Search Results (1,089)

Guided bone regeneration (GBR) membrane has proven to be a fundamental tool in the realm of bone defect repair. In this study, we develop a mussel-inspired composite biomaterial through polydopamine-assisted, combining gelatin–WPU matrix with the ion-release behavior of Cu–MSNs for augmented bone regeneration. The optimized composite membrane exhibits enhanced mechanical stability, demonstrating a tensile strength of 11.23 MPa (representing a 2.3-fold increase compared to Bio-Gide^®), coupled with significantly slower degradation kinetics that retained 73.3% structural integrity after 35-day immersion in physiological solution. Copper ions act as angiogenic agents to promote blood vessel growth and as antimicrobial agents to prevent potential infections. The combined effect of these components creates a biomimetic environment that is ideal for cell adhesion, growth, and differentiation. This research significantly contributes to the development of advanced biomaterials that combine regeneration and infection-prevention functions. It provides a versatile and effective solution for treating bone injuries and defects, offering new hope for patients in need. Full article

Acute pancreatitis (AP) an inflammatory condition caused by the premature activation of pancreatic proteases, leads to organ damage, systemic inflammation, and multi-organ failure. Severe acute pancreatitis (SAP) has high morbidity and mortality, affecting the liver, kidneys, and lungs. Autophagy maintains pancreatic homeostasis, with VMP1-mediated selective autophagy (zymophagy) preventing intracellular zymogen activation and acinar cell death. This study examines the protective role of VMP1 (Vacuole Membrane Protein 1)-induced autophagy using ElaI-VMP1 transgenic mice in a necrohemorrhagic SAP model (Hartwig’s model). ElaI-VMP1 mice show significantly reduced pancreatic injury, including lower necrosis, edema, and inflammation, compared to wild-type (WT) mice. Biochemical markers (lactate dehydrogenase-LDH-, amylase, and lipase) and histopathology confirm that VMP1 expression mitigates pancreatic damage. Increased zymophagy negatively correlates with acinar necrosis, reinforcing its protective role. Beyond the pancreas, ElaI-VMP1 mice exhibit preserved liver, kidney, and lung histology, indicating reduced systemic organ damage. The liver maintains normal architecture, kidneys show minimal tubular necrosis, and lung inflammation features are reduced compared to WT mice. Our results confirm that zymophagy functions as a protective pathophysiological mechanism against pancreatic and extrapancreatic tissue injury in SAP. Further studies on the mechanism of VMP1-mediated selective autophagy in AP are necessary to determine its relevance and possible modulation to prevent the severity of AP. Full article

Background/Objectives: Lactate, classically considered a metabolic byproduct of anaerobic glycolysis, is implicated in ischemic acidosis and neuronal injury. The recent evidence highlights its potential role in sustaining metabolic networks and neuroprotection. This study investigates lactate’s compensatory mechanisms in ischemic brain injury by analyzing post-ischemic metabolic enrichments and inter-regional metabolite correlations. Methods: Dynamic metabolic profiling was conducted using ¹³C-labeled glucose combined with ¹H-¹³C NMR spectroscopy to quantify the metabolite enrichment changes in a murine cerebral ischemia model (n = 8). In vivo validation included intracerebroventricular pH-neutral lactate infusion in ischemic mice to assess the behavioral, electrophysiological, and mitochondrial outcomes. In vitro, HT22 hippocampal neurons underwent oxygen–glucose deprivation (OGD) with pH-controlled lactate supplementation (1 mM), followed by the evaluation of neuronal survival, mitochondrial membrane potential, and glycolytic enzyme expression. Results: NMR spectroscopy revealed a 30–50% reduction in most cerebral metabolites post-ischemia (p < 0.05), while the quantities of lactate and the related three-carbon intermediates remained stable or increased. Correlation analyses demonstrated significantly diminished inter-metabolite coordination post-ischemia, yet lactate and glutamate maintained high metabolic activity levels (r > 0.80, p < 0.01). Lactate exhibited superior cross-regional metabolic mobility compared to those of the other three-carbon intermediates. In vivo, lactate infusion improved the behavioral/electrophysiological outcomes and reduced mitochondrial damage. In the OGD-treated neurons, pH-neutral lactate (7.4) reduced mortality (p < 0.05), preserved the mitochondrial membrane potential (p < 0.05), and downregulated the glycolytic enzymes (HK, PFK, and PKM; p < 0.01), thereby attenuating H⁺ production. Conclusions: Under ischemic metabolic crisis, lactate and the three-carbon intermediates stabilize as critical substrates, compensating for global metabolite depletion. pH-neutral lactate restores energy flux, modulates the glycolytic pathways, and provides neuroprotection by mitigating acidotoxicity. Full article

