Current pharmaceutical design最新文献

Introduction: Salvianolic acid B (SAB), as one of the major water-soluble compounds of Salvia miltiorrhiza, has proved to effectively reduce elevated portal pressure in cirrhotic rats. However, the short halflife and in vivo retention time of SAB affect its pharmacodynamics. Therefore, in this study, we prepared albumin nanoparticles loaded with SAB (SAB-ALB-NPs) to improve the in vivo retention time of the drug and enhance bioavailability.

Methods: We prepared and characterized SAB-ALB-NPs, including particle size, PDI, zeta potential, stability, EE, in-vitro release, and pharmacokinetics. Subsequently, we investigated the effects and potential mechanisms of SAB-ALB-NPs in CCl4-induced portal hypertension (PHT) mice models, and it was found that angiotensin- II (Ang-II) induced proliferation and contraction in hepatic stellate cells (HSCs). The CCl4 (0.3:1 in corn oil, 1mL/kg) was injected repeatedly, leading to the PHT mice model. The effect of SAB-ALB-NPs on PHT mice was evaluated by hematoxylin-eosin, Sirius red staining, immunohistochemistry, and western blot.

Results: We successfully prepared SAB-loaded albumin nanoparticles with smaller-sized particles, lower PDI and zeta potential with stable properties, and higher EE. Importantly, the SAB-ALB-NPs notably prolonged the in vitro release of SAB. SAB-ALB-NPs significantly reduced portal pressure, inhibited inflammation (decrease the concentration of TNF-α and IL-6) and hepatotoxicity of the liver (down-regulated the level of ALT and AST) against fibrous tissue hyperplasia, and reduced collagen deposition in the liver. Afterward, we used Ang-II to facilitate the proliferation of HSCs and induce HSC cell contraction. Cotreatment of SAB-ALB-NPs markedly inhibited Ang II-induced effects on cell proliferation and contraction and improved apoptosis. Importantly, SAB-ALB-NPs were preliminarily found to inhibit the expression of RhoA and ROCK II in Ang-II- treated HSC and CCl4-induced PHT mice, suggesting that SAB-ALB-NPs may participate in the regulation of RhoA/ROCK II pathway.

Conclusion: SAB-ALB-NPs improved portal hypertension by suppressing inflammation and inhibiting HSCs activation and proliferation to attenuate liver fibrosis. This therapeutic function of SAB-ALB-NPs may be owing to SAB-ALB-NPs regulating the RhoA/ROCK2 pathway, which may be one of its molecular mechanisms for reducing portal hypertension.

Introduction: Pulmonary fibrosis (PF) is a chronic pulmonary disorder with unknown etiology and an irreversible course. Traditional Chinese medicine (TCM) possesses promising clinical benefits for PF treatment through a multi-component and multi-target approach. This study evaluates the efficacy of Yangyin Yifei Tongluo Wan (YF), a traditional formulation, in the treatment of PF, and further explores the underlying mechanism.

Methods: A bleomycin (BLM)-induced PF mouse model was established. Mice were administered with low-, medium-, and high-dose YF (1.5, 3, and 6 g/kg/d, respectively). The fibrosis degree of mouse lung tissues was evaluated by morphometric measurements and hydroxyproline (HYP) analysis. Network pharmacology-based bioinformatics were employed for constructing a network involving components, targets, and disease, and YF's potential mechanism and molecular targets for PF therapy were explored. This was further validated by TUNEL staining, Western blot, RT-qPCR, and ELISA in BLM-treated mice.

Results: YF could relieve PF in BLM-treated mice in a dose-dependent manner, evidenced by a notable decrease in collagen deposition, and collagen I and III, HYP, fibronectin, vimentin, and α-SMA expressions. Network pharmacology revealed that JAK2/STAT3 signaling pathway-mediated alveolar epithelial cell apoptosis may be a potential therapeutic target for YF in treating PF. In vivo assays confirmed that YF's antifibrosis effect on BLM-induced PF was ascribed to the suppression of alveolar epithelial cell apoptosis and disruption of the JAK2/STAT3 signaling pathway.

