Search Results (33,573)

Background/Objectives: Ecballium elaterium is a widely distributed species and is one of the earliest recorded in traditional medicine. With global temperatures rising, this study aimed to investigate the changes in E. elaterium plantlets subjected to thermal stress. The goal was to understand how thermal stress affects morphology, physiology, and bioactive metabolite production, both for ecological adaptation and potential therapeutic applications. Methods: Seedlings were cultivated under controlled conditions and subjected to either the control temperature (22 °C) or the heat stress temperature (35 °C) for one week. Morphological and anatomical traits were assessed, along with physiological parameters such as chlorophyll content, malondialdehyde (MDA), hydrogen peroxide (H₂O₂), L-proline, soluble sugars, and total phenolic content. Methanolic leaf extracts from both groups were analyzed via LC-HRMS/MS and examined in vitro for cytotoxic activity against three human cancer cell lines: MCF-7 (breast), DU-145 (prostate), and SH-SY5Y (neuroblastoma). Results: Heat stress reduced dry mass and stomatal density but increased the diameter of the root transition zone, indicating anatomical adaptation. Leaves exhibited elevated oxidative stress markers and altered metabolite accumulation, while the roots showed a more integrated stress response. LC-HRMS/MS profiling revealed significant shifts in Cucurbitacin composition. Extracts from heat-stressed plants displayed stronger cytotoxicity, particularly toward DU-145 and SH-SY5Y cells, correlating with higher levels of glycosylated Cucurbitacins. Conclusions: E. elaterium demonstrates organ-specific thermotolerance mechanisms, with heat stress enhancing the production of bioactive metabolites. These stress-induced phytochemicals, especially Cucurbitacins, hold promise for future cancer research and therapeutic applications. Full article

Hamamelis virginiana (witch hazel) is traditionally used in dermatology for its antibacterial and anti-inflammatory effects. However, the number of studies on its chemical composition and potentials in skin protection remains limited. This study aimed to investigate the qualitative and quantitative composition of polyphenolic compounds in the leaves and bark of the plant, as well as to explore their antioxidant, anti-inflammatory, and extracellular matrix (ECM)-protective activities in skin-relevant cell models. Human dermal fibroblasts and keratinocytes were exposed to oxidative and inflammatory stimuli and pretreated with leaf and bark extracts. ROS levels, antioxidant enzyme activity (SOD, GPx, CAT), pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), and inhibition of collagenase, hyaluronidase, and elastase were assessed. Both extracts strongly reduced ROS levels, enhanced SOD activity, and significantly decreased pro-inflammatory cytokines. Bark extract also exhibited potent inhibitory activity against collagenase and elastase. UPLC-DAD-MS analysis revealed that both plant parts contained high levels of tannins; however, the leaf extract showed a more diverse composition, including more complex tannin forms and a significant amount of flavonoids from the quercetin and kaempferol class. In conclusion, H. virginiana leaf and bark extracts demonstrate multifunctional antioxidant and anti-inflammatory properties, supporting their potential use in cosmeceuticals and dermatological formulations targeting skin aging and inflammation. Full article

Mitochondria-associated membranes (MAMs) are essential for cellular homeostasis. MAMs are specialized contact sites located between the endoplasmic reticulum (ER) and mitochondria and control apoptotic pathways, lipid metabolism, autophagy initiation, and calcium signaling, processes critical to the survival and function of neurons. Although this area of membrane biology remains understudied, increasing evidence links MAM dysfunction to the etiology of major neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). MAMs consist of a network of protein complexes that mediate molecular exchange and ER–mitochondria tethering. MAMs regulate lipid flow in the brain, including phosphatidylserine and cholesterol; disruption of this process causes membrane instability and impaired synaptic function. Inositol 1,4,5-trisphosphate receptor—voltage-dependent anion channel 1 (IP3R-VDAC1) interactions at MAMs maintain calcium homeostasis, which is required for mitochondria to produce ATP; dysregulation promotes oxidative stress and neuronal death. An effective therapeutic approach for altering neurodegenerative processes is to restore the functional integrity of MAMs. Improving cell-to-cell interactions and modulating MAM-associated proteins may contribute to the restoration of calcium homeostasis and lipid metabolism, both of which are key for neuronal protection. MAMs significantly contribute to the progression of neurodegenerative diseases, making them promising targets for future therapeutic research. This review emphasizes the increasing importance of MAMs in the study of neurodegeneration and their potential as novel targets for membrane-based therapeutic interventions. Full article

