Search Results (194)

Finger millet (Eleusine coracana L.) is a nutrient-dense cereal with high flavonoid content, yet the mechanisms regulating its secondary metabolite biosynthesis remain underexplored. Various exogenous stimuli can readily activate the enzymatic pathways and gene expression associated with flavonoid biosynthesis in plants, which are regulated by developmental cues. Research has established that methyl jasmonate (MeJA) application enhances secondary metabolite production in plant systems. This investigation examined MeJA’s influence on flavonoid accumulation and physiological responses in finger millet sprouts to elucidate the molecular mechanisms underlying MeJA-mediated flavonoid accumulation. The findings revealed that MeJA treatment significantly suppressed sprout elongation while enhancing the biosynthesis of total flavonoids and phenolic compounds. MeJA treatment triggered oxidative stress responses, with hydrogen peroxide and superoxide anion concentrations increasing 1.84-fold and 1.70-fold compared to control levels at 4 days post-germination. Furthermore, the antioxidant defense mechanisms in finger millet were upregulated following treatment, resulting in significant enhancement of catalase and peroxidase enzymatic activities and corresponding transcript abundance. MeJA application augmented the activities of key phenylpropanoid pathway enzymes—phenylalanine ammonia-lyase (PAL) and cinnamate 4-hydroxylase (C4H)—and upregulated their respective gene expression. At 4 days post-germination, EcPAL and EcC4H transcript levels were elevated 3.67-fold and 2.61-fold, respectively, compared to untreated controls. MeJA treatment significantly induced the expression of downstream structural genes and transcriptional regulators. This study provides a deeper understanding of the mechanism of flavonoid accumulation in foxtail millet induced by MeJA, and lays a foundation for exogenous conditions to promote flavonoid biosynthesis in plants. Full article

Nanotherapeutics have emerged as novel unparalleled drug delivery systems (DDSs) for the treatment of neurodegenerative disorders. By applying different technological approaches, nanoparticles can be engineered to possess different functionalities. In recent years, the developed, stimuli-responsive nanocarriers stand out as novel complex DDSs ensuring selective and specific drug delivery in response to different endogenous and exogenous stimuli. Due to the multifaceted pathophysiology of the nervous system, a major challenge in modern neuropharmacology is the development of effective therapies ensuring high efficacy and low toxicity. Functionalization of the nanocarriers to react to specific microenvironmental changes in the nervous system tissues or external stimulations significantly enhances the efficacy of drug delivery. This review discusses the microenvironmental characteristics of some common neurological diseases in-depth and provides a comprehensive overview on the progress of the development of exogenous and endogenous stimuli-sensitive nanocarriers for the treatment of Alzheimer’s and Parkinson’s disease. Full article

CLAVATA3 (CLV3)/endosperm surrounding region (CLE) peptides have been reportedly involved in plant growth and development, as well as responses to abiotic stresses. However, the stress resilience of most CLE genes in cotton remains largely unknown. Here, induced expression pattern analysis showed that GhCLE25 was obviously responsive to osmotic and salt treatments, indicating that GhCLE25 was involved in abiotic stress tolerance. Furthermore, silencing GhCLE25 or the exogenous application of CLE25p effectively led to reduced and enhanced drought tolerance, respectively, as indicated by the activities of the plants’ POD, SOD, CAT, and MDA contents, as well as their height and fresh weight. We found that the knockdown of GhCLE25 promoted seedling growth and development, with a higher plant height and fresh weight in GhCLE25-silenced plants in comparison to control plants. In addition, a comparative transcriptome analysis of TRV:00 versus TRV:GhCLE25 and Mock versus CLE25p revealed that the CLE25-mediated signaling pathway is mainly involved in defense response and phytohormone signaling. Collectively, these findings indicate diverse roles of CLE25 in regulating plant growth and response to environmental stimuli and highlight the potential utilization of CLE25 to improve drought stress in modern agriculture via CLE25p spraying. Full article

