European journal of pharmacology最新文献

{"title":"The effect of cancer-associated mutations on ligand binding and receptor function – A case for the 5-HT2C receptor","authors":"Chenlin Feng ,&nbsp;Rongfang Liu ,&nbsp;Reno Brooks ,&nbsp;Xuesong Wang ,&nbsp;Willem Jespers ,&nbsp;Marina Gorostiola González ,&nbsp;Gerard J.P. van Westen ,&nbsp;Erik H.J. Danen ,&nbsp;Laura H. Heitman","doi":"10.1016/j.ejphar.2024.177081","DOIUrl":"10.1016/j.ejphar.2024.177081","url":null,"abstract":"<div><div>The serotonin 5-HT_2C receptor is a G protein-coupled receptor (GPCR) mainly expressed in the central nervous system. Besides regulating mood, appetite, and reproductive behavior, it has been identified as a potential target for cancer treatment. In this study, we aimed to investigate the effects of cancer patient-derived 5-HT_2C receptor mutations on ligand binding and receptor functionality. By filtering the sequencing data from the Genomic Data Commons data portal (GDC), we selected 12 mutations from multiple cancer types. We found that the affinity of the endogenous agonist serotonin (5-HT) and inverse agonist mesulergine were both drastically decreased by mutations L209H^ECL2 and F328S^6.52, which are located in the orthosteric binding pocket. In the calcium-flux assay, the potency of 5-HT was decreased at F328S^6.52, while a trend of increased efficacy was observed. In contrast, 5-HT displayed higher affinity at E306K^6.30 and E306A^6.30, while a trend of decreased efficacy was observed. These two mutations may disrupt the conserved ionic interaction between E^6.30 and R^3.50, and thus increase the constitutive activity of the receptor. The inhibitory potency of mesulergine was increased at E306A^6.30 but not E306K^6.30. Lastly, P365H^7.50 decreased the expression level of the receptor by more than ten-fold, which prevented further functional analyses. This study shows that cancer-associated mutations of 5-HT_2C receptor have diverse effects on ligand binding and function. Such mutations may affect serotonin-mediated signaling in tumor cells as well as treatment strategies targeting this receptor.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177081"},"PeriodicalIF":4.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-Based solutions for current challenges in regenerative medicine","authors":"Pedram Asadi Sarabi ,&nbsp;Mahshid Shabanpouremam ,&nbsp;Amir Reza Eghtedari ,&nbsp;Mahsa Barat ,&nbsp;Behzad Moshiri ,&nbsp;Ali Zarrabi ,&nbsp;Massoud Vosough","doi":"10.1016/j.ejphar.2024.177067","DOIUrl":"10.1016/j.ejphar.2024.177067","url":null,"abstract":"<div><div>The emergence of Artificial Intelligence (AI) and its usage in regenerative medicine represents a significant opportunity that holds the promise of tackling critical challenges and improving therapeutic outcomes. This article examines the ways in which AI, including machine learning and data fusion techniques, can contribute to regenerative medicine, particularly in gene therapy, stem cell therapy, and tissue engineering. In gene therapy, AI tools can boost the accuracy and safety of treatments by analyzing extensive genomic datasets to target and modify genetic material in a precise manner. In cell therapy, AI improves the characterization and optimization of cell products like mesenchymal stem cells (MSCs) by predicting their function and potency. Additionally, AI enhances advanced microscopy techniques, enabling accurate, non-invasive and quantitative analyses of live cell cultures. AI enhances tissue engineering by optimizing biomaterial and scaffold designs, predicting interactions with tissues, and streamlining development. This leads to faster and more cost-effective innovations by decreasing trial and error. The convergence of AI and regenerative medicine holds great transformative potential, promising effective treatments and innovative therapeutic strategies. This review highlights the importance of interdisciplinary collaboration and the continued integration of AI-based technologies, such as data fusion methods, to overcome current challenges and advance regenerative medicine.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177067"},"PeriodicalIF":4.