Current pharmaceutical design最新文献

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Polymeric Microneedles: Advancing Potential Through Innovative Manufacturing, Polymer Design, and Characterization Techniques. 聚合物微针:通过创新制造、聚合物设计和表征技术推进潜力。
IF 2.8 4区 医学
Current pharmaceutical design Pub Date : 2025-07-28 DOI: 10.2174/0113816128376011250706183030
Caroline Lamie, Athina-Myrto Chioni, Natividad Garrido-Mesa, Amr Elshaer
{"title":"Polymeric Microneedles: Advancing Potential Through Innovative Manufacturing, Polymer Design, and Characterization Techniques.","authors":"Caroline Lamie, Athina-Myrto Chioni, Natividad Garrido-Mesa, Amr Elshaer","doi":"10.2174/0113816128376011250706183030","DOIUrl":"https://doi.org/10.2174/0113816128376011250706183030","url":null,"abstract":"<p><p>Microneedles (MNs) represent a transformative technology in pharmaceutics, offering a minimally invasive method for drug delivery that enhances patient compliance and therapeutic efficacy. By enabling transdermal administration, MNs provide a promising option to conventional routes of drug delivery, such as injections and oral administration, which may cause discomfort and lead to poor adherence. This review provides a comprehensive analysis of polymeric MNs, with a particular focus on their fabrication techniques, polymer selection strategies, and pharmaceutical characterization methods. It critically examines the latest advancements in manufacturing approaches, emphasizing the role of biocompatible and biodegradable polymers in enhancing drug solubility, stability, and controlled release. This review provides insights into the current landscape of polymeric MN applications in drug delivery , highlighting their potential to revolutionize therapeutic interventions across diverse medical fields. Ongoing advancements in polymeric MN technology could lead to significant improvements in patient outcomes, positioning MNs as a cornerstone of the next generation of drug delivery systems.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Navigating the Complex Landscape of Autism Spectrum Disorder: Challenges and Opportunities in Diagnosis, Treatment, and Supports. 导航自闭症谱系障碍的复杂景观:诊断,治疗和支持的挑战和机遇。
IF 2.8 4区 医学
Current pharmaceutical design Pub Date : 2025-07-24 DOI: 10.2174/0113816128400132250716142203
Arun Kumar Sharma, Sant Kumar Verma, Sidharth Mehan
{"title":"Navigating the Complex Landscape of Autism Spectrum Disorder: Challenges and Opportunities in Diagnosis, Treatment, and Supports.","authors":"Arun Kumar Sharma, Sant Kumar Verma, Sidharth Mehan","doi":"10.2174/0113816128400132250716142203","DOIUrl":"https://doi.org/10.2174/0113816128400132250716142203","url":null,"abstract":"<p><p>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by persistent deficits in social communication and interaction, as well as restricted, repetitive patterns of behaviour, interests, or activities. Despite advancements in our understanding of ASD, identification, screening, diagnosing, and treating this condition present significant challenges. This review article comprehensively examines the current diagnostic and treatment landscape for ASD, addressing key issues and opportunities for improvement. The diagnostic criteria for ASD, as outlined in the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5), provide a framework for identifying the condition. Still, the heterogeneity of presentation and the presence of comorbidities contribute to diagnostic complexity. Early intervention is crucial for improving outcomes in individuals with ASD; however, accessing timely and appropriate interventions can be challenging. A diverse range of interventions exists for individuals with ASD, including behavioural therapies, pharmacological treatments, gene expression, and alternative therapies. However, the efficacy and accessibility of these treatments vary, and navigating the treatment landscape can be daunting for caregivers and clinicians alike. Moreover, due to the persistence of healthcare disparities, , underserved populations face barriers to diagnosis and treatment. Transitioning to adulthood poses unique challenges for individuals with ASD, including finding employment and accessing support services. Additionally, ASD affects not only individuals diagnosed with the condition but also their families and caregivers. Addressing caregiver stress and burnout is essential for providing holistic care to individuals with ASD and their families. This review also identifies areas needing further research, such as personalized medicine and healthcare disparities, and discusses policy implications for enhancing ASD care and support. By highlighting research needs and policy considerations, this review aims to inform future efforts to improve ASD Screening, diagnosis, and treatment, ultimately striving to enhance outcomes for individuals with ASD and their families.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive Evaluation of Triptolide's Therapeutic Mechanisms in Diabetic Kidney Disease via Meta-Analysis, Network Pharmacology, Molecular Docking, and Mendelian Randomization. 通过荟萃分析、网络药理学、分子对接和孟德尔随机化综合评价雷公藤甲素治疗糖尿病肾病的机制。
