Bioimpacts最新文献

Vitiligo, a chronic autoimmune disorder characterized by the presence of depigmented skin patches, remains a therapeutic challenge due to its multifactorial pathogenesis and the absence of highly effective treatment options. Although the exact etiology of vitiligo is not fully understood, factors such as genetic factors, oxidative stress, autoimmunity, and inflammation are implicated in the destruction of melanocytes. Current therapeutic strategies primarily focus on modulating immune responses and alleviating oxidative stress. Conventional treatments, including topical corticosteroids, phototherapy, and immunosuppressive agents, often exhibit limited efficacy and are associated with significant side effects, limiting their long-term application. In recent years, nanotechnology has emerged as a transformative approach in drug delivery systems, offering precise targeting, enhanced drug bioavailability, and minimized systemic toxicity. Nanocarrier-based systems especially lipid-based nanoparticles (LNPs) effectively address critical barriers in vitiligo treatment, such as poor drug solubility, rapid degradation, and inadequate skin penetration. Moreover, controlled drug release mechanisms offered by LNPs ensure sustained therapeutic drug levels at the target site, improving efficacy and reducing the frequency of administration. This review provides an overview of vitiligo, its pathogenesis, and the limitations of conventional treatments while highlighting recent advancements in LNPs-based drug delivery systems as a promising strategy for the effective management of vitiligo.

Introduction: Enzyme-mimic nanomaterials, or nanozymes, have received much attention in fundamental and practical research. Laccases are crucial for environmental remediation and biotechnology. Inspired by the structure of the active site and the electron transfer mechanism of laccase, a simple laccase-like platform was designed in this work.

Methods: In this work, ovalbumin (OVA) was isolated and purified from hen egg white and conjugated with the transition metal ion (Cu²⁺), resulting in a soluble biopolymer (OVA‒Cu complex). Using a colorimetric method based on guaiacol oxidation, the catalytic performance of the complex was assessed, and its laccase‒like activity was verified.

Results: The kinetic parameters (K_m and V_max values) of the laccase‒mimic complex were calculated to be 0.026 mM and 0.7 μM min^-1, respectively. The prepared complex showed excellent catalytic activity with a similar K_m value to the natural laccase enzyme at the same mass concentration. Analysis of the synthesized system's capacity to decolorize malachite green (MG) showed its strong decolorizing potential. The outcomes demonstrated that MG can be degraded up to 84% in the presence of the OVA‒Cu complex in one hour. The decolorization metabolites were tested for toxicity against Escherichia coli and Staphylococcus aureus. The results demonstrated that less hazardous metabolites were produced after degrading MG by the OVA‒Cu complex. In addition, a 5:3:1 artificial neural network (ANN) was created to predict the decolorization efficiency (DE (%)) of MG.

Conclusion: Based on these results, it is evident that the OVA‒Cu complex has the potential to take the role of natural laccases in a variety of biosensing, environmental protection, and biotechnology applications.

Introduction: Intrahepatic cholangiocarcinoma (IH-CCA) is a malignancy characterized with limited response to standard chemotherapeutic strategies due to development of drug resistance. We aim to investigate new immune-therapeutic strategy through using AUNP-12 as an immune checkpoint blocker in chemically induced IH-CCA mice model.

Methods: Mice were randomly divided into 2 groups; normal control group and disease group. The disease group was further subdivided into 5 subgroups assigned according to treatment modality. The Immunotherapeutic mechanism of AUNP-12 was investigated through analysis of PD-1/PD-L1 levels and IFN-γ Levels in the tumor microenvironment. Immunohistochemical analysis of CD3⁺T lymphocytes and TGF-β was performed.

Results: We reported that AUNP-12 significantly decreased levels of PD-1/PD-L1 at the site of tumor with subsequent activation of CD3⁺T lymphocytes that secrete IFN-γ which specifically lysis tumor cells. AUNP-12 also acts through downregulation of TGF-β signaling in IH-CCA mice group treated with AUNP-12.

