Search Results (3,215)

Advanced therapy medicinal products (ATMPs), especially effective against cancer, remain costly due to their reliance on genetically modified T cells. Contamination during production is a major concern, as traditional quality control methods involve samplings, which can themselves introduce contaminants. It is therefore necessary to develop methods for detecting contamination without sampling and, if possible, in real time. In this article, we present a white light spectroscopy method that makes this possible. It is based on shape analysis of the absorption spectrum, which evolves from an approximately Gaussian shape to a shape modified by the 1/λ component of bacterial absorption spectra when contamination develops. A warning value based on this shape descriptor is proposed. It is demonstrated that a few hours are sufficient to detect contamination and trigger an alarm to quickly stop the production. This time-saving should reduce the cost of these new drugs, making them accessible to as many people as possible. This method can be used regardless of the type of contaminants, provided that the shape of their absorption spectrum is sufficiently different from that of pure T cells so that the shape descriptor is efficient. Full article

Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterized by inflammation, demyelination, axonal degeneration, and gliosis. Its pathophysiology involves a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation, ultimately leading to progressive neurodegeneration and functional decline. Although significant advances have been made in disease-modifying therapies (DMTs), many patients continue to experience disease progression and unmet therapeutic needs. Drug repurposing—the identification of new indications for existing drugs—has emerged as a promising strategy in MS research, offering a cost-effective and time-efficient alternative to traditional drug development. Several compounds originally developed for other diseases, including immunomodulatory, anti-inflammatory, and neuroprotective agents, are currently under investigation for their efficacy in MS. Repurposed agents, such as selective sphingosine-1-phosphate (S1P) receptor modulators, kinase inhibitors, and metabolic regulators, have demonstrated potential in promoting neuroprotection, modulating immune responses, and supporting remyelination in both preclinical and clinical settings. Simultaneously, artificial intelligence (AI) is transforming drug discovery and precision medicine in MS. Machine learning and deep learning models are being employed to analyze high-dimensional biomedical data, predict drug–target interactions, streamline drug repurposing workflows, and enhance therapeutic candidate selection. By integrating multiomics and neuroimaging data, AI tools facilitate the identification of novel targets and support patient stratification for individualized treatment. This review highlights recent advances in drug repurposing and discovery for MS, with a particular emphasis on the emerging role of AI in accelerating therapeutic innovation and optimizing treatment strategies. Full article

Cholangiocarcinoma (CCA) is highly prevalent in the Greater Mekong sub-region, especially northeastern Thailand, where infection with the liver fluke Opisthorchis viverrini is a major etiological factor. Limited therapeutic options and the absence of reliable early diagnosis tools impede effective disease control. Atractylodes lancea (Thunb.) DC.—long used in Thai and East Asian medicine, contains atractylodin (ATD), a potent bioactive compound with anticancer potential. Here, we developed ATD-loaded poly(lactic co-glycolic acid) nanoparticles (ATD PLGA NPs) and evaluated their antitumor efficacy against CCA. The formulated nanoparticles had a mean diameter of 229.8 nm, an encapsulation efficiency of 83%, and exhibited biphasic, sustained release, reaching a cumulative release of 92% within seven days. In vitro, ATD-PLGA NPs selectively reduced the viability of CL-6 and HuCCT-1 CCA cell lines, with selectivity indices (SI) of 3.53 and 2.61, respectively, outperforming free ATD and 5-fluorouracil (5-FU). They suppressed CL-6 cell migration and invasion by up to 90% within 12 h and induced apoptosis in 83% of cells through caspase-3/7 activation. Micronucleus assays showed lower mutagenic potential than the positive control. In vivo, ATD-PLGA NPs dose-dependently inhibited tumor growth and prolonged survival in CCA-xenografted nude mice; the high-dose regimen matched or exceeded the efficacy of 5-FU. Gene expression analysis revealed significant downregulation of pro-tumorigenic factors (VEGF, MMP-9, TGF-β, TNF-α, COX-2, PGE₂, and IL-6) and upregulation of the anti-inflammatory cytokine IL-10. Collectively, these results indicate that ATD-PLGA NPs are a promising nanotherapeutic platform for targeted CCA treatment, offering improved anticancer potency, selectivity, and safety compared to conventional therapies. Full article

