Pharmaceuticals最新文献

{"title":"Neuroprotective Effect of Methylene Blue in a Rat Model of Traumatic Optic Neuropathy.","authors":"Nicolás S Ciranna, Ronan Nakamura, Rafael Peláez, Álvaro Pérez-Sala, Patricia Sarrión, Juan C Fernández, Alejandra Paganelli, Agustín P Aranalde, Ulises P Ruiz, Juan J López-Costa, César F Loidl, Alfredo Martínez, Manuel Rey-Funes","doi":"10.3390/ph18060920","DOIUrl":"10.3390/ph18060920","url":null,"abstract":"<p><p><b>Background</b>: Traumatic optic neuropathy (TON) represents a major cause of vision loss worldwide, and treatment options are limited. Here, we study whether methylene blue (MB), a free radical scavenger, is able to prevent morphological and electrophysiological hallmarks of neuropathy in an animal model of TON. <b>Methods</b>: The left eyes of Wistar rats were subjected to intraorbital nerve crush (IONC) while the right ones were sham operated. The group of rats treated with MB (n = 16) received five intraperitoneal injections with 2.0 mg/kg MB in the 24 h following IONC while the control group (n = 16) received just vehicle (PBS) as a control. Twenty-one days after surgery, scotopic full field (scERG), scotopic oscillatory potentials (OP), photopic full field (phERG) and pattern (PERG) electroretinography were performed for retinal function assessment. Furthermore, the number of cell nuclei in the ganglion cell layer (GCL) was recorded in post mortem histological sections. <b>Results</b>: IONC induced very significant reductions in electrophysiological parameters including scotopic a- and b-wave, OPs, photopic b-wave, PhNR amplitude and N2 amplitude. In addition, it also generated a significant prolongation of the N2 implicit time, indicating a profound impact on retinal function. This was further corroborated by a very significant reduction in the number of neuronal nuclei in the GCL, suggesting an intense loss and functional impairment of retinal ganglion cells. MB treatment was able to prevent, partially or completely, all those parameters, indicating the efficiency of such approach. <b>Conclusions</b>: Since MB is already approved for clinical use and presents a high safety profile, it could be repurposed as a neuroprotective drug for ophthalmological applications once proper phase 2 clinical trials are accomplished.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507726","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":"3D-QSAR Design of New Bcr-Abl Inhibitors Based on Purine Scaffold and Cytotoxicity Studies on CML Cell Lines Sensitive and Resistant to Imatinib.","authors":"David Cabezas, Thalía Delgado, Guisselle Sepúlveda, Petra Krňávková, Veronika Vojáčková, Vladimír Kryštof, Miroslav Strnad, Nicolás Ignacio Silva, Javier Echeverría, Christian Espinosa-Bustos, Guido Mellado, Jiao Luo, Jaime Mella, Cristian O Salas","doi":"10.3390/ph18060925","DOIUrl":"10.3390/ph18060925","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Bcr-Abl inhibitors such as imatinib have been used to treat chronic myeloid leukemia (CML). However, the efficacy of these drugs has diminished due to mutations in the kinase domain, notably the T315I mutation. Therefore, in this study, new purine derivatives were designed as Bcr-Abl inhibitors based on 3D-QSAR studies. <b>Methods:</b> A database of 58 purines that inhibit Bcr-Abl was used to construct 3D-QSAR models. Using chemical information from these models, a small group of new purines was designed, synthesized, and evaluated in Bcr-Abl. Viability assays were conducted on imatinib-sensitive CML cells (K562 and KCL22) and imatinib-resistant cells (KCL22-B8). In silico analyses were performed to confirm the results. <b>Results:</b> Seven purines were easily synthesized (<b>7a</b>-<b>g</b>). Compounds <b>7a</b> and <b>7c</b> demonstrated the highest inhibition activity on Bcr-Abl (IC₅₀ = 0.13 and 0.19 μM), surpassing the potency of imatinib (IC₅₀ = 0.33 μM). <b>7c</b> exhibited the highest potency, with GI₅₀ = 0.30 μM on K562 cells and 1.54 μM on KCL22 cells. The GI₅₀ values obtained for non-neoplastic HEK293T cells indicated that <b>7c</b> was less toxic than imatinib. Interestingly, KCL22-B8 cells (expressing Bcr-Abl^T315I) showed greater sensitivity to <b>7e</b> and <b>7f</b> than to imatinib (GI₅₀ = 13.80 and 15.43 vs. >20 μM, respectively). In silico analyses, including docking and molecular dynamics studies of Bcr-Abl^T315I, were conducted to elucidate the enhanced potency of <b>7e</b> and <b>7f</b>. Thus, this study provides in silico models to identify novel inhibitors that target a kinase of significance in CML.