Search Results (6,134)

With the rapid development of global aquaculture, the frequent occurrence of fish diseases has had a serious impact on the efficiency of aquaculture and the ecological environment. Antimicrobial peptides, as a kind of natural immune active substance existing in organisms, participate in innate immunity and adaptive immunity. Due to their extensive antibacterial properties and low toxicity, they have gradually become a hot topic in scientific research. This article reviews the classification, tissue distribution, mechanism of action, extraction, and synthesis techniques of antimicrobial peptides (AMPs) derived from fish, as well as their applications in disease prevention in aquaculture, product preservation, and antibiotic substitution. Although antimicrobial peptides are expected to become alternatives to antibiotics, challenges such as environmental stability, production costs, and regulatory frameworks remain to be addressed. This article holds that antimicrobial peptides derived from fish are a feasible strategy for sustainable aquaculture. The future development direction lies in biotechnology-driven optimization, carrier innovation, and combined application with traditional antibiotics. Full article

Bone fractures are often treated using invasive methods involving osteosynthesis plates. These plates are typically made of metallic materials such as titanium or steel. However, their high stiffness relative to bone tissue can contribute to the undesirable stress shielding effect. Therefore, there is a growing interest in developing new, more friendly biocompatible materials with improved mechanical properties. A promising candidate is a polymer composite made of high-strength PEEK reinforced with carbon fibers, which was the subject of this study. The aim of this work was a numerical analysis of osteosynthesis plates made from conventional materials and from PEEK-CF composite. The study also included geometric modification of the composite plate using topology optimization methods to reduce the stress shielding effect. The obtained results confirmed that the use of a geometrically optimized composite osteosynthesis plate can reduce bone unloading and ensure an appropriate stress distribution in the implant–bone system. Full article

Background/Objective: Basal cell carcinoma (BCC) is the most common cutaneous malignancy, arising from epidermal basal cells or the outer root sheath of the pilosebaceous unit. Despite its generally indolent clinical behavior, BCC exhibits substantial histopathological heterogeneity, which may reflect underlying biological differences among its subtypes. This study aimed to evaluate the expression of Wnt/β-catenin pathway components and tumor-associated markers—including COX-2, Ki-67, tryptase, CD1a, and WNT3A—across different histopathological subtypes of BCC. Methods: This retrospective cross-sectional study included 100 formalin-fixed paraffin-embedded (FFPE) BCC specimens retrieved between January 2006 and September 2015. After the exclusion of three cases due to inadequate tissue quality, the tumors were classified into nodular (n = 60), infiltrative (n = 16), superficial (n = 9), and other subtypes (n = 12). The immunohistochemical expressions of COX-2, Ki-67, CD1a, intratumoral and peritumoral tryptase, β-catenin, and WNT3A were assessed and compared among the BCC subtypes. Results: No significant differences were observed among the BCC subtypes regarding age or sex distribution. The expression levels of COX-2, Ki-67, CD1a, and mast cell-associated markers (intratumoral and peritumoral tryptase) did not differ significantly among the groups (all p > 0.05). Conversely, β-catenin expression was significantly higher in the infiltrative subtype compared with the other histological variants (p = 0.001). WNT3A immunoexpression was uniformly negative across all evaluated cases. Conclusions: Most of the evaluated immunohistochemical markers did not differentiate among the BCC subtypes. However, the significantly increased β-catenin expression observed in the infiltrative subtype suggests a potential association with tumor growth patterns rather than serving as a specific discriminative marker, thereby highlighting the biological heterogeneity of BCC. Although WNT3A expression was uniformly negative in all cases, this finding should be interpreted cautiously and does not allow for definitive conclusions regarding its role in Wnt pathway activation. Overall, these results support the need for further investigation into the Wnt/β-catenin pathway heterogeneity in BCC. Full article

