Biomedicine & Pharmacotherapy最新文献_第2页

Unlocking the molecular mechanisms of anticancer and immunomodulatory potentials of cariprazine in triple negative breast cancer 揭示卡哌嗪在三阴性乳腺癌中的抗癌和免疫调节潜力的分子机制

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-19 DOI: 10.1016/j.biopha.2025.117931

Aleksandar Lazovic , Bojana Simovic Markovic , Irfan Corovic , Tijana Markovic , Marija Andjelkovic , Bojan Stojanovic , Ivan Jovanovic , Marina Mitrovic

{"title":"Unlocking the molecular mechanisms of anticancer and immunomodulatory potentials of cariprazine in triple negative breast cancer","authors":"Aleksandar Lazovic , Bojana Simovic Markovic , Irfan Corovic , Tijana Markovic , Marija Andjelkovic , Bojan Stojanovic , Ivan Jovanovic , Marina Mitrovic","doi":"10.1016/j.biopha.2025.117931","DOIUrl":"10.1016/j.biopha.2025.117931","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC), a highly invasive type of cancer, is difficult to treat due to insufficient specific targets and low survival rates. Current therapy often encounters drug resistance or relapse; thus, repurposing existing drugs could revolutionize cancer treatment. This study examined the anticancer effects of the antipsychotics Cariprazine (CAR), Olanzapine (OLZ), and Clozapine (CLZ), and the immunomodulatory potential of CAR, <em>in vitro</em> and <em>in vivo</em> in TNBC models. <em>In vitro</em>, CAR, OLZ, and CLZ significantly inhibited the proliferation of TNBC cells. This inhibition occurred via the induction of mitochondrial apoptosis, G0/G1 cell cycle arrest, and the suppression of autophagy, as evidenced by the down-regulation of Bcl-2, p62, and pAKT; the upregulation of Bax and active caspase 3; the decrease of ΔΨM; and the promotion of cytochrome c release. In addition, CAR inhibited MDA-MB-231 cells migration. <em>In vivo</em>, CAR inhibited tumor growth in the 4T1 xenograft model without causing adverse effects and resulted in the mRNA upregulation caspase 9, p53, p21, and Beclin-1. In addition, CAR influenced the immune response by promoting the production of proinflammatory cytokines TNF-α, IFN-γ, IL-17, and IL-1β and increasing the percentage of TNF-α<sup>+</sup>, IL-17<sup>+</sup>, IL-1β<sup>+</sup>, and IFN-γ<sup>+</sup> CD3<sup>+</sup> splenocytes. In conclusion, compared with other antipsychotics, 5-FU, and cisplatin, CAR exerted the most potent anticancer activity in TNBC <em>in vitro</em> and <em>in vivo</em>. This efficacy may be attributed to its ability to regulate apoptosis and autophagy, promote G0/G1 cell cycle arrest, and modulate antitumor immune response, suggesting its therapeutic potential in breast cancer.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117931"},"PeriodicalIF":6.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436746","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}

引用次数: 0

1-benzyl-6-nitro-4-phenyl-4-(methoxycarbonyl)-2(1H)-pyridinone, a novel pirfenidone derivative, alleviate hepatic fibrosis through T cells 1-苄基-6-硝基-4-苯基-4-(甲氧羰基)-2(1H)-吡啶酮，一种新型吡非尼酮衍生物，通过 T 细胞缓解肝纤维化

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-19 DOI: 10.1016/j.biopha.2025.117907

Meng-Xue Hu , Jia-Qi Li , Hong-Wei Zhang , Yu-Kun Ma , Bao-Jing Zhao , Lei Xiao , Wei Liang , Yamin Wang , Chun Wang , Cheng-Gui Wu , Ting-Ting Liu

