Search Results (1,117)

Osteoarthritis (OA) is primarily a degenerative disease triggered by joint inflammation and oxidative stress. While Aster glehni is an edible and traditionally medicinal herb, the beneficial effect of A. glehni on OA progression remains unknown. This study aimed to investigate the effect of A. glehni extract (AGE) and its primary biological compound—3,5-dicaffeoylquinic acid (3,5-DCQA)—on inflammation and oxidative stress in chondrocytes. AGE effectively inhibited the expression of interleukin (IL)-6, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-1, and MMP-13 in chondrocytes stimulated by IL-1β for 24 h. In contrast, 3,5-DCQA did not inhibit IL-6, COX-2, and MMP expressions under the same conditions. However, when chondrocytes were stimulated by IL-1β for a short duration (6 h), 3,5-DCQA suppressed IL-6, COX-2, and MMP expressions. The inhibition of IL-6, COX-2, and MMP expressions by AGE was associated with the p38 kinase and nuclear factor-κB signaling pathways, but not ERK and JNK signaling pathways. Furthermore, AGE prevented cell apoptosis and reduced intracellular reactive oxygen species levels in chondrocytes induced by hydrogen peroxide (H₂ O₂). AGE restored the decreased superoxide dismutase 1 and catalase mRNA expressions caused by H₂ O₂. Collectively, AGE may protect against cartilage deterioration by inhibiting inflammation and oxidative stress, making it a promising therapeutic agent for alleviating OA. Full article

A novel, cost-effective, label-free biosensing strategy has been established for real-time quantification of alkaline phosphatase (ALP) activity, integrating the Tyndall effect with smartphone imaging technology. This method utilizes a handheld laser diode to probe the enzyme-triggered in situ assembly of Cu-guanosine monophosphate (Cu-GMP) coordination polymers, which exhibit tunable Tyndall scattering properties. In the absence of ALP, Cu²⁺ ions chelate with GMP to form Cu-GMP coordination polymers, generating an intense Tyndall effect. Conversely, ALP-mediated hydrolysis of GMP disrupts the formation of Cu-GMP coordination polymers, resulting in diminished light scattering. The intensity of the Tyndall effect is directly proportional to the concentration of Cu-GMP coordination polymers, which in turn correlates with ALP activity levels. A comprehensive investigation of experimental parameters was conducted, including pH, incubation temperature, GMP concentration, incubation time, synthesis duration, and CuSO₄ concentration. Under optimized conditions, the developed smartphone-assisted colorimetric assay enables the detection of ALP activity within the range of 0.375–3.75 U/mL, with a limit of detection of 0.184 U/mL. The application of this method to serum samples yielded recovery rates ranging from 102.6% to 109.0%. In summary, this smartphone-based colorimetric platform offers a portable and versatile approach for instrument-free detection of ALP activity, with potential applications in point-of-care diagnostics and resource-limited settings. Full article

Biomolecule-driven smart materials represent a paradigm shift in pharmacology, transitioning drug delivery from a passive process to an active, programmable, and highly specific intervention. These systems, constructed from or functionalized with biological macromolecules such as nucleic acids, peptides, proteins, and polysaccharides, are engineered to sense and respond to specific pathophysiological cues or external triggers. This review provides a comprehensive analysis of this rapidly evolving field. We first delineate the fundamental principles of stimuli-responsive actuation, categorizing systems based on their response to endogenous (pH, redox, enzymes, ROS) and exogenous (temperature, light, magnetic fields) triggers. We then conduct an in-depth survey of the primary biomolecular architectures, examining the unique design space offered by DNA nanotechnology, the functional versatility of peptides and proteins, and the biocompatibility of polysaccharides. Key therapeutic applications in oncology, inflammatory diseases, and gene therapy are discussed, highlighting how these intelligent systems are being designed to overcome critical biological barriers and enhance therapeutic efficacy. Finally, we address the formidable challenges—spanning biocompatibility, manufacturing scalability, and regulatory navigation—that constitute the “bench-to-bedside” chasm. We conclude by exploring future perspectives, including the development of multi-stimuli responsive, logic-gated systems and the transformative potential of artificial intelligence in designing the next generation of personalized nanomedicines. Full article