The modern livestock industry incorporates widely used antibiotic growth promoters into animal feed at sub-therapeutic levels to enhance growth performance and feed efficiency. However, this practice contributes to the emergence of antibiotic-resistant pathogens in livestock, which may be transmitted to humans through the food chain, thereby diminishing the efficacy of antibiotics in treating bacterial infections. Current research explores the potential of essential oils from derived medicinal plants as alternative phytobiotics. This review examines modern encapsulation strategies that incorporate essential oils into natural-origin matrices to improve their stability and control their release both in vitro and in vivo. We discuss a range of encapsulation approaches utilizing polysaccharides, gums, proteins, and lipid-based carriers. This review highlights the increasing demand for antibiotic alternatives in animal nutrition driven by regulatory restrictions, and the potential benefits of essential oils in enhancing feed palatability and stabilizing the intestinal microbiome in monogastric animals and ruminants. Additionally, we address the economic viability and encapsulation efficiency of different matrix formulations. Full article

This study, conducted in Southern Italy in 2023, investigated the effects of a dynamic agrivoltaics (AV) system on microclimate, water consumption, plant growth, and essential oil yield in six medicinal species: lavender (Lavandula angustifolia L. ‘Royal purple’), lemmon thyme (Thymus citriodorus (Pers.) Schreb. ar. ‘Aureus’), common thyme (Thymus vulgaris L.), rosemary (Salvia rosmarinus Spenn. ‘Severn seas’), mint (Mentha spicata L. ‘Moroccan’), and sage (Salvia officinalis L. subsp. Officinalis). Due to the rotating solar panels, two distinct ground zones were identified: a consistently shaded area under the panels (UP), and a partially shaded area between the panels (BP). These were compared to an adjacent full-sun control area (T). Microclimate parameters, including solar radiation, air and leaf infrared temperature, and soil temperature, were recorded throughout the cultivation season. Reference evapotranspiration (ET_O) was calculated using Turc’s method, and crop evapotranspiration (ET_C) was estimated with species-specific crop coefficients (K_C). Results showed significantly lower microclimatic values in the UP plot compared to both BP and especially T, resulting in ET_C reductions of 81.1% in UP and 13.1% in BP relative to T, an advantage in water-scarce environments. Growth and yield responses varied among species and treatment plots. Except for mint, all species showed a significant reduction in fresh biomass (40.1% to 48.8%) under the high shading of UP compared to T. However, no biomass reductions were observed in BP. Notably, essential oil yields were higher in both UP and BP plots (0.60–2.63%) compared to the T plot (0.51–1.90%). These findings demonstrate that dynamic AV systems can enhance water use efficiency and essential oil yield, offering promising opportunities for sustainable, high-quality medicinal crop production in arid and semi-arid regions. Full article

The emergence of SARS-CoV-2 variants highlights the urgent need for novel therapeutic strategies, particularly entry inhibitors that could efficiently prevent viral infection. Medicinal herbs and herbal combination formulas have long been recognized for their effects in treating infectious diseases and their antiviral properties, thus providing abundant resources for the discovery of antiviral candidates. While many candidates have been suggested to have antiviral activity against SARS-CoV-2 infection, few have been validated for their mechanisms, including possible effects on viral entry. This study aimed to identify SARS-CoV-2 entry inhibitors from medicinal herbs and herbal formulas that are known for heat-clearing and detoxifying properties and/or antiviral activities. A SARS-CoV-2 pseudoparticle (SARS-CoV-2pp) system was used to assess mechanism-specific entry inhibition. Our results showed that the methanol extract of Anemarrhena asphodeloides rhizome, as well as the water extracts of Cimicifuga foetida rhizome, Xiao Chai Hu Tang (XCHT), and Sheng Ma Ge Gen Tang (SMGGT), have substantial inhibitory effects on the entry of SARS-CoV-2pps into host cells. Given the observation that Cimicifuga foetida exhibited the most potent inhibition and is a constituent of SMGGT, we further investigated the major compounds of the herb and identified caffeic acid as a bioactive component for blocking SARS-CoV-2pp entry. Entry inhibition of Cimicifuga foetida and caffeic acid was validated on both wild-type and the currently dominant JN.1 strain SARS-CoV-2pp systems. Moreover, caffeic acid was able to both inactivate the pseudoparticles and prevent their entry into pretreated host cells. The results support the traditional use of these herbal medicines and underscore their potential as valuable resources for identifying active compounds and developing therapeutic entry inhibitors for the management of COVID-19. Full article

