İrem Kiriş, Merve Karayel Başar, Büşra Gürel, Tomasz Mroczek, Ahmet Tarık Baykal
{"title":"O-demethyl galantamine alters protein expression in cerebellum of 5xFAD mice.","authors":"İrem Kiriş, Merve Karayel Başar, Büşra Gürel, Tomasz Mroczek, Ahmet Tarık Baykal","doi":"10.55730/1300-0152.2692","DOIUrl":"https://doi.org/10.55730/1300-0152.2692","url":null,"abstract":"<p><strong>Background/aim: </strong>Alzheimer's disease (AD), one of the most common health issues, is characterized by memory loss, severe behavioral disorders, and eventually death. Despite many studies, there are still no drugs that can treat AD or stop it from progressing. Previous in vitro tests showed that O-demethyl galantamine (ODG) might have therapeutic potential owing to its 10 times higher acetylcholinesterase inhibitory activity than galantamine (GAL).</p><p><strong>Materials and methods: </strong>We aimed to assess the effect of ODG at the molecular level in a 12-month-old 5xFAD Alzheimer's mouse model. To this end, following the administrations of ODG and GAL (used as a positive control), protein alterations were investigated in the cortex, hippocampus, and cerebellum regions of the brain. Surprisingly, GAL altered proteins prominently in the cortex, while ODG exclusively exerted its effect on the cerebellum.</p><p><strong>Results: </strong>GNB1, GNB2, NDUFS6, PAK2, and RhoA proteins were identified as the top 5 hub proteins in the cerebellum of ODG-treated mice. Reregulation of these proteins through Ras signaling and retrograde endocannabinoid signaling pathways, which were found to be enriched, might contribute to reversing AD-induced molecular changes.</p><p><strong>Conclusion: </strong>We suggest that, since it targets specifically the cerebellum, ODG may be further evaluated for combination therapies for AD.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"48 3","pages":"163-173"},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dilek Demircan Çeker, Volkan Baysungur, Serdar Evman, İlker Kolbaş, Abdurrahim Gördebil, Sinem M Nalbantoğlu, Yusuf Tambağ, Ömer Kaçar, Ahmet Midi, Hatice Aslanoğlu, Nülüfer Kara, Nilgün Algan, Ayberk Boyacioğlu, Betül Karademir Yilmaz, Ali Şahin, Hivda Ülbeği Polat, Abidin Şehitoğullari, Ali Osman Çibikdiken, Mücahit Büyükyilmaz, İbrahim Berkan Aydilek, Abdulkerim Eneş, Sevde Küçüker, Fatih Karakaya, İhsan Boyaci, Mahmut Gümüş, Onur Şenol, Merve Öztuğ, Evren Saban, Ömer Soysal, Nur Büyükpinarbaşili, Akif Turna, Mehmet Zeki Günlüoğlu, Aslı Çakir, Şaban Tekin, Uygar Tazebay, Abdullah Karadağ
{"title":"LUNGBANK: a novel biorepository strategy tailored for comprehensive multiomics analysis and P-medicine applications in lung cancer.","authors":"Dilek Demircan Çeker, Volkan Baysungur, Serdar Evman, İlker Kolbaş, Abdurrahim Gördebil, Sinem M Nalbantoğlu, Yusuf Tambağ, Ömer Kaçar, Ahmet Midi, Hatice Aslanoğlu, Nülüfer Kara, Nilgün Algan, Ayberk Boyacioğlu, Betül Karademir Yilmaz, Ali Şahin, Hivda Ülbeği Polat, Abidin Şehitoğullari, Ali Osman Çibikdiken, Mücahit Büyükyilmaz, İbrahim Berkan Aydilek, Abdulkerim Eneş, Sevde Küçüker, Fatih Karakaya, İhsan Boyaci, Mahmut Gümüş, Onur Şenol, Merve Öztuğ, Evren Saban, Ömer Soysal, Nur Büyükpinarbaşili, Akif Turna, Mehmet Zeki Günlüoğlu, Aslı Çakir, Şaban Tekin, Uygar Tazebay, Abdullah Karadağ","doi":"10.55730/1300-0152.2696","DOIUrl":"https://doi.org/10.55730/1300-0152.2696","url":null,"abstract":"<p><strong>Background/aim: </strong>LUNGBANK was established as part of Project LUNGMARK, pioneering a biorepository dedicated exclusively to lung cancer research. It employs cutting-edge technologies to streamline the handling of biospecimens, ensuring the acquisition of high-quality samples. This infrastructure is fortified with robust data management capabilities, enabling seamless integration of diverse datasets. LUNGBANK functions not merely as a repository but as a sophisticated platform crucial for advancing lung cancer research, poised to facilitate significant discoveries.