Current pharmaceutical biotechnology最新文献

Background: The relationship between uterine fibroids and keloid/hypertrophic scars has been contradictory. Our research employs a bidirectional Mendelian Randomization (MR) approach to establish a clearer understanding of this potential causal link.

Objective: This study aimed to determine the effect of uterine fibroids on keloid/hypertrophic scars and the effect of keloid/hypertrophic scars on uterine fibroids.

Purpose: We aimed to demonstrate the relationship between uterine fibroids and keloid/ hypertrophic scars.

Method: Our bidirectional MR study utilized summarized data from genome-wide association studies (GWAS) focused on European populations. Our primary tool for establishing causality was the Inverse-Variance Weighted (IVW) method. To reinforce the IVW findings, we also applied four alternative MR methods: MR-Egger, Maximum Likelihood, Weighted Mode, and Weighted Median.

Result: The IVW method indicated a significant causal link, with uterine fibroids greatly raising the likelihood of developing keloids (Odds Ratio [OR] = 1.202, 95% Confidence Interval [CI]: 1.045-1.381; P=0.010) and hypertrophic scars (OR = 1.256, 95% CI: 1.039-1.519; P=0.018). Parallel results were observed with the MR-Egger, Maximum Likelihood, Weighted Mode, and Weighted Median methods. Sensitivity analyses indicated robustness in these findings, with no evidence of heterogeneity or horizontal pleiotropy. Conversely, the reverse MR analysis did not demonstrate an increased risk of uterine fibroids due to keloids or hypertrophic scars.

Conclusion: This study elucidates a significant causal effect of uterine fibroids on the development of keloid and hypertrophic scars, offering valuable insights into their pathogenesis and potential therapeutic targets.

Proteases, a group of hydrolytic enzymes catalyzing the hydrolysis of peptide bonds, play pivotal roles in various physiological processes and have emerged as key contributors to the pathogenesis of diverse diseases. This work provides an insight into the impact of protease activity on different disease contexts, highlighting their involvement in cancer, inflammatory disorders, cardiovascular diseases, infectious diseases, and neurodegenerative conditions. In cancer, proteases facilitate tumor growth, invasion, and metastasis, while in inflammatory diseases, dysregulated protease activity exacerbates tissue damage and inflammation. Cardiovascular diseases involve proteases in extracellular matrix remodeling, affecting arterial structure. In infectious diseases, proteases play crucial roles in pathogen invasion and immune evasion. Neurodegenerative diseases are characterized by protease dysregulation, contributing to protein misfolding and aggregation. As research progresses, understanding the intricate relationships between proteases and diseases becomes essential for developing targeted therapeutic strategies. This review aims to provide a comprehensive glimpse into the diverse impact of protease activities on various diseases, emphasizing their potential as crucial players in the landscape of disease pathology and potential therapeutic interventions.

Phytosterols are bioactive substances found naturally in the cell membranes of plants and have an arrangement of molecules similar to that of fat, which is produced by mammalian cells. They are widely distributed as dietary sources of lipids in plants, such as nuts, seeds, olive oil, and legumes. This review provides a summary of the efficacy of BS in treating lifestyle problems, as well as an appraisal of previous research. Data was collected from PubMed, ScienceDirect, Scopus, and Google scholar (1968 -2024) using standard keywords "β-sitosterol," "Classification," "Biosynthesis," "Pharmacokinetics," "Herbal nutraceutical," "Analytical," "Structure," "Pharmacological effect." A total of 222 studies were included in this review. Numerous in vitro and in vivo investigations have shown that BSs exhibit several biological properties such as calming and anxiolytic effects; narcotic and immune-stimulating effects; antibacterial, antineoplastic, inflammation-causing, lipid-lowering, and hepatoprotective effects; and antioxidant, anti-diabetic, and wound-healing effects in contrast to respiratory and non-alcoholic fatty liver disease illnesses. β-sitosterol is a promising natural substance for the management of cholesterol and inflammation. However, further studies are needed to understand its pharmacological consequences and determine its best use in clinical applications. β-Sitosterol, also known as "plant sterol ester," is often present in plants and has several applications, notably in medicine and the food industry. Experimental research on β-sitosterol provides unequivocal evidence that phytosterol can be supplemented with other methods to combat serious illnesses. Such a high potential identifies this substance as a noteworthy medication for the future based on its composition. Although β-sitosterol has anticancer and anti-inflammatory properties and is useful in human clinical trials for enlarged prostates, its mechanism of action remains unclear.

