Applications In Medicine Research Articles

A comprehensive review: medicinal applications and diverse synthetic strategies of pyrimidine-based compounds leveraging Suzuki and Sonogashira reactions

A comprehensive review: medicinal applications and diverse synthetic strategies of pyrimidine-based compounds leveraging Suzuki and Sonogashira reactions

Biodiversity and Bioprospecting of Fungal Endophytes from Houttuynia cordata Thunb. as a Potential Antibacterial and Anticancer Agent.

Endophytic fungi are considered a new source of bioactive compounds that have important applications in agriculture and medicine. This study aims to investigate the biodiversity and potential of endophytic fungi isolated from Houttuynia cordata Thunb. as antimicrobials and anticancer agents. Out of ten isolated endophytes, four species have never been reported to be associated with H. cordata: Ceratobasidium sp., Cladosporium sp., Phomopsis sp., and Fusarium sp. The antibacterial activity assay revealed that the ethyl acetate extract of Ceratobasidium sp. HCS-3 possessed most potent antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, its cytotoxic activity test showed the promising anticancer activity on lung cancer A549, osteosarcoma MG-63, and cervical cancer HeLa cells with IC50 of 4.55 ±1.16, 32.14 ±2.78, and 1.54 ±0.66 ppm, respectively. Furthermore, metabolite profiling identified 66 compounds suggesting that benzoic acid, farnesol, and cyclopeptides may contribute to the antibacterial activity, while 4-methoxycinnamic acid may have anticancer potential.

Advances in Metabolic Engineering for the Accumulation of Astaxanthin Biosynthesis.

Astaxanthin, a lipophilic carotenoid renowned for itsstrong antioxidant activity, holds significant commercial value across industries such as feed, food, and cosmetics. Although astaxanthin can be synthesized through chemical methods, it may contain toxic by-products in the synthesized astaxanthin, limiting its application inmedicine or functional food. Natural astaxanthin can be extracted from algae, however, the cultivation cycle of algae is relatively longercompared to microorganisms. With the advancement of synthetic biology and metabolic engineering, the method of microbial fermentation has emerged asa promising strategy for the large-scale production of astaxanthin. This article provides a comprehensive overview of the research progress in astaxanthin biosynthesis, highlighting the use ofthe natural host Xanthophyllomyces dendrorhous, andthe heterologous hosts Yarrowia lipolytica and Saccharomyces cerevisiae. Additionally, future research prospects are also discussed.

Genotype-specific responses to in vitro drought stress in myrtle (Myrtus communis L.): integrating machine learning techniques.

Myrtle (Myrtus communis L.), native to the Mediterranean region of Türkiye, is a valuable plant with applications in traditional medicine, pharmaceuticals, and culinary practices. Understanding how myrtle responds to water stress is essential for sustainable cultivation as climate change exacerbates drought conditions. This study investigated the performance of selected myrtle genotypes under in vitro drought stress by employing tissue culture techniques, rooting trials, and acclimatization processes. Genotypes were tested under varying polyethylene glycol (PEG) concentrations (1%, 2%, 4%, and 6%). Machine learning (ML) algorithms, including Gaussian process (GP), support vector machine (SVM), Random Forest (RF), and Extreme Gradient Boosting (XGBoost), were utilized to model and predict micropropagation and rooting efficiency. The research revealed a genotype-dependent response to drought stress. Black-fruited genotypes exhibited higher micropropagation rates compared to white-fruited ones under stress conditions. The application of ML models successfully predicted micropropagation and rooting efficiency, providing insights into genotype performance. The findings suggest that selecting drought-tolerant genotypes is crucial for enhancing myrtle cultivation. The results underscore the importance of genotype selection and optimization of cultivation practices to address climate change impacts. Future research should explore the molecular mechanisms of stress responses to refine breeding strategies and improve resilience in myrtle and similar economically important crops.

Lensless super-resolved quantitative phase imaging with cm-level lateral translations of two glass plates.

