine Cell Model.

Nowadays, with consumers' requirements shifting towards more natural solutions and the advent of nutraceutical-based approaches, new alternatives for obesity management are being developed. This work aimed to show, for the first time, the potential of avocado oil-fortified cheese as a viable foodstuff for obesity management through complex in vitro cellular models. The results showed that oleic and palmitic acids' permeability through the Caco-2/HT29-MTX membrane peaked at the 2h mark, with the highest apparent permeability being registered for oleic acid (0.14 cm/s). Additionally, the permeated compounds were capable of modulating the metabolism of adipocytes present in the basal compartment, significantly reducing adipokine (leptin) and cytokine (MPC-1, IL-10, and TNF-α) production. The permeates (containing 3.30 µg/mL of palmitic acid and 2.16 µg/mL of oleic acid) also presented an overall anti-inflammatory activity upon Raw 264.7 macrophages, reducing IL-6 and TNF-α secretion. Despite in vivo assays being required, the data showed the potential of a functional dairy product as a valid food matrix to aid in obesity management.

A chemical study of yoghurt produced under isostatic pressure during storage.

Yoghurt fermented under sub-lethal high pressure (10, 20, 30 and 40 MPa at 43 °C), and afterward placed under refrigeration (4 °C for 23 days) was studied and compared with yoghurt fermented at atmospheric pressure (0.1 MPa). For a deeper analysis, metabolite fingerprinting by nuclear magnetic resonance (NMR), sugars and organic acids assessment by high performance liquid chromatography (HPLC), total fatty acids (TFA) determination and quantification by gas chromatography with a flame ionization detector (GC-FID) were performed. Metabolomic analyses revealed that only 2,3-butanediol, acetoin, diacetyl and formate vary with the increase of pressure and probable relation with pressure influenced diacetyl reductase, acetoin reductase and acetolactate decarboxylase. Yoghurts fermented at 40 MPa had the lowest content in lactose (39.7 % of total sugar reduction) and the less content in TFA (56.1 %). Further research is of interest to understand more about fermentation processes under sub-lethal high pressure.

Bigels as Delivery Systems of Bioactive Fatty Acids Present in Functional Edible Oils: Coconut, Avocado, and Pomegranate.

Bioactive fatty acids possess several benefits for human health; however, these molecules show a reduced oxidative stability and consequently reduced bioavailability. This work aimed to develop novel bigels as a strategy to protect bioactive fatty acids present in three different vegetable oils with nutritional attributes (coconut oil, avocado oil, and pomegranate oil) during passage through the gastrointestinal tract (GIT). Bigels were prepared using monoglycerides-vegetable oil oleogel and carboxymethyl cellulose hydrogel. These bigels were analyzed in terms of structure and rheological characteristics. According to the rheological properties, bigels exhibited a solid-like behavior since G' was higher than G". The results showed that the proportion of oleogel was essential to the viscosity of the final formulation as an increase in this fraction was responsible for an increase in viscosity. The fatty acids profile was evaluated before and after simulated GIT. The bigels protected the fatty acids against degradation; in the case of coconut oil, the reduction of key fatty acids was 3 times lower; for avocado oil, 2 times lower; and for pomegranate oil, 1.7 times lower. These results suggest that bigels can be used as part of an important strategy for bioactive fatty acid delivery for food applications.

Potential Biological Properties of Lycopene in a Self-Emulsifying Drug Delivery System.

In recent years, lycopene has been highlighted due to its antioxidant and anti-inflammatory properties, associated with a beneficial effect on human health. The aim of this study was to advance the studies of antioxidant and anti-inflammatory mechanisms on human keratinocytes cells (HaCaT) of a self-emulsifying drug delivery system (SEDDS) loaded with lycopene purified from red guava (nanoLPG). The characteristics of nanoLPG were a hydrodynamic diameter of 205 nm, a polydispersity index of 0.21 and a zeta potential of -20.57, providing physical stability for the nanosystem. NanoLPG demonstrated antioxidant capacity, as shown using the ORAC methodology, and prevented DNA degradation (DNA agarose). Proinflammatory activity was evaluated by quantifying the cytokines TNF-α, IL-6 and IL-8, with only IL-8 showing a significant increase (p < 0.0001). NanoLPG showed greater inhibition of the tyrosinase and elastase enzymes, involved in the skin aging process, compared to purified lycopene (LPG). In vitro treatment for 24 h with 5.0 µg/mL of nanoLPG did not affect the viability of HaCaT cells. The ultrastructure of HaCaT cells demonstrated the maintenance of morphology. This contrasts with endoplasmic reticulum stresses and autophagic vacuoles when treated with LPG after stimulation or not with LPS. Therefore, the use of lycopene in a nanoemulsion may be beneficial in strategies and products associated with skin health.

