Attractive Source Research Articles

Investigating the clinical significance of E2F5 expression in circulating extracellular vesicles in prostate carcinoma.

Prostate-specific antigen (PSA) based screening strategy has caused a marked improvement in prostate cancer detection and reduction in associated mortality. However, its specificity and sensitivity is not optimal for differentiating different forms of prostate cancer, resulting in overtreatment of indolent tumors. E2F5, a member of the family of transcription factors plays essential roles during many cellular processes. E2F5 amplification is a major event in PCa. A liquid biopsy is a minimally invasive procedure to investigate the cancer-related molecules in circulating tumor cells (CTCs), cell-free DNA, and extracellular vesicles (EVs). Serum and plasma are attractive sources of EV-based biomarkers as blood sample acquisition is a minimally invasive procedure. Given, the shortcomings of PSA as a serum marker, the suitability of E2F5 expression and chemical properties of EVs can be used for the diagnosis of clinically significant prostate cancer. To technically refine the current histopathology-based diagnosis of PCa by adding it to the molecular readouts specific to disease states and biochemical fingerprints of EVs. The study included 100 TRUS-biopsied tissues, 50 representing 4 Gleason grades and another 50 representing BPH. Expression of E2F5 was studied in all the qualified tissues by Immunohistochemistry (IHC). Blood from patients was collected and EVs were isolated and characterized. E2F5 was highly upregulated through all Gleason grades, the maximum being in Gleason 10(5 + 5) and the minimum in Gleason 7(3 + 4), as compared to BPH. The EVs isolated from blood plasma were within 30-200 nm in size. E2F5, being a transcription factor, is highly overexpressed in malignant biopsy tissues, through all Gleason grades. BPH tissues served as control samples. EVs from blood plasma might serve as a potential liquid biopsy marker for predicting disease progression and better prognosis.

Stromal Vascular Fraction of Adipose Tissue: Prospects for Use in the Treatment of Osteoarthritis and Articular Cartilage Injuries (Literature Review)

Summary. Osteoarthritis (OA) is a chronic, progressive, degenerative-dystrophic joint disease primarily caused by damage to the articular cartilage. Conservative pharmacological treatment of OA consists of prescribing nonsteroidal anti-inflammatory drugs, chondroprotectors, hyaluronic acid injections, and therapeutic blockades with glucocorticosteroids. The use of orthobiological agents represents an alternative method in OA treatment. Among the variety of orthobiological approaches, adipose tissue serves as a new and attractive source of stem cells for the treatment of OA. The stromal vascular fraction creates an environment where stem cells can interact and stimulate regeneration.

Secretome and Proteome of Extracellular Vesicles Provide Protein Markers of Lung and Colorectal Cancer

Colorectal cancer (CRC) and lung cancer (LC) are leading causes of cancer-related mortality, highlighting the need for minimally invasive diagnostic, prognostic, and predictive markers for these cancers. Proteins secreted by a tumor into the extracellular space directly, known as the tumor secretome, as well as proteins in the extra-cellular vesicles (EVs), represent an attractive source of biomarkers for CRC and LC. We performed proteomic analyses on secretome and EV samples from LC (A549, NCI-H23, NCI-H460) and CRC (Caco2, HCT116, HT-29) cell lines and targeted mass spectrometry on EVs from plasma samples of 20 patients with CRC and 19 healthy controls. A total of 782 proteins were identified across the CRC and LC secretome and EV samples. Of these, 22 and 44 protein markers were significantly elevated in the CRC and LC samples, respectively. Functional annotation revealed enrichment in proteins linked to metastasis and tumor progression for both cancer types. In EVs isolated from the plasma of patients with CRC, ITGB3, HSPA8, TUBA4A, and TLN1 were reduced, whereas FN1, SERPINA1, and CST3 were elevated, compared to healthy controls. These findings support the development of minimally invasive liquid biopsy methods for the detection, prognosis, and treatment monitoring of LC and CRC.