IF 2.6 4区 医学
Current pharmaceutical design Pub Date : 2025-07-23 DOI: 10.2174/0113816128367671250714100708
Jing Ni, Siyuan Song, Yi Wei, Qiling Zhang, Wei Li, Jiangyi Yu
{"title":"Comprehensive Evaluation of Triptolide's Therapeutic Mechanisms in Diabetic Kidney Disease via Meta-Analysis, Network Pharmacology, Molecular Docking, and Mendelian Randomization.","authors":"Jing Ni, Siyuan Song, Yi Wei, Qiling Zhang, Wei Li, Jiangyi Yu","doi":"10.2174/0113816128367671250714100708","DOIUrl":"https://doi.org/10.2174/0113816128367671250714100708","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic kidney disease (DKD) is a devastating complication of diabetes for which there are few potent treatments.Triptolide (TP), an active compound from Tripterygium wilfordii, has shown potential in early studies, but its therapeutic mechanisms in DKD are not fully understood. This study aims to systematically evaluate TP's efficacy and mechanisms using meta-analysis, network pharmacology, molecular docking, and Mendelian randomization (MR).</p><p><strong>Methods: </strong>A comprehensive search across Chinese and English databases identified animal randomized controlled trials (RCTs) assessing the effects of TP on DKD. A total of 27 studies were incorporated, and a metaanalysis was conducted via Review Manager. TP's drug and disease targets were identified through network pharmacology and molecular docking, while bioinformatics methods were employed to explore the mechanisms. MR analysis was performed to assess potential causal relationships between TP and DKD-related targets.</p><p><strong>Results: </strong>Meta-analysis showed that TP significantly reduced urinary protein, blood lipids, and glucose levels, while improving renal function, renal weight, and renal index (all p < 0.05). Seven core targets-IFNG, CXCL8, TNF, TGFB1, IL2, IL4, and RELA-were identified via network pharmacology, involving key pathways such as lipid-atherosclerosis, AGE-RAGE, and IL-17 signaling. Molecular docking demonstrated strong binding affinities between TP and these targets, with binding energies below -7.00 kJ/mol. Although MR analysis did not establish direct causal relationships between these core genes and DKD, a significant negative correlation between TNF, IL4, and GFR was observed, suggesting their involvement in DKD progression.</p><p><strong>Discussion: </strong>TP may exert therapeutic effects on DKD through coordinated regulation of immune and inflammatory pathways. The integration of multi-omics approaches supports its multi-target pharmacological mechanisms. Although MR analysis did not confirm direct causal relationships, the identified gene associations further reinforce the potential biological relevance of TP. However, this study was primarily based on public datasets and lacks experimental validation in vivo and in vitro.</p><p><strong>Conclusion: </strong>TP exerts therapeutic effects on DKD through multi-target and multi-pathway mechanisms, primarily involving immunomodulation, anti-inflammation, anti-oxidation, and anti-fibrosis processes.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comprehensive Meta-Analysis on the Impact of the MDM2 SNP 309 T>G Gene Variant in Leukemia Susceptibility. MDM2 SNP 309t>g基因变异对白血病易感性影响的综合meta分析。
IF 2.6 4区 医学
Current pharmaceutical design Pub Date : 2025-07-23 DOI: 10.2174/0113816128368759250527073556
Tarika Naik, Henu Kumar Verma, Madhubala Mulkalwar, Dinesh Mishra, Lvks Bhaskar