In this Letter, we propose a new, to the best of our knowledge, lensless on-chip holographic microscopy platform, which can acquire sub-pixel-shifting holograms through centimeter (cm)-level lateral translations. An LED light source is used to illuminate the sample, and two orthogonally tilted step-structure glass plates are inserted into the optical path. By merely displacing the glass plates under cm-level precision, a series of holograms with sub-pixel displacements can be obtained. Combined with our improved pixel super-resolution (PSR) algorithm, high-quality PSR phase imaging can be achieved. Tests on the high-resolution USAF1951 target demonstrate that the system can achieve a half-width resolution of 870 nm by a camera with a pixel size of 1.67 µm. Additionally, imaging experiments were conducted on phase-type sinusoidal gratings, yeasts, red blood cells, and lilium ovary sections, respectively. The results show that the system can achieve large field-of-view, high-resolution phase imaging under low-cost hardware conditions and holds promise for its applications in biology and medicine.

STREAMLINING REGULATORY DOCUMENTATION: EXPLORING THE COMMON TECHNICAL DOCUMENT (CTD) AND ELECTRONIC SUBMISSION, WITH EMPHASIS ON M SERIES ACCORDING TO ICH GUIDELINES

A number of regulatory bodies have worked together to create the Common Technical Document (CTD), including the United States Food and Drug Administration, the European Medicines Agency, and the Japanese Ministry of Health. This standardized format facilitates the collection and submission of regulatory documentation pertaining to applications for new medicines. Since its inception in 2000, the CTD has been widely adopted internationally, including by nations such as Canada, Australia, and India. The CTD aims to streamline the submission process, reduce duplication of effort, and facilitate regulatory evaluations by providing a uniform structure for technical documentation. This article outlines the guidelines and organization of the CTD, including its modules covering administrative information, quality, non-clinical studies, and clinical trials. The CTD’s significance lies in its ability to improve regulatory efficiency, promote data transparency, and expedite the availability of new medicines to patients. However, challenges persist, such as variations in regional requirements and the need for continued adaptation to evolving technological standards. Electronic submissions and improved information management are two ways in which the new electronic CTD (eCTD) has improved submission procedures. Despite some ongoing issues, the CTD and eCTD represent significant advancements in regulatory documentation, with the potential for further innovation and global adoption in the future.

Microbiome Geographic Population Structure (mGPS) Detects Fine-Scale Geography.

Over the past decade, sequencing data generated by large microbiome projects showed that taxa exhibit patchy geographical distribution, raising questions about the geospatial dynamics that shape natural microbiomes and the spread of antimicrobial resistance (AMR) genes. Answering these questions requires distinguishing between local and non-local microorganisms and identifying the source sites for the latter. Predicting the source sites and migration routes of microbiota has been envisioned for decades but was hampered by the lack of data, tools, and understanding of the processes governing biodiversity. State-of-the-art biogeographical tools suffer from low resolution and cannot predict biogeographical patterns at a scale relevant to ecological, medical, or epidemiological applications. Analyzing urban, soil, and marine microorganisms, we found that some taxa exhibit regional-specific composition and abundance, suggesting they can be used as biogeographical biomarkers. We developed the Microbiome Geographic Population Structure (mGPS), a machine-learning-based tool that utilizes microbial relative sequence abundances to yield a fine-scale source site for microorganisms. mGPS predicted the source city for 92% of the samples and the within-city source for 82% of the samples, though they were often only a few hundred meters apart. mGPS also predicted soil and marine sampling sites for 86% and 74% of the samples, respectively. We demonstrated that mGPS differentiated local from non-local microorganisms and used it to trace the global spread of AMR genes. mGPS's ability to localize samples to their waterbody, country, city, and transit stations opens new possibilities in tracing microbiomes and has applications in forensics, medicine, and epidemiology.

