Biomedicine & Pharmacotherapy最新文献

{"title":"Rational design and therapeutic potential of MyD88 inhibitory peptide in psoriasis","authors":"Mariya Farooq ,&nbsp;Bilal Ahmad ,&nbsp;Ji Hye Han ,&nbsp;Mahesh Chandra Patra ,&nbsp;Abdul Waheed Khan ,&nbsp;Hongjoon Choi ,&nbsp;Hana Seo ,&nbsp;Hongseo Choi ,&nbsp;Moon Suk Kim ,&nbsp;Wook Kim ,&nbsp;Sangdun Choi","doi":"10.1016/j.biopha.2024.117801","DOIUrl":"10.1016/j.biopha.2024.117801","url":null,"abstract":"<div><div>Myeloid differentiation primary-response 88 (MyD88) is a crucial adaptor protein for initiating immune responses via Toll-like receptors (TLRs). This study employed a rational peptide design approach to develop MyD88 inhibitory peptides targeting the MyD88 interaction interface. The designed peptide, MyDIP2–4, was evaluated for its efficacy in inhibiting MyD88-dependent signaling in human and mouse cell lines. <em>In vitro</em> analyses demonstrated that MyDIP2–4 effectively inhibited MyD88-mediated signaling in both the TLR- and IL-1R-mediated pathways. Surface plasmon resonance experiments confirmed that MyDIP2–4 specifically interacted with MyD88 in a concentration-dependent manner. In an imiquimod-induced psoriasis model, MyDIP2–4 significantly inhibited disease progression, as evidenced by a reduction in psoriasis area and severity index scores. Histological staining revealed decreased epidermal thickness, while immunohistochemical analysis showed downregulation of IL-17 levels following treatment. These findings suggest that MyDIP2–4 is a promising candidate for the treatment of psoriasis. Targeting the Toll/interleukin-1 receptor domain of MyD88 through rational peptide design offers a novel strategy for developing therapeutics for autoimmune diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117801"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged incubation with Δ9-tetrahydrocannabinol but not with cannabidiol induces synaptic alterations and mitochondrial impairment in immature and mature rat organotypic hippocampal slices","authors":"Costanza Mazzantini ,&nbsp;Lorenzo Curti ,&nbsp;Daniele Lana ,&nbsp;Alessio Masi ,&nbsp;Maria Grazia Giovannini ,&nbsp;Giada Magni ,&nbsp;Domenico E. Pellegrini-Giampietro ,&nbsp;Elisa Landucci","doi":"10.1016/j.biopha.2024.117797","DOIUrl":"10.1016/j.biopha.2024.117797","url":null,"abstract":"<div><div><em>Cannabis</em> derivatives are among the most widely used psychoactive substances in the world, which leads to growing medical concerns regarding its chronic use and abuse especially among adolescents. Exposure to THC during formative years produces long-term behavioral alterations that share similarities with symptoms of psychiatric and neurodevelopmental disorders. In this study, we have analyzed the functional and molecular mechanisms that might underlie these alterations. Rat organotypic hippocampal slices were cultured for 2 days (immature) or 10 days (mature) <em>in vitro</em> and then exposed for 7 days to THC (1 µM) or CBD (1 µM). At the end of the treatment, slices were analyzed by Western blotting, electrophysiological recordings, RT-PCR, and fluorescence microscopy to explore the molecular and functional changes in the hippocampus. A prolonged (7-day) exposure to THC reduced the expression levels of pre- (synaptophysin, vGlut1) and post-synaptic (PSD95) proteins in both immature and mature slices, whereas CBD significantly increased the expression levels of PSD95 only in immature slices. In addition, THC significantly reduced the passive properties and the intrinsic excitability of membranes and increased sEPSCs in CA1 pyramidal cells of immature but not mature slices. Exposure to both cannabinoids impaired mitochondrial function as detected by the reduction of mRNA expression levels of mitobiogenesis genes such as VDAC1, UCP2, and TFAM. Finally, THC but not CBD caused tissue disorganization and morphological modifications in CA1 pyramidal neurons, astrocytes and microglia in both immature and mature slices. These results are helpful to explain the specific vulnerability of adolescent brain to the effects of psychotropic cannabinoids.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117797"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Christensenella minuta mitigates behavioral and cardiometabolic hallmarks of social defeat stress” [Biomed. Pharmacother. 