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Microalgae of different evolutionary origins are typically found in rivers, lakes, and oceans, providing more than 45% of global primary production. They provide not only a food source for animals, but also affect microbial ecosystems through symbioses with microorganisms or secretion of some metabolites. Derived from amino acids, polyamines are present in almost all types of organisms, where they play important roles in maintaining physiological functions or against stress. Microalgae can produce a variety of distinct polyamines, and the polyamine content is important to meet the physiological needs of microalgae and may also affect other species in the environment. In addition, some polyamines produced by microalgae have medical or nanotechnological applications. Previous studies on several types of microalgae have indicated that the putative polyamine metabolic pathways may be as complicated as the genomes of these organisms, which contain genes originating from plants, animals, and even bacteria. There are also several novel polyamine synthetic routes in microalgae. Understanding the nature of polyamines in microalgae will not only improve our knowledge of microalgal physiology and ecological function, but also provide valuable information for biotechnological applications.

Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark. Literature search in databases as PUBMED and ISI Web of Science in combination with manual search was used to answer the following five questions: (1)Can resveratrol be recommended in the prevention or treatment of human diseases?; (2)Are there observed \"side effects\" caused by the intake of resveratrol in humans?; (3)What is the relevant dose of resveratrol?; (4)What valid data are available regarding an effect in various species of experimental animals?; (5)Which relevant (overall) mechanisms of action of resveratrol have been documented? The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Finally, we suggest directions for future research in resveratrol regarding its mechanism of action and its safety and toxicology in human subjects.

Thyroid hormone analogues—particularly, l -thyroxine (T 4 ) has been shown to be relevant to the functions of a variety of cancers. Integrin αvβ3 is a plasma membrane structural protein linked to signal transduction pathways that are critical to cancer cell proliferation and metastasis. Thyroid hormones, T 4 and to a less extend T 3 bind cell surface integrin αvβ3, to stimulate the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway to stimulate cancer cell growth. Thyroid hormone analogues also engage in crosstalk with the epidermal growth factor receptor (EGFR)-Ras pathway. EGFR signal generation and, downstream, transduction of Ras/Raf pathway signals contribute importantly to tumor cell progression. Mutated Ras oncogenes contribute to chemoresistance in colorectal carcinoma (CRC); chemoresistance may depend in part on the activity of ERK1/2 pathway. In this review, we evaluate the contribution of thyroxine interacting with integrin αvβ3 and crosstalking with EGFR/Ras signaling pathway non-genomically in CRC proliferation. Tetraiodothyroacetic acid (tetrac), the deaminated analogue of T 4 , and its nano-derivative, NDAT, have anticancer functions, with effectiveness against CRC and other tumors. In Ras -mutant CRC cells, tetrac derivatives may overcome chemoresistance to other drugs via actions initiated at integrin αvβ3 and involving, downstream, the EGFR-Ras signaling pathways.

Background Most tail-anchored (TA) membrane proteins are delivered to the endoplasmic reticulum through a conserved posttranslational pathway. Although core mechanisms underlying the targeting and insertion of TA proteins are well established in eukaryotes, their role in mediating TA protein biogenesis in plants remains unclear. We reported the crystal structures of algal arsenite transporter 1 (ArsA1), which possesses an approximately 80-kDa monomeric architecture and carries chloroplast-localized TA proteins. However, the mechanistic basis of ArsA2, a Get3 (guided entry of TA proteins 3) homolog in plants, for TA recognition remains unknown. Results Here, for the first time, we present the crystal structures of the diatom Pt-Get3a that forms a distinct ellipsoid-shaped tetramer in the open (nucleotide-bound) state through crystal packing. Pulldown assay results revealed that only tetrameric Pt-Get3a can bind to TA proteins. The lack of the conserved zinc-coordination CXXC motif in Pt-Get3a potentially leads to the spontaneous formation of a distinct parallelogram-shaped dimeric conformation in solution, suggesting a new dimer state for subsequent tetramerization upon TA targeting. Pt-Get3a nonspecifically binds to different subsets of TA substrates due to the lower hydrophobicity of its α-helical subdomain, which is implicated in TA recognition. Conclusions Our study provides new insights into the mechanisms underlying TA protein shielding by tetrameric Get3 during targeting to the diatom’s cell membrane.