Background: Most of the grasslands in China are experiencing varying degrees of degradation, desertification, and salinization (collectively referred to as the “three degradations”), posing a serious threat to the country’s ecological security. Agropyron desertorum, known for its wide distribution, strong adaptability, and resistance, is an excellent grass species for the ecological restoration of grasslands affected by the “three degradations”. This study focused on two currently popular varieties of A. desertorum, exploring their salt tolerance mechanisms and identifying candidate genes for salt and alkali tolerance. Methods: Transcriptome sequencing was performed on two varieties of A. desertorum during the seed germination and seedling stages under varying degrees of saline–alkali stress. At the seed stage, we measured the germination rate, relative germination rate, germination index, and salt injury rate under different NaCl concentrations. During the seedling stage, physiological indicators, including superoxide dismutase (SOD), peroxidase (POD), malondialdehyde (MDA), proline (PRO), soluble protein (SP), and catalase (CAT), were analyzed after exposure to 30, 60, 120, and 180 mM NaCl for 12 days. Analysis of differentially expressed genes (DEGs) at 6 and 24 h post-treatment with 120 mM NaCl revealed significant differences in the salt stress responses between the two cultivars. Results: Our study indicates that during the seed stage, A. desertorum (Schult.) exhibits a higher relative germination potential, relative germination rate, and relative germination index, along with a lower relative salt injury rate compared to A. desertorum cv. Nordan. Compared with A. desertorum cv. Nordan, A. desertorum (Schult.) has higher salt tolerance, which is related to its stronger antioxidant activity and different antioxidant-related pathways. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the key biological processes and pathways involved in salt tolerance, including plant hormone signal transduction, antioxidant defense, and cell membrane stability. Conclusions: A. desertorum (Schult.) exhibits stronger salt tolerance than A. desertorum cv. Nordan. Salt stress at a concentration of 30–60 mM promotes the germination of the seeds of both Agropyron cultivars. The two Agropyron plants mainly overcome the damage caused by salt stress through the AsA-GSH pathway. This study provides valuable insights into the molecular mechanisms of salt tolerance in Agropyron species and lays the groundwork for future breeding programs aimed at improving salt tolerance in desert grasses. Full article

Pulsed field ablation (PFA) is an emerging technology that utilizes ultra-short high-voltage electric pulses to create nanopores in cell membranes, leading to cell death through irreversible electroporation (IRE). PFA is touted to be highly tissue-selective, which may mitigate the risk of collateral injury to vital adjacent structures. In the field of cardiac electrophysiology, initial studies have shown promising results for acute pulmonary vein isolation (PVI) and lesion durability, with overall freedom from recurrent atrial arrhythmia comparable to traditional thermal ablation modalities. While further large studies are required for long-term efficacy and safety data, PFA has the potential to become a preferred energy source for cardiac ablation for some indications. This review outlines the basic principles and biophysics of IRE and its application to cardiac electrophysiology through a review of the existing preclinical and clinical data. Full article

Background: The egg-laying performance of hens is primarily regulated by ovarian follicle growth and development; these follicles are susceptible to oxidative damage caused by excessive reactive oxygen species (ROS). Oxidative damage can lead to follicular atresia and impaired reproductive performance. Melatonin (MT), a known endogenous antioxidant, plays a role in regulating oxidative damage, but its precise mechanisms in mitigating H₂O₂-induced oxidative damage via mitophagy regulation in granulosa cells remain unclear. Methods: An in vitro oxidative damage model was established by determining the optimal H₂O₂ concentration using CCK-8 fluorescence quantification. The optimal MT concentration was identified through fluorescence quantification and catalase (CAT) activity assays. The protective effects of MT against H₂O₂-induced oxidative damage in follicular granulosa cells were investigated using flow cytometry, Western blotting, ELISA, and quantitative fluorescence analysis. Results: An in vitro oxidative damage model was established using H₂O₂-induced granulosa cells, characterized by P53 and LC3-II upregulation and LC3-I and BCL-2 downregulation. The optimal MT concentration for reducing cellular injury was determined. MT co-treatment enhanced CAT, GSH, and SOD activities, decreased LC3-II/LC3-I conversion, and increased P62 expression. Furthermore, MT reduced autophagic vesicle formation and restored mitochondrial membrane potential, demonstrating its protective effect against H₂O₂-induced oxidative damage. Conclusions: Melatonin alleviates H₂O₂-induced oxidative damage in chicken follicular granulosa cells by modulating antioxidant defense, autophagy, and mitochondrial function. These findings provide newer insights to our understanding of the regulatory mechanisms underlying the alleviation of the H₂O₂-induced oxidative damage in granulosa cells during ovarian follicle development in chickens. Full article

