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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
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
{"title":"hsa-miR-34a-5p enhances temozolomide anti-tumoral effects on glioblastoma: in-silico and in-vitro study.","authors":"Mahdi Abdoli Shadbad, Amir Baghbanzadeh, Behzad Baradaran","doi":"10.17179/excli2023-6404","DOIUrl":"https://doi.org/10.17179/excli2023-6404","url":null,"abstract":"<p><p>Glioblastoma multiform (GBM) is a commonly diagnosed brain neoplasm with a poor prognosis. Accumulating evidence has highlighted the significance of microRNA (miR) dysregulation in tumor development and progression. This study investigated the effect of hsa-miR-34a-5p and its combination with temozolomide on GBM, the related molecular mechanisms, and the signaling pathway using <i>in-silico</i> and <i>in-vitro</i> approaches. The <i>in-silico</i> tumor bulk and single-cell RNA sequencing analyses were done on TCGA-GTEx, CGGA, GSE13276, GSE90603, and GSE182109 datasets. After selecting the A172 cell line, hsa-miR-34a-5p mimics were transfected, and the cell viability, migration, cell cycle, clonogenicity, and apoptosis of studied groups were studied using MTT, scratch, flow cytometry, colony formation, and Annexin V/PI assays. The mRNA expression of <i>CASP9</i>, <i>CASP3</i>, <i>CASP8</i>, <i>MMP2</i>, <i>CD44</i>, <i>CDK6</i>, <i>CDK4</i>, <i>CCND1</i>, <i>RAF1</i>, <i>MAP2K1</i>, <i>MET</i>, <i>SRC</i>, and <i>CD274</i> was studied using qRT-PCR method. hsa-miR-34a-5p downregulated <i>RAF1</i> expression, as the signaling factor of the MAPK pathway. The combined treatment significantly downregulated the expression of <i>MET</i>, <i>SRC</i>, and <i>MAP2K1</i>, leading to the inhibition of the MET/MAPK pathway compared to temozolomide. Besides exerting anti-tumoral effects on the cell viability, migration, cell cycle, apoptosis, and clonogenicity of A172 cells, its combination with temozolomide enhanced temozolomide anti-tumoral effect. Compared to temozolomide, the combined treatment significantly decreased <i>CDK4</i>, <i>CDK6</i>, <i>CCND1</i>, and <i>MMP2</i> expression. hsa-miR-34a-5p targets <i>RAF1</i>, as the signaling factor of the MAPK pathway, and potentiates the temozolomide anti-tumoral effect on A172 cells.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"384-400"},"PeriodicalIF":4.6,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11036064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857155","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
Overall review of curative impact and barriers of CAR-T cells in osteosarcoma. 全面回顾CAR-T细胞在骨肉瘤中的治疗效果和障碍。
IF 4.6 3区 生物学
EXCLI Journal Pub Date : 2024-03-06 eCollection Date: 2024-01-01 DOI: 10.17179/excli2023-6760
Guilin Li, Hong Wang, Vafa Meftahpour
{"title":"Overall review of curative impact and barriers of CAR-T cells in osteosarcoma.","authors":"Guilin Li, Hong Wang, Vafa Meftahpour","doi":"10.17179/excli2023-6760","DOIUrl":"https://doi.org/10.17179/excli2023-6760","url":null,"abstract":"<p><p>Osteosarcoma (OS) is a rare form of cancer and primary bone malignancy in children and adolescents. Current therapies include surgery, chemotherapy, and amputation. Therefore, a new therapeutic strategy is needed to dramatically change cancer treatment. Recently, chimeric antigen receptor T cells (CAR-T cells) have been of considerable interest as it has provided auspicious results and patients suffering from low side effects after injection that resolve with current therapy. However, there are reports that cytokine release storm (CRS) can be observed in some patients. In addition, as researchers have faced problems that limit and suppress T cells, further studies are required to resolve these problems. In addition, to maximize the therapeutic benefit of CAR-T cell therapy, researchers have suggested that combination therapy could be better used to treat cancer by overcoming any problems and reducing side effects as much as possible. This review summarizes these problems, barriers, and the results of some studies on the evaluation of CAR-T cells in patients with osteosarcoma.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"364-383"},"PeriodicalIF":4.6,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11036068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874571","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
Pre-emptive paracetamol reduces intra-operative opioid use in patients undergoing day-case oncologic breast surgery. 日间乳腺肿瘤手术患者术前服用扑热息痛可减少术中阿片类药物的使用。
IF 4.6 3区 生物学
EXCLI Journal Pub Date : 2024-02-29 eCollection Date: 2024-01-01 DOI: 10.17179/excli2023-6804
Daniah Alsaadi, Lyndon Low, James Ting, Michael Craughwell, John McDonnell, Aoife Lowery, Karl Sweeney
{"title":"Pre-emptive paracetamol reduces intra-operative opioid use in patients undergoing day-case oncologic breast surgery.","authors":"Daniah Alsaadi, Lyndon Low, James Ting, Michael Craughwell, John McDonnell, Aoife Lowery, Karl Sweeney","doi":"10.17179/excli2023-6804","DOIUrl":"https://doi.org/10.17179/excli2023-6804","url":null,"abstract":"<p><p>Minimization of intra-operative opioid use is an area of ongoing research interest with several potential benefits to the patient. Pre-emptive analgesia, defined as the administration of an analgesic before surgery to prevent establishment of central sensitization of pain, is one avenue that has been explored to achieve this. A retrospective observational study was undertaken to examine the effect of pre-emptive paracetamol on intra-operative opioid requirements. The medical and operative data of 156 patients who underwent day-case wide local excision and sentinel lymph node biopsy with and without regional block surgery at our center between October 2019 and May 2022 was carried out. Data were collected on demographics, total intra-operative and immediate post-operative opioid consumption. 57 patients did not receive pre-emptive paracetamol while 90 did. Baseline characteristics were similar. Our results showed a statistically significant reduction in morphine (p <0.029) and remifentanil (p <0.007) consumption in patients who received a regional block and pre-emptive paracetamol. Those who did not receive a regional block and were given pre-emptive paracetamol had a decrease in OxyNorm (p <0.022) requirements. A combination of general anesthesia (GA), regional block and pre-emptive paracetamol reduced intra-operative consumption of Fentanyl, OxyNorm, diclofenac, dexketoprofen, and clonidine (P <0.001) when compared to just GA alone. Use of pre-emptive paracetamol in reduction of intra-operative opioid requirements showed promising results but larger studies may strengthen the evidence for this association. A multimodal analgesic approach that utilizes pre-emptive paracetamol can be a viable method to decrease intra-operative of analgesic requirements.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"356-363"},"PeriodicalIF":4.6,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11036063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859187","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
Plasticity and resistance of cancer stem cells as a challenge for innovative anticancer therapies - do we know enough to overcome this? 癌症干细胞的可塑性和抗药性是创新抗癌疗法面临的挑战--我们是否有足够的知识来克服这一挑战?