Osteoarthritis in dogs is commonly managed with non-steroidal anti-inflammatory drugs (NSAIDs), nutraceuticals, and other medications aimed at alleviating pain and inflammation. Although NSAIDs are generally considered the most effective option, their use is contraindicated in certain conditions due to adverse side effects. Consequently, there has been growing interest in alternative or complementary therapies, such as acupuncture, laser therapy, and their combination. Laser acupuncture involves stimulating traditional acupuncture points with low-intensity laser light, producing anti-inflammatory, analgesic, anti-edematous, and bio-stimulatory effects. In this study, 19 dogs with osteoarthritis were assigned to two groups: 10 received laser acupuncture treatment (Group T) using a dual-wavelength system delivering continuous and pulsed, synchronized emissions, while 9 served as controls (Group C). After 30 days, only Group T showed significant improvement (p < 0.01), with reduced pain and improved joint mobility. Significant reductions in LDH and CPK were observed in Group T, along with changes in inflammatory markers (IL-6 and IL-10, though not TNF-α) and a significant increase in biological antioxidant potential. These preliminary findings indicate that laser acupuncture, applied according to a standardized protocol and adapted to the site of disease, may represent a viable non-invasive therapeutic option for canine osteoarthritis, particularly in cases where pharmacological treatment is contraindicated or ineffective. Further large-scale, randomized controlled trials are warranted to confirm these results and establish long-term efficacy. Full article

Mitochondria, as the metabolic hubs of cells, play a pivotal role in maintaining cardiovascular homeostasis through dynamic regulation of energy metabolism, redox balance, and calcium signaling. Cardiovascular diseases (CVDs), including heart failure, ischemic heart disease, cardiomyopathies, and myocardial infarction, remain the leading cause of global mortality, with mitochondrial dysfunction emerging as a unifying pathological mechanism across these conditions. Emerging evidence suggests that impaired mitochondrial transport systems—critical gatekeepers of metabolite flux, ion exchange, and organelle communication—drive disease progression by disrupting bioenergetic efficiency and exacerbating oxidative stress. This review synthesizes current knowledge on mitochondrial transport proteins, such as the voltage-dependent anion channels, transient receptor potential channels, mitochondrial calcium uniporter, and adenine nucleotide translocator, focusing on their structural–functional relationships and dysregulation in CVD pathogenesis. We highlight how aberrant activity of these transporters contributes to hallmark features of cardiac pathology, including metabolic inflexibility, mitochondrial permeability transition pore destabilization, and programmed cell death. Furthermore, we critically evaluate preclinical advances in targeting mitochondrial transport systems through pharmacological modulation, gene editing, and nanoparticle-based delivery strategies. By elucidating the mechanistic interplay between transport protein dysfunction and cardiac metabolic reprogramming, we address a critical knowledge gap in cardiovascular biology and provide a roadmap for developing precision therapies. Our insights underscore the translational potential of mitochondrial transport machinery as both diagnostic biomarkers and therapeutic targets, offering new avenues to combat the growing burden of CVDs in aging populations. Full article

Background/Objectives: Systemic toxicities to key organs like the heart, liver, and kidneys impair the efficacy of chemotherapy in cancer treatment. These toxicities are caused by oxidative stress, inflammation, mitochondrial malfunction and ferroptosis, causing clinical morbidity and possibly impaired adherence to treatment. This review, also, examines how magnesium, selenium, zinc and vitamin D protect against chemotherapy-induced cardiotoxicity, hepatotoxicity and nephrotoxicity. Methodology: A complete literature search of PubMed (MEDLINE), Scopus, Cochrane Library and Embase was used to synthesize data till 29 June 2025. Studies included randomized and non-randomized trials, cohort studies, case series (≥3 patients), and relevant systematic reviews. To contextualize pathways, preclinical in vivo and in vitro studies were studied independently. Patients undergoing systemic chemotherapy and magnesium, selenium, zinc or vitamin D therapies were eligible. Supplementation’s safety and organ-specific toxicity were investigated. Results: Magnesium protected against cisplatin-induced nephrotoxicity via modulating renal transporters and oxidative defenses across chemotherapy regimens. Selenium supplementation has strong antioxidant and anti-inflammatory characteristics, especially in avoiding cardiac and hepatic injury, although its nephroprotective potential was formulation-dependent. Zinc’s activity was connected to metallothionein-mediated redox stabilization, inflammatory regulation, and cardiac and hepatic resilience. Vitamin D and its analogs reduced cardiotoxicity and nephrotoxicity through mitochondrial preservation and immunomodulatory signaling. Conclusions: To date, magnesium, selenium, zinc, and vitamin D have been shown to reduce chemotherapy-related organ toxicities. Preclinical studies are promising, but randomized clinical trials are needed to prove therapeutic effectiveness and oncologic safety. Full article

