Chong-Chao Hsieh , Hsuan-Fu Kuo , Hsiao-Hsuan Wang , Mo Da-Sang Hua , I-Line Chen , Jia-Ling Lin , Yi-Ching Lo , Zi-Jing Lin , Yung-Hsiang Chen , Yur-Ren Kuo , Chih-Hsin Hsu , Po-Len Liu
{"title":"Plumbagin improves pulmonary vascular remodeling in PAH via miR-21-5p/MMP/TIMP regulation, with diagnostic implications for cardiac function","authors":"Chong-Chao Hsieh , Hsuan-Fu Kuo , Hsiao-Hsuan Wang , Mo Da-Sang Hua , I-Line Chen , Jia-Ling Lin , Yi-Ching Lo , Zi-Jing Lin , Yung-Hsiang Chen , Yur-Ren Kuo , Chih-Hsin Hsu , Po-Len Liu","doi":"10.1016/j.biopha.2025.118604","DOIUrl":"10.1016/j.biopha.2025.118604","url":null,"abstract":"<div><div>Pulmonary arterial hypertension (PAH) is a progressive cardiopulmonary disorder characterized by extensive pulmonary vascular remodeling and right ventricular dysfunction. Recent investigations have identified microRNA-21–5p (miR-21–5p) as a key driver of pulmonary artery smooth muscle cells (PASMCs) phenotypic transformation and extracellular matrix (ECM) dysregulation, thereby exacerbating disease pathology. In this study, we investigated the therapeutic potential of Plumbagin (PL)<strong>,</strong> a natural naphthoquinone compound, in attenuating PAH progression via modulation of the miR-21–5p and ECM remodeling. Using a monocrotaline (MCT)-induced PAH mouse model along with cultured human PASMCs, we evaluated the effects of PL on miR-21–5p expression<strong>,</strong> bone morphogenetic protein receptor type 2 (BMPR2) levels, and ECM-related factor expression. PL treatment significantly mitigated pulmonary vascular remodeling in the animal model. Mechanistically, PL suppressed miR-21–5p levels, restored BMPR2 expression, and reversed PASMC phenotypic switching, while modulating key ECM regulators including matrix metalloproteinase (MMP)-7, MMP-19, and tissue inhibitor of metalloproteinases-3 (TIMP-3). Clinical validation using serum samples from patients with PAH revealed that elevated miR-21–5p and MMP-7 levels correlated with increased disease severity, whereas higher MMP-19 and TIMP-3 levels were inversely associated. Collectively, these findings highlight targeting the miR-21–5p and ECM dynamics as a promising therapeutic strategy for PAH management and underscore the translational potential of PL in improving patient outcomes.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118604"},"PeriodicalIF":7.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune cell dynamics and their role in cardiac injury: Mechanisms and therapeutic implications","authors":"Chunlei Liu , Rihan Wu , Hao Yang , Yongming Yao","doi":"10.1016/j.biopha.2025.118608","DOIUrl":"10.1016/j.biopha.2025.118608","url":null,"abstract":"<div><div>Cardiovascular injury initiates a temporally regulated immune cascade that governs both tissue damage and repair. Neutrophils, macrophages, dendritic cells, and T cells contribute distinct yet overlapping functions during acute inflammation, resolution, and chronic remodeling. This review synthesizes recent findings from single-cell transcriptomics, spatial omics, immunometabolism, and neuroendocrine–immune interactions to delineate immune cell dynamics across major cardiac diseases, including myocardial infarction, heart failure, viral myocarditis, hypertensive remodeling, and sepsis-induced cardiomyopathy. We further examine how immune cells communicate with cardiomyocytes, fibroblasts, endothelial cells, and neurohormonal regulators to shape the myocardial microenvironment. Particular emphasis is placed on macrophage polarization, regulatory T cell activity, extracellular vesicle–mediated signaling, and metabolic checkpoints as key determinants of immune behavior. Based on these mechanistic insights, we propose a framework for precision immunotherapy that integrates immune profiling, metabolic status, and neuroendocrine cues to guide individualized interventions. Emerging strategies—including low-dose interleukin-2, immune checkpoint blockade, mesenchymal stem cell–derived extracellular vesicles, and immunometabolic reprogramming—are highlighted as promising means to recalibrate immunity toward tissue repair. Overall, this review provides a translational perspective aimed at shifting cardiovascular therapy from non-specific immunosuppression to adaptive, stage-specific immunomodulation.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118608"},"PeriodicalIF":7.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaveena Autar , Xiufang Guo , Haley Powell , Aakash Patel , Mridu Malik , Marcella Grillo , Nesar Akanda , Narasimhan S. Narasimhan , Will Bogen , Christopher Long , Ramy M. Ammar , James Hickman
