Search Results (294)

Malaria persists as a paradigmatic model of co-evolutionary complexity, emerging from the dynamic interplay among a human host, Anopheles vectors, and Plasmodium falciparum parasites. In human populations, centuries of selective pressures have sculpted an intricate and heterogeneous immunogenetic landscape. Classical adaptations, such as hemoglobinopathies, are complemented by a diverse array of genetic polymorphisms that modulate innate and adaptive immune responses. These genetic traits, along with the acquisition of functional immunity following repeated exposures, mitigate disease severity but are continually challenged by the parasite’s highly evolved mechanisms of antigenic variation and immunomodulation. Such host adaptations underscore an evolutionary arms race that perpetually shapes the clinical and epidemiological outcomes. Intermediaries in malaria transmission have evolved robust responses to both natural and anthropogenic pressures. Their vector competence is governed by complex polygenic traits that affect physiological barriers and immune responses during parasite development. Recent studies reveal that these mosquitoes exhibit rapid behavioral and biochemical adaptations, including shifts in host-seeking behavior and the evolution of insecticide resistance. Mechanisms such as enhanced metabolic detoxification and target site insensitivity have emerged in response to the widespread use of insecticides, thereby eroding the efficacy of conventional interventions like insecticide-treated bed nets and indoor residual spraying. These adaptations not only sustain transmission dynamics in intervention saturated landscapes but also challenge current vector control paradigms, necessitating the development of innovative, integrated management strategies. At the molecular level, P. falciparum exemplifies evolutionary ingenuity through extensive genomic streamlining and metabolic reconfiguration. Its compact genome, a result of strategic gene loss and pruning, is optimized for an obligate parasitic lifestyle. The repurposing of the apicoplast for critical anabolic functions including fatty acid, isoprenoid, and haem biosynthesis highlights the parasite’s ability to exploit host derived nutrients efficiently. Moreover, the rapid accumulation of mutations, coupled with an elaborate repertoire for antigenic switching and epigenetic regulation, not only facilitates immune escape but also accelerates the emergence of antimalarial drug resistance. Advanced high throughput sequencing and functional genomics have begun to elucidate the metabolic epigenetic nexus that governs virulence gene expression and antigenic diversity in P. falciparum. By integrating insights from molecular biology, genomics, and evolutionary ecology, this study delineates the multifaceted co-adaptive dynamics that render malaria a recalcitrant global health threat. Our findings provide critical insights into the molecular arms race at the heart of host–pathogen vector interactions and underscore promising avenues for the development of next generation therapeutic and vector management strategies aimed at sustainable malaria elimination. Full article

The membranes of halophilic archaea are a source of novel biomaterials, mainly of isoprenoid nature, with therapeutic properties practically unraveled. Here, we explored the antitumoral activity of neutral archaeolipids (NAs, such as bacterioruberin, astaxanthin, and dihydrosqualene) present in the total archaeolipids (TAs) (a fraction from the first step of lipid extraction by the modified Blight and Dyer technique) extracted from halophilic archaea Halorubrum tebenquichense, and formulated as TA-nanoarchaeosomes (TA: polar archaeolipids (PAs): Tween 80, 5:5:4 w:w:w, TA-nanoARC). The structure of 300.3 ± 84.2 nm TA-nanoARC of 0.59 ± 0.12 polydispersity index and −20 ± 3.7 mV ζ potential as determined by SAXS modelling, revealed that NA reduced the hydrophobic core and enlarged its hydrophilic section in comparison to TA-lacking bilayers (nanoARC), while preserving the width (~50 Å) and unilamellarity. Stable to storage and nebulization, TA-nanoARC was cytotoxic on A549 cells after 48 h, with an IC50 expressed as [bacterioruberin] of 0.15 μg/mL (~0.20 µM), comparable to or lower than the IC50 of docetaxel or cisplatin. Such cytotoxicity was exerted at a concentration harmless to macrophages (mTHP-1 cells). Besides, the conditioned medium from TA-nanoARC nebulized on A549 cells reduced the expression of the CD204/SRA-1, an M2 phenotype marker, and induced pro-inflammatory activity, comparable to or to a greater extent than that induced by lipopolysaccharide, including IL-6 and TNF-α, in mTHP-1 as a model of tumor-associated macrophages. The endocytosis of TA-nanoARC by A549 cells induced Lysotracker red fluorescence to fade and blur. This suggested the internalization of the highly viscous and ordered TA-nanoARC rich in NAs and subsequent lysosomal dysfunction (and not its antioxidant activity), as responsible for the selective damage on A549 cells. These are the first results showing that nebulized TA-nanoARC, lethal to A549 cells and modulating mTHP-1 cell phenotype, may act as antitumorals in the absence of cytotoxic drugs. Full article