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological evaluation of a new nanoformulation in the erectile tissue of rabbits and humans","authors":"Iury A. Paz ,&nbsp;Pedro M. Silva Filho ,&nbsp;Alexandre S. Leitão Junior ,&nbsp;Tatiana Oliveira Pessoa ,&nbsp;Renata O. Santiago ,&nbsp;Nádia Osório de Oliveira ,&nbsp;Elisane Longhinotti ,&nbsp;Eduardo H.S. Sousa ,&nbsp;Luiz G.F. Lopes ,&nbsp;Claudia F. Santos ,&nbsp;Manassés C. Fonteles ,&nbsp;Nilberto R.F. Nascimento","doi":"10.1016/j.ejphar.2024.177071","DOIUrl":"10.1016/j.ejphar.2024.177071","url":null,"abstract":"<div><div>The failure of achieving a penile erection for satisfactory sexual intercourse is known as erectile dysfunction (ED). The primary mediator for penile erection is nitric oxide (NO). ED is often associated with endothelial/nitrergic dysfunction characterized by a reduction of the bioavailability of NO. Phosphodiesterase-5 inhibitors (PDE-5Is) clinical efficacy in the treatment of ED depends on the integrity of the NO-sGC-PKG pathway. In the present study, we probed the effect of sodium nitroprusside incorporated into mesoporous silica nanoparticles (MPSi-NP), which traps cyanide and slowly releases NO. MPSi-NP induced a maximal relaxation of 92.8 ± 5.2% in rabbit corpora cavernosa (RbCC), blunted by a soluble guanylate cyclase (sGC) inhibitor and blockers of calcium-dependent potassium channels. MPSi-NP abolished spontaneous contractions of human corpora cavernosa (HCC) strips. In addition, MPSi-NP induced maximal relaxation of phenylephrine precontracted HCC by 118.6 ± 3.6%, and in comparison, tadalafil induced a maximal relaxation of HCC by 98.3 ± 1.2%. Similarly, the sGC inhibitor blocked the MPSi-NP relaxation. MPSi-NP potentiated the relaxation induced by tadalafil. MPSi-NP increased cGMP levels in HCC strips by 2.6-fold and increased by 3.5-fold the phosphorylation level of the VASP protein, which is a downstream target to PKG. MPSi-NP effectively relaxes RbCC and HCC by activating the sGC-PKG pathway and potentiates the tadalafil response. MPSi-NP could be helpful in conditions where nitric oxide availability is decreased. A topical gel formulation of MPSi-NP could be used as a rescue therapy to treat true non-responders of PDE5Is drugs.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177071"},"PeriodicalIF":4.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Action of cocaine- and amphetamine-regulated transcript (CART) peptide to attenuate cisplatin-induced emesis in Suncus murinus (house musk shrew)","authors":"Zengbing Lu ,&nbsp;Sze Wa Chan ,&nbsp;Bin Jiang ,&nbsp;Dexuan Cui ,&nbsp;Ichiro Sakata ,&nbsp;Takafumi Sakai ,&nbsp;Xiaofei Huang ,&nbsp;Julia Yuen Hang Liu ,&nbsp;Tak Wah Dominic Chan ,&nbsp;John A. Rudd","doi":"10.1016/j.ejphar.2024.177072","DOIUrl":"10.1016/j.ejphar.2024.177072","url":null,"abstract":"<div><div>Cocaine- and amphetamine-regulated transcript (CART) peptide is a brain-gut neuropeptide that has been implicated in a range of physiological functions including appetite, which is disturbed during chemotherapy. The aims of the present study were to identify the distribution and expression of CART mRNA and CART peptide, and to examine the potential of CART (55–102) to attenuate cisplatin-induced emesis in <em>Suncus murinus</em>. CART mRNA and peptide were detected throughout the entire brain, including the forebrain, hypothalamus, and brainstem, and also in the gut wall and stomach. In conscious, freely moving animals, intracerebroventricular administration of CART (55–102) did not modulate food and water intake or alter locomotor activity when administered alone. Cisplatin induced emesis and upregulated the expression of CART mRNA in the brainstem. However, CART (55–102) reduced the number of cisplatin-induced retches. Both CART (55–102) and cisplatin increased the number of c-Fos positive cells in the nucleus tractus solitarius, lateral hypothalamus, paraventricular hypothalamus, and bed nucleus of the stria terminalis (BNST), compared to saline-treated animals, whereas cisplatin also induced c-Fos expression in the area postrema (AP), arcuate nucleus, and central nucleus of the amygdala. Pre-treatment with CART (55–102) significantly attenuated the increased c-Fos positive cells in the BNST and AP. These data indicate that CART mRNA and peptide were localized to regions involved in reward/enforcement, emotion, feeding and emesis. The anti-emetic effect of CART (55–102) against cisplatin-induced emesis may involve both the forebrain limbic system and the brainstem.