{"title":"Developing a functional non-animal CNS stress model utilizing long-term potentiation with human iPSC-cortical neurons to evaluate therapeutics","authors":"Kaveena Autar , Xiufang Guo , Haley Powell , Aakash Patel , Mridu Malik , Marcella Grillo , Nesar Akanda , Narasimhan S. Narasimhan , Will Bogen , Christopher Long , Ramy M. Ammar , James Hickman","doi":"10.1016/j.biopha.2025.118556","DOIUrl":"10.1016/j.biopha.2025.118556","url":null,"abstract":"<div><div>Cortisol, the main stress hormone of the hypothalamic-pituitary-adrenal (HPA) axis, has been hypothesized to cause considerable detriment to cognitive function in both a time and concentration-dependent manner. However, there is a current lack of functional <em>in vitro</em> models available to evaluate the stress condition. Long-term potentiation (LTP) has served as a quantitative correlate for memory and learning through <em>in vitro</em> neuronal network responses to electrical stimuli, where a high-frequency stimulation (HFS) protocol on microelectrode arrays (MEAs) evaluates synaptic integrity related to higher-order cognition. As a novel alternative to animal studies, this study has employed a human iPSC-cortical neuron organ-on-a-chip (HoaC) system to establish a stress phenotype for synaptic dysfunction and evaluate the effects of therapeutic compounds to ameliorate stress-induced cognitive dysfunction. In our HoaC system, cortisol exposure was found to alter cortical neuron LTP, synaptic integrity, cellular morphology, and electrophysiology, confirming a cortisol-induced stress phenotype consistent with previous findings. Using this novel system, we investigated the ability of <em>Echinacea purpurea</em> and its active ingredient, dodeca-2E,4E,8Z,10Z-tetraenoic acid N-isobutyl amide (dodeca), to mitigate stress-induced functional decline. Following exposure to chronic stress (1 µM cortisol dosing for 7 days), both <em>Echinacea purpurea</em> and dodeca were found to significantly alleviate cortisol-induced cortical neuron stress in a time-dependent rescue of LTP. Together, these results characterize a novel, biologically-relevant model of neurological stress, and highlight its utility in identifying new therapeutic compounds capable of restoring stress-induced cortical neuron network deficits.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118556"},"PeriodicalIF":7.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Therapeutic role of resveratrol treatment on inflammation and oxidative stress-mediated renal and cardiac dysfunction in isoproterenol (ISO) administered ovariectomized female Long Evans rats","authors":"Tahmina Yasmin , Mirza Alimullah , Md Junaeid Rahman , Shamima Sultana , Shanaz Siddiqua , Ishrat Jahan , Sohel Rana , Nusrat Subhan , Ferdous Khan , Md Ashraful Alam , Nasrin Akhter","doi":"10.1016/j.biopha.2025.118571","DOIUrl":"10.1016/j.biopha.2025.118571","url":null,"abstract":"<div><div>This study aimed to evaluate the protective effects of resveratrol on renal and cardiac dysfunction in isoproterenol (ISO) administered ovariectomized female Long Evans rats. ISO was administered at 50 mg/kg (twice weekly) to induce infarct-like symptoms, while resveratrol was given daily at 100 mg/kg for two weeks. All animals received a standard chow diet and water <em>ad libitum</em>. The echocardiography was done on day 14 for all rats to acquire functional data. On day 15, rats were sacrificed, and plasma and tissue samples were collected for analysis. Various markers, including malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein products (AOPP), catalase, superoxide dismutase (SOD), glutathione (GSH), creatinine kinase – muscle brain (CK-MB), myeloperoxidase (MPO), creatinine, and uric acid, were assessed. This investigation revealed that ISO impaired antioxidant defenses, while resveratrol treatment helped restore redox balance and prevented cardiac and renal injury. Resveratrol treatment preserved the ejection fraction (EF%), fractional shortening (FS%), and lowered cardiac mass in ISO-administered rats. Gene expression analysis revealed that ISO downregulated key antioxidant mediators, while upregulating the pro-inflammatory genes. Resveratrol reversed these effects, suggesting reduced oxidative stress and inflammation. The histopathological analysis supported the protective role of resveratrol, showing reduced tissue damage and collagen deposition in heart and kidney tissues. Moreover, network pharmacology analysis showed potential interactions with key molecular pathways for resveratrol. In conclusion, resveratrol mitigated ISO-induced cardiac and renal damage by enhancing antioxidant defenses and suppressing inflammation, suggesting its potential clinical application in preventing or treating oxidative stress-related cardiovascular and renal disorders.