Anticontractile factors secreted by perivascular adipose tissue (PVAT) play an important role in regulating vascular tone. This process is driven by the neurotransmitter norepinephrine (NE), but recent data show that adrenergic innervation in PVAT is sparse. How limited innervation might initiate broad responses through PVAT depots remains unknown. Here, we used Ca²⁺ imaging with genetically encoded sensors, selective drugs, immunolabeling and a conditional ablation model to test the hypothesis that gap junction coupling among PVAT adipocytes contributes to how signals initiated by NE are distributed through PVAT depots. Despite exhibiting differing sensitivities to NE, adipocytes in aortic and mesenteric PVAT and in white adipose tissue displayed robust expression of the gap junction protein connexin-43 (Cx43). Blocking gap junction coupling with the drug carbenoxolone (Cbx) limited NE-evoked Ca²⁺ responses among adipocytes, while blocking Cx43 hemichannels with the mimetic peptide 43Gap26 had no significant effect. Fluorescence recovery after photobleaching (FRAP) in mPVAT was decreased in the presence of Cbx, suggesting impaired gap junction communication. Wire myography recordings of mesenteric arteries showed that the EC₅₀ for NE was higher in samples with intact PVAT than those without; however, this effect was not significantly different in samples from mice that lacked Cx43 in adipocytes. Analysis of multiple connexins showed that adipocytes upregulate Cx26 gene expression when Cx43 is deleted. These observations support the conclusion that Cx43-mediated gap junction coupling among PVAT adipocytes contributes to distributing signals initiated by NE; however, how this mechanism contributes to regulating vessel constriction remains unclear. This, and how potential compensatory mechanisms are enacted in adipocytes lacking Cx43, should be addressed in future work. Full article

In impedance imaging, the incompatibility and nonlinearity of the inverse problem lead to problems such as blurred boundaries and severe artifacts in the reconstructed images, making it difficult to meet the requirements for precise identification of multi-layer tissue structures in the legs. To this end, this paper proposes a post-processing algorithm for leg EIT that integrates the boundary attention mechanism, with a Wasserstein generative adversarial network as the training framework, cyclic residual U-Net as the generator, and the boundary attention module embedded in the RecurrentBlock. This leads to adaptive enhancement of the ability to extract organizational boundary features through a three-path fusion of spatial attention, channel attention, and learnable Laplacian edge enhancement. A leg anatomy prior constraint loss function was designed, integrating six constraints—pixel loss, edge loss, hierarchical tissue constraint, total variation regularization, structural similarity loss, and histogram matching—to guide the reconstruction results to conform to the multi-layered tissue structure features of the leg. A simulation dataset of leg sections containing multiple tissues such as skin, fat, muscle, bone, blood vessels, and nerves was constructed, and the pre-reconstructed images were obtained using the hybrid total variation regularization algorithm as the network input. The simulation results show that, under noise-free and different signal-to-noise ratio conditions, the proposed BAM-R2UNet algorithm achieves the best performance in RMSE, SSIM and PSNR metrics compared with HTV, DnCNN and standard U-Net algorithms, can remove artifacts, accurately restore the boundary and conductivity distribution of leg tissues, and has stronger anti-noise robustness. Full article