Selective Activity of an Anthocyanin-Rich, Purified Blueberry Extract upon Pathogenic and Probiotic Bacteria.

Blueberry extracts have been widely recognized as possessing antimicrobial activity against several potential pathogens. However, the contextualization of the interaction of these extracts with beneficial bacteria (i.e., probiotics), particularly when considering the food applications of these products, may be of importance, not only because their presence is important in the regular gut microbiota, but also because they are important constituents of regular and functional foodstuffs. Therefore, the present work first sought to demonstrate the inhibitory effect of a blueberry extract upon four potential food pathogens and, after identifying the active concentrations, evaluated their impact upon the growth and metabolic activity (organic acid production and sugar consumption) of five potential probiotic microorganisms. Results showed that the extract, at a concentration that inhibited L. monocytogenes, B. cereus, E. coli and S. enteritidis (1000 µg mL-1), had no inhibitory effect on the growth of the potential probiotic stains used. However, the results demonstrated, for the first time, that the extract had a significant impact on the metabolic activity of all probiotic strains, resulting in higher amounts of organic acid production (acetic, citric and lactic acids) and an earlier production of propionic acid.

Can Growth of Nannochloropsis oculata under Modulated Stress Enhance Its Lipid-Associated Biological Properties?

Nannochloropsis oculata is well-recognized as a potential microalgal source of valuable compounds such as polyunsaturated fatty acids, particularly, eicosapentaenoic acid (EPA). The content and profile of these lipids is highly dependent on the growth conditions and can, therefore, be tailored through modulation of the growth parameters, specifically, temperature. Moreover, biological activities are composition dependent. In the present work, lipid extracts obtained from N. oculata, grown under constant temperature and under modulated temperature stress (to increase EPA content; Str) were characterized by GC-FID and several bioactivities were evaluated, namely, antioxidant (L-ORACFL), cytotoxic (MTT), adipolytic, anti-hepatic lipid accumulation (steatosis), and anti-inflammatory properties. Both extracts exhibited antioxidant activity (c.a. 49 µmol Troloxequivalent/mgextract) and the absence of toxicity (up to 800 µg/mL) toward colon and hepatic cells, adipocytes, and macrophages. They also induced adipolysis and the inhibition of triglycerides hepatic accumulation, with a higher impact from Str. In addition, anti-inflammatory activity was observed in the lipopolysaccharide-induced inflammation of macrophages in the presence of either extract, since lower levels of pro-inflammatory interleukin-6 and interferon-ß were obtained, specifically by Str. The results presented herein revealed that modulated temperature stress may enhance the health effects of N. oculata lipid extracts, which may be safely utilized to formulate novel food products.

Chitosan Nanoparticles as Bioactive Vehicles for Textile Dyeing: A Proof of Concept.

In recent years bioactive textiles have risen to the forefront of consumers perception due to their potential protection against virus, fungi and bacteria. However, traditional textile staining is an eco-damaging process that and current methods of textile functionalization are expensive, complicated and with great environmental impact. With that in mind, this work sought to show a possible solution for this problematic through the usage of a novel one step textile dyeing and functionalization method based upon nanoencapsulated textile dyes (NTDs). To do so navy blue everzol NTDs were produced with chitosan, cotton dyed, characterized through FTIR and SEM and biological potential evaluated through biocompatibility screening and antimicrobial activity against skin pathogens. The data obtained showed that NTDs effectively dyed the target textile through a coating of the cotton fibre and that NTDs formed hydrogen bonds with the cellulose fibre via electrostatic interactions of the chitosan amino groups with cotton sulphate groups. From a biocompatibility perspective NTDs dyed cotton had no deleterious effects upon a skin cell line, as it promoted cellular metabolism of HaCat cells, while traditionally died cotton reduced it by 10%. Last but not least, NTDs dyed cotton showed significant antimicrobial activity as it reduced viable counts of MRSA, MSSA and A. baumannii between 1 and 2 log of CFU while traditional dyed cotton had no antimicrobial activity. Considering these results the novel method proposed shows is a viable and ecological alternative for the development of antimicrobial textiles with potential biomedical applications.