Our previous study found that 2-phenyl-4-quinolone (2-PQ) derivatives are antimitotic agents, and we adopted the drug design concept of scaffold hopping to replace the 2-aromatic ring of 2-PQs with a 4-aromatic ring, representing 4-phenyl-2-quinolones (4-PQs). The 4-PQ compounds, whose structural backbones also mimic analogs of podophyllotoxin (PPT), maybe a new class of anticancer drugs with simplified PPT structures. In addition, 4-PQs are a new generation of anticancer lead compounds as apoptosis stimulators. On the other hand, previous studies showed that 4-arylcoumarin derivatives with 5-, 6-, and 7-methoxy substitutions displayed remarkable anticancer activities. Therefore, we further synthesized a series of 5-, 6-, and 7-methoxy-substituted 4-PQ derivatives (19–32) by Knorr quinoline cyclization, and examined their anticancer effectiveness. Among these 4-PQs, compound 22 demonstrated excellent antiproliferative activities against the COLO205 cell line (50% inhibitory concentration (IC50) = 0.32 μM) and H460 cell line (IC50 = 0.89 μM). Furthermore, we utilized molecular docking studies to explain the possible anticancer mechanisms of these 4-PQs by the docking mode in the colchicine-binding pocket of the tubulin receptor. Consequently, we selected the candidate compounds 19, 20, 21, 22, 25, 27, and 28 to predict their absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. Pharmacokinetics (PKs) indicated that these 4-PQs displayed good drug-likeness and bioavailability, and had no cardiotoxic side effects or carcinogenicity, but we detected risks of drug–drug interactions and AMES toxicity (mutagenic). However, structural modifications of these 4-PQs could improve their PK properties and reduce their side effects, and their promising anticancer activities attracted our attention for further studies.

Integrin αvβ3, a cell surface receptor, participates in signaling transduction pathways in cancer cell proliferation and metastasis. Several ligands bind to integrin αvβ3 to regulate proliferation and metastasis in cancer cells. Crosstalk between the integrin and other signal transduction pathways also plays an important role in modulating cancer proliferation. Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) activates the downstream integrin FAK to stimulate biological activities including cancer proliferation and metastasis. Blockage of signals related to integrin αvβ3 was shown to be a promising target for cancer therapies. 3,3′,5,5′-tetraiodothyroacetic acid (tetrac) completely binds to the integrin with the thyroid hormone to suppress cancer proliferation. The (E)-stilbene analog, resveratrol, also binds to integrin αvβ3 to inhibit cancer growth. Recently, nanotechnologies have been used in the biomedical field for detection and therapeutic purposes. In the current review, we show and evaluate the potentiation of the nanomaterial carrier RGD peptide, derivatives of PLGA-tetrac (NDAT), and nanoresveratrol targeting integrin αvβ3 in cancer therapies.

Background Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a pivotal mechanism in cancer progression and therapeutic resistance. Concurrently, glycosylation, as a key post-translational modification, plays a critical role in regulating cell signaling, immune evasion, and metastasis. Although both processes are independently implicated in tumor biology, the intersection between ferroptosis and glycosylation remains largely unexplored. Methods We performed a comprehensive pan-cancer multi-omics analysis, integrating bulk transcriptomics, epigenomics, and single-cell RNA sequencing datasets. Ferroptosis and glycosylation-related genes were curated from The Molecular Signatures Database (MSigDB), leading to the identification of the metal ion transporter, SLC39A14 (solute carrier family 39 member 14), as a key intersecting gene. A ferroptosis-related gene signature was constructed using machine learning and Cox regression models, followed by survival analyses, immune microenvironment profiling, and a pathway enrichment analysis across The Cancer Genome Atlas (TCGA) cohort. Results SLC39A14 was found to be significantly upregulated across multiple tumor types and associated with a poor prognosis, immune-stromal infiltration, and ferroptosis resistance. Among all cancer types analyzed, glioblastoma multiforme (GBM) and kidney renal cell carcinoma (KIRC) exhibited the significantly prognostic associations and the most pronounced differential expression of SLC39A14. Single-cell analysis revealed that SLC39A14 expression was enriched between stromal and immune populations, hypoxic perivascular niches, confirming its microenvironment-specific functions. These findings were corroborated by DNA methylation data showing promoter hypomethylation of SLC39A14 in tumors compared to normal tissues. Functionally, SLC39A14 was highly enriched in pathways related to angiogenesis, the epithelial-to-mesenchymal transition, cytokine signaling, and oxidative stress adaptation including vascular endothelial growth factor (VEGF) and cell metabolism-related signaling. A nomogram integrating SLC39A14 expression with clinical parameters improved overall survival predictions. Conclusions In this study, we identified SLC39A14 as a dual regulator at the interface of ferroptosis and glycosylation, with significant impacts on tumor microenvironmental remodeling and therapeutic resistance. By leveraging multi-omics and single-cell transcriptomic data, we establish SLC39A14 as a promising prognostic biomarker and therapeutic target, particularly in brain and kidney cancers where ferroptosis modulation could offer novel clinical strategies.