Thyroid cancer (TC), the most prevalent endocrine neoplasia, has shown a progressive incidence, highlighting the need for new therapeutic approaches—especially for radioiodine-refractory cases, often associated with mutations in genes such as BRAF, RAS, and TP53. This review proposes a mechanistic model that highlights two interrelated characteristics of the tumor microenvironment (TME): redox imbalance and chronic inflammation, key elements in tumor progression and treatment resistance. Thus, natural phenolic compounds, such as curcumin, quercetin, resveratrol, and epigallocatechin gallate (EGCG), function not as simple antioxidants but as pleiotropic agents that reprogram the TME. A central mechanism of action for these compounds is the modulation of the purinergic axis (CD39/CD73/adenosine), a critical immune-metabolic checkpoint. By selectively inducing lethal oxidative stress in tumor cells, suppressing pro-survival inflammatory pathways—such as that mediated by nuclear factor kappa B (NF-κB)—and destabilizing the immunosuppressive shield conferred by adenosine, certain phytochemicals demonstrate the potential to restore immune surveillance and promote tumor apoptosis. In this context, a critical analysis of the evidence related to targeting purinergic signals becomes essential, since pharmacological reinforcement of this pathway, especially when combined with immunotherapies based on immune checkpoint blockade, emerges as a promising strategy for overcoming therapeutic resistance. Full article

Salt–alkaline soil poses a significant challenge to soybean productivity. While plant growth-promoting rhizobacteria (PGPR) offer a sustainable strategy for stress mitigation, their field-level application remains underexplored. Here, a field experiment was conducted in the Yellow River Delta of Shandong, China, a typical salt–alkaline region. In this study, we evaluated the effectiveness of Bacillus velezensis 41S2 in enhancing soybean performance under salt–alkaline soil through integrated field trials and transcriptomic analysis. Inoculation with strain 41S2 significantly improved plant biomass, yield components, and seed yield under salt–alkaline soil, and notably increased seed protein and isoflavone contents. Physiological analyses revealed that strain 41S2 markedly reduced hydrogen peroxide (H₂O₂) accumulation, indicating alleviation of oxidative stress. Moreover, strain 41S2 modulated the levels of soluble sugars and amino acids, contributing to osmotic regulation and carbon–nitrogen (C-N) metabolic balance. Transcriptome profiling further indicated that strain 41S2 upregulated genes involved in antioxidant response, C–N metabolism, and phenylpropanoid biosynthesis, highlighting its role in coordinating multilayered stress response pathways. Overall, these findings highlight the potential of B. velezensis 41S2 as a multifunctional bioinoculant for improving salt tolerance and presents a promising tool for sustainable crop production and ecological restoration in salt–alkaline soil. Full article

Background/Objectives: Generalized anxiety disorder (GAD) is one of the most commonly diagnosed anxiety disorders in primary care. The global lifetime prevalence of GAD is estimated at 3.7%, ranging from 1.6% in low-income countries to 5.0% in high-income countries, underscoring its widespread impact. Given the frequent co-occurrence of GAD with obesity, this association has important clinical implications, particularly for screening, prevention, and treatment strategies. The aim of this review is to identify potential biological mechanisms linking obesity and GAD, summarize the current state of knowledge in this area, and highlight existing research gaps, as well as directions for future research. Methods: This narrative review is based on the literature published between 2015 and 2025 concerning the co-occurrence of GAD and obesity, with a focus on potential shared mechanisms including HPA axis dysregulation, chronic inflammation, oxidative stress, insulin resistance, gut–brain axis and microbiota dysbiosis, sleep disturbance, and maladaptive eating behaviors. Results/Conclusions: A growing body of evidence suggests an important, albeit still ambiguously defined, relationship between obesity and GAD. GAD and obesity may reinforce each other, leading to a mutually reinforcing relationship. Despite growing interest, high-quality prospective and interventional studies focusing specifically on GAD are lacking. A potentially effective therapeutic approach should be integrated and multidisciplinary, combining psychological, pharmacological, and lifestyle interventions. It may also be beneficial for clinicians to consider routine assessment of anxiety in patients with obesity and, conversely, to monitor metabolic risk in individuals with GAD. Such an approach, targeting both mental and metabolic domains, holds promise for improving outcomes. Full article