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key modulator of low-density lipoprotein cholesterol (LDL-C) levels and emerged as an attractive therapeutic target for the treatment of hypercholesterolemia and cardiovascular diseases. Although statins and ezetimibe have been widely used to manage these disorders, concerns regarding side effects and high costs have driven ongoing efforts to search for alternative therapeutic candidates. To date, several classes of PCSK9 inhibitors, including monoclonal antibodies, oligonucleotides, proteins, and peptides, have been approved or are under clinical trials. In this review, we summarize 57 newly identified compounds derived from natural products showing inhibitory effects against PCSK9 reported between 2020 and April 2025. These compounds were isolated from 18 plants species and belong to various structural classes, including isoprenoids, flavonoids, alkaloids, and phenolic derivatives. Full article

Volatile compounds greatly affect tomato aroma, but systematic analysis of volatiles in tomatoes is limited by detection techniques. Here, HS-SPME Arrow-GC × GC-Q/TOFMS was employed to analyze tomato flavor profiles across different cultivation times. To investigate the effects of light and temperature on aroma profiles, three tomato samples across different cultivation periods, including S1 (harvested on May 30th, with lowest temperature and light conditions), S2 (harvested on August 10th, with the highest temperature and light), and S3 (harvested on June 27th, with moderate temperature and light), were analyzed. Overall, 227 volatiles were identified, belonging to 9 aroma categories. Hexanal, (E)-2-hexenal, nonanal, (E)-2-Octenal, trans-geranylacetone, 6-methyl-5-hepten-2-one, 3,4-Octadiene, 7-methyl-, and citral were found to be the key volatiles contributing most significantly to differentiating the samples across cultivation periods, imparting grassy and floral–fruity notes, respectively. The S1 tomatoes had a distinct grassy aroma, whereas the S3 tomatoes had a floral/fruity fragrance. Most differential metabolites were correlated with fatty acid, amino acid, and isoprenoid pathways. S1 tomatoes were characterized by fatty aldehydes (mainly C6/C9), and S2 tomatoes contained high concentrations of fatty alcohols. S3 tomatoes were positively correlated with isoprenoid-derived volatiles. These variations might be caused by the fluctuations in daily temperature and light intensity. This work establishes a foundational reference for assessing environmental effects on tomato flavor profiles. Full article

All forms of vitamin A have a similar structure and physiological functions in the body. These compounds can be classified as retinoids, including moieties with a common structure of four isoprenoid units of natural or synthetic origin. Vitamin A is generally uptake from products of animal origin (retinol and its derivatives) or from plants as provitamin A (carotenoids). Vitamin A is fat-soluble, so it is easily absorbed and transported in the body. The main storage sites are the liver and adipose tissue. Excessive amounts of the vitamin may lead to the development of different abnormal processes in the human body. Apart from being crucial for retina conditions and functions and the immune system, vitamin A is also deeply involved in DNA repair mechanisms. Its antioxidant nature helps to reduce the oxidative damage to DNA by neutralizing free radicals and thus decreasing the oxidative stress. On the other hand, vitamin A deficiency leads to lower antioxidant enzyme activity, which results in the weakening of the defense system against free radicals. This study aims to elucidate the mechanisms of DNA repair and determine the role of carotenoids, vitamin A, and its derivatives as contributing factors in this process. This review synthesizes the current knowledge on the dual role of vitamin A in DNA integrity by examining the conditions under which it acts as a genotoxic agent versus a facilitator of DNA repair. This article also discusses the role of vitamin A in inhibiting oxidative stress and its anti- and pro-cancer impact. Full article

