Biomedicine & Pharmacotherapy最新文献

{"title":"Fenofibrate treatment during lactation prevents liver and adipose tissue associated metabolic dysfunction in a rat model of childhood obesity","authors":"Lucas Paulo Jacinto Saavedra ,&nbsp;Scarlett Rodrigues Raposo ,&nbsp;Ana Letícia Manso Assakawa ,&nbsp;Naiara Cristina Lucredi ,&nbsp;Maria Natália Chimirri Peres ,&nbsp;Silvano Piovan ,&nbsp;Gessica Dutra Gonçalves ,&nbsp;Veridiana Mota Moreira ,&nbsp;Letícia Ferreira Barbosa ,&nbsp;Diana Sousa ,&nbsp;Flávia Caroline Farias dos Santos ,&nbsp;Andreia Amaro ,&nbsp;Marcos Divino Ferreira-Junior ,&nbsp;Jones Bernardes Graceli ,&nbsp;Paulo Matafome ,&nbsp;Jurandir Fernando Comar ,&nbsp;Rodrigo Mello Gomes ,&nbsp;Josep C. Jiménez-Chillarón ,&nbsp;Douglas Lopes Almeida ,&nbsp;Paulo Cezar de Freitas Mathias","doi":"10.1016/j.biopha.2025.118166","DOIUrl":"10.1016/j.biopha.2025.118166","url":null,"abstract":"<div><div>Childhood obesity and associated comorbidities in adulthood are of great concern worldwide. Evidence highlights the importance of lactation in later disease development. In this sense, obese children are at great risk of developing adult obesity, insulin resistance, type 2 diabetes, and cardiovascular disease at adulthood. PPARα activation during lactation promotes the expression of key enzymes involved in lipid oxidation, and it was associated with reduced adiposity in children. Therefore, we hypothesized that an animal model of childhood obesity, small litter (SL), would lead to the development of obesity and metabolic dysfunction in adulthood, which could be prevented by postnatal PPARα agonism. Wistar dams had their litter reduced, leading to postnatal overfeeding and obesity early in life. SL male pups were treated with fenofibrate, an PPARα agonist, during lactation, from postnatal day (PND) 1 until weaning (PND21), to verify whether PPARα activation prevents the developmental programming at adulthood (PND120). Childhood obesity induced by postnatal overfeeding leads to decreased markers for oxidative metabolism during infancy, leading to increased visceral adiposity and oxidative stress, insulin resistance, hepatic microvesicular steatosis, and increased fibroblast growth factor 21 (<em>Fgf21</em>) expression, followed by decreased brown adipose tissue (BAT) sympathetic nerve activity and decreased <em>Fgfr1</em> hypothalamic expression in adulthood. Agonist-induced PPARα activation during lactation mitigated the development of aforementioned alterations in adulthood. Postnatal fenofibrate treatment prevents the developmental programming of visceral obesity, liver-associated metabolic dysfunction and BAT autonomic sympathetic hypoactivity in an animal model of childhood obesity.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118166"},"PeriodicalIF":6.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083999","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":"Stereological insights into the protective effects of agmatine on hippocampal damage induced by aluminum nanoparticles","authors":"Vahid Reza Ostovan ,&nbsp;Yosra Abdolahpoor ,&nbsp;Bahar Rostami ,&nbsp;Zahra Esmaili ,&nbsp;Maryam Moosavi","doi":"10.1016/j.biopha.2025.118163","DOIUrl":"10.1016/j.biopha.2025.118163","url":null,"abstract":"<div><h3>Background</h3><div>Aluminum (Al) exposure has been implicated in neurodegenerative disorders, particularly Alzheimer’s disease (AD). Due to their small size and increased bioavailability, Al oxide nanoparticles (Al-NP) exhibit greater neurotoxicity than bulk Al, leading to hippocampal damage, neuronal loss, and cognitive decline. This study investigates whether agmatine, a polyamine with neuroprotective properties, mitigates Al-NP-induced memory impairment and hippocampal neurodegeneration.