Bioimpacts最新文献

Breast cancer (BC) is a persistent global health challenge, necessitating innovative therapeutic strategies. Recently, nanotechnology has appeared as a transformative methodology to treat BC, suggesting precise targeting, controlled drug delivery, and improved imaging capabilities. This review offers a current overview of the latest innovations around nanotechnology for BC therapy in the field of new nanomedicines and nano-based drug delivery methods by carefully examining the utilization of nanoparticles to enhance the effectiveness of both new and old medications and to enable targeted evaluation using disease markers. Key topics include early detection, targeted drug delivery, multimodal imaging, and combination therapies. The paper underscores the probability of using nanotechnology to reshape BC management landscape and outlines potential future directions.

Introduction: The potential clinical application of mesenchymal stem cells (MSCs) in cell-based treatment makes them particularly interesting. The use of MSC-engaged therapies in cancer treatment is becoming more and more promising. Although the specifics of their activity have not yet been conclusively established, a variety of growth factors released by these cells are known to provide such multifunctional qualities.

Methods: Through the measurement of cytokine levels, Annexin-V, and possible signaling pathways linked to apoptosis, we have assessed the impact of MSCs on CD34⁺leukemic stem cells (LSCs) enriched from the KG1-a cell line. Additionally, culture medium was taken from the experimental and control groups for the IL-2 and IL-4 measurement following a 7-day co-culture.

Results: Co-culture conditions were observed to promote early and late apoptosis, although this increase just was statistically significant in late apoptosis. The co-cultured conditioned media clearly showed a large amount of IL-2, but there was an insignificant rise in IL-4. Also, MSCs significantly increased the protein expression of P16, P21, and p-P38 and significantly decreased C-Myc, and TERC.

Conclusion: It can be concluded that the mentioned effects of IL-2 cytokine released from MSCs on CD34⁺LSCs maybe were applied by the components of P16, P21, and p-P38, C-Myc signaling pathways.

Introduction: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). CD4⁺ CD25^+hi Tregs, which normally suppress immune responses, exhibit impaired function in MS. Treg-derived extracellular vesicles (EVs) carry immunoregulatory proteins and miRNAs that modulate T-cell activity. However, EVs from MS patients show reduced suppressive capacity, suggesting their dysfunction contributes to MS pathogenesis. This highlights EVs' potential role in MS development and therapy.

Methods: Tregs were differentiated from naïve T cells isolated from peripheral blood mononuclear cells (PBMCs) of healthy donor, then transduced with B2M-shRNA lentivirus to generate HLA class I-knockdown Tregs. Extracellular vesicles-including natural vesicles, cytochalasin B-induced artificial vesicles, and ultrasound-induced artificial vesicles-were isolated from Tregs and characterized by scanning electron microscopy (SEM), nanoparticle tracking analysis (NTA), flow cytometry, and Western blot. Their effects on healthy donor and MS patient PBMCs were evaluated via flow cytometry and ELISA (IL-6, IL-10, IFN-γ).

Results: Ultrasonication yielded a higher number оf vesicles enriched with key immunosuppressive proteins, including PD-1 and Tim-3, compared to cytochalasin B. Functional assays demonstrated the ability оf ultrasonication-induced AVs to suppress inflammatory markers, such as IFNγ, and modulate the cytokine profile in both healthy and MS-derived PBMCs.

Conclusion: Developing effective MS therapies remains challenging. While cellular therapies face limitations like Treg dysfunction and CNS delivery issues, allogeneic EVs offer a promising alternative due to their scalability, low immunogenicity, and blood-brain barrier penetration. We developed Treg-derived artificial vesicles (TrAVs) that maintain immunosuppressive properties and modulate PBMC responses, suggesting therapeutic potential for MS. Further research is needed to optimize production and validate efficacy in disease models.

Introduction: Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality, and effective therapeutic options are limited. MicroRNA‑372‑3p (miR‑372‑3p) has been implicated in HCC, yet its exact role is unclear.

