Bioimpacts最新文献

Introduction: The classical swine fever virus (CSFV) causes significant economic losses in the livestock industry. While the existing E2 marker vaccine offers protection against infections, it is characterized by delayed immunity and reduced effectiveness over time. Optimizing the existing vaccine is crucial to better control CSFV outbreaks worldwide. This study aimed to improve the existing E2 marker vaccine for CSFV by integrating NS3 T lymphocyte-inducing epitopes into the conserved E2 protein sequence and using mRNA technology for vaccine delivery.

Methods: The design and evaluation of the vaccine were carried out exclusively through in silico methods. T lymphocyte epitopes were identified from the CSFV NS3 protein using multiple epitope prediction tools. A vaccine construct was formed after linking the predicted NS3 epitopes, E2 protein, and an immunogenic adjuvant. Molecular docking and dynamics simulations were performed to analyze the interaction between the adjuvant used and its immune receptor. Signal peptides were incorporated into the design, and mRNA sequences with varying codon usage biases were generated using LinearDesign. The mRNA sequence with minimum free energy (MFE) and codon adaptation index (CAI) closest to the controls was selected as the final design.

Results: Twenty epitopes with high binding affinity to major histocompatibility complexes (MHCs) were identified from the CSFV NS3 protein. The vaccine construct with swine CD154 adjuvant demonstrated high antigenicity, making it the optimal choice for the final vaccine design. Molecular docking and dynamics simulations confirmed the adjuvant's strong affinity and stable interaction with its canonical receptor, swine CD40. Moreover, the final vaccine design exhibited higher populations of lymphocytes and antibodies compared to the components of the commercialized E2 marker vaccine in immune simulation. The final mRNA vaccine sequence exhibited a higher MFE and CAI than the two licensed mRNA vaccine controls.

Conclusion: The mRNA vaccine designed in this study serves as a potential CSFV vaccine candidate. In vivo and in vitro validation is needed to confirm its efficacy.

Numerous researchers have examined the environmental and regional characteristics, as well as the mother's dwelling air quality during pregnancy, that influence children's lung disease. The most common type of medicine is Western medicine, however Chinese medicine is more effective at treating lung conditions in youngsters. The common cold, pneumonia, bronchitis, asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are among the respiratory ailments that traditional Chinese medicine (TCM) is frequently used to treat. TCM has qualities like resolving a variety of issues, focusing on several areas, and reducing harmful side effects. TCM has justified its anti-asthma, bronchiolitis, and pulmonary fibrosis (PF) effect in clinical practice but its underlying mechanism and specific role in mentioned disease are still unknown. According to some animal research, the traditional recipe, precise measurements, and organic substances extracted from TCM could considerably reduce changes in the structure of the airways and show anti-inflammatory properties. By examining these results and information, we will talk about the potential Patho mechanism that underlies asthmatic airway inflammation and remodeling as well as the special function of TCM in asthma treatment by controlling various signaling pathways. We provide a summary of the developments in research on TCM extracts for the treatment of asthma, bronchiolitis, PF, and lung cancer in this review paper. Additionally, we shall discuss a few cellular aspects.

Introduction: Prostate cancer (PCa) often progresses to castration-resistant prostate cancer (CRPC), which is linked to higher treatment resistance and recurrence rates. This highlights the urgent need for new therapeutic options. Natural products, especially flavonoids, have shown promise in reducing drug resistance and possess both antioxidant and anticancer effects. Developing drugs that specifically target CRPC could offer significant therapeutic advantages.

Methods: Chrysosplenetin B (CspB) was extracted and purified from the herb Laggera pterodonta (DC.) Benth. using traditional flavonoid extraction techniques, followed by high-performance liquid chromatography (HPLC) for purity assessment and nuclear magnetic resonance (NMR) for structural identification. The effect of CspB on the viability of PCa cells was evaluated using the Cell Counting Kit-8 assay. Subsequently, transcriptome analysis was conducted, and cell cycle progression was assessed through flow cytometry in conjunction with propidium iodide (PI) staining. Additionally, western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to confirm the expression levels of relevant proteins and genes.