Background: Transfection is vital for gene therapy, mRNA treatments, CAR-T cell therapy, and regenerative medicine. While viral vectors are effective, non-viral systems like lipid nanoparticles (LNPs) offer safer, more flexible alternatives. This work explores emerging non-viral transfection technologies to improve delivery efficiency and therapeutic outcomes. Methods: This review synthesizes the current literature and recent advancements in non-viral transfection technologies. It focuses on the mechanisms, advantages, and limitations of various delivery systems, including lipid nanoparticles, biodegradable polymers, electroporation, peptide-based carriers, and microfluidic platforms. Comparative analysis was conducted to evaluate their performance in terms of transfection efficiency, cellular uptake, biocompatibility, and potential for clinical translation. Several academic search engines and online resources were utilized for data collection, including Science Direct, PubMed, Google Scholar Scopus, the National Cancer Institute’s online portal, and other reputable online databases. Results: Non-viral systems demonstrated superior performance in delivering mRNA, siRNA, and antisense oligonucleotides, particularly in clinical applications. Biodegradable polymers and peptide-based systems showed promise in enhancing biocompatibility and targeted delivery. Electroporation and microfluidic systems offered precise control over transfection parameters, improving reproducibility and scalability. Collectively, these innovations address key challenges in gene delivery, such as stability, immune response, and cell-type specificity. Conclusions: The continuous evolution of transfection technologies is pivotal for advancing gene and cell-based therapies. Non-viral delivery systems, particularly LNPs and emerging platforms like microfluidics and biodegradable polymers, offer safer and more adaptable alternatives to viral vectors. These innovations are critical for optimizing therapeutic efficacy and enabling personalized medicine, immunotherapy, and regenerative treatments. Future research should focus on integrating these technologies to develop next-generation transfection platforms with enhanced precision and clinical applicability. Full article

Recently, a number of natural biologically active substances have been proven to be attractive alternatives to conventional anticancer medicine or as adjuvants in contemporary combination therapies. Although lignin-based materials were previously accepted as waste materials with limited usefulness, recent studies increasingly report the possibility of their use for novel applications in various industrial branches, including biomedicine. In this regard, the safety, efficiency, advantages and limitations of lignin compounds for in vitro/in vivo applications remain poorly studied and described. This study was carried out to investigate the possibility of using newly synthesized, alkali lignin-based micro-/nano-biopolymer formulations (Lignin@Formulations/L@F) as carriers for substances with antioxidant and/or anticancer effectiveness. Moreover, we tried to assess the opportunity for using an electro-assisted approach for achieving improved intracellular internalization. An investigation was conducted on an in vitro panel of breast cell lines, namely two breast cancer lines with different metastatic potentials and one non-tumorigenic line as a control. The characterization of all tested formulations was performed via DLS (dynamic light scattering) analysis. We developed an improved separation procedure via size/charge unification for all types of Lignin@Formulations. Moreover, in vitro applications were investigated. The results demonstrate that compared to healthy breast cells, both tested cancer lines exhibited slight sensitivity after treatment with different formulations (empty or loaded with antioxidant substances). This effect was also enhanced after applying electric pulses. L@F loaded with Quercetin was also explored only on the highly metastatic cancer cell line as a model for the breast cancer type most aggressive and non-responsive to traditional treatments. All obtained data suggest that the tested formulations have potential as carriers for the electro-assisted delivery of natural antioxidants such as Quercetin. Full article

Aronia melanocarpa (black chokeberry) is a medicinally valuable small fruit species, yet its commercial propagation remains limited by low rooting and genotype-specific responses. This study developed an efficient, callus-free micropropagation and rooting protocol using a Shrub Plant Medium (SPM) supplemented with 5 mg/L BAP in large 660 mL jars, which yielded up to 27 shoots per explant. Optimal rooting (100%) was achieved with 0.5 mg/L NAA + 0.25 mg/L IBA in half-strength SPM. In the second phase, supervised machine learning models, including Random Forest (RF), XGBoost, Gaussian Process (GP), and Multilayer Perceptron (MLP), were employed to predict morphogenic traits based on culture conditions. XGBoost and RF outperformed other models, achieving R² values exceeding 0.95 for key variables such as shoot number and root length. These results demonstrate that data-driven modeling can enhance protocol precision and reduce experimental workload in plant tissue culture. The study also highlights the potential for combining physiological understanding with artificial intelligence to streamline future in vitro applications in woody species. Full article

