Search Results (4,296)

Michelia compressa, a member of the Magnoliaceae family, is an evergreen tree of considerable significance in both landscape gardening and industrial production. However, during its introduction to northern subtropical regions in China, this species often suffers from frost damage, which limits its widespread application. The utilization of housekeeping genes is essential when performing gene family analyses under abiotic stress conditions. Additionally, auxin response factor (ARF) transcription factors (TF) play a crucial role in plant responses to abiotic stresses; however, their specific function in cold stress responses within M. compressa has not been systematically investigated. Ten housekeeping genes were selected from transcriptome data for evaluation using quantitative real-time PCR (qRT-PCR). The optimal housekeeping gene identified through screening was used for verification of gene family analysis. Additionally, key genes underwent functional validation. Analysis conducted with GeNorm, NormFinder, and BestKeeper identified 28S as the optimal reference gene for M. compressa under cold stress. Furthermore, an analysis of the ARF gene family using full-length transcriptome data revealed a total of 48 McoARF genes, which clustered into three groups alongside the Arabidopsis thaliana ARFs. Among these, eight selected McoARF genes exhibited significantly elevated expression levels in leaves under cold stress and demonstrated tissue specificity. Functional validation revealed that transgenic plants overexpressing McoARF13 displayed elevated levels of reactive oxygen species (ROS), hydrogen peroxide (H₂O₂), and malondialdehyde (MDA), as well as increased activities of peroxidase (POD) and superoxide dismutase (SOD) in leaves under cold stress. This study represents the inaugural screening of housekeeping genes in M. compressa under cold stress conditions, accompanied by an analysis of the ARF gene family. The functional validation of McoARF13 was successfully conducted, offering valuable insights into the molecular mechanisms that underlie cold stress response in M. compressa. Full article

Translating preclinical findings into effective clinical cancer immunotherapies remains a major challenge, mainly because conventional in vitro and animal models often fail to capture the complexity, dynamics, and species-specific features of human immune responses. Organ-on-a-chip (OoC) technologies that combine engineered tissue architectures with precisely controlled microfluidic transport provide human-relevant microphysiological platforms for mechanistic studies of immune–tumor interactions and evaluation of therapeutic efficacy and immunotoxicity under defined microenvironmental conditions. However, immune responses involve time-dependent and interconnected processes, including immune cell trafficking, cytokine programs, metabolic shifts, and cytolysis, that are not adequately resolved by static or endpoint assays. Engineering immune-competent OoC systems therefore requires coordinated design of platform architectures, immune cell incorporation strategies, and integrated measurement workflows capable of capturing dynamic and state-dependent responses. In this review, we summarize engineering strategies for building immune-competent OoC platforms for cancer immunotherapy, focusing on platform architectures, immune cell incorporation methods, and fit-for-purpose assay workflows. Emphasis is placed on embedded sensing modalities (e.g., cytokine, oxygen, and impedance readouts) that provide valuable kinetic and state-variable data. Finally, we discuss key translational challenges, including reproducibility, standardization, and benchmarking, and outline near-term priorities to accelerate the adoption of immune-competent OoC systems in immunotherapy research and development. Full article

Pregnancy is characterized by progressive maternal hyperlipidemia, including increased triglycerides, total cholesterol, and low-density lipoprotein, with dynamic fluctuations in high-density lipoprotein. Excess maternal free fatty acids induce oxidative stress through reactive oxygen species, causing mitochondrial dysfunction, lipid peroxidation, activation of inflammatory pathways, and epigenetic remodeling in the placenta and fetal tissues. These molecular alterations impair placental lipid transport and nutrient sensing, leading to hypertrophy of fetal liver, myocardium, and adipose tissue, while disrupting neonatal glucose and lipid homeostasis and increasing susceptibility to perinatal complications and long-term metabolic disorders. This review aims to evaluate mechanistic pathways linking maternal lipid metabolism, oxidative stress, placental function, and fetal organ remodeling. Mechanistic and translational studies were identified through searches of PubMed, Scopus, the Cochrane Library, and Web of Science (2000–2025) using predefined keywords including lipid metabolism, free fatty acids, oxidative stress, placental lipid transport, epigenetics, DNA methylation, fetal programming, and perinatal outcomes. Evidence indicates that maternal lipid imbalance drives placental oxidative and epigenetic modifications, directly contributing to fetal organ hypertrophy and neonatal metabolic dysregulation. In conclusion, maternal dyslipidemia represents a modifiable determinant of fetal organ hypertrophy and long-term metabolic risk, supporting the clinical relevance of maternal lipid monitoring and targeted metabolic interventions during pregnancy. Full article