Stability Indicating HPTLC Method for Estimation of Cubebin in Crude Drug and Marketed Formulations

Background: Cubebin is a naturally occurring lactone lignan isolated from the plant species Piper cubeba. It exhibits a range of biological activities, including anti-inflammatory, antimicrobial, and anticancer properties. This compound has garnered significant interest for its potential therapeutic applications in traditional and modern medicine. Aim: This study aimed to develop a novel stability-indicating High-Performance Thin Layer Chromatography (HPTLC) technique that is simple yet precise in estimating cubebin in crude drug and marketed formulations. Method: Cubebin was estimated using precoated TLC silica gel 60 F254 plate as a stationary phase and n-hexane: ethyl acetate: formic acid: methanol (6:3.5:0.5:0.3 v/v/v/v) as a mobile phase with the chamber saturation time of 20 mins. Key Findings: Cubebin was detected and quantified at the wavelength of 283nm. The Rf value of cubebin in standard solution, Piper cubeba extract, Dhanwantari Vati, and Khadiradi Vati was found to be 0.494±0.0015, 0.492±0.002, 0.490±0.0020, 0.499±0.001 respectively. The calibration curve exhibited linearity within the range of 3000-13000 ng per band with a correlation coefficient (r2) of Cubebin was 0.9968. The method developed was utilized for the quantitation of cubebin in Piper cubeba and both the marketed formulations. Conclusion: A novel HPTLC method was developed and validated in accordance to ICH guidelines for the analysis of cubebin in crude drug and marketed formulations. The method was found to be simple, precise, accurate, and specific. This method is suitable for quality control and stability testing of cubebin-containing formulations.

Review of Medicinal Plant classification System

Previous studies in the fields of botanical sciences and medicine have looked closely at the categorization and identification of therapeutic plants. In the past, scholars have delved into conventional knowledge bases with the goal of deciphering the botanical characteristics and medicinal applications of many plant species, establishing the foundation for contemporary research. Nevertheless, distinguishing and categorizing a wide range of medicinal plant species proved to be a significant obstacle for studies. The challenge was precisely identifying and classifying the subtle and unique characteristics shared by various plant species. These obstacles impeded the creation of thorough and accurate classification schemes designed especially for medicinal plants. Our suggested Medicinal Plant Classification System uses a novel strategy that makes use of convolutional neural networks (CNNs) to overcome these difficulties. The CNN-based method greatly improves our classification system's accuracy and versatility while making it easier to identify subtle botanical features. For our work, CNNs seem to be an essential answer, demonstrating unmatched effectiveness in capturing various complex properties present in photos of medicinal plants. The flexibility, capacity for feature extraction, and hierarchical learning that CNNs possess highlight their critical role in creating a strong and adaptable classification system designed especially for the identification of medicinal plants.

Antibacterial Peptide Nisin Activates p53 Gene Expression and Triggers Apoptosis in Human Colon Cancer Cells

ABSTRACTAntimicrobial peptides (AMPs) are renowned for their broad‐spectrum efficacy against viruses, bacteria, and fungi, thereby holding promise for medicinal applications. Nisin, a bacteriocin synthesized by gram‐positive bacteria such as Lactobacillus and Streptococcus, has been used as a food preservative owing to its antimicrobial characteristics for decades. However, recent developments prompt further research on its application as therapeutic interventions, mainly focusing on anticancer activity. In line with this, the present study portrays the effects of nisin on human colorectal cancer cells and the underlying molecular mechanisms. A dose‐dependent decrease in cell viability with increasing concentrations of nisin was determined by the Alamar blue viability assay, which was supported by significant morphological changes in cells. Subsequently, we probed the apoptotic effects of nisin using EtBr/AO staining, confirming the induction of apoptosis upon nisin treatment, which was further confirmed by ELISA analysis. Elevated levels of Caspase 7 indicated increased apoptosis in nisin‐treated cells. As pharmaceutical p53 reactivation is considered as an attractive strategy to combat chemoresistance and adverse effects, the effect of nisin on p53 expression was determined by mRNA analysis. An upregulation in p53 expression in nisin‐treated cells compared to untreated controls suggests that bacterial nisin reactivates mutated p53. To assess cell cycle dynamics, we utilized PI flow cytometry, unveiling a G0/G1 phase arrest in nisin‐treated cells in contrast to untreated controls. In summary, our results strongly advocate the potential of nisin as a compelling candidate for drug development against colorectal cancer.

Alternative Method for Obtaining Human-Induced Pluripotent Stem Cell Lines and Three-Dimensional Growth: A Simplified, Passage-Free Approach that Minimizes Labor.