</div></div><div><h3>Methods</h3><div>Male Swiss mice (SWR/J) were randomly assigned to four groups: Control, Al-NP (10 mg/kg, oral), Al-NP + Agmatine (5 mg/kg or 10 mg/kg, intraperitoneal). Cognitive function was assessed using the Novel Object Recognition (NOR) test. Stereological analysis quantified hippocampal volume, as well as the volume and cell number of the CA1 and dentate gyrus (DG) sub-regions. Apoptosis was evaluated via cleaved caspase-3, Bax, and Bcl-2 expression using western blot analysis.</div></div><div><h3>Results</h3><div>Al-NP exposure significantly impaired memory performance, reduced hippocampal volume, and induced atrophy and neuronal loss in CA1 and DG. Molecular analysis revealed elevated cleaved caspase-3 expression, increased Bax, decreased Bcl-2, and an elevated Bax/Bcl-2 ratio, indicating activation of intrinsic apoptosis. Agmatine (10 mg/kg) effectively restored memory function, preserved hippocampal structure, and normalized apoptotic markers, suggesting its neuroprotective role.</div></div><div><h3>Conclusion</h3><div>Agmatine exerts potent neuroprotective effects against Al-NP-induced hippocampal toxicity by mitigating memory deficits, preventing neuronal loss, and suppressing apoptosis through downregulation of cleaved caspase-3 and modulation of Bax/Bcl-2 signaling. These structural and molecular changes may underlie its cognitive benefits. Given the role of hippocampal atrophy in AD, agmatine may be a promising candidate for preventing Al-related neurodegeneration and AD progression.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118163"},"PeriodicalIF":6.9,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070206","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":"Cimicifuga racemosa extract Ze 450 shifts macrophage immunometabolism and attenuates pro-inflammatory signaling","authors":"Madeline Günther ,&nbsp;Nicole Paczia ,&nbsp;Susanne Michels ,&nbsp;Bernd L. Fiebich ,&nbsp;Sebastian Vogt ,&nbsp;Jürgen Drewe ,&nbsp;Georg Boonen ,&nbsp;Veronika Butterweck ,&nbsp;Carsten Culmsee","doi":"10.1016/j.biopha.2025.118130","DOIUrl":"10.1016/j.biopha.2025.118130","url":null,"abstract":"<div><div>Extracts from the rhizomes of <em>Cimicifuga racemosa</em> (CRE) are well-studied for treating climacteric symptoms and considered as a safe alternative to hormone replacement therapy (HRT). Chronic low-grade inflammation, or “inflammaging,” resulting from the loss of oestrogen’s regulatory effect on the immune system, is increasingly recognized as a significant factor in the health of postmenopausal women, contributing to a higher risk for cardiovascular disease, osteoporosis, metabolic syndrome, and cognitive decline.</div><div>Recent studies have suggested that CRE may exert anti-inflammatory effects, though the underlying mechanisms remain unclear. In this study, we aimed to investigate the effects of <em>Cimicifuga racemosa</em> extract Ze 450 on lipopolysaccharide (LPS)-induced inflammation in macrophages, as macrophage inflammation is crucial in the pathogenesis of several metabolic diseases associated with menopause.</div><div>Our results demonstrated that CRE Ze 450 reduced the production of NO, IL-1α/β, IL-6, and IL-10, as well as the expression of the pro-inflammatory proteins iNOS, HIF-1α, and mTOR in LPS-stimulated macrophages. Moreover, we observed that Ze 450 induced a shift in energy production from oxidative phosphorylation (OXPHOS) to glycolysis. Mechanistically this was mediated by the modulation of TCA cycle and electron transport chain activity at an early stage, which was further accompanied by the reduction of metabolic signaling molecules such as succinate and citrate.</div><div>In conclusion, our study identifies a novel mode of action for the <em>Cimicifuga racemosa</em> extract Ze 450, demonstrating its ability to regulate mitochondrial function and macrophage metabolism, but also highlighting its potential to improve the climacteric symptoms by mitigating pro-inflammatory signaling.