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177072"},"PeriodicalIF":4.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of SIRT6 related signaling pathways of p-AKT/mTOR and NRF2/HO-1 by memantine contributes to curbing the progression of tamoxifen/HFD-induced MASH in rats","authors":"Yousra M. Ezz-Eldin ,&nbsp;Mohamed Gamal El-Din Ewees ,&nbsp;Marwa M. Khalaf ,&nbsp;Amany A. Azouz","doi":"10.1016/j.ejphar.2024.177069","DOIUrl":"10.1016/j.ejphar.2024.177069","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disorder marked by hepatic fat accumulation and inflammatory infiltrates which may evolve to cirrhosis. Clinical studies have demonstrated the higher risk of MASH development after tamoxifen (TAM) therapy, especially in obese patients. Therefore, we aimed to evaluate MASH induction by TAM combined with high fat diet (HFD) and the potential interference of memantine (MEMA) with MASH progression via modulation of SIRT6 and its related signaling pathways. MASH was induced in female Wistar rats by co-administration of TAM (25 mg/kg/day, <em>p.o.</em>) and HFD for 5 weeks. Liver function biomarkers, tissue triglyceride and cholesterol, MASH scoring, SIRT6 with its related signals, and lipid synthesis/oxidation markers were estimated. By comparison to MASH group, MEMA improved liver function indices (ALT, AST, ALP, albumin) and reduced the progression of MASH, evidenced by decreased accumulation of lipids in hepatic tissue, improved histological features, and reduced MASH scoring. MEMA enhanced hepatic SIRT6 and downregulated p-AKT/mTOR signaling, that subsequently reduced expressions of the lipid synthesis biomarkers (SREBP1c, SCD), while elevating the lipid oxidation markers (PPAR-α, CPT1). Moreover, MEMA enhanced NRF2/HO-1 signaling, with subsequently improved antioxidant defense and pro-inflammatory/anti-inflammatory cytokines balance. Analysis of SIRT6 correlations with p-AKT/mTOR, NRF2/HO-1, SREBP1c, and PPAR-α further confirmed our results. Consequently, we conclude that MEMA could interfere with MASH progression, at least in part, via enhanced SIRT6 expression and modulation of its related p-AKT/mTOR and NRF2/HO-1 signaling pathways, eventually reducing liver steatosis and inflammation. That could be a promising therapeutic modality for curbing MASH progression.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177069"},"PeriodicalIF":4.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatheliachromen mitigates methylglyoxal-induced myotube atrophy by activating Nrf2, inhibiting ubiquitin-mediated protein degradation, and restoring mitochondrial function","authors":"Yu-Fan Chuang ,&nbsp;Lin Cheng ,&nbsp;Wan-Hsuan Chang ,&nbsp;Szu-Yin Yu ,&nbsp;Hung-Te Hsu ,&nbsp;Li-Mei An ,&nbsp;Chia-Hung Yen ,&nbsp;Fang-Rong Chang ,&nbsp;Yi-Ching Lo","doi":"10.1016/j.ejphar.2024.177070","DOIUrl":"10.1016/j.ejphar.2024.177070","url":null,"abstract":"<div><h3>Background</h3><div>Methylglyoxal (MGO) is a potent precursor of glycative stress that leads to oxidative stress and muscle atrophy in diabetes. Spatheliachromen (FPATM-20), derived from <em>Ficus pumila</em> var. <em>awkeotsang</em>, exhibited potential antioxidant activity.</div></div><div><h3>Purpose</h3><div>This study aimed to evaluate the potential impact and underlying mechanisms of FPATM-20 on MGO-induced myotube atrophy and mitochondrial dysfunction in mouse skeletal C2C12 myotubes.</div></div><div><h3>Methods</h3><div>Atrophic and antioxidant factors were evaluated using immunofluorescence, enzyme-linked immunosorbent assay, and western blotting. Mitochondrial function was assessed using the ATP assay and Seahorse Cell Mito Stress Test. The glycogen content was determined using periodic acid-Schiff staining. Molecular docking was performed to determine the interaction between FPATM-20 and Keap1.</div></div><div><h3>Results</h3><div>In myotubes treated with MGO, FPATM-20 activated the Nrf2 pathway, reduced ROS levels, enhanced antioxidant defense, and increased glycogen content. FPATM-20 improved myotube viability and size, upregulated myosin heavy chain (MyHC) expression, modulated ubiquitin-proteasome molecules (nuclear FoxO3a, atrogin-1, MuRF-1, and p62/SQSTM1), and inhibited apoptosis (Bax/Bcl-2 ratio and cleaved caspase 3). Moreover, FPATM-20 restored mitochondrial function, including mitochondrial membrane potential, mitochondrial oxygen consumption rate, and mitochondrial biogenesis pathway (nuclear PGC-1α/TFAM/FNDC5). The inhibition of Nrf2 with ML385 reversed the effects of FPATM-20 on MGO. Furthermore, molecular docking confirmed the binding of FPATM-20 to Keap1, a suppressor of Nrf2, showing the crucial role of Nrf2 in protective effects.