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118571"},"PeriodicalIF":7.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanofibers for paclitaxel delivery: A promising avenue for cancer therapy","authors":"Alireza Noori , Mojdeh Salehi Namini , Ehsaneh Azaryan , Mahshid Ataei , Nima Beheshtizadeh","doi":"10.1016/j.biopha.2025.118607","DOIUrl":"10.1016/j.biopha.2025.118607","url":null,"abstract":"<div><div>Paclitaxel (PTX), a potent anticancer agent, is hindered by its poor water solubility, systemic toxicity, and non-targeted delivery, limiting its clinical efficacy in treating various types of cancer. To overcome these challenges, researchers have developed numerous nanoformulations, including inorganic nanoparticles, polymeric nanoparticles, and liposomes, for PTX delivery. However, the potential of nanofibers as PTX carriers remains underexplored. This review aims to bridge this knowledge gap by providing a comprehensive overview of nanofiber-based systems for PTX delivery. By highlighting the unique advantages of nanofibers; such as their superior drug loading capacity, enhanced stability, and ease of manipulation and implantation; this review underscores their promise as effective carriers for PTX. We examine the materials used in nanofiber fabrication, the interactions between PTX and nanofibers that influence drug release, and the key factors governing release mechanisms. Additionally, we discuss the therapeutic efficacy of PTX-loaded nanofibers in treating various cancers, highlighting innovative strategies to enhance PTX's anticancer effects. Special attention is given to the integration of nanofibers with complementary therapies, such as radiotherapy and hyperthermia, to achieve synergistic outcomes. Finally, we outline future directions for research, including the development of multifunctional systems that eliminate residual cancer cells while promoting tissue healing post-surgery, and the scale-up of production using novel methods like electro-centrifugal spinning to enable clinical translation. This article aims to provide valuable insights into the current state of nanofiber-based PTX delivery, inspire further advancements in the field, and pave the way for their clinical application.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118607"},"PeriodicalIF":7.5,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A millifluidic esophagus on-a-chip model for evaluating a natural remedy-mediated mucosal repair in GERD","authors":"Maria Elisabetta Federica Palamà , Ketty Gianesin , Elisa Caracciolo , Maurizio Aiello , Silvia Scaglione , Paolo Lucchese , Vincenzo Savarino","doi":"10.1016/j.biopha.2025.118609","DOIUrl":"10.1016/j.biopha.2025.118609","url":null,"abstract":"<div><div>Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder, characterized by the retrograde flow of gastric contents into the esophagus, causing symptoms such as heartburn and regurgitation. Although many patients with symptomatic GERD show no visible mucosal injury, impairment of its integrity at microscopic level is considered a relevant factor contributing to symptom generation and inflammation. In this scenario, protection of esophageal mucosa by topical agents has become a potential therapeutic approach. We investigated the protective and regenerative effects of a new natural formulation (GSE Reflusolve Rapid), using a dynamic culture based on MIVO® esophagus-on-chip platform, compared to an alginate/carbonate-based product. Results demonstrate that both products preserved esophageal integrity following acid stimulation, mitigating transepithelial electrical resistance (TEER) decline and upregulating MUC5B expression. Moreover, the natural formulation showed a significant reduction in IL-8 levels (<em>p</em> < 0.05) in contrast to the alginate-based formulation, despite the lack of a buffer action. TEER measurement, FITC-dextran permeability assay and histological analysis showed also the reparative properties of both mucosal protectants after acidic insult. In particular, the natural formulation showed a more pronounced and uniform expression of MUC5B throughout the tissue. These findings highlight that GSE Reflusolve Rapid may be a valid alternative to control long-term GERD-symptoms.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118609"},"PeriodicalIF":7.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eduardo Hernández-Álvarez , Carlos J. Bethencourt-Estrella , Meriam Ben Youssef , Atteneri López-Arencibia , Jacob Lorenzo-Morales , Isabel L. Bazzocchi , José E. Piñero , Ignacio A. Jiménez