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118130"},"PeriodicalIF":6.9,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070207","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":"Enhancing T cell cytotoxicity against lung cancer with an αPD-L1 protein engager and gemcitabine combination therapy","authors":"Chutamas Thepmalee ,&nbsp;Nunghathai Sawasdee ,&nbsp;Saruda Thongyim ,&nbsp;Naravat Poungvarin ,&nbsp;Pa-thai Yenchitsomanus ,&nbsp;Aussara Panya","doi":"10.1016/j.biopha.2025.118161","DOIUrl":"10.1016/j.biopha.2025.118161","url":null,"abstract":"<div><div>The overexpression of programmed cell death ligand 1 (PD-L1), a critical immune checkpoint protein, is associated with poor prognosis and reduced survival in lung cancer patients. Monoclonal antibodies targeting the PD-1/PD-L1 axis have been approved to disrupt this interaction and prevent immune cell exhaustion. Herein, to enhance the efficacy of PD-1/PD-L1 blockade, we investigated a bispecific αPD-L1 × αCD3 protein engager (αPD-L1 × αCD3 BIPE). The αPD-L1 × αCD3 BIPE consists of an anti-CD3 single-chain variable fragment (scFv) linked to an anti-PD-L1 scFv, allowing it to bind to CD3-positive T cells simultaneously and PD-L1-overexpressing cancer cells. In co-culture assays with T cells and non-small cell lung cancer (NSCLC) cell lines—A549, NCI-H460, and NCI-H1975—treatment with the BIPE significantly enhanced T-cell-mediated cytotoxicity. The killing efficiency correlated with PD-L1 expression levels, with the highest cytotoxic activity observed in NCI-H1975 (high PD-L1 expression), followed by NCI-H460 (moderate PD-L1 expression) and A549 (low PD-L1 expression). Furthermore, combining the BIPE with the standard chemotherapeutic agent gemcitabine further improved anti-tumor activity. This effect was likely due to gemcitabine-induced upregulation of PD-L1 and MHC class I expression on cancer cells, enhancing T-cell recognition and cytotoxicity. These findings suggest that combining αPD-L1 × αCD3 BIPE with gemcitabine is promising for enhancing immune checkpoint blockade and augmenting anti-tumor immunity in NSCLC.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118161"},"PeriodicalIF":6.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070162","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 effects of zinc oxide nanoparticles encapsulated within chitosan-camphor against hydatid cysts through suppressing oxidative stress, inflammation, and DNA damage","authors":"Hossein Amirafshari ,&nbsp;Ruaa Majid Khazaal ,&nbsp;Abdolrazagh Marzban ,&nbsp;Kourosh Cheraghipour ,&nbsp;Leila Masoori ,&nbsp;Asghar Sepahvand ,&nbsp;Hossein Mahmoudvand","doi":"10.1016/j.biopha.2025.118128","DOIUrl":"10.1016/j.biopha.2025.118128","url":null,"abstract":"<div><div>Nanoencapsulation refers to the process of enclosing bioactive compounds within nanoparticles to facilitate their targeted delivery to specific sites within the body. The objective of the current study was to synthesize zinc nanoparticles encapsulated within chitosan-camphor (ZNP-CC) and to assess the <em>in vitro, ex vivo,</em> and <em>in vivo</em> effects of ZNP-CC on protoscoleces (PTX) and hydatid cysts of <em>Echinococcus granulosus</em>. ZNP-CC at various concentrations, particularly at 10 and 15 mg/mL, significantly reduced the viability of PTX <em>in vitro</em> and <em>ex vivo</em> by 100 % (p &lt; 0.001). Treatment with ZNP-CC at 1/2 IC50 and IC50 notably stimulated <em>caspase-3</em> (p &lt; 0.01) and upregulated the expression levels of the DNA damage genes in PTX by &gt; 2-fold change. Treatment with ZNP-CC led to significant reduction in the number, size, and weight of hydatid cysts in mice; whereas, caused a substantial reduction in oxidative stress and a notable increase in the activities of GPx and SOD was observed. ZNP-CC mainly in combination with AZ at 