Polygonum capitatum (PC) is an ethnomedicine with reported antibacterial and anti-inflammatory activities and has been clinically used in urinary tract infection (UTI)-related disorders. However, its in vivo exposure characteristics and metabolically associated therapeutic mechanisms in acute pyelonephritis (AP) remain insufficiently understood. To address this issue, this study aimed to evaluate the therapeutic effects of PC in an Escherichia coli (E. coli)-induced rat model of AP and to explore constituents and metabolic pathways associated with its activity. Different PC extracts were screened for antibacterial and anti-inflammatory activities, and the 70% ethanol extract was selected for further study. Seven major compounds were quantified by HPLC. In AP rats, the pharmacokinetic profiles of these compounds in plasma and the renal cortex were analyzed by microdialysis-coupled HPLC-MS/MS. Pharmacodynamic evaluation included urinary bacterial load, urinalysis, renal function, inflammatory cytokines, and renal histopathology. Exploratory PK–PD analysis, untargeted renal metabolomics, and targeted metabolomics of the tryptophan–kynurenine (Trp–Kyn) pathway were also performed. The 70% ethanol extract of PC exhibited the strongest antibacterial and anti-inflammatory activities. The total content of seven active compounds was 3.85%, with gallic acid being the predominant compound (3.42%). Pharmacokinetic analysis revealed that gallic acid, protocatechuic acid, methyl gallate, and quercitrin achieved relatively high systemic exposure and renal distribution. In AP rats, the pharmacokinetic profiles of several compounds were altered, with increased plasma exposure of protocatechuic acid, vanillic acid, ethyl gallate, and syringic acid, while protocatechuic acid also showed higher exposure in the renal cortex. PC treatment reduced urinary bacterial load, improved renal function and urinalysis parameters, alleviated histopathological injury, and decreased inflammatory mediator levels, particularly in renal tissue. Exploratory PK–PD correlations were observed between several compounds and selected pharmacodynamic indicators. Metabolomic analysis suggested disturbances in glycerophospholipid metabolism and the Trp–Kyn pathway in AP rats, some of which were partially reversed after PC treatment. PC showed antibacterial and anti-inflammatory effects in AP rats. Gallic acid, protocatechuic acid, methyl gallate, and quercitrin may be candidate constituents associated with the therapeutic effects of PC, while modulation of glycerophospholipid metabolism and the Trp–Kyn pathway may be involved in its action against AP. These findings provide preclinical pharmacological evidence supporting the therapeutic potential of PC in AP. Full article

The SHI-related sequence (SRS) transcription factors are vital plant regulators involved in development and stress responses. Given that biosynthesis of the valuable anticancer drug camptothecin (CPT) in Camptotheca acuminata is influenced by developmental and environmental cues, we hypothesized that SRS genes play key regulatory roles in the CPT biosynthetic pathway. To test this hypothesis and characterize the SRS family in this medicinally crucial plant, we performed a genome-wide identification of CaSRS genes and focused our analysis on their potential functional link to CPT biosynthesis. Eight distinct CaSRS genes were identified and classified into three phylogenetic subgroups. Comprehensive characterization—including phylogenetic relationships, gene structures, conserved motifs, chromosomal distribution, and synteny with Arabidopsis thaliana, Catharanthus roseus, and Ophiorrhiza pumila—provided foundational insights into the family. Crucially, integrated analysis of multi-tissue expression profiles revealed significant correlations between specific CaSRS genes (CaSRS2, CaSRS3, and CaSRS5) and key CPT biosynthetic genes. Promoter cis-regulatory element analysis further indicated that these CaSRS genes possess binding sites associated with stress and hormone responses known to modulate CPT production. These convergent lines of evidence strongly implicate CaSRS2, CaSRS3, and CaSRS5 as potential regulators of CPT biosynthesis. Collectively, this study first identifies specific CaSRS gene candidates for functional validation and provides a crucial foundation for understanding the role of the CaSRS family in regulating CPT biosynthesis in C. acuminata. Full article

Systematic surveillance of World Organization for Animal Health (WOAH)-listed protozoan parasites is essential for maintaining the sanitary status of seafood exports and detecting the introduction of exotic pathogens into coastal ecosystems. In 2023, we examined wild Mediterranean mussels Mytilus galloprovincialis and Pacific oysters Crassostrea gigas collected from small harbors adjacent to ten major trading ports along the west and south coasts of Korea to assess the occurrence of WOAH-listed protozoan parasites and emerging Perkinsus species. A total of 1080 mussels and 1080 oysters from 18 sites were sampled in spring and autumn, and gill and digestive gland tissues were pooled from six individuals for DNA extraction. Species-specific PCR assays targeting Perkinsus marinus, P. olseni, P. beihaiensis, Bonamia ostreae, B. exitiosa, and Marteilia refringens were performed using previously validated primer sets and positive controls. All PCR assays were negative for the six protozoan parasite species in both host species across all sampling sites, indicating no detectable infections in port-adjacent wild mussel and oyster populations during the survey period. These negative results contrast with recent reports of P. marinus in wild C. gigas and B. ostreae in Ostrea denselamellosa on the west coast of Korea, suggesting that infections may currently be focal, transient, and host-specific rather than widespread in port-associated M. galloprovincialis and C. gigas populations. The present study provides baseline data on the distribution of protozoan parasites in bivalves inhabiting high-risk harbor environments and underscores the need for continued surveillance of transboundary shellfish diseases that is closely coupled with environmental monitoring. Full article