{"title":"Comprehensive Meta-Analysis on the Impact of the MDM2 SNP 309 T>G Gene Variant in Leukemia Susceptibility.","authors":"Tarika Naik, Henu Kumar Verma, Madhubala Mulkalwar, Dinesh Mishra, Lvks Bhaskar","doi":"10.2174/0113816128368759250527073556","DOIUrl":"https://doi.org/10.2174/0113816128368759250527073556","url":null,"abstract":"<p><strong>Introduction: </strong>Genetic factors play a significant role in the development of leukemia. The overexpression of MDM2 is associated with the progression of certain leukemias. This meta-analysis investigates the relationship between the MDM2 SNP 309T>G and various forms of leukemia across global populations.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted to retrieve genotyping data from twenty casecontrol studies related to MDM2 SNP 309T>G polymorphism and leukemia. A random-effects model was used to calculate the pooled odds ratio (OR) and 95% confidence interval (95% CI) for the association analysis. MetaGenyo software was utilized to conduct statistical analyses in this meta-analysis.</p><p><strong>Results: </strong>The findings indicate a significant association between MDM2 309 SNPT>G polymorphism and leukemia in Asian and Caucasian populations. Additionally, this polymorphism is associated with an increased risk of Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML), implying that MDM2 may play a role in the pathogenesis of these specific forms of leukemia.</p><p><strong>Conclusion: </strong>This meta-analysis suggests that MDM2 may represent a susceptibility gene for leukemia risk.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Angiogenesis and Resistance Mechanisms in Glioblastoma: Targeting Alternative Vascularization Pathways to Overcome Therapy Resistance. 胶质母细胞瘤的血管生成和抵抗机制:靶向替代血管形成途径以克服治疗抵抗。
IF 2.6 4区 医学
Current pharmaceutical design Pub Date : 2025-07-22 DOI: 10.2174/0113816128367551250703122830
Ozal Beylerli, Ilgiz Gareev, Elmar Musaev, Tatiana Ilyasova, Sergey Roumiantsev, Vladimir Chekhonin
{"title":"Angiogenesis and Resistance Mechanisms in Glioblastoma: Targeting Alternative Vascularization Pathways to Overcome Therapy Resistance.","authors":"Ozal Beylerli, Ilgiz Gareev, Elmar Musaev, Tatiana Ilyasova, Sergey Roumiantsev, Vladimir Chekhonin","doi":"10.2174/0113816128367551250703122830","DOIUrl":"https://doi.org/10.2174/0113816128367551250703122830","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Glioblastoma (GBM), the most aggressive form of primary brain tumor in adults, remains a significant clinical challenge due to its high recurrence and poor prognosis. Characterized by rapid growth, invasiveness, and resistance to therapy, GBM relies on a sophisticated vascular network to sustain its progression. Angiogenesis, the process of forming new blood vessels, is central to meeting the metabolic demands of the tumor. To address this issue, there is a growing consensus on the need for multi-pronged therapeutic strategies that not only inhibit angiogenesis but also disrupt alternative neovascular mechanisms. Promising approaches include combining anti-angiogenic drugs with agents targeting pathways like neurogenic locus notch homolog protein (NOTCH), Wnt, and C-X-C motif chemokine receptor 4 (CXCR4)/stromal cellderived factor 1 alpha (SDF-1α) to impede vessel co-option, VM, and GSC trans-differentiation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The search strategy consisted of using material from the PubMed data, focusing on key terms such as: \"angiogenesis\", \"glioblastoma\", \"glioma\", \"oncogenesis\", \"anti-VEGF treatment\", \"signaling pathways\", \"hypoxia\", \"vessels\", \"resistance\", and \"neurosurgery.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Аs a result of the analysis of existing recent studies, GBM exhibits an adaptive capacity to utilize various neovascular mechanisms, including vessel co-option, vasculogenic mimicry (VM), and the transdifferentiation of glioma stem cells (GSCs) into vascular-like structures, to circumvent traditional antiangiogenic therapies. Initial successes with anti-angiogenic treatments targeting vascular endothelial growth factor (VEGF) showed improvements in progression-free survival. Still, they failed to significantly impact the overall survival due to the tumor's activation of compensatory pathways. Hypoxia, a critical driver of angiogenesis, stabilizes hypoxia-inducible factors (HIF-1α and HIF-2α), which upregulate pro-angiogenic gene expression and facilitate adaptive neovascular responses. These adaptations include vessel co-option, where tumor cells utilize pre-existing vasculature, and VM, where tumor cells form endothelial-like channels independent of typical angiogenesis. Moreover, the role of GSCs in forming new vascular structures through transdifferentiation further complicates treatment, enabling the tumor to maintain its blood supply even when VEGF pathways are blocked.