Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie最新文献_第6页

Isoliquiritigenin alleviates SLC7A11-mediated efferocytosis inhibition to promote wounds healing in diabetes. 异桔梗皂苷缓解 SLC7A11 介导的渗出抑制，促进糖尿病患者的伤口愈合。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-19 DOI: 10.1016/j.biopha.2024.117578

Xiaokang Gong, Jinhong Cai, Wenbiao Zheng, Jiehe Huang, Tao Chen, Weijie Chen, Xin Zheng

{"title":"Isoliquiritigenin alleviates SLC7A11-mediated efferocytosis inhibition to promote wounds healing in diabetes.","authors":"Xiaokang Gong, Jinhong Cai, Wenbiao Zheng, Jiehe Huang, Tao Chen, Weijie Chen, Xin Zheng","doi":"10.1016/j.biopha.2024.117578","DOIUrl":"10.1016/j.biopha.2024.117578","url":null,"abstract":"The healing process of chronic wounds often progresses slowly and is fraught with challenges, imposing increasing economic burdens and physical suffering on patients. Managing persistent wound inflammation and stimulating angiogenesis are crucial elements in promoting wound healing. Plants have been playing a key role in traditional medicine, and their abundant bioactive components continually inspire the development and innovation of new drugs. Isoliquiritigenin (ISL), a flavonoid compound derived from licorice roots known as chalcone, has demonstrated multifaceted pharmacological potential. However, its effects on diabetic wounds and the detailed mechanisms remain to be investigated. Through in-depth exploration using network pharmacology, we successfully predicted potential therapeutic targets of ISL for ischemic diseases. The revealed mechanisms primarily focused on the critical pathway of efferocytosis. Subsequent in vivo experiments demonstrated that ISL significantly enhanced the efferocytosis of dendritic cells (DC), improving the functional behaviors of endothelial cells. Further research indicated that ISL promoted DC efferocytosis by regulating SLC7A11-mediated glycolysis. Notably, the overexpression of SLC7A11 diminished the positive effects of ISL, suggesting a potential antagonistic role of SLC7A11 in the regulatory process. In the wounds of diabetic mice, we observed that ISL accelerated DC efferocytosis and angiogenesis, resulting in faster wound closure and better tissue repair. In summary, this study not only demonstrates the broad potential of ISL in managing diabetic wounds but also delves deeply into its mechanisms, laying a solid theoretical foundation for future clinical applications.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117578"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482989","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}

引用次数: 0

Melittin treatment suppressed malignant NSCLC progression through enhancing CTSB-mediated hyperautophagy. 美利汀通过增强CTSB介导的低自噬作用抑制了恶性非小细胞肺癌的进展。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-18 DOI: 10.1016/j.biopha.2024.117573

Yuhan Wang, Tailei Yuan, Longyue He, Jingjing Huang, Nodemsahajoel Wilfred, Wenhui Yang, Mingming Jin, Gang Huang, Changlian Lu

{"title":"Melittin treatment suppressed malignant NSCLC progression through enhancing CTSB-mediated hyperautophagy.","authors":"Yuhan Wang, Tailei Yuan, Longyue He, Jingjing Huang, Nodemsahajoel Wilfred, Wenhui Yang, Mingming Jin, Gang Huang, Changlian Lu","doi":"10.1016/j.biopha.2024.117573","DOIUrl":"10.1016/j.biopha.2024.117573","url":null,"abstract":"Melittin is preclinically investigated as anticancer agent in multiple tumor types. But its regulation role and regulatory mechanism regarding NSCLC is unknown. In our investigation, Proteomic test was employed to identify proteins that expressed abnormally in cancer cells and that with Melittin treatmented. The results showed CTSB was one of the Top proteins with different expression levels in the lysosomes of Melittin-treatmented cancer cells and showed an up-regulation trend. CTSB expression was increased in NSCLC cancer tissues compared to adjacent normal tissues, as demonstrated in lung cancer tissue chips experiment. However, Melittin treatment increased the CTSB level in lysosomes, which inhibited the malignant progression of NSCLC. We hypothesized that the relative homeostasis of CTSB in cancer cells was destroyed, and CTSB exerts its hydrolytic effect excessively, resulting in excessive autophagy of cancer cells, thus inhibiting the malignant progression of cancer cells. The direct combination of Melittin and CTSB was proposed by molecular docking technique, LiP-SMap was used to analyze the target genes and active components extracted from high-throughput sequencing proteomic data, and successfully verified that melittin was successfully demonstrated to directly target CTSB-binding. In vivo and in vitro studies have shown that Melittin treatment inhibits the malignant progression of A549 and HCC1833 cells and animal tumors, namely non-small cell lung cancer, by promoting CTSB-mediated hyperautophagy. CTSB-specific inhibitor CA-074 Me and autophagy inhibitor 3-MA treatment reversed the inhibit effect of Melittin to the malignant progression of NSCLC. Taken together, Melittin treatment inhibited malignant progression regarding NSCLC through enhancing CTSB-mediated hyperautophagy.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117573"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482991","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}

