Current pharmaceutical biotechnology最新文献

Background: Dilated Cardiomyopathy (DCM) is a debilitating cardiovascular disorder that challenges current therapeutic strategies. The exploration of novel drug repositioning opportunities through gene expression analysis offers a promising avenue for discovering effective treatments.

Objective: This study aims to identify potential drug repositioning opportunities and lead compounds for DCM treatment by optimizing gene expression characteristics using published data.

Methods: Our approach involved analyzing DCM expression profiles from the Gene Expression Omnibus database and identifying differentially expressed genes with GEO2R. A protein interaction network was constructed using the STRING database and visualized with Cytoscape. Enrichment analyses were conducted on these genes through the Omicshare platform, followed by the identification of candidate compounds via the Connectivity Map (CMAP) and validation through molecular docking. The Coremine Medical database was utilized to predict potential herbal medicines.

Results: We identified 29 differentially expressed genes, highlighting MYH6, NPPA, and NPPB as central to DCM pathology. Enrichment analyses indicated significant impacts on biological processes, such as organ morphogenesis and inflammatory responses. The AGE-RAGE signaling pathway was notably affected. From over 6,100 compounds analyzed, tenoxicam emerged as a promising candidate, with Radix Salviae Miltiorrhizae (Danshen) being suggested as a potential herbal treatment.

Conclusion: This study underscores the utility of bioinformatics in uncovering new therapeutic candidates for DCM, offering a foundational step towards novel drug development.

Objectives: This study aimed to comprehensively investigate the molecular landscape of gastric cancer (GC) by integrating various bioinformatics tools and experimental validations.

Methodology: GSE79973 dataset, limma package, STRING, UALCAN, GEPIA, OncoDB, cBioPortal, DAVID, TISIDB, Gene Set Cancer Analysis (GSCA), tissue samples, RT-qPCR, and cell proliferation assay were employed in this study.

Results: Analysis of the GSE79973 dataset identified 300 differentially expressed genes (DEGs), from which COL1A1, COL1A2, CHN1, and FN1 emerged as pivotal hub genes using protein-protein interaction network analysis. Subsequent validation across The Cancer Genome Atlas (TCGA) datasets confirmed their up-regulation in GC tissues compared to normal controls. Promoter methylation analysis revealed decreased methylation levels of these hubs in GC tissues, suggesting their potential role in tumorigenesis. Mutational analysis using cBioPortal showcased frequent mutations in these genes, particularly FN1, further highlighting their significance in GC pathogenesis. Survival analysis indicated their correlation with reduced overall survival rates among GC patients, supported by the development of a robust prognostic model. Prediction of hub-associated miRNAs and gene enrichment analysis provided insights into their regulatory mechanisms and downstream pathways, implicating their involvement in extracellular matrix remodeling and cell migration. Drug sensitivity analysis revealed correlations between hub gene expression and drug response, while RT-qPCR validation confirmed their upregulation in clinical GC samples. Finally, functional assays demonstrated the impact of FN1 knockdown on cellular proliferation, colony formation, and wound healing capacities.

Conclusion: Overall, this study elucidates the crucial role of COL1A1, COL1A2, CHN1, and FN1 in GC pathogenesis and underscores their potential as diagnostic markers and therapeutic targets.

Alzheimer's disease (AD) remains a major challenge in developing effective treatments due to its complex pathophysiology, including the accumulation of amyloid-beta plaques and tau tangles. Small interfering RNA (siRNA) technology offers promise for targeted gene silencing, but effective delivery to the central nervous system remains a significant obstacle. Viral vectors have emerged as potent delivery vehicles for transporting siRNA to neural tissues. This review explores the utilization of viral vectors for siRNA delivery in AD, focusing on delivery strategies and challenges. We discuss the design and optimization of viral vectors, targeting strategies, and safety considerations. Additionally, we examine recent advancements and prospects for enhancing viral vector-mediated siRNA delivery in AD.

Introduction: Iron oxide nanozyme was synthesized from the fruit peel extract of pomegranate, which served as a reducing agent during the green synthesis. The scavenging of reactive oxygen species is often accompanied by immunomodulation following antiproliferative effects due to the crosstalk between the proteins involved in the inter-related signaling pathways.

Method: In the current study, the green synthesized nanozyme was studied for its ability to induce apoptosis in breast cancer cell lines. The free radical scavenging effect of the nanozyme was reflected as an extension of its intrinsic endogenous enzyme-mimicking property.