Clean and Green Bioconversion – A Comprehensive Review on Black Soldier Fly (Hermetia illucens) Larvae for Converting Organic Wastes to Quality Products

Abstract Food security remains a pressing global concern, exacerbated by population growth, diminishing agricultural lands, and climate uncertainties. As the demand for high-quality protein sources like eggs, meat, and milk escalates, conventional feed ingredients face challenges in meeting the burgeoning needs of livestock production. The projected increase in poultry and pig consumption further strains the availability of protein-rich feed sources, necessitating sustainable alternatives. Insects, notably black soldier fly larvae (BSFL), offer numerous advantages, including efficiently converting organic substrates into high-quality protein, fat, minerals, and vitamins. Their rapid reproduction, minimal environmental footprint, and ability to thrive on various organic materials make them an attractive protein source. However, consumer acceptance remains a hurdle, hindering their direct consumption despite their nutritional value. Incorporating BSFL into animal diets, especially poultry and swine, demonstrates promising results regarding growth and production. This review comprehensively overviews BSFL production systems, processing techniques, and nutritional profiles. Various factors influencing BSFL growth and feed quality are discussed, highlighting the importance of optimizing breeding systems and feed formulations. Processing methods are elucidated to ensure the safety and quality of BSFL-based products. Nutritional analysis reveals BSFL as a rich source of essential amino acids, fatty acids, and minerals, making them suitable replacements for soybean meal and fish meal. Despite the economic and environmental benefits of BSFL utilization, challenges persist, including regulatory issues, consumer perceptions, and production scalability. Standardized production protocols and legislative frameworks are needed to facilitate the widespread adoption of BSFL in animal feed industries. In conclusion, integrating BSFL into animal diets presents a promising solution to address protein shortages in livestock production while promoting sustainable resource utilization.

Extraction, Purification, and Next-Generation Sequencing (NGS) Analysis of DNA and RNA from Formalin-Fixed and Paraffin-Embedded (FFPE) Tissue.

Formalin fixed paraffin embedded (FFPE) tissues have long been used for immunohistological analyses. FFPE tissues can be stored at room temperature for several years enabling analyses to be performed later. Ease of storage and transport makes these tissues an attractive source of biological material. However, formalin fixation results in chemical modifications of proteins and nucleic acids that poses a major challenge to any type of analysis. Recovery of nucleic acids for quantitative assays is rendered difficult due to degradation resulting from fixation and long-term storage, producing low usable yields. Extensive efforts in the last 20years have led to significant improvements in use of FFPE tissues for DNA and RNA analyses and resulted in development of sensitive assays for a wide range of applications, including next-generation sequencing. In this chapter, we describe the optimization of methods for sequential extraction of DNA and RNA from FFPE tissue and subsequent preparation of DNA-seq and RNA-seq libraries for use with the Illumina platform using commercially available reagents/kits.

Analysis of hyperbolic crystals with non-square lattice for improving acoustic energy harvesting

Abstract With the increase in the production of small and low-power electrical devices, there has been an increased focus on creating a useful power source to replace the battery. The energy contained in acoustic waves is one of the attractive energy sources for powering low-power devices. The design and fabrication of metamaterials is one of the effective methods of harvesting acoustic energy that has recently attracted the attention of many researchers. As is presented in this article, the aim is to design and fabricate a novel metamaterial structure with optimal dimensions to improve acoustic energy harvesting in a specific frequency range using a piezoelectric patch. In this metamaterial, hyperbolic crystals with non-square lattice have been used for the first time. This analysis is simulated using the 3D version of Comsol software 6.0. In addition, artificial neural networks and genetic algorithms were used to select the optimal parameters. The results showed that using the non-square lattice of the hyperbolic crystal, more average energy can be harvested in the frequency range of 3310-4325 Hz than in the metamaterial with the cylindrical crystal. Furthermore, the maximum amount of voltage and power extraction with an optimal electrical resistance of 10 kΩ in the metamaterial with the hyperbolic crystals at a frequency of 3374.71 Hz is equal to 27.26 mV and 74.33 nW, respectively, which is much larger compared to the metamaterial with the cylindrical crystals under the same mass and conditions. The simulation results are compared and validated with the experimental results by fabricating the present metamaterial and conducting laboratory tests.

