Search Results (74)

Membrane transporters play a crucial role in any cell. Identifying the substrates they translocate across membranes is important for many fields of research, such as metabolomics, pharmacology, and biotechnology. In this study, we leverage recent advances in deep learning, such as amino acid sequence embeddings with protein language models (pLMs), highly accurate 3D structure predictions with AlphaFold 2, and structure-encoding 3Di sequences from FoldSeek, for predicting substrates of membrane transporters. We test new deep learning features derived from both sequence and structure, and compare them to the previously best-performing protein encodings, which were made up of amino acid k-mer frequencies and evolutionary information from PSSMs. Furthermore, we compare the performance of these features either using a previously developed SVM model, or with a regularized feedforward neural network (FNN). When evaluating these models on sugar and amino acid carriers in A. thaliana, as well as on three types of ion channels in human, we found that both the DL-based features and the FNN model led to a better and more consistent classification performance compared to previous methods. Direct encodings of 3D structures with Foldseek, as well as structural embeddings with ProstT5, matched the performance of state-of-the-art amino acid sequence embeddings calculated with the ProtT5-XL model when used as input for the FNN classifier. Full article

Plant genetics and chemotaxonomic analysis are considered key parameters in understanding evolution, plant diversity and adaptation. Korean Peninsula has a unique biogeographical landscape that supports various aromatic plant species, each with considerable ecological, ethnobotanical, and pharmacological significance. This review aims to provide a comprehensive overview of the chemotaxonomic traits, biological activities, phylogenetic relationships and potential applications of Korean aromatic plants, highlighting their significance in more accurate identification. Chemotaxonomic investigations employing techniques such as gas chromatography mass spectrometry, high-performance liquid chromatography, and nuclear magnetic resonance spectroscopy have enabled the identification of essential oils and specialized metabolites that serve as valuable taxonomic and diagnostic markers. These chemical traits play essential roles in species delimitation and in clarifying interspecific variation. The biological activities of selected taxa are reviewed, with emphasis on antimicrobial, antioxidant, anti-inflammatory, and cytotoxic effects, supported by bioassay-guided fractionation and compound isolation. In parallel, recent advances in phylogenetic reconstruction employing DNA barcoding, internal transcribed spacer regions, and chloroplast genes such as rbcL and matK are examined for their role in clarifying taxonomic uncertainties and inferring evolutionary lineages. Overall, the search period was from year 2001 to 2025 and total of 268 records were included in the study. By integrating phytochemical profiling, pharmacological evidence, and molecular systematics, this review highlights the multifaceted significance of Korean endemic aromatic plants. The conclusion highlights the importance of multidisciplinary approaches including metabolomics and phylogenomics in advancing our understanding of species diversity, evolutionary adaptation, and potential applications. Future research directions are proposed to support conservation efforts. Full article

The genus Datura L. has pharmacological activities due to its source of bioactive compounds. The effects of bioactive compounds can vary depending on species, geographical location, and environmental conditions. The purpose of this review is to summarize the most recent progress and to provide a comprehensive overview of studies concerning genetic alteration and bioactive compounds in the genus Datura, based on Scopus publications between 2015 and 2025. Throughout history, the genus Datura (Solanaceae) contains nine species of medicinal plants. A key component of elucidating the diversification process of congeneric species is identifying the factors that encourage species variation. A comparative gene family analysis provides an understanding of the evolutionary history of species by identifying common genetic/genomic mechanisms that are responsible for species responses to biotic and abiotic environments. The diverse range of bioactive compounds it contains contributes to its unique bioactivity. Datura contains tropane alkaloids (such as hyoscyamine and scopolamine), datumetine, withametelin, daturaolone, and atropine. Several compounds have been isolated and refined for use in treating various conditions as a result of recent progress in therapeutic development. Daturaolone, for example, is used to treat certain neurological disorders. In addition to providing renewed opportunities for the discovery of new compounds, these advancements also provide insights into the genetic basis for their biosynthesis. Our discussion also includes pitfalls as well as relevant publications regarding natural products and their pharmacological properties. The pace of discovery of bioactive compounds is set to accelerate dramatically shortly, owing to both careful perspectives and new developments. Full article