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507644","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":"Nerve Growth Factor in Pediatric Brain Injury: From Bench to Bedside.","authors":"Lorenzo Di Sarno, Serena Ferretti, Lavinia Capossela, Antonio Gatto, Valeria Pansini, Anya Caroselli, Luigi Manni, Marzia Soligo, Antonio Chiaretti","doi":"10.3390/ph18060929","DOIUrl":"10.3390/ph18060929","url":null,"abstract":"<p><p><b>Background:</b> Traumatic brain injury (TBI) and hypoxic-ischemic encephalopathy (HIE) are major causes of long-term neurological disability in children, with limited options for effective neuronal recovery. Recent research has highlighted the therapeutic potential of nerve growth factor (NGF) in promoting neural repair through mechanisms such as neuroprotection, neurogenesis, and the modulation of neuroinflammation. This review evaluates the current evidence on NGF as a treatment strategy for pediatric brain injury, emphasizing its mechanisms of action and translational clinical applications. <b>Methods:</b> A comprehensive review was conducted using the PubMed, Scopus, and Cochrane CENTRAL databases to identify studies published between 1 January 1978 and 1 March 2025, investigating NGF in the context of brain injury. The inclusion criteria comprised studies assessing neurological outcomes through clinical scales, biochemical markers, neuroimaging, or electrophysiological examinations. <b>Results:</b> Seventeen studies met the inclusion criteria, encompassing both preclinical and clinical research. Preclinical models consistently demonstrated that NGF administration reduces neuroinflammation, enhances neurogenesis, and supports neuronal survival following TBI and HIE. Clinical studies, including case reports of pediatric patients treated with intranasal NGF, reported improvements in motor and cognitive function, neuroimaging findings, and electrophysiological parameters, with no significant adverse effects observed. <b>Conclusions:</b> NGF demonstrates significant promise as a neuroprotective and neuroregenerative agent in pediatric brain injury, with both experimental and early clinical evidence supporting its safety and efficacy. Large-scale controlled clinical trials are warranted to validate these preliminary findings and to determine the optimal dosage regimens and administration schedules for NGF in the treatment of TBI and HIE.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507724","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":"Ethanolic Extract of <i>Ganoderma mexicanum</i> Pat. Mycelium: A Source of Bioactive Compounds with Antiproliferative Activity and Potential PPAR-γ Natural Ligands.","authors":"Lucia T Angulo-Sanchez, Max Vidal-Gutiérrez, Heriberto Torres-Moreno, Martín Esqueda, Aldo Gutiérrez, Georgina Vargas, Juan Luis Monribot-Villanueva, José A Guerrero-Analco, César Muñoz-Bacasehua, Ramón Enrique Robles-Zepeda","doi":"10.3390/ph18060909","DOIUrl":"10.3390/ph18060909","url":null,"abstract":"<p><p><b>Background/Objective:</b><i>Ganoderma</i> spp. have long been studied for their bioactive pharmacological properties, and their biomass and extracts have been obtained from various sources. This study adopts a novel approach: enriching a liquid culture of <i>Ganoderma mexicanum</i> with a vineyard pruning waste extract to identify bioactive compounds with antiproliferative activity through enriched chromatographic fractions. <b>Methods:</b> The ethanolic extract from a mycelial culture was separated following a partitioning process, and the hexane fraction was subsequently separated in a chromatographic column. The fractions were evaluated for their antiproliferative properties against cancer cell lines. The interactions of the molecules identified with peroxisome proliferator-activated receptor gamma (PPAR-γ) were analyzed via molecular docking. <b>Results:</b> Three chromatographic fractions (FH11-FH13) exhibited antiproliferative activity which was significantly more effective against non-small lung cancer cells (A549). The cells treated with the crude extract and fractions presented a balloon-like morphology. A chemical analysis of the active fractions allowed us to identify four compounds: one fatty acid (9-Hydroxy-10E,12Z-octadecadienoic acid) and three triterpenes (ganoderic acids DM, TQ, and X). These compounds showed interactions with the PPAR-γ receptor through molecular docking. <b>Conclusions</b>: <i>Ganoderma mexicanum</i> is a promising source of compounds with antiproliferative activity that could serve as natural ligands for PPAR-γ and has possible applications in lung cancer therapy.