Search Results (5,188)

Background: Mitochondrial dysfunction is central to the pathogenesis of acute myocardial infarction (AMI), but mitochondria-related molecular biomarkers and mechanisms remain incompletely defined. This study aimed to identify mitochondria-associated biomarkers in AMI and elucidate their functional roles in mitochondrial dynamics, extracellular matrix (ECM) remodeling, and cardiac protection. Methods: Two GEO datasets (GSE19322, GSE71906) were analyzed to identify mitochondria-related differentially expressed genes (DE-MRGs) by intersecting DEGs with MitoCarta3.0 genes. Functional enrichment (GO/KEGG), LASSO regression, ROC curves, and nomogram modeling were employed to screen biomarkers. Immune infiltration profiling, GeneMANIA, GSEA, TF-mRNA and ceRNA network construction, and drug prediction analyses were performed. Expression validation was conducted via RT-qPCR, Western blot (WB), and immunohistochemistry (IHC) in murine AMI models and hypoxia-induced cardiomyocytes. Functional assays assessed cardiac performance (echocardiography), infarct size (TTC staining), fibrosis (Masson/Sirius red), oxidative stress (ROS), and ECM remodeling (MMP9/TIMP1 axis). Results: We identified 295 DE-MRGs, enriched in oxidative phosphorylation and mitochondrial metabolic pathways. Machine learning and validation analyses pinpointed MTFP1 and DNAJC28 as AMI biomarkers with strong diagnostic accuracy. In vivo and in vitro studies confirmed marked downregulation of MTFP1 post-AMI and under hypoxia. AAV9-mediated MTFP1 overexpression improved cardiac function, reduced infarct size, attenuated fibrosis, and decreased ROS levels. Mechanistically, MTFP1 upregulated phosphorylated DRP1 (Ser616) without altering total DRP1, balanced MMP9/TIMP1 activity, and suppressed fibrosis markers (COL1A1, α-SMA). Gelatin zymography indicated that MMP9 activation remained restrained despite elevated pro-MMP9, consistent with TIMP1-mediated regulation. Hypoxia-induced cardiomyocytes showed similar antifibrotic and antioxidative responses following MTFP1 overexpression. Conclusions: Our study identified MTFP1 as a novel mitochondria-related biomarker and therapeutic modulator in AMI. MTFP1 exerts cardioprotective effects by restoring mitochondrial fission balance and ECM remodeling through the p-DRP1/MMP9/TIMP1 signaling axis, attenuating fibrosis and oxidative stress. These findings provide mechanistic insight into mitochondria-targeted cardioprotection and highlight MTFP1 as a promising diagnostic and therapeutic target for AMI. Full article

This study aimed to investigate the effect and underlying mechanism of Taxus cuspidata seed oil (TCSO) on carbon tetrachloride (CCl₄)-induced hepatic fibrosis in mice. A mouse model of hepatic fibrosis was established by CCl₄ induction, and the model mice were subsequently treated orally with high dose or low dose TCSO for eight weeks. The degree of liver fibrosis and the mechanism of action were assessed through organ indices, serum biochemical markers, oxidative stress levels, histopathological examination, and molecular biological analyses. The results demonstrated that TCSO significantly reduced serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). Concurrently, it decreased the concentrations of liver fibrosis markers, including procollagen III (PC III), collagen IV (IV-C), hyaluronic acid (HA), and laminin (LN), and reduced hepatic collagen deposition. Furthermore, TCSO enhanced the activities of the antioxidants superoxide dismutase (SOD) and glutathione (GSH) while inhibiting the production of the lipid peroxidation product malondialdehyde (MDA), and it ameliorated histopathological alterations in liver tissue. Additionally, TCSO markedly downregulated the expression of key fibrogenic proteins, such as transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinases-1 (TIMP-1), thereby effectively suppressing the progression of hepatic fibrosis. In conclusion, TCSO ameliorates hepatic fibrosis in mice by reducing hepatotoxic enzyme activity and collagen deposition, enhancing antioxidant capacity, and downregulating the expression of fibrosis-related proteins. Full article