Conclusion: Our data indicated that AUNP-12 effectively harbors IH-CCA progression and improves the survival rate of mice. AUNP-12 acts as an immune check point blocker that specifically inhibits PD-1/PD-L1 binding, activates cytotoxic T-lymphocytes, and downregulates TGF-β signaling pathway.

[This corrects the article DOI: 10.34172/bi.30427.].

Hepatocellular carcinoma (HCC) is the most prevalent type of primary liver cancer, accounting for roughly 90% of all liver malignancies worldwide, and remains the leading cause of cancer death worldwide. Cirrhosis, viral hepatitis, non-alcoholic fatty liver disease (NAFLD), or liver injuries caused by alcohol are all chronic diseases that have a close association with the pathogenesis of HCC. A key factor in the progression of these diseases to HCC is the activation of the epidermal growth factor receptor (EGFR) signalling pathway. The ErbB family of receptor tyrosine kinases, which includes EGFR, is essential for inflammation, cell division, and liver regeneration. In HCC, EGFR expression and hyperactivation are closely associated with tumor growth, metastasis, and patient prognosis. This review explores the structural and functional aspects of EGFR, its signalling mechanisms in hepatocellular proliferation and apoptosis, its role in liver fibrosis, and the transition from chronic liver injury to advanced HCC. Moreover, crosstalk between EGFR-mediated pathways and other signalling pathways, such as PI3K/AKT/mTOR and MAPK/ERK, contributes to resistance to targeted therapies, suggesting that molecular regulation needs to be improved in strategies targeting EGFR and its downstream pathways.

Introduction: In this study, we utilized human endometrial mesenchymal stem cells (EnMSCs), along with a novel fibrous nanocomposite scaffold made of polyacrylonitrile/metal-organic-framework (PAN/MOF-Cu) for bone tissue engineering. Additionally, we investigated the impact of graphene quantum dots (GQDs) as a stimulant for promoting osteogenic regeneration.

Methods: To assess our approach's effectiveness, four groups of rats were evaluated for the extent of bone tissue regeneration in their calvarial defects, 10 weeks post-surgery. Histomorphometry studies used various tissue staining methods, such as H&E and Masson's trichrome. Additionally, protein structures were extracted from the Protein Databank (PDB) and subjected to Molecular Docking using Molegro software.

Results: The findings revealed that the PAN/MOF-Cu scaffold possesses remarkable characteristics conducive to cell adhesion and growth. Furthermore, histomorphometry analysis confirmed the osteoconductive properties of PAN/MOF-Cu, suggesting its significant potential for application in critical-sized bone defects, particularly when combined with EnMSCs. Additionally, the implantation of scaffold/EnMSCs/GQDs demonstrated a greater enhancement in forming new bone relative to the other experimental groups. This suggests that the presence of GQDs significantly enhances the process of bone repair. Docking results further indicated that GQDs can potentially act as agonists to ER, FGFR3, TGF-βR, and frizzled-8 during osteogenesis.

Conclusion: These findings provide further confirmation that the nanocomposite/cells/GQDs combination serves as an excellent platform for bone tissue engineering.

Introduction: About 45-50% of infertility occurs because of men's problems. Nowadays, stem cells are used to treat infertility. Spermatogonial stem cells (SSCs) with the capability of self-regeneration, differentiation, and the transfer of genetic data to the next generation have an essential efficacy in maintaining fertility. Sertoli cells (SCs) are influential in balancing SCC proliferation and differentiation. Considering the importance of SSCs in the infertility treatment, the present study sought to evaluate the differentiation impact of exosomes on SSCs in turning sperm.

Methods: SCs and SSCs of male mice were cultured based on the aim of the study. The identity of SCs came under immunocytochemistry scrutiny. The exosome was extracted from SCs using the kit. The scanning electron microscope and Western Blot technique were used to check the validity of the extracted exosome. Complementary DNA synthesis was performed after extracting RNA from treated SSCs. The VAZA, DAZ-L, Sycp3, and Haprin gene expression was evaluated using the real-time polymerase chain reaction method.