引用次数: 0

Apixaban trough concentrations in atrial fibrillation patients with reduced renal function. 肾功能减退的心房颤动患者的阿哌沙班谷浓度。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-28 DOI: 10.1016/j.biopha.2024.117613

Fadiea Al-Aieshy, Mika Skeppholm, Jonas Fyrestam, Fredrik Johansson, Anton Pohanka, Rickard E Malmström

{"title":"Apixaban trough concentrations in atrial fibrillation patients with reduced renal function.","authors":"Fadiea Al-Aieshy, Mika Skeppholm, Jonas Fyrestam, Fredrik Johansson, Anton Pohanka, Rickard E Malmström","doi":"10.1016/j.biopha.2024.117613","DOIUrl":"10.1016/j.biopha.2024.117613","url":null,"abstract":"Introduction: The direct factor Xa inhibitor apixaban is partially eliminated by the kidneys but is still prescribed at fixed doses without therapeutic drug monitoring across varying levels of renal function. If apixaban accumulates due to renal impairment, this may translate into safety concerns, e.g. the risk for bleeding. The purpose of this study was to measure apixaban trough concentrations in patients with different stages of renal function/renal impairment.Methods: Apixaban trough concentrations were measured using LC-MS/MS in patients with atrial fibrillation, having normal renal function (apixaban 5 mg BID, n=39), moderate renal impairment (apixaban 5 mg BID, n=40) and severe renal impairment (apixaban 2.5 mg BID, n=6). The median (min-max) relative eGFR values were 84.8 (71.7-111.4), 51.4 (31.3-67.2) and 23.0 (21.9-28.4) mL/min/1.73 m², in the three groups, respectively.Results: Patients with moderate renal impairment had significantly higher apixaban trough concentrations than patients with normal renal function. The median (min-max) trough concentrations were 59.8 ng/mL (15.5-170.9) for normal renal function, 128.9 ng/mL (41.4-295.4) for moderate renal impairment and 81.7 ng/mL (61.8-109.0) for severe renal impairment. The trough concentrations correlated significantly with renal function measured as relative/absolute eGFR creatinine/cystatin C.Conclusions: The standard dosing regimen of 5 mg apixaban BID renders exposure that is roughly twice as high in patients with moderately reduced renal function compared to patients with normal renal function. We suggest that patients with moderately reduced renal function ought to be monitored. Possibly, a dose reduction may be considered to achieve similar exposure as in patients with normal renal function.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117613"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523836","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}

引用次数: 0

Oleocanthal mitigates CoCl₂-induced oxidative damage and apoptosis via regulating MAPK pathway in human retinal pigment epithelial cells. 油菜黄素通过调节人视网膜色素上皮细胞的MAPK通路，减轻CoCl2诱导的氧化损伤和细胞凋亡。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-28 DOI: 10.1016/j.biopha.2024.117582