Induced pluripotent stem cells (iPSCs) hold significant promise for numerous applications in regenerative medicine, disease modeling, and drug discovery. However, the conventional workflow for iPSC generation, with cells grown under two-dimensional conditions, presents several challenges, including the need for specialized scientific skills such as morphologically assessing and picking colonies and removing differentiated cells during the establishment phase. Furthermore, maintaining established iPSCs in three-dimensional culture systems, while offering scalability, necessitates an enzymatic dissociation step for their further growth in a complex and time-consuming protocol. In this study, we introduce a novel approach to address these challenges by reprogramming somatic cells grown under three-dimensional conditions as spheres using a bioreactor, thereby eliminating the need for two-dimensional culture and colony picking. The iPSCs generated in this study were maintained under three-dimensional conditions simply by transferring spheres to the next bioreactor, without the need for an enzymatic dissociation step. This streamlined method simplifies the workflow, reduces technical variability and labor, and paves the way for future advancements in iPSC research and its wider applications. Key features • Establishment of induced pluripotent stem cells in a three-dimensional environment. • Maintenance and cryopreservation of iPSCs without the need for a dissociation step.

Complete chloroplast genome sequence of Artemisia littoricola (Asteraceae) from Dokdo Island Korea: genome structure, phylogenetic analysis, and biogeography study.

The Asteraceae family, particularly the Artemisia genus, presents taxonomic challenges due to limited morphological characteristics and frequent natural hybridization. Molecular tools, such as chloroplast genome analysis, offer solutions for accurate species identification. In this study, we sequenced and annotated the chloroplast genome of Artemisia littoricola sourced from Dokdo Island, employing comparative analyses across six diverse Artemisia species. Our findings reveal conserved genome structures with variations in repeat sequences and junction boundaries. Notably, the chloroplast genome of A. littoricola spans 150,985bp, consistent with other Artemisia species, and comprises 131 genes, including 86 protein-coding, 37 tRNA, and 8 rRNA genes. Among these genes, 16 possess a single intron, while clpP and ycf3 exhibit two introns each. Furthermore, 18 genes display duplicated copies within the IR regions. Moreover, the genome possesses 42 Simple Sequence Repeats (SSRs), predominantly abundant in A/T content and located within intergenic spacer regions. The analysis of codon usage revealed that the codons for leucine were the most frequent, with a preference for ending with A/U. While the chloroplast genome exhibited conservation overall, non-coding regions showed lower conservation compared to coding regions, with the Inverted Repeat (IR) region displaying higher conservation than single-copy regions. Phylogenetic analyses position A. littoricola within subgenus Dracunculus, indicating a close relationship with A. scoparia and A. desertorum. Additionally, biogeographic reconstructions suggest ancestral origins in East Asia, emphasizing Mongolia, China (North East and North Central and South Central China), and Korea. This study underscores the importance of chloroplast genomics in understanding Artemisia diversity and evolution, offering valuable insights into taxonomy, evolutionary patterns, and biogeographic history. These findings not only enhance our understanding of Artemisia's intricate biology but also contribute to conservation efforts and facilitate the development of molecular markers for further research and applications in medicine and agriculture.

Characterization and Molecular Engineering of a N-Methyltransferase from Edible Nelumbo nucifera Leaves Involved in Nuciferine Biosynthesis.

Lotus leaf, traditionally used as both edible tea and herbal medicine in Asia, contains nuciferine, a lipid-lowering and weight-loss compoud. The biosynthetic pathways of nuciferine in Nelumbo nucifera remain unclear. We characterized a specific N-methyltransferase, NnNMT, which had a novel function and catalyzed only nuciferine synthesis from the aporphine-type alkaloid N-nornuciferine. The expression profile of NnNMT was in agreement with BIA accumulation patterns in four tissues from three varieties, suggesting that NnNMT is involved in nucleiferine biosynthesis in Nelumbo nucifera. Protein engineering based on molecular docking and dynamic simulations revealed key residues (Y98, H208, F256, Y81, F329, G260, P76, and H80) crucial for NnNMT activity, with the F257A mutant showing increased efficiency. These findings enhance our understanding of aporphine alkaloid biosynthesis and support the development of lotus-based functional foods and medicinal applications.