Discussion: YF can block alveolar epithelial cell apoptosis through inactivation of the JAK2/STAT3 signaling, subsequently enhancing the resolution of PF.

Conclusion: YF may be a promising therapeutic candidate for PF treatment.

Advancements in biotechnology have played a key role in driving the development of protein- and peptide-based therapeutics. Drug delivery systems (DDSs) designed for proteins and peptides are carefully crafted to improve drug stability, enhance bioavailability, and reduce toxic side effects by ensuring precise delivery to targeted areas. However, despite their promising therapeutic potential, protein- and peptide-based drugs face substantial challenges due to their distinct physicochemical properties and biological barriers. Ongoing developments in protein- and peptide-based DDSs present valuable solutions to address these challenges, ultimately improving drug stability, delivery accuracy, and therapeutic efficacy. Researchers are actively working on creating innovative carrier technologies to further enhance the effectiveness and precision of these therapeutics. This review examines the wide-ranging applications of protein- and peptide-based therapeutics, explores advanced drug delivery techniques, and highlights various administration routes aimed at overcoming existing obstacles. In conclusion, this review offers a comprehensive understanding of protein- and peptide- based therapeutics as a viable alternative to conventional drug delivery systems, harnessing the power of cutting-edge biotechnological advancements.

Introduction: Diabetic neuropathy (DN) is a common complication of diabetes with limited therapeutic options. Given its complex pathophysiology involving oxidative stress, inflammation, and impaired nerve function, there is increasing interest in complementary therapies. This review aims to summarize the potential use of natural oils, both as dietary supplements and topical agents, for the prevention and management of DN.

Methods: A systematic literature search was conducted using databases such as SciFinder and PubMed for studies published from 1988 to January 2024. The search employed keywords including "diabetic neuropathy," "natural oils," and "bioactive constituents." Relevant studies involving preclinical and clinical evaluation of natural oils or their active compounds in DN were selected, analyzed, and categorized based on the type of oil, mode of application, and mechanism of action.

Results: Several natural oils of plant and animal origin demonstrated protective and therapeutic effects against DN in both animal models and limited clinical settings. Their beneficial effects were attributed to antiinflammatory and antioxidant properties, enhanced nerve conduction velocity, and modulation of vascular and neurotrophic factors. Both oral and topical applications contributed to symptom improvement.

Discussion: Due to the involvement of various signalling pathways and complex pathophysiology, DN has long been a condition with few acceptable treatment options. Although several natural oils have demonstrated activity against DN, very few clinical studies have been conducted to explore their therapeutic potential fully.

Conclusion: Natural oils represent a potential complementary strategy for managing DN. However, more rigorous clinical investigations are essential to confirm their safety, efficacy, and translational value.

Introduction: Polycystic ovarian syndrome (PCOS) is a hormonal condition that affects women of reproductive age. The purpose of this study was to identify the undiscovered molecular mechanisms by which Stachys lavandulifolia treats PCOS. Although Stachys lavandulifolia has been used to treat PCOS, its exact biological mechanism of action remains unknown.

Methods: We used a multifaceted strategy that included network pharmacology, molecular docking, and molecular dynamics simulations.

Results: Network pharmacology discovered 68 gene targets shared by Stachys lavandulifolia bioactive chemicals and PCOS-associated genes. Subsequent KEGG and Reactome analysis identified 18 enhanced pathways, including steroid hormone production, glucose homeostasis, and insulin resistance. Key genes involved in ovarian steroidogenesis and the hypothalamic-pituitary-ovarian axis (CYP19A1, Kiss1, human androgen receptor, oestrogen receptor alpha, and HSD17B1) were chosen for molecular docking.

Discussion: Molecular docking indicated that bioactive substances Myrsen, Agnol, Alpha Pyogenin, and Gamma Morolen have high binding affinities for the identified target proteins. Notably, the CYP19A1- Myrsen complex has the highest binding affinity at -9.0 kcal/mol. Additional molecular dynamics simulations indicated that the CYP19A1-Myrsen complex had increased flexibility and mobility, indicating a stable and effective association.

