Current pharmaceutical biotechnology最新文献

Polymeric nanoparticles (PNPs) are considered to be a revolutionary method for drug delivery and offer significantly more advantages than conventional drug delivery systems. This review synthesizes recent research on biodegradable polymers in drug delivery, emphasizing their properties, modifications, toxicity, and applications in drug absorption. It consolidates key insights from 193 research papers to offer a comprehensive overview of the field, addressing existing research gaps and highlighting various applications. Polymers can be classified based on their structure, source, and biodegradability, which are crucial for assessing their environmental impact and suitability for various applications. Polymers are categorized into two main groups based on biodegradability: biodegradable and non-biodegradable. The primary aim of this review is to elucidate the diverse applications of natural and synthetic biodegradable polymeric nanoparticles, which include cancer treatment, diabetes management, pulmonary drug delivery, and the treatment of ocular infections, all of which are thoroughly explored in this review. Additionally, the role of polymer-based hydrogels is explored as a promising solution in drug delivery. These hydrogels address issues such as poor stability and enhance treatment efficacy by ensuring the sustained release of drugs.

Background: In view of the increasing resistance of Candida species, it is necessary to explore alternative strategies. In this context, essential oils have emerged as promising options, among which the essential oil of Astronium urundeuva (M. Allemão) Engl. has shown potential, as it is traditionally used in folk medicine for the treatment of inflammation and multiple infections. Thus, the aim of this study was to evaluate the chemical profile, anti- Candida activity, and Fluconazole (FCZ) potentiating effect of the essential oil extracted from the leaves of A. urundeuva (EOAU) and its ability to inhibit the virulence mechanism in Candida species.

Methods: The essential oil was obtained via hydrodistillation and characterized using gas chromatography-mass spectrometry. To evaluate the antifungal effects and the modulating activity of Fluconazole (FCZ), the essential oil was diluted in DMSO (1 mL) and SDB medium (9 mL) and tested on 3 Candida strains using the serial microdilution method. In addition, a morphological transition assay was used to evaluate its capacity to inhibit fungal virulence.

Results: The major constituent of EOAU was the monoterpene β-myrcene (71.07%). The results indicate that the essential oil exhibits an antifungal effect, with C. tropicalis being the most susceptible species. At subinhibitory concentrations (MC/8), the EOAU enhanced the action of fluconazole against C. krusei and C. tropicalis. The EOAU strongly inhibited the morphological transition in C. tropicalis.

Conclusion: EOAU is rich in β-myrcene and exhibits an interesting fungistatic effect, making it a great natural candidate for inhibiting Candida spp. virulence.

Aims: To optimize the culture process of Mesenchymal Stem Cells (MSCs) and enhance their biological functions.

Background: MSCs have shown great potential in treating various diseases due to their low immunogenicity and potent paracrine effects. However, the inherent heterogeneity of MSC populations, which can vary depending on the culture conditions, may challenge large-scale clinical application.

Objective: This study investigates the inconsistency of MSCs cultured in different media, from the transcriptional level to biological functions.

Method: RNA sequencing was used to identify different expressed genes of MSCs separated and expanded in three media, which were then validated with qPCR. In vitro assays, including proliferation, tube formation, wound healing, multilineage differentiation, paracrine secretome and injured hepatocyte protection assay, were performed to verify the potential differences among three groups.

Result: MSCs cultured in platelet lysate-containing medium exhibited high expression of genes involved in extracellular matrix regulation, collagen metabolic processes, and angiogenesis, whereas those cultured in serum-free medium demonstrated high expression of genes associated with DNA replication and chromosome segregation. MSCs cultured under serum-containing medium indicated high levels of genes associated with extracellular matrix regulation, cartilage development, and chemotaxis. The results of functional comparative experiments were consistent with the differences in their gene expression patterns. Notably, MSCs cultured in the serum- containing system exhibited greater protective effect against hepatocyte activity.

Conclusion: Different culture conditions affect the biological functions of MSCs. Optimal conditions should be investigated for applications. Next, an in vivo model should be established to evaluate differences in MSC tissue repair function under various culture conditions.

Introduction: The crystallization of heme into β-hematin and its subsequent conversion to hemozoin has garnered significant interest as a promising target for the development of novel antimalarial therapies, particularly through the heme detoxification pathway. Furthermore, the therapeutic efficacy of chloroquine (CQ) has been widely recognized, with several studies highlighting its role as an inhibitor of β-hematin and hemozoin formation.

Methodology: This study reports the synthesis of two novel CQ-derived compounds, 7- chloroquinolin-4-amine (CQC1) and 7-chloro-4-(¹-oxidaneyl)-3,4-dihydroquinoline (CQC2), and evaluates their individual inhibitory effects on β-hematin formation.

Results: Notably, comparative analysis of the experimental data revealed significant variability in the IC50 values for these compounds, which correspond to the concentration required to inhibit 50% of β-hematin synthesis. The impact of incubation time and compound concentration on IC50 values was also investigated.