Plants produce an extensive repertoire of secondary metabolites, developed over evolutionary time to support survival. Among these, D-limonene, a monoterpene exuded by citrus fruits, has demonstrated a broad range of pharmacological activities. This review elucidates limonene’s biological versatility, spanning antioxidant, anti-inflammatory, antitumor, antidiabetic, neuroprotective, and gastroprotective domains. Synthesizing data from both preclinical and early-phase clinical research, we explore its molecular mechanisms, ranging from reactive oxygen species mitigation and apoptosis induction to metabolic remodeling and neurotransmitter modulation. Special attention is given to limonene’s emerging role in oncological therapeutics, notably in breast and liver cancers, and its capacity to ameliorate pathophysiological hallmarks of diabetes and neurodegeneration. Its low toxicity and high bioavailability support its potential as a safe adjunct or alternative in phytotherapy. This review advocates for continued investigation into limonene’s translational potential across a spectrum of neoplastic and non-neoplastic diseases. Full article

Fabry disease is a rare genetic disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A (AGAL), resulting in the accumulation of globotriaosylceramides (Gb3) in tissues and organs. This buildup leads to progressive, multi-systemic complications that severely impact quality of life and can be life-threatening. Interpreting the functional consequences of missense variants in the GLA gene remains a significant challenge, especially in rare diseases where experimental evidence is scarce. In this study, we present an integrative computational framework that combines structural, interaction, pathogenicity, and stability data from both in silico tools and experimental sources, enriched through expert curation and structural analysis. Given the clinical relevance of pharmacological chaperones in Fabry disease, we focus in particular on the structural characteristics of variants classified as “amenable” to such treatments. Our multidimensional analysis—using tools such as AlphaMissense, EVE, FoldX, and ChimeraX—identifies key molecular features that distinguish amenable from non-amenable variants. We find that amenable mutations tend to preserve protein stability, while non-amenable ones are associated with structural destabilisation. By comparing AlphaMissense with alternative predictors rooted in evolutionary (EVE) and thermodynamic (FoldX) models, we explore the relative contribution of different biological paradigms to variant classification. Additionally, the investigation of outlier variants—where AlphaMissense predictions diverge from clinical annotations—highlights candidates for further experimental validation. These findings demonstrate how combining structural bioinformatics with machine learning–based predictions can improve missense variant interpretation and support precision medicine in rare genetic disorders. Full article

Litsea species have been used for herbal medicine by many ethnic groups. However, defining the morphological characteristics of the species remains difficult, leading to confusion and misuse of Litsea names. We examined Litsea classification, focusing on folk taxonomy. A field survey revealed that Litsea cubeba, L. elliptica, L. mollis, L. glutinosa, and L. martabanica have the highest use values. Using headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME-GC-MS) analysis and multivariate statistical methods, we examined metabolites from these species to assess consistency across plant parts. Principal coordinate analysis (PCoA) and cluster analysis revealed distinct metabolite patterns, grouping species into four significant clusters: Group I (L. elliptica and L. martabanica), Group II (L. martabanica roots), Group III (L. cubeba and L. mollis bark and roots), and Group IV (L. glutinosa and L. cubeba and L. mollis leaves). Chemical compounds are clustered by species rather than by plant parts. Our study reveals a significant correlation (p < 0.05) between phylogenetic distances and chemical differences among Litsea species, elucidating the evolutionary links through metabolite variations. This predictive approach could help with more efficient selection for traditional medicine discovery and should be the first to be pharmacologically tested for drug development. Full article