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507721","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":"Evaluation of Statins Use in Hemodialysis Patients: A Retrospective Analysis of Clinical and Safety Outcomes.","authors":"Abdulmalik S Alotaibi, Mohamed A Albekery, Ahmed A Alanazi, Ibrahim S Alhomoud, Khalid A Alamer, Mohammad Shawaqfeh, Reem H Alshammari, Fayez Alhejaili, Muthana Al Sahlawi, Ibrahim Aldossary, Hajar Adel Aljuayl, Mohammad Alkathiri, Shmeylan Alharbi, Abdulkareem Albekairy, Abdulmalik Alkatheri","doi":"10.3390/ph18060911","DOIUrl":"10.3390/ph18060911","url":null,"abstract":"<p><p><b>Background:</b> Lipid metabolism disturbances are common in end-stage renal disease (ESRD) patients on hemodialysis (HD), leading to dyslipidemia, which is characterized by abnormal plasma lipids and lipoproteins. Although large randomized controlled trials have generally not demonstrated a survival benefit associated with statin therapy among patients receiving hemodialysis, limited observational studies have reported potential associations with improved clinical outcomes in this population. <b>Methods</b>: This retrospective cohort study investigated the clinical and safety outcomes of statin use in ESRD patients on HD with documented dyslipidemia over a two-year period from 1 January 2018 to 30 December 2019. The primary endpoints evaluated the clinical outcomes of statins by assessing changes in specific lipid parameters, including low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C). The secondary endpoints assessed safety by monitoring liver enzymes and creatine kinase (CK) levels. <b>Results</b>: Among 179 participants, diabetes mellitus was present in 134 patients (74.9%), while 168 patients (93.9%) had hypertension. Cardiovascular events occurred in 95 patients (53.1%). Statin therapy was administered to 146 patients (82.0%), with atorvastatin being the most frequently prescribed statin (69.3%). Modest reductions in LDL-C levels were observed in the rosuvastatin and atorvastatin groups, whereas slight increases were noted in the simvastatin and non-statin groups. None of these within-group changes were statistically significant. In the atorvastatin group, LDL-C decreased slightly from 2.058 to 2.003 mmol/L. The rosuvastatin group experienced a more pronounced LDL-C reduction from 2.607 to 2.113 mmol/L. Conversely, the simvastatin group showed an LDL-C increase from 1.550 to 1.901 mmol/L. Among the non-statin group, LDL-C increased from 2.678 to 2.820 mmol/L. Liver enzyme and CK levels fluctuated slightly but remained within normal ranges. <b>Conclusions</b>: This study evaluated statin therapy in hemodialysis patients with dyslipidemia. Although modest reductions in LDL-C levels were observed in the atorvastatin and rosuvastatin groups, statin therapy did not reduce the incidence of atherosclerotic events in hemodialysis patients with dyslipidemia. Additionally, statin use was not associated with any clinically or statistically significant effects.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507732","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":"Ferulic Acid as an Anti-Inflammatory Agent: Insights into Molecular Mechanisms, Pharmacokinetics and Applications.","authors":"Jiaying Liu, Yu Guan, Le Yang, Heng Fang, Hui Sun, Ye Sun, Guangli Yan, Ling Kong, Xijun Wang","doi":"10.3390/ph18060912","DOIUrl":"10.3390/ph18060912","url":null,"abstract":"<p><p>Ferulic acid (FA), a hydroxycinnamic acid derivative, is a key bioactive component in traditional medicinal plants including <i>Angelica sinensis</i> and <i>Asafoetida</i>. Accumulating evidence supports its therapeutic efficacy in inflammatory disorders, such as rheumatoid arthritis (RA) and ulcerative colitis (UC). FA exerts anti-inflammatory effects through (1) the regulation of inflammatory cytokine levels; (2) modulation of signaling pathways such as nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and janus kinase/signal transducer and activator of transcription (JAK/STAT); (3) amelioration of oxidative stress; and (4) regulation of immune cell homeostasis. At the pharmacokinetic level, studies show that FA is rapidly absorbed but exhibits low bioavailability, mainly due to the influence of metabolic pathways and food matrix characteristics. This review systematically summarizes the literature on the anti-inflammatory effects of FA, covering molecular mechanisms, pharmacokinetic characteristics, and application scenarios. Preclinical studies show that FA has low toxicity and good safety, demonstrating potential for development as a novel anti-inflammatory drug. However, its clinical translation is hindered by bottlenecks such as low bioavailability and insufficient human clinical data. Future research should prioritize developing novel drug delivery systems and conducting large-scale clinical trials to facilitate its clinical translation.