The increasing global demand for energy and the urgent need to mitigate climate change have driven the search for sustainable alternatives to fossil fuels, with biofuels emerging as a promising solution. However, the low yields and inefficiencies in biofuel production processes necessitate advanced strategies to enhance their commercial viability. Metabolic engineering has become a pivotal tool in optimizing microbial pathways to improve biofuel production, addressing these challenges through innovative genetic and synthetic biology approaches. This review highlights the role of metabolic engineering in enhancing biofuel production by focusing on microbial engineering for lignocellulosic biomass utilization, strategies to overcome inhibitor effects, and pathway optimization for biofuels like n-butanol and iso-butanol. It also explores the production of advanced biofuels from fatty acid and isoprenoid pathways, emphasizing the use of model organisms such as Escherichia coli and Saccharomyces cerevisiae. Key insights include the application of CRISPR/Cas9 and multiplex automated genome engineering for precise genetic modifications, as well as metabolic flux analysis to optimize pathway efficiency. Additionally, the review discusses synthetic biology methodologies to rewire metabolic networks and improve biofuel yields, providing a comprehensive overview of current advancements and their implications for industrial-scale production. Full article

Photosynthetic organisms such as cyanobacteria have the potential for the sustainable production of complex organic molecules due to their ability to use light as an energy source to fix CO₂ and assimilate inorganic nutrients. Over the past decade, large efforts have been put into the metabolic engineering of cyanobacteria to produce various compounds such as alcohols, isoprenoids, biopolymers, and recombinant proteins. Forskolin is a structurally complex labdane-type diterpenoid with eight chiral carbon atoms and is naturally produced in the root cork of the plant Plectranthus barbatus. Forskolin is a potent cAMP activator indicated as a pharmaceutical for a variety of diseases. In the plant, forskolin biosynthesis from geranylgeranyl diphosphate involves six enzymes: two terpene synthases, three cytochrome P450s, and a single acetyltransferase. In this work, we express all six biosynthetic genes from Plectranthus barbatus in Synechocystis sp. PCC. 6803 and demonstrate heterologous production of this complex diterpenoid in a phototroph cyanobacterium. Forskolin titers reached 25.0 ± 4.4 µg/L and the forskolin was entirely secreted into the media. The forskolin-producing Synechocystis strain and empty vector control were cultivated in a photobioreactor for 8 days. Both strains showed similar chlorophyll a contents, and the forskolin-producing strain reached a slightly higher OD₇₃₀ than the control. Forskolin began accumulating in the supernatant after 4 days and increased over time. These results indicate that forskolin production did not negatively impact cell growth. Full article

Protein prenylation is a crucial post-translational modification that involves the formation of a covalent bond between isoprenoid lipids and the cysteine residues of specific proteins. This modification plays a significant role in determining protein localization, facilitating protein–protein interactions, and ultimately influencing protein function within the cellular context. Prenylation is a conserved process observed across various kingdoms of life, including plants, animals, fungi, and protists. This review aims to consolidate existing knowledge regarding the mechanisms underlying protein prenylation, encompassing the biosynthetic pathways of isoprenoids in plants and the processing involved in the prenylation modification. Furthermore, it highlights the implications of alterations in protein prenylation on plant development, signaling pathways, and stress responses. The review also addresses the similarities in modification mechanisms between plants and animals, as well as the diversity of their functional implications. Finally, it outlines prospective research directions of the plant prenylation mechanisms and the potential applications in the field of biotechnology. Full article

The Onocleaceae family, a small group within the Pteridophytes, comprises four genera, but has been phytochemically studied mainly for Pentarhizidium orientale, Pentarhizidium intermedium, and Matteuccia struthiopteris. To date, a total of 91 compounds have been isolated from these three species, including 15 flavonoids, 48 flavonoid glycosides, 6 stilbenes, 4 isocoumarins, 2 phthalides, 3 chromones, 2 lignan glycosides, 8 isoprenoid derivatives, and 3 phenolic compounds. Notably, most flavonoids and flavonoid glycosides possess C-methyl groups at the C-6 and/or C-8 positions, with several conjugated to (S)-3-hydroxy-3-methylglutaryl (HMG) moieties. Although not all isolates have been evaluated for their pharmacological activities, several compounds have demonstrated bioactivities such as antiviral, anti-inflammatory, α-glucosidase inhibitory, aldose reductase inhibitory, and antioxidant effects. Full article