Result & discussion: The cell cycle analysis revealed that the cell death induced by nanozyme mainly affected the G0/G1 phase. The expression of RelA/p65 and the inflammatory mediators affected by the nanozyme established the role of the Fe3O4 nanozyme in immunomodulation along with its antiproliferative activity.

Conclusion: This is the first report on the antiproliferative and immunomodulatory activities expressed by the biomimetic iron oxide nanozyme.

Background: Wound healing is a complex procedure frequently delayed in patients with underlying chronic conditions. Despite essential advances in tissue engineering and regenerative medicine, wound healing remains challenging, warranting novel methods for promoting wound healing. It has been demonstrated that exosomes are one of the main secretory products of different cell types, such as Mesenchymal Stem Cells (MSCs), for regulating various biological processes, including wound healing. Henceforth, understanding these exosome effects might assist in improving wound management and highlight a novel therapeutic model for cell-free therapies with reduced side effects for repairing wounds.

Methods: This systematic review involved conducting research electronically on scholarly scientific databases, including PubMed, Science Direct, and Scopus. Eligibility checks were performed based on predefined selection criteria. Finally, thirty-nine studies were considered.

Results: Exosomes have been indicated to use multitargeted pathways to improve wound healing by modulating numerous dysregulated signaling cascades involved in cell proliferation, cell cycle regulation, metastasis, apoptosis, and angiogenesis.

Conclusion: The outcome of this review might guide pre-clinical and clinical studies on the role of exosomes in skin wound healing.

Background: The increasing prevalence of antibiotic-resistant bacteria necessitates exploring nanotechnology as a potential solution for microbial elimination.

Objectives: This study aimed to investigate the antimicrobial and antioxidant effects of silver nanoparticles synthesized using aqueous extract from the Ephedra gerardiana (E. gerardiana) plant (EG@AgNPs).

Methods: Optimal synthesis conditions, including silver nitrate concentration, time, and temperature, were determined. Characterization of EG@AgNPs was conducted, which was followed by antimicrobial assessment against eight bacterial strains and one fungal strain. Additionally, the antioxidant properties of EG@AgNPs were evaluated using the DPPH method.

Results: XRD analysis confirmed EG@AgNPs synthesis. DLS analysis revealed a hydrodynamic diameter of 22 nm. FT-IR analysis confirmed the presence of functional groups from the E. gerardiana plant extract in EG@AgNPs. FESEM and TEM images depicted spherical nanoparticles ranging in size from 10 to 20 nm. Antimicrobial investigations using the broth microdilution method demonstrated that E. gerardiana plant extract at 7.5 mg/ml inhibited only Streptococcus mutans and Candida albicans growth, with no antimicrobial effects observed at lower concentrations. However, EG@AgNPs significantly enhanced the antimicrobial properties of the E. gerardiana plant extract. Notably, these nanoparticles exhibited the most significant effect on E. coli and the least on S. salivaris, with MIC value of 125 and 2000 μg/ml, respectively. Furthermore, they inhibited C. albicans growth at a concentration of 62.5 μg/ml. An assessment of the antioxidant properties of EG@AgNPs indicated a significant increase in antioxidant activity.

Conclusion: The E. gerardiana plant extract has emerged as a promising option for silver nanoparticle synthesis. These nanoparticles have been found to exhibit potent antimicrobial properties against Gram-positive and Gram-negative bacterial species, as well as C. albicans. Additionally, they have demonstrated antioxidant properties.

Objective: Combining immune checkpoint inhibitors and antiangiogenic agents offers a promising strategy to counteract the cooperative promotion of solid tumor growth by immune checkpoints and intratumoral angiogenesis.

Methods: We investigated the potential of thalidomide (THD) and anti-PD-1 antibody (PD-1 mAb) in suppressing tumor growth, enhancing immunity, and inhibiting angiogenesis.

Results: THD exhibited regulatory effects on PD-1 in CD4+ T cells and PD-L1 in cancer cells, along with tumor growth inhibition in A549 and Lewis lung carcinoma (LLC) cell lines. Combined with PD-1 mAb, THD increased intracellular IL-2 and IFN-γ expression in CD4+ T cells, enhanced granzyme (Gzm-B) expression in peripheral blood mononuclear cells (PBMCs), and reduced TNF-α expression in CD4+ T cells. In C57BL/6 mice, THD plus PD-1 mAb decreased LLC-derived lung tumor weight and volume, boosted CD8+ T cell infiltration in tumors, and reduced CD34+ intratumoral microvessel density.

