Current pharmaceutical biotechnology最新文献

Cervical cancer has become a major worldwide health concern that demands attention to women's health and often needs more effective and specialized treatment options. Cervical cancer claims the lives of over 300,000 women globally, ranking as the fourth most prevalent cancer among women. The tumor microenvironment (TME) shapes a distinctive landscape for tumor survival, characterized by factors like immunosuppression, hypoxia, acidity, and nutrient scarcity. Comprising tumor cells, immune cells, mesenchymal cells, cancer-associated fibroblasts, and extracellular matrix, the TME reprograms key aspects of tumor development, uncontrolled proliferation, invasion, metastasis, and response to treatments. Recognizing the TME's pivotal role in tumor progression and treatment responsiveness, targeting the TME has emerged as a potential strategy in cancer therapy. This publication delves into recent TME research, offering a comprehensive overview of the specific functions of each TME component in cancer development and progression. Based on the reviewed literature, it appears that women with cervical cancer may benefit from more effective therapy, fewer side effects, and a higher quality of life in the future. By addressing pressing problems and unmet needs in the field, this review has the potential to significantly alter the course of cervical cancer treatment in the future. Furthermore, it outlines the primary therapeutic targets identified by researchers, which may prove valuable in treating tumors.

Neurological disorders are devastating conditions affecting both cognitive and motorrelated functions in aged people. Yet there is no proper medication to treat these illnesses, and the currently available medications can only provide symptomatic relief to the patients. All neurological disorders share the same etiology, such as oxidative stress, mitochondrial dysfunction, neurochemical deficiency, neuronal loss, apoptosis, endoplasmic reticulum stress, neuroinflammation, and disease-related protein aggregation. Nowadays, researchers use antioxidant-based strategies to prevent or halt the disease progression. Nerolidol, a strong antioxidant, possesses various biological activities and properties that treat cardiotoxicity, nephrotoxicity, neurotoxicity, and many other diseases. Many recent publications and research studies highlight the beneficial effect of nerolidol on brain disorders. In Alzheimer's disease, nerolidol shows neuroprotection by decreasing amyloid plaque formation, lipid peroxidation, cholinergic neuronal loss, locomotor dysfunction, neuroinflammation, and hippocampal damage via enhancing antioxidant expression. Also, it shows neuroprotection against rotenone-induced neurotoxicity by inhibiting microglial activation. Another study reported that nerolidol shows antiepileptic effects in animal models by suppressing kindling-induced memory impairment by decreasing oxidative stress. It has been found that NRL administration increases the antioxidant levels, decreasing the proinflammatory cytokine release as well as decreasing the apoptotic protein and cerebral infarct size. In conclusion, nerolidol tends to reverse the harmful effects of disease-related factors, including OS, neuroinflammation, protein aggregation, and apoptosis, making nerolidol a choiceable drug for the management of neurological disorders. The purpose of this review is to discuss the mechanism of nerolidol in treating various neurological disorders.

Objective: Atherosclerosis (AS) is an inflammatory disease of arterial intima driven by lipids. Liver X receptor alpha (LXRα) and peroxisome proliferator-activated receptor alpha (PPARα) agonists are limited in the treatment of AS due to their off-target effects and serious side effects. Therefore, this study was designed to construct a novel nanoparticle (NP) and evaluate its mechanism of action on inflammation inhibition and lipid reduction in AS.

Methods: We synthesized cRGD-platelet@MnO/MSN@PPARα/LXRα NPs (cRGD-platelet- NPs) and confirmed their size, safety, and targeting ability through various tests, including dynamic light scattering and immunofluorescence. In vivo and in vitro experiments assessed cell proliferation, apoptosis, inflammation, and plaque formation. Finally, the NF-κB signaling pathway expression in rat aorta was determined using a western blot.

Results: The synthesis of cRGD-platelet-NPs was successful; the particle size was approximately 150 nm, and the PDI was below 0.3. They could be successfully absorbed by cells, exhibiting high safety in vivo and in vitro. The cRGD-platelet-NPs successfully reduced plaque formation, improved lipid profiles by lowering LDL-cholesterol, total cholesterol, and triglycerides, and raised HDL-cholesterol levels. Additionally, they decreased inflammatory markers in the serum and aortic tissue, suggesting reduced inflammation. Immunohistochemistry and western blot analyses indicated that these NPs could not only promote M2 macrophage polarization but also suppress the NF-κB signaling pathway.

Conclusion: The newly developed cRGD-platelet-NPs with high safety are a promising approach to AS treatment, which can regulate ABCA1, reduce the formation of AS plaques, and enhance cholesterol efflux. The mechanism may involve the suppression of the NF-κB signaling pathway.