100 mg/kg, resulted in a significant decrease in the expression of <em>TNF-α, NF-κB p65, TLR4,</em> and <em>IL-1β</em> genes. The serum levels of liver function parameters following treatment with ZNP-CC at the specified doses did not show a significant difference (p &gt; 0.05). This investigation demonstrated that ZNP-CC, especially in combination with AZ, markedly mitigated hydatid cyst infection in murine models by reducing oxidative stress and inflammation while normalizing serum levels of liver function factors. Furthermore, we observed promising scolicidal effects of ZNP-CC through the induction of apoptosis and DNA damage.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118128"},"PeriodicalIF":6.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070158","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":"Identification and designing an analgesic opioid cyclic peptide from Defensin 4 of Mesobuthus martensii Karsch scorpion venom with more effectiveness than morphine","authors":"Fatemeh Aliakbari ,&nbsp;Saman Rahmati ,&nbsp;Ali Ghanbari ,&nbsp;Hamid Madanchi ,&nbsp;Ali Rashidy-Pour","doi":"10.1016/j.biopha.2025.118139","DOIUrl":"10.1016/j.biopha.2025.118139","url":null,"abstract":"<div><div>Considering the limitations of use and side effects of existing analgesics, the discovery of new analgesics is necessary. Venoms of organisms are an important source of analgesic peptides. In this study, using computational biology methods such as molecular docking simulation, molecular dynamics, and predictions of physicochemical and biological properties based on various machine learning algorithms, a non-toxic 9-amino acid peptide from Defensin 4 of <em>Mesobuthus martensii Karsch</em> scorpion venom was discovered for the first time and named Buthicyclin. The peptide was synthesized cyclically by creating a disulfide bond, and its secondary structure was determined by Circular Dichroism (CD). Next, peptide toxicity was evaluated using MTT, hemolysis, and lethal dose (LD₅₀) methods. Subsequently, in animal tests using Tail-flick, Hot plate, and Formalin-induced paw-licking methods, the analgesic effects of Buthicyclin in acute and inflammatory pain were evaluated, and its possible analgesic mechanism was determined. Buthicyclin has a coil-like structure and can be considered a cyclic coil with a disulfide bond. This peptide is non-toxic so its LD₅₀ of this peptide was higher than 20 mg/kg. All analgesic tests showed that Buthicyclin peptide, at 1 mg/kg and 2 mg/kg (significantly greater), was more potent and stable than 2 mg/kg morphine in all time intervals. The results also indicated that Buthicyclin could exert its analgesic effects through binding to opioid receptors. Given the potent and long-lasting analgesic effects of Buthicyclin and its non-toxicity, Buthicyclin can be considered a promising candidate for new analgesic drugs. However, this claim requires more preclinical and clinical trials.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118139"},"PeriodicalIF":6.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070161","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":"p16INK4a downregulation alleviates temporomandibular joint osteoarthritis combined with type 2 diabetes by driving M2 polarization","authors":"Jilin Cai ,&nbsp;Leqi Zhang ,&nbsp;Qingqing Du ,&nbsp;Moxu Wang ,&nbsp;Xiaojie Ma ,&nbsp;Yuyi Chen ,&nbsp;Yuli Wang ,&nbsp;Hua Yuan","doi":"10.1016/j.biopha.2025.118172","DOIUrl":"10.1016/j.biopha.2025.118172","url":null,"abstract":"<div><div>Temporomandibular joint osteoarthritis (TMJOA), sometimes combined with type 2 diabetes (T2DM-TMJOA), has a restricting effect on quality of life and currently has few efficacious treatment options. As such, this project sought to determine the role of <em>p16INK4a</em> (<em>p16</em>) in T2DM-TMJOA development. In vivo, <em>p16</em> knockout (P16KO) mice experienced less condylar bone loss and altered macrophage polarities from the inflammatory M1 to anti-inflammatory M2. In vitro, <em>p16</em> knockdown (P16KD) or MS37452 treatment of THP-1 cells under high glucose and high palmitoleic acid conditions inhibited inflammatory angiogenesis and lymphangiogenesis, and supported osteogenic differentiation, respectively. Mechanistically, P16KD modelling restored mitochondrial functionality, limited intracellular iron accumulation, and polarized M2 macrophages through glutathione (GSH). Collectively, these data identify <em>p16</em> as a critical regulator of T2DM-TMJOA and provide evidence for a future treatment strategy by therapeutic inhibition of <em>p16</em>.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118172"},"PeriodicalIF":6.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070159","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":"Galanin(1−15) and Naltrexone: A novel approach for alcohol use disorder in rats, involving the mesolimbic system","authors":"Marta Flores-Gómez ,&nbsp;Noelia Cantero-García ,&nbsp;Juan Pedro Pineda-Gómez,&nbsp;Amel Moh-Ahmed,&nbsp;Antonio Flores-Burgess,&nbsp;Zaida Díaz-Cabiale,&nbsp;Carmelo Millón","doi":"10.1016/j.biopha.2025.118170","DOIUrl":"10.1016/j.biopha.2025.118170","url":null,"abstract":"<div><div>Alcohol Use Disorder (AUD) is a highly prevalent psychiatric and represents a significant public health challenge. Naltrexone (NTX), a mu-opioid receptor antagonist widely used for AUD treatment, has limited efficacy due to side effects and variability in patient response. Interactions between the full-length GAL molecule and the opioid system have been demonstrated. In our recent studies, we showed that the Galanin (1−15) fragment [GAL(1−15)] decreased alcohol seeking along with alcohol consumption. This study aims to examine the effects of GAL(1−15)+NTX on alcohol-seeking behavior and alcohol consumption, as well as the involvement of the mesolimbic system. In rats, we assessed GAL(1−15)+NTX in reward-seeking and the role of GALR2 using the antagonist M871 in the self-administration test. In addition, GAL(1−15)+NTX effects were studied on voluntary alcohol using the two-bottle choice paradigm. Locomotor activity and stereotyped behaviors, along with dopamine release in the dorsal striatum following alcohol injections, were assessed. Moreover, we have analyzed the transcriptional changes of C-Fos, MOR, POMPC, and dopamine receptors in the ventral tegmental area, nucleus accumbens and the hypothalamus. GAL(1−15)+NTX combination reduced alcohol seeking in self-administration and two-bottle choice consumption, with GALR2 involved in the effect. In addition, GAL(1−15)+NTX attenuated alcohol-induced locomotor activity and stereotyped behaviors linked to reduced dopamine release in the dorsal striatum. Notably, these effects were associated with C-Fos, MOR, and dopamine receptor changes, suggesting that the mesolimbic pathway, including the opioid system, is involved in GAL(1−15)+NTX effects. These results open up the possibility of using GAL(1−15) with NTX as a novel strategy in AUD.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118170"},"PeriodicalIF":6.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070157","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":"Neurorestorative properties of 2-butoxytetrahydrofuran from Holothuria scabra via activation of stress resistance and detoxification in a 6-OHDA-induced C. elegans model of Parkinson’s disease","authors":"Sukrit Promtang ,&nbsp;Tanatcha Sanguanphun ,&nbsp;Pawanrat Chalorak ,&nbsp;Darunee Rodma ,&nbsp;Rungsarit Sunan ,&nbsp;Laurence S. Pe ,&nbsp;Nakorn Niamnont ,&nbsp;Supin Chompoopong ,&nbsp;Prasert Sobhon ,&nbsp;Krai Meemon","doi":"10.1016/j.biopha.2025.118158","DOIUrl":"10.1016/j.biopha.2025.118158","url":null,"abstract":"<div><div><em>Holothuria