Molecular Markers, Immune Therapy, and Non-Small Cell Lung Cancer-State-of-the-Art Review for Surgeons.

Background: Lung cancer is a leading cause of cancer deaths in the United States. An increasing understanding of relevant non-small cell lung cancer (NSCLC) biomarkers has led to the recent development of molecular-targeted therapies and immune checkpoint inhibitors that have revolutionized treatment for patients with advanced and metastatic disease. The purpose of this review is to provide surgeons with a state-of-the-art understanding of the current medical and surgical treatment trends and their implications in the future of management of NSCLC. Materials and Methods: A systematic search of PubMed was conducted to identify English language articles published between January 2010 and March 2024 focusing on molecular markers, tumor targeting, and immunotherapy in the diagnosis and treatment of NSCLC. Case series, observational studies, randomized trials, guidelines, narrative reviews, systematic reviews, and meta-analyses were included. Results: There is now increasing data to suggest that molecular-targeted therapies and immune therapies have a role in the neoadjuvant setting. Advances in intraoperative imaging allow surgeons to perform increasingly parenchymal-sparing lung resections without compromising tumor margins. Liquid biopsies can noninvasively detect targetable mutations in cancer cells and DNA from a blood draw, potentially allowing for earlier diagnosis, personalized therapy, and long-term monitoring for disease recurrence. Conclusions: The management of NSCLC has advanced dramatically in recent years fueled by a growing understanding of the cancer biology of NSCLC. Advances in medical therapies, surgical techniques, and diagnostic and surveillance modalities continue to evolve but have already impacted current treatment strategies for NSCLC, which are encompassed in this review.

Minimally Invasive with Maximal Yield: A Narrative Review of Current Practices in Mediastinal Lymph Node Staging in Non-Small Cell Lung Cancer.

Background: Lung cancer remains the leading cause of cancer deaths in the United States despite declining incidence and improved outcomes because of advancements in early detection and development of novel therapies. Accurate mediastinal lymph node staging is crucial for determining prognosis and guiding treatment decisions, particularly for non-small cell lung cancer (NSCLC). Materials and Methods: A systematic search of PubMed was conducted to identify English language articles published between January 2010 and January 2024 focusing on preoperative lymph node staging in adults with NSCLC. Case series, observational studies, randomized trials, guidelines, narrative reviews, systematic reviews, and meta-analyses were included. Results: Various imaging modalities, surgical and nonsurgical procedures for mediastinal lymph node staging were reviewed, including positron emission tomography with computed tomography, cervical mediastinoscopy, video-assisted cervical mediastinoscopy, anterior mediastinotomy, video-assisted thoracoscopy, endobronchial ultrasound-guided fine needle aspiration (EBUS-FNA), transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), and computed tomography-guided percutaneous lymph node biopsy. EBUS-FNA emerged as the preferred initial staging procedure because of its high sensitivity and low complication rate. Combining it with other procedures or confirmatory testing may be helpful in determining appropriate treatment. Conclusions: Although cervical mediastinoscopy remains a valuable confirmatory procedure in select cases, its role as a first-line staging modality is diminishing with the widespread adoption of EBUS-FNA and EUS-FNA. The combination of EBUS-FNA and EUS-FNA allows access to nearly all mediastinal lymph node stations with high diagnostic accuracy. Future research may further refine the selection criteria for invasive mediastinal staging procedures, ultimately optimizing patient outcomes in the management of NSCLC.

Unveiling the Antioxidant Therapeutic Functionality of Sustainable Olive Pomace Active Ingredients.