Background: Danhong injection (DHI), a standardized traditional Chinese medicine formulation, has shown clinical benefits in treating cerebrovascular diseases. Blood–brain barrier (BBB) disruption is a key pathological feature of ischemic stroke, but its modulation by DHI under hyperlipidemic conditions remains unclear. This study aimed to investigate the protective effects and mechanisms of DHI in cerebral ischemia/reperfusion injury (CI/RI) under hyperlipidemia, focusing on BBB integrity and the Wnt/β-catenin signaling pathway. Methods: Rats were divided into control, ischemic, hyperlipidemic, and treatment subgroups to evaluate DHI’s dose-dependent effects and pathway specificity using DKK1 inhibition. Assessments included neurological scores, TTC and Nissl staining, TEM, and molecular analyses (qRT-PCR/Western blot/immunofluorescence/immunohistochemistry). Results: DHI significantly improved neurological function, reduced cerebral infarct size, and alleviated cortical damage. DHI treatment upregulated the expression of tight junction proteins (Claudin-5, Occludin, ZO-1) and downregulated MMP-9 expression. Mechanistically, DHI promoted the nuclear translocation of β-catenin and increased the expression of Wnt3α, p-GSK-3β, and Cyclin D1, thereby activating the Wnt/β-catenin pathway. Additionally, DHI treatment increased the count of NeuN-positive neurons, suppressed astrocyte activation, and markedly reduced IgG infiltration in the ischemic cerebral cortex. These effects were reversed by DKK1. Conclusions: The results indicate that DHI protects BBB integrity and alleviates CI/RI in hyperlipidemic rats independently of direct lipid-lowering activity. Specifically, DHI activates the Wnt/β-catenin pathway by enhancing β-catenin nuclear translocation, which in turn mediates the upregulation of tight junction proteins and suppression of MMP-9, ultimately preserving BBB integrity. These findings support its therapeutic potential in ischemic stroke with comorbid hyperlipidemia. Full article

Natural compounds are increasingly recognized as valuable sources of pharmacologically active agents for cancer therapy. Among them, plant-derived triterpenoids attract attention due to their structural diversity and broad biological activity. Roburic acid (RA), a tetracyclic triterpenoid, has previously been shown to exert antiproliferative effects in colorectal cancer (CRC) cells with limited cytotoxicity. In the present study, we investigated the cellular mechanisms underlying RA activity in CRC cells, focusing on cell cycle regulation, mitochondrial function, apoptosis, oxidative stress, and DNA integrity. RA treatment markedly suppressed CRC cell proliferation, resulting in G₀/G₁ cell cycle arrest and downregulation of key proliferation markers. Mitochondrial analysis revealed an early reduction in mitochondrial membrane potential (MMP) following RA exposure, indicating mitochondrial dysfunction. Importantly, these effects occurred in the absence of intracellular reactive oxygen species (ROS) generation and without induction of DNA strand breaks, demonstrating a non-pro-oxidant and non-genotoxic profile of RA. Apoptotic features were observed mainly at higher concentrations and after prolonged exposure and were strongly dependent on cell line and assay type. Overall, RA limits CRC cell growth predominantly through cytostatic mechanisms, including cell cycle arrest and mitochondrial modulation, while apoptosis is a secondary, context-dependent response. The lack of oxidative stress and genotoxicity distinguishes RA from many conventional cytotoxic agents and supports its further investigation as a non-genotoxic anticancer compound. Full article

Increasing evidence suggests that intratumoral microorganisms and their metabolites can modulate cancer initiation and progression. However, the composition and functional role of intratumoral bacteria in canine mammary tumors (CMTs) remain unclear. In this study, we investigated the functional significance of tumor-derived Staphylococcus in CMTs, focusing on its effects on the proliferation and migration of CMT-U27 cells. 16S rRNA sequencing revealed reduced alpha diversity in CMT tissues, with Staphylococcus pseudintermedius identified as the most frequently isolated species. Functional assays, including CCK-8, wound healing, RT-qPCR, and Western blot analyses, demonstrated that intratumoral Staphylococcus pseudintermedius significantly enhanced cellular proliferation and migration. Mechanistically, Staphylococcus pseudintermedius significantly upregulated the expression of TLR2, as well as the phosphorylation levels of PI3K, Akt and P70S6K. The inhibition of TLR2 using C29 suppressed the mRNA expression of VEGF, MMP9, MMP2, and EGFR. Collectively, these findings indicate that intratumoral Staphylococcus pseudintermedius promotes the proliferation and migration of CMT-U27 cells through activation of the TLR2/PI3K/Akt pathway, highlighting a functional link between tumor-associated bacteria and cancer progression. Full article

