Current pharmaceutical design最新文献

Nanoemulsions have gained popularity as drug delivery vehicles owing to the enhanced solubility of insoluble drugs, the augmented stability of photo- and thermosensitive substances, and the facilitation of transdermal permeation of efficacy substances. As the cell surfaces of the skin, cornea, gastrointestinal mucosa, and other cells in living organisms carry negative charges, cationic nanoemulsions (CNE) mainly promote drug absorption through electrostatic effects. In this review, a brief characterization of CNEs is provided, and the types of cationic agents and their roles in nanoemulsions, including cationic surfactants, cationic lipids, cationic polymers, cationized polysaccharides, and phytosphingosine (PS), are discussed. In addition, the current application circumstances of CNEs in ocular drug delivery, mucosal drug delivery, and transdermal drug delivery systems are elaborated on, and the crucial matters that require attention during the research process are briefly discussed. Eventually, the extensive application prospects of CNEs are envisioned.

Background: Healthcare is rapidly leveraging machine learning to enhance patient care, streamline operations, and address complex medical issues. Though ethical issues, model efficiency, and algorithmic bias exist, the COVID-19 pandemic highlighted its usefulness in disease outbreak prediction and treatment optimization.

Aim: This article aims to discuss machine learning applications, benefits, and the ethical and practical challenges in healthcare.

Discussion: Machine learning assists in diagnosis, patient monitoring, and epidemic prediction but faces challenges like algorithmic bias and data quality. Overcoming these requires high-quality data, impartial algorithms, and model monitoring.

Conclusion: Machine learning might revolutionize healthcare by making it more efficient and better for patients. Full acceptance and the advancement of technologies to improve health outcomes on a global scale depend on resolving ethical, practical, and technological concerns.

Parkinson's Disease (PD) is a neurodegenerative disorder of the central nervous system (CNS). Given the increasing age of the general population, PD has emerged as a significant public health and societal concern, impacting both individual well-being and socioeconomic progress. The present interventions have proven insufficient in impeding the progressive nature of PD. Consequently, it is imperative to promptly identify efficacious strategies for the prevention and treatment of PD. Icaritin (ICT) is a flavonoid extracted from Epimedium Brevicornu Maxim that is a phytoestrogen with antitumour, anti-inflammatory, antioxidant, antiaging, and neuroprotective properties. This paper reviews the protective effect of ICT on dopaminergic neurons through anti-oxidative stress, improving mitochondrial function, inhibiting neuroinflammatory responses, reducing Lewy body formation, and decreasing apoptosis. The primary objective of this article is to provide valuable insights and serve as a reference for the potential use of ICT in the prevention and treatment of PD.

Nanotechnology has emerged as a promising avenue for targeted drug delivery to the small intestine, offering precise control over drug release and enhanced therapeutic efficacy. This review discusses recent advancements and challenges in nanotechnology-based approaches for targeted drug delivery to the small intestine. The small intestine presents unique challenges for drug delivery, including enzymatic degradation, low permeability, and rapid transit time. Nanotechnology offers solutions to these challenges by providing carriers capable of protecting drugs from degradation, enhancing their absorption, and facilitating site-specific delivery. Various nanocarrier systems have been explored for targeted drug delivery to the small intestine, including liposomes, polymeric nanoparticles, dendrimers, and solid lipid nanoparticles. These carriers can be functionalized with ligands targeting specific receptors or transporters expressed on the intestinal epithelium, enabling efficient uptake and intracellular delivery of drugs. Additionally, nanotechnology enables the controlled release of drugs, allowing for sustained and/or triggered release profiles tailored to the physiological conditions of the small intestine. This precise control over drug release can improve therapeutic outcomes while minimizing systemic side effects. Despite the significant progress in nanotechnology-based drug delivery to the small intestine, several challenges remain. These include achieving sufficient drug loading capacity, ensuring biocompatibility and safety of nanocarriers, and addressing regulatory concerns associated with their clinical translation. In conclusion, nanotechnology holds immense potential for targeted drug delivery to the small intestine, offering solutions to overcome the limitations of conventional drug delivery systems. Addressing the remaining challenges will be crucial for realizing the full therapeutic benefits of nanotechnology in treating diseases affecting the small intestine.

CNS illnesses specified by slow deprivation of especially preganglionic neurons, as opposed to the selective static neuronal loss caused by a toxic or metabolic condition, are known as Neurodegenerative disorders. Neurodegenerative disorders are differentiated clinically by behavioral or cognitive problems. The management and treatment of neurodegenerative disorders pose significant challenges, necessitating a multidimensional approach. While primarily designed for psychiatric conditions, antipsychotics have shown potential in ameliorating behavioral and psychological symptoms in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. This review explores the existing literature, highlighting the potential benefits, risks, and considerations associated with incorporating antipsychotics into the treatment paradigm for neurodegenerative disorders. Additionally, it discusses the evolving landscape of personalized treatment strategies, emphasizing the need for a multidisciplinary approach to optimize patient outcomes in the complex realm of neurodegenerative disorder management.

Introduction: Atrophic vaginitis (AV) is a common and frequently occurring disease, lacking effective curative measures. Exploring the mechanism of vaginal mucosal homeostasis from the perspective of metabolites has great research prospects.