Facial bone fractures represent a significant clinical challenge due to their impact on function, aesthetics, and quality of life. Despite advances in imaging and surgical techniques, early and accurate assessment of the healing process remains limited. Conventional diagnostic methods often detect complications, such as delayed union or non-union, too late for optimal intervention. Oxidative stress—an imbalance between reactive oxygen species (ROS) and antioxidant defenses—plays a critical role in bone regeneration. In this review, biomarkers are presented in two main categories: (1) oxidative damage biomarkers (lipid peroxidation products: malondialdehyde, 4-hydroxynonenal, and F2-isoprostanes) and (2) antioxidant biomarkers (glutathione, enzymatic antioxidants: SOD, GPx, CAT). Their potential as non-invasive diagnostic and prognostic tools in craniofacial fracture healing is evaluated, along with emerging therapeutic strategies. Monitoring their levels in blood samples may provide real-time insights into the dynamics of fracture repair, enabling earlier detection of healing disturbances and informing personalized treatment approaches. Full article

Background and Objectives: Methamphetamine (METH) is a potent psychostimulant known to induce neurotoxicity and neurodegeneration, leading to cognitive impairment. This study aimed to explore cubebin’s potential neuroprotective effects against METH-induced cognitive deficits by investigating its ability to suppress lipid peroxidation and pro-inflammatory markers and modulate neurotransmitter levels. Material and Methods: A total of 30 rats were taken and randomly grouped into five groups: group I—control; group II—METH 100 mg/kg/i.p.; group III—METH + cubebin (10 mg/kg/p.o.); group IV—METH + cubebin (20 mg/kg/p.o.); and group V—cubebin per os at 20 mg/kg. After a 14-day oral regimen, behavioral activities were assessed utilizing the Morris water maze (MWM). Biochemical analysis included neurotransmitters, including dopamine (DA), norepinephrine (NE), and gamma-aminobutyric acid (GABA); oxidative stress markers (malondialdehyde (MDA); nitric oxide (NO), catalase (CAT), reduced glutathione (GSH)); inflammatory cytokines [interleukin (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)]; neurotrophic factors (BDNF, CREB); and apoptotic markers (caspase-3 and caspase-9). Furthermore, molecular docking and simulation studies were conducted. Results: Treatment with cubebin led to a marked reduction in latency during the MWM task. It significantly modulated the oxidative stress markers (SOD, GSH, CAT, MDA, and NO), inflammatory cytokines (IL-6, IL-1β, TNF-α), neurotrophic factors (CREB, BDNF), apoptotic markers (NFkB, caspase-3, caspase-9), and neurotransmitters (NE, DA, and GABA) in METH-induced memory-impaired rats. The results of molecular dynamics simulation (MDS) provided insight into the mechanisms that associate proteins CREB, BDNF, and caspase-3 in conformational dynamics upon binding to cubebin. Conclusions: In conclusion, cubebin administration improved cognitive function in rats by modulating antioxidant enzyme activity, reducing pro-inflammatory cytokines, and regulating neurotransmitter levels, demonstrating its potential neuroprotective effects against MA-induced neurodegeneration. Full article

Background/Objectives: Following the recent publication of reassuring outcomes from the ARA MED 330 protocol regarding long-term insulin use in pilots, combined with continuous advancements in diabetes technology, European aeromedical examiners are increasingly optimistic about establishing more flexible medical requirements for insulin-treated aviation professionals. These professionals have historically been considered unfit for duty due to hypoglycemic risks. According to current research, hypoglycemia, the primary incapacitation risk for flight crew, is considered virtually non-existent among air traffic controllers (ATCOs). Additionally, stress-induced hyperglycemia also represents a low-frequency risk in these professionals, who are experienced in managing highly stressful operational environments. This study presents a narrative review examining stress and its metabolic effects in healthy individuals, ATCOs, and people with diabetes (PwD). Methods: This narrative review was conducted based on a comprehensive PubMed search performed by two independent reviewers (GAR and AM) spanning January 2023 to January 2025. The search strategy focused on English-language, peer-reviewed studies involving human participants and addressed stress, glucose regulation, and occupational factors in ATCOs and people with diabetes. Additional relevant articles were identified through reference screening. A total of 33 studies met the inclusion criteria. Studies focusing solely on oxidative or molecular mechanisms were excluded from the analysis. Results: Stressful events consistently triggered the expected hyperglycemic reaction in both healthy individuals and PwD. However, the literature indicates ATCOs demonstrate remarkable stress resilience and adaptation to the demanding conditions of their work environment, suggesting a unique occupational profile regarding metabolic stress responses. Conclusions: These findings contribute valuable insights to ongoing discussions regarding aeromedical fitness standards. The evidence suggests that ATCOs may not face the same metabolic risks as flight crews, indicating that current medical certification processes for insulin-treated aviation professionals warrant reconsideration in light of this emerging evidence. This research supports the potential for more individualized, occupation-specific aeromedical standards that better reflect the actual risk profiles of different aviation roles. Full article