</div></div><div><h3>Conclusions</h3><div>FPATM-20 protects myotubes from MGO toxicity by activating the Nrf2 antioxidant defense, reducing protein degradation and apoptosis, and enhancing mitochondrial function. Thus, FPATM-20 may be a novel agent for preventing skeletal muscle atrophy.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177070"},"PeriodicalIF":4.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antidepressant-like and antistress effects of the ACTH(4–10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress","authors":"Ludmila S. Inozemtseva ,&nbsp;Ksenia A. Yatsenko ,&nbsp;Natalya Yu Glazova ,&nbsp;Andrey A. Kamensky ,&nbsp;Nikolai F. Myasoedov ,&nbsp;Natalia G. Levitskaya ,&nbsp;Igor A. Grivennikov ,&nbsp;Oleg V. Dolotov","doi":"10.1016/j.ejphar.2024.177068","DOIUrl":"10.1016/j.ejphar.2024.177068","url":null,"abstract":"<div><div>Current antidepressant therapy shows substantial limitations, and there is an urgent need for the development of new treatment strategies for depression. Stressful events and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis play an important role in the pathogenesis of depression. HPA axis activity is self-regulated by negative feedback at several levels including adrenocorticotropic hormone (ACTH)-mediated feedback. Here, we investigated whether noncorticotropic synthetic analogs of the ACTH(4–10) fragment, ACTH(4–7)-Pro-Gly-Pro (Semax) and Ac-Nle4-<em>cyclo</em>[Asp5-His6-D-Phe7-Arg8-Trp9-Lys10]ACTH(4–10)-NH2 (Melanotan II (MTII), a potent agonist of melanocortin receptors), have potential antidepressant activity in a chronic unpredictable stress (CUS) rat model of depression. Stressed and control male adult Sprague-Dawley rats received daily intraperitoneal injections of saline or a low dose (60 nmol/kg of body weight (BW)) of Semax or MTII. Rats were monitored for BW and hedonic status, as measured in the sucrose preference test. We found that chronic treatment with Semax and MTII reversed or substantially attenuated CUS-induced anhedonia, BW gain suppression, adrenal hypertrophy and a decrease in the hippocampal levels of BDNF. In the forced swim test, no effects of the CUS procedure or peptides on the duration of rat immobility were detected. Our findings show that in the CUS paradigm, systemically administered ACTH(4–10) analogs Semax and MTII exert antidepressant-like effects on anhedonia and hippocampal BDNF levels, and attenuate markers of chronic stress load, at least in male rats. The results support the argument that ACTH(4–10) analogs and other noncorticotropic melanocortins may have promising therapeutic potential for the treatment and prevention of depression and other stress-related pathologies.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177068"},"PeriodicalIF":4.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights on pharmacological and therapeutic potentials of trimetazidine beyond anti-anginal drug: A comprehensive review","authors":"Dhirendra Singh ,&nbsp;Joy Oladimeji-Salami ,&nbsp;Abidemi James Akindele","doi":"10.1016/j.ejphar.2024.177062","DOIUrl":"10.1016/j.ejphar.2024.177062","url":null,"abstract":"<div><div>Trimetazidine (TMZ) is a beneficial and well-tolerable anti-anginal drug which has protective action towards ischemia and reperfusion injury. TMZ performs its anti-ischemic effect by modifying cardiac metabolism without shifting the hemodynamic functions, so it represents an outstanding complementary perspective to the general angina treatment. TMZ possesses a positive impact on the inflammatory profile, and also endothelial function furthermore displays various benefits through minimising the number, as well as the intensity of angina strikes and ameliorating the clinical indication and symptoms of myocardium ischemia. It is administrated as monotherapy along with a combination of different antianginal drugs. Apart from anti-angina action, in recent years TMZ has shown various pharmacological activities such as neuroprotective, renal protective, hepato-protective, cardio-protective effects, and other beneficial pharmacological activities. We select to write the present review article to cover the different pharmacological and therapeutic potentials of TMZ.