Olive pomace (OP) is the main residue that results from olive oil production. OP is rich in bioactive compounds, including polyphenols, so its use in the treatments of diseases related to oxidative stress, such as cancer, could be considered. The present work aimed to study the biological properties of different OP extracts, obtained by ohmic heating-assisted extraction and conventional heating, using water and 50% ethanol, in the treatment and prevention of colorectal cancer through Caco-2 cell models. Additionally, an in-silico analysis was performed to identify the phenolic intestinal absorption and Caco-2 permeability. The extracts were chemically characterized, and it was found that the Ohmic-hydroethanolic (OH-EtOH) extract had the highest antiproliferative effect, probably due to its higher content of phenolic compounds. The OH-EtOH induced potential modifications in the mitochondrial membrane and led to apoptosis by cell cycle arrest in the G1/S phases with activation of p53 and caspase 3 proteins. In addition, this extract protected the intestine against oxidative stress (ROS) caused by H2O2. Therefore, the bioactive compounds present in OP and recovered by applying a green technology such as ohmic-heating, show promising potential to be used in food, nutraceutical, and biomedical applications, reducing this waste and facilitating the circular economy.

Artichoke extracts with potential application in chemoprevention and inflammatory processes

Abstract The aim of this work is to study three cultivars of artichoke (Cynara cardunculus var. scolymus): Gauchito, Guri and Oro Verde in terms of their in vitro chemoprevention and anti-inflammatory properties. These cultivars show good productive performance. The phenolic composition of their fresh leaves and edible bracts was analyzed by high performance liquid chromatography and high resolution mass spectrometry (HPLC-HRMS), showing mainly caffeoylquinic acids and flavonoids. Caffeoylquinic acids were quantified and the highest content was found in Gauchito cultivar. In this cultivar, the content of dicaffeoylquinic acids in fresh bracts was six times higher than that in fresh leaves (10064.5 ± 378.3 mg/kg versus 1451.0 ± 209.3 mg/kg respectively). Luteolin flavonoids were detected in leaves. The extracts from fresh bracts and leaves were assessed in their in vitro bioactivity against human neuroblastoma cells (SH-SY5Y). Inhibition of SH-SY5Y cells proliferation by Gauchito and Guri leaf extracts (8 µg/mL) was higher than 50 %. The leaf extracts of the same cultivars showed an inhibitory effect on human interferon IFN-I, decreasing its activity 50% at 40 µg/mL. Interestingly, the bract extracts did not show in vitro bioactivity at these concentrations, nor did the pure compounds chlorogenic acid, cynarin, apigenin and luteolin (at 2 µg/mL). These results suggest that Gauchito and Guri leaf extracts have potential for human neuroblastoma chemoprevention and treatment of inflammatory processes.

Lipid Digestibility and Polyphenols Bioaccessibility of Oil-in-Water Emulsions Containing Avocado Peel and Seed Extracts as Affected by the Presence of Low Methoxyl Pectin.

In this study, the digestibility of oil-in-water (O/W) emulsions using low methoxyl pectin (LMP) as surfactant and in combination with avocado peel (AP) or seed (AS) extracts was assessed, in terms of its free fatty acid (FFA) release and the phenolic compound (PC) bioaccessibility. With this purpose, AP and AS were characterized by UPLC-ESI-MS/MS before their incorporation into O/W emulsions stabilized using LMP. In that sense, AP extract had a higher content of PCs (6836.32 ± 64.66 mg/100 g of extract) compared to AS extract (1514.62 ± 578.33 mg/100 g of extract). Both extracts enhanced LMP's emulsifying properties, leading to narrower distributions and smaller particle sizes compared to those without extracts. Similarly, when both LMP and the extracts were present in the emulsions the FFA release significantly increased. Regarding bioaccessibility, the PCs from the AS extracts had a higher bioaccessibility than those from the AP extracts, regardless of the presence of LMP. However, the presence of LMP reduced the bioaccessibility of flavonoids from emulsions containing either AP or AS extracts. These results provide new insights regarding the use of PC extracts from avocado peel and seed residues, and the effect of LMP on emulsion digestibility, and its influence on flavonoids bioaccessibility.

Phenolic-Rich Extracts from Avocado Fruit Residues as Functional Food Ingredients with Antioxidant and Antiproliferative Properties.

