Search Results (2,137)

Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk., commonly known as divaricate siler, is a well-known medicinal plant from the Apiaceae family. Its natural habitat is rapidly declining owing to the harvesting of its roots, used as fángfēng in traditional Oriental medicine. This underutilized herb may serve as a valuable source of bioactive phenolic compounds, which can potentially be influenced by salicylic acid (SA) elicitation—a practical method to increase the concentration of valuable substances in plants. A field study showed that foliar application of SA on one-year-old S. divaricata positively influenced the total phenolic content in the herb, with the highest increase observed at 1.0 mM SA. Liquid chromatography–mass spectrometry (LC–MS) data became increasingly complex with rising SA levels, identifying up to 48 compounds, including cinnamoyl quinic acids (CQAs), dihydrofurochromones (DFCs), and flavonol O-glycosides (FOGs), most reported for the first time in this species. The highest concentrations of CQAs, DFCs, and FOGs in plants treated with 1.0 mM SA were 83.14, 3.75, and 60.53 mg/g, respectively, compared to 42.76, 0.95, and 40.73 mg/g in untreated (0.0 mM SA) plants. Nine in vitro antioxidant assays revealed strong radical-scavenging and nitric oxide (NO)- and Fe²⁺-chelating activities in 1.0 mM SA-treated plants, indicating robust antioxidative properties of the S. divaricata herb. Thus, foliar application of SA considerably enriches the herb with target antioxidants, increasing its medicinal value, which is reflected in the plant’s biological response. This could potentially reduce the overexploitation of natural populations of S. divaricata, helping to preserve this valuable plant. Full article

Leishmaniasis is an infectious disease common in tropical and subtropical regions worldwide. This study aimed to develop a topical meglumine antimoniate gel (MA-gel) for the treatment of cutaneous leishmaniasis. The MA-gel was characterized in terms of morphology, pH, swelling, porosity, rheology, and thermal properties by differential scanning calorimetry (DSC). Biopharmaceutical evaluation included in vitro drug release and ex vivo skin permeation. Safety was evaluated through biomechanical skin property measurements and cytotoxicity in HaCaT and RAW 267 cells. Leishmanicidal activity was tested against promastigotes and amastigotes of Leishmania infantum, and in silico studies were conducted to explore possible mechanisms of action. The composition of the MA-gel included 30% MA, 20% Pluronic^® F127 (P407), and 50% water. Scanning electron microscopy revealed a sponge-like and porous internal structure of the MA-gel. This formula exhibited a pH of 5.45, swelling at approximately 12 min, and a porosity of 85.07%. The DSC showed that there was no incompatibility between MA and P407. Drug release followed a first-order kinetic profile, with 22.11 µg/g/cm² of the drug retained in the skin and no permeation into the receptor compartment. The MA-gel showed no microbial growth, no cytotoxicity in keratinocytes, and no skin damage. The IC₅₀ for promastigotes and amastigotes of L. infantum were 3.56 and 23.11 µg/mL, respectively. In silico studies suggested that MA could act on three potential therapeutic targets according to its binding mode. The MA-gel demonstrated promising physicochemical, safety, and antiparasitic properties, supporting its potential as a topical treatment for cutaneous leishmaniasis. Full article

Male-factor infertility accounts for approxiamately half of all infertility cases globally, yet therapeutic options remain limited for individuals with no retrievable spermatozoa, such as those with non-obstructive azoospermia (NOA). In recent years, artificial gametogenesis has emerged as a promising avenue for fertility restoration, driven by advances in two complementary strategies: organotypic in vitro spermatogenesis (IVS), which aims to complete spermatogenesis ex vivo using native testicular tissue, and in vitro gametogenesis (IVG), which seeks to generate male gametes de novo from pluripotent or reprogrammed somatic stem cells. To evaluate the current landscape and future potential of these approaches, a narrative, semi-systematic literature search was conducted in PubMed and Scopus for the period January 2010 to February 2025. Additionally, landmark studies published prior to 2010 that contributed foundational knowledge in spermatogenesis and testicular tissue modeling were reviewed to provide historical context. This narrative review synthesizes multidisciplinary evidence from cell biology, tissue engineering, and translational medicine to benchmark IVS and IVG technologies against species-specific developmental milestones, ranging from rodent models to non-human primates and emerging human systems. Key challenges—such as the reconstitution of the blood–testis barrier, stage-specific endocrine signaling, and epigenetic reprogramming—are discussed alongside critical performance metrics of various platforms, including air–liquid interface slice cultures, three-dimensional organoids, microfluidic “testis-on-chip” devices, and stem cell-derived gametogenic protocols. Particular attention is given to clinical applicability in contexts such as NOA, oncofertility preservation in prepubertal patients, genetic syndromes, and reprocutive scenarios involving same-sex or unpartnered individuals. Safety, regulatory, and ethical considerations are critically appraised, and a translational framework is outlined that emphasizes biomimetic scaffold design, multi-omics-guided media optimization, and rigorous genomic and epigenomic quality control. While the generation of functionally mature sperm in vitro remains unachieved, converging progress in animal models and early human systems suggests that clinically revelant IVS and IVG applications are approaching feasibility, offering a paradigm shift in reproductive medicine. Full article