Life and death of Pseudokirchneriella subcapitata: physiological changes during chronological aging.

The green alga Pseudokirchneriella subcapitata is widely used in ecotoxicity assays and has great biotechnological potential as feedstock. This work aims to characterize the physiology of this alga associated with the aging resulting from the incubation of cells for 21 days, in the OECD medium, with continuous agitation and light exposure, in a batch mode. After inoculation, cells grow exponentially during 3 days, and the culture presents a typical green color. In this phase, "young" algal cells present, predominantly, a lunate morphology with the chloroplast occupying a large part of the cell, maximum photosynthetic activity and pigments concentration, and produce starch as a reserve material. Between the 5th and the 12th days of incubation, cells are in the stationary phase. The culture becomes less green, and the cells stop dividing (≥ 99% have one nucleus) and start to age. "Old" algal cells present chloroplast shrinkage, an abrupt decline of chlorophylls content, and photosynthetic capacity (Fv/Fm and ɸPSII), accompanied by a degradation of starch and an increase of neutral lipids content. The onset of the death phase occurs after the 12th day and is characterized by the loss of cell membrane integrity of some algae (cell death). The culture stays, progressively, yellow, and the majority of the population (~93%) is composed of live cells, chronologically "old," with a significant drop in photosynthetic activity (decay > 75% of Fv/Fm and ɸPSII) and starch content. The information here achieved can be helpful when exploring the potential of this alga in toxicity studies or in biotechnological applications. KEY POINTS: • Physiological changes of P. subcapitata with chronological aging are shown • "Young" algae exhibit a semilunar shape, high photosynthetic activity, and accumulated starch • "Old"-live algae show reduced photosynthetic capacity and accumulated lipids.

Antiadhesive and Antibiofilm Effect of Malvidin-3-Glucoside and Malvidin-3-Glucoside/Neochlorogenic Acid Mixtures upon Staphylococcus.

Several reports on the biological activity of anthocyanin-rich extracts have been made. However, despite the association of said activity with their anthocyanin content, to the best of our knowledge, there are no previous works regarding the antimicrobial, antibiofilm and/or antiadhesive properties of anthocyanins alone. Therefore, the present work aimed to determine the effects of malvidin-3-glucoside, a major component of a previously reported extract, and the impact of its association with neochlorogenic acid (the only non-anthocyanin phenolic present in said extract), upon several Staphylococcus strains with varying resistance profiles. Results show that, while malvidin-3-glucoside and malvidin-3-glucoside/neochlorogenic acid mixtures were unable to considerably inhibit bacterial growth after 24 h, they still possessed an interesting antibiofilm activity (with reductions of biofilm entrapped cells up to 2.5 log cycles, metabolic inhibition rates up to 81% and up to 51% of biomass inhibition). When considering the bacteria's capacity to adhere to plain polystyrene surfaces, the inhibition ranges were considerably lower (21% maximum value). However, when considering polystyrene surfaces coated with plasmatic proteins this value was considerably higher (45% for adhesion in the presence of extract and 39% for adhesion after the surface was exposed to extract). Overall, the studied anthocyanins showed potential as future alternatives to traditional antimicrobials in adhesion and biofilm formation prevention.

Medium-chain triglycerides and conjugated linolenic acids in functional yogurts: impact of GIT and potential biological activities.

In recent years, bioactive lipids particularly medium-chain triglycerides and conjugated linolenic fatty acids have obtained more attention due to their possible applicability in obesity metabolism modulation. These compounds are capable to increase thermogenesis and reduce weight gain through the modulation of key neurohormones such as leptin and adiponectin. The purpose of this work was to develop functional yogurts through the addition of coconut (rich in medium-chain fatty acids) or pomegranate oils (rich in conjugated linolenic acids). The presence of these oils led to a significant alteration in the nutritional value of yogurts, showing a capacity to reduce the accumulation of lipids in hepatocytes and increase the release of triglycerides in adipocytes. These results demonstrate that functional yogurts can be a valuable strategy for obesity prevention.

