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The therapeutic potential of angiotensin-converting enzyme inhibitor enalapril to ameliorate muscle atrophy in a murine model. 血管紧张素转换酶抑制剂依那普利改善小鼠模型肌肉萎缩的治疗潜力。
IF 4.6 3区 生物学
EXCLI Journal Pub Date : 2024-04-25 eCollection Date: 2024-01-01 DOI: 10.17179/excli2023-6822
Sima Seifi, Seyedeh Elnaz Nazari, Amir Avan, Nima Khalili-Tanha, Fereshteh Asgharzadeh, Fatemeh Babaei, Ghazaleh Khalili-Tanha, Seyyedeh Zahra Asghari, Mahdieh Darroudi, Gordon A Ferns, Abdoljalal Marjani, Majid Khazaei
{"title":"The therapeutic potential of angiotensin-converting enzyme inhibitor enalapril to ameliorate muscle atrophy in a murine model.","authors":"Sima Seifi, Seyedeh Elnaz Nazari, Amir Avan, Nima Khalili-Tanha, Fereshteh Asgharzadeh, Fatemeh Babaei, Ghazaleh Khalili-Tanha, Seyyedeh Zahra Asghari, Mahdieh Darroudi, Gordon A Ferns, Abdoljalal Marjani, Majid Khazaei","doi":"10.17179/excli2023-6822","DOIUrl":"10.17179/excli2023-6822","url":null,"abstract":"<p><p>Muscle atrophy due to limb immobilization and inactivity is a common consequence of many diseases and treatment processes. One of the systems activated in inflammatory conditions is the renin-angiotensin system (RAS). The present study was conducted with the aim of investigating the effects of one of the angiotensin-converting enzyme (ACE) inhibitors, enalapril, on improving muscle atrophy caused by immobility. The study was conducted in three groups: a control, an atrophy, and an atrophy group treated with enalapril on Balb/c mice. After tying a splint to cause atrophy in one of the legs, daily treatment with enalapril intraperitoneally (dissolved in DMSO) at a dose of 10 mg/kg/day was done for 7 days. On the eighth day, the splint was opened and half of the mice were evaluated. Then, in the recovery phase, treatment with enalapril was continued in the remaining mice for 10 days without a splint. At the end of each phase, the mice were examined for the muscle strength of the lower limb muscles, and histological and biochemical analyses were subsequently carried out. The tissue level of the oxidative stress index MDA was evaluated, which showed a significantly lower level in the enalapril group compared to the atrophy group (*P<0.1). Also, inflammatory factors in the enalapril group showed a decrease compared to the atrophy group. The strength of four limbs in the mice of the treatment group (-18.36 ± 1.70 %) was significantly higher than that of the atrophy group (-30.33 ± 3 %) at the end of the atrophy phase and also after 10 days of recovery. The results suggest that the use of enalapril that reduces the activation of angiotensin II-dependent pro-oxidant and pro-inflammatory pathways may improve the functional disorder and muscle necrosis in the murine model of muscle atrophy.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"600-611"},"PeriodicalIF":4.6,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondrial fatty acid beta-oxidation: a possible therapeutic target for skeletal muscle lipotoxicity in peripheral artery disease myopathy. 线粒体脂肪酸 beta-氧化:外周动脉疾病肌病中骨骼肌脂肪毒性的可能治疗靶点。
IF 4.6 3区 生物学
EXCLI Journal Pub Date : 2024-04-23 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7004
Cassandra E Bradley, Emma Fletcher, Trevor Wilkinson, Andrew Ring, Lucas Ferrer, Dimitrios Miserlis, Pal Pacher, Panagiotis Koutakis
{"title":"Mitochondrial fatty acid beta-oxidation: a possible therapeutic target for skeletal muscle lipotoxicity in peripheral artery disease myopathy.","authors":"Cassandra E Bradley, Emma Fletcher, Trevor Wilkinson, Andrew Ring, Lucas Ferrer, Dimitrios Miserlis, Pal Pacher, Panagiotis Koutakis","doi":"10.17179/excli2024-7004","DOIUrl":"10.17179/excli2024-7004","url":null,"abstract":"<p><p>Peripheral artery disease (PAD) is an atherosclerotic disease impacting over 200 million individuals and the prevalence increases with age. PAD occurs when plaque builds up within the peripheral arteries, leading to reduced blood flow and oxygen supply to the outer extremities. Individuals who experience PAD suffer from ischemia, which is typically accompanied by significant damage to skeletal muscles. Additionally, this tissue damage affects mitochondria, causing them to become dysregulated and dysfunctional, resulting in decreased metabolic rates. As there is no known cure for PAD, researchers are exploring potential therapeutic targets by examining coexisting cardiovascular conditions and metabolic risk factors, such as the aging process. Among these