6-Gingerol modulates miRNAs and PODXL gene expression via methyltransferase enzymes in NB4 cells: an in silico and in vitro study.

This investigation delves into the influence of predicted microRNAs on DNA methyltransferases (DNMTs) and the PODXL gene within the NB4 cell line, aiming to elucidate their roles in the pathogenesis of acute myeloid leukemia (AML). A comprehensive methodological framework was adopted to explore the therapeutic implications of 6-gingerol on DNMTs. This encompassed a suite of bioinformatics tools for protein structure prediction, docking, molecular dynamics, and ADMET profiling, alongside empirical assessments of miRNA and PODXL expression levels. Such a multifaceted strategy facilitated an in-depth understanding of 6-gingerol's potential efficacy in DNMT modulation. The findings indicate a nuanced interplay where 6-gingerol administration modulated miRNA expression levels, decreasing in DNMT1 and DNMT3A expression in NB4 cells. This alteration indirectly influenced PODXL expression, contributing to the manifestation of oncogenic phenotypes. The overexpression of DNMT1 and DNMT3A in NB4 cells may contribute to AML, which appears modulable via microRNAs such as miR-193a and miR-200c. Post-treatment with 6-gingerol, DNMT1 and DNMT3A expression alterations were observed, culminating in the upregulation of miR-193a and miR-200c. This cascade effect led to the dysregulation of tumor suppressor genes in cancer cells, including downregulation of PODXL, and the emergence of cancerous traits. These insights underscore the therapeutic promise of 6-gingerol in targeting DNMTs and microRNAs within the AML context.

Critical Aggregation Concentration Can be a Predictor of Doxorubicin Delivery Performance of Self-Assembling Amphiphilic Peptides with Different Hydrophobic Tails.

Amphiphilic peptides hold great potential as drug delivery systems. A popular peptide design approach has been to place amino acids in the peptide sequence based on their known properties. On the other hand, the directed discovery approach aims to screen a sequence space for a desired property. However, screening amphiphilic peptides for desirable drug delivery properties is not possible without a quantity that is predictive of these properties. We studied the predictive power of critical aggregation concentration (CAC) values on the drug delivery performance of a series of amphiphilic peptides with different hydrophobic tails and close CAC values. The CAC values were predicted by our previously developed model and doxorubicin was used as a model hydrophobic drug. All peptides showed close drug loading, entrapment efficiency, and release profile. They also formed similar spherical particles by assembling in reverse ß-sheet arrangements regardless of drug presence. Moreover, the assembled particles were able to accumulate doxorubicin inside ordinary as well as drug-resistant breast cancer cells and enhance its toxicity up to 39 and 17 folds, respectively. It can be concluded that similar drug delivery properties displayed by the peptides can be attributed to their similar hydrophilic-lipophilic balance as reflected in their close CAC values.

Phage display technology for fabricating a recombinant monoclonal ScFv antibody against tetanus toxin.

Tetanus is a specific infectious disease, often associated with lower immunization in developing countries and catastrophic events (such as earthquakes). Millions of people, especially children, die every year from tetanus disease. Therefore, it is necessary to devise a rapid and sensitive detection method for tetanus toxin to ensure an early diagnosis and clinical treatment of tetanus. The current study looks at developing a novel, high specific, low-cost, and sensitive ScFv antibody. It is capable of tetanus detection immunoassays in clinical diagnosis, suspicious foods, and water monitoring. For this regard, a high-quality phage display antibody library (8.7 × 107 PFU/ml) was constructed. Tetanus-specific antibodies with high affinity retrieved from libraries. After phage rescue and four rounds of biopanning, clone screening was performed by phage ELISA. Recombinant antibodies expressed from the AC8 clone showed the highest affinity for tetanus. SDS-PAGE and western blotting confirmed the presence of a high-quality, pure ScFv band at 32 kDa. ELISA was used to determine the affinity value, estimated to be around 10-8 M. The results suggest that the proposed detection method by ScFv antibodies is an alternative diagnostic tool enabling rapid and specific detection of the tetanus toxin.

Hydrogel nanocomposite based on alginate/zeolite for burn wound healing: In vitro and in vivo study.

Objectives: The main objective of the current assay was to evaluate the antibacterial and regenerative effects of hydrogel nanocomposite containing pure natural zeolite (clinoptilolite) integrated with alginate (Alg) as wound healing/dressing biomaterials. Materials and Methods: The zeolites were size excluded, characterized by SEM, DLS, XRD, FTIR, and XRF, and then integrated into Alg hydrogel followed by calcium chloride crosslinking. The Alg and alginate zeolite (Alg/Zeo) hydrogel was characterized by swelling and weight loss tests, also the antibacterial, hemocompatibility, and cell viability tests were performed. In animal studies, the burn wound was induced on the back of rats and treated with the following groups: control, Alg hydrogel, and Alg/Zeo hydrogel. Results: The results showed that the hydrodynamic diameter of zeolites was 367 ± 0.2 nm. Zeolites did not show any significant antibacterial effect, however, the hydrogel nanocomposite containing zeolite had proper swelling as well as hemocompatibility and no cytotoxicity was observed. Following the creation of a third-degree burn wound on the back of rats, the results indicated that the Alg hydrogel and Alg/Zeo nanocomposite accelerated the wound healing process compared with the control group. Re-epithelialization, granulation tissue thickness, collagenization, inflammatory cell recruitment, and angiogenesis level were not significantly different between Alg and Alg/Zeo nanocomposite. Conclusion: These findings revealed that although the incorporation of zeolites did not induce a significant beneficial effect in comparison with Alg hydrogel, using zeolite capacity in hydrogel for loading the antibiotics or other effective compounds can be considered a promising wound dressing.