Surgical trauma triggers oxidative and inflammatory responses that contribute to postoperative complications. Although the antioxidant and anti-inflammatory effects of ketamine have been reported, the impact of anesthesia duration on these mechanisms remains unclear. Forty-two male Wistar rats were randomized into healthy control (HG), ketamine only (KET; 60 mg/kg, i.p.), or laparotomy plus ketamine with 0–4 additional ketamine doses at 20 min intervals (KET + L, KET + L1–L4). At 24 h, levels of MDA, tGSH, SOD, CAT, IL-1β, IL-6, TNF-α, adrenaline and noradrenaline were measured in tail-vein blood. One-way ANOVA with Tukey’s post hoc test was used. Laparotomy under single-dose ketamine increased MDA and pro-inflammatory cytokines and decreased tGSH, SOD, CAT, ADR, and NDR versus HG and KET (all p < 0.001). After laparotomy, repeated ketamine dosing produced graded decreases in MDA and cytokines and increases in tGSH, SOD, CAT, ADR, and NDR toward control levels; effects were most pronounced in KET + L4 (all p < 0.001). Ketamine alone did not differ significantly from HG. In rats, ketamine modulates postoperative biological stress in a duration-dependent manner; prolonging anesthesia reduces oxidative–inflammatory load and restores catecholaminergic tone. These findings strongly support revisiting dose–duration protocols and underscore the need for mechanistic and clinical studies. Full article

Background: Multiple mechanisms might lead to cancer-related hypercoagulability. In brain tumors, podoplanin, via its ability to activate platelets, seems to play a crucial role in developing venous thromboembolism (VTE). Different stimuli (including activated platelets) can trigger the release of prothrombotic neutrophil extracellular traps (NETs) by neutrophils. It remains to be elucidated whether podoplanin-induced platelet aggregates might also impact NET formation and subsequent hypercoagulability and thrombosis. Methods: Patients with glioma were enrolled in this prospective observational cohort study. The primary endpoint was VTE. Immunohistochemical staining of NETs (via citrullinated histone H3 [H3Cit]) and neutrophils (via myeloperoxidase [MPO]) was conducted in glioma specimens and correlated with intravascular platelet clusters (via CD61) and podoplanin. Results: In total, 154 patients were included. H3Cit+ tumor vessels were found in 45/154 cases. H3Cit were significantly associated with increased intravascular platelet clusters (CD61− vs. CD61+ vs. CD61++ vs. CD61+++: 3.7% (1/27) vs. 18.6% (11/59) vs. 39.4% (13/33) vs. 57.1% (20/35), p < 0.001) and podoplanin expression (PDPN− vs. PDPN+: 14.3% (7/49) vs. 36.2% (38/105), p = 0.007) in the tumor tissue. Furthermore, H3Cit+ tumor vessels were significantly associated with tumor-infiltrating MPO+ neutrophils (H3Cit− vs. H3Cit+, median [Q1-Q3]: 6.0 [3.3–12.3] vs. 12.5 [5.9–22.0] cells/mm², p < 0.001) and with D-dimer levels (H3Cit− vs. H3Cit+: 0.53 [0.32–1.10] vs. 0.84 [0.46–2.75] µg/mL, p = 0.034). The VTE risk was not linked to H3Cit+ tumor vessels (p = 0.613, log-rank). Conclusions: H3Cit in tumor vessels was not associated with VTE. However, H3Cit was linked to a local procoagulant phenotype in glioma, thereby potentially contributing to a systemic hypercoagulable state and thrombus formation. Full article

The Northeast region in China is a major maize-producing area; however, low-temperature stress (TS) limits maize (Zea mays L.) seed germination, affecting population establishment and yield. In order to systematically explore the regulation mechanism of maize radicle which is highly sensitive to low-temperature environment response to TS, seeds of ZD958 and DMY1 were used to investigate germination responses under 15 °C (control) and 5 °C (TS) conditions. Phenotypic, physiological, transcriptomic, and metabolomic analyses were conducted on the radicles after 48 h of TS treatment. TS caused reactive oxygen species (ROS) imbalance and oxidative damage in radicle cells, inhibiting growth and triggering antioxidant defenses. Integrated transcriptomic and metabolomic analyses revealed that flavonoid metabolism may play a pivotal role in radicle responses to TS. Compared with the control treatment, ZD958 and DMY1 under TS treatment significantly increased (p < 0.01) the total flavonoid content, total antioxidant capacity, 4-coumarate-CoA ligase activity, and dihydroflavonol 4-reductase activity by 15.99% and 16.01%, 18.41% and 18.54%, 63.54% and 31.16%, and 5.09% and 7.68%, respectively. Despite genotypic differences, both followed a shared regulatory logic of “low-temperature signal-driven—antioxidant redirection—functional synergy.” This enabled ROS scavenging, redox balance, and antioxidant barrier formation, ensuring basal metabolism and radicle development. Full article