Red blood cell (RBC) production from bone marrow hematopoietic stem cells (BMHSCs) in vitro overlooks the mechanical signals of the bone marrow niche and overly relies on growth factors. Considering that the fate of hematopoietic stem cells (HSCs) is determined by the natural bone marrow microenvironment, differences in mechanical microenvironments provide a reference for the regulation of HSC differentiation. This study seek to reveal the role of mechanobiology cues in erythropoiesis and provide a new perspective for the design of in vitro erythropoiesis platforms. The hydrogel platforms we designed simulate the stiffness gradient of the bone marrow niche to culture HSCs and induce their differentiation into the erythroid system. Cells on the low-stiffness scaffold have higher potential for erythrocyte differentiation and faster differentiation efficiency and promote erythrocyte differentiation after erythropoietin (EPO) restriction. In vivo transplantation experiments demonstrated that these cells have the ability for continuous proliferation and differentiation into mature erythrocytes. By combining mechanical cues with in vitro erythrocyte production, this method is expected to provide insights for in vitro hematopoietic design and offer a scalable cell manufacturing platform for transfusion medicine. Full article

The regio- and stereoselective adjacent bifunctionalization of olefins with amine and halogen groups can be effectively accomplished through catalytic haloamination methods. Stereoselective haloamination has emerged as a pivotal methodology for the introduction of halogen functional groups into chiral amines, demonstrating substantial applications in medicinal chemistry and organic synthesis. Since 1999, significant advancements have been achieved in this field, driven by innovations in catalytic systems and methodologies. The stereoselective haloamination of both functionalized and nonfunctionalized alkenes employing chiral catalysts has emerged as a prominent area of research. This review provides a comprehensive overview of the research progress in stereoselective haloamination reactions from 1999 to 2023. It examines the innovations in catalyst design that have facilitated more efficient and selective transformations. The review also analyzes the optimization of reaction conditions, which has been crucial in improving the overall performance and applicability of these reactions. Furthermore, it explores the diverse range of haloamination reactions that have been developed, emphasizing their potential for the synthesis of complex and valuable chemical structures. Additionally, this review offers insightful perspectives on future research directions in stereoselective haloamination reactions. Full article

Gene therapy is a groundbreaking strategy in regenerative medicine, enabling precise cellular behavior modulation for tissue repair. In situ nucleic acid delivery systems aim to directly deliver nucleic acids to target cells or tissues to realize localized genetic reprogramming and avoid issues like donor cell dependency and immune rejection. The key to success relies on biomaterial-engineered delivery platforms that ensure tissue-specific targeting and efficient intracellular transport. Viral vectors and non-viral carriers are strategically modified to enhance nucleic acid stability and cellular uptake, and integrate them into injectable or 3D-printed scaffolds. These scaffolds not only control nucleic acid release but also mimic native extracellular microenvironments to support stem cell recruitment and tissue regeneration. This review explores three key aspects: the mechanisms of gene editing in tissue repair; advancements in viral and non-viral vector engineering; and innovations in biomaterial scaffolds, including stimuli-responsive hydrogels and 3D-printed matrices. We evaluate scaffold fabrication methodologies, nucleic acid loading–release kinetics, and their biological impacts. Despite progress in spatiotemporal gene delivery control, challenges remain in balancing vector biocompatibility, manufacturing scalability, and long-term safety. Future research should focus on multifunctional “smart” scaffolds with CRISPR-based editing tools, multi-stimuli responsiveness, and patient-specific designs. This work systematically integrates the latest methodological advances, outlines actionable strategies for future investigations and advances clinical translation perspectives beyond the existing literature. Full article