In recent years, bioactive constituents from plants have been investigated as an alternative to synthetic approaches of therapeutics. Mangiferin (MGF) is a xanthone glycoside extracted from Mangifera indica and has shown numerous medicinal properties, such as antimicrobial, anti-diarrhoeal, antiviral, anti-inflammatory, antihypertensive, anti-tumours, and anti-diabetic effects. However, there are numerous challenges to its effective therapeutic usage, including its low water solubility, limited absorption, and poor bioavailability. Nano formulation approaches in recent years exhibited potential for the delivery of phytoconstituents with key benefits of high entrapment, sustained release, enhanced solubility, stability, improved pharmacokinetics, and site-specific drug delivery. Numerous techniques have been employed for the fabrication of MGF-loaded Nano formulations, and each technique has its advantages and limitations. The nanocarriers that have been employed to fabricate MGF nanoformulations for various therapeutic purposes include; polymeric nanoparticles, nanostructure, lipid carriers, polymeric micelles, Nano emulsions, microemulsion & self-microemulsifying drug delivery system, solid lipid nanoparticles, gold nanoparticles, carbon nanotubes, transfersomes, nanoliposomes, ethosomes & transethosomes, and glycethosomes. Different biopharmaceutical characteristics (size, shape, entrapment efficiency, zeta potential, in vitro drug release, ex vivo drug permeation,, and in vivo studies) of the mentioned MGF-loaded nanocarriers have been methodically discussed. Patent reports are also included to further strengthen the potential of MGF in the management of diseases.

Introduction: The macrolide-resistant Bordetella pertussis (MRBp) has appeared in Asia and has even been prevalent in China. Since the antibiotic sensitivity test is not carried out in the clinical setting, macrolide is still the first choice of antibiotic in MRBp infection. Further, the macrolide therapy for pertussis needs to be revised. Macrolide has always shown a positive effect on other macrolide-resistant bacterium infections in clinical applications. However, the mechanism of macrolide on MRBp remains unclear.

Objective: The objective of this study was to investigate the effect of virulence of MRBp under the sub-MIC erythromycin.

Methods: This study evaluated a representative isolate BP19147 (ptxP1/fhaB3-MRBp) under a series of sub-inhibitory concentrations of erythromycin. We measured the growth curve, biofilm formation, and autoaggregation assay under Stainer and Scholte (SS) broth. The relative gene expression was detected by RT-qPCR.

Results: The proteomics was detected by label-fee DIA. The growth ability and virulence factors of MR isolate BP19147 were inhibited by sub-MIC of erythromycin and had a concentration- dependent effect. From the proteomics results, the pertussis toxin, filamentous haemagglutinin, and pertactin did not show a statistical difference (p >0.05). Other virulence factors (including dermonecrotic toxin, Invasive Adenylate cyclase/haemolysin. etc) showed a statistical difference (p <0.05). In the KEGG enrichment, the BvgAS system, biofilm formation, and some adaptive systems were inhibited by erythromycin.

Conclusion: The sub-MIC of erythromycin may reduce the virulence of MRBp, which will provide a theoretical basis for the rational use of erythromycin for MRBp infection and help the development of new antibiotics.

Skin cancer, which comprises both melanoma and non-melanoma forms, is frequently diagnosed as the predominant malignancy among today's population. Existing treatments are often prolonged and complex, have a low rate of success, and have side effects. This complexity leads to poor patient adherence and increases the risk of disease recurrence. Ethosomes, extensively studied for their applications in topical and transdermal therapies, are distinguished by their high ethanol content, which facilitates enhanced skin penetration and efficient drug delivery. Compared to traditional liposomes, ethosomes offer notable advantages due to their unique composition, demonstrating potential efficacy in treating various skin conditions, including basal cell carcinoma, squamous cell carcinoma, and melanoma. The present review provides a brief introduction to skin melanoma and its pathogenesis, signalling pathways, biomarkers, the need for ethogel-based drug delivery, applications of ethosomes against skin cancer, and clinical trials.

Fungal infections contribute to over 1.5 million fatalities each year, with cutaneous mycoses standing as prominent global infections. The spectrum of these mycoses varies widely, encompassing enduring afflictions like ringworm, localized infections such as tinea capitis, recurrent instances like vaginal candidiasis, and potentially fatal systemic infections impacting multiple organ systems. The escalating recognition of the health and socioeconomic ramifications associated with fungal pathogens underscores their importance in contemporary discourse. On a global scale, projections indicate that over 300 million individuals experience significant fungal infections annually, resulting in a mortality rate exceeding 1.5 million deaths per year. Alarmingly, resistance to commonly used antifungal drugs was on the rise, with some reports suggesting that over 10% of Candida bloodstream isolates worldwide were resistant to fluconazole, a commonly prescribed antifungal medication. Therefore, there is an immediate need to increase the accessibility of new antifungal medications while minimizing their costs and adverse effects. Fungi, as heterotrophic organisms, acquire nutrients through absorption. Their filamentous structure, composed of hyphae, facilitates efficient nutrient uptake by secreting enzymes that break down complex organic matter into simpler compounds. These organisms exhibit remarkable adaptability in responding to environmental cues, adjusting growth rates, and altering morphological features. Fungi regulate their metabolism intricately, undergoing various metabolic pathways for energy production and utilizing diverse substrates for respiration. Additionally, they exhibit distinctive reproductive strategies, employing both sexual and asexual modes of reproduction, contributing to their genetic diversity and resilience in diverse ecosystems. We now have more information than ever on the origins of infection as well as the physiology of fungi cells, giving us the chance to use it to produce new generations of antifungals. This review includes various novel antifungal drug targets showing their possible effects via different mechanisms aiming at vital functions like GPI synthesis, cell wall synthesis, hyphal growth, and other essential pathways responsible for fungal growth.