Background: Abnormal activation of Angiotensin II (Ang II) serves as a primary trigger for myocardial hypertrophy and cardiac injury. Isoquercitrin (IQ) and Quercetin (Que) possess anti-inflammatory and anti-apoptotic properties, but their protective effects against Ang II-induced cardiac injury remain unclear. This study aimed to investigate the mechanisms and therapeutic efficacy of IQ and Que in heart failure. Methods: Cytotoxic effects of IQ and Que on Ang II-induced H9c2 rat cardiomyocyte apoptosis models were assessed in vitro using the CCK-8 assay. Reactive Oxygen Species (ROS) generation and apoptotic fluorescence levels were measured. WB analysis examined protein expression in inflammatory and apoptotic pathways. In vivo heart failure model was established in mice, with cardioprotective effects of IQ and Que evaluated via echocardiography. Molecular docking was employed to analyze ligand–target interactions. Results: IQ outperformed Que in promoting cell viability and decreasing ROS. IQ exhibited a more potent inhibitory effect on apoptosis through regulating Bax, Caspase-3, CytoC, and Bcl-2 and demonstrated superior suppression of cardiac inflammation by inhibiting phosphorylation of ERK, JNK, and P38. Compared with Que, IQ more effectively attenuated Ang II-induced cardiac injury by ameliorating reductions in EF% and FS%, suppressing ST-segment elevation, and significantly reducing serum levels of CK-MB, LDH, ANP, BNP, and FFA in a heart failure model. Molecular docking verified stronger binding affinity of IQ for key targets. Conclusions: IQ demonstrates superior cardioprotection over Que by regulating MAPK signaling and mitochondrial apoptosis pathways, supporting its potential as a therapeutic candidate for heart failure. Full article

Background: Primary dysmenorrhea (PD) is a common gynecological condition among women of reproductive age, often leading to pain and functional limitations. Myofascial release (MFR) has been suggested as a potential non-pharmacological intervention. This study aimed to investigate the immediate effects of a single MFR session on pain intensity, menstrual symptoms, and uterine artery hemodynamics in women with PD. Methods: In this randomized controlled trial, 34 women with PD were randomly assigned to either the MFR group (n = 18) or the placebo MFR group (n = 16). All participants received 10 min of thermotherapy followed by 30 min of either MFR or placebo MFR. Pain intensity (NRS), pressure pain thresholds (PPT) at myofascial trigger points, menstrual symptoms (MDQ-T), and uterine artery pulsatility index (PI) and resistance index (RI) were assessed at three time points: baseline, immediately after the intervention, and 3 h post-intervention. Results: Both groups demonstrated significant within-group reductions in pain intensity and menstrual symptoms post-intervention (p < 0.01), with no significant group-by-time interaction. However, significant interaction effects were observed for the PI and RI of the right uterine artery, showing greater reductions in the MFR group compared to the placebo group at 3 h post-intervention (p < 0.05). Conclusions: A single MFR session resulted in improvements in uterine hemodynamics, suggesting autonomic modulation as a potential mechanism. Although subjective symptom improvements were observed in both groups, only MFR showed objective vascular benefits. These findings support the physiological plausibility of MFR in PD management and suggest its potential application as a personalized, non-pharmacological intervention. Further studies are warranted to explore its long-term and individualized therapeutic effects. Full article