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;This review highlights the necessity for comprehensive and targeted treatment strategies that encompass the full spectrum of neovascular mechanisms in GBM. Such strategies are crucial for developing more effective therapies that can extend patient survival and improve overall treatment outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;To address the challenge of understanding tumor angiogenesis and ways to inhibit it, there is a growing consensus on the need for multifaceted therapeutic strat","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Loss of CD99L2 Contributed to Temozolomide Resistance and Glioblastoma Tumorigenesis Based on Genome-scale CRISPR/Cas9 Screening. 基于基因组级CRISPR/Cas9筛选的CD99L2缺失促进替莫唑胺耐药性和胶质母细胞瘤的发生
IF 2.6 4区 医学
Current pharmaceutical design Pub Date : 2025-07-18 DOI: 10.2174/0113816128386002250701113848
Zeen Sun, Mengke Cui, Zenghao Deng, Lu Zhou, Feiyue Zeng, Zhaoqian Liu, Yingzi Liu
{"title":"Loss of CD99L2 Contributed to Temozolomide Resistance and Glioblastoma Tumorigenesis Based on Genome-scale CRISPR/Cas9 Screening.","authors":"Zeen Sun, Mengke Cui, Zenghao Deng, Lu Zhou, Feiyue Zeng, Zhaoqian Liu, Yingzi Liu","doi":"10.2174/0113816128386002250701113848","DOIUrl":"https://doi.org/10.2174/0113816128386002250701113848","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma Multiforme (GBM) is a highly aggressive and fatal brain malignancy, with Temozolomide (TMZ) serving as the first-line chemotherapeutic treatment. However, over 50% of patients do not respond to TMZ, and the underlying mechanisms remain unclear. This study utilized the GeCKO library to identify novel genes involved in TMZ resistance and to explore their functions.</p><p><strong>Methods: </strong>Loss-of-function genes related to TMZ resistance in GBM cells were identified using the GeCKO library and Next-Generation Sequencing (NGS), validated by qPCR and CCK-8 assays. CD99L2 function was assessed through proliferation, migration, and EdU assays in U251 and U87 cells. Tumor samples from 55 stage IV GBM patients were analyzed to explore the correlation between CD99L2 expression and Progression- Free Survival (PFS).</p><p><strong>Results: </strong>GeCKO library screening identified seven genes associated with TMZ resistance. After validation, CD99L2 was confirmed as a key contributor to TMZ resistance. Knockdown of CD99L2 increased the IC50 of U251 and U87 cells by 1.39- and 1.54-fold, respectively. Conversely, CD99L2 overexpression reduced the IC50 by 0.52- and 0.58-fold. CD99L2 knockdown also promoted tumor proliferation and aggressiveness. Additionally, higher CD99L2 expression was associated with longer PFS in GBM patients (median PFS: 7.87 months vs. 2.7 months, P=0.0003).</p><p><strong>Discussion: </strong>The functions of CD99L2 remain poorly understood. A few studies have reported that CD99L2 may serve as an adhesion molecule modulating inflammatory responses. One study has shown that CD99L2 is highly expressed in the brain and affects neuronal excitability. These findings suggest that CD99L2 may play a positive role in the body's defense against glioma.</p><p><strong>Conclusion: </strong>This study demonstrated that CD99L2 knockdown promotes TMZ resistance and tumorigenesis in GBM, suggesting its potential as a novel biomarker for TMZ resistance.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lipid-Based Nanocarriers as a Promising Delivery System in the Management of Acne. 脂质纳米载体在痤疮治疗中的应用前景广阔。
IF 2.6 4区 医学
Current pharmaceutical design Pub Date : 2025-07-17 DOI: 10.2174/0113816128404408250707111455
Soumya Ranjan Masanta, Neha Nilam, Abhisek Pal, Biswakanth Kar, Priyanka Dash, Deepak Pradhan, Jitu Halder, Chandan Das, Vineet Kumar Rai, Saroj Kumar Rout, Goutam Ghosh, Goutam Rath