Copper oxide nanoparticles (CuO-NPs) induce neurological diseases, including neurobehavioral defects and neurodegenerative diseases. Direct evidence indicates that CuO-NPs induce inflammation in the central nervous system and cause severe neurotoxicity. However, the mechanism of CuO-NP-induced damage to the nervous system has rarely been studied, and the toxicity of different CuO-NP particle sizes and their copper ion (Cu²⁺) precipitation in microglia (BV2 cells) is worth exploring. Therefore, this study investigated CuO-NPs with different particle sizes (small particle size: S-CuO-NPs; large particle size: L-CuO-NPs), Cu²⁺ with equal molar mass (replaced by CuCl₂ [Equ group]), and Cu²⁺ precipitated in a cell culture solution with CuO-NPs (replaced by CuCl₂ [Pre group]), and examined the mechanism of action of each on BV2 microglia after co-culture for 12 h and 24 h. The activity of BV2 cells decreased, the morphology was damaged, and the apoptosis rate increased in all the exposed groups. Toxicity increased time- and dose-dependently, and was highest in the Equ group, followed by the S-CuO-NPs, L-CuO-NPs, and Pre groups, respectively. Subsequently, we investigated the mechanism of S-CuO-NP-induced cell injury, and revealed that S-CuO-NPs induced oxidative stress and inflammatory response and increased the membrane permeability of BV2 cells. Moreover, S-CuO-NPs reduced the ratio of p-CSF-1R/CSF-1R, p-PLCγ2/PLCγ2, p-extracellular signal-regulated kinase (ERK)/ERK, p-Nrf2/Nrf2, and Bcl-2/Bax protein expression in microglia, and elevated cleaved caspase-3 expression. The CSF-1R/PLCγ2/ERK/Nrf2 apoptotic pathway was activated. The downregulation of CX3CR1, CSF-1R, brain-derived neurotrophic factor (BDNF), and IGF-1 protein expression indicates impairment of the repair and protection functions of microglia in the nervous system. In summary, our results reveal that CuO-NPs promote an increase in inflammatory molecules in BV2 microglia through oxidative stress, activate the CSF-1R/PLCγ2/ERK/Nrf2 pathway, cause apoptosis, and ultimately result in neurofunctional damage to microglia. Full article

The disruption of microglial homeostasis and cytokine release are critical for neuroinflammation post-injury and strongly implicated in retinal neurodegenerative diseases like glaucoma. This study examines microglial responses to chemical hypoxia induced by cobalt chloride (CoCl₂) in BV-2 murine microglial cells, focusing on signaling pathways and proteomic alterations. We assessed the protective effects of monoclonal antibodies against TNFα and IL-1β. CoCl₂ exposure led to decreased cell viability, reduced mitochondrial membrane potential, increased lactate dehydrogenase release, elevated reactive oxygen species generation, and activation of inflammatory pathways, including nitric oxide synthase (iNOS), STAT1, and NF-κB/NLRP3. These responses were significantly mitigated by treatment with anti-TNFα and anti-IL-1β, suggesting their dual role in reducing microglial damage and inhibiting inflammatory reactivity. Additionally, these treatments reduced apoptosis by modulating ATF4 and the p38 MAPK/caspase-3 pathways. Label-free quantitative mass spectrometry-based proteomics and Gene Ontology revealed that CoCl₂ exposure led to the upregulation of proteins primarily involved in endoplasmic reticulum and catabolic processes, while downregulated proteins are associated with biosynthesis. Anti-TNFα and anti-IL-1β treatments partially restored the proteomic profile toward normalcy, with network analysis identifying heat shock protein family A member 8 (HSPA8) as a central mediator in recovery. These findings offer insights into the pathogenesis of hypoxic microglial impairment and suggest potential therapeutic targets. Full article