Increasing the stomatal aperture is a crucial strategy for enhancing the rate of CO₂ absorption, which ultimately contributes to increased plant yield through improved photosynthetic activity. The successful implementation of this strategy depends on the rapid identification of positive regulatory environmental stimuli that promote stomatal opening. However, current research on stomatal opening regulation has predominantly focused on Arabidopsis and other crops, with comparatively less attention given to leafy vegetables. In this study, Chinese cabbage was selected as the experimental material. A suitable method for isolating stomata from Chinese cabbage was developed by comparing the advantages and disadvantages of several commonly used stomatal isolation techniques. Subsequently, an effective method for observing stomatal aperture was established through an investigation of the time and concentration dependence on potassium-containing solutions. Utilizing this observation method, the stomatal aperture response to twelve environmental stimuli was examined to facilitate the rapid screening of a formula to enhance stomatal opening. The stomatal aperture observation protocol involved incubating the abaxial epidermis, obtained via the epidermal peeling method, in an opening solution containing 0.5% KCl (pH 6.0) under light for 5 h. The results indicated that stomatal opening is concentration dependent on external environmental stimuli. The exogenous application of 100 µM Ca²⁺ (33.5%), 50 µM brassinosteroid (43.5%), and 10 µM cytokinin (43.4%) resulted in an increase in stomatal aperture of over 30%. This research provides a foundation for manipulating the stomatal opening of Chinese cabbage to enhance production. Full article

Skin is a highly differentiated tissue, in which various signaling molecules play critical roles in the differentiation and proliferation of keratinocytes. Among these, the second messenger calcium and its gradient across skin layers are pivotal in regulating keratinocyte differentiation. Additionally, a diverse array of cellular signaling molecules has been identified as essential for promoting keratinocyte differentiation, thereby maintaining skin integrity and barrier function. The barrier function of the skin provides essential protection against exogenous stimuli and pathogens while maintaining structural stability. The homeostatic processes of skin differentiation are modulated by these second messengers and various signaling molecules. Thus, this review highlights the components associated with keratinocyte differentiation and their biological and pathophysiological roles, as well as redox-sensitive differentiation factors in the modulation of skin homeostasis. This review aims to enhance our understanding of skin physiology and provide insights that may facilitate the development of novel therapeutic strategies for skin diseases. Full article

The gasotransmitter hydrogen sulfide (H₂S; also termed sulfide) generally acts as a vasodilator in the systemic vasculature but causes a paradoxical constriction of pulmonary arteries (PAs). In light of evidence that a fall in the partial pressure in oxygen (pO₂) increases cellular sulfide levels, it was proposed that a rise in sulfide in pulmonary artery smooth muscle cells (PASMCs) is responsible for hypoxic pulmonary vasoconstriction, the contraction of PAs which develops rapidly in lung regions undergoing alveolar hypoxia. In contrast, pulmonary hypertension (PH), a sustained elevation of pulmonary artery pressure (PAP) which can develop in the presence of a diverse array of pathological stimuli, including chronic hypoxia, is associated with a decrease in the expression of sulfide -producing enzymes in PASMCs and a corresponding fall in sulfide production by the lung. Evidence that PAP in animal models of PH can be lowered by administration of exogenous sulfide has led to an interest in using sulfide-donating agents for treating this condition in humans. Notably, intracellular H₂S exists in equilibrium with other sulfur-containing species such as polysulfides and persulfides, and it is these reactive sulfur species which are thought to mediate most of its effects on cells through persulfidation of cysteine thiols on proteins, leading to changes in function in a manner similar to thiol oxidation by reactive oxygen species. This review sets out what is currently known about the mechanisms by which H₂S and related sulfur species exert their actions on pulmonary vascular tone, both acutely and chronically, and discusses the potential of sulfide-releasing drugs as treatments for the different types of PH which arise in humans. Full article

Recent advancements in nanotechnology have revolutionized cancer therapy—one of the most pressing global health challenges and a leading cause of death—through the development of liposomes (L), lipid-based nanovesicles known for their biocompatibility and ability to encapsulate both hydrophilic and lipophilic drugs. More recent innovations have led to the creation of stimuli-responsive L that release their payloads in response to specific endogenous or exogenous triggers. Dual- and multi-responsive L, which react to multiple stimuli, offer even greater precision, improving therapeutic outcomes while reducing systemic toxicity. Additionally, these smart L can adjust their physicochemical properties and morphology to enable site-specific targeting and controlled drug release, enhancing treatment efficacy while minimizing adverse effects. This review explores the latest advancements in endogenous stimuli-responsive liposomal nanocarriers, as well as dual- and multi-responsive L that integrate internal and external triggers, with a focus on their design strategies, mechanisms, and applications in cancer therapy. Full article

