Tracing the volatilomic fingerprint of grape pomace as a powerful approach for its valorization.

The huge amount of grape pomace (GP) generated every year worldwide, particularly in Europe, creates negative impacts at the economic and environmental levels. As far as we know, scarce research has been done on the volatilomic fingerprint of GP. To meet consumer demand for healthy foods, there is a growing interest in the characterization of particular volatile organic metabolites (VOMS) in GP that can be used for industrial applications, including the food industry. In this study, the volatilomic fingerprint of GP obtained from different Vitis vinifera L. grapes was established by solid phase microextraction (HS-SPME) combined to gas chromatography-mass spectrometry (GC-MS), to explore the properties of most dominant VOMs in a context of its application on marketable products. A total of 52 VOMs belonging to different chemical families were identified. Alcohols, carbonyl compounds, and esters, are the most dominant, representing 38.8, 29.3, and 24.2% of the total volatile profile of the investigated GP, respectively. Esters (e.g., isoamyl acetate, hexyl acetate, ethyl hexanoate) and alcohols (e.g., 3-methyl butan-2-ol, hexan-1-ol) can be used as flavoring agents with potential use in the food industry, and in the cosmetic industry, for fragrances production. In addition, the identified terpenoids (e.g., menthol, ylangene, limonene) exhibit antioxidant, antimicrobial, and anticancer, biological properties, among others, boosting their potential application in the pharmaceutical industry. The obtained results revealed the potential of some VOMs from GP to replace synthetic antioxidants, colorants, and antimicrobials used in the food industry, and in the cosmetic and pharmaceutical industry, meeting the increasing consumer demand for natural alternative compounds.

The Fingerprint of Fortified Wines-From the Sui Generis Production Processes to the Distinctive Aroma.

The fortified wines that originated in Mediterranean countries have, in common, a high alcohol content to increase their shelf-life during long journeys to northern Europe and the American continent. Nowadays, the world's better-known wines, including Marsala, Madeira, Port, and Sherry, due to their high alcoholic content, sweet taste, and intense aromatic profile, are designated as dessert wines and sometimes served as aperitifs. This review gives an overview of the traditional vinification process, including the microbiota and autochthonous yeast, as well as the regulatory aspects of the main Italian, Portuguese, and Spanish fortified wines. The winemaking process is essential to defining the volatile organic compounds (VOCs) that characterize the aroma of each fortified wine, giving them an organoleptic fingerprint and "terroir" characteristics. The various volatile and odorous compounds found in fortified wines during the oxidative aging are discussed in the last part of this review.

The Flavor Chemistry of Fortified Wines-A Comprehensive Approach.

For centuries, wine has had a fundamental role in the culture and habits of different civilizations. Amongst numerous wine types that involve specific winemaking processes, fortified wines possess an added value and are greatly honored worldwide. This review comprises the description of the most important characteristics of the main worldwide fortified wines-Madeira, Port, Sherry, Muscat, and Vermouth-structured in three parts. The first part briefly describes the chemistry of wine flavor, the origin of typical aroma (primary, secondary and tertiary), and the influencing parameters during the winemaking process. The second part describes some specificities of worldwide fortified wine, highlighting the volatile composition with particular emphasis on aroma compounds. The third part reports the volatile composition of the most important fortified wines, including the principal characteristics, vinification process, the evolution of volatile organic compounds (VOCs) during the aging processes, and the most important odor descriptors. Given the worldwide popularity and the economic relevance of fortified wines, much research should be done to better understand accurately the reactions and mechanisms that occur in different stages of winemaking, mainly during the oxidative and thermal aging.

In Vitro and In Vivo Tumor Models for the Evaluation of Anticancer Nanoparticles.

Multiple studies about tumor biology have revealed the determinant role of the tumor microenvironment in cancer progression, resulting from the dynamic interactions between tumor cells and surrounding stromal cells within the extracellular matrix. This malignant microenvironment highly impacts the efficacy of anticancer nanoparticles by displaying drug resistance mechanisms, as well as intrinsic physical and biochemical barriers, which hamper their intratumoral accumulation and biological activity.Currently, two-dimensional cell cultures are used as the initial screening method in vitro for testing cytotoxic nanocarriers. However, this fails to mimic the tumor heterogeneity, as well as the three-dimensional tumor architecture and pathophysiological barriers, leading to an inaccurate pharmacological evaluation.Biomimetic 3D in vitro tumor models, on the other hand, are emerging as promising tools for more accurately assessing nanoparticle activity, owing to their ability to recapitulate certain features of the tumor microenvironment and thus provide mechanistic insights into nanocarrier intratumoral penetration and diffusion rates.Notwithstanding, in vivo validation of nanomedicines remains irreplaceable at the preclinical stage, and a vast variety of more advanced in vivo tumor models is currently available. Such complex animal models (e.g., genetically engineered mice and patient-derived xenografts) are capable of better predicting nanocarrier clinical efficiency, as they closely resemble the heterogeneity of the human tumor microenvironment.Herein, the development of physiologically more relevant in vitro and in vivo tumor models for the preclinical evaluation of anticancer nanoparticles will be discussed, as well as the current limitations and future challenges in clinical translation.

Current challenges and emerging opportunities of CAR-T cell therapies.

Infusion of chimeric antigen receptor (CAR)-genetically modified T cells (CAR-T cells) have led to remarkable clinical responses and cancer remission in patients suffering from relapsed or refractory B-cell malignancies. This is a new form of adoptive T cell therapy (ACT), whereby the artificial CAR enables the redirection of T cells endogenous antitumor activity towards a predefined tumor-associated antigen, leading to the elimination of a specific tumor. The early success in blood cancers has prompted the US Food and Drug Administration (FDA) to approve the first CAR-T cell therapies for the treatment of CD19-positive leukemias and lymphomas in 2017. Despite the emergence of CAR-T cells as one of the latest breakthroughs of cancer immunotherapies, their wider application has been hampered by specific life-threatening toxicities, and a substantial lack of efficacy in the treatment of solid tumors, owing to the strong immunosuppressive tumor microenvironment and the paucity of reliable tumor-specific targets. Herein, besides providing an overview of the emerging CAR-technologies and current clinical applications, the major hurdles of CAR-T cell therapies will be discussed, namely treatment-related life-threatening toxicities and the obstacles posed by the immunosupressive tumor-microenvironment of solid tumors, as well as the next-generation strategies currently designed to simultaneously improve safety and efficacy of CAR-T cell therapies in vivo.

Insights on the Formulation of Recombinant Proteins.

Recombinant proteins are large and complex molecules, whose therapeutic activity highly depends on their structure. Formulation of biopharmaceuticals aims at stabilizing protein conformation, promoting its efficacy, and preventing safety concerns, such as immunogenicity. Currently, the rational design of formulations is possible due to the availability of several techniques for molecule characterization and an array of both well-known and new excipients. Also, high-throughput technologies and Quality by Design approaches are trending and have been contributing to the advancement of the field. Still, there is a search for alternatives that ensure quality of the medicines through its life cycle, particularly for highly concentrated formulations, such as monoclonal antibodies. There is also a demand for strategies that improve protein delivery and more comfortable administration to the patients, especially with the arising of recombinant proteins in the treatment of chronic diseases, such as autoimmune conditions or heart diseases. In this chapter, current and future advancements regarding recombinant protein formulation and its impact in drug development and approval will be addressed.