180 (2024) 117377]","authors":"Ana Agusti ,&nbsp;Gara Verónica Molina-Mendoza ,&nbsp;María Tamayo ,&nbsp;Valerio Rossini ,&nbsp;María Carmen Cenit ,&nbsp;Carlos Francés-Cuesta ,&nbsp;Verónica Tolosa-Enguis ,&nbsp;Eva María Gómez Del Pulgar ,&nbsp;Alejandra Flor-Duro ,&nbsp;Yolanda Sanz","doi":"10.1016/j.biopha.2024.117806","DOIUrl":"10.1016/j.biopha.2024.117806","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117806"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cisplatin-eugenol Pt(IV) prodrugs target colon cancer stem cells: A novel strategy for enhanced anticancer efficacy","authors":"Vojtech Novohradsky ,&nbsp;Tomer Babu ,&nbsp;Hana Kostrhunova ,&nbsp;Menucha Plaskow ,&nbsp;Lenka Markova ,&nbsp;Sourav Acharya ,&nbsp;Dan Gibson ,&nbsp;Viktor Brabec","doi":"10.1016/j.biopha.2025.117854","DOIUrl":"10.1016/j.biopha.2025.117854","url":null,"abstract":"<div><div>Platinum(IV) compounds possess distinct properties that set them apart from platinum(II) compounds. Often designed as prodrugs, they are reduced within cancer cells to their active platinum(II) form, enabling their cytotoxic effects. Their versatility also lies in their ability to be functionalized and conjugated with bioactive molecules to enhance cancer cell targeting. This report introduces new prodrugs that combine antitumor cisplatin with axially coordinated eugenol, leveraging their synergistic action to target cancer stem cells. A third bioactive ligand, 4-phenylbutyrate or octanoate, was added to further enhance biological activity, creating 'triple action' prodrugs. These new platinum(IV) prodrugs offer a novel approach to cancer therapy by improving targeting, increasing efficacy, overcoming drug resistance, and reducing tumor invasiveness while sparing healthy tissue.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117854"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silibinin alleviates house dust mite induced allergic airway inflammation by inhibiting NLRC4 inflammasome and MMP-9 expression","authors":"So-Won Pak ,&nbsp;Woong-Il Kim ,&nbsp;Se-Jin Lee ,&nbsp;Sin-Hyang Park ,&nbsp;Young-Kwon Cho ,&nbsp;Joong-Sun Kim ,&nbsp;Jong-Choon Kim ,&nbsp;Sung-Hwan Kim ,&nbsp;In-Sik Shin","doi":"10.1016/j.biopha.2025.117823","DOIUrl":"10.1016/j.biopha.2025.117823","url":null,"abstract":"<div><div>Silibinin, a major compound of silymarin, has been reported to alleviate respiratory diseases including acute lung injury, asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis through its antifibrotic, anti-inflammatory, and antioxidant properties. However, the specific mechanisms underlying its therapeutic effects, particularly in allergic asthma, are not fully understood. With the increasing prevalence and impact of allergic asthma, there is a need to elucidate the exact underlying mechanisms of its potential treatment effects. Herein, we investigated the therapeutic effects of silibinin on allergic asthma using house dust mite (HDM)-exposed mice and an HDM-stimulated human bronchial epithelium cell line, focusing on the roles of the NLR family CARD domain containing 4 (NLRC4) inflammasome and matrix metalloproteinase-9 (MMP-9). To induce airway inflammation, HDM extracts were instilled intranasally on days 0, 4, 8, and 12 to mice. Silibinin (20 and 40 mg/kg) was orally administered daily from days 0–12. The results showed that silibinin treatment attenuated allergic immune responses induced by HDM exposure, as evidenced by decreased airway hyperresponsiveness, reduced inflammatory cells and cytokines, lower immunoglobulin E levls, and decreased mucus production. Furthermore, silibinin treatment suppressed NLRC4 inflammasome activation and downregulated MMP-9 expression in the lungs. In HDM-stimulated cells, silibinin treatment decreased inflammatory cytokine levels and the expression of NLRC4 and interleukin-1β, indicating inhibition of NLRC4 inflammasome activation. Overall, our data demonstrated that silibinin alleviated allergic responses in HDM-induced asthmatic mice by inhibiting NLRC4 inflammasome activation and MMP-9 expression, underscoring its therapeutic potential in the treatment of asthma.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117823"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to “The HOTTIP (HOXA transcript at the distal tip) lncRNA: Review of oncogenic roles in human” [Biomed. Pharmacother. 