Pharmaceuticals最新文献

{"title":"Bevacizumab in Platinum-Sensitive Recurrent Epithelial Ovarian Cancer: A Risk-Stratified Analysis.","authors":"İrem Öner, Pınar Karaçin","doi":"10.3390/ph18060850","DOIUrl":"10.3390/ph18060850","url":null,"abstract":"<p><p><b>Background and Objectives:</b> Epithelial ovarian cancer (EOC) is a complex disease characterized by heterogeneous clinical, pathological, and molecular features. Diagnosed frequently at advanced stages, it presents significant challenges in treatment due to the risks of resistance and recurrence. While bevacizumab, by inhibiting angiogenesis, offers a valuable therapeutic option for platinum-sensitive recurrent ovarian cancer (PSROC), its impact on overall survival (OS) remains incompletely understood. This retrospective study aims to compare treatment responses in high- and low-risk groups of patients with PSROC and to evaluate the effects of bevacizumab on survival within these risk strata. <b>Materials and Methods:</b> This retrospective study included patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV EOC who received chemotherapy or chemotherapy plus bevacizumab for platinum-sensitive recurrence. Patients were classified according to risk groups, and their clinicopathological characteristics were compared. Survival analyses and adverse events regarding risk groups and bevacizumab use were examined. In this study, the effect of bevacizumab on survival in patients with PSROC was evaluated for the first time according to risk stratification, and the relationship between treatment response and survival was investigated according to recurrence localization. <b>Results:</b> Of the 174 patients included in this study, 102 (58.6%) were classified as low risk and 72 (41.4%) were classified as high risk. Significant differences in survival were observed between the risk groups. In the low-risk group, progression-free survival and overall survival were markedly longer compared to the high-risk group. Median PFS was 13.7 months in the low-risk group and 10.8 months in the high-risk group (<i>p</i> = 0.007). Median OS was 36.5 and 23.5 months, respectively (<i>p</i> = 0.003). In low-risk patients, the addition of bevacizumab to chemotherapy significantly increased median PFS (13.5 months vs. 9.7 months, <i>p</i> = 0.029); however, this advantage did not translate into a significant overall survival benefit (39.4 months vs. 33.3 months, <i>p</i> = 0.669). Conversely, in the high-risk group, bevacizumab use provided significant benefits in both PFS and OS. Median PFS was 13.9 months in the bevacizumab group and 8.8 months in the control group (<i>p</i> < 0.001). Median OS was calculated as 36.5 and 23.2 months, respectively (<i>p</i> < 0.001). <b>Conclusions:</b> Our study is among the first to comprehensively compare the effectiveness of bevacizumab treatment in patients with platinum-sensitive recurrent ovarian cancer based on clinical risk groups and recurrence patterns using real-world data. The current literature lacks a comprehensive analysis that simultaneously evaluates these two critical parameters. In this respect, our study aims to contribute to developing more personalized treatment s","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving the Dosing Schedules of Targeted Anticancer Agents.","authors":"Dominique Levêque","doi":"10.3390/ph18060848","DOIUrl":"10.3390/ph18060848","url":null,"abstract":"<p><p>Beyond developing new agents, cancer treatment can also be optimized by modifying the dosing regimen of approved drugs. Academic teams have experimented with different ways of improving drug regimens, leading to off-label practices for therapeutic and/or economic purposes, and currently, drug regulatory agencies have begun to reappraise this often-neglected topic. This concept also considers the patient's perspective in terms of quality of life and convenience, including the concept of time toxicity. Overall, the optimization of drug dosing of anticancer agents may be viewed on three sides: the improvement of the benefits/risks balance (patient), the improvement of the convenience of the treatment (patient, healthcare professionals), and the