Results: CspB was found to inhibit the proliferation of PC3, DU145, and LNCaP cells in a dose-dependent manner, with a stronger effect noted in PC3 and DU145 cells. Transcriptomic analysis revealed that CspB treatment led to cell cycle arrest, particularly in PC3 cells. Flow cytometry with PI staining confirmed that CspB caused G1 phase cell cycle arrest in PC3 cells. Moreover, CspB treatment significantly increased the expression of essential members of the Cip/Kip family, including CIP1/P21 and KIP1/P27, as well as CDKN2B (P15) and CDKN2D (P19) from the INK4 family. Additionally, CspB exposure notably raised the expression of the G1 phase-negative regulatory gene CDKN1C, while key cell cycle regulators like CDK6 and E2F1 were significantly downregulated at the protein level.

Conclusion: Our findings indicate that CspB effectively inhibits the proliferation of CRPC cells by reducing the activity of cell cycle proteins and cyclin-dependent kinase (CDK) complexes while upregulating the expression of P21 and P27 and inducing G1 phase cell cycle arrest. These results highlight the potential of CspB as a promising candidate for developing therapeutic agents aimed at targeting CRPC.

Introduction: Hydroxyapatite (HA), the main mineral component of bone, can be synthesized and utilized in the bone lesion treatments because of its high bioactivity and osteoconductive property. HA extraction from fish bones has received special attention given its low cost and easier extraction protocol compared to other sources. The present study compared the biocompatibility and bone repair of commercial nano hydroxyapatite (nHA) powder with that extracted from carp and human bones in vitro and in vivo.

Methods: First, nHA powders were prepared, and their physical and structural properties were studied using XRD, FTIR, FE-SEM and EDS analyses. Next, the powders were used to make porous scaffolds for which the physicochemical, structural, mechanical and biological properties were evaluated. The in vitro biocompatibility and osteogenic differentiation were tested on MC3T3-E1 cells, respectively, by MTT assay in three time periods and Alizarin red staining. Furthermore, the scaffolds were implanted after creation of critical-size lesions in the skulls of female rats, and the histological investigation was conducted by H&E staining at two time points.

Results: The morphological and phase analyses showed the successful fabrication of porous nHA scaffolds with 60.68%, 61.38, and 63.27% for carp, human and commercial nHA scaffolds, respectively. The scaffolds showed different biodegradability behavior where the human nHA scaffolds degrade more rapidly. The results of mechanical tests indicated that the scaffolds made up of human extracted nHA powder had the lowest strength and stiffness (3.13 and 37.37 KPa, respectively). The strength and stiffness of the scaffolds fabricated by carp extracted and commercial nHA were 17.14 and 19.01 Kpa, and 251.79 and 140.49 Kpa, respectively. The MTT test results showed that the greatest cell viability rate was in the carp nHA scaffolds after 10 days (146.08%). Moreover, the AR staining indicated the formation of mineralized nodules caused by the scaffolds in all groups. However, the mineralization seemed to be superior in human, and carp extracted groups. Furthermore, in vivo in all three groups bone repair occurred at the critical-size lesion sites, while scaffolds biodegradation was also observed. The scaffolds made up of carp and human nHA exhibited the highest rate of ossification and maturation of bone tissue among different scaffolds after 8 weeks. The rate of tissue response to these scaffolds was higher than the scaffolds made of commercial nHA after 4 and 8 weeks, postoperatively.

Conclusion: The carp extracted nHA scaffolds perform comparable to human extracted nHA, and may be used for clinical applications.

Introduction: Quantum dots (QDs) are semiconductor nanocrystals with inherent fluorescence having several advantages over traditional fluorescent probes including their small size (5-10 nm), tunable excitation and emission spectra, ease of surface functionalization, and robust photostability that makes them ideal candidates for in vivo imaging. The behavior of QDs is highly dependent on the surface functionality. In vivo toxicity of QDs in biological systems is the major limitation hindering their translation to clinics.

Methods: In the present study, cytotoxicity of water soluble ZnSe/CdS core shell QDs capped with oleic acid was evaluated against human hepatocellular carcinoma cell line-Hep3B, Human Embryonic Kidney cell line-HEK 293 and Ehlrich Ascitic cells-EAC. To assess its in vivo therapeutic efficacy, the initial animal toxicity studies of OA capped ZnSe/ CdS QDs were done in Balb/c mice. Serum stability, pharmacokinetics, biodistribution and γ-scintigraphic imaging were observed in mice after intravenous (i.v) injection of QDs at a dose of 10 nM/kg/200 µL/mice up to 28 days.

