Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie最新文献

{"title":"Induction of Ca²⁺-dependent autophagy and concurrent lysosomal alkalinization underlies the cytotoxic effects of NNC-55-0396 on glioblastoma cells.","authors":"Anna Visa, Maria Casals, Lía Alza, Judit Herreros, Carles Cantí","doi":"10.1016/j.biopha.2024.117690","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117690","url":null,"abstract":"<p><p>Diverse agents targeting (macro)autophagy, a critical metabolic stress response in cancer cells, have been proposed for cancer therapy. In previous studies, we showed that NNC-55-0396 (NNC) induces glioblastoma cell death by activating the Unfolded Protein Response (UPR) of ER stress and increasing cytosolic Ca²⁺ levels. Here, we report that NNC affects both ends of the autophagy process, causing extensive cytoplasmic vacuolation. Our results show that: (1) NNC induces autophagy downstream of UPR and Ca²⁺ signaling pathways, thus silencing IRE1α/JNK1 or inhibiting Ca²⁺/IP₃R signaling prevents NNC-induced vacuolation. (2) Silencing ATG5 delays cell death, indicating that autophagy induction plays a role in NNC's cytotoxic effects. (3) NNC and other Ca²⁺-mobilizing agents transcriptionally upregulate p62/SQSTM1, an autophagosome cargo receptor, highlighting a role for this protein in the response to NNC. (4) Studies using tandem fluorescent-tagged LC3 and electron microscopy, however, further reveal that NNC blocks late-stage autophagy that leads to enlarged degradative compartments accumulating ubiquitin-tagged cargoes. (5) Finally, NNC impedes pro-cathepsin-B processing, an effect that is reversed with a weak acid co-treatment, suggesting that lysosomal dysfunction due to increased intraluminal pH is the underlying cause of the autophagy blockade. Together, these findings underscore a multi-level dysregulation of autophagy that contributes to NNC's anti-tumoral effects.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117690"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic metabolic effects of novel gut-oriented small-molecule GPR119 agonists in diet-induced obese mice.","authors":"Mohan Patil, Dinesh Thapa, Leon N Warne, Ricky R Lareu, Elena Dallerba, Jerome Lian, Massimiliano Massi, Rodrigo Carlessi, Marco Falasca","doi":"10.1016/j.biopha.2024.117675","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117675","url":null,"abstract":"<p><p>The pharmacological activation of G-protein coupled receptor-119 (GPR119) modulates glucose, energy, and hepatic lipid homeostasis in type-2 diabetes (T2D). We developed synthetic small-molecule GPR119 agonists targeting gastrointestinal receptors. This study investigates the chronic metabolic effects of lead candidates, ps297 and ps318, individually and in combination with sitagliptin, a dipeptidyl peptidase-IV (DPP-IV) inhibitor, in high-fat diet (HFD)-induced obese (DIO) mice. In a 10-week dose-escalation protocol, DIO mice were orally treated with the investigational agents alone (10-90 mg/kg/day) and in combination with sitagliptin (20 mg/kg/day). Weekly body weight, food intake, and random blood glucose levels were monitored during the treatment phase. Post-treatment, an intraperitoneal glucose tolerance test (ipGTT), estimation of plasma biomarkers and haematological assessment were conducted. The treatment's effect on hepatic steatosis was studied by estimating liver biomarkers and histological examinations. Ten-week sitagliptin combination therapy with the investigational entities restored incretins, insulin, and other metabolic hormonal secretions, accompanied by improved glucose homeostasis and retarded weight gain. Interestingly, monotherapy with investigational agents improved liver health by reducing liver weight, liver enzymes, and inflammation. Hepatic effects were further enhanced by co-administration of sitagliptin, evident by amelioration in hepatic steatosis endpoints such as liver weight, plasma liver enzyme concentrations, hepatic triglycerides (TG), total cholesterol (CHO), hydroxyproline content, and cytokine levels. Histopathological investigations confirmed regression in hepatic steatosis in the combination groups. These findings demonstrate the therapeutic potential of novel gut-oriented GPR119 agonists in combination with a DPP-IV inhibitor to ameliorate metabolic dysfunction-associated steatohepatitis (MASH), warranting further mechanistic investigations.