In this study, the total phenolic compounds content and profile, the nutritional value, the antioxidant and antiproliferative activities of avocado peel, seed coat, and seed extracts were characterized. Additionally, an in-silico analysis was performed to identify the phenolic compounds with the highest intestinal absorption and Caco-2 permeability. The avocado peel extract possessed the highest content of phenolic compounds (309.95 ± 25.33 mMol GA/100 g of extract) and the lowest effective concentration (EC50) against DPPH and ABTS radicals (72.64 ± 10.70 and 181.68 ± 18.47, respectively). On the other hand, the peel and seed coat extracts had the lowest energy densities (226.06 ± 0.06 kcal/100 g and 219.62 ± 0.49 kcal/100 g, respectively). Regarding the antiproliferative activity, the avocado peel extract (180 ± 40 µg/mL) showed the lowest inhibitory concentration (IC50), followed by the seed (200 ± 21 µg/mL) and seed coat (340 ± 32 µg/mL) extracts. The IC50 of the extracts induced apoptosis in Caco-2 cells at the early and late stages. According to the in-silico analysis, these results could be related to the higher Caco-2 permeability to hydroxysalidroside, salidroside, sakuranetin, and luteolin. Therefore, this study provides new insights regarding the potential use of these extracts as functional ingredients with antioxidant and antiproliferative properties and as medicinal agents in diseases related to oxidative stress such as cancer.

In vitro digestibility and release of a mango peel extract encapsulated within water-in-oil-in-water (W1/O/W2) emulsions containing sodium carboxymethyl cellulose.

Mango peel is a rich source of phenolic compounds (PC), which can be used in food fortification. The use of water-in-oil-in-water (W1/O/W2) emulsions represents a potential strategy to encapsulate, protect and incorporate PC from mango peel into food products. Moreover, even though non-digestible biopolymers are usually incorporated into emulsions to enhance stability, little is known about the effect on the digestibility and release of PC. In this study, a mango peel extract (MPE) was encapsulated using W1/O/W2 emulsions containing sodium carboxymethyl cellulose (CMC; 0, 0.5, 1.0% w/w) in W2, and their colloidal stability, lipid digestibility kinetics (free fatty acid release), and release (in terms of antioxidant activity) under in vitro digestion conditions were evaluated. The presence of CMC in emulsions caused flocculation of droplets, which remained unchanged during the gastric phase, suggesting that bridging flocculation occurred. Moreover, a slower lipid digestion rate was observed in emulsions containing CMC, with k-values ranging between 0.21 and 0.25 min-1, compared to emulsions without CMC (around 0.14 min-1). However, although CMC may slow down the lipolysis reaction during the first 40 min due to physical or steric hindrance, at the end of the intestinal phase, emulsions with or without CMC had a similar final FFA release. Moreover, MPE release was triggered under gastric conditions, probably by osmotic imbalance, showing a constant antioxidant activity value during the intestinal phase only in emulsions containing CMC. This study provides relevant insights to design double emulsions as delivery systems of water-soluble bioactive compounds with antioxidant activity, such as PC.

A common genetic mechanism underlies morphological diversity in fruits and other plant organs.

Shapes of edible plant organs vary dramatically among and within crop plants. To explain and ultimately employ this variation towards crop improvement, we determined the genetic, molecular and cellular bases of fruit shape diversity in tomato. Through positional cloning, protein interaction studies, and genome editing, we report that OVATE Family Proteins and TONNEAU1 Recruiting Motif proteins regulate cell division patterns in ovary development to alter final fruit shape. The physical interactions between the members of these two families are necessary for dynamic relocalization of the protein complexes to different cellular compartments when expressed in tobacco leaf cells. Together with data from other domesticated crops and model plant species, the protein interaction studies provide possible mechanistic insights into the regulation of morphological variation in plants and a framework that may apply to organ growth in all plant species.

Gallic Acid Content and an Antioxidant Mechanism Are Responsible for the Antiproliferative Activity of 'Ataulfo' Mango Peel on LS180 Cells.