</p><p><strong>Materials and methods: </strong>LUNGBANK was meticulously designed to optimize every stage of biospecimen handling, from collection and storage to processing. Rigorous standard operating procedures and stringent quality control measures guarantee the integrity of collected biospecimens. Advanced data management protocols facilitate the efficient integration and analysis of various datasets, enhancing the depth and breadth of research possibilities in lung cancer.</p><p><strong>Results: </strong>LUNGBANK has amassed a comprehensive collection of biospecimens essential for unraveling the intricate molecular mechanisms of lung cancer. The integration of state-of-the-art technologies ensures the acquisition of top-tier data, fostering breakthroughs in translational and histological research. Moreover, the establishment of patient-derived systems by LUNGBANK underscores its pivotal role in personalized medicine approaches.</p><p><strong>Conclusion: </strong>The establishment of LUNGBANK marks a significant milestone in addressing the critical challenges of lung cancer research. By providing researchers with high-quality biospecimens and advanced research tools, LUNGBANK not only supports Project LUNGMARK's objectives but also contributes extensively to the broader landscape of personalized medicine. It promises to enhance our understanding of lung cancer initiation, progression, and therapeutic interventions tailored to individual patient needs, thereby advancing the field towards more effective diagnostic and therapeutic strategies.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"48 3","pages":"203-217"},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The apoptotic effect of garlic <i>(Allium sativum)</i> derived SEVs on different types of cancer cell lines in vitro.","authors":"Naz Ünsal, Polen Koçak Denizci, Hazal Yilmaz, Fikrettin Şahin, Merve Yildirim Canpolat","doi":"10.55730/1300-0152.2694","DOIUrl":"https://doi.org/10.55730/1300-0152.2694","url":null,"abstract":"<p><strong>Background/aim: </strong>Small extracellular vesicles (SEVs) are known to have an impact on the physiological conditions of target cells, are a critical component of cell-to-cell communication, and have been implicated in a variety of diseases. Although it has been proposed that edible plant-derived nanoparticles have an effect on communication with mammalian cells, the influence of these nanoparticles on cancer cell development has yet to be explored.</p><p><strong>Materials and methods: </strong>In order to characterize small extracellular vesicles obtained from garlic, specific SEV surface markers, antibodies, and size detections were identified using scanning electron microscopy and nanoparticle tracking analysis. Human hepatoma (Hep3B), human neuroblastoma (SH-SY5Y), human pancreatic adenocarcinoma (Panc-1a), human glioblastoma (U87), prostate cancer (PC-3), and human umbilical vein endothelial (HUVEC) cell lines were treated with garlic SEVs to examine their anticancer properties.</p><p><strong>Results: </strong>Annexin V FITC/PI staining for apoptosis, mRNA, and protein expression levels via RT-PCR and ELISA indicated that garlic SEVs triggered apoptosis by activating the intrinsic pathway. Our findings support the idea that SEVs produced from garlic may trigger apoptotic cell death in cancer cells while having no effect on healthy cells.</p><p><strong>Conclusion: </strong>It was discovered that plant SEVs had anti-cancer effects by activating caspase-mediated apoptosis.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"48 3","pages":"182-191"},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ayca Ece Nezir, Zeynep Büşra Bolat, Ongun Mehmet Saka, Itır Ebru Zemheri, Sevgi Gülyüz, Umut Uğur Özköse, Özgür Yilmaz, Asuman Bozkir, Fikrettin Şahin, Dilek Telci