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117675"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photoaging protective effect of enzyme extracted pomegranate peel against oxidative damage in UVB-irradiated HaCaT cells.","authors":"Yeok Boo Chang, Hae Dun Kim, Sang Min Kim, Ji Hoon Lim, Moon Jea Woo, Hyung Joo Suh, Kyungae Jo","doi":"10.1016/j.biopha.2024.117679","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117679","url":null,"abstract":"<p><p>In this study, the ultraviolet B (UVB)-induced skin photoaging inhibitory activity of pomegranate peel extract with increased ellagic acid content through enzymatic hydrolysis was evaluated in HaCaT cells. Among various enzymes, Viscozyme with high tannase and β-glucosidase activities was used, and 1.0 % Viscozyme was added to hydrolyze pomegranate peel for 2 h at 40°C to establish the optimal reaction conditions for high ellagic acid content. Subsequently, when cells were treated with enzyme extracted pomegranate peels (40 μg/mL), the gene expression of matrix metalloproteinases (MMP)-2 and 13, which play key role in skin elasticity and moisture, and the protein expression of MMP13 were downregulated compared to the UVB-control group (UVB-C). In addition, the protein expression levels of tissue inhibitors, metalloproteinase-1 and 2, and collagen type I alpha 1 were upregulated, the gene expression of hyaluronic acid synthase-1, and filaggrin significantly increased, and interleukin-1β increased by photoaging was decreased. Furthermore, compared to the UVB-C, there was a significant increase in the gene expression of superoxide dismutase-1 and glutathione peroxidase, which resulted in a decrease in reactive oxygen species and malondialdehyde levels. These results were confirmed to be due to the inhibition of the mitogen-activated protein kinase pathway and downregulation of the protein expression of phosphorylated extracellular signal-regulated kinase, c-Jun N-terminal kinase, and P38. In conclusion, pomegranate peel, from which ellagic acid was extracted using Viscozyme, showed a reactive oxygen species inhibitory effect in UVB-irradiated HaCaT cells and thus may have a significant potential as a cosmetic ingredient with anti-aging effects.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117679"},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cooperative tumor inhibition by CpG-oligodeoxynucleotide and cyclic dinucleotide in head and neck cancer involves T helper cytokine and macrophage phenotype reprogramming.","authors":"Zaida Nur Imana, Jen-Chih Tseng, Jing-Xing Yang, Yi-Ling Liu, Po-Yen Lin, Ming-Hsi Huang, Linyi Chen, Yunping Luo, Chien-Chia Wang, Guann-Yi Yu, Tsung-Hsien Chuang","doi":"10.1016/j.biopha.2024.117692","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117692","url":null,"abstract":"<p><p>Head and neck cancer ranks as the sixth most common cancer worldwide, highlighting the critical need for the development of new therapies to enhance treatment efficacy. The activation of innate immune receptors given their potent immune stimulatory properties aid in the eradication of cancer cells. In this study, we investigated the immune mechanism and anti-tumor function of a Toll-like receptor 9 (TLR9) agonist, CpG-oligodeoxynucleotide-2722 (CpG-2722), in combination with cyclic dinucleotides, which are agonists of stimulator of interferon genes (STING). Our results revealed that CpG-2722 stimulation increased the expression of Th1 pro-inflammatory cytokines. Stimulation by STING agonists exhibited lower expression of Th1 cytokines but higher expression of Th2 cytokines compared to CpG-2722. However, the combination of these two agonists significantly enhanced Th1 cytokines while reducing Th2 cytokines. Moreover, in vivo experiment showed that both CpG-2722 and 2'3'-c-di-AMP suppressed head and neck tumor growth, with their combination proving more effective than the use of these agonists alone. The combined treatment cooperatively promoted the production of Th1 cytokines and type I interferons, while suppressing Th2 cytokines in the tumors as observed in vitro. Additionally, it led to the accumulation of M1 macrophages, dendritic cells, and T cells, shaping a favorable tumor microenvironment for T cell-mediated tumor killing. The anti-tumor activity of the CpG-2722 and 2'3'-c-di-AMP combination depends on the macrophage presence but does not directly activate M1 macrophage polarization, instead working through a reprogrammed cytokine profile. Furthermore, this combination shows a cooperative anti-tumor activity with anti-PD-1 in treating head and neck tumors. Overall, these findings highlight a Th response and macrophage phenotype reprograming involved functional mechanism underlying the cooperative activity of the combination of TLR9 and STING agonists in the immunotherapy of head and neck cancer.