Human activities have triggered microplastic pollution, and estuaries have emerged as critical yet understudied ecosystems in Chile. This study investigated sediment microplastic pollution in the Lenga (highly industrialized) and Tubul-Raqui (fisheries village) ecosystems, characterized by contrasting anthropogenic impacts, in the Biobío Region, Chile. Microplastic particles, including fibers, foam, fragments, and film, were detected in both estuaries. The Lenga estuary, heavily industrialized, exhibited a significantly higher total abundance of microplastics compared to the Tubul-Raqui estuary. However, the mean concentrations of microplastics in the studied estuaries are notably lower than those reported in other global studies, aligning more closely with levels found in less polluted estuaries around the world. FTIR analyses identified six types of polymers in Lenga, with polyamide (PA) being the most prevalent, constituting 35% of all polymers detected. Conversely, in Tubul-Raqui, polyvinyl chloride (PVC) emerged as the predominant polymer, comprising 25% of the total. Furthermore, significant correlations were observed with sediment physico-chemical parameters, such as organic matter and pH. These findings confirm the existence of microplastic pollution in both estuaries, highlighting the necessity of continued monitoring and assessment of potential environmental impacts in these ecologically valuable ecosystems. Full article

This study presents experimental and geochemical modeling results that validate a fluid-mixing model for baryte and sulfide mineralization in vein-type hydrothermal systems, with reference to the Mykonos granodiorite, Cyclades. Synthetic Ba-rich hydrothermal fluids, representing those released during retrograde alteration of granitoids, were mixed with SO₄²⁻-bearing solutions, simulating Miocene seawater under controlled conditions (200–300 °C, <100 bars). Baryte precipitated rapidly upon mixing, accompanied by the co-precipitation of sulfides, such as sphalerite, chalcopyrite, galena, and minor native silver. The experiments reproduced key mineral assemblages observed in the Mykonos vein system, emphasizing the importance of a second fluid boiling at 250 °C, and redox shifts as triggers for ore formation. Complementary geochemical simulations (Solveq) constrained the stability fields of Ba–sulfate and base-metal sulfides, highlighting the critical influence of pH (5.0–6.2) and SO₄²⁻/H₂S ratios on mineral precipitation. The integration of experimental and simulation approach supports a robust model for baryte–sulfide deposition in shallow, extensional settings, where fault-controlled fluid flow promotes episodic mixing and boiling of magmatic and seawater-derived ore fluids. Full article

Background/Objectives: Barium titanate (BaTiO₃)-based nanocarriers have emerged as versatile and promising platforms for targeted drug delivery, owing to their unique combination of biocompatibility, piezoelectric and ferroelectric properties, as well as responsiveness to external stimuli. These multifunctional ceramic nanoparticles can be precisely engineered to enable spatiotemporally controlled release of therapeutic agents, triggered by physical stimuli such as ultrasound, light, magnetic fields, temperature changes, and pH variations. Such an approach enhances treatment efficacy while reducing systemic side effects. Methods: This review provides a comprehensive overview of the latest advancements in the development and biomedical application of BaTiO₃-based nanocarriers. Special emphasis is placed on modern synthesis strategies, surface functionalization methods, and the integration of BaTiO₃ with other functional nanomaterials to create hybrid systems with improved therapeutic performance. Key challenges in clinical translation are also discussed, including biocompatibility assessment, biodistribution, and regulatory requirements. Conclusions: BaTiO₃-based nanocarriers show promise as materials well suited for advanced biomedical applications. The paper concludes with an outline of future research directions aimed at optimizing these advanced nanosystems for precision and personalized medicine, with applications in oncology, anti-infective therapy, and regenerative medicine. Full article

Background/Objectives: Biodegradable and pH-responsive nanocarriers using zwitterionic moieties represent a promising avenue for targeted delivery of chemotherapeutics. The present study addresses this by developing zwitterionic nanoparticles based on polylactic acid/poly(ethylene adipate) (PLA/PEAd) copolymers grafted with SBMA, designed to combine acid-triggered drug release with stealth-like biocompatibility. Methods: A series of polylactic acid/poly(ethylene adipate) (PLA/PEAd) copolymers with varying compositions (95/5, 90/10, and 75/25 w/w) were synthesized via ring-opening polymerization, followed by controlled radical grafting of the zwitterionic monomer [2-(Methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), which was then successfully grafted upon their backbone. The resulting zwittenionic copolymers were thoroughly characterized for their structural and physicochemical properties, displaying tunable molecular weights of 3200–4900 g/mol, enhanced hydrophilicity and controlled degradation, with mass loss ranging from 8% to 83% over 30 days, depending on PEAd content and pH. Paclitaxel-loaded nanoparticles of spherical shape with sizes ranging from 220 to 565 nm were then fabricated. Drug release was pH-dependent with significantly higher release at pH 5.0 (up to ~79% for PLAPEAd7525-SBMA) compared to pH 7.4 (~18–35%). Hemolysis assays demonstrated excellent hemocompatibility, and cytotoxicity studies showed strong anticancer activity (>80% cell death in MDA-MB-231) with lower toxicity toward iMEFs, especially for PEAd-rich formulations. Conclusions: Our findings underline the potential of SBMA-functionalized PLA/PEAd nanoparticles as effective nano-carriers for tumor-targeted chemotherapy. Full article