Sleep is the most important physiological function of all animals studied to date. Sleep disorders include narcolepsy, which is characterized by excessive daytime sleepiness, disruption of night sleep, and muscle weakness—cataplexy. Narcolepsy is known to be caused by the degeneration of orexin-synthesizing neurons (hypocretin (HCRT) neurons or orexin neurons) in the hypothalamus. In mammals, HCRT neurons primarily regulate the sleep/wake cycle, nutrition, reward seeking, and addiction development. The hypocretin system of the brain is involved in a number of neurological disorders. The distinctive pathologies associated with the disruption of HCRT neurons are narcolepsy and cataplexy, which are caused by the loss of hypocretin neurons that produce HCRT. In Danio, the hypocretin system is also involved in the regulation of sleep and wakefulness. It is represented by a single hcrt gene that encodes the peptides HCRT1 and HCRT2, as well as one HCRT receptor (HCRTR), which is structurally closest to the mammalian HCRTR2. The overexpression of the hcrt gene in Danio rerio larvae causes wakefulness, whereas the physical destruction of HCRT cells or a pharmacological blockade of the type 2 hypocretin receptor leads to fragmentation of sleep in fish larvae, which is also observed in patients with narcolepsy. These data confirm the evolutionary conservatism of the hypocretin system. Thus, Danio rerio is an ideal model for studying the functions of HCRT neural networks and their functions. Full article

Ferns represent the second-largest group of vascular plants, yet their genomic resources lag far behind. Here, we present a chromosome-scale genome assembly of Cibotium barometz (L.) J. Sm., a medicinally important fern species. The 3.49 Gb genome, assembled into 66 chromosomes with 99.41% sequence anchorage, revealed an exceptionally high proportion (83.93%) of repetitive elements, dominated by recently expanded LTR retrotransposons. We identified 30,616 protein-coding genes, providing insights into fern-specific gene families. Genomic analyses uncover the evolutionary dynamics of 513 key biosynthetic genes, particularly those involved in terpenoid and flavonoid production. Expression profiling across tissues revealed tissue-specific regulation of these pathways, with notable upregulation of chalcone synthase genes in roots. Our structural analysis of 1-deoxy-d-xylulose-5-phosphate synthase, a key enzyme in terpenoid biosynthesis, demonstrated high conservation across land plants while highlighting fern-specific adaptations. The identification of multiple isoforms for key enzymes points to potential gene-duplication events or the evolution of fern-specific variants. This genome provides a foundation for understanding fern biology, evolution, and the molecular basis of their medicinal properties. It also offers valuable resources for conservation efforts and pharmacological research, paving the way for sustainable utilization of this valuable medicinal plant and advancing our understanding of plant diversity and natural product biosynthesis. Full article

In eukaryotic cells, the endoplasmic reticulum is particularly important in post-translational modification of proteins before they are released extracellularly or sent to another endomembrane system. The correct three-dimensional folding of most proteins occurs in the ER lumen, which has an oxidative environment that is essential for the formation of disulfide bridges, which are important in maintaining protein structure. The ER is a versatile organelle that ensures the correct structure of proteins and is essential in the synthesis of lipids and sterols, in addition to offering support in the maintenance of intracellular calcium. Consequently, the cells needed to respond to demands caused by physiological conditions and pathological disturbances in the organelle homeostasis, leading to proper functioning of the cell or even programmed cell death. Disturbances to the ER function trigger a response to the accumulation of unfolded or misfolded proteins, known as the unfolded protein response. Such disturbances include abiotic stress, pharmacological agents, and intracellular pathogens, such as viruses. When misfolded proteins accumulate in the ER, they can undergo ubiquitination and proteasomal degradation through components of the ER-associated degradation system. Once a prolonged activity of the UPR pathway occurs, indicating that homeostasis cannot be reestablished, components of this pathway induce cell death by apoptosis. Here, we discuss how viruses have evolved ways to counteract UPR responses to maximize replication. This evolutionary viral ability is important to understand cell pathology and should be taken into account when designing therapeutic interventions and vaccines. Full article