Methods: We compared the metabolic profiles of vaginal secretions between AV patients and healthy individuals via liquid chromatography-tandem mass spectrometry (LC-MS/MS). We further explored effective and sensitive metabolites and metabolic pathways for senile vaginitis through bioinformatics analysis and experimental verification. Through untargeted metabolomics analysis, we screened 561 differential metabolites in two groups of vaginal secretion samples. These differential metabolites were mainly concentrated in fatty acids/carboxylic acids, glycerophospholipids, organic oxides, steroids, and their derivatives. They were mainly enriched in purine metabolism, diabetic cardiomyopathy generation, and choline metabolism pathways.

Results: The receiver operating characteristic analysis showed the metabolites (e.g., guggulsterone, umbelliprenin, and inosinic acid) to have good discrimination ability for the AV group. In addition, we also explored the potential mechanism of action of umbelliprenin at the cellular level.

Conclusion: This study is expected to provide a new perspective for understanding the relationship between metabolites and the pathogenesis of AV.

Chronic Kidney Disease (CKD) affects about 37 million Americans. Approximately 20% of patients with high blood pressure and 33% of patients with diabetes have kidney disease. CKD is most common among people aged 65 or older and is slightly more common in women. It substantially impacts certain ethnic groups more than others and is associated with a huge financial burden. End-Stage Kidney Disease (ESKD) is treated with dialysis or a kidney transplantation. CKD and ESKD are very detrimental and expensive illnesses, demanding creative therapeutic interventions to enable better management and enhanced clinical outcomes. Toward this goal, agents from various novel drug classes showed promising safety and efficacy in patients with varying severity of CKD in several phase 2 studies. This concise review will shed light on the clinical trials of runcaciguat, cotadutide, osocimab, and Endothelin Receptor Antagonists (ERAs) in patients with CKD and/or ESKD. These drugs were retrieved following surveying the Clinical Trial database as well as the Pubmed database, both maintained by the US National Library of Medicine.

Neurodegenerative disorders (NDs) are highly prevalent among the aging population. It primarily affects the central nervous system (CNS), but the effects are also observed in the peripheral nervous system. Neural degeneration is a progressive loss of structure and function of neurons, which may ultimately involve cell death. The blood-brain barrier (BBB), which separates peripheral blood circulation from the central nervous system, is essential for maintaining intracerebral homeostasis. Drug delivery systems based on nanomaterials (NDDSs) employ nanoparticles (NPs) as their drug transport vehicles. Moreover, nanotechnologybased methods usually involve numerous nanosized carrier platforms, which potentiate the effect of the therapeutic agents in the therapy of NDs, especially in diagnosis and drug delivery, with negligible side effects. In addition, nanotechnology-based techniques have offered several strategies to cross BBB to intensify the bioavailability of drug moieties in the brain. In the last few years, diverse kinds of nanoparticles (NPs) have been developed by incorporating various biocompatible components (e.g., polysaccharide-based NPs, polymeric NPs, selenium NPs, AuNPs, protein-based NPs, gadolinium NPs, etc.), that showed great therapeutic benefits against NDs. The discussion concluded with a look at the opportunities and problems that come with NDDSs in modern basic and clinical research.

Introduction: The increasing use of antibiotics coupled with the lack of innovative and effective antimicrobial agents has increased the development of antimicrobial resistance (AMR) worldwide. To overcome the AMR-associated prolonged disease duration and increased mortality rates, new antimicrobial agents are in high demand. In this context, hydrazone and oxadiazole derivatives are endowed with remarkable biocidal activity, becoming profitable scaffolds in the design of antimicrobial candidates.

Method: In this study, the antimicrobial effects of N-acyl hydrazones 1-15 and 2,5-substituted 1,3,4- oxadiazoles 16-27 against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, Bacillus subtilis ATCC 6633, and clinically isolated Shigella sonnei, Klebsiella pneumoniae, and Candida albicans were evaluated. For this purpose, Kirby-Bauer disc diffusion and MIC tests were carried out, indicating that most of these compounds were active against tested microorganisms. Particularly, several compounds proved active against E. coli, whereas S. aureus showed higher resistance. The genotoxic potential of most active compounds was determined by in vitro alkaline comet assay, and they were found to be non-toxic at studied concentrations.

Results: Finally, molecular docking and dynamics (MD) studies identified four compounds as potential inhibitors of bacterial DNA gyrase B (GyrB).

Conclusion: Further exploration of molecular determinants revealed favourable drug-like properties, highlighting the potential of these molecules for subsequent hit-to-lead optimization studies.

The human skin, being the largest organ, provides defense against bacteria, toxins, and ultraviolet radiation. The skin may experience changes like dryness, photodamage, oxidative damage, and inflammation. This review explores sources of fatty acids and how they can prevent skin damage, with the goal of determining their potential for preventing skin aging. The role and significance of various mechanistic pathways and molecular targets involved in skin aging are highlighted. By using current research findings, this review contributes to a comprehensive understanding of how fatty acids may serve as a proactive approach to promoting youthful skin and mitigating the signs of skin aging. In addition to treating specific skin conditions, nutraceuticals offer immense potential to minimize, postpone, or prevent premature skin aging. The substances that are most frequently employed include carotenoids, polyunsaturated fatty acids, plant polyphenols, bioactive peptides, oligosaccharides, and vitamins. Numerous human trials have demonstrated the impact of supplementing with these items on indicators of aging. The most pertinent clinical and non-clinical investigations are assessed in this review. Based on the comprehensive understanding of the significant role of fatty acids in addressing skin aging, this review may open doors and offer avenues for future explorations.