Mango "Ataulfo" peel is a rich source of polyphenols (PP), with antioxidant and anti-cancer properties; however, it is unknown whether such antiproliferative activity is related to PP's antioxidant activity. The content (HPLC-DAD), antioxidant (DPPH, FRAP, ORAC), and antiproliferative activities (MTT) of free (FP) and chemically-released PP from mango 'Ataulfo' peel after alkaline (AKP) and acid (AP) hydrolysis, were evaluated. AKP fraction was higher (µg/g DW) in gallic acid (GA; 23,816 ± 284) than AP (5610 ± 8) of FR (not detected) fractions. AKP fraction and GA showed the highest antioxidant activity (DPPH/FRAP/ORAC) and GA's antioxidant activity follows a single electron transfer (SET) mechanism. AKP and GA also showed the best antiproliferative activity against human colon adenocarcinoma cells (LS180; IC50 (µg/mL) 138.2 ± 2.5 and 45.7 ± 5.2) and mouse connective cells (L929; 93.5 ± 7.7 and 65.3 ± 1.2); Cheminformatics confirmed the hydrophilic nature (LogP, 0.6) and a good absorption capacity (75%) for GA. Data suggests that GA's antiproliferative activity appears to be related to its antioxidant mechanism, although other mechanisms after its absorption could also be involved.

Polyglutamic acid-PEG nanocapsules as long circulating carriers for the delivery of docetaxel.

Recently we reported for the first time a new type of nanocapsules consisting of an oily core and a polymer shell made of a polyglutamic acid-polyethylene glycol (PEG-PGA) grafted copolymer with a 24% w/w PEG content. The goal of the work presented here has been to develop a new version of these nanocapsules, in which the shell is made of a di-block PEG-PGA copolymer with a 57% w/w PEG content and to evaluate their potential for improving the biodistribution and pharmacokinetics of the anticancer drug docetaxel (DCX). A comparative analysis of the biodistribution of fluorescently labeled PGA-PEG nanocapsules versus PGA nanocapsules or a control nanoemulsion (containing the same oil than the nanocapsules) showed that the nanocapsules, and in particular PEGylated nanocapsules, have significantly higher half-life, MRT (Mean Residence Time) and AUC (Area under the Curve) than the nanoemulsion. On a separate set of experiments, PGA-PEG nanocapsules were loaded with DCX and their antitumor efficacy was evaluated in a xenograft U87MG glioma mouse model. The results showed that the survival rate for mice treated with DCX-loaded nanocapsules was significantly increased over the control Taxotere®, while the antitumoral effect of both formulations was comparable (60% tumor growth inhibition with respect to the untreated mice). These results highlight the potential use of these novel nanocapsules as a new drug delivery platform in cancer therapy.

[Mango: agroindustrial aspects, nutritional/functional value and health effects]. / El mango: aspectos agroindustriales, valor nutricional/funcional y efectos en la salud.

OBJECTIVE: To review and discuss the latest information on agroindustrial, functional and nutritional value of one of the most produced/consumed fruit crop in México: The mango. METHODS: A search was conducted in several databases (PubMed, Cochrane, ScienceDirect) and public repositories (Google Scholar) on Mangifera indica L. This information was further sub-classified into agroindustrial, nutritional, functional aspects and health effects. RESULTS: One out of twenty mangoes consumed worldwide is Mexican. The variety "Ataulfo" variety is the most important crop. Minimal processing of its pulp (MP) generates peel (MC) and seeds as biowastes, which have nutraceutical potential. MP and MC are good sources of ascorbate, fructose, soluble (MP, starches and rhamnogalacturonans) and insoluble (MC, lignin and hemicelluloses) dietary fibers as well as functional lipids (MP). MP and MC are good sources of monomeric (MP) phenolic compounds (PC) such as gallic and protocatehuic acids and polymeric PC (MC) such as -PGG with associated anti-obesigenic, anti-inflammatory, anti-carcinogenic and anti-diabetic potential. However, these benefits are dependent on their bioaccessibility (release from its food matrix) and metabolic fate (bioavailability). DISCUSSION: Mango is a valuable source of antioxidant compounds with proven health benefits. However, factors such as its variety, seasonality, pre and post-harvest handling, extraction of bioactives and some physiological barriers, can modify their nutraceutical potential.