{"title":"1-benzyl-6-nitro-4-phenyl-4-(methoxycarbonyl)-2(1H)-pyridinone, a novel pirfenidone derivative, alleviate hepatic fibrosis through T cells","authors":"Meng-Xue Hu , Jia-Qi Li , Hong-Wei Zhang , Yu-Kun Ma , Bao-Jing Zhao , Lei Xiao , Wei Liang , Yamin Wang , Chun Wang , Cheng-Gui Wu , Ting-Ting Liu","doi":"10.1016/j.biopha.2025.117907","DOIUrl":"10.1016/j.biopha.2025.117907","url":null,"abstract":"<div><div>Hepatic fibrosis (HF) is a pathological process in many liver diseases, which lack of specific agents. Pirfenidone (PFD) derivatives are potential new drug. The purpose of this study was to investigate the effect and immunological mechanism of PFD derivatives on HF. A total of 11 PFD derivatives were designed, synthesized and screened. 1-benzyl-6-nitro-4-phenyl-4-(methoxycarbonyl)-2(1 H)-pyridinone (code: Compound 5) had optimal effect on inhibiting nitric oxide release, hepatic stellate cells (HSCs) and T cell proliferation, which suggested that Compound 5 showed anti-inflammatory, anti-fibrosis and immunoregulation effects. Compound 5 inhibited the proliferation of HSC-T6 and T cell in dose-dependent manner, the IC<sub>50</sub> was 10.19 μM and 17.16 μM, respectively. Compound 5 inhibited the differentiation of CD8<sup>+</sup>T cells and promoted the differentiation of T<sub>regs</sub> in the splenic T lymphocyte of CCl<sub>4</sub>-induced mouse HF model. Besides, Compound 5 promoted HSC-T6 apoptosis in dose-dependent manner, accompanied by the down-regulation of α-smooth muscle actin (α-SMA) and collagen-I (Col-I). In terms of mechanism, Compound 5 had no significant effect on glucose uptake of T cells. But it inhibited non-esterified fatty acid (NEFA) secretion of T cell by inhibiting the phosphorylation of PI3K-AKT-mTOR signal, which related to the metabolism of T cell. Subsequently, Compound 5 affected α-SMA and Col-I expression of HSC-T6 by T cell modulating in cell co-culture.</div></div><div><h3>Conclusion</h3><div>Compound 5 is a promising new drug against HF by the dual role of inhibiting HSCs and modulating T cells lipid metabolism, which affects the immune microenvironment of HF.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117907"},"PeriodicalIF":6.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436747","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}

引用次数: 0

Pharmacological interactions of sulforaphane and gabapentin in a murine fibromyalgia-like pain model

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-18 DOI: 10.1016/j.biopha.2025.117929

Ik-Yahalcab Zamora-Díaz , María Eva González-Trujano , David Martínez-Vargas , G. Fernando Moreno-Pérez , Alberto Hernandez-Leon , Hugo Fernando Narváez-González , Rosa Ventura-Martínez , Francisco Pellicer , Francisco Javier López-Muñoz

{"title":"Pharmacological interactions of sulforaphane and gabapentin in a murine fibromyalgia-like pain model","authors":"Ik-Yahalcab Zamora-Díaz , María Eva González-Trujano , David Martínez-Vargas , G. Fernando Moreno-Pérez , Alberto Hernandez-Leon , Hugo Fernando Narváez-González , Rosa Ventura-Martínez , Francisco Pellicer , Francisco Javier López-Muñoz","doi":"10.1016/j.biopha.2025.117929","DOIUrl":"10.1016/j.biopha.2025.117929","url":null,"abstract":"<div><div>Therapeutic management of a chronic painful syndrome such as fibromyalgia (FM) lacks effective and safe single or combined analgesics. Current medications such as gabapentin (GPB) or pregabalin are moderately effective but in the presence of several adverse effects. Natural products derived from cruciferous vegetables such as sulforaphane (SFN) produce neuroprotective effects due to their potent antioxidant and anti-inflammatory properties. However, it is unknown whether positive or negative pharmacological interactions may occur when GBP and SFN are combined. The aim of this study was to estimate the pharmacological interaction of GBP and SFN in FM-like pain induced in rats. Time course curves of antiallodynic and antihyperalgesic effects were constructed for both SFN (3.16, 31.6, and 100 mg/kg, i.p.) and GBP (10, 31.6, and 100 mg/kg, i.p.) by recording behavioral responses every 30 min and up to 4 h afterward, from which dose-response effects were also obtained to decide the dosage combination. An electrocorticographic (ECoG) recording in mice and docking analysis were also explored to explain the pharmacological interaction. Our results demonstrated significant and dose-dependent antiallodynic and antihyperalgesic effects in their individual administration. While a combination of intermediate doses of these drugs enhanced their effects producing the same level as that obtained by using only 1/3 of the individual dose in each case. The ECoG recording and docking analysis suggest that calcium channels could be partly involved in the drug interaction. This study provides preclinical evidence that SFN alone and in combination with GBP may be beneficial for relieving FM-like pain at certain doses.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117929"},"PeriodicalIF":6.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429829","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}

引用次数: 0

Rb1 restores palmitic acid-induced reduction of Ca2+ influx by activating PLC in EA cells and PLD in MOVAS cells