Non-clinical safety evaluation of Yongdamsagan-tang water extract: A 13-week subchronic oral toxicity study in Sprague Dawley rats.

Despite the continued clinical application of traditional herbal medicines, scientific evidence such as toxicological safety profile of Yongdamsagan-tang water extract (YSTW) has not yet been established. The purpose of this study was to investigate the potential toxicity profile of YSTW following a 13-week repeated oral administration at various concentrations to Sprague Dawley rats. YSTW was administered orally to rats once daily at doses of 0, 1000, 2000, and 5000 mg/kg bw/day for 13 weeks. During the experimental period, there were no significant toxicological changes related to YSTW treatment. These results indicate that the administration of YSTW for 13 weeks in the rat resulted in no signs of toxicity at up to 5000 mg/kg bw/day, which was considered the no-observed-adverse-effect level.

Optimization of solvent cooling crystallization process for separating phenanthrene from 9-fluorenone by COSMO-RS and solubility calculation approach

Phenanthrene (Phe) and fluorene (Flu) are crucial chemical intermediates with applications in materials, medicine, and pesticides. However, conventional separation methods struggle to effectively isolate phenanthrene from fluorene due to their similar physical properties. To address this challenge, a reaction–separation coupling technique was employed to convert fluorene into 9-fluorenone (9-Fluo), followed by the separation of phenanthrene from 9-fluorenone using solvent-cooling crystallization. Initially, the relative solubilities of phenanthrene and 9-fluorenone in 2072 solvents were calculated using COSMO-RS for preliminary screening. Among various conventional short-chain aliphatic alcohols and low-carbon saturated hydrocarbons, methanol, and cyclohexane were identified as the most effective solvents based on their solubility selectivity (SS). The molecular interactions between phenanthrene or 9-fluorenone and these solvents were analyzed using theoretical methods such as σ-potential/profile, infinite dilution activity coefficients in COSMO-RS, and Hansen solubility parameters, with further confirmation from FTIR tests. The optimal liquid–solid ratios were determined using both phase diagram measurements and solubility calculations. The reaction conversion of fluorene to 9-fluorenone was complete regardless of the raw material used. Phenanthrene and 9-fluorenone were effectively separated using methanol and cyclohexane with optimum liquid–solid mass ratios of 1.6:1 and 2.8:1, respectively. In the model mixture, the contents of phenanthrene and 9-fluorenone exceeded 98 wt%, with yields above 91 wt%. For anthracene residue, the content of 9-fluorenone reached 93.98 wt% with a yield of 84.52 wt%, while its content was only 76.58 wt% due to the accumulation of other components in phenanthrene.

Equimolar Cross-Coupling Using Reactive Coiled Coils for Covalent Protein Assemblies.

Biocompatible cross-coupling reactions enable the efficient covalent attachment of large biomolecules at near-stoichiometric ratios, ensuring the stability and integrity of the resulting products. We present an affinity-based peptide platform utilizing coiled coils containing reactive side chains for proximity-driven protein cross-coupling in the presence of a cross-linking agent. This platform supports both chemical synthesis and recombinant expression, using canonical amino acids to generate reactive affinity tags. Employing the E3/R3 coiled coil pair as a scaffold, we design four complementary coils with cysteine residues as cross-linking sites, achieving >90% conversion to covalent heterodimeric coupling products using 3,4-dibromomaleimide. Equimolar mixtures of proteins with reactive coils at their termini yield near-quantitative heterodimeric cross-coupling products. The strategic selection of complementary coiled coil pairs and cross-linking agents enables orthogonal assembly of macromolecules with diverse architectures. This method offers a versatile approach for creating covalent fusion proteins, enhancing their stability and functionality for applications in chemical biology, biotechnology, and medicine.