mitigation of the financial impact (health insurance, patient). Examples of dose reassessments of targeted therapies (approved since 1997) are chosen to illustrate the context. Suboptimal/overdosed regimens are found for certain molecularly targeted agents, mostly based on the ancient concept of maximum tolerated dose in oncology. This underlines the lack of comparative effective dose trials before approval. Fortunately, dosing regimens of newly approved molecularly targeted agents is going to evolve with the hope of more convenient and better tolerated treatments. This optimization will bring greater benefit to patients and to healthcare professionals but without addressing the economic issue.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Reprogramming in Melanoma: An Epigenetic Point of View.","authors":"Stefano Giuliani, Celeste Accetta, Simona di Martino, Claudia De Vitis, Elena Messina, Edoardo Pescarmona, Maurizio Fanciulli, Gennaro Ciliberto, Rita Mancini, Italia Falcone","doi":"10.3390/ph18060853","DOIUrl":"10.3390/ph18060853","url":null,"abstract":"<p><p>Metabolic reprogramming and epigenetic alterations are fundamental hallmarks of cancer cells, contributing to adaptation, progression, and resistance. In melanoma, high metabolic-epigenetic plasticity enables the rapid modulation of cell states in response to environmental and therapeutic pressures. Recent studies have highlighted a bidirectional crosstalk between cellular metabolism and epigenetic regulation. Epigenetic modifications influence the transcriptional control of metabolic genes, thereby shaping metabolic phenotypes. Conversely, specific metabolites are essential cofactors or substrates for epigenetic enzymes, directly modulating the epigenome. Understanding the intricate mechanisms of this interaction offers opportunities for the development of innovative tumor management that combines epigenetic, metabolic, and therapy interventions. In this review, we summarize the latest evidence on the role of the metabolism-epigenetics axis in melanoma and discuss its potential clinical implications, aiming to provide a comprehensive overview of metabolic/epigenetic interconnections.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination Treatment with Free Doxorubicin and Inductive Moderate Hyperthermia for Sarcoma Saos-2 Cells.","authors":"Valerii E Orel, Anatolii G Diedkov, Vasyl V Ostafiichuk, Sergii A Lyalkin, Igor O Tkachenko, Denys L Kolesnyk, Valerii B Orel, Olga Yo Dasyukevich, Oleksandr Yu Rykhalskyi, Oleksii V Movchan, Alexander Yu Galkin, Anna B Prosvietova","doi":"10.3390/ph18060852","DOIUrl":"10.3390/ph18060852","url":null,"abstract":"<p><p><b>Background:</b> Osteosarcoma (OS) is the most common primary malignant bone tumor. Doxorubicin (DOX) is extensively used in OS chemotherapy, yet improving patient outcomes remains challenging. This study investigated the effect of free DOX combined with inductive moderate hyperthermia (IMH) on Saos-2 human OS cells. <b>Methods</b>: Cell viability was assessed by trypan blue exclusion. Flow cytometry analyzed apoptosis, necrosis, and reactive oxygen species (ROS) in cells exposed to control (no treatment), IMH (42 MHz frequency, 500 μT magnetic field induction, 564 V/m electric field strength, 15 W output power, and 30 min duration) alone, DOX (0.06 μg/mL) alone, or DOX combined with IMH. The expression of p14^ARF tumor suppressor and epidermal growth factor receptor (EGFR) was evaluated by immunocytochemistry. Spatial autocorrelation analysis quantified the heterogeneity of p14^ARF and EGFR distributions in acquired images. <b>Results</b>: The half maximal inhibitory concentration (IC₅₀) of DOX in Saos-2 cells had minimal variation between 48 h (0.060 ± 0.01 μg/mL) and 72 h (0.055 ± 0.003 μg/mL). DOX + IMH resulted in a 15% increase in early apoptosis and a 20% elevation in ROS levels compared with DOX alone. Immunocytochemical analysis revealed a 37% increase in p14^ARF and a 32% reduction in EGFR expression following combined treatment in comparison to DOX alone. Image analysis showed that DOX + IMH treatment caused the highest Moran's index values for p14^ARF and EGFR, reflecting less heterogeneous spatial distributions (<i>p</i> < 0.05). <b>Conclusions</b>: IMH enhanced DOX-induced cytotoxicity in Saos-2 cells by initiating ROS-mediated apoptosis and reducing heterogeneity of cellular responses.