Conclusion: Our findings identify potential gene pathways and interactions through which Stachys lavandulifolia bioactive chemicals exert their therapeutic benefits in PCOS. This study establishes a solid platform for future research into Stachys lavandulifolia as a potential PCOS therapy.

Introduction: The zebrafish (Danio rerio), which lives in tropical freshwater, is thought to be one of the best animal models for studying drugs and their effects. This model is unique for its fast growth, clear embryos, genetic similarity to humans, and low cost for experiments. Literature-based data were gathered and shared so that future researchers in the field of pharmacology could get an idea of what kind of work could be done.

Methods: Journal sources like Scopus, Springer, MDPI, and PubMed were used. Seventy-four research papers from 2000 to 2025 were reviewed, but some from before 2020 were added because they were more scientifically sound. Articles about fish that aren't zebrafish were left out.

Results: In order to perform preclinical investigations of several ailments, including diabetes, cancer, cardiovascular disease, and neurological disorders, researchers are using zebrafish as an animal model. The reason behind its use is its similar genetic pattern, similar physiology, rapid development, and optical transparency.

Discussion: Researchers have found heart-healthy phospholipids, antitumor peptides, and anti-diabetic chemicals in zebrafish models, which makes them a great way to study human pathophysiology. In vivo studies using zebrafish are also easy to expand and cost-effective.

Conclusion: The emerging zebrafish model is indispensable for translational investigation. This model works as a bridge connecting in vitro assays to mammalian models. The present article is an attempt to showcase the current perspective on the pharmacological model in view of drug discovery involving zebrafish.

Introduction: Statins are widely prescribed for cardiovascular disease prevention, but their potential to increase diabetes risk has prompted regulatory warnings. Different statin drugs have varying physicochemical properties, yet comprehensive comparative assessments of their individual diabetes-related safety profiles remain limited in post-marketing surveillance data. Therefore, this study aimed to evaluate and compare the risk of diabetes-related adverse events among different statin drugs using pharmacovigilance data.

Methods: We analyzed adverse event reports from the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2022. Diabetes-related adverse events were identified using relevant MedDRA Preferred Terms. Four pharmacovigilance algorithms-Reporting Odds Ratio (ROR), Medicines and Healthcare products Regulatory Agency (MHRA) standard method, Bayesian Confidence Propagation Neural Network, and Multi-Item Gamma Poisson Shrinkage-were employed to detect signals. Positive signals were defined when all four methods showed significance. Outcome severity and time-to-event were also analyzed.

Results: Among 13,438,409 ADE reports, 63,583 identified statins as primary suspect drugs, with 11,562 reporting diabetes-related events. Positive signals were detected for atorvastatin, rosuvastatin, simvastatin, pravastatin, and pitavastatin. Signal strength ranking showed atorvastatin had the strongest association (ROR 36.70; 95% CI 35.92-37.51), followed by rosuvastatin (ROR 9.63; 95% CI 9.10-10.19), pitavastatin (ROR 5.46; 95% CI 4.03-7.41), simvastatin (ROR 2.96; 95% CI 2.54-3.45), and pravastatin (ROR 2.82; 95% CI 2.14-3.71). In patients under 45, only atorvastatin showed a positive signal. Atorvastatin was associated with a higher risk of serious adverse events (PRR=1.37; 95% CI: 1.09-1.71) with a median time to event of 1,012 days.

Discussion: Our findings revealed differences in diabetes-related risk profiles among statins, with atorvastatin demonstrating the strongest signals across different age groups. The observed risk hierarchy may be attributed to differences in lipophilicity, potency, and metabolic effects. The age-dependent patterns and extended timeto- event for diabetic events underscore the importance of long-term monitoring, complementing clinical trial data with post-marketing surveillance evidence for improved statin selection.

Conclusion: Different statins demonstrate varying associations with diabetes-related adverse events, with atorvastatin showing the strongest signal across age groups. These findings may inform clinical decisionmaking when prescribing statins, particularly for patients with pre-existing diabetes risk factors.