Serving as central signalling organelles and hubs of metabolism, mitochondria are essential for cellular homeostasis. Mitochondrial disease can arise from mutations to nuclear or mitochondrial DNA, which result in disruptions to normal mitochondrial function. This generates a suite of rare disorders which are multi-system and often fatal. Variable tissue distribution of mitochondria, alongside a high degree of heterogeneity in associated phenotype, has resulted in an inadequate understanding and characterisation of mitochondrial disease. Addressing this issue is therefore crucial for better clinical management and patient outcomes. Cholesterol dyshomeostasis is a potential pathological hallmark of numerous mitochondrial diseases. Cholesterol is an essential lipid and bioactive compound involved in numerous mitochondrial and cellular processes. A growing number of studies have reported perturbations to cholesterol biosynthesis, cholesterol import, and cholesterol ratios in cell and animal models and individuals with mitochondrial disease, suggesting it could be a unifying feature of these disparate and variable disorders. This review summarises the current experimental evidence for the role of cholesterol dyshomeostasis in mitochondrial disease. It will further discuss reports of statin intolerance, generally attributed to off-target action on mitochondrial structures, in the context of this evidence. Ultimately, the necessity of further integrative clinical and experimental studies exploring the potential of cholesterol dyshomeostasis as a pathological hallmark of mitochondrial disease will be highlighted. Full article

Introduction: Microplastic (MP) contamination can endanger marine ecosystems and indirectly affect the well-being of humans through the ingestion of marine species. While most research investigates the digestive system, such as the gills and gastrointestinal tract of fish, it still fails to address a major oversight in understanding MP deposition in edible tissues, which is the primary route of human exposure. The differences in contamination levels among pelagic, demersal, and benthic fish in Malaysian waters remain poorly understood. This preliminary study uses Laser Direct Infrared Imaging (LDIR), a new, high-resolution, automated technique, to examine synthetic MP contamination in the edible portion of fish. Materials and Methods: The MPs were extracted from the edible tissue of three fish species representing pelagic (Fish A), benthic (Fish B), and demersal (Fish C) using KOH and sieved onto a gold mesh filter before analysis using LDIR. Results and Discussion: LDIR identified 162 MP particles, revealing clear differences by polymer type and habitat. Pelagic species mostly contained polyethylene (PE) and rubber (n = 8). Demersal species had mostly polyethylene terephthalate (PET) with small amounts of PE and rubber (n = 57). Benthic species showed the highest load, dominated by PET and polypropylene (PP) (n = 97). The morphological assessment of the MPs indicated that the polymers in pelagic fish were smaller, with an area of 2047.82 µm² and a circularity range of 0.14–0.74, indicating consistent shape. Conversely, MPs are irregular and larger in benthic fish, with areas up to 38,837.50 µm² and circularities ranging from 0.02 to 0.81. This pattern reflects specific accumulation related to habitat and potential environmental degradation processes. Conclusions: This preliminary study demonstrates the effectiveness of LDIR for detecting MPs in edible fish tissues. The findings provide a fundamental dataset on MP contamination in edible tissue and emphasize its distribution across ecological zones. Nevertheless, broader research is required to substantiate these data and assess the implications of MP contamination for the environmental stability of human and marine well-being. Full article