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Combination Studies of Novel Dipeptide Nitriles with Curcumin for a Potent Synergistic Action Against Rhodesain, Cysteine Protease of <i>Trypanosoma brucei rhodesiense</i>.","authors":"Carla Di Chio, Josè Starvaggi, Santo Previti, Fabiola De Luca, Benito Natale, Sandro Cosconati, Tanja Schirmeister, Maria Zappalà, Roberta Ettari","doi":"10.3390/ph18060847","DOIUrl":"10.3390/ph18060847","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Rhodesain is a cysteine protease crucial for the life cycle of <i>Trypanosoma brucei rhodesiense</i>, a parasite that causes the lethal form of human African trypanosomiasis. For these reasons, rhodesain is considered an important target for the drug discovery process of novel antitrypanosomal agents. <b>Methods:</b> In the present work, we carried out a combination study of two novel synthetic nitriles, <b>Nitrile 1</b> and <b>Nitrile 2</b>, with curcumin, the golden multitarget nutraceutical obtained from <i>Curcuma longa</i> L., which we demonstrated to inhibit rhodesain in a non-competitive manner. We calculated the combination index (CI) in both the combination studies by using the Chou and Talalay method. <b>Results:</b> Comparing the CI values of the combinations <b>Nitrile 1</b> + curcumin and <b>Nitrile 2</b> + curcumin, we assessed that the inhibitory effect of the combination <b>Nitrile 2</b> + curcumin against rhodesain was much more potent than that of the other combination. At the IC₅₀ value, in the case of the combination <b>Nitrile 1</b> + curcumin an additive effect occurred, while in the case of <b>Nitrile 2 +</b> curcumin, we observed a moderate synergism: at 99% of the effect, the synergism induced by the combination <b>Nitrile 2 +</b> curcumin was much stronger than the synergism promoted by the combination <b>Nitrile 1</b> + curcumin (CI = 0.3843 <i>vs</i> 0.6622, respectively). <b>Conclusions:</b> The co-administration of dipeptide nitriles with curcumin enhances rhodesain inhibition through synergistic effects. Notably, <b>Nitrile 2</b> + curcumin exhibits a stronger synergy at higher inhibition levels, indicating a greater therapeutic potential.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Potential Association Between Inhaled Corticosteroid and Face Aging Risk: A Mendelian Randomization Study.","authors":"Junpeng Li, Yaqiong Liu, Gujie Wu, Shanye Yin, Lin Cheng, Wenjun Deng","doi":"10.3390/ph18060846","DOIUrl":"10.3390/ph18060846","url":null,"abstract":"<p><p><b>Background</b>: Asthma is one of the most prevalent chronic diseases, affecting more than 300 million individuals globally. Inhaled corticosteroids (ICSs) are recommended as the primary therapy for managing and preventing asthma symptoms in current treatment guidelines. However, long-term use of ICSs could lead to multiple side effects, including skin changes. <b>Methods</b>: We identified ICS target genes using DrugBank and DGIdb databases and derived genetic instruments from cis-eQTL data in whole-blood samples (n = 31,684). GWAS data for facial aging traits (n = 423,999) and plasma metabolites (1400 metabolites, n = 8000) were analyzed. DNA methylation QTL (mQTL) data were used to explore epigenetic regulation. Mendelian randomization (MR) and colocalization analyses were performed to assess causality and shared genetic loci. <b>Results</b>: MR analysis suggested a significant link between genetically proxied ICSs (ORMDL3) and face aging in the European population. Further mediation analysis indicated that 5-Hydroxylysine partially mediates the relationship between ICSs and face aging. In addition, our analysis revealed the pleiotropic association of some novel DNA methylation sites of ORMDL3 with face aging, suggesting the possible regulatory mechanism that are involved in face aging. <b>Conclusions</b>: These findings, while exploratory, raise the hypothesis that ICSs may impact face aging through upregulation of ORMDL3 expression and 5-hydroxylysine metabolism and highlight the need for further pharmacological and clinical research to validate these potential effects.