{"title":"PEtOx-DOPE nanoliposomes functionalized with peptide 563 in targeted <i>BikDDA</i> delivery to prostate cancer.","authors":"Ayca Ece Nezir, Zeynep Büşra Bolat, Ongun Mehmet Saka, Itır Ebru Zemheri, Sevgi Gülyüz, Umut Uğur Özköse, Özgür Yilmaz, Asuman Bozkir, Fikrettin Şahin, Dilek Telci","doi":"10.55730/1300-0152.2693","DOIUrl":"https://doi.org/10.55730/1300-0152.2693","url":null,"abstract":"<p><strong>Background: </strong>Nanocarrier-based systems have cultivated significant improvements in prostate cancer therapy. However, the efforts are still limited in clinical applicability, and more research is required for the development of effective strategies. Here, we describe a novel nanoliposomal system for targeted apoptotic gene delivery to prostate cancer.</p><p><strong>Methods: </strong>Poly (2-ethyl-2-oxazoline) (PEtOx) dioleoyl phosphatidylethanolamine (DOPE) nanoliposomes were conjugated with the prostate-specific membrane antigen (PSMA)-targeting peptide GRFLTGGTGRLLRIS (P563) and loaded with <i>BikDDA</i>, a mutant form of the proapoptotic Bik. We selected 22Rv1 cells with moderate upregulation of PSMA to test the in vitro uptake, cell death, and in vivo anticancer activity of our formulation, P563-PEtOx-DOPE-BikDDA.</p><p><strong>Results: </strong><i>BikDDA</i> was upregulated in 22Rv1 cells, inducing cell death, and CD-1 nude mice xenografts administered with the formulation showed significant tumor regression.</p><p><strong>Conclusion: </strong>We suggest that P563-PEtOx-DOPE-BikDDA nanoliposomes can serve as prominent gene carriers against prostate cancer.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"48 3","pages":"174-181"},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Merve Öztuğ, Evren Kilinç, Zeynep A Öztuğ Durer, Emel Baloğlu
{"title":"Proteomic investigation of acute and chronic hypoxia/reoxygenation responsive proteins and pathways in H9C2 cardiomyoblasts.","authors":"Merve Öztuğ, Evren Kilinç, Zeynep A Öztuğ Durer, Emel Baloğlu","doi":"10.55730/1300-0152.2695","DOIUrl":"https://doi.org/10.55730/1300-0152.2695","url":null,"abstract":"<p><strong>Background/aim: </strong>Ischemic heart diseases continue to be a significant global cardiovascular problem in today's world. Myocardial reperfusion (R) is provided with an effective and rapid treatment; however, it can lead to fatal results, as well as ischemia (I). This study aims to use proteomic analysis to assess proteins and pathways in H9C2 cardiomyoblast cells exposed to hypoxic conditions, followed by reoxygenation, representing I/R injury for both short and long terms, reflecting acute and chronic hypoxia, respectively. Utilizing advanced techniques, our goal is to identify and characterize key proteins undergoing alterations during these critical phases.</p><p><strong>Materials and methods: </strong>H9C2 cardiomyoblasts, a commonly used cell line for simulating in vivo I/R damage, were exposed to normoxia and hypoxia (0.4% O<sub>2</sub>) in six experimental groups: normoxia (3h), acute hypoxia (3h), acute hypoxia (3h) + reoxygenation (3h), normoxia (21h), chronic hypoxia (21h), and chronic hypoxia (21h) + reoxygenation (3h). Analyses were conducted using Nano LC/MSMS from tryptic digest of the whole cell lysates. Proteins were quantified using the label-free quantification (LFQ) algorithm in Proteome Discoverer 2.4.</p><p><strong>Results: </strong>Proteomic analysis resulted in identification of 2383 protein groups. Proteins that differentially expressed in the various groups were identified (p < 0.05 among mean values for groups). Short-term hypoxia induces mitochondrial damage, energy demand, and cytoskeletal modifications. Chronic hypoxia triggers metabolic shifts, stress-response proteins, and extracellular matrix alterations. Data are available via ProteomeXchange with identifier PXD047994.</p><p><strong>Conclusion: </strong>Our research provides in-depth insights into how H9C2 cardiomyoblasts respond to both short-term and prolonged oxygen deprivation. Understanding hypoxia-related pathophysiology provides avenues for therapeutic intervention in hypoxia-related disorders.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"48 3","pages":"192-202"},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Süheyla Pınar Çelik, Damla Nur Parilti, Leyla Açik, Mehmet Muhittin Yalçin, İlhan Yetkin, Eldeniz Yunusov