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507738","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":"Combined Network Pharmacology, Transcriptomics and Metabolomics Strategies Reveal the Mechanism of Action of Lang Chuang Wan to Ameliorate Lupus Nephritis in MRL/lpr Mice.","authors":"Cuicui Li, Guoxin Ji, Xinru Zhang, Hang Yu, Zhimeng Li, Bo Yang, Zhuangzhuang Yao, Shilei Wang, Tongwei Jiang, Shumin Wang","doi":"10.3390/ph18060916","DOIUrl":"10.3390/ph18060916","url":null,"abstract":"<p><p><b>Background</b>: Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) and is difficult to cure. Lang Chuang Wan (LCW) has been widely used in clinical practice as a treatment for SLE and LN, but its active ingredients and mechanism of action have not been elucidated. To address this, we aim to analyze LCW's chemical components and clarify its mechanisms in treating LN. <b>Methods</b>: We utilized ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to analyze the components of LCW and assessed its effects on MRL/lpr mice through ELISA, H&E staining, Masson's trichrome staining, and IgG immunofluorescence. Then, we further explored the mechanisms of action through network pharmacology, transcriptomics, and metabolomics, and validated with Western blot. <b>Results</b>: LCW contained 1303 chemical components, primarily flavonoids and terpenoids. It significantly improved kidney pathology and normalized levels of serum ANA, anti-dsDNA, anti-Sm, C3, C4, Cr, BUN, IL-6, IL-10, IL-17, TNF-α, and urinary protein (UP) in MRL/lpr mice. Network pharmacology, transcriptomics, and metabolomics indicated that LCW's therapeutic effect on LN involved the PI3K/AKT pathway, confirmed by Western blot showing LCW's suppression of the PI3K/AKT/mTOR pathway. <b>Conclusions</b>: LCW alleviates pathological symptoms in MRL/lpr mice by inhibiting the PI3K/AKT/mTOR signaling pathway, providing insights into its therapeutic mechanisms for lupus nephritis.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507678","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":"Effect of Acoustic Pressure on Temozolomide-Loaded Oleic Acid-Based Liposomes and Its Safety to Brain Tissue.","authors":"Vasilisa D Dalinina, Vera S Shashkovskaya, Iman M Khaskhanova, Daria Yu Travnikova, Nelly S Chmelyuk, Dmitry A Korzhenevskiy, Vsevolod V Belousov, Tatiana O Abakumova","doi":"10.3390/ph18060910","DOIUrl":"10.3390/ph18060910","url":null,"abstract":"<p><p><b>Background:</b> Glioblastoma (GBM) is a highly aggressive primary brain tumor with limited therapeutic options, particularly due to the limited blood-brain barrier (BBB) permeability. Nanoparticle-based drug delivery systems, such as liposomes, can prolong drugs' circulation time and enhance their accumulation within brain tumors, thereby improving therapeutic outcomes. Controlled drug release further contributes to high local drug concentrations while minimizing systemic toxicity. Oleic acid (OA), a monounsaturated fatty acid, is commonly used to enhance drug loading and increase lipid membrane fluidity. In this study, we developed liposomal formulations with optimized temozolomide (TMZ)'s loading and analyze its response to focused ultrasound (FUS). <b>Methods</b>: We synthetized OA-based liposomes with different lipid composition, performed physicochemical characterization (DLS, TEM) and analyzed the TMZ loading efficiency. Different FUS parameters were tested for effective OA-based liposomes destruction. Safety of selected parameters was evaluated in vivo by MRI, histological staining and RT-PCR of pro-inflammatory cytokines. <b>Results</b>: All the formulations exhibited comparable hydrodynamic diameters; however, OA-containing liposomes demonstrated a significantly higher TMZ encapsulation efficiency and enhanced cytotoxicity in U87 glioma cells. Moreover, it was shown that OA-liposomes were disrupted at lower acoustic pressures (5 MPa), while conventional liposomes required higher thresholds (>8 MPa). A safety analysis of FUS parameters indicated that pressures exceeding 11 MPa induced brain edema, necrotic lesions and elevated cytokine levels within 72 h post-treatment. <b>Conclusions</b>: These results suggest that OA-based liposomes possess favorable characteristics, with an increased sonosensitivity for the site-specific delivery of TMZ, offering a promising strategy for glioma treatment.