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117692"},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel chitosan-peptide system for cartilage tissue engineering with adipose-derived stromal cells.","authors":"Agata Tymińska, Natalia Karska, Aneta Skoniecka, Małgorzata Zawrzykraj, Adrianna Banach-Kopeć, Szymon Mania, Jacek Zieliński, Karolina Kondej, Katarzyna Gurzawska-Comis, Piotr M Skowron, Robert Tylingo, Sylwia Rodziewicz-Motowidło, Michał Pikuła","doi":"10.1016/j.biopha.2024.117683","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117683","url":null,"abstract":"<p><p>The natural healing process of cartilage injuries often fails to fully restore the tissue's biological and mechanical functions. Cartilage grafts are costly and require surgical intervention, often associated with complications such as intraoperative infection and rejection by the recipient due to ischemia. Novel tissue engineering technologies aim to ideally fill the cartilage defect to prevent disease progression or regenerate damaged tissue. Despite many studies on designing biocompatible composites to stimulate chondrogenesis, only few focus on peptides and carriers that promote stem cell proliferation or differentiation to promote healing. Our research aimed to design a carbohydrate chitosan-based biomaterial to stimulate stem cells into the chondrogenesis pathway. Our strategy was to combine chitosan with a novel peptide (UG28) that sequence was based on the copin protein. The construct stimulated human adipose-derived stem cells (AD-SCs) cells to undergo chondrogenic differentiation. Chitosan 75/500 allows AD-SCs to grow and has no harmful effects on the cells. The combination of UG28 peptide with the chitosan composite offers promising properties for cell differentiation, indicating its potential for clinical applications in cartilage regeneration.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117683"},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Sialogogic effects through olfactory stimulation with mastic resin and α-pinene volatiles in vivo\" [Biomed. Pharmacother. 168 (2023) 1-9].","authors":"Mouri R J Faruque, Kamran Nazmi, Annina van Splunter, Marja L Laine, Floris J Bikker","doi":"10.1016/j.biopha.2024.117661","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117661","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"117661"},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Dual regulatory effects of neferine on amyloid-β and tau aggregation studied by in silico, in vitro, and lab-on-a-chip technology\" [Biomed. Pharmacother. 172 (2024) 1-14/116226].","authors":"Yunkwon Nam, Ritu Prajapati, Sujin Kim, Soo Jung Shin, Da Yeon Cheong, Yong Ho Park, Hyun Ha Park, Danyou Lim, Yoojeong Yoon, Gyudo Lee, Hyun Ah Jung, Insu Park, Dong-Hyun Kim, Jae Sue Choi, Minho Moon","doi":"10.1016/j.biopha.2024.117686","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117686","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"117686"},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Celastrol reduces IL-1β induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo\" [Biomed. Pharmacother., 91 (2017) 208-219].","authors":"Jian Chen, Jun Xuan, Yun-Tao Gu, Ke-Si Shi, Jun-Jun Xie, Jiao-Xiang Chen, Zeng-Ming Zheng, Yu Chen, Xi-Bang Chen, Yao-Sen Wu, Xiao-Lei Zhang, Xiang-Yang Wang","doi":"10.1016/j.biopha.2024.117631","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117631","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"117631"},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Mechanism of chromium-induced toxicity in lungs, liver, and kidney and their ameliorative agents\" [Biomed. Pharmacother. 151, July 2022, 113119].","authors":"Rituraj Chakraborty, Kaviyarasi Renu, Mohamed Ahmed Eladl, Mohamed El-Sherbiny, Dalia Mahmoud Abdelmonem Elsherbini, Arshi Khalid Mirza, Balachandar Vellingiri, Mahalaxmi Iyer, Abhijit Dey, Abilash Valsala Gopalakrishnan","doi":"10.1016/j.biopha.2024.117629","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117629","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"117629"},"PeriodicalIF":0.0,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to \"Preconditioning with endoplasmic reticulum stress alleviated heart ischemia/reperfusion injury via modulating IRE1/ATF6/RACK1/PERK and PGC-1α in diabetes mellitus\" [Biomed. Pharmacother. 118 (2019) 109407].","authors":"Bing Yan, Suhuan Liu, Xuejun Li, Yali Zhong, Fei Tong, Shuyu Yang","doi":"10.1016/j.biopha.2024.117591","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117591","url":null,"abstract":"","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":" ","pages":"117591"},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}