Methods: We established miR‑372‑3p‑overexpressing HCC cell lines (HepG2, SNU‑449, JHH‑4) via lentiviral transduction. Malignant phenotypes were assessed with MTT, transwell migration/invasion, and colony‑formation assays. Transcriptomic changes were analyzed by RNA‑sequencing followed by Gene Set Enrichment Analysis. Lipid metabolism was examined using BODIPY/Oil Red O staining, triglyceride quantification, FAOBlue assays, and organelle colocalization imaging. Candidate targets of miR‑372‑3p were computationally predicted and validated by dual‑luciferase reporter assays.

Results: miR‑372‑3p overexpression significantly reduced cell proliferation by more than 50%, migration by over 30%, invasion by over 30%, and colony formation by more than 50%, supporting its tumor-suppressive role. Transcriptomic analysis identified 1,759 downregulated genes, significantly enriched in pathways associated with fatty acid oxidation (FAO). miR‑372‑3p‑overexpressing cells exhibited increased lipid droplet accumulation, with triglyceride levels elevated by more than 50% and an approximate 50% reduction in FAO activity, indicating defective use under glucose-deprived conditions. High-resolution organelle imaging further revealed diminished physical contacts between lipid droplets and mitochondria, as well as a similar disruption in lipid droplet-lysosome interactions. Dual-luciferase reporter assays confirmed CPT1A and ACSL4 as direct targets of miR‑372‑3p.

Conclusion: miR‑372‑3p functions as a tumor suppressor in HCC by directly downregulating CPT1A and ACSL4, thereby inhibiting FAO and disrupting lipid metabolism. Targeting this miRNA and FAO axis may offer a novel therapeutic strategy for HCC.

Introduction: Cardiovascular disease is a leading cause of death worldwide. Tissue engineering offers a promising solution for promoting tissue regeneration at the infarcted site. In this study, beta-tricalcium phosphate (βTCP) was incorporated into poly(ε-caprolactone) (PCL) and gelatin (Gel) fibers for cardiac patch applications.

Methods: Electrospun scaffolds were prepared via electrospinning a 1:1 (w/w) mixture of PCL and Gel, embedding varying concentrations of βTCP at 0.25, 0.5, 1, and 3 wt.%. The scaffolds were analyzed through scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), tensile strength testing, hemolysis assays, toxicity testing, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) for marker gene expression. Furthermore, subcutaneous scaffold implantation was performed to assess in vivo angiogenesis in NMRI mice. Tissue samples were examined using hematoxylin and eosin (H&E) staining and immunohistochemistry.

Results: According to the results, βTCP was uniformly distributed throughout the fiber scaffold, exhibiting a smooth, unbranched morphology with fiber diameters of approximately 75 μm. Specifically, the mean diameters for PCL-Gel and PCL-Gel-βTCP at 3 wt.% were 45.01 ± 2.82 μm and 100.91 ± 11.69 μm, respectively. Mechanical property assessments revealed that the elastic modulus of the scaffolds was suitable for usage as a tissue-engineered cardiac patch. Scaffolds containing βTCP exhibited favorable blood compatibility and indicated no cytotoxicity at the tested concentrations. Furthermore, the expression levels of cardiac marker genes (Actn4, Connexin43, and TrpT2) were elevated in the treatment groups in conjunction with the escalation of βTCP dosage. Fiber composites with 1% βTCP were selected as the optimal scaffold for in vivo examination. This scaffold demonstrated a significantly enhanced cell migration rate, with a growth in capillary formation observed in the immunohistochemistry analysis.

Conclusion: The fibrous PCL-Gel-βTCP-1% scaffold showed optimal cell proliferation, blood compatibility and vascularization. These properties highlight its promise for cardiac tissue engineering.