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507704","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":"Microenvironment and Tumor Heterogeneity as Pharmacological Targets in Precision Oncology.","authors":"Stelvio Tonello, Roberta Rolla, Paolo Amedeo Tillio, Pier Paolo Sainaghi, Donato Colangelo","doi":"10.3390/ph18060915","DOIUrl":"10.3390/ph18060915","url":null,"abstract":"<p><p>Tumor diseases are characterized by high interindividual and intratumoral heterogeneity (ITH). The development and progression of neoplasms outline complex networks of extracellular and cellular signals that have yet to be fully elucidated. This narrative review provides a comprehensive overview of the literature related to the cellular and molecular mechanisms underlying the heterogeneity of the tumor mass. Furthermore, it examines the possible role of the tumor microenvironment in the development and support of the neoplasm, in order to highlight its potential in the construction of a diagnostic-therapeutic approach to precision medicine. Many authors underline the importance of the tumor microenvironment (TME) as it actively takes part in the growth of the neoplastic mass and in the formation of metastases and in the acquisition of resistance to anticancer drugs. In specific body districts, the ideal conditions occur for the TME establishment, particularly the inflammatory state, the recruitment of cell types, the release of specific cytokines and growth factors, hypoxic conditions. These components actively intervene by enabling tumor progression and construction of physical barriers shaped by the extracellular matrix that contribute to forming peripheral tolerance by intervention of myeloid precursors and the polarization of M2 macrophages. In recent years, ITH and the TME have assumed an important position in cancer research and pharmacology as they enable understanding the dense network of communication existing between the neoplasm and the surrounding environment, and to monitor and deepen the effects of drugs with a view to develop increasingly precise and effective therapies. In the last decade, knowledge of TME has been exploited to produce targeted molecular agents (inhibitory small molecules, monoclonal antibodies, gene therapy). Nonetheless, the bibliography shows the need to study ITH through new prognostic and predictive biomarkers (e.g., ctDNA and CTCs) and to increase its basic biology knowledge. Precision medicine is a new opportunity in the treatment of oncological diseases that is transforming the development of new drug approaches and their clinical use. Biology and biotechnologies are providing the bases for this revolution.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507708","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":"Curcumin-like Compound Inhibits Proliferation of Adenocarcinoma Cells by Inducing Cell Cycle Arrest and Senescence.","authors":"Rafael Fonseca, Yasmin Dos Santos Louzano, Cindy Juliet Cristancho Ortiz, Matheus de Freitas Silva, Maria Luiza Vieira Felix, Guilherme Álvaro Ferreira-Silva, Ester Siqueira Caixeta, Bruno Zavan, Claudio Viegas, Marisa Ionta","doi":"10.3390/ph18060914","DOIUrl":"10.3390/ph18060914","url":null,"abstract":"<p><p><b>Background:</b> Lung cancer is the leading cause of cancer-related death in the male sex worldwide. Non-small cell lung cancer (NSCLC) is the most prevalent type, accounting for 80-85% of cases, and lung adenocarcinoma is the most common and lethal NSCLC subtype, being responsible for ca. 50% of deaths. Despite new therapeutic strategies, lung cancer mortality rates remain high, highlighting the need for the development of new drugs. <b>Objectives:</b> We investigated the pharmacological potential of a series of curcumin-like compounds using two lung adenocarcinoma cell lines as models. <b>Methods and Results:</b> Cell viability assay led to the identification of PQM-214 as the hit compound, and other methodologies were employed to investigate the mechanisms underlying its antitumor potential, including cell cycle analysis, mitotic index determination, assessment of clonogenic capacity, senescence-associated β-galactosidase and annexin V assays, quantitative PCR, and Western blot analyses. The mechanism of action of PQM-214 was investigated in A549 cells, revealing that it effectively inhibits cell proliferation by inducing cell cycle arrest, apoptosis, or senescence. Cell cycle key regulators were significantly modulated by PQM-214, with cyclin E2, <i>MYC</i>, and <i>FOXM1</i> being downregulated, while senescence markers such as cyclin D1, <i>CDKN1A</i> (p21), <i>IL-8</i>, <i>TIMP1</i>, and <i>TIMP2</i> were upregulated. Moreover, Western blot results revealed upregulation of cyclin D1 and p21 in PQM-214-treated samples, with a downregulation of cyclin B. <b>Conclusions</b>: PQM-214 seems to act on different molecular targets in lung adenocarcinoma cells, inhibiting cell proliferation and inducing apoptosis. Further studies will be conducted to explore whether PQM-214 can also act as a senolytic agent, which would reinforce its anticancer potential.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507682","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}