Background: Punica granatum L. (pomegranate) is a medicinal plant traditionally used for its antimicrobial and antioxidant effects. Recent evidence supports its expanding applications in dermatology and dermocosmetics. Purpose: This systematic review aimed to evaluate the skin-related biological activities of pomegranate extracts, identify the key bioactive compounds involved, and elucidate the underlying molecular mechanisms relevant to skin health and aging. Methods: A total of 732 studies were screened using AIReviewer clustering. Fifty-four original articles were selected on the basis of inclusion criteria prioritizing molecular evidence, in vitro and in vivo assays, and clinical relevance. Results: Pomegranate extracts exhibit a broad range of dermocosmetic properties, including antioxidant, anti-inflammatory, antibacterial, wound healing, moisturizing, photoprotective, and collagen-preserving effects. These effects are primarily attributed to ellagitannins (punicalagin and punicalin), ellagic and gallic acid, triterpenoids (oleanolic, maslinic, and asiatic acids), flavonoids (quercetin and catechins), anthocyanins, and fatty acids (punicic acid). Pomegranate extracts modulate oxidative stress by scavenging reactive oxygen species and upregulating Nrf2-mediated antioxidant pathways. They inhibit matrix metalloproteinases (MMP-1 and MMP-3), suppress proinflammatory cytokines (TNF-α and IL-6), and stimulate fibroblast proliferation, extracellular matrix remodeling, and hyaluronic acid synthesis. Their photoprotective activity provides enhanced UVB resistance and higher SPF values. Recent advances in fermentation and nanotechnology have been shown to increase the bioavailability and stability of compounds found in pomegranate, offering new formulation strategies. Conclusions: Pomegranates are a promising source of multifunctional phytochemicals with validated dermocosmetic applications. Their incorporation into advanced delivery systems may increase their therapeutic potential for skin protection, regeneration, and antiaging interventions. Full article

Artocarpin, a prenylated flavonoid isolated from Artocarpus altilis heartwood, has emerged as a promising multi-targeted bioactive compound for combating UV-induced skin aging. This review provides a comprehensive overview of the molecular mechanisms and photoprotective efficacy of artocarpin across in vitro, in vivo and clinical study, based on the peer-reviewed literature published between 2012 and 2025, retrieved from PubMed, Scopus, and Web of Science. Delivery strategies designed to overcome the inherent physicochemical limitations of artocarpin on skin penetration are also discussed. Artocarpin demonstrates antioxidant effects through both direct free radical scavenging and activation of the Nrf2-ARE pathway, providing sustained cellular defense. Its anti-inflammatory properties target multiple signaling cascades, including the NF-κB and MAPK pathways, effectively mitigating UV-induced inflammatory response. The compound maintains dermal matrix homeostasis by inhibiting matrix metalloproteinase-1 (MMP-1) expression while preserving collagen synthesis and fibroblast mechanical function. Additionally, artocarpin exhibits selective apoptosis modulation, being cytoprotective in normal keratinocytes while acting as pro-apoptotic in damaged or abnormal cells, thereby supporting tissue homeostasis. It also inhibits melanogenesis through anti-inflammatory mechanisms rather than direct tyrosinase inhibition. Furthermore, artocarpin has been shown to induce autophagic cell death in certain cell lines; however, its role in UV-induced skin damages remains to be clarified. Despite these promising biological activities, the poor water solubility (<0.1 mg/mL) and high lipophilicity (log P ≈ 5) of artocarpin significantly limit its skin penetration. Lipid-based delivery systems, including liposomes, transfersomes, ethosomes, and nanostructured lipid carriers (NLCs), are presented as effective strategies to enhance transepidermal delivery, with each system offering distinct mechanistic advantages. Further investigations should prioritize the safety of artocarpin within each delivery system, as well as the synergistic co-encapsulation with complementary natural antioxidants to simultaneously target multiple mechanisms involved in UV-induced skin damage, thereby broadening its application in the cosmeceutical industry. Full article