Insights into the Molecular Structure, Stability, and Biological Significance of Non-Canonical DNA Forms, with a Focus on G-Quadruplexes and i-Motifs

This article provides a comprehensive examination of non-canonical DNA structures, particularly focusing on G-quadruplexes (G4s) and i-motifs. G-quadruplexes, four-stranded structures formed by guanine-rich sequences, are stabilized by Hoogsteen hydrogen bonds and monovalent cations like potassium. These structures exhibit diverse topologies and are implicated in critical genomic regions such as telomeres and promoter regions of oncogenes, playing significant roles in gene expression regulation, genome stability, and cellular aging. I-motifs, formed by cytosine-rich sequences under acidic conditions and stabilized by hemiprotonated cytosine–cytosine (C:C+) base pairs, also contribute to gene regulation despite being less prevalent than G4s. This review highlights the factors influencing the stability and dynamics of these structures, including sequence composition, ionic conditions, and environmental pH. Molecular dynamics simulations and high-resolution structural techniques have been pivotal in advancing our understanding of their folding and unfolding mechanisms. Additionally, the article discusses the therapeutic potential of small molecules designed to selectively bind and stabilize G4s and i-motifs, with promising implications for cancer treatment. Furthermore, the structural properties of these DNA forms are explored for applications in nanotechnology and molecular devices. Despite significant progress, challenges remain in observing these structures in vivo and fully elucidating their biological functions. The review underscores the importance of continued research to uncover new insights into the genomic roles of G4s and i-motifs and their potential applications in medicine and technology. This ongoing research promises exciting developments in both basic science and applied fields, emphasizing the relevance and future prospects of these intriguing DNA structures.

Engineering synthetic agonists for targeted activation of Notch signaling.

Notch signaling regulates cell fate decisions and has context-dependent tumorigenic or tumor suppressor functions. Although there are several classes of Notch inhibitors, the mechanical force requirement for Notch receptor activation has hindered attempts to generate soluble agonists. To address this problem, we engineered synthetic Notch agonist (SNAG) proteins by tethering affinity-matured Notch ligands to antibodies or cytokines that internalize their targets. This bispecific format enables SNAGs to "pull" on mechanosensitive Notch receptors, triggering their activation in the presence of a desired biomarker. We successfully developed SNAGs targeting six independent surface markers, including the tumor antigens PDL1, CD19, and HER2, and the immunostimulatory receptor CD40. SNAGs targeting CD40 increase expansion of central memory γδ T cells from peripheral blood, highlighting their potential to improve the phenotype and yield of low-abundance T cell subsets. These insights have broad implications for the pharmacological activation of mechanoreceptors and will expand our ability to modulate Notch signaling in biotechnology.

Segmentation study of nanoparticle topological structures based on synthetic data.

Nanoparticles exhibit broad applications in materials mechanics, medicine, energy and other fields. The ordered arrangement of nanoparticles is very important to fully understand their properties and functionalities. However, in materials science, the acquisition of training images requires a large number of professionals and the labor cost is extremely high, so there are usually very few training samples in the field of materials. In this study, a segmentation method of nanoparticle topological structure based on synthetic data (SD) is proposed, which aims to solve the issue of small data in the field of materials. Our findings reveal that the combination of SD generated by rendering software with merely 15% Authentic Data (AD) shows better performance in training deep learning model. The trained U-Net model shows that Miou of 0.8476, accuracy of 0.9970, Kappa of 0.8207, and Dice of 0.9103, respectively. Compared with data enhancement alone, our approach yields a 1% improvement in the Miou metric. These results show that our proposed strategy can achieve better prediction performance without increasing the cost of data acquisition.

The complete chloroplast genome of Erodium cicutarium (Linnaeus) l’ Héritier ex Aiton 1789 (Geraniaceae): genome characterization and phylogenetic consideration

Erodium cicutarium is an annual herbaceous plant valued for its applications in traditional medicine. However, the chloroplast genome of E. cicutarium has yet to be reported. In this study, we assembled chloroplast genomes of Erodium cicutarium using Illumina sequencing reads. The chloroplast genome was 114,652 bp long, harbored 111 complete genes, and its overall GC content was 39.1%. In Maximum Likelihood (ML) and Bayesian inference (BI) trees, the 13 Erodium species divided into three main clades, with E. cicutarium and E. carvifolium forming a monophyletic group, suggesting a close relationship between the two species. The E. cicutarium cp genome presented in this study lays a good foundation for the Erodium.