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico Investigation of TATA-Binding Protein as a Therapeutic Target for Chagas Disease: Insights into FDA Drug Repositioning.","authors":"Carlos Gaona-López, Domingo Méndez-Álvarez, Alonzo Gonzalez-Gonzalez, Guadalupe Avalos-Navarro, Alma D Paz-González, Adriana Moreno-Rodríguez, Benjamín Nogueda-Torres, Gildardo Rivera","doi":"10.3390/ph18060845","DOIUrl":"10.3390/ph18060845","url":null,"abstract":"<p><p><b>Background:</b> Parasitic diseases, particularly Chagas disease caused by <i>Trypanosoma cruzi</i>, primarily affect developing countries but are now spreading to wealthier nations due to changing migration patterns. With approximately 8 to 9 million cases annually and a rise in drug resistance and side effects, there is an urgent need for new therapeutic approaches. <b>Objectives:</b> This study aimed to identify potential pharmacological compounds to target the TATA Binding Protein (TBP) of <i>T. cruzi</i>. <b>Methods:</b> Over eleven thousand FDA-approved pharmacological compounds were analyzed using in silico methods, including homology modeling, molecular docking, and molecular dynamics simulations. In addition, in vitro assays were conducted to assess the trypanocidal activity of promising candidates against <i>T. cruzi</i> epimastigotes and their selectivity toward macrophage J774.2. <b>Results:</b> Two compounds, DB00890 and DB07635, emerged as promising candidates, demonstrating significant potential against <i>T. cruzi</i> TBP. Compound DB00890 had trypanocidal activity against <i>T. cruzi</i> epimastigotes, with IC₅₀ values of 70.4 µM (SI 2.84) and 37.3 µM (SI 5.36) for the NINOA and A1 strains, respectively. <b>Conclusions:</b> Our findings suggest DB00890 is a promising candidate for the development of new agents against Chagas disease, with the potential for targeted therapies that minimize side effects. These results provide a strong foundation for further research into novel treatments for parasitic diseases caused by <i>T. cruzi</i>.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraoperative Confocal Laser Endomicroscopy Detects Prostate Cancer at the Single-Cell Level with High Specificity and in Real Time: A Preclinical Proof of Concept.","authors":"Ann-Christin Eder, Jessica Matthias, Francois Lacombe, Lisa-Charlotte Domogalla, Antoine Jacques, Nils Steinacker, Gaetan Christien, Elodie Martin, Aline Criton, Matthias Eder","doi":"10.3390/ph18060841","DOIUrl":"10.3390/ph18060841","url":null,"abstract":"<p><p>In prostate cancer (PCa) surgery, precise tumor margin identification remains challenging despite advances in surgical techniques. This study evaluates the combination of tumor-specific near-infrared imaging with the PSMA-targeting molecule PSMA-914 and optical endomicroscopy (NIR-pCLE) for single-cell-level tumor identification in a preclinical proof of concept. <b>Methods:</b> NIR-pCLE imaging of varying PSMA-914 concentrations was performed on PSMA-positive LNCaP and PSMA-negative PC-3 cells using Cellvizio^® 100 with pCLE Confocal Miniprobes™. To identify optimal PSMA-914 dosing for in vivo imaging, different doses (0-10 nmol) were evaluated using NIR-pCLE, Odyssey CLx imaging, and confocal microscopy in an LNCaP tumor-bearing xenograft model. A proof of concept mimicking a clinical workflow was performed using 5 nmol [⁶⁸Ga]Ga-PSMA-914 in LNCaP and PC-3 tumor xenografts, including PET/MRI, in/ex vivo NIR-pCLE imaging, and microscopic/macroscopic imaging. <b>Results:</b> NIR-pCLE detected PSMA-specific fluorescence at concentrations above 30 nM in vitro. The optimal dose was identified as 5 nmol PSMA-914 for NIR-pCLE imaging with cellular resolution in LNCaP xenografts. PET/MRI confirmed high tumor uptake and a favorable distribution profile of PSMA-914. NIR-pCLE imaging enabled real-time, single-cell-level detection of PSMA-positive tissue, visualizing tumor heterogeneity, confirmed by ex vivo microscopy and imaging. <b>Conclusions:</b> This preclinical proof of concept demonstrates the potential of intraoperative PSMA-specific NIR-pCLE imaging to visualize tissue structures in real time at cellular resolution. Clinical implementation could provide surgeons with valuable additional information, potentially advancing PCa patient care through improved surgical precision.