We investigate the potential of frequent repeat imagery acquired by the PlanetScope Dove small satellite constellation to overcome temporal and spatial limitations in automated surface topography mapping. While individual PlanetScope Dove stereo pairs produce low-quality Digital Surface Models (DSMs) with large height uncertainties, the high temporal frequency enables multiple DSMs to enhance accuracy through multiple-pair image matching. We present a fully automated SETSM framework by improving the quality of PlanetScope Dove DSMs based on SETSM Multi-Pair Matching Procedure (SETSM MMP). This framework enhances stereo pair quality through an optimized stereo pair selection by sequential conditional filtering and a Weighted Stereo Pair Index (WSPI). A novel inter-plane vertical coregistration, which minimizes scaling errors between single stereo pair DSMs, was developed to improve consistency and accuracy in DSM quality without reference surfaces. Applied to the cloud-obscured Pantasma crater region in Nicaragua, the optimized stereo pair selection automatically selects well-defined stereo pairs. The inter-plane vertical coregistration without existing reference surfaces achieves up to a 43% Root Mean Square Error (RMSE) reduction and 26% improvement in distribution within a 5 m vertical error. DSM quality correlated strongly with tile size, stereo pair convergence angle, asymmetric angle and terrain-dependent scale variability. The proposed framework provides fully automatic, high quality PlanetScope Dove DSMs without Ground Control Points (GCPs). Full article

Alterations in glutathione and its metabolism contribute to oxidative stress in COPD, but the role of S-glutathionylation (PSSG) and its major regulator glutaredoxin 1 (Grx1) remains unclear. This study investigated the Grx1/PSSG axis in sputum of COPD patients and its associations with lung function and inflammation, as well as Grx1 secretion in mouse models and in cell culture. In patients with an acute exacerbation, PSSG levels were significantly decreased in sputum, while Grx1 protein and total Grx activity were increased compared to stable COPD. No differences were observed between healthy smokers and stable patients. PSSG levels correlated negatively with sputum neutrophils, IL-8 and IL-1β, but positively with lung function parameters, whereas Grx1 showed the opposite pattern. Enhanced Grx1 levels were also detected in bronchoalveolar lavage fluid from mice exposed to cigarette smoke or chronic pulmonary inflammation. Moreover, epithelial cells and macrophages secreted Grx1 in response to pro-inflammatory mediators, and Grx1 modulated expression of MMPs by macrophages in vitro and in vivo. In conclusion, this study identifies the Grx1/PSSG redox axis as a potential important factor in COPD pathogenesis, especially during exacerbations. Further research should examine in more detail the intricate relation of extracellular Grx1 with lung function and inflammation. Full article

Carbon dioxide (CO₂) emissions resulting from natural gas flaring are significant contributors to atmospheric greenhouse gases, posing a substantial risk to the Earth’s climate by exacerbating global warming. As a response, both the oil industry and government authorities are actively exploring cost-effective strategies to address this issue through carbon capture, utilization, and storage (CCUS), as well as reducing natural gas flaring and CO₂ leaks in the oil fields to mitigate the adverse consequences of greenhouse gas emissions. This study presents a numerical investigation of CO₂ utilization for enhanced oil recovery (EOR) and associated CO₂ retention in unconventional reservoirs, using the Bakken Formation as a representative case. A compositional reservoir model is developed to simulate CO₂ Huff-n-Puff (HnP) processes in a fractured horizontal well. The model incorporates dual-porosity and dual-permeability formulations, fluid–rock interactions, and an equation-of-state-based compositional framework to capture multiphase flow behavior. Key operational parameters, including reservoir pressure, injection rate, injection duration, and CO₂ molecular diffusion, are systematically evaluated to assess their impact on oil recovery and CO₂ retention. The results show that lower bottom-hole pressures enhance oil recovery through increased drawdown, while operating pressures near the minimum miscibility pressure (MMP) improve CO₂ solubility and overall retention. Extended injection durations and higher diffusion coefficients increase CO₂ dissolution in the oil phase but exhibit diminishing marginal benefits beyond an optimal injection time. The study quantifies residual and solubility trapping mechanisms during the operational timeframe of CO₂-EOR and provides mechanistic insights into optimizing CO₂-HnP performance in tight formations. The proposed framework establishes a technical basis for integrating CO₂-EOR with emission mitigation strategies in unconventional reservoirs. Full article