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-18 DOI: 10.1016/j.biopha.2025.117927

In-Young Choi , Yoo Jin Kim , So Young Kim , Min Kyung Lee , Geun Hee Seol

{"title":"Rb1 restores palmitic acid-induced reduction of Ca2+ influx by activating PLC in EA cells and PLD in MOVAS cells","authors":"In-Young Choi , Yoo Jin Kim , So Young Kim , Min Kyung Lee , Geun Hee Seol","doi":"10.1016/j.biopha.2025.117927","DOIUrl":"10.1016/j.biopha.2025.117927","url":null,"abstract":"<div><div>Recent interest has focused on the role of Ca<sup>2+</sup> in regulating health problems, including cardiovascular disease and colorectal cancer. The inverse correlation between colon cancer and serum Ca<sup>2+</sup> underlines the importance of understanding intracellular Ca<sup>2+</sup> dynamics. Studies are also evaluating the contributions of abnormalities in Ca²⁺ homeostasis and intracellular dysfunction to the pathogenesis of metabolic syndrome as a precursor of cardiovascular disease. In this study, we investigated the changes of Ca<sup>2+</sup> dynamics and ginsenoside Rb<sub>1</sub> (Rb<sub>1</sub>)-induced recovery in two vascular cell lines exposed to palmitic acid (PA), the most abundant active ingredient in palm oil. The mechanism underlying the Rb<sub>1</sub>-induced recovery was examined in a store operated Ca<sup>2+</sup> entry model by Ca<sup>2+</sup> store depletion. PA reduced the Ca<sup>2+</sup> influx in both EA.hy926 (EA) and MOVAS cells, and this change was restored by Rb<sub>1</sub>. In EA cells, the Rb<sub>1</sub>-induced restoration was abolished by U73122 or 2-APB. In MOVAS cells, meanwhile, the effect of Rb<sub>1</sub> was abolished by FIPI, U73122 and U73343. Under normal conditions, Rb<sub>1</sub> itself altered phospholipid signaling (PLC in EA cells and PLD in MOVAS cells), but did not affect Ca<sup>2+</sup> homeostasis. These differences resulted in differences in downstream actions, as KB-R7943 and nifedipine inhibited Rb<sub>1</sub>-mediated Ca<sup>2+</sup> influx recovery only in MOVAS cells. In conclusion, Rb<sub>1</sub> rescues the PA-induced Ca<sup>2+</sup> influx by appropriately activating PLC in EA cells and PLD in MOVAS cells. This demonstrates that Ca<sup>2+</sup> dynamics are elaborately regulated via intracellular Ca<sup>2+</sup> signaling networks, suggesting a potential strategy for maintaining vascular Ca<sup>2+</sup> homeostasis in hyperlipidemic environments.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117927"},"PeriodicalIF":6.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429830","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}

引用次数: 0

Aspalathin, a key flavonoid in rooibos, restores STAT6-mediated immune dysregulation in atopic dermatitis

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-18 DOI: 10.1016/j.biopha.2025.117926

Inyoung Yang , Na-Hee Jeong , Young-Ae Choi , Dong Kyu Choi , Hyun-Shik Lee , Taeg Kyu Kwon , Soyoung Lee , Sang-Hyun Kim

{"title":"Aspalathin, a key flavonoid in rooibos, restores STAT6-mediated immune dysregulation in atopic dermatitis","authors":"Inyoung Yang , Na-Hee Jeong , Young-Ae Choi , Dong Kyu Choi , Hyun-Shik Lee , Taeg Kyu Kwon , Soyoung Lee , Sang-Hyun Kim","doi":"10.1016/j.biopha.2025.117926","DOIUrl":"10.1016/j.biopha.2025.117926","url":null,"abstract":"<div><div>Atopic dermatitis (AD), a chronic inflammatory skin disease whose incidence is increasing worldwide, requires the development of alternative treatments due to limited treatment options and concerns about side effects of therapeutic agents. Aspalathin (ASP) is the primary flavonoid found in rooibos, an herb traditionally used for allergies and eczema, accounting for over 40 % of the total flavonoid content, especially in its unfermented state (Green rooibos). This research conducted a thorough investigation into the pharmacological properties of ASP on AD, emphasizing local responses via activated keratinocytes, systemic responses involving T cells and basophils, and an integrated assessment using an AD mouse model. Topical application of ASP significantly reduced AD phenotypes, including erythema, scaling, and increased skin thickness, in AD mouse model. Histological analysis indicated a decrease in the infiltration of immune cells in skin lesions. Moreover, ASP down-regulated inflammatory markers, including T helper (Th)1 and Th2 cytokines, in both skin tissues and activated mouse T cells. In particular, ASP significantly reduced serum immunoglobulin (Ig)E and IgG2a levels. ASP suppressed the expression of cytokines linked to allergy and inflammation in T cells, basophils, and keratinocytes. Mechanistically, ASP exhibited anti-inflammatory properties by inhibiting STAT6 and NFAT1 activation in AD mouse skin and in activated T cells, basophils, and keratinocytes. In conclusion, ASP displayed pronounced effectiveness in relieving AD by sophisticated modulation of immune responses across both local and systemic domains. These findings highlight ASP's promise as a therapeutic intervention for AD, providing a solid scientific basis for future exploration and development.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117926"},"PeriodicalIF":6.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436740","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}