Bridged polysilsesquioxanes (BPSs) are emerging biomaterials composed of synergistic inorganic and organic components. These materials have been investigated as ideal carriers for therapeutic and diagnostic systems for their favorable properties, including excellent biocompatibility, physiological inertia, tunable size and morphology, and their extensive design flexibility of functional organic groups to satisfy diverse application requirements. Stimuli-responsive BPSs can be activated by both endogenous and exogenous stimuli, offering a precise, safe, and effective platform for the controlled release of various targeted therapeutics. This review aims to provide a comprehensive overview of stimuli-responsive BPSs, focusing on their synthetic strategies, biocompatibility, and biodegradability, while critically assessing their capabilities for controlled release in response to specific stimuli. Furthermore, practical suggestions and future perspectives for the design and development of BPSs are presented. This review highlights the significant role of stimuli-responsive BPSs in advancing biomedical research. Full article

Background: Strains XG04 and XGT2 of Lentinus edodes (Berk.) Singer demonstrate a high degree of genomic similarity, with XGT2 representing a systematic selection of XG04 and exhibiting enhanced phenotypic traits. Methods: An investigation into the differences between these strains was conducted using untargeted metabolomics to identify potential causal factors. Five exogenous inducers were assessed for their relationship with the observed phenotypes, and their impacts on fruiting body characteristics were analyzed. Results: Notably, the exogenous inducer rolipram, at a concentration of 0.4%, was found to increase cAMP expression levels in L. edodes primordia, which subsequently affected gill development, leading to the formation of gill-free fruiting bodies. Morphological differences between the two strains were evident; XG04 exhibited a spherical morphology with absent gills, rendering it commercially unviable, whereas XGT2 displayed a thicker cap and a more robust stipe, maintaining its characteristic umbrella shape. Conclusions: As the concentration of rolipram increased, both cap retraction and gill reduction in XGT2 occurred in a dose-dependent manner. The endogenous cAMP levels in the fruiting bodies were measured before and after rolipram treatment, revealing that the cap retraction and gill reduction in XGT2 progressed in a dose-dependent manner alongside increasing cAMP expression levels. Furthermore, a positive correlation was observed between cAMP levels and rolipram concentration. This study provides a foundation for improving the quality and productivity of mushroom cultivation by manipulating fruiting body characteristics through external stimuli. Full article

Background: Cancer is one of the leading causes of death worldwide. The tumor microenvironment makes the tumor difficult to treat, favoring drug resistance and the formation of metastases, resulting in death. Methods: Stimuli-responsive nanoparticles have shown great capacity to be used as a powerful strategy for cancer treatment, diagnostic, as well as theranostic. Nanocarriers are not only able to respond to internal stimuli such as oxidative stress, weakly acidic pH, high temperature, and the high expression of particular enzymes, but also to external stimuli such as light and paramagnetic characteristics to be exploited. Results: In this work, stimulus-responsive nanocarriers functionalized with arginine-glycine-aspartic acid (Arg-Gly-Asp) sequence as well as mimetic sequences with the capability to recognize integrin receptors are analyzed. Conclusions: This review highlights the progress that has been made in the development of new nanocarriers, capable of responding to endogenous and exogenous stimuli essential to combat cancer. Full article

Osteoarthritis (OA), a common and disabling degenerative joint disease, affects millions of people worldwide and imposes a considerable burden on patients and society due to its high prevalence and economic costs. The pathogenesis of OA is closely related to the progressive degradation of articular cartilage and the accompany inflammation; however, articular cartilage itself cannot heal and modulate the inflammation due to the lack of nerves, blood vessels, and lymph-vessels. Therefore, reliable and effective methods to treat OA remain highly desired. Local administration of drugs or bioactive materials by intra-articular injection of the delivery system represents a promising approach to treat OA, especially considering the prolonged joint retention, cartilage or chondrocytes targeting, and stimuli-responsive release to achieve precision OA therapy. This article summarizes and discusses the advances in the currently used delivery systems (nanoparticle, hydrogel, liposome, and microsphere) and then focuses on their applications in OA treatment from the perspective of endogenous stimulus (redox reactions, pH, enzymes, and temperature) and exogenous stimulus (near-infrared, magnetic, and ultrasound)-responsive release. Finally, the challenges and potential future directions for the development of nano-delivery systems are summarized. Full article