Metastasis is a complex, multistep process in which cancer spreads from its original tumor to other sites in the body. During metastasis, tumor cells move away from the primary tumor and intravasate into the lymphatics or circulation. Surviving tumor cells can then extravasate into and remain in distant tissues until they once again begin to proliferate, forming secondary tumors. An excess of reactive oxygen species (ROS) can promote metastasis, dependent on the ROS molecule, its level of excess, and the examined step within the metastatic cascade. Here, we highlight recent studies where ROS promote epithelial-to-mesenchymal transition, cell migration and invasion, circulating tumor cell survival and disseminated tumor cell dormancy. Additionally discussed are novel in vivo ROS detection methods, FDA-approved therapies and clinical trials that manipulate ROS to improve cancer patient survival. Since metastasis is the major cause of cancer-related death, a better understanding of this process and ROS as a contributing factor will help to identify novel targets for inhibition or prevention. Full article

Ferroptosis of mesenchymal stem cells (MSCs) is a critical bottleneck restricting the efficiency of ruminant biological breeding. Phloretin, a natural bioactive polyphenol, exhibits potential ferroptosis-inhibitory activity. However, the regulatory effects and underlying mechanisms of phloretin on ruminant MSCs remain poorly understood. This study aimed to investigate the effects of phloretin on ferroptosis and elucidate its underlying molecular mechanisms. Herein, we isolated and cultured adipose-derived mesenchymal stem cells (AD-MSCs) from adipose tissue of a 9-day-old Leizhou goat and established a ferroptosis model in these cells using RSL3. We detected cell viability, proliferation, migration, ferroptosis-related indexes and key protein expression. The results showed that phloretin (25 and 50 μM) dose-dependently inhibited ferroptosis in goat AD-MSCs, reducing intracellular ferrous ion (Fe²⁺), reactive oxygen species (ROS) and lipid peroxidation levels, restoring glutathione content, and ameliorating mitochondrial structural damage. Mechanistically, phloretin exerted its anti-ferroptosis effects through direct antioxidant activity, activation of the Nrf2/HO-1/GPX4 signaling pathway and Fe²⁺ chelation. Nrf2 and GPX4 were key targets in this process. These results provide preliminary in vitro evidence and a theoretical basis for the potential application of phloretin in future research related to meat goat production and ruminant breeding. Full article

Background: Renin is a hypoperfusion marker and a good index of renin–angiotensin–aldosterone system (RAAS) activity. The purpose of this study was to evaluate whether the plasma renin concentration (PRC) can represent a tissue perfusion marker for predicting mortality in patients with circulatory shock in intensive care. Methods: This prospective study included patients aged 18 years or older who were hospitalized in the intensive care unit (ICU). A total of 69 patients were enrolled, of whom 37 had circulatory shock and were all diagnosed with septic shock according to Sepsis-3 criteria, while 32 patients did not have shock. Patient groups were compared, and survival analysis was carried out. Mortality predictions of PRC, lactate and combined tests (including PRC, mottling scores, central venous saturation of oxygen, C-reactive protein, procalcitonin, and lactate) were investigated with ROC analysis. Results: ICU 28-day mortality was 36.2% (n = 25) and was significantly higher in patients with circulatory shock than those without (CS:21, 56.8% vs. NS:4, 12.5%, respectively, p < 0.001). The survival was significantly higher in patients without circulatory shock than those with shock (17 vs. 16 days; p = 0.038). The increase in mottling score (HR: 1.64 [95%CI: 1.15–2.33]; p < 0.01) and PRC (HR = 1.01 [95%CI: 1.00–1.02]; p < 0.05) levels and the decrease in glomerular filtration rate (GFR) (HR = 0.98 [95%CI: 0.96–0.99]; p < 0.05) were associated with decreased survival times in the ICU patients (p < 0.001). Combined tests yielded better prediction of mortality than PRC level alone. Conclusions: PRC may reflect circulatory shock and predict survival in critically ill patients; however, larger prospective studies incorporating serial PRC measurements are needed before it can be recommended as an independent biomarker of mortality. Full article