Conclusion: The findings suggest that increasing the concentration and incubation time of both CQ derivatives led to a reduction in their IC50 values, with both compounds demonstrating enhanced inhibitory activity relative to commercial chloroquine (CQ).

Background: Bacterial cellulose, which is used in many fields from biomedicine to electronics, is promising as an alternative wound dressing instead of traditional gauze in wound treatment.

Objectives: The objective of this study was to evaluate the potential use of cellulose produced by acetic acid bacteria isolated from rotten fruits as a wound dressing.

Methods: In our study, rotten fruit samples were incubated in Hestrin-Schramm (HS) Broth medium. Then, a loopful of the pellicle-forming samples was taken and inoculated onto Hestrin- Schramm (HS) agar using the streak culture method and bacteria were isolated. Identification of bacteria was performed using the BLAST program after 16S rRNA sequence analysis. Physicochemical properties and morphological characterization of bacterial cellulose produced by static culture were examined using Fourier transform infrared (FTIR) and scanning electron microscopy (SEM), respectively, and the swelling ratio was investigated. Antibiotic susceptibilities of bacterial cellulose membranes impregnated with different concentrations of gentamicin (50 μg/mL, 100 μg/mL, 200 μg/mL) against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 were determined by the disk diffusion method.

Results: The bacteria isolated from rotten fruits were identified as Acetobacter tropicalis NBRC 16470. The structure of cellulose produced by static culture was confirmed by a peak at 3,240 cm-1 in FTIR analysis and fibril structures in SEM analysis. Bacterial cellulose had a swelling ratio of 27.37± 2 .99 fold. The zone diameters formed by bacterial cellulose disk (50 μg/mL gentamicin) and gentamicin (10 μg) disk against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 were almost the same.

Conclusion: The production of bacterial cellulose, which has the potential to be used as a wound dressing from rotten fruits, is important in terms of recycling and low cost.

Flavonoids, plant-derived polyphenolic compounds, have garnered significant attention for their broad-spectrum antimicrobial potential, encompassing antibacterial, antifungal, and antiviral activities. These bioactive molecules exert their effects through multiple mechanisms, including disruption of microbial cell membranes, inhibition of nucleic acid synthesis, suppression of biofilm formation, and interference with key bacterial enzymes. Notable flavonoids such as quercetin, apigenin, and kaempferol exhibit potent activity against bacterial pathogens like Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, as well as fungal pathogens such as Aspergillus fumigatus and Candida albicans. Furthermore, flavonoids can potentiate the efficacy of conventional antibiotics by inhibiting bacterial efflux pumps, a critical mechanism contributing to antibiotic resistance. Recent advancements in structure-activity relationship (SAR) studies have underscored the influence of structural modifications- such as prenylation, hydroxylation, and methoxylation-on the antimicrobial potency of flavonoids. By highlighting these insights, this review provides a unique perspective on flavonoid-based antimicrobial strategies, particularly their synergistic potential with existing antibiotics. These findings position flavonoids as promising candidates for novel antimicrobial therapies, particularly in the face of increasing antibiotic-resistant pathogens. However, further research is needed to elucidate their precise mechanisms and optimize their therapeutic applications.

Background: The combination of Gardeniae Fructus (ZZ) and Scutellariae Radix (HQ) is a traditional Chinese medicine used for Alzheimer's disease (AD). However, the molecular mechanisms underlying its anti-dementia effects, particularly its multi-component synergy and pathway modulation, remain poorly understood.

Objective: Our study employed an integrated systems pharmacology approach to mechanistically decode the anti-AD properties of ZZ-HQ, combining network pharmacology predictions, molecular docking simulations, and experimental validation to identify critical bioactive components, molecular targets, and therapeutic pathways.

Methods: A comprehensive network pharmacology analysis was performed to identify bioactive compounds within the ZZ-HQ complex and their potential protein targets associated with AD. Molecular docking was utilized to predict and assess the binding interactions between key bioactive compounds and AD-related protein targets. Experimental validation focused on baicalin, a major active compound in the ZZ-HQ complex, evaluating its effects on cell viability, apoptosis regulation, oxidative stress reduction, and the activation of the PI3K/Akt signaling pathway.

Results: Fifty-four bioactive compounds were identified in the ZZ-HQ complex, interacting with 258 AD-associated proteins. Key compounds, such as baicalein and norwogonin, demonstrated strong binding affinities with pivotal proteins, including SRC and PIK3R1. Experimental studies further confirmed that baicalin significantly improved cell viability by activating the PI3K/Akt pathway, reducing apoptosis, and alleviating oxidative stress.

Conclusion: Our study uncovered the therapeutic potential of the ZZ-HQ combination in addressing AD through multi-target mechanisms, particularly via modulation of the PI3K/Akt pathway and oxidative stress. These findings provide a scientific basis for the pharmacological effects of ZZ-HQ and offer valuable insights for further research on its potential application in AD treatment.