Several attempts have been made to elucidate the pathogenesis of drug-induced gingival overgrowth (DIGO), which is triggered by the chronic use of certain drugs that fall into three main categories: anticonvulsants, immunosuppressants, and calcium channel blockers. Previous research suggests that cytokines and impaired cellular functions play a role in DIGO. Of particular interest are macrophages, immune cells that can switch between M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes in response to exogenous signals and stimuli. An imbalance between M1 and M2 macrophage populations may underlie DIGO. M1 may contribute to the initial tissue damage in DIGO, while M2 may then attempt to repair the damage with anti-inflammatory mechanisms. To test the hypothesis that drugs associated with DIGO could influence macrophage polarization, human monocytes (precursors of macrophages) were induced to differentiate into M0-naïve macrophages and then exposed to drugs: diphenylhydantoin, gabapentin, mycophenolate, and amlodipine. Quantitative real-time PCR amplification was used to measure the expression of specific genes associated with macrophage polarization. All of the drugs tested induced M0 macrophages to overexpress genes typical of the M1 phenotype, such as CCL5, CXCL10, and IDO1. This investigation provides the first evidence of a link between drugs that cause DIGO and M1 pro-inflammatory macrophage polarization. The knowledge gained from this research could be valuable for future DIGO treatment strategies. Full article

In the present study, a customized device (Epi-ExPer) was designed and fabricated to facilitate an epithelial organ culture, allowing for controlled exposure to exogenous chemical stimuli and accommodating the evaluation of permeation of the tissue after treatment. The Epi-ExPer system was fabricated using a stereolithography (SLA)-based additive manufacturing (AM) method. Human and porcine oral epithelial mucosa tissues were inserted into the device and exposed to resinous monomers commonly released by dental restorative materials. The effect of these xenobiotics on the morphology, viability, permeability, and expression of relevant markers of the oral epithelium was evaluated. Tissue culture could be performed with the desired orientation of air-liquid interface (ALI) conditions, and exposure to xenobiotics was undertaken in a spatially guarded and reproducible manner. Among the selected monomers, HEMA and TEGDMA reduced tissue viability at high concentrations, while tissue permeability was increased by the latter. Xenobiotics affected the histological image by introducing the vacuolar degeneration of epithelial cells and increasing the expression of panCytokeratin (pCK). Epi-ExPer device offers a simple, precise, and reproducible study system to evaluate interactions of oral mucosa with external stimuli, providing a biocompatibility and permeability assessment tool aiming to an enhanced in vitro/ex vivo-to-in vivo extrapolation (IVIVE) that complies with European Union (EU) and Food and Durg Administration (FDI) policies. Full article

The exposome encompasses all endogenous and exogenous exposure individuals encounter throughout their lives, including biological, chemical, physical, psychological, relational, and socioeconomic factors. It examines the duration and intensity of these types of exposure and their complex interactions over time. This interdisciplinary approach involves various scientific disciplines, particularly toxicology, to understand the long-term effects of toxic exposure on health. Factors like air pollution, racial background, and socioeconomic status significantly contribute to diseases such as metabolic, cardiovascular, neurodegenerative diseases, infertility, and cancer. Advanced analytical methods measure contaminants in biofluids, food, air, water, and soil, but often overlook the cumulative risk of multiple chemicals. An exposome analysis necessitates sophisticated tools and methodologies to understand health interactions and integrate findings into precision medicine for better disease diagnosis and treatment. Chronic exposure to environmental and biological stimuli can lead to persistent low-grade inflammation, which is a key factor in chronic non-communicable diseases (NCDs), such as obesity, cardiometabolic disorders, cancer, respiratory diseases, autoimmune conditions, and depression. These NCDs are influenced by smoking, unhealthy diets, physical inactivity, and alcohol abuse, all shaped by genetic, environmental, and social factors. Dietary patterns, especially ultra-processed foods, can exacerbate inflammation and alter gut microbiota. This study investigates the exposome’s role in the prevention, development, and progression of NCDs, focusing on endogenous and exogenous factors. Full article

Gastrointestinal diseases have been among the main concerns of medical and scientific societies for a long time. Several studies have emphasized the critical role of oxidative stress in the pathogenesis of the most common gastrointestinal diseases. To provide a comprehensive overview of gastrointestinal diseases caused by oxidative stress, their biological aspects, molecular mechanisms and specific pathways, the results of the most recent published articles from the online databases were studied considering both the upper and lower parts of the digestive tract. The results revealed that although the oxidative stress in each part of the digestive system manifests itself in a specific way, all these diseases arise from the imbalance between the generation of the reactive intermediates (especially reactive oxygen species) and the antioxidant defense system. Annual incidence and mortality statistics of gastrointestinal diseases worldwide emphasize the urgent need to find an effective and non-invasive treatment method to overcome these life-threatening problems. Therefore, in the next step, a variety of nanomedicurfines developed to treat these diseases and their effect mechanisms were investigated precisely. Furthermore, the most important nanomedicines responsive to endogenous and exogenous stimuli were evaluated in detail. This review could pave the way to open a new horizon in effectively treating gastrointestinal diseases. Full article