Regulated cell death is essential for development, tissue homeostasis, host defense, and disease. Beyond apoptosis, it is now clear that other forms of cell death, including ferroptosis, pyroptosis, and necroptosis, also contribute to pathology, often in interconnected rather than isolated ways. Within this broader framework, the transcriptional intermediary factor 1 (TIF1) family, comprising TRIM24, TRIM28, TRIM33, and TRIM66, has emerged as an important group of regulators linking stress adaptation, cell-state control, and cell death susceptibility. Although these proteins belong to the same family, they influence cell death through distinct and context-dependent mechanisms. Across the TIF1 family, apoptosis is by far the most extensively studied cell death phenotype, whereas links to ferroptosis, pyroptosis, and necroptosis remain more limited, more context dependent, and more unevenly distributed across individual members. Cell death often becomes evident when TIF1-dependent stress-buffering programs are disrupted, highlighting both their biological importance and potential therapeutic relevance. At the same time, family-level differences are emerging, while the underlying mechanisms remain incompletely understood, and recent advances in this field have not been synthesized. This review summarizes how TIF1 family members intersect with different cell death programs, discusses emerging translational opportunities and challenges, and highlights key mechanistic questions for future study. Full article

Background/Objectives: Platelet-rich fibrin (PRF) is widely used in regenerative medicine and dentistry because of its ability to deliver growth factors and cellular components that support tissue healing. However, accurate quantification of platelets and leukocytes within PRF matrices remains challenging, as indirect subtraction-based methods may not reliably reflect the true cellular composition. This study aimed to apply a direct fibrinolytic digestion–flow cytometry approach for precise cellular quantification and to systematically evaluate the effects of different centrifugation protocols on PRF cellular composition and fibrin architecture. Methods: PRF clots were generated using high-speed protocols (leukocyte- and platelet-rich fibrin [L-PRF] and concentrated growth factors [CGF]) and low-speed protocols (advanced PRF [A-PRF] and A-PRF+). Cellular content was quantified using a fibrinolytic digestion-based approach with tissue plasminogen activator, followed by flow cytometry analysis. Histological evaluation was performed to assess fibrin architecture and cellular distribution. Results: L-PRF and CGF exhibited significantly greater platelet enrichment than A-PRF. T-lymphocyte counts were elevated across all PRF groups, with significantly higher levels observed in L-PRF and CGF than in A-PRF. Monocyte and neutrophil levels were reduced following PRF preparation; however, A-PRF retained significantly higher neutrophil levels than CGF, whereas B-lymphocyte levels showed a moderate increase without significant intergroup differences. Histologically, high-speed protocols produced pronounced cellular stratification and denser fibrin networks, whereas low-speed protocols demonstrated a more homogeneous leukocyte distribution within a porous fibrin matrix. Conclusions: Centrifugation protocols significantly influence PRF cellular composition and fibrin architecture. The direct fibrinolytic digestion–flow cytometry approach provides a reliable method for accurate cellular quantification and may facilitate the standardization and optimization of PRF preparation protocols for regenerative applications. Full article

Woody plants in managed and natural ecosystems are increasingly exposed to arthropod pest pressure, posing challenges for sustainable plant protection. This study evaluates trunk injection as a pest management strategy in woody species, with emphasis on plant-mediated processes shaping interactions between host plants and herbivorous arthropods. Two experimental systems were investigated: a greenhouse experiment with Gleditsia triacanthos and a field experiment with Quercus petraea. Systemic active ingredients (acetamiprid and abamectin) were applied using both experimental and professional injection devices, and their effectiveness was assessed against Tetranychus urticae and a complex of foliar-feeding insects. In the greenhouse experiment, trunk injection reduced T. urticae populations compared with untreated controls and soil drench treatments, with reductions of 55.6–58.4% for larvae, 65.7–67.5% for eggs, and 28.7% for adults, although foliar application achieved higher suppression (up to 81.2% for eggs). In the field experiment, treatments reduced leaf discoloration (from 16.3% in control to 1.45–3.80%) and skeletonization (from 15.1% to 9.95–12.7%), with more moderate effects on defoliation. Differences among feeding guilds suggest that responses to systemically distributed compounds depend on feeding behavior and canopy position. Both pressurized and non-pressurized methods enabled uptake and translocation of active compounds within plant tissues. Localized injuries were observed at injection points, including internal necrosis. Overall, trunk injection represents a viable approach for pest management in woody plants, highlighting the role of plant-mediated processes in shaping treatment outcomes under contrasting conditions. Full article