引用次数: 0

Mitotane activates ATF4/ATF3 axis triggering endoplasmic reticulum stress in adrenocortical carcinoma cells

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-17 DOI: 10.1016/j.biopha.2025.117917

Aurora Schiavon , Laura Saba , Carlotta Evaristo , Jessica Petiti , Ymera Pignochino , Giulio Ferrero , Giorgia Giordano , Cristina Tucciarello , Soraya Puglisi , Giuseppe Reimondo , Massimo Terzolo , Marco Lo Iacono

{"title":"Mitotane activates ATF4/ATF3 axis triggering endoplasmic reticulum stress in adrenocortical carcinoma cells","authors":"Aurora Schiavon , Laura Saba , Carlotta Evaristo , Jessica Petiti , Ymera Pignochino , Giulio Ferrero , Giorgia Giordano , Cristina Tucciarello , Soraya Puglisi , Giuseppe Reimondo , Massimo Terzolo , Marco Lo Iacono","doi":"10.1016/j.biopha.2025.117917","DOIUrl":"10.1016/j.biopha.2025.117917","url":null,"abstract":"<div><div>Adrenocortical Carcinoma is a rare and aggressive endocrine malignancy, that arises from cells of one of the three cortical layers of the adrenal gland. Radical surgery is the only curative treatment, even if recurrence rates are high. Therapeutic options are limited, with mitotane as the cornerstone of medical therapy. Despite 50 years of clinical use, the mechanism of action of mitotane has not yet been fully established, possibly due to the drug’s susceptibility to interaction with confounding factors that reduce its biological activity. In the present study, we evaluated by RNAseq the effect of mitotane on gene expression in the H295R cell line, in an environment free of known confounding factors. Our approach allowed us to identify transcriptional deregulation of the ATF4/ATF3 axis, often involved in ER stress. These results were also validated by ddPCR in independent experiments. Mitotane-mediated ATF4 overexpression was also confirmed at the protein level. We observed how an incremental concentration of mitotane could deregulate main biological pathways. Further, we confirmed, both at RNAseq and ddPCR level, the mitotane-mediated downmodulation of genes such as <em>STAR</em>, <em>CYP11A1</em>, <em>CYP21A2</em>, and <em>HSD3B2</em>, highlighting its effect on steroid hormones biosynthesis. Through our approach, we identified biological pathways altered by mitotane in early response stages and with low drug concentrations. Some of these pathways could potentially be investigated in the future as functional biomarkers to monitor adrenocortical carcinoma treatment or as new pharmacological targets for this rare disease.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117917"},"PeriodicalIF":6.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429828","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}

引用次数: 0

The fungal protein Lingzhi-8 ameliorates psoriasis-like dermatitis in mice through gut CD103+ tolerogenic dendritic cells, retinaldehyde dehydrogenase 2, and Dectin-1

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-16 DOI: 10.1016/j.biopha.2025.117910

Chen-Yu Wang , Jen-Yu Wang , Yi-Yi Chou , Chi-Chien Lin , Yu-Tsun Lin , Chi-Sheng Wu , Jr-Shiuan Lin , Ching-Liang Chu