Carotenoids are part of a diverse group of isoprenoid compounds. Due to the many properties they possess, they may become an alternative to synthetic additives in various industrial sectors. The increase in consumer demand and awareness determines research into extracting them from plants, algae and microorganisms. The extraction of carotenoids from plants is an inefficient method and generates additional production costs. On the other hand, the carotenoid potential of microorganisms, especially among yeasts, has not been fully exploited. The diversity of yeast species and strains influences the extraction of many fractions of carotenoids, including the less known ones such as thorulene and tholuradine. The developed adaptability of yeast enables the optimisation of their culture, which facilitates the understanding of their metabolic pathways. At the same time, the coordination of carotenoid and lipid synthesis may prevent their degradation or the loss of their bioactive properties. Application research has been conducted mainly in the feed industry, where their colouring and antimicrobial or immunomodulating properties are used. In the medical and pharmaceutical fields, there is not much research due to safety restrictions and the necessity of the high purity of the fractions. This review also highlights the overlooked aspect of carotenoids’ biodegradability, which is required to exploit the bioactive properties of microbial carotenoids. Full article

Bacterial pigments have gained significant attention across multiple industries due to their natural hues and unique functional properties. Beyond coloration, some of these pigments exhibit antibacterial activity, making them particularly valuable in the textile industry as sustainable alternatives to synthetic antimicrobial treatments. Bacteria produce a vast array of pigments through diverse biosynthetic pathways, which reflect their metabolic adaptability and ecological roles. These pathways are influenced by environmental factors such as pH, temperature, and nutrient availability. Key pigments, including carotenoids, melanin, violacein, and prodigiosin, are synthesised through distinct mechanisms, often involving tightly regulated enzymatic reactions. For example, carotenoid biosynthesis relies on isoprenoid precursors, while melanin formation involves the oxidation of aromatic amino acids. Understanding these pathways provides insights into bacterial survival strategies, stress responses, and interactions with their environment. This review examines the dyeing potential of bacterial pigments on natural and synthetic fabrics, highlighting advancements in environmentally friendly extraction methods to minimise the ecological impact. Additionally, it explores safety, biocompatibility, and industrial challenges associated with bacterial pigment applications. Finally, future perspectives on integrating these pigments into various industries are discussed, emphasising their potential as bio-based solutions for sustainable and functional materials. Full article

The root conformation of soybean is critical to achieve physiological activities such as nodulation and nitrogen fixation; however, the molecular determinants behind genotypic differences in its early development remain poorly described. In this study, we compared the characteristics of the soybean varieties HN75 and HN76 and examined developmental disparities in their root architectural characteristics and the transcriptomic profiles of radicles between them. The plant height and 100-grain weight of HN75, which had a longer growth cycle of 170 days, were slightly higher than those of HN76, which had a shorter growth cycle of 120 days. However, the numbers of pods and grains per plant were slightly lower. In terms of quality traits, HN75 had a higher oil content (23.40% versus 21.50%), whereas HN76 had a higher protein content (41.39% versus 35.71%). HN75 exhibited markedly superior root elongation (13.27 cm versus 10.15 cm), enhanced lateral root proliferation, and significantly greater nodule formation (19.53 versus 8.60 nodules per plant) relative to HN76 at 30 days post-germination, notwithstanding comparable nodule biomass. Chronobiological analysis (0–96 h post-germination) identified a pivotal developmental window of 48–72 h post-germination. Transcriptomic profiling of radicle tissues revealed 4792 differentially expressed genes (DEGs) in HN75 compared to 896 in HN76 during this critical interval, indicating substantially heightened transcriptional activity in HN75. Functional annotation enrichment demonstrated that HN75 DEGs were significantly enriched in phytohormone signalling cascades and isoprenoid biosynthetic pathways, whereas HN76 DEGs were predominantly associated with protein processing within the endoplasmic reticulum. We screened for eight genes (Glyma 10G071400, Glyma 13G057500, Glyma 08G016900, Glyma 09G028000, Glyma 18G265800, Glyma 03G032800, Glyma 02G064100, and Glyma 01G238600) that may play a role in the critical period of radicle development by performing network analyses and verified their dramatic changes in expression during this period by qRT-PCR. These results elucidate varietal-specific physiological and molecular mechanisms governing early radicle development in soybeans. These findings unravel mechanisms governing leguminous radicle development while establishing molecular blueprints for engineering cultivation protocols that would enhance soybean sustainability in edaphically constrained environments. Full article