Background/Objective: Myocardial fibrosis (MF) is a prevalent pathological endpoint in various heart diseases, characterized by extracellular matrix (ECM) dysregulation and oxidative stress. Hyperoside (Hyp) plays a role in regulating cardiac oxidative stress and fibrosis. This study aimed to elucidate whether Hyp regulates isoproterenol (ISO)-induced MF in mice by modulating the GATA4/HIF-1α signaling pathway and reducing oxidative stress. Methods: The binding affinity of Hyp to GATA4 and HIF-1α was assessed through molecular docking and dynamics simulation. The MF model of mice was established by subcutaneous injection of ISO. Cardiac function was measured by echocardiography. Myocardial injury and collagen deposition were examined using H&E and Sirius red staining. Levels of fibrosis markers, oxidative stress indicators, and GATA4/HIF-1α pathway indicators in serum and heart tissue were quantified by ELISA, Western blot, RT-qPCR and flow cytometry. The distribution of myocardial marker proteins was visualized by immunofluorescence and immunohistochemistry. Results: Molecular docking revealed high binding affinity of Hyp to GATA4 and HIF-1α (binding energies < −5.0 kcal·mol⁻¹), and dynamics simulation showed that the complex’s structure remained stable over 100 nanoseconds (RMSD < 0.1 nm). High-dose Hyp (36 mg/kg) significantly improved cardiac function, myocardial injury, collagen deposition, and inflammatory infiltration in MF mice. Molecularly, Hyp effectively reduces oxidative stress and fibrosis through upregulating GATA4 and downregulating HIF-1α. Conclusions: Hyp suppresses oxidative stress by activating the GATA4/HIF-1α pathway, presenting a promising therapeutic target for the treatment of MF. Full article

Objective: The existing work was designed to appraise whether Secukinumab diminishes acute kidney injury in a Cisplatin- induced rat model and to explore the potential underlying mechanisms for this protective effect. Methods: In vivo study, rats were distributed haphazardly into five sets (six animals in each group): control, Secukinumab control, Cisplatin (8 mg/kg, a single dose, intraperitoneally (IP)), and two pretreated groups; Secukinumab (10 and 20 mg/kg single subcutaneous (SC) injection) + Cisplatin. Blood samples and kidney tissues were gathered and analyzed histopathologically and biochemically. In vitro investigation, MCF-7 human breast cancer cells were treated with Cisplatin alone with Secukinumab, and cell viability (MTT assay), combination index, and apoptosis-related markers were analyzed. Results: Secukinumab administration lowered serum levels of BUN, creatinine and LDH with marked elevation in renal TAC and a significant reduction in MDA, iNOS, KIM-1 and NGAL compared to Cisplatin. Additionally, Secukinumab pre-treatment markedly suppressed the inflammatory process and enhanced autophagy, reflected by elevated AMPKα1, SIRT1, and Beclin-1, accompanied by reduced P38 MAPK and NF-κB p65 (Phospho-Ser536) levels and expression levels of IL-6 and P62/SQSTM1 in kidney tissues, contrasted with the Cisplatin group. Secukinumab administration effectively protected against kidney injury, and histopathological examinations of the kidneys confirmed these results. On the other hand, in vitro study results revealed that the combination of Cisplatin and Secukinumab had a synergistic cytotoxic effect and an enhancing effect on the apoptotic pathway (increased P53 and BAX and decreased BCL-2). Secukinumab effectively protects against Cisplatin- induced acute kidney injury by decreasing oxidative stress, inflammation, and enhancing autophagy. Additionally, it synergizes with Cisplatin in vitro to promote cancer cell apoptosis, highlighting its dual reno-protective and anticancer potential. Full article