{"title":"The fungal protein Lingzhi-8 ameliorates psoriasis-like dermatitis in mice through gut CD103+ tolerogenic dendritic cells, retinaldehyde dehydrogenase 2, and Dectin-1","authors":"Chen-Yu Wang , Jen-Yu Wang , Yi-Yi Chou , Chi-Chien Lin , Yu-Tsun Lin , Chi-Sheng Wu , Jr-Shiuan Lin , Ching-Liang Chu","doi":"10.1016/j.biopha.2025.117910","DOIUrl":"10.1016/j.biopha.2025.117910","url":null,"abstract":"<div><div>The gut CD103<sup>+</sup> tolerogenic dendritic cells play a key role in maintaining immune balance by inducing oral tolerance, which has been implied in reducing autoimmunity. We recently reported that the oral administration of a fungal protein Lingzhi-8 (LZ-8) prevented autoimmune colitis in mice via maintaining barrier integrity. Here, we examined the functional effect of LZ-8 on gut CD103<sup>+</sup> DCs and on autoimmune psoriasis in a mouse model. After orally administered LZ-8 to mice, the numbers of CD103<sup>+</sup> DCs and their retinaldehyde dehydrogenase 2 (RALDH2) activities were increased in the mesenteric lymph nodes (mLNs), which were associated with increased regulatory T cell (Treg) in the spleen and LNs. This suggests that LZ-8 induces oral tolerance by enhancing the RALDH2 activity of CD103<sup>+</sup> DCs. In addition, the imiquimod (IMQ)-induced psoriasis-like dermatitis was attenuated in mice after LZ-8 pretreatment. In the mechanistic study, we generated gut CD103<sup>+</sup> DC-like cells from bone marrow (BM) of wild-type mouse and cultured them in the presence of retinoic acid (RA) <em>in vitro</em>. We found that LZ-8 directly enhanced the RALDH2 activity of these RA-primed CD103<sup>+</sup> DCs, which was dependent on Dectin-1 and Syk signaling pathways but not TLR4. Together, our study demonstrated that LZ-8 facilitated gut tolerogenic CD103<sup>+</sup> DC-mediated immunosuppression by enhancing RALDH2 activity, increasing Treg cell population, and signaling through Dectin-1 and Syk. Our findings provide a novel strategy for treating psoriasis and potentially other autoimmune diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117910"},"PeriodicalIF":6.9,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143421266","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}

引用次数: 0

Revolutionizing cancer treatment: The power of dendritic cell-based vaccines in immunotherapy

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-16 DOI: 10.1016/j.biopha.2025.117858

Mohsen Sheykhhasan , Amirhossein Ahmadieh-Yazdi , Reza Heidari , Mohsen Chamanara , Mohammad Akbari , Naresh Poondla , Piao Yang , Sara Malih , Hamed Manoochehri , Hamid Tanzadehpanah , Hanie Mahaki , Nashmin Fayazi Hosseini , Ashkan Dirbaziyan , Sharafaldin Al-Musawi , Naser Kalhor

{"title":"Revolutionizing cancer treatment: The power of dendritic cell-based vaccines in immunotherapy","authors":"Mohsen Sheykhhasan , Amirhossein Ahmadieh-Yazdi , Reza Heidari , Mohsen Chamanara , Mohammad Akbari , Naresh Poondla , Piao Yang , Sara Malih , Hamed Manoochehri , Hamid Tanzadehpanah , Hanie Mahaki , Nashmin Fayazi Hosseini , Ashkan Dirbaziyan , Sharafaldin Al-Musawi , Naser Kalhor","doi":"10.1016/j.biopha.2025.117858","DOIUrl":"10.1016/j.biopha.2025.117858","url":null,"abstract":"<div><div>In the modern time, cancer immunotherapies have increasingly become vital treatment options, joining long-established methods like surgery, chemotherapy, and radiotherapy treatment. Central to this emerging approach are dendritic cells (DCs), which boast a remarkable ability for antigen presentation. This ability is being leveraged to modulate T and B cell immunity, offering a groundbreaking strategy for tackling cancer. However, the percentage of patients experiencing meaningful benefits from this treatment remains relatively low, underscoring the ongoing necessity for further research and development in this field. This review offers a comprehensive analysis of the present-day progress in dendritic cell (DC)-based vaccines and recent efforts to enhance their efficacy. We explore the intricacies of DC function, from antigen capture to T cell stimulation, and discuss the outcomes of both preclinical and clinical trials across various cancer types. While the results are promising, the real-world application of DC-based vaccines is still nascent, posing multiple challenges that need to be overcome. These obstacles include optimizing the methods for DC generation and antigen loading, overcoming the immunosuppressive nature of the tumor microenvironment, and enhancing specificities of the immunologic response through personalized vaccines. The review concludes by emphasizing prospective opportunities for future research and emphasizing the critical need for extensive clinical trials. These trials are essential to validate the effectivity of DC-based vaccines and solidify their role in the broader spectrum of cancer immunotherapy options.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117858"},"PeriodicalIF":6.9,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143421265","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}