Background/Objectives: During the repair of a wounded epithelium, keratinocytes become invasive via the epithelial-to-mesenchymal transition (EMT) process. Usually temporary and controlled, EMT persists in a chronically inflamed epithelium and is exacerbated in epithelial dysplasia and dysregulated in invasive carcinomas. Here we investigated the effects that IL-1 beta, IL-6, and IL-8, inflammatory cytokines expressed in specimens from OPMDs and OSCCs, have on NOKs and OSCC cells. Methods: AKT activation and EMT induction were assessed along with cellular invasiveness. Results: IL-1 beta, IL-6, and IL-8 induced EMT in NOKs, ex novo conferring them invasive capacity. The same cytokines exacerbated the constitutive EMT and invasiveness of OSCC cells. Since these phenomena were accompanied by AKT activation, we tested whether they could be influenced by RTV, a long-used anti-HIV drug that was previously found to block the activation of human AKT and exert antitumor effects. We observed that therapeutic amounts of RTV counteract all the above-mentioned tumorigenic activities of ILs. Finally, consistent with the key role that AKT and EMT play in OSCC radio-resistance, RTV increased OSCC cells’ sensitivity to therapeutic doses of ionizing radiation. Conclusions: These preliminary in vitro findings encourage the use of RTV to prevent the malignant evolution of OPMDs, reduce the risk of OSCC metastasis, and improve the outcomes of anti-OSCC radiotherapy. Full article

Considering the high plasticity of FoxP3⁺ regulatory T (Treg) cells and Interleukin (IL)-17-producing Th17 cells, we hypothesized that a Th17 inflammatory milieu may impair the functional properties of Treg cells in chronic inflammatory arthritides. Therefore, a cross-sectional explorative analysis was set up in patients with psoriatic arthritis (PsoA), rheumatoid arthritis, or spondyloarthritis to investigate the features of Th17 and Treg cells. T cell subpopulation counts, FOXP3 mRNA expression, CpG methylation of the FOXP3 gene, and the suppressive capacity of isolated Treg cells were determined. Ex vivo analysis of PsoA-derived peripheral blood lymphocytes showed a Th17-mediated inflammation. It was accompanied by demethylation of the FOXP3 promotor and Treg-specific demethylated region (TSDR) in Treg cells which, however, resulted neither in elevated FOXP3 mRNA expression nor in increased suppressive Treg cell capacity. To clarify this conundrum, in vitro stimulation of isolated Treg cells with Th17-inducing cytokines (IL-1β, IL-6, IL-23, TGFβ), recombinant IL-17, or the anti-IL-17A antibody secukinumab was performed, demonstrating that cell culture conditions polarizing towards Th17, but not IL-17 itself, impair the suppressive function of Treg cells, accompanied by diminished FOXP3 mRNA expression due to hypermethylation of the FOXP3 promotor and TSDR. This potential causal relationship between Th17 inflammation and impaired Treg cell function requires attention regarding the development of immunomodulatory therapies. Full article

Lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy approved for advanced melanoma, demonstrates promise for treating other solid tumors, including endometrial cancer (EC). The current study evaluates the feasibility of manufacturing TILs from EC tumors using Iovance’s proprietary 22-day Gen2 manufacturing process. Key parameters, including TIL yield, viability, immune phenotype, T-cell receptor clonality, and cytotoxic activity, were assessed. Of the 11 EC tumor samples processed at research scale, 10 (91%) successfully generated >1 × 10⁹ viable TIL cells, with a median yield of 1.1 × 10¹⁰ cells and a median viability of 82.8%. Of the four EC tumor samples processed at full scale, all achieved the pre-specified TVC and viability targets. Putative tumor-reactive T-cell clones were maintained throughout the manufacturing process. Functional reactivity was evidenced by the upregulation of 4-1BB in CD8+ T cells, OX40 in CD4+ T cells, and increased production of IFN-γ and TNF-α upon autologous tumor stimulation. Furthermore, antitumor activity was confirmed using an in vitro autologous tumor organoid killing assay. These findings demonstrate the feasibility of ex vivo TIL expansion from EC tumors. This study provides a rationale for the initiation of the phase II clinical trial IOV-END-201 (NCT06481592) to evaluate lifileucel in patients with advanced EC. Full article