Thallium (Tl) is a non-essential and highly toxic heavy metal capable of replacing potassium (K⁺) in biological systems, leading to mitochondrial dysfunction, oxidative stress, and inhibition of protein synthesis. In humans, the estimated oral lethal dose ranges from 10 to 15 mg/kg, with acute mortality rates of 6–15% and chronic neurological sequelae in up to 55% of survivors. Environmental releases of thallium of up to 5000 metric tons annually from industrial and mining activities, combined with its high oral bioavailability and nonspecific multisystemic symptoms, underscore the urgent need for more effective therapeutic strategies. This review summarizes current evidence on Tl toxicity, including its mechanisms of action, clinical manifestations, and available treatments. It emphasizes the strategic selection of biological models: simple organisms such as Caenorhabditis elegans and Drosophila melanogaster enable high-throughput screening and early biomarker detection; zebrafish (Danio rerio) provide vertebrate-level evaluation of multi-organ effects; and rodent models offer systemic toxicokinetic and therapeutic validation. Human-derived organoids and induced pluripotent stem cell (iPSC) systems recreate tissue-specific microenvironments, allowing translational assessment of mitochondrial, neuronal, and cardiac toxicity. Integrating these models within a tiered and complementary framework, alongside environmental and clinical surveillance, can accelerate the development of targeted treatments and strengthen public health responses to Tl exposure. Full article

Storage of Blood units determines the accumulation of harmful substances, such as malondialdehyde (MDA) and free hemoglobin (fHb). These may lead to several complications, including cardiovascular, neurodegenerative, and metabolic disorders in recipients. The objective of this study was to evaluate the concentrations of MDA and fHb in canine leukoreduced (LR) and non-leukoreduced (NLR) packed red blood cells (pRBC) during the storage period of six weeks. Blood samples were collected from six healthy adult Weimaraner dogs (three females and three males). Whole blood was stored in citrate-phosphate-dextrose saline-adenine-glucose-mannitol additive solution (CPD-SAGM) bags and, for each donor, two pRBC units (one NLR and one LR) were produced and stored at 4 °C for 42 days. Samples were collected on days 0, 7, 14, 21, 28, 35, and 42, and analyzed for malondialdehyde (MDA) using a canine-specific ELISA method, and for free hemoglobin (fHb) using the Harboe direct spectrophotometric method. The results demonstrated a statistically significant reduction in MDA accumulation in LR-pRBC compared to NLR-pRBC blood units and lower values of fHb in LR at T6. However, no significant difference in fHb levels were demonstrated. These findings suggest that leukoreduction may limit oxidative stress during blood storage, reducing the potential adverse effects of transfusions related to oxidative damage. Full article

The widespread use of rare earth elements (REEs) in agriculture, particularly Lanthanum (La), raises concerns about their ecological impact on non-target organisms. We investigated the direct and indirect effects of La on the insect pest Spodoptera littoralis and its host plant, Brassica rapa. Direct exposure to La-supplemented diets reduced larval growth, survival, and egg production. Interestingly, a transgenerational effect was observed, where larvae from La-exposed parents exhibited increased resilience, showing no performance reduction on the same diets. Indirectly, La accumulation in plants mediated a hormetic response in herbivores, increasing larval weight at low concentrations but reducing it at high concentrations, while modulating their oxidative stress and detoxification gene expression. From the plant perspective, La exposure amplified herbivory-induced calcium signalling and altered the expression of key genes related to calcium and reactive oxygen species pathways. These findings reveal the complex ecological risks of La accumulation in agroecosystems, affecting both plants and insects directly and through novel transgenerational effects. Full article