{"title":"Unlocking withaferin-A: Structural design toward next-generation antikinetoplastid agents","authors":"Eduardo Hernández-Álvarez , Carlos J. Bethencourt-Estrella , Meriam Ben Youssef , Atteneri López-Arencibia , Jacob Lorenzo-Morales , Isabel L. Bazzocchi , José E. Piñero , Ignacio A. Jiménez","doi":"10.1016/j.biopha.2025.118591","DOIUrl":"10.1016/j.biopha.2025.118591","url":null,"abstract":"<div><div>Current therapies for Chagas disease and leishmaniasis have limited efficacy, significant toxicity, and suboptimal cure rates. In this context, natural products represent a powerful tool for the discovery and development of new agents to overcome these limitations. Here we report the synthesis, antikinetoplastid activity, and proposed mechanism of action of a unique class of withaferin A derivatives (<strong>2</strong>-<strong>19</strong>). These compounds showed a potent inhibitory effect on the proliferation of <em>Trypanosoma cruzi</em> epimastigotes (compounds <strong>5</strong>, <strong>6</strong>, <strong>12</strong>-<strong>14</strong>, <strong>16</strong> and <strong>17</strong>) and <em>Leishmania amazonensis</em> promastigotes (compounds <strong>4</strong>-<strong>6</strong>, <strong>9</strong>, <strong>12</strong>-<strong>14</strong>, <strong>16</strong> and <strong>17</strong>). Notably, compounds <strong>14</strong> and <strong>16</strong> emerged as the most promising compounds, exhibiting higher potency than the reference drug, against promastigotes and amastigotes stage of <em>L. amazonensis</em>, along with a high selectivity index on a normal eukaryotic cell line. Additionally, compounds <strong>14</strong> and <strong>16</strong> induced apoptosis-like programmed cell death on <em>L. amazonensis</em>, mediated by the disruption of ATP levels, mitochondrial membrane potential, and chromatin condensation, and energy depletion. These findings reinforce the therapeutic potential of withanolides, providing strong support for the continued development of withaferin A (WA) derivatives as potential antikinetoplastid agents.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118591"},"PeriodicalIF":7.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyung-Goo Kim , Mohammad Abdur Rashid , Michael Poleschuk , Faheem Ullah , Sang Hoon Lee , Sang Hoon Kim , Bo Qin , X.F. Steven Zheng , Mi-Hyeon Jang
{"title":"Cognitive dysfunction in chemobrain: Molecular mechanisms and therapeutic implications","authors":"Hyung-Goo Kim , Mohammad Abdur Rashid , Michael Poleschuk , Faheem Ullah , Sang Hoon Lee , Sang Hoon Kim , Bo Qin , X.F. Steven Zheng , Mi-Hyeon Jang","doi":"10.1016/j.biopha.2025.118581","DOIUrl":"10.1016/j.biopha.2025.118581","url":null,"abstract":"<div><div>Chemotherapy-induced cognitive impairment (CICI), commonly referred to as chemobrain, is a prevalent side effect of cancer treatment that severely affects survivors' quality of life. Chemotherapeutic agents, including cisplatin, doxorubicin, and paclitaxel, cross the blood-brain barrier (BBB) and induce neurotoxicity, resulting in cognitive dysfunction. These agents trigger reactive oxygen species (ROS) generation, cause mitochondrial dysfunction, and induce DNA damage, all of which impair synaptic plasticity and neurogenesis. Mitochondrial dysfunction is central to chemobrain, as it disrupts ATP production, increases oxidative stress, and leads to neuronal apoptosis. Furthermore, mitochondrial DNA (mtDNA) damage caused by agents like cisplatin impairs oxidative phosphorylation, exacerbating neuronal degeneration. The molecular mechanisms of chemobrain likely involve several key players, including NAMPT-dependent NAD+ depletion and increased levels of Cyclooxygenase-2 (COX-2), which collectively exacerbate oxidative stress and neuroinflammation. Another important molecular target is the Adenosine A2A receptor (A2AR). When activated, it contributes to synaptic dysfunction and cognitive decline, particularly in chemotherapy-related cognitive deficits in the hippocampus. This review explores the complex interplay of these core pathologies in chemobrain and discusses how targeting these pathways could offer a therapeutic strategy to alleviate cognitive impairments in cancer survivors.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118581"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melissa J. Lucero , Christina Lisk , Delaney Swindle , Francesca Cendali , Saini Setua , Kiruphagaran Thangaraju , Alamzeb Khan , David I. Pak , Quintin O’Boyle , Shuwei Lu , Robert Tolson , Seth Zaeske , Saqib Khan , Nishant Rana , Natalie Westover , Pavel Davizon-Castillio , Gemlyn George , Kathryn Hassell , Rachelle Nuss , Nathan Brinkman , David C. Irwin