Introduction: Recombinant protein vaccines against infectious diseases, based on immunogenic antigen identification and employing polymeric nanoparticles as a delivery system, can provoke immune responses comparable to or better than traditional vaccines. The production of a safe and immunogenic vaccine against diphtheria was achieved by preparing sodium alginate nanoparticles containing recombinant diphtheria toxoid (CRM197).

Methods: Alginate nanoparticles loaded with CRM197 were prepared using the ionic-gelation method and thoroughly characterized. Safety and immunogenicity studies were conducted in an animal model for comparison with commercial vaccines. Antibody responses were evaluated using both qualitative and quantitative measurements, as determined by the toxin neutralization test (TNT) and indirect ELISA, respectively. IgG subclasses in the sera of immunized mice and possible pathological lesions in vital tissues of all immunized mouse groups were investigated.

Results: Nanoparticles with or without CRM197 were synthesized by the ionic gelation method. LE and LC measurements showed ˃80% and ˃20%, respectively, indicating stable and persistent release without a bursting pattern. In vivo studies showed safety and enhanced immunogenicity in mice immunized with the CRM197- loaded sodium alginate nanoparticles, with higher levels of total anti-CRM197 IgG and subclasses than those induced by conventional vaccines.

Discussion: Reducing antigen usage in vaccine production while increasing immunogenicity and safety compared with traditional vaccines are the goals of new vaccine development, which were achieved in the current study.

Conclusion: Engineered alginate nanoparticles loaded with recombinant diphtheria antigen (CRM197) demonstrated in vitro controlled and slow release, as well as safety and immunogenicity profiles against diphtheria in vivo. Nanoparticles containing CRM197 antigens equivalent to adult and children doses showed high levels of IgG1 and IgG2a, confirming the combined responses of the humoral and cellular immune systems.

Head and neck cancers, particularly Head and Neck Squamous Cell Carcinoma (HNSCC), encompass a diverse group of malignancies with intricate cellular landscapes. The Tumor Microenvironment (TME) is characterized by constant communication between cancer cells and their surrounding cells. Stromal components, immune infiltrates, and Extracellular Matrix (ECM) elements all play crucial roles in this process. These dialogues shape tumor behavior, spread, and treatment resistance. At the molecular level, DNA Damage Response (DDR) by tumoral cells can reduce cell elimination via Ionizing Radiation (IR). Human Papillomavirus (HPV) infection, in some cases, further complicates the picture. Recent findings highlight how these molecular responses, as well as immune modulation, remodeling cell metabolism, enhanced growth factors, and hypoxia in TME, can influence tumor responses to IR. These findings may lead to strategies for radiosensitizing head and neck cancers. Unraveling these interactions is key to developing more effective treatments. This review focuses on different mechanisms of radioresistance in head and neck cancers. Then, we provide an overview of different targets and potential adjuvants or drugs for radiosensitization of these malignancies.

Bowel cancer, known as colorectal cancer (CRC), is among the most common types of newly diagnosed cancers and a leading cause of cancer-related deaths. Despite advances in medical technology and screening programs, gaps in the detection of colorectal cancer patients persist, leading to delayed diagnoses and poorer outcomes. Therefore, new approaches using artificial intelligence-based analysis with gene panels and traditional risk factors for risk prediction and identification of cases at high risk are urgently warranted. Artificial Intelligence (AI) has emerged as a promising tool to enhance early detection and screening efficacy. Moreover, early detection is crucial for successful treatment and improved survival rates. However, conventional screening methods, such as colonoscopy and fecal occult blood tests (FOBT), have their limitations, including cost, invasiveness, and patient compliance. As a result, many individuals go undiagnosed until the disease has progressed to an advanced stage. In aggregate, the integration of AI in CRC detection holds great promise for bridging the existing gaps and improving patient outcomes. As technology continues to evolve, AI algorithms will become even more sophisticated, accurate, and scalable. Collaboration between clinicians, researchers, and AI developers is essential to harness the full potential of AI for earlier detection and better management of CRC, ultimately saving lives and reducing the global burden of disease.