The mammalian epidermis forms a critical barrier against environmental insults and water loss. The formation of its outermost layer, the stratum corneum, involves a rapid terminal differentiation process that has traditionally been explained by the “bricks and mortar” model. Recent advances reveal a more dynamic mechanism governed by intracellular liquid–liquid phase separation (LLPS). This review proposes that the lifecycle of the granular layer is orchestrated by LLPS. Evidence is synthesized showing that keratohyalin granules (KGs) are biomolecular condensates formed by the phase separation of the intrinsically disordered protein filaggrin (FLG). The assembly, maturation, and pH-triggered dissolution of these condensates are essential for cytoplasmic remodeling and the programmed flattening of keratinocytes, a process known as corneoptosis. In parallel, an LLPS-based signaling pathway is described in which the kinase RIPK4 forms condensates that activate the Hippo pathway, promoting transcriptional reprogramming and differentiation. Together, these structural and signaling condensates drive skin barrier formation. This review further reinterprets atopic dermatitis, ichthyosis vulgaris, and Bartsocas-Papas syndrome as diseases of aberrant phase behavior, in which pathogenic mutations alter condensate formation or material properties. This integrative framework offers new insight into skin biology and suggests novel opportunities for therapeutic intervention through biophysics-informed biomaterial and regenerative design. Full article

The development of pH-responsive liposomes represents a promising strategy for targeted drug delivery, enhancing therapeutic efficacy while minimizing toxicity and side effects. These innovative nanocarriers are typically synthesized via the thin film hydration method and can be further modified to exhibit stimuli-responsive behavior. pH-responsive liposomes are biocompatible, biodegradable, and capable of encapsulating both hydrophilic and hydrophobic drugs, increasing their versatility in drug delivery. In this mini-review, we explore the mechanism of action of pH-responsive liposomes, analyzing the factors that influence both their intracellular and extracellular behavior. Various formulations are examined, and their characteristics are compared to optimize therapeutic outcomes. Furthermore, we discuss the potential applications in anticancer therapy, in gene therapy, and in bacterial infections as vaccines and diagnostic agents. Full article

Coccidiosis due to Eimeria tenella remains a major constraint on the poultry industry. Previous studies have revealed that E. tenella infection triggers apoptosis in host cells. The mitochondrial permeability transition pore (MPTP) plays a pivotal role in the apoptosis and necrosis observed in infected host cells. However, the effect of MPTP opening on mitochondrial apoptotic factors remains unclear. To elucidate the dynamic changes in apoptotic signals during MPTP-mediated apoptosis in host cells infected with E. tenella, we established a chicken embryo caecal epithelial cell infection model. Cyclosporin A (CsA) was used to inhibit the MPTP. The infection rate was assessed by Hematoxylin and eosin (H&E) staining, whereas MPTP opening and the abundances of the mitochondrial apoptotic factors Smac, Endo G, and AIF were determined by flow cytometry and ELISA, respectively. The results revealed that both the degree of MPTP opening was markedly reduced in the E. tenella+CsA group compared to the E. tenella group (p < 0.05). Between 24 and 120 h post-infection (hpi), the cytoplasmic levels of Smac, Endo G, and AIF were significantly elevated in the E. tenella group compared with the control group (p < 0.05), while their mitochondrial levels were markedly decreased (p < 0.05). In contrast, mitochondrial expression of these factors was restored in the E. tenella+CsA group (p < 0.05), accompanied by a reduction in their cytoplasmic abundance (p < 0.05). These findings indicate that E. tenella promotes MPTP-dependent release of mitochondrial pro-apoptotic factors into the cytosol during the mid-to-late stages of infection, whereas pharmacological inhibition of the MPTP limits this redistribution. Full article