Ultra-high dose rate radiotherapy known as Flash radiotherapy (FLASH-RT) offers tremendous opportunities to improve the therapeutic ratio of radiotherapy by sparing the normal tissue while maintaining similar tumoricidal efficacy. However, the underlying biophysical basis of the FLASH effect remains under active investigation with several proposed mechanisms involving oxygen depletion, altered free-radical chemistry, and differential biological responses. This article provides an overview of available experimental and computational tools that can be utilized to probe the tumor and normal tissue microenvironment. We analyze in vitro, ex vivo, and in vivo systems used to study FLASH responses. We describe various computational and imaging technologies that can potentially aid in understanding the biophysics of FLASH-RT and lead to safer clinical translational. Full article

Botanical gardens serve as vital centers for ex situ conservation, maintaining diverse plant species under controlled conditions. Terrestrial orchids, despite their wide diversity and distribution, often occur in small and declining populations, making their conservation increasingly urgent. This study aimed to examine the potential for establishing the first specialized orchidarium in Serbia, focusing on the native orchid species of the Fruška Gora region. A SWOT analysis, combined with site assessment data, was employed to identify key strengths, weaknesses, opportunities, and threats, informing the development of a functional zoning plan. The results indicate that such an orchidarium would offer a threefold benefit: strengthening ex situ conservation, advancing scientific research and environmental education, and promoting sustainable tourism. The proposed design consists of eight distinct zones, three of which reflect natural habitats of selected orchid species. The planned integration of a seed gene bank in the central zone, along with living plant collections and a nearby in vitro culture laboratory, establishes a comprehensive framework for the sustainable management of orchid genetic resources in the region, forming a foundation for future research and preservation. Full article

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by tissue damage in multiple organs caused by autoantibodies and the resulting immune complexes. One possible way for complement system contribution to onset of autoimmune disorder could be realized by the impairment of C1q-mediated apoptotic clearance as part of human homeostasis. The capacity of C1q to bind early apoptotic cells could be decreased or even lost in the presence of anti-C1q antibodies. A monoclonal anti-idiotypic single-chain (scFv) antibody was selected from the phage library Griffin1” to recognize anti-C1q autoantibodies, purified from sera of lupus nephritis patients. Lupus-prone MRL/lpr mice were injected weekly with scFv A1 fragment-binding anti-C1q antibodies. The number of in vitro and ex vivo studies with collected cells, sera, and organs from the treated animals was performed. scFv treatment changed the percentage of different B-, T-, and NK-cell subpopulations as well as plasma cells and plasmablasts in the spleen and bone marrow. An increase in the levels of splenocyte proliferation, anti-C1q antibodies, and the number of plasma cells producing anti-dsDNA and anti-C1q antibodies were also observed in scFv-treated animals. High levels of proteinuria and hematuria combined with unstable levels of IL10 and IFNγ promote the development of severe lupus and shorten the survival of treated MRL/lpr mice. Therapy with the scFv A1 antibody resulted in BCR recognition on the surface of anti-C1q-specific B-cells and had a disease progression effect, enhancing lupus symptoms in the MRL/lpr mouse model of SLE. Full article

Transdermal drug delivery (TDD) is an increasingly important non-invasive method for administering active pharmaceutical ingredients (APIs) through the skin barrier, offering advantages such as improved therapeutic efficacy and reduced systemic side effects. As demand increases for patient-friendly and minimally invasive treatment options, TDD has attracted substantial attention in research and clinical practice. This review summarizes recent advances enhancing skin permeability through chemical enhancers (e.g., ethanol, fatty acids, terpenes), physical (e.g., iontophoresis, microneedles, sonophoresis), and nanotechnological methods (e.g., liposomes, ethosomes, solid lipid nanoparticles, and transferosomes). A comprehensive literature analysis, including scientific publications, regulatory guidelines, and patents, was conducted to identify innovative methods and materials used to overcome the barrier properties of the stratum corneum. Special emphasis was placed on in vitro, ex vivo, and in vivo evaluation techniques for such as Franz diffusion cells for assessing drug permeation and skin interactions. The findings highlight the importance of active physical methods, passive nanostructured systems, and chemical penetration enhancers. In conclusion, integrating multiple analytical techniques is essential for the rational design and optimization of effective transdermal drug delivery systems. Full article