comorbidities, type-two diabetes mellitus and obesity are particularly common in PAD cases. These conditions, along with aging itself, are associated with an elevated accumulation of ectopic lipids within skeletal muscles, similar to what is observed in PAD. Researchers have attempted to reduce excess lipid accumulation by increasing the rate of fatty acid beta oxidation. Manipulating acetyl coenzyme A carboxylase 2, a key regulatory protein of fatty acid beta oxidation, has been the primary focus of such research. When acetyl coenzyme A carboxylase 2 is inhibited, it interrupts the conversion of acetyl-CoA into malonyl-CoA, resulting in an increase in the rate of fatty acid beta oxidation. By utilizing samples from PAD patients and applying the pharmacological strategies developed for acetyl coenzyme A carboxylase 2 in diabetes and obesity to PAD, a potential new therapeutic avenue may emerge, offering hope for improved quality of life for individuals suffering from PAD.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"523-533"},"PeriodicalIF":4.6,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Navigating neurological disorders: harnessing the power of natural compounds for innovative therapeutic breakthroughs. 导航神经系统疾病:利用天然化合物的力量实现创新治疗突破。
IF 4.6 3区 生物学
EXCLI Journal Pub Date : 2024-04-23 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7051
Rapuru Rushendran, Rukaiah Fatma Begum, Ankul Singh S, Pavithra Lakshmi Narayanan, Chitra Vellapandian, Bhupendra G Prajapati, Pijush Kumar Paul
{"title":"Navigating neurological disorders: harnessing the power of natural compounds for innovative therapeutic breakthroughs.","authors":"Rapuru Rushendran, Rukaiah Fatma Begum, Ankul Singh S, Pavithra Lakshmi Narayanan, Chitra Vellapandian, Bhupendra G Prajapati, Pijush Kumar Paul","doi":"10.17179/excli2024-7051","DOIUrl":"10.17179/excli2024-7051","url":null,"abstract":"<p><p>Novel treatments are needed as neurological issues become more frequent worldwide. According to the report, plants, oceans, microorganisms, and animals contain interesting drug discovery compounds. Alzheimer's, Parkinson's, and stroke reviews emphasize neurological disorders' complexity and natural substances' safety. Learn about marine-derived and herbal substances' neuroprotective characteristics and applications. Molecular pathways show these substances' neurological healing effects. This article discusses clinical usage of Bryostatin-1, Fucoidan, Icariin, Salvianolic acid, Curcumin, Resveratrol, etc. Their potential benefits for asthma and Alzheimer's disease are complex. Although limited, the study promotes rigorous scientific research and collaboration between traditional and alternative medical practitioners. Unexplored natural compounds, quality control, well-structured clinical trials, and interdisciplinary collaboration should guide future study. Developing and employing natural chemicals to treat neurological illnesses requires ethical sourcing, sustainability, and public awareness. This detailed analysis covers natural chemicals' current state, challenges, and opportunities in neurological disorder treatment. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"534-569"},"PeriodicalIF":4.6,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intranasal CEPO-FC prevents attention deficits in streptozotocin-induced rat model of Alzheimer's disease: Focus on synaptic plasticity-related factors. 鼻内 CEPO-FC 可预防链脲佐菌素诱导的阿尔茨海默病大鼠模型的注意力缺陷:关注突触可塑性相关因素
IF 4.6 3区 生物学
EXCLI Journal Pub Date : 2024-04-22 eCollection Date: 2024-01-01 DOI: 10.17179/excli2023-6818
Zahra Mansouri, Fariba Khodagholi, Jalal Zaringhalam, Fatemeh Abbaszadeh, Rasoul Ghasemi, Nader Maghsoudi
{"title":"Intranasal CEPO-FC prevents attention deficits in streptozotocin-induced rat model of Alzheimer's disease: Focus on synaptic plasticity-related factors.","authors":"Zahra Mansouri, Fariba Khodagholi, Jalal Zaringhalam, Fatemeh Abbaszadeh, Rasoul Ghasemi, Nader Maghsoudi","doi":"10.17179/excli2023-6818","DOIUrl":"10.17179/excli2023-6818","url":null,"abstract":"<p><p>Alzheimer's disease remains an issue of great controversy due to its pathology. It is characterized by cognitive impairments and neuropsychiatric symptoms. The FDA approved medications for this disease, can only mitigate the symptoms. One reason for the lack of effective medications is the inaccessibility of the brain which is encompassed by the blood-brain barrier, making intranasal (IN) route of administration potentially advantageous. Male Wistar