IF 3.8 3区 生物学
EXCLI Journal Pub Date : 2024-02-29 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-6972
Agnieszka Knopik-Skrocka, Alicja Sempowicz, Oliwia Piwocka
{"title":"Plasticity and resistance of cancer stem cells as a challenge for innovative anticancer therapies - do we know enough to overcome this?","authors":"Agnieszka Knopik-Skrocka, Alicja Sempowicz, Oliwia Piwocka","doi":"10.17179/excli2024-6972","DOIUrl":"10.17179/excli2024-6972","url":null,"abstract":"<p><p>According to the CSC hypothesis, cancer stem cells are pivotal in initiating, developing, and causing cancer recurrence. Since the identification of CSCs in leukemia, breast cancer, glioblastoma, and colorectal cancer in the 1990s, researchers have actively investigated the origin and biology of CSCs. However, the CSC hypothesis and the role of these cells in tumor development model is still in debate. These cells exhibit distinct surface markers, are capable of self-renewal, demonstrate unrestricted proliferation, and display metabolic adaptation. CSC phenotypic plasticity and the capacity to EMT is strictly connected to the stemness state. CSCs show high resistance to chemotherapy, radiotherapy, and immunotherapy. The plasticity of CSCs is significantly influenced by tumor microenvironment factors, such as hypoxia. Targeting the genetic and epigenetic changes of cancer cells, together with interactions with the tumor microenvironment, presents promising avenues for therapeutic strategies. See also the Graphical abstract(Fig. 1).</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"335-355"},"PeriodicalIF":3.8,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11036066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848677","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
Molecular targeted therapies for cutaneous squamous cell carcinoma: recent developments and clinical implications. 皮肤鳞状细胞癌的分子靶向疗法:最新进展和临床意义。
IF 4.6 3区 生物学
EXCLI Journal Pub Date : 2024-02-27 eCollection Date: 2024-01-01 DOI: 10.17179/excli2023-6489
Harpreet Singh, Hitesh Chopra, Inderbir Singh, Sourav Mohanto, Mohammed Gulzar Ahmed, Shruti Ghumra, Anmol Seelan, Manisha Survase, Arvind Kumar, Amrita Mishra, Arun Kumar Mishra, Mohammad Amjad Kamal
{"title":"Molecular targeted therapies for cutaneous squamous cell carcinoma: recent developments and clinical implications.","authors":"Harpreet Singh, Hitesh Chopra, Inderbir Singh, Sourav Mohanto, Mohammed Gulzar Ahmed, Shruti Ghumra, Anmol Seelan, Manisha Survase, Arvind Kumar, Amrita Mishra, Arun Kumar Mishra, Mohammad Amjad Kamal","doi":"10.17179/excli2023-6489","DOIUrl":"https://doi.org/10.17179/excli2023-6489","url":null,"abstract":"<p><p>Cutaneous Squamous Cell Carcinoma (cSCC) is a common and potentially fatal type of skin cancer that poses a significant threat to public health and has a high prevalence rate. Exposure to ultraviolet radiation on the skin surface increases the risk of cSCC, especially in those with genetic syndromes like xerodermapigmentosum and epidermolysis bullosa. Therefore, understanding the molecular pathogenesis of cSCC is critical for developing personalized treatment approaches that are effective in cSCC. This article provides a comprehensive overview of current knowledge of cSCC pathogenesis, emphasizing dysregulated signaling pathways and the significance of molecular profiling. Several limitations and challenges associated with conventional therapies, however, are identified, stressing the need for novel therapeutic strategies. The article further discusses molecular targets and therapeutic approaches, i.e., epidermal growth factor receptor inhibitors, hedgehog pathway inhibitors, and PI3K/AKT/mTOR pathway inhibitors, as well as emerging molecular targets and therapeutic agents. The manuscript explores resistance mechanisms to molecularly targeted therapies and proposes methods to overcome them, including combination strategies, rational design, and optimization. The clinical implications and patient outcomes of molecular-targeted treatments are assessed, including response rates and survival outcomes. The management of adverse events and toxicities in molecular-targeted therapies is crucial and requires careful monitoring and control. The paper further discusses future directions for therapeutic advancement and research in this area, as well as the difficulties and constraints associated with conventional therapies.</p>","PeriodicalId":12247,"journal":{"name":"EXCLI Journal","volume":"23 ","pages":"300-334"},"PeriodicalIF":4.6,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11036065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855789","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}
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