Results: IC₅₀ of OA capped QDs against Hep3B was 29.85 µg/mL at 24 hours. QDs toxicity was primarily due to the generation of reactive oxygen species as observed by LDH release in Hep3B cells. Negligible haemolysis indicated that OA capped QDs were biocompatible. OA capped QDs mainly accumulated in the liver and spleen with no retention in kidneys.

Conclusion: OA capped ZnSe/ CdS QDs exhibited enhanced anti-cancer efficacy against Hep3B and EAC cell line. Further, minimum accumulation and retention were observed in vital organs in Balb/c mice protecting them from potential adverse side effects, underlining their potential for biomedical applications.

Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) in linking innate and adaptive immune responses. In addition to presenting antigens to T cells, DCs must also provide co-stimulatory signals along with cytokines for T cells to induce an appropriate cellular immune response. Tolerance is also established and maintained by DCs under homeostatic circumstances. There is remarkable phenotypic heterogeneity in DCs, each with different functional flexibility and specific expression of various markers. The three primary categories of DCs comprise conventional DCs (cDCs), plasmacytoid DCs (pDCs), and monocyte-derived DCs (moDCs). Langerhans cells (LCs) are another type of DCs, which are found in the skin's epidermal layer. DCs may be positioned or triggered inappropriately as a result of dysregulation of DC. This phenomenon can cause an imbalance in immune responses and even immune-related pathological disorders, i.e., autoimmune diseases and malignancies. Herein, by reviewing the ontogeny, biology, characteristics, and function of DCs subsets in immune system, we discuss the contribution of these cells in the mentioned immune-related disorders.

Introduction: LncRNAs interact with miRNAs and mRNAs that can have a special expression pattern in a specific cell type. We investigated the specific lncRNAs, miRNAs, and mRNAs in different groups of prostate cancer (PC).

Methods: The mRNAs with significant expression differences were first analyzed using the GEO and TCGA databases. The lncRNAs and miRNAs were then identified in the miRWalk2, miRmap, OncomiR, miRGator 3.0, miRCancerDB, LncRNA2target, TANRIC, LncRNADisease, Lnc2Cancer v3.0, and LncBase. Seventy subjects, including sixty PC patients classified as local, locally advanced, biochemical relapse, metastatic, and benign groups, as well as ten normal individuals, were then included. Finally, real-time PCR determined the expression of the candidate biomarkers.

Results: The bioinformatics analysis detected candidate 6 miRNAs, 6 lncRNAs, and 6 mRNAs in different groups of PC patients. Unlike the significant decrease in candidate tumor suppressors, the expression levels of specific onco-lncRNA, onco-miRNA, and oncogenes exhibited a substantial increase in different groups of the patients compared to the normal group. The expression of lncRNAs, including LINC01128 (P=0.0182), LINC02246 (P<0.0001), and LINC02288 (P<0.0001), LINC00857 (P<0.0001), GNAS-AS1 (P<0.0001), and LINC02371 (P<0.0001), the expression of miRNAs, including miR-217 (P<0.0001), miR-375 (P<0.0001), miR-203a (P<0.0001), miR-876 (P=0.0046), miR-27b (P<0.0001), and miR-152 (P<0.0001), and the expression of oncogenes, including ST14 (P<0.0001), CD24 (P<0.0001), CDH1 (P<0.0001), DSC2 (P<0.0001), TGFB3 (P<0.0001), and MYL2 (P=0.0186) had significant changes at different groups of PC patients.

Conclusion: Our results identified promising biomarkers that play a role in specific groups of prostate cancer patients. Detecting specific biomarkers may be an effective strategy for different groups of PC patients.