Tumor oxygenation is a key determinant of cancer biology and treatment response, correlating with angiogenesis, recurrence, and malignant progression. Hypoxia is a defining feature of glioblastoma (GBM) and adult diffuse gliomas, generating low-oxygen niches that promote invasion, stem-like states, immune suppression, and resistance to radiotherapy and temozolomide, contributing to poor outcomes. Measuring tissue partial pressure of oxygen (pO₂) and mapping its spatial heterogeneity can, therefore, inform mechanistic understanding and therapeutic development, including hypoxia-activated prodrugs, hypoxia-responsive gene therapy, and optimized radiotherapy planning. Although direct pO₂ assessment is challenging, invasive probes and multimodal imaging can characterize regional hypoxia pre-operatively, support patient stratification, monitor treatment effects, and improve outcome prediction. This review summarizes oxygen dynamics in GBM; analyzes causes of hypoxia (rapid growth outpacing supply, diffusion-limited hypoxia, and abnormal/chaotic vasculature); compares methods to quantify oxygenation from direct measurements to noninvasive imaging surrogates; and evaluates preclinical and clinical strategies that target hypoxia to enhance standard therapy, including barriers to translation. We further integrate oxygenation with cell signaling and redox biology: oxygen gradients are transduced via hypoxia-inducible factor programs and redox-sensitive pathways (NRF2/KEAP1, NOX-derived ROS, nitric oxide/S-nitrosylation, and sulfur metabolic routes), shaping mesenchymal-like transitions and cell-death programs such as ferroptosis. Framing oxygenation as both a microenvironmental and redox-signaling variable positions oxygen imaging as an entry point to biomarker-guided therapies that exploit oxidative vulnerabilities. Full article

Dietary protein oxidation impairs animal health, yet effective interventions remain limited. This study investigated whether quercetin (Q) supplementation protects against protein-oxidized soybean meal (OS)-induced oxidative stress and inflammatory injury in rats. A 2 × 2 factorial experiment was conducted with 48 three-week-old Sprague-Dawley rats randomly assigned to four dietary treatments (n = 12): fresh soybean meal (FS), FS + 400 mg/kg Q, OS, and OS + 400 mg/kg Q for 28 days. Serum biochemistry, intestinal and hepatic histology, antioxidant status, inflammatory markers, and transcriptomic pathways were analyzed. As a result, OS feeding elevated serum glucose and urea nitrogen, induced duodenal, jejunal and hepatic lesions, reduced total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) activity, glutathione (GSH) level, increased reactive oxygen species (ROS) and malondialdehyde (MDA) content (p < 0.05), and increased IgG and IL-6 levels (p < 0.05). Transcriptomic analysis revealed upregulation of heme biosynthesis and ROS synthesis pathways in jejunum and liver (p < 0.05). Q supplementation mitigated these adverse effects by improving antioxidant status, reducing inflammatory lesions, downregulating heme and ROS pathways, and normalizing the expression of key genes (Ccl20, RT1-M2) and protein (Ccl20) in jejunum (p < 0.05), and key genes (Duox1, Cyp4a2) and protein (Duox1) in liver (p < 0.05). These findings demonstrate that Q alleviates OS-induced oxidative stress, inflammation, and tissue damage through the modulation of heme and ROS pathways. Full article

Carbon monoxide (CO) is a poisonous gas because it disrupts functional oxygen transport of red blood cell (RBC) by binding heme of hemoglobin with high affinity. Contrarily, endogenous CO, which is constantly generated in the process of heme degradation by heme oxygenase, functions as a gaseous mediator necessary for maintaining physiological homeostasis. This toxicological (Yin) and physiological (Yang) duality presents a distinctive problem in medical and pharmaceutical applications, prompting the central question of this review: How can strict control over CO’s exposure dynamics, magnitude, kinetics, and tissue context be achieved to enable its safe therapeutic use? Here, we integrate the Yin and Yang of CO through an innovative exposure-engineering framework, leveraging the inherent RBC characteristics to offer a novel conceptualization for therapeutic development. We highlight the role of native RBCs as a biologically grounded platform that can convert hemoglobin binding—classically viewed as the basis of CO toxicity—into a measurable and controllable buffering mechanism. Then, reconciling the Yin and Yang of CO based on RBCs enables medical and pharmaceutical modulation that is attractive for clinical situations, therapeutics and diagnostics. Finally, we discuss key translational challenges—local concentration control, patient-specific risk stratification, manufacturability and critical quality attributes, and regulatory positioning—and outline how quantifiable exposure control can enable the safe clinical development of RBC-based CO therapy. Full article