This study investigated the effects of different PRP doses and application strategies on sperm quality in goats during cryopreservation. Semen samples were collected weekly from six Boer goats and treated with PRP either by means of pre-incubation or supplementation of the semen extender at concentrations of 10, 20, and 40 × 10⁶ platelets/mL. Computer-assisted sperm analysis (CASA) was performed after equilibration and again after thawing to assess sperm motility parameters, including progressive motility. Post-thaw sperm functional integrity was further evaluated using flow cytometry, including assessments of plasma membrane integrity, acrosome integrity, high mitochondrial membrane potential (hMMP), sperm viability, oxidative stress, and DNA integrity. The results demonstrated that pre-incubation with PRP at 10 × 10⁶ platelets/mL (pre-PRP10) yielded the most pronounced improvements in total and progressive motility after thawing, as well as in plasma membrane integrity, viability, and mitochondrial activity, while significantly reducing oxidative stress and DNA fragmentation compared with other PRP doses and application strategies. Supplementation of the extender with PRP at 20 × 10⁶ platelets/mL also showed favorable effects on functional sperm parameters; however, it did not result in significant improvements in oxidative stress or DNA fragmentation. In contrast, the highest PRP dose (40 × 10⁶ platelets/mL) did not confer additional benefits. None of the PRP treatments improved post-thaw acrosome integrity. In conclusion, these findings highlight the importance of PRP dose optimization and direct sperm–PRP interaction, identifying pre-incubation with PRP at 10 × 10⁶ platelets/mL as the most effective approach for enhancing post-thaw sperm quality in goats. Full article

Sweet potato (Ipomoea batatas L.) is cultivated globally and generates a large quantity of plant-derived residues, including leaves, stems, and non-commercial cull roots, which remain insufficiently utilized despite their potential functional value. Although the antioxidant properties of sweet potato leaves have been reported, comparative investigations of different plant parts evaluated under the same experimental conditions, particularly in relation to skin-associated biological functions, are still limited. In this study, aqueous extracts prepared from sweet potato leaves, stems, and cull roots were obtained using a food-grade extraction process suitable for practical application. The phenolic composition and biological properties of the extracts were comparatively analyzed. Antioxidant capacity was examined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, ferric reducing antioxidant power (FRAP), as well as assays associated with superoxide dismutase (SOD)-like and catalase-related activities. Skin-related biological responses were further evaluated by measuring elastase and collagenase inhibition, type I procollagen synthesis, and matrix metalloproteinase-1 (MMP-1) secretion in CCD-986Sk human dermal fibroblasts. Among the tested samples, the leaf-derived aqueous extract exhibited a higher total phenolic content, greater accumulation of chlorogenic acid, and stronger antioxidant responses compared with stem and cull root extracts. In addition, the leaf extract showed more pronounced effects on collagen metabolism, including enhanced procollagen synthesis and reduced MMP-1 secretion, while maintaining acceptable cell viability within the tested concentration range. Overall, these results demonstrate clear tissue-dependent functional differences among sweet potato residues and indicate that leaf-derived extracts represent a promising functional material for skin-related and cosmetic applications. Full article