rats underwent stereotaxic surgery to induce an Alzheimer's disease model via intracerebroventricular (ICV) streptozotocin injection, and Carbamylated Erythropoietin-Fc (CEPO-FC), a derivative of Erythropoietin without its harmful characteristics, was administered intranasally for ten consecutive days. Cognition performance for memory and attention was assessed using the Novel Object Recognition Test and the Object-Based Attention Test respectively. Depression like behavior was evaluated using the Forced Swim Test. Western blotting was done on the extracted hippocampus to quantify STIM proteins. Calbindin, PSD-95, Neuroplastin, Synaptophysin and GAP-43 genes were assessed by Realtime PCR. Behavioral tests demonstrated that IN CEPO-FC could halt cognition deficits and molecular investigations showed that, STIM proteins were decreased in Alzheimer's model, and increased after IN CEPO-FC treatment. Calbindin and PSD-95 were downregulated in our disease model and upregulated when treated with IN CEPO-FC. While Neuroplastin, and GAP-43 expressions remained unchanged. This study suggests that IN CEPO-FC in low doses could be promising for improving cognition and synaptic plasticity deficits in Alzheimer's disease and since IN route of administration is a convenient way, choosing IN CEPO-FC for clinical trial might worth consideration. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"491-508"},"PeriodicalIF":4.6,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","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 okadaic acid, azaspiracid-1, yessotoxin and their binary mixtures on human intestinal Caco-2 cells. okadaic acid、azaspiracid-1、yessotoxin 及其二元混合物对人体肠道 Caco-2 细胞的影响。
IF 4.6 3区 生物学
EXCLI Journal Pub Date : 2024-04-22 eCollection Date: 2024-01-01 DOI: 10.17179/excli2023-6884
Jimmy Alarcan, Albert Braeuning
{"title":"Effects of okadaic acid, azaspiracid-1, yessotoxin and their binary mixtures on human intestinal Caco-2 cells.","authors":"Jimmy Alarcan, Albert Braeuning","doi":"10.17179/excli2023-6884","DOIUrl":"10.17179/excli2023-6884","url":null,"abstract":"<p><p>Phycotoxins are responsible for foodborne intoxications. Symptoms depend on the ingested toxins but mostly imply gastro-intestinal and neurological disorders. Importantly, humans are exposed to combinations of several phycotoxins, resulting in possible mixture effects. Most previous studies, however, have been focused on single toxin effects. Thus, the aim of this study was to examine the effects of binary mixtures of three main phycotoxins, okadaic acid (OA), azaspiracid-1 (AZA1) and yessotoxin (YTX), on human intestinal Caco-2 cells. The focus was placed on cell viability studies and inflammation responses using a multi-parametric approach to assess cell population (nuclei staining), cell metabolism/viability (reductase activity and lysosomal integrity), and release of inflammation markers (e.g., interleukins). Mixture effects were evaluated using the concentration addition (CA) and independent action (IA) models. Our assays show that none of the toxins had an impact on the cell population in the tested concentration range. Only OA modulated reductase activity, while all three toxins had strong effects on lysosomal integrity. Furthermore, all toxins triggered the release of interleukin 8 (IL-8), with OA being most potent. Mixture effect analysis showed additivity in most cases. However, supra-additivity was observed in regards to IL-6 and IL-8 release for combinations implying high concentrations of OA. This study extends the knowledge on mixture effects of phycotoxins in human cells.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"509-522"},"PeriodicalIF":4.6,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Breaking boundaries: the transformative role of exercise in managing multiple sclerosis. 打破界限:运动在控制多发性硬化症中的变革作用。
IF 4.6 3区 生物学
EXCLI Journal Pub Date : 2024-04-15 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-6932
Saber Saedmocheshi, Narimen Yousfi, Karim Chamari