The heavy metal cadmium (Cd) affects the global livestock production economy mainly through the contamination of feed raw materials and secondary contamination in feed processing, and it also poses a serious threat to food safety and human health. The nucleotide-binding oligomerization domain-like pyrin-domain-containing protein 3 (NLRP3) inflammasome is a key regulatory element of pyroptosis, which is engaged in kidney injury. Meanwhile, autophagy is also involved in renal inflammation. Mammalian target of rapamycin (mTOR) plays an important role in pyroptosis and autophagy, but its function in Cd-induced kidney injury remains unclear. In this study, we explored the role of mTOR-mediated autophagy and pyroptosis in kidney injury caused by Cd exposure and elucidated its underlying mechanism. Our data showed that Cd exposure reduced the integrity of kidney cell membranes, increased the expression of pyroptosis-associated proteins, and promoted the release of inflammatory cytokines. Subsequently, a notable attenuation in Cd-induced pyroptosis was observed following the administration of CY-09, an NLRP3 inhibitor. In addition, Cd exposure promoted autophagy in kidney cells. Importantly, in both in vivo and in vitro experiments, rapamycin, an mTOR inhibitor, downregulated the expression of pyroptosis-related proteins, thereby significantly improving Cd-induced kidney injury. In summary, our results indicate that mTOR-mediated autophagy has a significant protective effect on NLRP3 inflammasome-dependent kidney injury induced by Cd exposure, thus providing new insights into the prevention and treatment of Cd poisoning. Full article

This study aims to explore the protective effects of Hong-bai-lan-shen (HBLS) extract, a traditional Chinese medicine compound, on myocardial injury based on metabolomics. H9C2 cells were cultured with HBLS extract for 12 h, and then the cells were cultured in a CoCl₂-containing medium, a model simulating the ischemic-hypoxic damage in myocardial cells, for an additional 12 h. The cell viability, cytotoxicity, intracellular metabolite and reactive oxygen species (ROS), mitochondrial membrane potential, apoptosis, and adenosine monophosphate-activated protein kinase (AMPK) signal pathway were determined. The results showed that HBLS extract significantly increased cell viability, stabilized cell morphology, reduced lactate dehydrogenase (LDH) release and ROS production, blocked cysteine-aspartic acid protease 3 (caspase-3) and bcl-2-associated X protein (Bax) expression and decreased apoptotic cell numbers. Meanwhile, HBLS increased membrane potential and the expression of B-cell lymphoma-2 (Bcl-2). Additionally, HBLS extract upregulated the expression of AMPK, PI3K, and protein kinase B (AKT) (p < 0.05, p < 0.01). These findings suggest that HBLS extract has a protective effect on myocardial cells by regulating the AMPK signal pathway and may be a promising therapeutic candidate for ischemic heart disease. Full article

Background/Objectives: The extract from aerial yam bulbils (AYB) contains various bioactive compounds, yet the mechanisms underlying its effects on APAP-induced liver injury need to be investigated further. This study sought to pursue the effects of AYB extract and the potential mechanisms involved in mitigating APAP-induced hepatotoxicity. Methods: TIB-73 cells were pretreated with AYB extract (10, 20, and 40 μg/mL) for 24 h and treated with APAP for 24 h to induce cytotoxicity. Results: Analysis of apoptosis-related proteins revealed that AYB extract exerts anti-apoptotic effects and inhibiting the MAPK signaling pathways, thereby reducing apoptotic cell death. Additionally, AYB extract significantly suppressed ROS overproduction by enhancing the expression of endogenous antioxidants and reducing the endoplasmic reticulum (ER) stress in APAP-treated cells, indicating that AYB extract inhibits APAP-induced oxidative stress. AYB extract effectively preserved mitochondrial membrane potential (MMP), maintained mitochondrial function-related genes, reduced mitochondrial oxidative stress, and mitigated mitochondrial damage, thereby preserving mitochondrial integrity. Additionally, AYB extract activated the Nrf2-related signaling pathway through nuclear translocation, leading to the upregulation of downstream antioxidative target genes. Diosgenin, a compound with known antioxidant properties and hepatoprotective effects, was identified in significant quantities in the AYB extract, suggesting that it may contribute to the observed hepatoprotective effects. Conclusions: Overall, these findings demonstrate that AYB extract, with its antioxidative properties, effectively protects TIB-73 cells from APAP-induced liver injury. Full article