Ko-Chieh Huang, Yi-Fen Chiang, Mohamed Ali, Shih-Min Hsia

{"title":"Oleocanthal mitigates CoCl2-induced oxidative damage and apoptosis via regulating MAPK pathway in human retinal pigment epithelial cells.","authors":"Ko-Chieh Huang, Yi-Fen Chiang, Mohamed Ali, Shih-Min Hsia","doi":"10.1016/j.biopha.2024.117582","DOIUrl":"10.1016/j.biopha.2024.117582","url":null,"abstract":"Retinal hypoxia causes severe visual impairment and dysfunction in retinal pigment epithelial (RPE) cells, triggering a cascade of events leading to cellular apoptosis. Oxidative stress induced by hypoxia plays a significant role in the development of retinal diseases; however, the precise pathogenesis remains unclear. Oleocanthal, a phenolic compound in extra virgin olive oil, is known for its diverse biological properties. This study aims to investigate the potential anti-oxidative effects of oleocanthal against CoCl2-induced hypoxia in ARPE-19 cells. The cell culture model enabled the evaluation of apoptosis, DNA damage, and ROS levels using MTT assay, Western blot, Annexin V/PI staining, JC-1 staining, MitoSOX, H2DCFDA, immunocytochemistry, and comet assays. Our results showed that oleocanthal effectively protected RPE cells against CoCl2-induced damage by enhancing cell viability, reducing DNA damage, and decreasing ROS levels. Moreover, oleocanthal attenuated CoCl2-induced MMP loss by elevating the JC-1 aggregate/monomer ratio. Furthermore, CoCl2-induced cell apoptosis via up-regulating MAPK signaling, while oleocanthal mitigated this effect. These findings shed light on the molecular mechanisms underlying oleocanthal's protection against oxidative stress induced by hypoxia, offering potential insights for the development of novel therapeutic agents for retinal hypoxia.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117582"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523837","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}

引用次数: 0

Inhalation of H₂/O₂ (66.7 %/33.3 %) mitigates depression-like behaviors in diabetes mellitus complicated with depression mice via suppressing inflammation and preventing hippocampal damage. 通过抑制炎症和防止海马损伤，吸入 H2/O2（66.7 %/33.3 %）可减轻糖尿病并发抑郁症小鼠的抑郁样行为。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-14 DOI: 10.1016/j.biopha.2024.117559

Huaju Fan, Yanhua Shi, Haiqiang Liu, Xiaofei Zuo, Yanmei Yang, Hao Yin, Yanyan Li, Xianghui Wang, Li Liu, Fengjiao Wang, Huifang Han, Qianying Wu, Nana Yang, Yaohui Tang, Guohua Lu

{"title":"Inhalation of H2/O2 (66.7 %/33.3 %) mitigates depression-like behaviors in diabetes mellitus complicated with depression mice via suppressing inflammation and preventing hippocampal damage.","authors":"Huaju Fan, Yanhua Shi, Haiqiang Liu, Xiaofei Zuo, Yanmei Yang, Hao Yin, Yanyan Li, Xianghui Wang, Li Liu, Fengjiao Wang, Huifang Han, Qianying Wu, Nana Yang, Yaohui Tang, Guohua Lu","doi":"10.1016/j.biopha.2024.117559","DOIUrl":"10.1016/j.biopha.2024.117559","url":null,"abstract":"Diabetes mellitus complicated with depression (DD) is a prevalent psychosomatic disorder. It is characterized by severe cognitive impairment, and associated with high rates of disability and mortality. Although conventional treatment options are available, the efficacy of these regimens in managing DD remains limited. Molecular hydrogen (H2), a selective hydroxyl radical scavenger, has shown therapeutic potential in the treatment of various systemic diseases. This study aims to investigate the therapeutic effects of H2 on DD. A DD mouse model was established through intraperitoneal injection of streptozotocin (STZ, 150 mg/kg) and lipopolysaccharide (LPS, 0.5 mg/kg). Following the induction of DD, the mice were treated with H2/O2 (66.7 %/33.3 %)inhalation for 7 days. Behavioral assessments were conducted by standard behavioral tests, and the levels of inflammatory cytokines in peripheral blood serum and hippocampal tissue were measured using enzyme-linked immunosorbent assay (ELISA). Furthermore, magnetic resonance imaging (MRI) scans and immunofluorescence staining of the hippocampus were performed to evaluate hippocampal structural integrity. The results demonstrated that inhalation of H2/O2 (66.7 %/33.3 %) significantly ameliorated depressive behaviors and symptoms in DD mice, reversed hippocampal volume reduction, decreased inflammatory cytokine levels in peripheral blood serum and hippocampal tissue, and inhibited the activation of A1 astrocytes in the hippocampus. Our study suggests that H2/O2 (66.7 %/33.3 %) inhalation therapy may offer a promising treatment strategy for DD and its associated symptoms.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117559"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482988","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}