{"title":"NAMPT, IL-6, and vaspin gene expressions and serum protein levels in type 2 diabetes mellitus and related complication.","authors":"Süheyla Pınar Çelik, Damla Nur Parilti, Leyla Açik, Mehmet Muhittin Yalçin, İlhan Yetkin, Eldeniz Yunusov","doi":"10.55730/1300-0152.2688","DOIUrl":"https://doi.org/10.55730/1300-0152.2688","url":null,"abstract":"<p><strong>Background/aim: </strong>Type 2 diabetes mellitus (T2DM) is the most common type of diabetes and occurs due to insufficient insulin secretion or inability to use existing insulin and the effects of environmental factors. Although there are many studies on the pathophysiology of T2DM, the mechanisms contributing to the pathogenesis of insulin resistance and pancreatic beta-cell dysfunction have not been completely elucidated. Some adipokines secreted from adipose tissue, which are the primary regulators of insulin resistance, affect immune and inflammatory functions. Altered adipokine profiles have been observed in obesity and T2DM, leading to severe metabolic risks and changes in insulin sensitivity.</p><p><strong>Materials and methods: </strong>This study used quantitative PCR and ELISA techniques to analyze samples from individuals without diabetes (control group) and with T2DM (macrovascular and microvascular complications and without complications) for at least 10 years.</p><p><strong>Results: </strong>The mRNA expression and protein levels of NAMPT, IL-6, and vaspin genes were determined. While there was no significant difference in NAMPT, IL-6, and vaspin mRNA expression levels between diabetic groups, there was a significant decrease between the patient and control groups (p < 0.001). For serum protein levels, NAMPT protein levels decreased significantly in the uncomplicated group, while IL-6 and vaspin protein levels increased significantly in both microvascular and macrovascular complication groups (p < 0.001).</p><p><strong>Conclusion: </strong>The correlations between gene expressions, clinical parameters, and protein levels are crucial to understanding the implications of the findings.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"48 2","pages":"133-141"},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nonsmall-cell lung cancer treatment: current status of drug repurposing and nanoparticle-based drug delivery systems.","authors":"Tuğba Gül Inci, Serap Acar, Dilek Turgut-Balik","doi":"10.55730/1300-0152.2687","DOIUrl":"https://doi.org/10.55730/1300-0152.2687","url":null,"abstract":"<p><p>Drug repurposing is the strategy of drug utilization for a treatment option other than the intended indications. This strategy has witnessed increased adoption over the past decades, especially within cancer nanomedicine. Cancer nanomedicine has been facilitated through nanoparticle-based (NP-based) delivery systems which can combat nonsmall-cell lung cancer (NSCLC) via recent advances in nanotechnology and apply its benefits to existing drugs. The repurposing of drugs, coupled with NP-based drug delivery systems, presents a promising avenue for achieving effective therapeutic solutions with accelerated outcomes. This review aims to present an overview of NSCLC treatments, with a specific focus on drug repurposing. It seeks to elucidate the latest advances in clinical studies and the utilization of NP-based drug delivery systems tailored for NSCLC treatment. First, the molecular mechanisms of Food and Drug Administration (FDA)-approved drugs for NSCLC, including ROS1 tyrosine kinase inhibitors (TKI) like repotrectinib, approved in November 2023, are detailed. Further, in vitro studies employing a combination strategy of drug repurposing and NP-based drug delivery systems as a treatment approach against NSCLC are listed. It includes the latest study on nanoparticle-based drug delivery systems loaded with repurposed drugs.