Tetrasubstituted dihydrothiophenes represent a class of heterocyclic compounds with significant potential in various fields, particularly in medicinal chemistry and materials science. In this work, we have developed an eco-friendly and efficient method for synthesizing such compounds, using porcine pancreatic lipase (PPL) as a biocatalyst to promote the cyclization reaction between β-ketothioamides and β-nitrostyrenes. Through this approach, sixteen tetrasubstituted dihydrothiophenes were successfully synthesized, and all of them achieved high yields, ranging from 80% to 96%. This research not only expands the application scope of lipase in organic synthesis, demonstrating its versatility beyond traditional hydrolytic reactions, but also provides a new environmentally friendly pathway for the production of tetrasubstituted dihydrothiophenes, which is of great significance for advancing related fields of chemical synthesis. Full article

Today’s primary challenges include identifying efficient, affordable, and environmentally sustainable substances to serve as raw materials in industrial, agricultural, and medicinal applications. This study aimed to evaluate the chemical composition and biological properties (namely antioxidant and allelopathic activities) of the methanolic extract derived from the above-ground portions of Artemisia judaica collected in Jazan, Saudi Arabia. GC-MS was used to evaluate the chemical composition of the methanolic extract derived from Artemisia judaica. GC-MS analysis revealed a total of 22 volatile compounds in the extract. The most prominent compounds identified were 2-ethylhexanoic acid, 5-hydroxy-6-(1-hydroxyethyl)-2,7-dimethoxynaphtho-quinone, and piperitone. The extract demonstrated strong antioxidant activity in both the DPPH and ABTS radical scavenging assays, comparable to the standard antioxidant ascorbic acid. The IC₅₀ value for the extract was 31.82 mg/mL in the DPPH assay and 39.93 mg/mL in the ABTS testing. Additionally, the extract exhibited dose-dependent inhibition of seed germination, root growth, and shoot growth of the weed Chenopodium murale in allelopathic bioassays. The most significant suppression was observed in shoot growth with an IC₅₀ value of 45.90 mg/mL, which was lower than the IC₅₀ values for root development and seed germination of C. murale, recorded at 56.16 mg/mL and 88.80 mg/mL, respectively. Furthermore, the findings indicated that methanolic extracts had significant lethal toxic effects on the life cycle of Aedes aegypti. Future research will focus on extracting uncontaminated substances and evaluating the biological effects of each specific constituent. Full article

To address the problems of the time consumption, labor intensiveness, easy contamination, uneven drying, and impact on the medicinal efficacy of Fritillaria ussuriensis in the traditional drying method, the hot-air-drying characteristics of Fritillaria ussuriensis were studied. The changes in the moisture ratio and drying rate of Fritillaria ussuriensis under different hot-air-drying conditions (45 °C, 55 °C, 65 °C) were compared and analyzed. Six common mathematical models were used to fit the moisture change law, and it was found that the cubic model was the most suitable for describing the drying characteristics of Fritillaria ussuriensis. The R² values after fitting under the three temperature conditions were all greater than 0.99, and the maximum was achieved at 45 °C. Based on the principle of hot-air drying, a drying device for Fritillaria ussuriensis with a processing capacity of 15 kg/h was designed. It adopted a thermal circulation structure of inner and outer drying ovens, with the heating chamber separated from the drying chamber. The structural parameters were optimized based on Fluent simulation analysis. After optimization, the temperature of each layer was stable at 338 K ± 2 K, and the pressure field and velocity field were evenly distributed. The drying process parameters of Fritillaria ussuriensis were optimized based on response surface analysis, and the optimal process parameters were obtained as follows: inlet temperature: 338 K (65 °C), inlet air velocity: 3 m/s, and drying time: 10 h. The simulation results showed that the predicted moisture content of Fritillaria ussuriensis under the optimal working conditions was 12.58%, the temperature difference of Fritillaria ussuriensis at different positions was within 0.8 °C, and the humidity deviation was about 1%. A prototype of the drying device was built, and the drying test of Fritillaria ussuriensis was carried out. It was found that the temperature and moisture content of Fritillaria ussuriensis were consistent with the simulation results and met the design requirements, verifying the rationality of the device structure and the reliability of the simulation model. This design can significantly improve the distribution of the internal flow field and temperature field of the drying device, improve the drying quality and production efficiency of Fritillaria ussuriensis, and provide a technical reference for the Chinese herbal medicine-drying industry. Full article