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Efficacy and Safety Herbal Medicine for Symptom Management After HIFU Treatment in Adenomyosis: A Systematic Review and Meta-Analysis.","authors":"Eun-Jin Kim, Young-Shin Shim, Hyun-Kyung Sung, Sang-Yeon Min","doi":"10.3390/ph18060843","DOIUrl":"10.3390/ph18060843","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Adenomyosis (AM) is a hormone-dependent gynecological disorder that negatively impacts the quality of life and fertility of reproductive-age women. This study aimed to evaluate the effectiveness of herbal medicine (HM) as a post-treatment strategy following high-intensity focused ultrasound (HIFU) therapy. <b>Methods</b>: English, Chinese, and Korean databases were systematically searched up to 24 March 2025. Eligible randomized controlled trials (RCTs) compared HM administration after HIFU therapy with HIFU therapy alone. Statistical analyses included mean difference (MD), standardized mean difference (SMD), and risk ratio (RR) with 95% confidence intervals (CIs). Evidence quality was assessed using GRADE approach. The protocol was registered with INPLASY (No.: INPLASY202530088). <b>Results</b>: Fourteen RCTs involving 1259 patients were included in the review. HM administration after HIFU therapy showed superior efficacy over HIFU therapy alone in reducing uterine volume (MD = -11.84, 95% CI: -13.74 to -9.95; <i>p</i> < 0.00001), adenomyotic lesion volume (MD = -2.86, 95% CI: -3.29 to -2.43; <i>p</i> < 0.00001), serum CA125 levels (SMD = -1.49, 95% CI: -2.41 to -0.58; <i>p</i> < 0.00001), serum estradiol (E2) levels (SMD = -1.28, 95% CI: -1.54 to -1.03; <i>p</i> < 0.0001), and improvements in dysmenorrhea (MD = -0.54, 95% CI: -1.06 to -0.02; <i>p</i> < 0.00001) <b>Conclusions</b>: HM may be an effective and safe adjunct to HIFU for managing AM. However, further high-quality RCTs with long-term follow-up are needed to validate these findings.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating TnP as a Potential Therapeutic Agent for Retinopathy in Zebrafish Models.","authors":"João Gabriel Santos Rosa, Jefferson Thiago Gonçalves Bernardo, Yolanda Álvarez, Breandán Kennedy, Carla Lima, Monica Lopes-Ferreira","doi":"10.3390/ph18060840","DOIUrl":"10.3390/ph18060840","url":null,"abstract":"<p><p><b>Background</b>: The retina plays a vital role in vision, and its impairment can cause significant visual deficits. Current retinal disease treatments range from conventional anti-inflammatory drugs to advanced anti-VEGF therapies and monoclonal antibodies. TnP, a novel synthetic peptide in preclinical development, has demonstrated therapeutic potential in chronic inflammatory conditions such as multiple sclerosis and asthma due to its immunomodulatory properties. Using zebrafish-which share significant genetic homology with humans-we investigated TnP's effects on retinopathy models mimicking diabetic retinopathy (DR) through either cobalt chloride (CoCl₂)-induced hypoxia or light-induced retinal damage (LIRD). <b>Methods</b>: We employed two retinal injury models (CoCl₂-induced hypoxia and LIRD) and subjected them to TnP treatment, assessing the outcomes through visual-motor response testing and histological examination. <b>Results</b>: CoCl₂ exposure impaired swimming activity, while light damage reduced the movement distance. Both models induced distinct retinal morphological changes. Although TnP failed to reverse most injury effects, it specifically restored the inner plexiform layer (IPL)'s thickness. <b>Conclusions</b>: Our findings suggest that TnP may enhance neuronal plasticity by promoting cell proliferation and synaptic connectivity. While showing promise as a therapeutic candidate for retinal and neurodegenerative disorders, TnP might achieve optimal efficacy when combined with complementary treatments.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}