Rare diseases, defined as conditions affecting fewer than 200,000 people in the United States or less than 1 in 2,000 people in Europe, pose significant challenges for healthcare systems and pharmaceutical research. This comprehensive review examines the evolving landscape of orphan drug development, analyzing scientific, economic, and regulatory challenges while highlighting recent technological breakthroughs and innovative approaches. We explore how artificial intelligence, next-generation sequencing, and personalized medicine are revolutionizing rare disease research and treatment development. The review details key advances in therapeutic approaches, including gene therapy, cell-based treatments, and drug repurposing strategies, which have led to breakthrough treatments for previously untreatable conditions. We analyze the impact of international collaborations, such as the International Rare Diseases Research Consortium, and discuss how regulatory frameworks worldwide have evolved to accelerate orphan drug development. The paper highlights the growing market for orphan drugs, projected to reach $242 billion by 2024 while examining the complex challenges of ensuring treatment accessibility and economic sustainability. We assess innovative clinical trial designs, patient registry development, and emerging strategies in personalized medicine that are transforming the field. Despite notable advancements, significant gaps remain in diagnosis, treatment accessibility, and sustainable funding for rare disease research. The review concludes by proposing specific actions for enhancing international collaboration, improving patient registries, and aligning incentives to address the unmet medical needs of rare disease patients, emphasizing the critical role of continued public-private partnerships and technological innovation in advancing orphan drug development.

Owing to the lack of appropriate selective treatments, hepatocellular carcinoma (HCC) remains one of the major reasons of cancer associated death. Chronic liver failure nearly always accompanies HCC, and doctors usually detect it only after the disease has progressed beyond the point where curative therapies are possible. Despite the fact that HCC has distinct morphological and phenotypic patterns, therapeutic options are limited to comparatively homogeneous drugs such as multi-targeted tyrosine kinase blockers and immune checkpoint blockers. Multiple studies evaluating the effectiveness of different medications have yielded disappointing findings, indicating that HCC has poor immunity to chemotherapy, which is exacerbated by multidrug resistance. As a result, more successful therapies addressing HCC's disordered metabolic and molecular pathways are needed. The quite often change in sequence of genes and molecular targets in HCC patients are telomerase reverse transcriptase, Wnt/-catenin signaling pathway oncogene (CTNNB1), and the TP53 gene, according to integrated genomic profiling. Furthermore, new approaches like genome-scale metabolic replicas may be utilized to explicate the basic cancer specific metabolism, allowing for such exploration of promising biomarkers and drug candidates. The clinical implications of metabolic network driven heterogeneity of HCCcaseson the basis of redox response, metabolite use, and subtype specific pathways could help accelerate the advancement of personalised medicine. Another interesting strategy is microRNA- based therapy which involves miRNA antagonists to block oncogenic miRNAs and miRNA substitution, which entails reintroducing a tumor-suppressor miRNA to restore function following a functional impairment. The existing and evolving clinical purpose in context of molecular targets and metabolic network-based approaches are summarised in this review, paving the way for successful HCC patient care.

Background: Oropharyngeal candidiasis (OPC), a fungal infection affecting the mouth and throat, imposes a substantial burden on vulnerable populations such as HIV/AIDS patients, cancer treatment recipients, and the elderly. Conventional antifungal medications are encountering increasing resistance and side effects, necessitating the exploration of novel therapeutic approaches.

Objectives: This review proposes a comprehensive strategy for developing a novel natural product- based antifungal formulation targeting OPC. The approach involves harnessing promising natural compounds with established antifungal properties and employing advanced delivery systems like mucoadhesive microemulsions to improve efficacy and minimize adverse effects. Additionally, the review explores the integration of computational methods to expedite the identification and development of potent antifungal agents.

Methods: A comprehensive literature review was conducted using databases such as PubMed, Scopus, and Web of Science. Search terms included combinations of "oropharyngeal candidiasis," "natural antifungal agents," "flavonoids," "mucoadhesive microemulsions," "computational drug discovery," and "in vitro/in vivo studies." Priority was given to studies published within the last ten years.

Results: The review identifies promising natural compounds with antifungal activity against Candida species commonly associated with OPC. Additionally, several studies highlight the potential of computational tools such as molecular docking and in silico ADMET for rapidly identifying natural compounds with potent antifungal activity and favorable pharmacokinetic and safety profiles. A brief overview of in vitro and in vivo experiments is provided, emphasizing their role in validating the safety and efficacy of the proposed natural product-based antifungal formulation. Formulation and analytical aspects are also discussed.

Conclusion: The multidisciplinary approach outlined, incorporating natural products, computational methods, advanced preclinical in vitro and in vivo experiments, and advanced delivery systems, offers promise for the rapid, cost-effective development of safe and effective optimized formulations to address the growing challenge of OPC, particularly in vulnerable populations.