Results: The cells known as spermatogonia cells treated with exosomes tend to experience an increase in gene expression during the third and fourth weeks after being stimulated by exosomes obtained from SCs. Specifically, the significantly increased expression of the VAZA, DAZ-L, Sycp3, and Haprin genes suggested that these cells had entered the stage of spermatogenesis.

Conclusion: The results indicated the induction of SSCs by exosomes, confirming their capability to differentiate into sperm-like cells and express some genes related to the haploid index.

Introduction: Identifying gene-disease associations is crucial for advancing medical research and improving clinical outcomes. Nevertheless, the rapid expansion of biomedical literature poses significant obstacles to extracting meaningful relationships from extensive text collections.

Methods: This study uses deep learning techniques to automate this process, using publicly available datasets (EU-ADR, GAD, and SNPPhenA) to classify these associations accurately. Each dataset underwent rigorous pre-processing, including entity identification and preparation, word embedding using pre-trained Word2Vec and fastText models, and position embedding to capture semantic and contextual relationships within the text. In this research, three deep learning-based hybrid models have been implemented and contrasted, including CNN-LSTM, CNN-GRU, and CNN-GRU-LSTM. Each model has been equipped with attentional mechanisms to enhance its performance.

Results: Our findings reveal that the CNN-GRU model achieved the highest accuracy of 91.23% on the SNPPhenA dataset, while the CNN-GRU-LSTM model attained an accuracy of 90.14% on the EU-ADR dataset. Meanwhile, the CNN-LSTM model demonstrated superior performance on the GAD dataset, achieving an accuracy of 84.90%. Compared to previous state-of-the-art methods, such as BioBERT-based models, our hybrid approach demonstrates superior classification performance by effectively capturing local and sequential features without relying on heavy pre-training.

Conclusion: The developed models and their evaluation data are available at https://github.com/NoorFadhil/Deep-GDAE.

Introduction: Breast cancer represents a significant global health challenge, underscoring the need for innovative therapeutic strategies. This study explores the therapeutic potential of etoposide (ETO)-loaded graphene oxide (GO) nanogels to enhance the efficacy of breast cancer treatments.

Methods: ETO-GO nanogels were synthesized and characterized using field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), and Fourier-transform infrared spectroscopy (FT-IR). Cytotoxicity was evaluated through MTT assays on MCF-7 breast cancer cells and normal HUVEC cells. Apoptosis induction was assessed using DAPI staining, flow cytometry, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to analyze changes in gene expression.

Results: Characterization confirmed the formation of uniform, spherical nanogels with high ETO encapsulation efficiency. EDS and FT-IR analyses validated the successful loading of the drug onto the GO matrix. Cytotoxicity assays revealed a dose-dependent response, with significantly stronger effects observed in MCF-7 cells (20% viability at 100 µg/mL) than HUVEC cells (40% viability at the same concentration), indicating selective cytotoxicity. Apoptosis was verified through DAPI staining, which showed characteristics of nuclear fragmentation, and flow cytometry, identifying 15.35% of the treated cells as apoptotic. qRT-PCR analysis demonstrated an upregulation of pro-apoptotic genes (CASP3, CASP8, CASP9, BAX, PTEN) by as much as 8.3-fold, alongside a marked downregulation of the anti-apoptotic gene Bcl-2, confirming the potent induction of apoptosis by the nanogels.

Conclusion: ETO-GO nanogels show promising potential for targeted breast cancer therapy, providing enhanced drug delivery and selective cytotoxicity. These findings warrant further in vivo studies to validate their clinical applicability.

Optimal skin healing is a sophisticated, coordinated process involving cellular and molecular interactions. Disruptions in this process can result in chronic wounds, necessitating medical intervention, particularly when the damage surpasses the body's regenerative capabilities. In response, novel therapies, especially tissue engineering and stem cell treatments, have been devised to restore tissue architecture and maximum functionality. Stem cells, which can differentiate into diverse cell types and regulate immune responses, hold significant potential for wound healing. Research demonstrates that integrating stem cells with scaffolds expedites this process, with numerous therapies advancing from laboratory studies to clinical trials. This review examines fundamental principles, classifications of stem cells, mechanisms, therapeutic applications, and challenges associated with stem cell encapsulation in wound healing.