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"985 ","pages":"Article 177062"},"PeriodicalIF":4.2,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potency of marine collagen/pectin scaffolds - Fabrication, characterization and evaluation","authors":"Weslen Vedakumari Sathyaraj ,&nbsp;Yovan Raja Pravin ,&nbsp;Lokesh Prabakaran ,&nbsp;Anbalagan Gokulnath ,&nbsp;Jayavardhini Bhoopathy ,&nbsp;Selvarajan Rajendran","doi":"10.1016/j.ejphar.2024.177066","DOIUrl":"10.1016/j.ejphar.2024.177066","url":null,"abstract":"<div><div>Skin is an important vital organ that must be given proper care and protection from external damage and harmful microbes. If injured, it must be treated with an ideal wound dressing material with potent hemostatic and non-toxic properties. In the present study, fish collagen (FC) was extracted from the fins and tails of Black pomfret (<em>Parastromateus niger)</em>. The isolated fish collagen was homogenized with pectin (P) and freeze dried to obtain fish collagen/pectin (FC/P) scaffolds. Scanning electron microscopic analysis showed the porous nature of scaffolds with intermittent holes. UV–Visible and Fourier infrared spectroscopic analyses demonstrated the physicochemical properties of FC/P scaffolds. Hemolytic assay performed using human blood demonstrated the percentage of hemolysis as 0.5 %. <em>In vitro</em> blood clotting assay carried out to determine the hemostatic behaviour displayed the formation of blood clot within 60 s in the presence of FC/P scaffolds. 95 % of cells were viable with the highest concentration of FC/P scaffold used for MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Scratch wound assay demonstrated complete closure of wound in FC/P scaffold treated cells after 48 h of treatment. Chick embryo chorioallantoic membrane (CAM) assay showed the development of new blood vessels within 6 h of incubation with the FC/P scaffolds, thereby proving their angiogenic potency. These results indicate the potential use of FC/P scaffolds as effective biomaterials for tissue regenerative applications.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177066"},"PeriodicalIF":4.2,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoechinulin B, a natural product from Antarctic fungus, attenuates acute liver injury by inhibiting excessive cell adhesion","authors":"Han Sun ,&nbsp;Xu Pang ,&nbsp;Jian-Rui Li ,&nbsp;Hu Li ,&nbsp;Mei Tang ,&nbsp;Tao Zhang ,&nbsp;Li-Yan Yu ,&nbsp;Zong-Gen Peng","doi":"10.1016/j.ejphar.2024.177065","DOIUrl":"10.1016/j.ejphar.2024.177065","url":null,"abstract":"<div><div>Abnormal cell adhesion between leukocytes and endothelial cells is closely associated with the development of numerous inflammation-related diseases, with adhesion molecules playing a crucial role. The disruption of cell adhesion directly or indirectly inhibits excessive cell adhesion and thus produces a therapeutic effect. However, there are only a few clinically available antagonists of cell adhesion. One of the biggest challenges is the development of novel and efficient cell adhesion inhibitors. Recently, the anti-inflammatory pharmacological activity of natural products of microbial origin has also received increasing attention. Here, we obtained a potential cell adhesion inhibitor isoechinulin B, an indole diketopiperazine derivative, from the Antarctic fungus <em>Aspergillus</em> sp. CPCC 401072, which is active against cell adhesion. Isoechinulin B decreased the expression of vascular endothelial adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) by inhibiting the activation of the NF-κB signaling pathway, thereby inhibiting cell adhesion between leukocytes and endothelial cells to reduce macrophage infiltration in the liver and significantly attenuate lipopolysaccharide-induced acute liver injury in mice.</div></div><div><h3>Conclusion</h3><div>Isoechinulin B is a novel cell adhesion inhibitor derived from fungi found in extreme environments.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"984 ","pages":"Article 177065"},"PeriodicalIF":4.2,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}