{"title":"Lipid-Based Nanocarriers as a Promising Delivery System in the Management of Acne.","authors":"Soumya Ranjan Masanta, Neha Nilam, Abhisek Pal, Biswakanth Kar, Priyanka Dash, Deepak Pradhan, Jitu Halder, Chandan Das, Vineet Kumar Rai, Saroj Kumar Rout, Goutam Ghosh, Goutam Rath","doi":"10.2174/0113816128404408250707111455","DOIUrl":"https://doi.org/10.2174/0113816128404408250707111455","url":null,"abstract":"<p><strong>Introduction: </strong>Acne vulgaris is a prevalent dermatological condition resulting from inflammation, follicular hyperkeratinization, and bacterial growth. Standard treatments, whether topical or oral, frequently encounter challenges such as limited skin penetration, drug instability, and undesirable side effects. The report found that lipid-based nanocarriers have emerged as a promising alternative, demonstrating the potential for enhanced therapeutic effectiveness, better skin bioavailability, controlled drug release, and targeted delivery specifically to sebaceous glands, which help minimize systemic side effects.</p><p><strong>Aim: </strong>This review article aims to explore the therapeutic potential of various lipid nanocarriers, including Solid Lipid Nanoparticles (SLNs), Nanostructured Lipid Carriers (NLCs), liposomes, microemulsions, niosomes, and ethosomes particularly by examining the mechanisms through which they penetrate the stratum corneum and deeper skin layers to enhance drug delivery.</p><p><strong>Methodology: </strong>This review comprehensively surveys lipid-based nanocarriers for acne vulgaris treatment, drawing from a systematic literature search across Google Scholar, Science Direct, Scopus, Web of Science, and PubMed for publications between 2015 and 2025. The search strategy employed keywords such as \"lipid nanocarrier,\" \"acne vulgaris,\" \"animal models,\" or \"preclinical studies,\" and \"clinical trials\" to capture the research landscape.</p><p><strong>Results: </strong>The review compiles evidence from multiple preclinical experiments and clinical trials regarding the effectiveness of lipid nanocarriers in managing acne. It explores the different pathways these lipid nanocarriers use to permeate the skin and reach target sites. Additionally, it also covers different patents filed by various researchers focusing on the application of lipid nanocarriers for acne management.</p><p><strong>Conclusion: </strong>Lipid nanocarriers represent a significant advancement in dermatological drug delivery, particularly for acne management. By leveraging various skin penetration mechanisms to improve drug targeting to the pilosebaceous unit, they offer potential for more effective treatment compared to conventional methods. While promising, ongoing research and development are necessary to overcome current limitations and fully harness the potential of lipid nanocarriers in clinical practice.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-Cell Transcriptome and Microbiome Profiling Uncover Ileal Immune Impairment in Intrauterine Growth-Retarded Piglets. 单细胞转录组和微生物组分析揭示了宫内生长迟缓仔猪的回肠免疫损伤。
IF 2.6 4区 医学
Current pharmaceutical design Pub Date : 2025-07-17 DOI: 10.2174/0113816128411269250707073647
Yiwen He, Yawei Guo, Xuqing Liang, Hong Hu, Xia Xiong, Xihong Zhou
{"title":"Single-Cell Transcriptome and Microbiome Profiling Uncover Ileal Immune Impairment in Intrauterine Growth-Retarded Piglets.","authors":"Yiwen He, Yawei Guo, Xuqing Liang, Hong Hu, Xia Xiong, Xihong Zhou","doi":"10.2174/0113816128411269250707073647","DOIUrl":"https://doi.org/10.2174/0113816128411269250707073647","url":null,"abstract":"<p><strong>Introduction: </strong>Impaired intestinal immune function is commonly observed in neonates with intrauterine growth retardation (IUGR), yet its underlying mechanisms and regulatory pathways remain poorly understood. Therefore, we aimed to investigate gene regulatory patterns and microbiota alterations in IUGR piglets.</p><p><strong>Methods: </strong>Three newborn IUGR piglets and three normal littermates were selected from the same sow and sacrificed at seven days of age. Ileal digesta was collected for 16S rRNA amplicon sequencing (16S-seq), and ileum segments were dissociated for single-cell RNA sequencing (scRNA-seq).</p><p><strong>Results: </strong>The scRNA-seq results revealed a reduced proportion of plasma B cells in IUGR piglets, along with alterations in the distribution of various T cell subsets. KEGG pathway analysis further indicated a downregulation of the B cell receptor signaling pathway in B cells from IUGR piglets. In contrast, both the T cell receptor signaling pathway and antigen processing and presentation were attenuated in T cells. Pseudotime trajectory analysis suggested that the differentiation of B cells was impaired in IUGR piglets. SCENIC analysis revealed that GATA3, IRF2, and BCL11A were downregulated in T cells of IUGR piglets. The 16S-seq results revealed that α-diversity was lower in IUGR piglets. At the genus level, the relative abundance of <i>Prevotella</i> was significantly lower in IUGR piglets.</p><p><strong>Discussion: </strong>Significant changes were identified in the proportions of B and T cells, their associated signaling pathways, and intestinal microbiota composition in IUGR piglets, suggesting underlying immune dysfunction and dysbiosis.</p><p><strong>Conclusion: </strong>We identified novel immune-related transcription factors and key microbes as potential therapeutic targets, shedding light on strategies for preventing and treating IUGR.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of Chitosan-Coated Liposomes for Oral Delivery of Nadolol: Preparation, Characterization, and in vitro Permeability Studies. 纳多洛尔口服壳聚糖包被脂质体的研制:制备、表征和体外渗透性研究。