Neuropathic pain, a chronic condition resulting from somatosensory system damage, remains a significant clinical challenge due to its complex pathophysiology and inadequate response to traditional therapies. Oxidative stress, characterized by an imbalance between free radicals production and antioxidant defenses, plays a pivotal role in the development and maintenance of neuropathic pain. Mesenchymal stem cells (MSCs) are multipotent stromal cells with the ability to differentiate into various cell types and possess immunomodulatory, anti-inflammatory, and regenerative properties, making them promising candidates for novel pain management strategies. Preclinical studies demonstrate that MSCs can reduce inflammation, scavenge reactive oxygen species (ROS), promote nerve regeneration, and modulate pain signaling pathways. Various administration routes, including intravenous and intrathecal, have been investigated to optimize MSC delivery and efficacy. Additionally, MSC-derived extracellular vesicles (EVs) represent a cell-free alternative with substantial therapeutic potential. Despite encouraging preclinical findings, further research is needed to refine MSC-based therapies, including the exploration of combination treatments and rigorous clinical trials, to translate these promising results into effective clinical applications for neuropathic pain relief. This review explores the therapeutic potential of MSCs in alleviating oxidative stress-mediated neuropathic pain.

Introduction: Predicting drug-protein interactions is critical in drug discovery, but traditional laboratory methods are expensive and time-consuming. Computational approaches, especially those leveraging machine learning, are increasingly popular. This paper introduces VASVDD, a multi-step method to predict drug-protein interactions. First, it extracts features from amino acid sequences in proteins and drug structures. To address the challenge of unbalanced datasets, a Support Vector Data Description (SVDD) approach is employed, outperforming standard techniques like SMOTE and ENN in balancing data. Subsequently, dimensionality reduction using a Variational Autoencoder (VAE) reduces features from 1074 to 32, improving computational efficiency and predictive performance.

Methods: The proposed method was evaluated on four datasets related to enzymes, G-protein-coupled receptors, ion channels, and nuclear receptors. Without preprocessing, the Gradient Boosting Classifier showed bias towards the majority class. However, balancing and dimensionality reduction significantly improved accuracy, sensitivity, specificity, and F1 scores. VASVDD demonstrated superior performance compared to other dimensionality reduction methods, such as kernel principal component analysis (kernel PCA) and Principal Component Analysis (PCA), and was validated across multiple classifiers, achieving higher AUROC values than existing techniques.

Results: The results highlight VASVDD's effectiveness and generalizability in predicting drug-target interactions. The method outperforms state-of-the-art techniques in terms of accuracy, robustness, and efficiency, making it a promising tool in bioinformatics for drug discovery.

Conclusion: The datasets analyzed during the current study are not publicly available but are available from the corresponding author upon reasonable request and source code are available on GitHub: https://github.com/alirezakhorramfard/vasvdd.

Introduction: Dendritic cells (DCs) possess specialized abilities to present antigens and stimulate T cells, making them essential in triggering adaptive immune responses. Thalidomide and its derivatives are classified as a group of medications that possess immunomodulatory properties. Numerous studies have demonstrated the contentious impact of these drugs on DCs. Therefore, the objective of the present study was to assess the influence of Thalidomide therapy on the maturation and stimulation of monocyte-derived DCs, and subsequently examine the consequences of these treated DCs on the immune responses of autologous T cells.

Methods: The immature DCs derived from monocytes were subjected to exposure to Thalidomide and Lipopolysaccharides (LPS) on the fifth day of differentiation, followed by a 24-hour incubation period. On the sixth day, the phenotypic features of the DCs in both the control and treatment groups were assessed using flow cytometry. Subsequently, the gene expression in both the DCs and autologous T cells co-cultured with the DCs was evaluated using the real-time PCR method.

Results: Thalidomide-treated DCs exhibited a significant augmentation in the expression of maturation and stimulatory surface markers CD11c, HLA-DR, and CD86 (P ≤ 0.01), as well as gene expression of TNF-α and IL-12 (P ≤ 0.01) when compared to the control group. Furthermore, co-culture of Thalidomide-treated DCs with T cells increased T-bet and IFN-γ (P ≤ 0.01) expression, while diminished FOXP3 and TGF-β (P ≤ 0.01) expression compared to T cells co-cultured with untreated DCs.

Conclusion: Our findings indicate that in vitro Thalidomide treatment shifts DCs towards an immunogenic state and elevates their T helper 1 inducing capacity, which may be efficient in immunotherapy of various cancers.