Understanding chronic kidney disease (CKD) through the lens of evolutionary biology highlights the mismatch between our Paleolithic-optimized genes and modern diets, which led to the dramatically increased prevalence of CKD in modern societies. In particular, the Standard American Diet (SAD), high in carbohydrates and ultra-processed foods, causes conditions like type 2 diabetes (T2D), chronic inflammation, and hypertension, leading to CKD. Autosomal dominant polycystic kidney disease (ADPKD), a genetic form of CKD, is characterized by progressive renal cystogenesis that leads to renal failure. This review challenges the fatalistic view of ADPKD as solely a genetic disease. We argue that, just like non-genetic CKD, modern dietary practices, lifestyle, and environmental exposures initiate and accelerate ADPKD progression. Evidence shows that carbohydrate overconsumption, hyperglycemia, and insulin resistance significantly impact renal health. Additionally, factors like dehydration, electrolyte imbalances, nephrotoxin exposure, gastrointestinal dysbiosis, and renal microcrystal formation exacerbate ADPKD. Conversely, carbohydrate restriction, ketogenic metabolic therapy (KMT), and antagonizing the lithogenic risk show promise in slowing ADPKD progression. Addressing disease triggers through dietary modifications and lifestyle changes offers a conservative, non-pharmacological strategy for disease modification in ADPKD. This comprehensive review underscores the urgency of integrating diet and lifestyle factors into the clinical management of ADPKD to mitigate disease progression, improve patient outcomes, and offer therapeutic choices that can be implemented worldwide at low or no cost to healthcare payers and patients. Full article

Scorpions, an ancient group of venomous invertebrates, have existed for over 430 million years. Their toxins, important for predation and defense, exhibit a variety of biological and pharmacological activities. Research on scorpion toxins has spanned decades. Notably, the toxin genes of Mesobuthus martensii (Scorpiones: Buthidae), a well-known Chinese herbal medicine, have been described at genomic and proteomic levels. However, previous studies primarily focused on the toxin genes expressed in the venom glands, overlooking their expression in multiple tissues. This study analyzed transcriptomes from 14 tissues of M. martensii. Gene annotation revealed 83 toxin and toxin-like genes, including those affecting sodium, potassium, calcium, and chloride ion channels. Approximately 70% of toxin genes were highly expressed in the vesicle; additionally, some exhibited low or no expression in the vesicle while showing high expression in other tissues. Beyond the vesicle, high expression levels of toxin genes were observed in metasoma segments II-V, blood, lateral eyes, chelicerae, legs, pedipalp chelae, femurs, and patellae. This expression pattern suggests that toxin genes are recruited from multiple tissues and may help prevent intraspecific harm during courtship and competition for prey. These findings inspire further research into the evolutionary recruitment process of scorpion toxins. Full article

Kaempferia parviflora, a medicinal plant widely used in Southeast Asia, has been validated clinically for its diverse pharmaceutical applications. Despite extensive research in pharmacology, there is a notable lack of cytogenetic and genomic research, primarily due to limited genetic information. Simple Sequence Repeat (SSR) is considered a robust class of molecular markers frequently used in biodiversity studies. In this study, we adopted Microsatellite Capture Sequencing (MiCAPs) to obtain SSR sequences for marker development. We identified 13,644 SSRs and developed and validated ten sets of SSR markers through capillary electrophoresis. The ten primer sets generated 27 alleles, with an average Polymorphism Information Content (PIC) of 0.36. Principle Coordinate Analysis (PCoA) distinguished two types of K. parviflora, consistent with classification by leaf margin color (red and green). A neighbor-joining dendrogram of seven Zingiberaceae species was constructed with the SSR-containing sequences. The 2-c value of K. parviflora is first reported here as 3.16 ± 0.03; the genome size is estimated at 3090.48 Mbp. The newly developed molecular markers are crucial for variety identification and the conservation of wild resources. Additionally, the cytogenetic and phylogenetic information provides valuable insights into the genetic diversity and evolutionary relationships. Full article