{"title":"Combined haptoglobin and hemopexin therapy for the treatment of cardiopulmonary dysfunction in sickle cell disease","authors":"Melissa J. Lucero , Christina Lisk , Delaney Swindle , Francesca Cendali , Saini Setua , Kiruphagaran Thangaraju , Alamzeb Khan , David I. Pak , Quintin O’Boyle , Shuwei Lu , Robert Tolson , Seth Zaeske , Saqib Khan , Nishant Rana , Natalie Westover , Pavel Davizon-Castillio , Gemlyn George , Kathryn Hassell , Rachelle Nuss , Nathan Brinkman , David C. Irwin","doi":"10.1016/j.biopha.2025.118595","DOIUrl":"10.1016/j.biopha.2025.118595","url":null,"abstract":"<div><div>Hemolysis and the downstream consequences of cell-free hemoglobin (Hb) and heme contribute to the development of sickle cell disease pulmonary hypertension (SCD-PH). The plasma concentrations of Hb and heme scavenger proteins haptoglobin (Hp) and hemopexin (Hpx) in sickle cell patients are observed to be significantly lower than healthy donors. The unchecked exposure to Hb and heme contribute to vasculopathy and aberrant cardiac function. This is consistent with vascular remodeling co-localized within iron rich macrophages. Based on these observations in patients, we hypothesize that a joint Hb and heme scavenger approach, combining Hp + Hpx as a therapeutic will attenuate hemolysis driven SCD-PH progression in a SCD mouse model. To test the hypothesis, we utilized our validated Berk-SS mouse model of SCD-PH driven by a 10-week moderate hypoxia exposure and weekly subcutaneous administration of Hp + Hpx. At study termination, we analyzed changes in cardiopulmonary iron deposition, right ventricular and pulmonary functional parameters, and multi-omic indices associated with SCD-PH. Our data demonstrates that Hp+Hpx improves pulmonary vascular resistance and right ventricular function including stiffness, afterload, cardiac output, ventricular to vascular coupling ratio, pulmonary vascular resistance and medial hypertrophy. Histological evaluation of lung and right ventricular tissue demonstrates attenuation of cardiopulmonary pathology. Finally, a multi-omic analysis of whole lung and heart tissue demonstrates a rebalancing of proteins related to PH, iron, inflammation, and oxidative stress. This data provides strong pre-clinical evidence for the clinical study of combined Hb and heme scavenger proteins in the treatment of PH-associated SCD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118595"},"PeriodicalIF":7.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yoonsu Kim , Minjung Cho , Chang-Jin Jeon , Gyuhyeong Goh , Myungjin Kim
{"title":"Neuroinflammatory suppression with protocatechuic acid attenuates Alzheimer’s disease phenotypes in 5 ×FAD transgenic mice","authors":"Yoonsu Kim , Minjung Cho , Chang-Jin Jeon , Gyuhyeong Goh , Myungjin Kim","doi":"10.1016/j.biopha.2025.118598","DOIUrl":"10.1016/j.biopha.2025.118598","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a complex pathobiology that includes neuroinflammation, the accumulation of extracellular amyloid-beta (Aβ) plaque, and intracellular neurofibrillary tangles comprising tau. Increasing evidence suggests that the aberrant activation of glial cells, including microglia and astrocytes, is a significant early characteristic that accelerates neuroinflammatory processes in the development of AD. Protocatechuic acid (PCA), a natural phenolic compound, has been investigated for its anti-inflammatory properties in various pathological conditions. Here, we demonstrated that administration of PCA significantly ameliorated neuroinflammation as well as cognitive deficits in the 5 ×FAD mouse model of AD, which overexpresses human amyloid precursor protein (<em>APP</em>) and presenilin-1 (<em>PSEN1</em>) genes carrying five familial Alzheimer's disease (FAD) mutations, leading to accelerated Aβ deposition. We further confirmed that PCA treatment significantly reduced microglial activation and downregulated the production of pro-inflammatory cytokines, astrogliosis, and tau hyperphosphorylation, thereby preserved the integrity of hippocampal neurons. Our RNA sequencing analysis revealed that PCA treatment restored the transcriptomic profile of hippocampal tissues in 5 ×FAD mice, particularly by downregulating genes associated with innate immune and inflammatory responses. Moreover, PCA alleviated gut dysbiosis and enhanced the integrity of the intestinal barrier. The findings suggest that PCA may serve as a promising therapeutic agent for early intervention in AD to mitigate its progression.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118598"},"PeriodicalIF":7.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}