IF 2.6 4区 医学
Current pharmaceutical design Pub Date : 2025-07-16 DOI: 10.2174/0113816128401910250706133608
Esra İpekci, Emre Şefik Çağlar, Mustafa Sinan Kaynak, Evren Gündoğdu, Neslihan Üstündağ Okur
{"title":"Development of Chitosan-Coated Liposomes for Oral Delivery of Nadolol: Preparation, Characterization, and <i>in vitro</i> Permeability Studies.","authors":"Esra İpekci, Emre Şefik Çağlar, Mustafa Sinan Kaynak, Evren Gündoğdu, Neslihan Üstündağ Okur","doi":"10.2174/0113816128401910250706133608","DOIUrl":"https://doi.org/10.2174/0113816128401910250706133608","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to enhance the oral bioavailability of Nadolol (NDL), a β-blocker used in the management of hypertension, by incorporating it into a liposome-based delivery system. To improve the formulation's stability, mucoadhesion, and permeability, chitosan coating was applied.</p><p><strong>Methods: </strong>Liposomes were prepared via the ethanol injection method using soy phosphatidylcholine and diacetyl phosphate. Chitosan coating was applied by adding chitosan solution (1% v/v acetic acid) at different chitosan-to-lipid ratios (0.1-0.4 w/w). The optimal formulation was selected based on particle size, PDI, and zeta potential. Characterization included encapsulation efficiency, drug loading, enzymatic stability, drug release, and Caco-2-based cytotoxicity and permeability assays.</p><p><strong>Results: </strong>The particle size and polydispersity index of the optimized formulations, L1-NDL, L2-NDL, L1C-NDL, and L2C-NDL, were measured as 27.02 ± 0.18 nm, 24.55 ± 0.22 nm, 160.10 ± 3.17 nm, 161.00 ± 2.30 nm, 0.39 ± 0.01, 0.37 ± 0.01, 0.19 ± 0.01, and 0.18 ± 0.02. Encapsulation efficiencies of 56.01 ± 3.70% and 43.87 ± 1.24% were recorded for L1C-NDL and L2C-NDL, respectively, while drug loading capacities were 61.47 ± 2.03% and 67.80 ± 0.74%, respectively. In an enzymatic degradation study, it was found that chitosan coating increased the stability of liposomes in the gastric media. The <i>in vitro</i> release was higher at both pH 1.2 and 6.8. Caco-2 assays confirmed >95% cell viability and enhanced permeability in the apical-tobasolateral direction. In the permeability study, chitosan-coated liposomal formulations demonstrated enhanced transport in the apical-to-basolateral direction, indicating improved intestinal permeability.</p><p><strong>Conclusion: </strong>Chitosan-coated liposomes improved NDL's stability and permeability, showing promise as an effective oral delivery system.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in Protein and Polypeptide Drug Analytics. 蛋白质和多肽药物分析研究进展。
IF 2.6 4区 医学
Current pharmaceutical design Pub Date : 2025-07-16 DOI: 10.2174/0113816128355706250626053659
Yuanli Mei, Hongmin Liu
{"title":"Advances in Protein and Polypeptide Drug Analytics.","authors":"Yuanli Mei, Hongmin Liu","doi":"10.2174/0113816128355706250626053659","DOIUrl":"https://doi.org/10.2174/0113816128355706250626053659","url":null,"abstract":"<p><p>With the rapid advancement of biotechnology, protein and peptide drugs have become increasingly widespread in the medical field, yet their metabolic processes are complex and require the assistance of modern analytical methods for research. Based on the latest domestic and international research, this paper systematically reviews the application of modern analytical methods in the metabolism of protein and peptide drugs. The research focuses on key technologies such as biological activity detection, mass spectrometry, and chromatography, elaborating on their principles, characteristics, and current state of development. The aim is to provide scientific evidence and technical support for drug development, and to promote in-depth research on the metabolism of protein and peptide drugs.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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