引用次数: 0

Verapamil attenuates myocardial ischemia/reperfusion injury by inhibiting apoptosis via activating the JAK2/STAT3 signaling pathway. 维拉帕米通过激活 JAK2/STAT3 信号通路抑制细胞凋亡，从而减轻心肌缺血再灌注损伤。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-13 DOI: 10.1016/j.biopha.2024.117568

Yang Zhao, Weiyi Huang, Fang Liu, Qiang Sun, Daifei Shen, Wenjun Fan, Danmei Huang, Yanmei Zhang, Fenfei Gao, Bin Wang

{"title":"Verapamil attenuates myocardial ischemia/reperfusion injury by inhibiting apoptosis via activating the JAK2/STAT3 signaling pathway.","authors":"Yang Zhao, Weiyi Huang, Fang Liu, Qiang Sun, Daifei Shen, Wenjun Fan, Danmei Huang, Yanmei Zhang, Fenfei Gao, Bin Wang","doi":"10.1016/j.biopha.2024.117568","DOIUrl":"10.1016/j.biopha.2024.117568","url":null,"abstract":"Apoptosis is a crucial pathological process in myocardial ischemia/reperfusion injury (MIRI). Verapamil (Ver), normally used to treat hypertension or heart rhythm disorders, also attenuates MIRI. The potential of Ver to inhibit apoptosis and thereby attenuate MIRI remains unclear, as does the mechanism. We established an in vivo mouse ischemia/reperfusion (I/R) model by occlusion of the left anterior descending coronary. To construct a hypoxia/reoxygenation model in vitro, H9c2 cardiomyocytes were immersed in a hypoxic buffer in a hypoxia/anaerobic workstation. Ver significantly improved cardiac function and reduced myocardial infarction size in I/R mice, while decreasing apoptosis. Both in vivo and in vitro, application of Ver activated the JAK2/STAT3 signaling pathway and elevated Bcl-2 expression, while decreasing Bax and cleaved caspase-3 levels. Treatment with AG490, a JAK2 inhibitor, partially counteracted the anti-apoptotic and the cardioprotective effect of Ver. Thus, we conclude that Ver alleviates MIRI by reducing apoptosis via the JAK2/STAT3 signaling pathway activation. These findings provide a novel mechanism of Ver in the treatment of MIRI.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117568"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483007","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}

引用次数: 0

Buparlisib and ponatinib inhibit aggressiveness of cholangiocarcinoma cells via suppression of IRS1-related pathway by targeting oxidative stress resistance. 布帕利西布和泊纳替尼通过抑制IRS1相关通路，靶向氧化应激抵抗，抑制胆管癌细胞的侵袭性。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-17 DOI: 10.1016/j.biopha.2024.117569

Waleeporn Kaewlert, Chadamas Sakonsinsiri, Worachart Lert-Itthiporn, Panupong Mahalapbutr, Saba Ali, Thanyada Rungrotmongkol, Apinya Jusakul, Napat Armartmuntree, Chawalit Pairojkul, Guofei Feng, Ning Ma, Somchai Pinlaor, Mariko Murata, Raynoo Thanan