Conclusion: This study highlights THD's role in modifying the tumor microenvironment to enhance PD-1 mAb efficacy, proposing a clinically feasible approach for improving PD-1 mAb treatment outcomes.

Alzheimer's disease (AD) is a neurological disorder that increases with age and must be treated immediately by worldwide healthcare systems. Internal neurofibrillary tau tangles and extracellular amyloid accumulation have been widely recognized as the primary causes of Alzheimer's disease. These degenerative age-related ailments are expected to proliferate exponentially as life expectancy rises. Experimental models of AD are essential for acquiring a deep knowledge of its pathogenesis and determining the viability of novel therapy options. Although there isn't a model that encompasses all the characteristics of real AD, these models are nonetheless highly helpful for the research of various modifications associated with it, even though they are only partially indicative of the disease circumstances being studied. Better knowledge of the advantages and disadvantages of each of the different models, as well as the use of more than one model to evaluate potential medications, would increase the effectiveness of therapy translation from preclinical research to patients. We outline the pathogenic characteristics and limitations of the main experimental models of AD in this review, including transgenic mice, transgenic rats, primates and non-primate models along with in-vitro cell culture models in humans. Additionally, it highlights the possible future of experimental modeling of AD and includes the co-morbid models.

Background: Silene undulata is historically used for inducing vivid and prophetic lucid dreams, but limited information exists on its phytochemical composition and potential pharmacological properties.

Objective: This study aimed to investigate the phytochemical composition of S. undulata through LC-MS/MS analysis and explore its potential serotonergic activity, which could support and confirm the traditional use of S. undulata as a dream-inducing plant.

Methods: LC-MS/MS analysis was conducted on S. undulata extract, identifying 51 phytochemicals, including norharman, harmalol, harmaline, harmine, and ibogaine alkaloids. ADMET and Molecular docking investigations were employed to assess the serotonergic potential of these compounds.

Results: The analysis revealed the presence of β-carboline alkaloids, such as norharman, harmalol, harmaline, harmine, and ibogaine, within S. undulata extract. ADMET analysis showed that these compounds have a favourable pharmacokinetic properties. In addition, molecular docking investigations showed that harmaline (-8.90 Kcal/mol), harmalol (-8.56 Kcal/mol), and ibogaine (-8.75 Kcal/mol) exhibited binding affinities comparable to the control molecule, LSD (-9.14 Kcal/mol), indicating potential agonistic activity at serotonin 5-HT2A receptor.

Conclusion: These findings provide insights into the potential therapeutic benefits of S. undulata, supporting its traditional use as a psychoactive plant. This study investigated the chemical constituents and potential serotonergic agonist activity of S. undulata for the first time. While promising, further research is necessary to uncover additional medicinal properties associated with the identified phytochemical components.

Pancreatic cancer kills millions of people worldwide each year and is one of the most prevalent causes of mortality that requires prompt therapy. A large number of people suffering from pancreatic cancer are detected at an advanced stage, with incurable and drug-resistant tumor, hence the overall survival rate of pancreatic cancer is less. The advance phase of this cancer is generated because of expression of the cancer-causing gene, inactivation of the tumorsuppressing gene, and deregulation of molecules in different cellular signalling pathways. The prompt diagnosis through the biomarkers significantly evades the progress and accelerates the survival rates. The overexpression of Mesothelin, Urokinase plasminogen activator, IGFR, Epidermal growth factor receptor, Plectin-1, Mucin-1 and Zinc transporter 4 were recognized in the diagnosis of pancreatic cancer. Nanotechnology has led to the development of nanocarriersbased formulations (lipid, polymer, inorganic, carbon based and advanced nanocarriers) which overcome the hurdles of conventional therapy, chemotherapy and radiotherapy which causes toxicity to adjacent healthy tissues. The biocompatibility, toxicity and large-scale manufacturing are the hurdles associated with the nanocarriers-based approaches. Currently, Immunotherapybased techniques emerged as an efficient therapeutic alternative for the prevention of cancer. Immunological checkpoint targeting techniques have demonstrated significant efficacy in human cancers. Recent advancements in checkpoint inhibitors, adoptive T cell therapies, and cancer vaccines have shown potential in overcoming the immune evasion mechanisms of pancreatic cancer cells. Combining these immunotherapeutic approaches with nanocarriers holds great promise in enhancing the antitumor response and improving patient survival.