scabra</em> (<em>H. scabra</em>), a marine organism traditionally known for its health benefits, has been utilized in both food and medicine. Our previous studies indicated that 2-butoxytetrahydrofuran (2-BTHF), which is isolated from <em>H. scabra</em>, possesses the potential to alleviate amyloid-β and α-synuclein accumulations associated with Alzheimer's and Parkinson's diseases (AD and PD), respectively. However, the mechanisms through which 2-BTHF mitigates PD-related neurotoxicity remain unclear. In this study, we investigated the effects of 2-BTHF on a 6-hydroxydopamine (6-OHDA)-induced <em>Caenorhabditis elegans</em> (<em>C. elegans</em>) model. Our results demonstrated that 2-BTHF recovered dopaminergic (DAergic) neurons from degeneration and restored dopamine-related behaviors. Furthermore, 2-BTHF reduced reactive oxygen species (ROS) production, preserved mitochondrial fluorescence, and decreased both mitochondrial and cytoplasmic unfolded protein responses (UPR^mt and UPR^cyto) activation. Transcriptome sequencing analysis revealed the critical roles of various systems, including the immune system, nervous system, glutathione (GSH) metabolism, xenobiotics, terpenoids, energy metabolism, cell growth and death, and aging-related longevity pathways. Additionally, 2-BTHF showed potential interactions with stress resistance and detoxification transcription factors, promoting the nuclear translocation of DAF-16 and SKN-1, which in turn activated their targets, including SOD-3, CTL-2, GCS-1, and GST-4. Moreover, 2-BTHF increased total GSH levels and reduced the <em>ced-3</em>-related cascade. This study demonstrates that 2-BTHF holds promise as a therapeutic agent for treating 6-OHDA-induced DAergic neurodegeneration in the <em>C. elegans</em> model.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118158"},"PeriodicalIF":6.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070160","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":"Macrophage immunometabolism dysregulation and inflammatory disorders","authors":"Karen Pomeyie ,&nbsp;Francis Abrokwah ,&nbsp;Daniel Boison ,&nbsp;Benjamin Amoani ,&nbsp;Foster Kyei ,&nbsp;Cynthia A. Adinortey ,&nbsp;Prince Amoah Barnie","doi":"10.1016/j.biopha.2025.118142","DOIUrl":"10.1016/j.biopha.2025.118142","url":null,"abstract":"<div><div>Macrophages are innate immune cells which are involved in triggering inflammation. Growing evidence shows that, macrophages respond to intracellular and extracellular cues which makes them adopt either anti-inflammatory or pro-inflammatory functions and phenotypes. Immunometabolism has been identified as one of the prominent factors which contributes massively towards the cessation and the development of inflammation as an immune response to infections and autoimmune diseases. However, when inflammation is poorly regulated, it leads to dire consequences. This illustrates that, understanding the role of immunometabolism in the regulation of inflammation, is paramount. In view of this, the review investigated the role of metabolic pathways such as: glycolysis, tricarboxylic acid cycle, pentose phosphate pathway, fatty acid oxidation, amino acid metabolism in macrophage reprogramming. The role of the intermediates and enzymes associated with these metabolic pathways in the regulation of, macrophage reprogramming and polarisation or activation was also reviewed. It was unveiled that, manipulating metabolic intermediates and enzymes could impact cellular immunometabolism. This eventually influences macrophage reprogramming and thus influences the generation of either a pro-inflammatory or anti-inflammatory response.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"188 ","pages":"Article 118142"},"PeriodicalIF":6.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948537","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}