{"title":"Buparlisib and ponatinib inhibit aggressiveness of cholangiocarcinoma cells via suppression of IRS1-related pathway by targeting oxidative stress resistance.","authors":"Waleeporn Kaewlert, Chadamas Sakonsinsiri, Worachart Lert-Itthiporn, Panupong Mahalapbutr, Saba Ali, Thanyada Rungrotmongkol, Apinya Jusakul, Napat Armartmuntree, Chawalit Pairojkul, Guofei Feng, Ning Ma, Somchai Pinlaor, Mariko Murata, Raynoo Thanan","doi":"10.1016/j.biopha.2024.117569","DOIUrl":"10.1016/j.biopha.2024.117569","url":null,"abstract":"Cholangiocarcinoma (CCA) is an oxidative stress-driven liver cancer with bile duct epithelial cell phenotypes and currently lacks effective treatments, making targeted drug therapy urgently needed. Oxidative stress plays a critical role in CCA carcinogenesis, involving cells with oxidative stress resistance via upregulation of the PI3K and MEKK3 signaling pathways. In this study, we investigated the antineoplastic efficacy of a PI3K inhibitor (buparlisib) and a multi-tyrosine kinase inhibitor (ponatinib) on CCA. The cytotoxicity of the drug combination was studied in vitro using CCA cell lines and in vivo using CCA xenograft models. It was found that the drug combination suppressed growth, colony formation, and migration abilities of CCA cells and induced oxidative damage, cell cycle arrest, and autophagy by suppressing MEKK3 and YAP1 through inhibition of insulin receptor substrate 1 (IRS1) signaling. Moreover, the drugs would potentially bind to the IRS1 protein, significanly decreasing IRS1 phosphorylation. Additionally, the drug combination significantly diminished the expression of YAP1, the cell proliferation marker and an antioxidant regulator, and increased oxidative stress-responsive markers in the xenograft model. In conclusion, targeting oxidative stress resistance with combined buparlisib and ponatinib suppressed tumor growth and migration by repressing IRS1-related pathways and ultimately inducing oxidative damage, suggesting the potential for targeted therapy and clinical trials in CCA patients over the use of a single drug.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117569"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482964","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}

引用次数: 0

Combined dapagliflozin and roxadustat effectively protected heart and kidney against cardiorenal syndrome-induced damage in rodent through activation of cell stress-Nfr2/ARE signalings and stabilizing HIF-1α. 达帕格列净和罗沙度他联合使用，通过激活细胞应激-Nfr2/ARE信号和稳定HIF-1α，有效保护啮齿类动物的心脏和肾脏免受心肾综合征引起的损伤。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-18 DOI: 10.1016/j.biopha.2024.117567

Pei-Hsun Sung, Ya Yue, Yi-Ling Chen, John Y Chiang, Ben-Chung Cheng, Chih-Chao Yang, Han-Tan Chai, Hon-Kan Yip

{"title":"Combined dapagliflozin and roxadustat effectively protected heart and kidney against cardiorenal syndrome-induced damage in rodent through activation of cell stress-Nfr2/ARE signalings and stabilizing HIF-1α.","authors":"Pei-Hsun Sung, Ya Yue, Yi-Ling Chen, John Y Chiang, Ben-Chung Cheng, Chih-Chao Yang, Han-Tan Chai, Hon-Kan Yip","doi":"10.1016/j.biopha.2024.117567","DOIUrl":"10.1016/j.biopha.2024.117567","url":null,"abstract":"Background: This study tested whether combined dapagliflozin (DAPA) and roxadustat (ROX) therapy was superior to a singular therapy in protecting heart and kidney functions in rats with cardiorenal syndrome (CRS).Methods and results: An in vitro study demonstrated that the cell survival (PI3K/Akt/mTOR)/cell stress (ERK1/2, JNK/p-38) signaling was significantly activated by combination therapy with ROX-DAPA (all p<0.001). Additionally, these two signaling pathways further significantly upregulated the hypoxia-induced factor (HIF)-1α which, in turn, significantly upregulated Nrf2/ARE (HO-1/NQO-1) and angiogenesis/cell-growth factors (EPO/SDF-1α/VEGF/FGF/IGF-2) and downregulated hypoxia-inducible factor prolyl-4-hydroxylase-1 (all p<0.001). Adult-male SD rats were categorized into Groups 1 (sham-operated control)/2 (CRS)/3 (CRS+ROX)/4 (CRS+DAPA)/5 (CRS+ROX+DAPA). By Day 60 after rodent CRS induction, the levels of BUN/creatinine and the ratio of urine protein to creatinine were lowest in Group 1, highest in Group 2, and significantly lower in Group 5 than in Groups 3 and 4; however, they were similar in the latter two groups, whereas the left-ventricular-ejection-fraction exhibited the opposite trend of creatinine among the groups (all p<0.0001). The protein expression levels of cell-survival (p-PI3K/p-Akt-p-mTOR)/cell-stress (p-JNK/p-p38/p-ERK1/2)/Nrf2-ARE (HO-1/NQO-1/SIRT1/SIRT3) signaling factors and angiogenesis factors (HIF-1α/VEGF/SDF-1α/FGF/IGF-2/EPO) significantly and progressively increased from Groups 1-5 (all p<0.0001).Conclusion: Combined DAPA-ROX therapy has a synergistic effect on protecting heart and kidney functions against CRS-induced damage in rodents.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117567"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482966","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}