Polymorphous Light Eruption (PLE) is a prevalent UV-induced photodermatosis characterized by abnormal immune responses, oxidative stress, and cutaneous inflammation. Alpha-glucosylrutin (AGR), a chemically modified flavonoid widely used for its antioxidant and photoprotective effects, has shown clinical efficacy; however, its synthetic origin and classification as a potential skin sensitizer and aquatic toxin raise safety and environmental concerns. These limitations underscore the need for safer, naturally derived alternatives. In this study, we investigated the comparative efficacy of quercetin (QC) and hesperidin (HPN)—two plant-based flavonoids—against AGR in in vitro and ex vivo models of sun-induced skin damage. An optimized QC:HPN 8:1 (w/w) complex significantly restored antioxidant enzyme activities (SOD: 4.11 ± 0.32 mU/mg; CAT: 1.88 ± 0.04 mU/mg) and suppressed inflammatory cytokine production (IL-6: 155.95 ± 3.17 pg/mL; TNF-α: 62.34 ± 0.72 pg/mL) more effectively than AGR. β-hexosaminidase secretion, a marker of allergic response, was reduced to 99.02 ± 1.45% with QC:HPN 8:1, compared to 121.33 ± 1.15% with AGR. QC alone exhibited dose-dependent cytotoxicity at ≥10 μg/mL, whereas HPN maintained >94% cell viability at all tested concentrations. These findings highlight the QC:HPN 8:1 complex as a safe, natural, and effective alternative to synthetic AGR for preventing and managing PLE and UV-induced dermal inflammation. Further research should focus on clinical validation and formulation development for topical use. Full article

Humulus lupulus L. (hop) is a multipurpose crop valued for its essential role in beer production and for its bioactive compounds with recognized medicinal properties. Otherwise, climate change represents a major challenge to agriculture, particularly impacting the cultivation of crops with stenoecious characteristics, such as hop. This highlights the urgent need to enhance crop resilience to adverse environmental conditions. The phytohormone abscisic acid (ABA) is a key regulator of plant responses to abiotic stress, yet the ABA signaling pathway remains poorly characterized in hop. Harnessing the publicly available hop genomics resources, we identified eight members of the PYRABACTIN RESISTANCE 1 LIKE ABA receptor family (HlPYLs). Phylogenetic and gene structure analyses classified these HlPYLs into the three canonical ABA receptor subfamilies. Furthermore, all eight HlPYLs are likely functional, as suggested by the protein sequence visual analysis. Expression profiling indicates that ABA perception in hop is primarily mediated by the HlPYL1-like and HlPYL8-like subfamilies, while the HlPYL4-like group appears to play a more limited role. Structure modeling and topology predictions of HlPYL1b and HlPYL2 provided insights into their potential functional mechanisms. To assess the physiological relevance of ABA signaling in hop, we evaluated the impact of exogenous ABA application during the ex vitro acclimatization phase. ABA-treated plants exhibited more robust growth, reduced stress symptoms, and improved acclimatization success. These effects were associated with reduced leaf transpiration and enhanced stomatal closure, consistent with ABA-mediated drought tolerance mechanisms. Altogether, this study provides the first comprehensive characterization of ABA receptor components in hop and demonstrates the practical utility of ABA in improving plant performance under ex vitro conditions. These findings lay the groundwork for further functional studies and highlight ABA signaling as a promising target for enhancing stress resilience in hop, with broader implications for sustainable agriculture in the face of climate change. Full article

An efficient in vitro propagation protocol for Eulophia bicallosa was developed using asymbiotic seed germination and protocorm proliferation. The effect of light on seed germination and development was evaluated on Vacin and Went (VW) medium under five conditions: darkness, white, green, red, and blue light for 24 weeks. Blue and red light significantly accelerated seed development, allowing progression to stage 5 within 24 weeks. For protocorm proliferation, six semi-solid culture media were tested. Half-strength Murashige and Skoog (½MS) medium yielded the best results after 8 weeks, producing the highest numbers of shoots (1.0), leaves (1.1), and roots (4.2) per protocorm, with 100% survival. The effects of organic additives were also evaluated using coconut water and potato extract. A combination of 200 mL L⁻¹ coconut water and 50 g L⁻¹ potato extract enhanced shoot formation (1.7 shoots), while 150 mL L⁻¹ coconut water with 50 g L⁻¹ potato extract increased both leaf (1.9) and root (8.8) numbers. The effects of cytokinins (benzyladenine (BA), kinetin (6-furfurylaminopurine), and thidiazuron (TDZ)) and auxins (indole-3-acetic acid (IAA), α-naphthalene acetic acid (NAA), indole-3-butyric acid (IBA), and 2,4-dichlorophenoxyacetic acid (2,4-D)) were investigated using ½MS medium supplemented with each plant growth regulator individually at concentrations of 0, 0.1, 0.5, 1.0, and 2.0 mg L⁻¹. Among the cytokinins, 0.1 mg L⁻¹ BA produced the highest survival rate (96%), while 1.0 mg L⁻¹ BA induced the greatest shoot formation (93%, 2.3 shoots). Among the auxins, 0.1 mg L⁻¹ IAA resulted in the highest survival (96%), and 1.0 mg L⁻¹ IAA significantly enhanced root induction (4.2 roots per protocorm). Acclimatization in pots containing a 1:1:1 (v/v) mixture of pumice, sand, and soil resulted in 100% survival. This protocol provides a reliable and effective approach for the mass propagation and ex situ conservation of E. bicallosa. Full article