Pomegranate Oil's Potential as an Anti-Obesity Ingredient.

In recent years, pomegranate oil has obtained more attention due to its content of conjugated linolenic acids and possible application in the prevention of many diseases. The purpose of this work was to evaluate the potential ability of pomegranate oil to modulate obesity-related metabolism and immune response using in vitro models. In this regard, pomegranate oil was characterized in terms of fatty acids profile, tocopherols and phytosterols, and antioxidant capacity. After evaluation of the safety profile, pomegranate oil's capacity to modulate obesity-related metabolism was evaluated through adipolysis and adipokines secretion quantification in 3T3-L1 differentiated adipocytes and hepatic lipid accumulation assay in Hep G2 hepatocytes. The immunomodulatory activity was evaluated in Caco-2 cells by quantification of pro-inflammatory cytokines IL-6, IL-8, and TNF-α. This oil showed high antioxidant capacity and was mainly composed of conjugated fatty acid, namely punicic acid. Its chemical composition was responsible for its capacity to reduce the lipid accumulation in Hep G2 cells and 3T3-L1 differentiated adipocytes. In short, pomegranate oil shows great potential for the development of functional foods and nutraceuticals targeting obesity.

PD-L1 expression in EBV associated gastric cancer: a systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis is to the summarize the evidence on programmed cell death protein ligand 1 (PD-L1) in Epstein-Barr virus associated gastric cancer (EBVaGC) and to estimate the expression rate of PD-L1 among this subtype of Gastric Cancer (GC). MATERIALS AND METHODS: For this study, PubMed®, EMBASE® and Web of Science® databases were searched for articles published until 1st November 2021. A total of 43 eligible publications with a total of 11,327 patients were included analysis based on inclusion and exclusion criteria. A total of 41 publications present data for proportion estimation and 33 for comparison of PD-L1 between EBV positive and negative GC. DerSimonian-Laird random-effects model was used for meta-analysis. RESULTS: The analysis showed that in EBVaGC the pooled positivity rate for PD-L1 was 54.6% (p < 0.001), with a high heterogeneity between the included studies, which was associated with variation on positivity criteria for PD-L1 expression. Overall, the study reveals an increased association between PD-L1 and EBVaGC (OR = 6.36, 95% CI 3.91-10.3, p < 0.001). Furthermore, the study revealed that GC with lymphoid stroma (GCLS) is highly associated with EBV (OR = 17.4, 95% CI 6.83-44.1, p < 0.001), with a pooled EBV positivity rate of 52.9% (p < 0.001). CONCLUSIONS: Patients with EBVaGC tend to show higher PD-L1 expression, which enhances EBV positivity as a promising marker for patient selection for immunotherapy targeted agents. A uniform criteria for PD-L1 positivity in tumor cells is needed, as well as further prospective studies to validate our findings and their prognostic significance.

Treatment optimization of locally advanced and metastatic pancreatic cancer (Review).

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumor types, being the sixth leading cause of mortality worldwide and the fourth in Europe. Globally, it has a mortality/incidence ratio of 98%, and the 5­year survival rate in Europe is only 3%. Although risk factors, such as obesity, diabetes mellitus, smoking, alcohol consumption and genetic factors, have been identified, the causes of PDAC remain elusive. Additionally, the only curative treatment for PDAC is surgery with negative margins. However, upon diagnosis, ~30% of the patients already present with locally advanced disease. In these cases, a multidisciplinary approach is required to improve disease­related symptoms and prolong patient survival. In the present article, a comprehensive review of PDAC epidemiology, physiology and treatment is provided. Moreover, guidelines on patient treatment are suggested. Among the different available therapeutic options for the treatment of advanced PDAC, results are modest, most likely due to the complexity of the disease, and so the prognostic remains poor. Molecular approaches based on multi­omics research are promising and will contribute to groundbreaking personalized medicine. Thus, economic investment that promotes research of pancreatic cancer will be critical to the development of more efficient diagnostic and treatment strategies.