Human adipose biology is strongly influenced by three-dimensional (3D) architecture, cell–cell interactions, and local oxygen availability maintained over a long-term culture period, features that are not reproduced in traditional two-dimensional (2D) culture systems. To address this gap, we established a long-term human adipose-derived stem cell (hASC) spheroid model using elastin-like polypeptide–polyethyleneimine (ELP-PEI) coating. The ELP-PEI coating facilitated stable spheroid formation and sustained adipogenic differentiation over 56 days. As spheroids enlarged and matured, they exhibited hallmark features of adipocytes, including lipid accumulation, morphological compaction, and transition out of the proliferative state. Glucose uptake increased during maturation and declined as spheroids became larger. This reduction coincided with a marked rise in hypoxia-inducible factor-1α (HIF-1α) expression, indicating the emergence of a hypoxic microenvironment within larger spheroids. Notably, inhibiting HIF-1α restored insulin-stimulated glucose uptake, demonstrating that hypoxia was the primary driver of impaired insulin responsiveness in late-stage spheroids. These findings position ELP-PEI-supported hASC spheroids as a practical and physiologically relevant platform for studying human adipocyte biology, particularly the development and reversibility of hypoxia-associated metabolic dysfunction. This model offers new opportunities for mechanistic studies and for evaluating therapeutic strategies targeting insulin resistance and adipose tissue pathology. Full article

Background: Unhealthy expansion of adipose tissue (AT) due to excessive dietary intake of omega-6 or overnutrition stimulates the overaccumulation of the extracellular matrix (ECM), resulting in AT metabolic dysregulation. Hypertrophic conditions, excessive adipose depots, and hypoxia stimulate the overproduction of collagenous and non-collagenous proteins, which pathophysiologically initiate the pro-fibrotic signaling pathway associated with fibrosis progression, resulting in atherosclerosis and cardiovascular diseases. Methods: We aimed to investigate adipocyte plasticity in response to a varying ratio of omega-3 (ω3) to omega-6 (ω6) supplementation during the chemically induced adipogenic differentiation of human mesenchymal stem cells. Additionally, changes in lipid accumulation, adipocyte hypertrophy and hyperplasia, active lipid metabolites, and inflammatory cytokine profiles were evaluated. Furthermore, conditioned media from adipocytes treated with different ω3/ω6 ratios were applied to platelets to assess inflammatory responses through prostaglandin and thromboxane measurements. Results: A 1:3 ratio of ω3/ω6 (20:60 µM) significantly reduced lipid accumulation, promoted brown-like adipocyte morphology, and decreased apoptosis and reactive oxygen species (ROS) generation, as confirmed via FACS analysis. Transcriptional control of adipose tissue expansion was confirmed by the downregulation of LIPIN1 and COL1A1 mRNA expression and p-prostaglandin12-R protein levels in a 1:3 ratio when compared with 1:1, 1:2, 1:4, or 2:6 ratios of ω3/ω6. Notably, a 1:3 ratio of fatty-acid-treated adipocyte-conditioned media-treated platelets significantly reduced platelet activation and aggregation, as evidenced by lower p-thromboxane A2 protein levels. Conclusions: Supplementation with a 1:3 (20:60 µM) ω3/ω6 ratio favored the development of lean adipocytes, evidenced by the decreased lipid storage achieved by mitochondrial thermogenesis, which attenuated minimal adipocyte expansion and metabolic inflammation. Full article

Chronic kidney disease (CKD) represents a growing medical, diagnostic and social challenge, and it is estimated to effect 8.5–9.8% of the global population and requires expensive modes of treatment, such as hemodialysis or renal transplants. Currently, a diagnosis of CKD is set based on the level of creatinine in the blood, which is the gold standard of renal function diagnostics. Unfortunately, decrease in GFR is secondary to damage of the kidney parenchyma and indicates that the best time to start more aggressive treatment has already passed. Therefore, several non-invasive methods have been proposed for predicting increased risk of CKD progression; however, in most of the cases kidney biopsy is essential. Currently, the greatest hopes for a method that can confirm CKD are associated with the development of MRI, the most tissue-specific imaging method, and it is already proven to be capable to detect inflammatory and edematous changes, fibrosis, as well as perfusion and oxygenation disturbances. Therefore, in our manuscript we decided to present up-to-date knowledge about kidney MRI from a clinical point of view. Full article