Colorectal cancer (CRC) constitutes a significant global health challenge, accounting for a considerable proportion of cancer cases and associated mortality. Projections indicate a potential increase in new cases by 2040, attributed to demographic factors such as aging and population growth. Although advancements in the understanding of CRC pathophysiology have broadened treatment options, challenges such as drug resistance and adverse effects persist, highlighting the necessity for enhanced diagnostic methodologies. Timely detection markedly improves survival rates; however, colonoscopy, regarded as the gold standard for CRC screening, is constrained by its invasiveness and reliance on practitioner expertise. Consequently, the development of novel diagnostic approaches is imperative. Cancer biomarkers, which serve as indicators of cancer progression, show significant promise for improving diagnosis, prognosis, and treatment strategies. This study investigates molecular and cellular biomarkers, including proteins, DNA mutations, methylation markers, and microRNAs, that are pivotal in precision medicine and the monitoring of CRC progression. Additionally, emerging biomarkers such as circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) present opportunities for early detection. Current Food and Drug Administration (FDA)-approved CRC biomarkers reflect a shift towards personalized medicine, enhancing patient compliance and clinical outcomes. Nevertheless, further research is essential for the discovery of novel biomarkers and for deepening the understanding of CRC etiology, thereby advancing personalized care. Addressing standardization challenges will be crucial for ensuring global patient access to biomarker-based strategies.

Introduction: Accurate and non-invasive blood glucose estimation is essential for effective health monitoring. Traditional methods are invasive and inconvenient, often leading to poor patient compliance. This study introduces a novel approach that leverages systolic-diastolic framing Mel-frequency cepstral coefficients (SDFMFCC) to enhance the accuracy and reliability of blood glucose estimation using photoplethysmography (PPG) signals.

Methods: The proposed method employs SDFMFCC for feature extraction, incorporating systolic and diastolic frames. The systolic and diastolic points are identified using the Savitzky-Golay filter, followed by local extrema detection. Blood glucose levels are estimated using support vector regression (SVR). The evaluation is performed on a dataset comprising 67 raw PPG signal samples, along with labeled demographic and biometric data collected from 23 volunteers (aged 20 to 60 years) under informed consent and ethical guidelines.

Results: The SDFMFCC-based approach demonstrates high accuracy (99.8%) and precision (0.996), with a competitive root mean square error (RMSE) of 26.01 mg/dL. The Clarke Error Grid analysis indicates that 99.273% of predictions fall within Zone A, suggesting clinically insignificant differences between estimated and actual glucose levels.

Conclusion: The study validates the hypothesis that incorporating a new framing method in MFCC feature extraction significantly enhances the accuracy and reliability of non-invasive blood glucose estimation. The results highlight that the SDFMFCC method effectively captures critical physiological variations in PPG signals, offering a promising alternative to traditional invasive methods.

Introduction: Mitochondrial DNA (mtDNA) copy number variations have been reported in multiple human cancers. Previous studies indicate that mitochondrial retrograde signaling regulates miR663, which plays a key role in tumorigenesis, including regulating apoptosis antagonizing transcription factor (AATF). This study investigates the expression of miR663 and AATF in relation to mtDNA copy number in invasive ductal carcinoma (IDC) of the breast.

Methods: Paired primary tumors and adjacent non-tumor tissues were analyzed to assess changes in miR663 and AATF expression using fold-change analysis. The mtDNA copy number was quantified using COX1 as the mitochondrial gene and COX4 as the nuclear control gene. To validate the findings, publicly available data from The Cancer Genome Atlas (TCGA) were also analyzed.

Results: A significant reduction in tumor miR663 expression was observed (fold change=0.139), with a strong correlation between miR663 and AATF expression. A significant Z-score difference was also detected between miR663 and mtDNA copy number. miR663 was predominantly expressed in grade I tumors but significantly downregulated in higher-grade tumors, whereas AATF expression increased with tumor grade. In silico analysis of TCGA data confirmed elevated AATF expression, with notable variations across breast cancer subtypes.

Conclusion: We observed reduced expression of miR663 and mtDNA copy number in breast tumors, along with variations in AATF levels across subtypes. The decrease in miR663 could be associated with lower mtDNA copy numbers and impaired retrograde signaling, impacting AATF expression and function. Our findings underscore the therapeutic promise of targeting the mtDNA/miR-663/AATF axis, which could lead to advancements in breast cancer treatment.

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.