(1) Background: Knee cartilage injury is at the top of the rising concerns among bone and joint disorder patients. Autologous chondrocyte implantation (ACI) is widely used to approach knee cartilage deterioration. Integrating autologous chondrocytes and periosteal patches aids in forming new cartilage-like tissue at the lesion area. This study uses a novel cell source from one-day-old porcine cartilage to fabricate a biomembrane as a substitute for periosteal membranes in cell implantation techniques for treating knee cartilage injuries. (2) Methods: Cells isolated from one-day-old porcine cartilage tissue were identified and assessed for their proliferation capability, differentiation ability, and membrane formation potential. The protein component of the biomembrane was also defined by proteomics. The cartilage repair ability was also confirmed using an in vitro transplantation model. (3) Results: Negative results for porcine infectious diseases are pivotal in selecting suitable piglets to provide cartilage tissue. The cells successfully obtained from one-day-old porcine cartilage exhibited stem-cell-like characteristics (CD34-, CD45-, CD90+, CD105+), including a high proliferation to 20 passages (doubling time: 1–2 days) and a capacity to differentiate into various cell types (osteogenesis, adipogenesis, and chondrogenesis). The stem cells were successfully applied in the fabrication of the biomembranes. The protein components of the biomembrane included an extracellular matrix and growth factors. The in vitro transplantation model showed that the biomembrane induced the repair ability of cartilage defects. (4) Conclusions: This study is the first to successfully harvest stem cells from one-day-old porcine cartilage for biomembrane fabrication for a knee cartilage injury therapeutic application. Full article

In the heart, Connexin 43 (Cx43) is involved in intercellular communication through gap junctions and exosomes. In addition, Cx43-formed hemichannels at the plasma membrane are important for ion homeostasis and cellular volume regulation. Through its localization within nuclei and mitochondria, Cx43 influences the function of the respective organelles. Several cardiovascular diseases such as heart failure, ischemia/reperfusion injury, hypertrophic cardiomyopathy and arrhythmias are characterized by Cx43 downregulation and a dysregulated Cx43 function. Accordingly, a putative therapeutic approach of these diseases would include the induction of Cx43 expression in the damaged heart, albeit such induction may have both beneficial and detrimental effects. In this review we discuss the consequences of increasing cardiac Cx43 expression, and discuss this manipulation as a strategy for the treatment of cardiovascular diseases. Full article

Unwanted abdominal fat is a common aesthetic concern treated through various interventions, including surgical and energy-based devices, often leading to inconsistent results. This study aimed to evaluate the feasibility of a localized, non-invasive microwave (MW) device for preferential heating of subcutaneous adipose tissue using a controlled electromagnetic field. Five female volunteers scheduled for abdominoplasty were enrolled, each undergoing a single MW treatment session five days prior to surgery. Histological analyses of adipose tissue and skin samples were conducted using Hematoxylin and Eosin staining and immunohistochemistry for Perilipin-1 and CD68. Epidermal and dermal layers remained unaffected, as evidenced by unaltered morphology in treated samples. In contrast, the absence of Perilipin-1 expression in disrupted fat cell membranes indicated adipocyte non-viability and irreversible injury. Inflammatory responses, including CD68-positive macrophages surrounding damaged adipocytes, were observed, suggesting the activation of the monocyte/macrophage system for the clearance of adipocyte residues. Microscopic and immunohistochemical findings demonstrate the effectiveness of the MW device in reducing subcutaneous fat. This study also discussed the underlying mechanisms involved in macrophage recruitment and the removal of adipocyte residues. Full article

Cardiomyopathies, a cause of heart failure, are a predominant cause of death globally and may lead to discernible myocardial abnormalities. Several therapeutic agents were discovered, developed, investigated, and evaluated to save patients’ lives and improve their quality of life. The effective administration of drugs improves therapeutic outcomes while reducing side effects. Nanoparticles (NPs) have been utilised for the delivery of therapeutic agents and demonstrate promise in reducing myocardial ischaemia/reperfusion injury. However, significant limitations of NPs include non-specific targeting and immunogenicity. To improve cardiac targeting and biocompatibility, surface modifications using a cardiac cell membrane (cCM) coating on the surface of NPs have been hypothesised. Here, cCMs were isolated from the human ventricular cell line (AC16), and mesoporous silica nanoparticles (MSNs) were synthesised and then coated with cCMs. The cardiac cell membrane-coated mesoporous silica nanoparticles (cCMCMSNs) did not significantly alter the encapsulation efficiency or the release profile of the loaded drug (Rhodamine B) in comparison to MSN. Moreover, cCMCMSNs demonstrated a significantly enhanced distribution of RhB specifically to cardiac cells, compared to other cell types, without causing cytotoxicity. To evaluate immune escape, cCMCMSNs were exposed to activated macrophages, demonstrating that cCMCMSNs were phagocytosed to a lesser extent than MSN. This study demonstrated the synthesis of cardiac cell membranes coated on the surface of nanoparticles as nanomedicine technologies that enhance selective drug delivery to cardiac cells, potentially offering an alternate method for drug administration in cardiovascular diseases. Full article