127(2020) 110158]","authors":"Soudeh Ghafouri-Fard ,&nbsp;Sepideh Dashti ,&nbsp;Mohammad Taheri","doi":"10.1016/j.biopha.2025.117868","DOIUrl":"10.1016/j.biopha.2025.117868","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117868"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting KEAP1-mediated IKKβ degradation strategy for colitis-associated colorectal carcinogenesis: The potential of xanthohumol","authors":"Young-Min Han ,&nbsp;Sun-Mi Yun ,&nbsp;Da-Young Lee ,&nbsp;Moon-Young Song ,&nbsp;Seong-Won Lee ,&nbsp;Woo-Sung Son ,&nbsp;Jun Hwan Yoo ,&nbsp;Changjin Lim ,&nbsp;Seok-Ho Kim ,&nbsp;Eun-Hee Kim","doi":"10.1016/j.biopha.2025.117879","DOIUrl":"10.1016/j.biopha.2025.117879","url":null,"abstract":"<div><div>In colitis-associated colorectal cancer (CAC), the NF-κB pathway, especially IKKβ, drives inflammation and cancer progression. However, no IKKβ inhibitors have been approved due to compensatory mechanisms. The challenge is to develop an anti-tumor agent that effectively targets IKKβ while overcoming these compensatory pathways. We <em>conducted in vitro</em> and <em>in vivo</em> experiments to evaluate the anti-cancer effects of synthesized xanthohumol (XN) targeting IKKβ. CAC was induced in mice, followed by XN treatment. Histological and molecular analyses, including cell viability assays, immunoblotting, and qRT-PCR, were performed. Human colon cancer cell lines were also used to investigate IKKβ’s role. RNA sequencing revealed elevated IKKβ expression in colorectal cancer human tissues, correlating with poor prognosis. XN significantly reduced adenocarcinoma formation and inflammation <em>in vivo</em> while decreasing IKKβ and NF-κB signaling in both models. XN binds to the C179 residue of IKKβ, inhibiting its activity. Additionally, our findings highlight KEAP1's role as an upstream regulator of IKKβ degradation. XN specifically interacts with the C288 residue of KEAP1, showing triple-binding affinity with IKKβ and KEAP1. These results indicate that XN promotes conditions where KEAP1 facilitates IKKβ degradation.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117879"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic regulation of macrophage function in kidney disease: New perspective on the interaction between epigenetics and immune modulation","authors":"Rui-zhi Tan ,&nbsp;Qiu-xiang Bai ,&nbsp;Long-hao Jia ,&nbsp;Yi-bing Wang ,&nbsp;Tong Li ,&nbsp;Jing-yi Lin ,&nbsp;Jian Liu ,&nbsp;Hong-wei Su ,&nbsp;Fahsai Kantawong ,&nbsp;Li Wang","doi":"10.1016/j.biopha.2025.117842","DOIUrl":"10.1016/j.biopha.2025.117842","url":null,"abstract":"<div><div>The interaction between renal intrinsic cells and macrophages plays a crucial role in the onset and progression of kidney diseases. In recent years, epigenetic mechanisms such as DNA methylation, histone modification, and non-coding RNA regulation have become essential windows for understanding these processes. This review focuses on how renal intrinsic cells (including tubular epithelial cells, podocytes, and endothelial cells), renal cancer cells, and mesenchymal stem cells influence the function and polarization status of macrophages through their own epigenetic alterations, and how the epigenetic regulation of macrophages themselves responds to kidney damage, thus participating in renal inflammation, fibrosis, and repair. Moreover, therapeutic studies targeting these epigenetic interaction mechanisms have found that the application of histone deacetylase inhibitors, histone methyltransferase inhibitors, various nanomaterials, and locked nucleic acids against non-coding RNA have positive effects on the treatment of multiple kidney diseases. This review summarizes the latest research advancements in these epigenetic regulatory mechanisms and therapies, providing a theoretical foundation for further elucidating the pathogenesis of kidney diseases and the development of novel therapeutic strategies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117842"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colistin treatment causes neuronal loss and cognitive impairment via ros accumulation and neuronal plasticity alterations","authors":"Laura Guzman ,&nbsp;Antoni Parcerisas ,&nbsp;Amanda Cano ,&nbsp;Elena Sánchez-López ,&nbsp;Ester Verdaguer ,&nbsp;Carme Auladell ,&nbsp;Yolanda Cajal ,&nbsp;Marta Barenys ,&nbsp;Antoni Camins ,&nbsp;Francesc Rabanal ,&nbsp;Miren