Objective: The objective of this study is to search for hydroxysafflor yellow A (HSYA) and Idiopathic sudden sensorineural hearing loss (ISSNHL)-related target genes and to study the treatment effects of HSYA on lipopolysaccharide (LPS)-induced endothelial cell injury.

Methods: We used network pharmacology to screen molecules related to HSYA and ISSNHL, then analyzed these molecules and their enriched biological processes and signaling pathways via Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). We selected inflammation-related hub genes for molecular docking determination by protein-protein interaction (PPI) analysis, and further verified them with in vitro experiments.

Results: Thirty-four HSYA-ISSNHL-related differential genes were obtained using drug-disease differential gene screening using online tools. Three key proteins, NF-κB, CASP3, and MAPK1, were selected according to Degree > 20. Among them, NF-κB is closely related to inflammation and ISSNHL. In in vitro experiments, HSYA reduced inflammatory (IL-6, TNF- α) and oxidative stress (ROS, SOD and MDA) indicators after LPS intervention, and the expression of NF-κB-related signaling pathway genes.

Conclusion: HSYA may reduce inflammation and oxidative stress by inhibiting the expression of the TLR4 / NF-κB-related signaling pathway, therefore protecting endothelial cells, which might be a potential mechanism of HSYA in ISSNHL treatment.

Aim: This study aimed to determine the phytoconstituents of Crateva religiosa bark (CRB) and evaluate the hypolipidemic effect of bioactive CRB extract by preventing adipocyte differentiation and lipogenesis.

Background: After performing the preliminary phytochemicals screening, the antioxidant activity of CRB extracts was determined through a DPPH (2, 2-diphenyl-1-picrylhydrazyl) assay. Ethyl acetate extract (CREAE) and ethanol extract (CRETE) of CRB were selected for chromatographic evaluation.

Method: The antihyperlipidemic potential was analyzed by molecular docking through the PKCMS software platform. Further, a 3T3-L1 cell line study via In vitro sulforhodamine B assay and western blotting was performed to confirm the prevention of adipocyte differentiation and lipogenesis Results: The total phenolic contents in CREAE and CRETE were estimated as 29.47 and 81.19 μg/mg equivalent to gallic acid, respectively. The total flavonoid content was found to be 8.78 and 49.08 μg/mg, equivalent to quercetin in CREAE and CRETE, respectively. CRETE exhibited greater scavenging activity with the IC50 value of 61.05 μg/ mL. GC-MS analysis confirmed the presence of three bioactive molecules, stigmasterol, gamma sitosterol, and lupeol, in CRETE. Molecular docking studies predicted that the bioactive molecules interact with HMG-CoA reductase, PPARγ, and CCAAT/EBP, which are responsible for lipid metabolism. In vitro, Sulforhodamine B assays revealed that CRETE dose-dependently reduced cell differentiation and viability. Cellular staining using 'Oil Red O' revealed a decreased lipid content in the CRETE-treated cell lines. CRETE significantly inhibited the induction of PPARγ and CCAAT/EBP expression, as determined through protein expression via western blotting.

Conclusion: The influence of CRETE on lipid metabolism in 3T3-L1 cells is potentially suggesting a new approach to managing hyperlipidemia.

Pharmaceutical research is increasingly focusing on transdermal drug delivery due to its potential for improved compliance and bioavailability. However, it is challenging due to the tight intracellular junctions present in the skin. Researchers have developed noninvasive methods, like transfersomes, to overcome these challenges. Transfersomes are ultra-deformable vesicles utilized for improved transdermal applications. They are made up of a phospholipid-rich lipid bilayer, an edge activator, and an ethanol/aqueous core. After topical treatment, transfersomes can penetrate deeper skin regions, delivering larger concentrations of active compounds. A transfersomal patch is applied to the skin and left for an extended period of time to allow a large dose of medication to permeate into the bloodstream. The transfersomal patch offers an advantage over the transfersomal gel because it allows the transfersomes to be applied under occlusive conditions, resulting in greater permeability, a lower amount of active medication, and a steady supply rather than a massive dose. This review represents the preparation and evaluation of transfersomal patches, recent research approaches, and future aspects of transfersomal patches. This study suggests that drug-loaded transfersomal patches could be a unique option to avoid invasive therapy.

Objective: The anticancer properties of recombinant α-luffin (LUF) are wellestablished. However, the cytotoxic effects of encapsulating LUF within niosomes on the SKBR3 breast cancer cell line have yet to be explored. Our study aimed to investigate whether this encapsulation strategy could improve cytotoxic effects.