{"title":"Breaking boundaries: the transformative role of exercise in managing multiple sclerosis.","authors":"Saber Saedmocheshi, Narimen Yousfi, Karim Chamari","doi":"10.17179/excli2024-6932","DOIUrl":"10.17179/excli2024-6932","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a prevalent cause of physical disability in adults, with inflammation-induced demyelination and neurodegeneration contributing to its etiology. This comprehensive review explores the multifaceted benefits of exercise in managing MS, including improvements in aerobic capacity, balance, muscle strength, immune and hormonal functions and mood. Various exercise modalities, such as aerobic, resistance, flexibility, and balance training, are discussed, along with tailored protocols for MS patients. Recommended exercise strategies are: aerobic exercise: 2-3x/week; 10-30 minutes (40 %-60 % of maximum heart rate (HR<sub>max</sub>), HIIT: 1x/week, five 30-90-second intervals at 90 %-100 % HR<sub>max</sub>, Resistance training: 2-3x/week, 5-10 exercises; 1-3 sets for each exercise, 8-15 repetitions/set. The review also examines the impact of exercise on neuroplasticity, cardiovascular responses, cytokine modulation, stress hormone regulation, brain structure, and function and fatigue perception. Emphasizing the importance of exercise in enhancing the quality of life for individuals with MS, the review proposes exercise prescriptions and highlights the promising link between physical activity, brain health, and improved hormonal and immune status in MS patients. This review aims to inform future research and guide clinical practices for effective MS management.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"475-490"},"PeriodicalIF":4.6,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Personality of marathon runners: a narrative review of recent findings. 马拉松运动员的性格:最新研究成果综述。
IF 4.6 3区 生物学
EXCLI Journal Pub Date : 2024-03-27 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-6907
Lorin Braschler, Mabliny Thuany, Claudio Andre Barbosa de Lira, Volker Scheer, Pantelis T Nikolaidis, Katja Weiss, Beat Knechtle
{"title":"Personality of marathon runners: a narrative review of recent findings.","authors":"Lorin Braschler, Mabliny Thuany, Claudio Andre Barbosa de Lira, Volker Scheer, Pantelis T Nikolaidis, Katja Weiss, Beat Knechtle","doi":"10.17179/excli2024-6907","DOIUrl":"10.17179/excli2024-6907","url":null,"abstract":"<p><p>Participation in marathons has dramatically increased over the last few years. Marathon running has many proven beneficial effects, especially on cardiovascular health and fitness. Most research has focused on physiologic and pathophysiologic adaptations in connection with endurance exercise. Nevertheless, marathon running also has a major impact on psychological aspects and positively influences mental health, which has only recently attracted research interest. The present narrative review aimed to review the personality traits of marathon runners with an emphasis on recent literature. Marathon runners show a distinct personality and highly characteristic personality traits needed to successfully finish such a demanding race, i.e., a strong sense of vigor, self-sufficiency, and intelligence as well as low scores in anger, fatigue, tension, and depression. Furthermore, personality differences are detectable between runners of different sexes, ages, and performance level groups. This has significant clinical implications for athletes, coaches and competition organizers, as these groups show different patterns of personality traits. Future studies should focus on changes in cognition and mood states pre-, during, and post-endurance events, as well as during training periods. Large-scale studies comparing personality differences by sex, age, and performance are also important for better clinical guidance. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"441-474"},"PeriodicalIF":4.6,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Detailed role of mesenchymal stem cell (MSC)-derived exosome therapy in cardiac diseases. 间充质干细胞(MSC)衍生的外泌体疗法在心脏疾病中的详细作用。
IF 4.6 3区 生物学
EXCLI Journal Pub Date : 2024-03-25 eCollection Date: 2024-01-01 DOI: 10.17179/excli2023-6538
Ali Hassanzadeh, Navid Shomali, Amin Kamrani, Hadi Nasiri, Javad Ahmadian Heris, Maryam Pashaiasl, Mohammadreza Sadeghi, Shahram Sadeghvand, Zahra Valedkarimi, Morteza Akbari