Objetivo: Revisar y discutir la información más reciente sobre el valor agroindustrial, funcional y nutricional de uno de los frutos de mayor cultivo, exportación y consumo en México: el Mango. Métodos: Se realizó una búsqueda en diversas bases de datos (PubMed, Cochrane, ScienceDirect) y documentos de libre acceso (Google Scholar) sobre Mangifera indica L. Esta información fue posteriormente sub-clasificada en aspectos agroindustriales, nutricionales, funcionales y efectos a la salud. Resultados: Uno de cada veinte mangos consumidos mundialmente, es mexicano. "Ataulfo" es la variedad la de mayor importancia agronómica. El procesamiento mínimo de su pulpa (MP) genera residuos de cáscara (MC) y semilla con alto potencial nutracéutico. MP y MC son buenas fuentes de ascorbato, fructosa, fibra dietarias soluble (MP, almidones y ramnogalacturonanos) e insoluble (MC, ligninas y hemicelulosa) y lípidos funcionales (MP). MP y MC poseen un perfil de compuestos fenólicos (CF) monoméricos (MP) como el acido gálico y el protocatehuico y poliméricos (MC) como la -PGG asociados con efectos anti-obesigénicos, anti-inflamatorios, anti-cancerigenos y anti-diabeticos. Estos beneficios son dependientes de la bioaccesibilidad (liberación de su matriz alimentaria) y destino metabólico (biodisponibilidad) de estos CF. Discusión: El mango resulta una valiosa fuente de compuestos antioxidantes con comprobado beneficio a la salud. Sin embargo, factores como la variedad, temporalidad de cultivos, tratamientos pre y post-cosecha, extracción de bioactivos y algunas barreras fisiológicas pueden modificar su potencial nutracéutico.

In vivo evaluation of poly-l-asparagine nanocapsules as carriers for anti-cancer drug delivery.

Here, we report the in vivo proof of-concept of a novel nanocarrier, poly-l-asparagine (PASN) nanocapsules, as an anticancer targeted drug delivery system. The nanocapsules were loaded with the fluorescent marker DiD (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate) and also with the model drug docetaxel to evaluate the biodistribution and efficacy profiles in healthy and glioma-bearing mice, respectively. Regardless of their cargo, the nanocapsules presented a size close to 180 nm, a surface charge around -40 mV and an encapsulation efficiency of 75-90%. The biodistribution study in healthy mice showed that PASN nanocapsules led to a two- and three-fold increment in the mean residence time (MRT) and area under the curve (AUC) values, respectively, compared to those of a non-polymeric nanoemulsion. Finally, the efficacy/toxicity study indicated that the encapsulated drug was as efficacious as the commercial formulation (Taxotere(®)), with the additional advantage of being considerably less toxic. Overall, these results suggest the potential of PASN nanocapsules as drug nanocarriers in anticancer therapy.

Hyaluronan nanocapsules as a new vehicle for intracellular drug delivery.

Here we report the development of new drug nanocarriers - named hyaluronan nanocapsules - for the intracellular delivery of hydrophobic anticancer drugs. These nanocapsules are composed of a lipid core and a shell of hyaluronic acid (HA). Nanocapsules were produced by a modified solvent displacement technique, which allows the formation of the polymer shell around the oily core using a cationic surfactant as an interphase bridge. The resulting nanocapsules have a size of ∼200 nm, a negative zeta potential and a spherical shape. The model drug docetaxel could be efficiently encapsulated within their core. The in vitro cell culture studies (NCI-H460 cancer cell line) showed that the cytotoxicity of docetaxel could be significantly enhanced due to its encapsulation within the nanocapsules. Interestingly, the nanocapsules were stable during storage and they could also be transformed into a powder by freeze-drying. These novel nanostructures hold promise as intracellular drug delivery systems.