Apical dominance and culture heterogeneity significantly limit the efficiency of olive micropropagation, hindering the rapid production of plantlets. This study explores how manipulating the explant origin (topophysis) and density can mitigate these challenges. Explants originating from apical and middle sections were cultivated at densities of 18, 24, and 30 explants per vessel. After 12 weeks, significant differences in the growth parameters were observed based on the explant origin and density. The middle-section explants exhibited superior shoot proliferation and node production, especially at higher densities. The callus weight also increased with the density, while the internode length remained relatively stable. Hormone analysis demonstrated the density-dependent spatial distribution pattern of aromatic and isoprenoid cytokinins. Notably, at higher densities, the aromatic free bases in the apical-section leaves showed migration toward the shoot apices, while this migration was less pronounced in the middle-section leaves. Isoprenoid cytokinins displayed complex distribution patterns, with free bases and O-glucosides often increasing toward the basal nodes. These findings demonstrate that optimizing the explant origin and density can effectively reduce apical dominance and enhance culture homogeneity in olive micropropagation. This approach offers a promising strategy for improving the micropropagation protocols for olive and potentially other woody plants, leading to more efficient and cost-effective production of high-quality plantlets for commercial use. Full article

Archaeal lipids, defining a primordial life domain alongside Bacteria and Eukarya, are distinguished by their unique glycerol-1-phosphate backbone and ether-linked isoprenoid chains. Serving as critical geochemical biomarkers, archaeal lipids like glycerol dialkyl glycerol tetraethers (GDGTs) underpin paleoclimate proxies, while their phylum-specific distributions illuminate phylogenetic divergence. Despite the maturity of Mass Spectrometry-based quantitative biomarkers—predominantly those with established structures—becoming well-established in geochemical research, systematic investigation of archaeal lipids as natural products has notably lagged. This deficit manifests across three key dimensions: (1) Extraction methodology lacks universal protocols adapted to diverse archaeal taxa and sample matrices. While comparative studies exist, theoretical frameworks guiding method selection remain underexplored. (2) Purification challenges persist due to the unique structures and complex isomerization profiles of archaeal lipids, hindering standardized separation protocols. (3) Most critically, structural characterization predominantly depends on decades-old foundational studies. However, the existing reviews prioritize chemical structural, biosynthetic, and applied aspects of archaeal lipids over analytical workflows. This review addresses this gap by adopting a natural product chemistry perspective, integrating three key aspects: (1) the clarification of applicable objects, scopes, and methodological mechanisms of various extraction technologies for archaeal lipids, encompassing both cultured and environmental samples; (2) the elucidation of separation principles underlying polar-gradient lipid fractionation processes, leveraging advanced chromatographic technologies; (3) the detailed exploration of applications for NMR in resolving complex lipid structures, with specialized emphasis on determining the stereochemical configuration. By synthesizing six decades of methodological evolution, we establish a comprehensive analytical framework, from lipids extraction to structural identification. This integrated approach constructs a systematic methodological paradigm for archaeal lipid analysis, bridging theoretical principles with practical implementation. Full article

Biogenic volatile organic compounds (BVOCs) significantly impact air quality and climate. Mechanical injury is a common stressor affecting plants in both natural and urban environments, and it has potentially large influences on BVOC emissions. However, the interspecific variability in wounding-induced BVOC emissions remains poorly understood, particularly for subtropical trees and shrubs. In this study, we investigated the effects of controlled mechanical injury on isoprenoid and aromatic compound emissions in a taxonomically diverse set of 45 subtropical broad-leaved woody species, 26 species without and in 19 species with BVOC storage structures (oil glands, resin ducts and glandular trichomes for volatile compound storage). Emissions of light-weight non-stored isoprene and monoterpenes and aromatic compounds in non-storage species showed moderate and variable emission increases after mechanical injury, likely reflecting the wounding impacts on leaf physiology. In storage species, mechanical injury triggered a substantial release of monoterpenes and aromatic compounds due to the rupture of storage structures. Across species, the proportion of monoterpenes in total emissions increased from 40.9% to 85.4% after mechanical injury, with 32.2% of this increase attributed to newly released compounds not detected in emissions from intact leaves. Sesquiterpene emissions, in contrast, were generally low and decreased after mechanical injury. Furthermore, wounding responses varied among plant functional groups, with evergreen species and those adapted to high temperatures and shade exhibiting stronger damage-induced BVOC emissions than deciduous species and those adapted to dry or cold environments. These findings suggest that mechanical disturbances such as pruning can significantly enhance BVOC emissions in subtropical urban forests and should be considered when modeling BVOC fluxes in both natural and managed ecosystems. Further research is needed to elucidate the relationship between storage structure characteristics and BVOC emissions, as well as their broader ecological and atmospheric implications. Full article