Heteronemin (Haimian jing) is a sesterterpenoid-type natural marine product that is isolated from sponges and has anticancer properties. It inhibits cancer cell proliferation via different mechanisms, such as reactive oxygen species (ROS) production, cell cycle arrest, apoptosis as well as proliferative gene changes in various types of cancers. Recently, the novel structure and bioactivity evaluation of heteronemin has received extensive attention. Hormones control physiological activities regularly, however, they may also affect several abnormalities such as cancer. L -Thyroxine (T 4 ), steroid hormones, and epidermal growth factor (EGF) up-regulate the accumulation of checkpoint programmed death-ligand 1 (PD-L1) and promote inflammation in cancer cells. Heteronemin suppresses PD-L1 expression and reduces the PD-L1-induced proliferative effect. In the current review, we evaluated research and evidence regarding the antitumor effects of heteronemin and the antagonizing effects of non-peptide hormones and growth factors on heteronemin-induced anti-cancer properties and utilized computational molecular modeling to explain how these ligands interacted with the integrin αvβ3 receptors. On the other hand, thyroid hormone deaminated analogue, tetraiodothyroacetic acid (tetrac), modulates signal pathways and inhibits cancer growth and metastasis. The combination of heteronemin and tetrac derivatives has been demonstrated to compensate for anti-proliferation in cancer cells under different circumstances. Overall, this review outlines the potential of heteronemin in managing different types of cancers that may lead to its clinical development as an anticancer agent.

Background Shrimp aquaculture has suffered huge economic losses over the past decade due to the outbreak of acute hepatopancreatic necrosis disease (AHPND), which is mainly caused by the bacteria Vibrio parahaemolyticus ( V. parahaemolyticus ) with the virulence pVA1 plasmid, which encodes a secretory photorhabdus insect-related (Pir) toxin composed of PirA and PirB proteins. The Pir toxin mainly attacks the hepatopancreas, a major metabolic organ in shrimp, thereby causing necrosis and loss of function. The pandemic of antibiotic-resistant strains makes the impact worse. Methods Mild pyrolysis of a mixture of polysaccharide dextran 70 and the crosslinker 1,8-diaminooctane at 180 ℃ for 3 h to form carbonized nanogels (DAO/DEX-CNGs) through controlled cross-linking and carbonization. The multifunctional therapeutic CNGs inherit nanogel-like structures and functional groups from their precursor molecules. Results DAO/DEX-CNGs manifest broad-spectrum antibacterial activity against Vibrio parahaemolyticus responsible for AHPND and even multiple drug-resistant strains. The polymer-like structures and functional groups on graphitic-carbon within the CNGs exhibit multiple treatment effects, including disruption of bacterial membranes, elevating bacterial oxidative stress, and neutralization of PirAB toxins. The inhibition of Vibrio in the midgut of infected shrimp, protection of hepatopancreas tissue from Pir toxin, and suppressing overstimulation of the immune system in severe V. parahaemolyticus infection, revealing that CNGs can effectively guard shrimp from Vibrio invasion. Moreover, shrimps fed with DAO/DEX-CNGs were carefully examined, such as the expression of the immune-related genes, hepatopancreas biopsy, and intestinal microbiota. Few adverse effects on shrimps were observed. Conclusion Our work proposes brand-new applications of multifunctional carbon-based nanomaterials as efficient anti- Vibrio agents in the aquatic industry that hold great potential as feed additives to reduce antibiotic overuse in aquaculture. Graphical Abstract

Food safety concerns regarding foodborne pathogen contamination have gained global attention due to its significant implications. In this study, we developed a detection system utilizing a PCR array combined with an automated magnetic bead-based system and CE technology to enable the detection of three foodborne pathogens, namely Salmonella enterica, Listeria monocytogenes, and Staphylococcus aureus. The results showed that our developed method could detect these pathogens at concentrations as low as 7.3 × 101, 6.7 × 102, and 6.9 × 102 cfu/mL, respectively, in the broth samples. In chicken samples, the limit of detection for these pathogens was 3.1 × 104, 3.5 × 103, and 3.9 × 102 cfu/g, respectively. The detection of these pathogens was accomplished without the necessity for sample enrichment, and the entire protocols, from sample preparation to amplicon analysis, were completed in approximately 3.5 h. Regarding the impact of the extraction method on detection capability, our study observed that an automated DNA extraction system based on the magnetic bead method demonstrated a 10-fold improvement or, at the very least, yielded similar results compared to the column-based method. These findings demonstrated that our developed model is effective in detecting low levels of these pathogens in the samples analyzed in this study. The PCR-CE method developed in this study may help monitor food safety in the future. It may also be extended to identify other foodborne pathogens across a wide range of food samples.