Gastric fold-inspired microwrinkled carbon nanotube sheets for harvesting mechanical energy of organ motion

Biomechanical energy from daily activities and organ motion is an attractive energy source because of its sustainability. Mechanical energy harvesters, including triboelectric, piezoelectric, and chemo-mechanical harvesters, are gaining significant attention for converting energy into electrical power for self-powered devices. Chemo-mechanical energy harvesters that utilize the piezoionic effect are particularly suited for harnessing the movements of organs, such as the heart, stomach, and lungs, in the electrolyte-rich environment of the human body. However, existing harvesters are inefficient because of their unidirectional response and high modulus, which hinder organ motion. In this paper, we propose a microwrinkled carbon nanotube (CNT) sheets harvester (MCSH), inspired by the gastric wrinkle morphology and featuring a low modulus (43.9 kPa), capable of multidirectional energy harvesting. The MCSH generates energy through the relaxoionic effect during unfolding and folding cycles, achieving an open-circuit voltage change of 11.6 mV and a peak current of 112.5 A kg−1 in 0.1 M HCl. Finally, the MCSH demonstrated stable energy generation in a human stomach model using simulated body fluids.

A proteomics–bioinformatics approach to assess the molecular and physicochemical properties of brewer's spent grain protein concentrates: Effect of alkali-heat treatment

Brewer's spent grain (BSG) can serve as an attractive protein source due to its low cost and excellent nutritional and functional attributes. Alterations induced by protein extraction process in the BSG protein molecules can affect their functionality and nutritive value. This study investigated the effects of moderate heating during alkaline extraction on the molecular-physicochemical properties of BSG proteins. To this end, BSG protein concentrates were extracted at either room temperature or 50 °C, followed by proteomics and bioinformatics analyses. It was observed that the sample extracted at 50 °C contained proteins with a higher molecular weight, longer length, and enhanced stability relative to the sample extracted at room temperature. The content of acidic proteins showed a 14 % increase due to extraction at 50 °C. A simultaneous decrease in the content of both highly hydrophilic and highly hydrophobic proteins occurred in the sample extracted at 50 °C, while increasing the content of mildly hydrophilic proteins by approximately 25 %. This sample also contained a higher content of essential amino acids. Moreover, the content of proteins with a very high extinction coefficient (>50000 M−1cm−1) increased by 26 % due to extraction at 50 °C. Overall, these findings demonstrate that moderate heating during alkaline extraction can modulate the physicochemical and molecular properties of BSG proteins, providing insights into tailoring their functionality for specific industrial applications.

Study on Pressurized Diesel Reforming with Electrophoretic Deposition Coated Structural Catalyst

Storing hydrogen in gas, liquid and hydrogen carrier form requires the continuous use of energy for conversion and storage. Therefore, on-site hydrogen production using liquid fuel reforming has a great advantage in a condition that must be stored for a long time. Diesel is the most attractive source for emergency generators or mobile power unit, because of its high volumetric and gravimetric energy density, storage stability, and its accessibility. For diesel reforming, precious metal catalysts has been commonly used for high fuel conversion and reforming efficiency. However, reforming high-carbon liquid fuels causes a number of difficulties, including catalyst deactivation due to coke formation, active metal aggregation due to high-temperature reforming, cracks and delamination in structural catalysts. To address these challenges, in this study, electrophoretic deposition (EPD) coating method is used to make a structural catalyst for pressurized reforming. This coating achieved high dispersion and sufficient porosity to promote the reforming performance. By comparing the fuel conversion rate and reforming efficiency of metal foam structural catalysts and monolith catalysts, the performance of EPD coated catalyst shows the higher performance. Furthermore, at the condition of SCR: 2.0, OCR: 0.55, GHSV: 3,000 h-1, T: 800ºC, and P: 8 bar(g), the EPD-coated catalyst lasted 196 hours. Therefore, we achieved high conversion to hydrogen while reducing the amount of precious metals, leading to enhanced cost-effectiveness of diesel-reforming catalysts.