The use of postmortem (autopsy) material in fundamental and applied biomedical research significantly facilitates the collection of biomaterial for statistically robust sample cohorts. However, natural adaptive processes to developing cellular stress in the early postmortem period, caused by oxygen and nutrient deprivation, trigger the activation of numerous genes promoting cell survival under stress. Many of these activated pathways are also crucial for tumor cell survival in vivo, as evidenced by various transcriptomic studies. This study aimed to investigate the potential influence of postmortem interval (PMI) duration on gene expression in normal and tumor tissues. Using a model of chemically induced hepatocellular carcinoma in mouse liver, we comparatively analyzed the dynamics of transcript levels for several genes (BRCA1, BRCA2, CHEK1, CHEK2, ATM, CDK12) in paired samples of normal and tumor tissue over a 24-h PMI using RT-qPCR. In normal tissue, gene expression increased significantly, while tumor tissue demonstrated relative transcriptional stability, with no substantial changes in the studied transcript levels. A critical finding was the observed convergence of expression profiles: initial differences between the tissues were completely eliminated by 24 h PMI. This pattern developed despite formally adequate RNA quality (RQN) and the absence of clear signs of progressive autolysis in histology, indicating the insufficiency of standard quality criteria for detecting postmortem changes. These findings collectively underscore the critical importance of minimizing and controlling PMI during the biobanking of oncological samples for reliable transcriptomic research. Full article

Background/Objectives: Biodegradable magnesium (Mg)-based biomaterials release Mg²⁺ ions during degradation and may promote vascular-related regeneration. However, their effects on lymphatic endothelial cells (LECs) and lymphangiogenesis remain unclear. This study investigated whether magnesium powder-derived ionic extracts could enhance lymphangiogenesis-related behaviors of LECs in vitro. Methods: Mg powder extracts were prepared and diluted for in vitro treatment. After viability screening, Mg (1:10), Mg (1:100), and Mg (1:1000) were selected for further analysis. LEC proliferation, migration, and tube formation were assessed, together with intracellular reactive oxygen species (ROS) levels and the expression of VEGFA, VEGFC, and VEGFR3. Results: Mg (1:10) and Mg (1:100) showed good cytocompatibility and significantly promoted LEC proliferation, migration, and tube formation compared with the control and Mg (1:1000) groups. These effects were accompanied by reduced intracellular ROS levels and increased expression of VEGFA, VEGFC, and VEGFR3. Conclusions: Magnesium powder-derived ionic extracts enhance lymphangiogenesis-related responses of LECs in vitro, particularly at the 1:10 and 1:100 dilutions. These findings support the potential of Mg-based biodegradable biomaterials for lymphatic tissue regeneration. Full article

Cellular senescence is a stress-induced type of irreversible cell cycle arrest, driven by telomere attrition, oxidative stress, DNA damage, mitochondrial dysfunction, oncogene activation, and chronic inflammation. Senescent cells remain metabolically active, secreting cytokines, chemokines, growth factors, matrix metalloproteinases, extracellular vesicles and oxidative mediators, comprising a senescence-associated secretory phenotype (SASP) that affects the tissue microenvironment. With aging, impaired immune clearance results in senescent cell accumulation, promoting inflammation, immunosuppression and fibrosis. Emerging evidence implicates cellular senescence in obstructive airway diseases, reflecting the lung’s continuous exposure to environmental and oxidative insults, and several pathways, including DNA damage response and p53/p21 and p16^INK4a signaling, telomere dysfunction, reactive oxygen species production, and mitochondrial defects, integrate stress signals to enforce senescence. In chronic obstructive pulmonary disease, a SASP-associated inflammatory milieu supports stress-induced tissue injury, while uncertainty still exists about the effects of chronic SASP on tumor suppression versus tumor promotion. In asthma, senescence processes have been associated with both Type(T)2-high and T2-low endotypes, underlying the interplay between environmental exposures, airway epithelial dysfunction and induced senescence mechanisms. Finally, in bronchiectasis, the neutrophilic, dysbiotic airway environment links dysregulated senescence with disease persistence and progression. Conventional therapies, antioxidants, serine protease inhibitors and novel senotherapeutic strategies represent promising approaches for therapeutic interventions. Full article