引用次数: 0

Treatment with Lactobacillus paracasei L30 extract induces osteogenic differentiation of human bone marrow mesenchymal stem cells in vitro

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-16 DOI: 10.1016/j.biopha.2025.117913

Inwook Kim , Sankyu Park , Jieun Kim , So Young Park , Jeongmin Seo , Sangho Roh

{"title":"Treatment with Lactobacillus paracasei L30 extract induces osteogenic differentiation of human bone marrow mesenchymal stem cells in vitro","authors":"Inwook Kim , Sankyu Park , Jieun Kim , So Young Park , Jeongmin Seo , Sangho Roh","doi":"10.1016/j.biopha.2025.117913","DOIUrl":"10.1016/j.biopha.2025.117913","url":null,"abstract":"<div><div>Bone-related diseases such as osteoporosis pose a significant health economic burden to countries around the world and, because current treatments are insufficient, more effective therapies are desperately needed. This study explored the potential of Lactobacillus paracasei L30 extract to influence the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs). Our results showed that L30 extract significantly enhanced the expression of osteogenic markers in hBM-MSCs, including alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and collagen type I alpha 1 (COL1A1). Mechanistic studies revealed that L30 extract activated the p38 MAPK and AKT signaling pathways, leading to phosphorylation of Glycogen synthase kinase-3 beta (GSK3β) and subsequent nuclear translocation of β-catenin. Conversely, inhibition of p38 MAPK, AKT, or knockdown of β-catenin significantly attenuated the osteogenic effects of L30 extract on hBM-MSCs. Furthermore, we found that L30 extract promoted osteogenic differentiation in primary osteoblast precursors isolated from mouse calvaria and enhances bone formation in ex vivo calvarial organ cultures. Therefore, the application of Lactobacillus paracasei L30 extract in such contexts could serve as a therapeutic approach for promoting bone formation. Collectively, our findings suggest a novel approach for the clinical management of bone-related disorders, with possible applications for treating diseases such as osteoporosis.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117913"},"PeriodicalIF":6.9,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143421267","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}

引用次数: 0

Effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, dapagliflozin and canagliflozin, on the musculoskeletal system in an experimental model of diabetes induced by high-fat diet and streptozotocin in rats

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-16 DOI: 10.1016/j.biopha.2025.117912

Piotr Londzin , Maria Zych , Aleksandra Janas , Szymon Siudak , Joanna Folwarczna

{"title":"Effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, dapagliflozin and canagliflozin, on the musculoskeletal system in an experimental model of diabetes induced by high-fat diet and streptozotocin in rats","authors":"Piotr Londzin , Maria Zych , Aleksandra Janas , Szymon Siudak , Joanna Folwarczna","doi":"10.1016/j.biopha.2025.117912","DOIUrl":"10.1016/j.biopha.2025.117912","url":null,"abstract":"<div><div>The effect of SGLT2 inhibitors, a new group of antidiabetic drugs, on the skeletal system is a matter of debate. There are concerns that they may unfavorably affect bones. The aim of the study was to investigate the effects of dapagliflozin and canagliflozin on musculoskeletal system in an experimental rat model of type 2 diabetes induced by a high-fat diet (HFD) and streptozotocin (STZ). The experiments were carried out on mature female rats. To induce diabetes, STZ was administered 2 weeks after the introduction of HFD. Administration of dapagliflozin (1.4 mg/kg p.o.) or canagliflozin (4.2 mg/kg p.o.) started 1 week after the STZ injection, and lasted 4 weeks. Skeletal muscle mass and strength, serum bone turnover marker concentration and other biochemical parameters, and bone mass, density, histomorphometric parameters and mechanical properties were determined. Diabetes induced decreases in skeletal muscle mass and osteoporotic changes, including decreases in bone density, and worsening of the histomorphometric parameters and cancellous bone mechanical properties. The SGLT2 inhibitors decreased glycemia and other diabetes-induced metabolic changes, and counteracted only some unfavorable effects of diabetes on bones. The effects of dapagliflozin and canagliflozin on metabolic parameters were similar, whereas there were some differences in their effects on the skeletal system. The study demonstrated possibility of differential skeletal effects of different SGLT2 inhibitors in diabetic conditions, indicating the need for caution concerning their use in patients at risk of bone fractures.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117912"},"PeriodicalIF":6.9,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143421268","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}

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