Hydrothermally Grown Dual-Phase Heterogeneous Electrocatalysts for Highly Efficient Rechargeable Metal-Air Batteries with Long-Term Stability

Metal-air batteries as alternatives to the existing lithium-ion battery are becoming increasingly attractive sources of power due to their high energy-cost competitiveness and inherent safety; however, their low oxygen evolution and reduction reaction (OER/ORR) performance and poor operational stability must be overcome prior to commercialization. Herein, it is demonstrated that a novel class of hydrothermally grown dual-phase heterogeneous electrocatalysts, in which silver-manganese (AgMn) heterometal nanoparticles are anchored on top of 2D nanosheet-like nickel vanadium oxide (NiV2O6), allows an enlarged surface area and efficient charge transfer/redistribution, resulting in a bifunctional OER/ORR superior to those of conventional Pt/C or RuO2. The dual-phase NiV2O6/AgMn catalysts on the air cathode of a zinc-air battery lead to a stable discharge–charge voltage gap of 0.83 V at 50 mA cm−2, with a specific capacity of 660 mAh g−1 and life cycle stabilities of more than 146 h at 10 mA cm−2 and 11 h at 50 mA cm−2. The proposed new class of dual-phase NiV2O6/AgMn catalysts are successfully applied as pouch-type zinc-air batteries with long-term stability over 33.9 h at 10 mA cm−2. Figure 1

Evaluation of the Anti-Cancer Potential of Extracellular Vesicles Derived from Human Amniotic Fluid Stem Cells: Focus on Effective miRNAs in the Treatment of Melanoma Progression.

Mesenchymal stromal cells (MSCs) and their secretome show intrinsic antitumor properties, however, the anti-cancer effects of MSCs remain debated and depend on the cancer type or model. MSCs derived from discarded samples, such as human amniotic fluid (hAFSC), have been introduced as an attractive and potent stem cell source for clinical applications due to their collection procedures, which minimize ethical issues. Until now, various studies have obtained controversial results and poor understanding of the mechanisms behind the effects of perinatal cells on cancer cells. To better clarify this aspect, protein and miRNA expression profiling isolated from Extracellular vesicles (EVs) secreted by hAFSCs, obtained in the II or III trimester, were evaluated. Bioinformatic analysis was performed aiming at evaluating differential expression, pathway enrichment, and miRNA-mRNA networks. We highlighted that most of the highest expressed proteins and miRNAs are mainly involved in antioxidant and anti-cancer effects. Indeed, in the presence of hAFSC-EVs, a reduction of the G2/M phase was observed on melanoma cell lines, an activation of the apoptotic pathway occurred and the migration and invasion ability reduced. Our data demonstrated that II or III trimester hAFSCs can release bioactive factors into EVs, causing an efficient anti-cancer effect inhibiting melanoma progression.

Identification of a novel NADPH generation reaction in the pentose phosphate pathway in Escherichia coli using mBFP.