Newly Developed Targeted Therapies Against the Androgen Receptor in Triple-Negative Breast Cancer: A Review.

Among different types of breast cancers (BC), triple-negative BC (TNBC) amounts to 15% to 20% of breast malignancies. Three principal characteristics of TNBC cells are (i) extreme aggressiveness, (ii) absence of hormones, and (iii) growth factor receptors. Due to the lack or poor expression of the estrogen receptor, human epidermal growth factor receptor 2, and progesterone receptor, TNBC is resistant to hormones and endocrine therapies. Consequently, chemotherapy is currently used as the primary approach against TNBC. Expression of androgen receptor (AR) in carcinoma cells has been observed in a subset of patients with TNBC; therefore, inhibiting androgen signaling pathways holds promise for TNBC targeting. The new AR inhibitors have opened up new therapy possibilities for BC patients carrying AR-positive TNBC cells. Our group provides a comprehensive review of the structure and function of the AR and clinical evidence for targeting the cell's nuclear receptor in TNBC. We updated AR agonists, inhibitors, and antagonists. We also presented a new era of genetic manipulating CRISPR/Cas9 and nanotechnology as state-of-the-art approaches against AR to promote the efficiency of targeted therapy in TNBC. SIGNIFICANCE STATEMENT: The lack of effective treatment for triple-negative breast cancer is a health challenge. The main disadvantages of existing treatments are their side effects, due to their nonspecific targeting. Molecular targeting of cellular receptors, such as androgen receptors, increased expression in malignant tissues, significantly improving the survival rate of breast cancer patients.

Novel Descriptors Derived from the Aggregation Propensity of Di- and Tripeptides Can Predict the Critical Aggregation Concentration of Longer Peptides.

Self-assembling amphiphilic peptides have recently received special attention in medicine. Nonetheless, testing the myriad of combinations generated from at least 20 coded and several hundreds of noncoded amino acids to obtain candidate sequences for each application, if possible, is time-consuming and expensive. Therefore, rapid and accurate approaches are needed to select candidates from countless combinations. In the current study, we examined three conventional descriptor sets along with a novel descriptor set derived from the simulated aggregation propensity of di- and tripeptides to model the critical aggregation concentration (CAC) of amphiphilic peptides. In contrast to the conventional descriptors, the radial kernel model derived from the novel descriptor set accurately predicted the critical aggregation concentration of the test set with a residual standard error of 0.10. The importance of aromatic side chains, as well as neighboring amino acids in the self-assembly, was emphasized by analysis of the influential descriptors. The addition of very long peptides (70-100 residues) to the data set decreased the model accuracy and changed the influential descriptors. The developed model can be used to predict the CAC of self-assembling amphiphilic peptides and also to derive rules to apply in designing novel amphiphilic peptides with desired properties.

Electroanalysis of isoniazid and rifampicin: Role of nanomaterial electrode modifiers.

Thanks to operational simplicity, speediness, possibility of miniaturization and real-time nature, electrochemical sensing is a supreme alternative for non-electrochemical methodologies in drug quantification. This review, highlights different nanotech-based sensory designs for electroanalysis of isoniazid and rifampicin, the most important medicines for patients with tuberculosis. We first, concisely mention analyses with bare electrodes, associated impediments and inspected possible strategies and then critically review the last two decades works with focus on different nano-scaled electrode modifiers. We organized and described the materials engaged in several categories: Surfactants modifiers, polymeric modifiers, metallic nanomaterials, carbon based nano-modifiers (reduced graphene oxide, multi-walled carbon nanotubes, ordered mesoporous carbon) and a large class of multifarious nano composites-based sensors and biosensors. The main drawbacks and superiorities associated with each array as well as the current trend in the areas is attempted to discuss. Summary of 79 employed electrochemical approaches for analysis of isoniazid and rifampicin has also been presented.

Rapid and Sensitive Detection of Staphylococcal Enterotoxin B by Recombinant Nanobody Using Phage Display Technology.

Staphylococcal enterotoxin B, from Staphylococcus aureus (S. aureus), is one of the most potent bacterial superantigens with profound toxic effects on the immune system. It is associated with food poisoning, toxic shock, atopic dermatitis, asthma, and nasal polyps in humans. The current diagnostic methods for staphylococcal enterotoxin are mainly based on traditional monoclonal antibodies which hardly meet the requirements for clinical applications, and hybridoma clones lose their ability to secrete antibodies during time. The present study investigates the development of a novel, highly specific, low-cost, and sensitive nanobody capable of being used in immunoassays for Staphylococcal enterotoxin B (SEB) detection in suspicious foods. For this purpose, Camelus dromedarius was immunized against SEB toxin. After obtaining acceptable titration, a high-quality phage display nanobody library (4 × 1010 PFU/ml) was constructed. High-affinity SEB-specific nanobodies were retrieved from constructed libraries. After phage rescue and five round of biopanning, clone screening was performed by phage ELISA. Recombinant nanobodies which were expressed from C7 and C21 clone showed the highest affinity for SEB. The presence of high quality and pure nanobody band at ~ 15 kDa was confirmed by SDS-PAGE and western blotting. The affinity constant which was measured by ELISA was calculated to be around 10-9 M. The results suggest that the proposed detection method by nanobodies is an alternative diagnostic tool enabling a rapid, inexpensive, and specific detection of the SEB.