Breast cancer is the most common malignant tumor among women worldwide, and its occurrence is closely associated with long-term exposure to environmental pollutants. Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants widely present in the living environment. Epidemiological studies indicate that exposure to PAHs increases the risk of breast cancer. PAH derivatives exhibit stronger toxicity or endocrine-disrupting activity than their parent compounds; however, research on their specific effects and mechanisms in breast cancer cells remains limited. For this purpose, this study selected 3-Hydroxybenz[a]anthracene, a PAH derivative with potential estrogenic activity, as the target compound. Using the estrogen receptor-positive breast cancer cell line MCF-7 as the model, we performed EdU staining, colony formation assays, scratch healing assays, Transwell invasion assays, and apoptosis assays and preliminarily examined changes in relevant signaling proteins via Western blot. Results indicate that 3-Hydroxybenz[a]anthracene promotes proliferation and migration in MCF-7 cells while inhibiting apoptosis under certain conditions, but it has no effect on cell invasion. Mechanistically, it upregulates key proteins including AKT, c-Myc, E-Cadherin, Vimentin, MMP2, MMP9 and Bcl-2 while downregulating p-AKT expression. This study confirms through in vitro experiments that 3-Hydroxybenz[a]anthracene exhibits estrogen-like effects and modulates malignant behavior in breast cancer cells by regulating relevant signaling pathways. These findings provide experimental evidence for further evaluating the potential role of this environmental contaminant in breast cancer initiation and progression. Full article

Sphingolipids (SL) are essential structural and bioactive components of cell membranes, remarkably involved in inflammatory signaling and membrane dynamics. Dysregulation of SL metabolism contributes to pathological inflammation and cellular stress. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (FXT), are known inhibitors of acid sphingomyelinase (aSMase), although their impact on macrophage SL remodeling and inflammatory responses remains unclear. Here, we investigated the modulation of FXT on SL species composition and inflammatory activation in THP-1-derived macrophages stimulated with inactivated SARS-CoV-2 particles, which is a model of viral-induced inflammation. Sphingolipidomic profiling revealed that FXT pre-treatment markedly reduced ceramide (Cer) species while increasing sphingomyelin (SM) and sphingosine-1-phosphate (S1P) levels, consistent with inhibition of the aSMase-Cer axis. These changes were accompanied by attenuation of proinflammatory components, including interleucin (IL)-6, IL-1β, and matrix metalloproteinase (MMP)-9, indicating that SL remodeling correlates with reduced macrophage activation. Despite pronounced alterations in membrane lipid composition, the quantification of extracellular vesicles (EVs) released by FXT-treated macrophages remained unchanged, however the EVs size distribution was smaller compared to non-treated cells. Altogether, our findings demonstrate that FXT reshapes SL metabolism and lipid membrane composition, thereby diminishing macrophage activation without affecting EVs biogenesis. This study emphasizes the immunometabolic role of SL on membrane reprogramming as a mechanism by which pharmacological aSMase inhibition modulates viral inflammation responses. Full article

Acute myocardial infarction can lead to ventricular remodelling, which affects ventricular function and survival prognosis. Therefore, improving ventricular remodelling has become a focus of research. This study aims to investigate the effect of Acanthopanax senticosus leaf saponins (ASS) on cardiac function and left ventricular remodelling in a rat model of myocardial infarction, and explore its potential mechanism. Coronary artery ligation was used to establish a rat model of myocardial infarction, and ASS was administered orally for 28 days. After 28 days, cardiac function was evaluated by hemodynamic detection, and the levels of myocardial enzymes, inflammatory cytokines, oxidative stress and fibrosis-related factors were detected. The degree of fibrosis was evaluated by immunohistochemical detection of collagen I and collagen III deposition. The expression levels of MMP-2, MMP-9 and TIMP-1 were checked by Western blot. Compared with the Sham group, the cardiac function of the Model group was significantly impaired, and ASS administration could improve this change. In addition, compared with the Model group, ASS significantly alleviated myocardial injury, reduced the release of inflammatory cytokines TNF-α and IL-β, improved the oxidative stress state, reduced the release of NT-propBNP, Ang II, ET-1 and inhibited myocardial fibrosis. Moreover, ASS could reduce the expression of MMP-2 and MMP-9, and increase the expression level of TIMP-1. In conclusion, ASS may inhibit left ventricular remodelling by reducing the expression of MMP-2 and MMP-9. Full article