{"title":"Detailed role of mesenchymal stem cell (MSC)-derived exosome therapy in cardiac diseases.","authors":"Ali Hassanzadeh, Navid Shomali, Amin Kamrani, Hadi Nasiri, Javad Ahmadian Heris, Maryam Pashaiasl, Mohammadreza Sadeghi, Shahram Sadeghvand, Zahra Valedkarimi, Morteza Akbari","doi":"10.17179/excli2023-6538","DOIUrl":"10.17179/excli2023-6538","url":null,"abstract":"<p><p>Coronary heart disease (CHD) continues to be the leading cause of morbidity and mortality. There are numerous therapeutic reperfusion methods, including thrombolytic therapy, primary percutaneous coronary intervention, and anti-remodeling drugs like angiotensin-converting enzyme inhibitors and beta-blockers. Despite this, there is no pharmacological treatment that can effectively stop cardiomyocyte death brought on by myocardial ischemia/reperfusion (I/R) injury. For the purpose of regenerating cardiac tissue, mesenchymal stem cell (MSC) therapy has recently gained more attention. The pleiotropic effects of MSCs are instead arbitrated by the secretion of soluble paracrine factors and are unrelated to their capacity for differentiation. One of these paracrine mediators is the extracellular vesicle known as an exosome. Exosomes deliver useful cargo to recipient cells from MSCs, including peptides, proteins, cytokines, lipids, miRNA, and mRNA molecules. Exosomes take part in intercellular communication processes and help tissues and organs that have been injured or are ill heal. Exosomes alone were found to be the cause of MSCs' therapeutic effects in a variety of animal models, according to studies. Here, we have focused on the recent development in the therapeutic capabilities of exosomal MSCs in cardiac diseases.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"401-420"},"PeriodicalIF":4.6,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bioengineering scalable and drug-responsive in vitro human multicellular non-alcoholic fatty liver disease microtissues encapsulated in the liver extracellular matrix-derived hydrogel. 封装在肝脏细胞外基质衍生水凝胶中的可扩展和具有药物响应性的体外人类多细胞非酒精性脂肪肝微组织生物工程。
IF 4.6 3区 生物学
EXCLI Journal Pub Date : 2024-03-25 eCollection Date: 2024-01-01 DOI: 10.17179/excli2023-6878
Negar Asadollahi, Mohammad Amin Hajari, Mahmoud Alipour Choshali, Mohammad Ajoudanian, Seyed Ali Ziai, Massoud Vosough, Abbas Piryaei
{"title":"Bioengineering scalable and drug-responsive in vitro human multicellular non-alcoholic fatty liver disease microtissues encapsulated in the liver extracellular matrix-derived hydrogel.","authors":"Negar Asadollahi, Mohammad Amin Hajari, Mahmoud Alipour Choshali, Mohammad Ajoudanian, Seyed Ali Ziai, Massoud Vosough, Abbas Piryaei","doi":"10.17179/excli2023-6878","DOIUrl":"10.17179/excli2023-6878","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) is a high-prevalence and progressive disorder. Due to lack of reliable <i>in vitro</i> models to recapitulate the consecutive phases, the exact pathogenesis mechanism of this disease and approved therapeutic medications have not been revealed yet. It has been proven that the interplay between multiple hepatic cell types and liver extracellular matrix (ECM) are critical in NAFLD initiation and progression. Herein, a liver microtissue (LMT) consisting of Huh-7, THP-1, and LX-2 cell lines and human umbilical vein endothelial cells (HUVEC), which could be substituted for the main hepatic cells (hepatocyte, Kupffer, stellate, and sinusoidal endothelium, respectively), encapsulated in liver derived ECM-Alginate composite, was bioengineered. When the microtissues were treated with free fatty acids (FFAs) including Oleic acid (6.6×10<sup>-4</sup>M) and Palmitic acid (3.3×10<sup>-4</sup>M), they displayed the key features of NAFLD, including similar pattern of transcripts for genes involved in lipid metabolism, inflammation, insulin-resistance, and fibrosis, as well as pro-inflammatory and pro-fibrotic cytokines' secretions and intracellular lipid accumulation. Continuing FFAs supplementation, we demonstrated that the NAFLD phenomenon was established on day 3 and progressed to the initial fibrosis stage by day 8. Furthermore, this model was stable until day 12 post FFAs withdrawal on day 3. Moreover, administration of an anti-steatotic drug candidate, Liraglutide (15 μM), on the NAFLD microtissues significantly ameliorated the NAFLD phenomenon. Overall, we bioengineered a drug-responsive, cost-benefit liver microtissues which can simulate the initiation and progression of NAFLD. It is expected that this platform could potentially be used for studying molecular pathogenesis of NAFLD and high-throughput drug screening. See also the graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"421-440"},"PeriodicalIF":4.6,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
hsa-miR-34a-5p enhances temozolomide anti-tumoral effects on glioblastoma: in-silico and in-vitro study. hsa-miR-34a-5p能增强替莫唑胺对胶质母细胞瘤的抗肿瘤作用:硅内和体外研究。
IF 4.6 3区 生物学
EXCLI Journal Pub Date : 2024-03-13 eCollection Date: 2024-01-01 DOI: 10.17179/excli2023-6404
Mahdi Abdoli Shadbad, Amir Baghbanzadeh, Behzad Baradaran
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