NADPH is a redox cofactor that drives the anabolic reactions. Although major NADPH generation reactions have been identified in Escherichia coli, some minor reactions have not been identified. In the present study, we explored novel NADPH generation reactions by monitoring the fluorescence dynamics after the addition of carbon sources to starved cells, using a metagenome-derived blue fluorescent protein (mBFP) as an intracellular NADPH reporter. Perturbation analyses were performed on a glucose-6-phosphate isomerase (PGI) deletion strain and its parental strain. Interestingly, mBFP fluorescence increased not only in the parental strain but also in the ΔPGI strain after the addition of xylose. Because the ΔPGI strain cannot metabolize xylose through the oxidative pentose phosphate pathway, this suggests that an unexpected NADPH generation reaction contributes to an increase in fluorescence. To unravel this mystery, we deleted the NADPH generation enzymes including transhydrogenase, isocitrate dehydrogenase, NADP+-dependent malic enzyme, glucose-6-phosphate dehydrogenase (G6PDH), and 6-phosphogluconate dehydrogenase (6PGDH) in the ΔPGI strain, and revealed that G6PDH and 6PGDH contribute to an increase in fluorescence under xylose conditions. In vitro assays using purified enzymes showed that G6PDH can produce NADPH using erythrose-4-phosphate (E4P) as a substitute for glucose-6-phosphate. Because the Km (0.65 mM) for E4P was much higher than the reported intracellular E4P concentrations in E. coli, little E4P must be metabolized through this bypass in the parental strain. However, the flux would increase when E4P accumulates in the cells owing to genetic modifications. This finding provides a metabolic engineering strategy for generating NADPH to produce useful compounds using xylose as a carbon source.IMPORTANCEBecause NADPH is consumed during the synthesis of various useful compounds, enhancing NADPH regeneration is highly desirable in metabolic engineering. In this study, we explored novel NADPH generation reactions in Escherichia coli using a fluorescent NADPH reporter and found that glucose-6-phosphate dehydrogenase can produce NADPH using erythrose-4-phosphate as a substrate under xylose conditions. Xylose is an abundant sugar in nature and is an attractive carbon source for bioproduction. Therefore, this finding contributes to novel pathway engineering strategies using a xylose carbon source in E. coli to produce useful compounds that consume NADPH for their synthesis.

Experimental Investigation of Ammonia/Oxygen/Argon Combustion: The Role of Equivalence Ratio and Nozzle Shape in a Constant Volume Combustion Chamber with Sub-chamber

The global rise in carbon emissions presents a rising challenge for current and future generations. In the pursuit of zero carbon emissions, ammonia (NH3) has emerged as an attractive alternative energy source. Ammonia offers a carbon-free fuel option with a higher energy density than liquid hydrogen while maintaining ease of transport and storage. However, ammonia still has its drawbacks, such as a high autoignition temperature, slow burning velocity, and low heating value, that demand further investigation of its combustion characteristics. This experiment was done to study the effect of nozzle shape and equivalence ratio (ɸ) on the combustion of an ammonia/oxygen/argon mixture using a constant volume combustor equipped with a sub-chamber. The fuels were premixed for 10 minutes and conditioned to an initial pressure of 0.2 MPa and an initial mixture temperature of 423 K. The results show that the different nozzle shapes each have their advantages in terms of pressure and jet speed. Overall, the lean mixtures (ɸ0.6 and ɸ0.8) consistently performed better compared to the stoichiometric mixtures (ɸ1.0) in all categories investigated in this study. The round nozzle generates higher pressure, while the special shape nozzle enhances jet speed, highlighting trade-offs between the two.

Showy birds on attractive food sources: rainbow lorikeets and their plant-related functions at a residential area in South-eastern Australia

Showy birds on attractive food sources: rainbow lorikeets and their plant-related functions at a residential area in South-eastern Australia

Origin of the intermolecular forces that produce donor–acceptor stacks in π-conjugated charge-transfer complexes

The attraction between π-conjugated planar electron donor and acceptor molecules that form many stable charge-transfer (CT) complexes has been explained by quantum chemical CT interactions, although the fundamental origin remains unclear. Here, we demonstrate the mechanism of CT complex formation by potential energy map analysis for TTF–CA and BTBT–TCNQ, using energy decomposition of intermolecular interaction by symmetry-adapted perturbation theory (SAPT) combined with coupled cluster calculation. We find that the source of attraction between donor and acceptor molecules is ascribed primarily to the dispersion force and also to the electrostatic force. In contrast, the contribution of CT interactions to the attractive forces is minimal. We demonstrate that the highly directional feature of the exchange repulsion force, coupled with the attractive dispersion and electrostatic forces, is crucial in determining the intermolecular arrangements of actual CT crystals. These findings are key for understanding the unique structural and electronic properties of π-conjugated CT complexes.