The gut is an intricate and diverse organ system for investigating visceral pattern generation. The gut made an early evolutionary breakthrough. There is evidence that the molecular mechanisms governing the development of gastrointestinal patterns are species-specific. Some have suggested using marine drugs to treat gastrointestinal disorders. The study, which used an integrated network pharmacology approach, aimed to find out how well fucoidan worked and what Fucus vesiculosus might be doing to help prevent digestive problems. Researchers gathered information on how potential bioactive components of brown seaweed and their associated targets interact with the disease gene targets of gastrointestinal disorders. We studied the signaling pathways linked to F. vesiculosus in the context of gut health treatments using a KEGG (Kyoto Encyclopedia of Genes and Genomes pathway) and GO (Gene ontology) enrichment analysis. We built and studied the protein–protein interaction (PPI) and compound-target networks using Cytoscape. PPI network analysis yielded a total of 44 important targets, including BCL2, ESR1, and STAT3. The KEGG enrichment analysis revealed a strong correlation between the signaling pathways used in the treatment and the prevention of gastrointestinal disorders. We docked significant genes with TNF, STAT3, BCL2, and ALB. Fucoxanthin and fucoidan possess beneficial properties for improving gut health by treating gastric-intestinal issues. This study showed that by controlling several targets and many pathways with multiple components, F. vesiculosus exhibited preventive effects against gastrointestinal disorders. Full article

Alternative splicing significantly enhances the diversity of the G protein-coupled receptor (GPCR) family, including the histamine H₃ receptor (H₃R). This post-transcriptional modification generates multiple H₃R isoforms with potentially distinct pharmacological and physiological profiles. H₃R is primarily involved in the presynaptic inhibition of neurotransmitter release in the central nervous system. Despite the approval of pitolisant for narcolepsy (Wakix^®) and daytime sleepiness in adults with obstructive sleep apnea (Ozawade^®) and ongoing clinical trials for other H₃R antagonists/inverse agonists, the functional significance of the numerous H₃R isoforms remains largely enigmatic. Recent publicly available RNA sequencing data have confirmed the expression of multiple H₃R isoforms in the brain, with some isoforms exhibiting unique tissue-specific distribution patterns hinting at isoform-specific functions and interactions within neural circuits. In this review, we discuss the complexity of H₃R isoforms with a focus on their potential roles in central nervous system (CNS) function. Comparative analysis across species highlights evolutionary conservation and divergence in H₃R splicing, suggesting species-specific regulatory mechanisms. Understanding the functionality of H₃R isoforms is crucial for the development of targeted therapeutics. This knowledge will inform the design of more precise pharmacological interventions, potentially enhancing therapeutic efficacy and reducing adverse effects in the treatment of neurological and psychiatric disorders. Full article

Considering the high evolutionary rate and great harmfulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is imperative to develop new pharmacological antagonists. Human angiotensin-converting enzyme-2 (ACE2) functions as a primary receptor for the spike protein (S protein) of SARS-CoV-2. Thus, a novel functional peptide, KYPAY (K5), with a boomerang structure, was developed to inhibit the interaction between ACE2 and the S protein by attaching to the ACE2 ligand-binding domain (LBD). The inhibition property of K5 was evaluated via molecular simulations, cell experiments, and adsorption kinetics analysis. The molecular simulations showed that K5 had a high affinity for ACE2 but a low affinity for the cell membrane. The umbrella sampling (US) simulations revealed a significant enhancement in the binding potential of this functional peptide to ACE2. The fluorescence microscopy and cytotoxicity experiments showed that K5 effectively prevented the interaction between ACE2 and the S protein without causing any noticeable harm to cells. Further flow cytometry research indicated that K5 successfully hindered the interaction between ACE2 and the S protein, resulting in 78% inhibition at a concentration of 100 μM. This work offers an innovative perspective on the development of functional peptides for the prevention and therapy of SARS-CoV-2. Full article