引用次数: 0

Dihydromyricetin treats pulmonary hypertension by modulating CKLF1/CCR5 axis-induced pulmonary vascular cell pyroptosis. 二氢杨梅素通过调节 CKLF1/CCR5 轴诱导的肺血管细胞热解来治疗肺动脉高压。

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-25 DOI: 10.1016/j.biopha.2024.117614

Qian Yan, Ping Li, Shasha Liu, Yang Sun, Chen Chen, Junpeng Long, Yuting Lin, Jinping Liang, Hanlong Wang, Ling Zhang, Hongbin Wang, Huiqin Wang, Songwei Yang, Meiyu Lin, Xuan Liu, Jiao Yao, Zhifeng Tian, Naihong Chen, Yantao Yang, Qidi Ai

{"title":"Dihydromyricetin treats pulmonary hypertension by modulating CKLF1/CCR5 axis-induced pulmonary vascular cell pyroptosis.","authors":"Qian Yan, Ping Li, Shasha Liu, Yang Sun, Chen Chen, Junpeng Long, Yuting Lin, Jinping Liang, Hanlong Wang, Ling Zhang, Hongbin Wang, Huiqin Wang, Songwei Yang, Meiyu Lin, Xuan Liu, Jiao Yao, Zhifeng Tian, Naihong Chen, Yantao Yang, Qidi Ai","doi":"10.1016/j.biopha.2024.117614","DOIUrl":"10.1016/j.biopha.2024.117614","url":null,"abstract":"Pulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by elevated pulmonary artery pressure and vascular remodeling, resulting in poor prognosis and increased mortality rates. Chemokine-like factor 1 (CKLF1) plays a significant role in inducing inflammation and cell proliferation, both of which are critical processes in the pathogenesis of various diseases. Dihydromyricetin (DMY) has garnered attention for its potent anti-inflammatory properties. This study evaluated the protective effects of DMY against PH, demonstrating that DMY treatment can mitigate pyroptosis in pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs) in vivo via the CKLF1/CCR5 axis. Results indicated significant improvements in hemodynamics, inflammatory responses, fibrosis, vascular remodeling, and right ventricular hypertrophy in PH rats following DMY treatment. Furthermore, the interaction between CKLF1 and CCR5 was investigated in CKLF1-/- rats after PH induction. DMY was found to downregulate CKLF1 expression and the inflammatory response in the lungs, with its therapeutic efficacy diminished following CKLF1 knockdown. This study underscores the therapeutic potential of DMY in the management of PH and lays a foundation for future research and clinical applications.","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"180 ","pages":"117614"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514588","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}

引用次数: 0

Corrigendum "The protective effect of shikonin on renal tubular epithelial cell injury induced by high glucose" [Biomed. Pharmacother. 98 (2018) 701-708]. Corrigendum "The protective effect of shikonin on renal tubular ephelial cell injury induced by high glucose" [Biomed. Pharmacother. 98 (2018) 701-708].

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-26 DOI: 10.1016/j.biopha.2024.117624

Yuna Tong, Junlan Chuan, Lan Bai, Jianyou Shi, Lei Zhong, Xingmei Duan, Yuxuan Zhu

引用次数: 0