A Study on iPSC-Associated Factors in the Generation of Hepatocytes.

Hepatocytes are an attractive cell source in hepatic tissue engineering because they are the primary cells of the liver, maintaining liver homeostasis through their intrinsic function. Due to the increasing demand for liver donors, a wide range of methods are being studied to obtain functionally active hepatocytes. iPSCs are one of the alternative cell sources, which shows great promise as a tool for generating hepatocytes. This study determined whether factors associated with iPSCs contributed to variation in hepatocyte-like cells derived from iPSCs. The factors of concern for the iPSCs included the culture system, the source of iPSCs, and cell seeding density for initiating the differentiation. Our results found iPSC-dependent variances among differentiated hepatocyte-like cells. The matrix used in culturing iPSCs significantly impacts cell morphologies, characteristics, and the expression of pluripotent genes, such as OCT4 and SOX2, varied in iPSCs derived from different sources. These characteristics, in turn, play a consequential role in determining the functional activity of the iPSC-derived hepatocyte-like cells. In addition, cell seeding density was observed to be an essential factor for the efficient generation of iPSC-derived hepatocyte-like cells, with 2- 4 × 10 cells/cm of seeding density resulting in good morphology and functionality. This study provides the baseline of effective differentiation protocols for iPSC-derived hepatocyte-like cells with the appropriate conditions, including cell culture media, iPSC source, and the seeding density of iPSCs.

Efficient extraction of interstitial fluid using an ultrasonic-powered replaceable hexagram-shaped hydrogel microneedle patch for monitoring of dermal pharmacokinetics and psoriatic biomarkers

Monitoring biomarkers and pharmacokinetics is crucial for the precise diagnosis and treatment of chronic skin diseases. Dermal interstitial fluid (ISF) presents an attractive alternative source of biomarkers and drugs to blood; however, a simple, efficient, and comfortable extraction method is lacking. Here, we combine high-precision 3D printing and micromolding to develop an ultrasonic-powered, replaceable hexagram-shaped hydrogel microneedle (HMN) patch. Hexagram-shaped HMNs exhibit superior mechanical strength and faster ISF extraction rates compared to cone, pyramid, and octagram shapes. The patch, attached to a holder and integrated with a commercial ultrasonic device via a customized connector, allows easy replacement after use. With ultrasound assistance, the patch extracts over 15 μL, 6 μL, and 4 μL of ISF from porcine skin ex vivo, healthy mouse skin, and psoriatic mouse skin in vivo, respectively, within 1 min. The recovered ISF, obtained via centrifugation from HMNs, is used to monitor the dermal pharmacokinetics of drugs (e.g., methotrexate) and psoriasis-related biomarkers (e.g., interleukin-17 and –22) in mouse models, showing trends comparable to those detected via skin biopsy and blood draw. This ultrasonic-powered, replaceable hexagram-shaped HMN patch holds great promise for advancing the diagnosis, treatment, and research of skin diseases.

Partial or complete replacement of soybean meal with black soldier fly larvae meal improves feed efficiency in laying hens between 22 to 30 weeks of age