Ettcheto","doi":"10.1016/j.biopha.2025.117839","DOIUrl":"10.1016/j.biopha.2025.117839","url":null,"abstract":"<div><div>The rise of antimicrobial resistance has made necessary the increase of the antibacterial arsenal against multidrug-resistant bacteria. In this context, colistin has re-emerged as a first-line antibiotic in critical situations despite its nephro- and neuro- toxicity at peripheral level. However, the mechanism underlying its toxicity remains unknown, particularly in relation to the central nervous system (CNS). Therefore, this study aimed to characterize the molecular mechanisms underlying colistin-induced neurotoxicity in the CNS through a combination of <em>in vitro</em> and <em>in vivo</em> molecular studies along with several <em>in vivo</em> behavioral tests. Following colistin treatment, mice exhibited a significant reduction in body weight together with renal impairment, and locomotor dysfunction. Moreover, our results demonstrated that colistin disrupted the blood-brain barrier, inducing astrogliosis, and triggering apoptosis-related processes probably through the accumulation of reactive oxygen species (ROS) and mitochondrial dysfunction. Further analysis on mice and primary neuronal cultures revealed that colistin administration altered neuronal plasticity by reducing the number of immature neurons in adult neurogenesis and altering the synaptic function through a reduction of the post-synaptic protein PSD95. All these alterations together finally lead to cognitive impairment and depression-like symptoms in mice. These findings provide novel insights into the mechanisms of colistin-induced neurotoxicity in the CNS, highlighting the need for careful monitoring of cognitive function in patients undergoing colistin treatment.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117839"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased opioid receptor availability and impaired neurometabolic coupling as signatures of morphine tolerance in male rats: A positron emission tomography study","authors":"Amélie Soyer ,&nbsp;Sarah Leterrier ,&nbsp;Sébastien Goutal ,&nbsp;Cassandre Corvo ,&nbsp;Wadad Saba ,&nbsp;Fabien Caillé ,&nbsp;Gregory Dal Bo ,&nbsp;Alexandra Winkeler ,&nbsp;Karine Thibault ,&nbsp;Claire Leroy ,&nbsp;Nicolas Tournier","doi":"10.1016/j.biopha.2025.117848","DOIUrl":"10.1016/j.biopha.2025.117848","url":null,"abstract":"<div><div>Translational neuroimaging techniques are needed to address the impact of opioid tolerance on brain function and quantitatively monitor the impaired neuropharmacological response to opioids at the CNS level. A multiparametric PET study was conducted in rats. Rats received morphine daily to induce tolerance (15 mg/kg/day for 5 days), followed by 2-day withdrawal. Then, opioid effects were precipitated using a buprenorphine challenge (0.1 mg/kg, s.c, BUP-challenge), which safely enables full occupancy of available mu-opioid receptors (MOR). The impact of the BUP-challenge on the pain threshold was estimated using the hot-plate test. The corresponding availability of MOR was estimated using [¹¹C]buprenorphine PET imaging (n = 4). The brain glucose metabolism was investigated using [¹⁸F]2-fluoro-D-deoxy-glucose ([¹⁸F]FDG) PET imaging after the BUP-challenge or saline (n = 5–6). Opioid tolerance was confirmed by the attenuated antinociceptive response to the BUP-challenge in morphine-treated rats compared to saline controls (p &lt; 0.001). In tolerant rats, [¹¹C]buprenorphine binding was decreased in MOR-rich regions (p &lt; 0.01), and the baseline uptake of [¹⁸F]FDG was decreased (p &lt; 0.05). The BUP-challenge decreased [¹⁸F]FDG uptake to a lower extent in tolerant rats compared with opioid-naive animals (p &lt; 0.05), suggesting impaired neurometabolic coupling. Moreover, the impact of the BUP-challenge on the neurometabolic connectivity across brain regions was disrupted by opioid tolerance. PET imaging enables the study of the decreased availability of MOR and impaired neurometabolic coupling as molecular signatures of opioid tolerance in rats. Combining molecular neuroimaging with a suitable pharmacological challenge may provide a translational and quantitative paradigm to explore opioid tolerance at the CNS level in parallel to pharmacodynamics.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117848"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}