Methods: Alpha-luffin was expressed, purified, and refolded. Then, this protein was utilized to craft an optimal formulation, guided by experimental design. In this work, we have explored various physicochemical properties, including particle size, polydispersity index, zeta potential, morphology, entrapment efficiency, drug release and kinetics, storage stability, and FTIR spectroscopy. Additionally, we have assessed the cellular uptake and cytotoxic effect of the optimized niosome formulation on the SKBR3 breast cancer cell line.

Results: The optimized niosome exhibited a mean diameter of 315±6.4 nm (DLS). Successful encapsulation of LUF into regularly shaped, spherical niosomes was achieved, with an encapsulation efficiency of 73.45±2.4%. Notably, Niosomal LUF (NLUF) exhibited significantly increased cytotoxicity against SKBR3 cells.

Conclusion: These findings suggest that niosomes loaded with LUF hold promise as a potential treatment strategy for breast cancer.

Plant fibers are strong, robust, flexible, versatile, renewable, and sustainable, making them valuable for many applications. Fibers from plants are now utilized in biomedical applications as reinforcements for biological composites to enhance the mechanical characteristics of composite biological materials including rigidity, tensile strength, and endurance. Reinforcement composites with hybrid components were explored in biodevices for prospective utilization in orthopedics, prosthetics, tissue fabrication, and surgical dressings. This review presents an overview of plant fibers, including their characteristics, influencing variables, and numerous applications. The text explores several methods for creating synthetic composites using common, sustainable fibers and the distinct characteristics of the resulting biological materials. The text also analyses many instances of composite hybrids and their application in the biological field. The results are summarised and suggestions for potential improvements are presented. The current research primarily examines the concept, specifications, efficiency, and potential advancements of composites with hybrid characteristics made from plant fibers.

Introduction: Nicotinamide Mononucleotide (NMN) has gained attention as a precursor to Nicotinamide Adenine Dinucleotide (NAD+) in recent years, commonly utilized in anti-aging therapies. The anti-aging effects of NMN on muscle and liver functions in middleaged and elderly people are still unclear.

Objective: Based on available randomized controlled trials, we conducted a meta-analysis to evaluate the impact of NMN on muscle and liver functions in middle-aged and elderly individuals.

Methods: We conducted searches on three electronic databases (PubMed, Embase, Web of Science) for randomized controlled trials involving NMN interventions in middle-aged and elderly populations. Through the Cochrane Handbook, we assessed the specific methodological quality. All statistical analyses were obtained by Stata15, and statistical significance was set as P<0.05.

Results: There were 412 participants from 9 studies in this meta-analysis. Based on changes in gait speed (SMD: 0.34 m/s, 95%CI [0.03, 0.66] p = 0.033), NMN had significant effects on muscle mass. Moreover, NMN had a better effect on ALT (SMD: -0.29 IU/L, 95%CI [-0.55, -0.03] p = 0.028). Subgroup analysis indicated that administering a small dose of NMN exerted the most prominent impact on Homeostasis Model Assessment-Insulin Resistance (HOMA-IR).

Conclusion: NMN has positive efficacy in enhancing muscle function, reducing insulin resistance and lowering aminotransferase levels in middle-aged and elderly individuals. NMN is an encouraging and considerable drug for anti-aging treatment.

Transdermal Drug Delivery Systems (TDDS) have emerged as a promising method for administering therapeutic agents due to their non-invasive nature and patient-friendly approach. However, the effectiveness of this system is limited to drugs with specific physicochemical properties that allow for transdermal delivery as the skin acts as a barrier. To address this limitation, researchers have been exploring alternative approaches to improve drug delivery through the stratum corneum, ensuring consistent drug distribution at controlled rates. Thirdgeneration delivery systems have been developed to facilitate the delivery of various drugs across the skin barrier by disrupting the stratum corneum while protecting deeper skin tissues from injury. This review has explored various approaches that have gained popularity in enhancing drug delivery through TDDS, including microneedle-mediated, nanoparticle-enabled, thermal ablation-enhanced, and electroporation-driven delivery systems. It has discussed the mechanisms of drug delivery and potential applications for different types of drugs and detailed the clinical studies. This review has also highlighted the significant advancements in TDDS, offering valuable insights into both the pharmaceutical field and biomedical applications. The continued exploration and refinement of these delivery systems, particularly with the incorporation of Internet-of-Things (IoT) technology, Artificial Intelligence (AI), and machine learning, hold promise for expanding the scope of therapeutic interventions.