Abstract The European Commission recently authorised the inclusion of insect meal in poultry feed. Black soldier fly larvae meal (BSF) has comparable nutritional value to soybean meal (SBM) and higher calcium content, making it an attractive alternative protein source for laying hens While a few studies have explored this objective, inconsistent results have been reported, likely due to variations in hen age, breed, husbandry systems, and sunflower meal composition across studies, making it difficult to draw clear conclusions. We hypothesised that partial or complete replacement of SBM with BSF has no adverse effects on egg production and quality in laying hens at the initiation of laying (22-30 weeks of age). This study consisted of three dietary treatments and nine replicates per treatment. Diets were a control diet, and two diets containing 5% (BSF5%) and 10% (BSF10%). The experimental unit was a pen (100 × 200 × 200 cm) of 14 Brown Nick laying hens resembling an aviary setting. We found that complete replacement of SBM with BSF10% in the diet of laying hens improved feed efficiency attributed to a lower feed intake in comparison to laying hens fed the BSF5% or the control diets, while production performance, body weight, and egg quality were maintained and the colour of the egg yolk increased. Therefore, replacing SBM with up to 10% BSF in brown laying hens in aviary pens at the initiation of laying had no adverse effects on production performance, chemical and physical characteristics, and sensory attributes of eggs. Maintaining production and egg quality with a lower intake of nutrients requires further investigation.

Origin of dedifferentiated adipocyte-derived cells (DFAT) during ceiling culture in an Adiponectin Cre-Recombinase mouse model.

Dedifferentiated adipose tissue-derived (DFAT) cells represent an attractive source of stem cells for tissue engineering and the potential treatment of several clinical conditions. Our objective was to determine whether DFAT cells originate from mature adipocytes and address whether contamination from the stromal vascular fraction (SVF) could be as a source for these cells. A murine adiponectin-creERT; mT/mG model was used with the excision of the cassette induced by tamoxifen injection for the cells expressing adiponectin (adipoq). This model allows distinguishing mature adipocytes (green fluorescence) from other SVF cell types (red fluorescence) based on the fluorescent protein expressed. Mature adipocytes and SVF cells were isolated from adipose tissues by collagenase digestion. Ceiling cultures were imaged by time-lapse microscopy. Confocal microscopy was used to follow cells over 21 days. Time-lapse microscopy experiments showed liposecretion occurring in mature adipocytes displaying green fluorescence. Confocal imaging allowed the identification of a heterogeneous cell population expressing green but also red fluorescence after 21 days of culture. Asymmetrical division of mature adipocytes was not observed. In conclusion, liposecretion of mature adipocytes is a phenomenon that can be observed in vitro and DFAT cells do originate from mature adipocytes. However, the population of DFAT cells is heterogenous.

Impact of Nordihydroguaiaretic Acid on Proliferation, Energy Metabolism, and Chemosensitization in Non-Small-Cell Lung Cancer (NSCLC) Cell Lines.

Lung cancer (LC) is the leading cause of cancer death worldwide. LC can be classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), with the last subtype accounting for approximately 85% of all diagnosed lung cancer cases. Despite the existence of different types of treatment for this disease, the development of resistance to therapies and tumor recurrence in patients have maintained the need to find new therapeutic options to combat this pathology, where natural products stand out as an attractive source for this search. Nordihydroguaiaretic acid (NDGA) is the main metabolite extracted from the Larrea tridentata plant and has been shown to have different biological activities, including anticancer activity. In this study, H1975, H1299, and A549 cell lines were treated with NDGA, and its effect on cell viability, proliferation, and metabolism was evaluated using a resazurin reduction assay, incorporation of BrdU, and ki-67 gene expression and glucose uptake measurement, respectively. In addition, the combination of NDGA with clinical chemotherapeutics was investigated using an MTT assay and Combenefit software (version 2.02). The results showed that NDGA decreases the viability and proliferation of NSCLC cells and differentially modulates the expression of genes associated with different metabolic pathways. For example, the LDH gene expression decreased in all cell lines analyzed. However, GLUT3 gene expression increased after 24 h of treatment. The expression of the HIF-1 gene decreased early in the H1299 and A549 cell lines. In addition, the combination of NDGA with three chemotherapeutics (carboplatin, gemcitabine, and taxol) shows a synergic pattern in the decrease of cell viability on the H1299 cell line. In summary, this research provides new evidence about the role of NDGA in lung cancer. Interestingly, using NDGA to enhance the anticancer activity of antitumoral drugs could be an improved therapeutic resource against lung cancer.