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"48 2","pages":"112-132"},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A novel algorithm for the virtual screening of extensive small molecule libraries against ERCC1/XPF protein-protein interaction for the identification of resistance-bypassing potential anticancer molecules.","authors":"Salma Ghazy, Lalehan Oktay, Serdar Durdaği","doi":"10.55730/1300-0152.2686","DOIUrl":"https://doi.org/10.55730/1300-0152.2686","url":null,"abstract":"<p><strong>Background and aim: </strong>Cancer cell's innate chemotherapeutic resistance continues to be an obstacle in molecular oncology. This theory is firmly tied to the cancer cells' integral DNA repair mechanisms continuously neutralizing the effects of chemotherapy. Amidst these mechanisms, the nuclear excision repair pathway is crucial in renovating DNA lesions prompted by agents like Cisplatin. The ERCC1/XPF complex stands center-stage as a structure-specific endonuclease in this repair pathway. Targeting the ERCC1/XPF dimerization brings forth a strategy to augment chemotherapy by eschewing the resistance mechanism integral to cancer cells. This study tracks and identifies small anticancer molecules, with ERCC1/XPF inhibiting potential, within extensive small-molecule compound libraries.</p><p><strong>Materials and methods: </strong>A novel hybrid virtual screening algorithm, conjoining ligand- and target-based approaches, was developed. All-atom molecular dynamics (MD) simulations were then run on the obtained hit molecules to reveal their structural and dynamic contributions within the binding site. MD simulations were followed by MM/GBSA calculations to qualify the change in binding free energies of the protein/ligand complexes throughout MD simulations.</p><p><strong>Results: </strong>Conducted analyses highlight new potential inhibitors AN-487/40936989 from the SPECS SC library, K219-1359, and K786-1161 from the ChemDiv Representative Set library as showing better predicted activity than previously discovered ERCC1/XPF inhibitor, CHEMBL3617209.</p><p><strong>Conclusion: </strong>The algorithm implemented in this study expands our comprehension of chemotherapeutic resistance and how to overcome it through identifying ERCC1/XPF inhibitors with the aim of enhancing chemotherapeutic impact giving hope for ameliorated cancer treatment outcomes.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"48 2","pages":"91-111"},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"miR-770-5p-induced cellular switch to sensitize trastuzumab resistant breast cancer cells targeting HER2/EGFR/IGF1R bidirectional crosstalk.","authors":"Senem Noyan, Bala Gür Dedeoğlu","doi":"10.55730/1300-0152.2690","DOIUrl":"https://doi.org/10.55730/1300-0152.2690","url":null,"abstract":"<p><strong>Background/aim: </strong>Studies highlighted the bidirectional crosstalk between the HER family members in breast cancer as resistance mechanism to anti-HER agents. Cross-signaling between HER2/EGFR and ER/IGF1R could play role in the development of resistance to therapeutics hence stimulating cell growth. To overcome this resistance, combined therapies targeting both pathways simultaneously have been proposed as an effective strategy. The involvement of miRNAs in resistance of targeted therapies like trastuzumab was demonstrated in recent studies. Hence the regulation of miRNAs in resistance state could reverse the cell behaviour to drugs. Previously we found that overexpression of miR-770-5p downregulated AKT and ERK expression through HER2 signaling and potentiated the effect of trastuzumab. In this study we examined the impact of miR-770-5p on trastuzumab resistance.</p><p><strong>Materials and methods: </strong>Cells were treated with tamoxifen or trastuzumab to examine their role in bidirectional crosstalk. The molecule mechanism of miR-770-5p on HER2/EGFR/IGF1R bidirectional crosstalk was explored by western blot. The expression of miR-770-5p in trastuzumab resistant cells was examined by q-PCR. To investigate the effect of miR-770-5p on cancer cell proliferation in trastuzumab resistance state, resistant cells were analyzed by iCELLigence real-time cell analyzer.</p><p><strong>Results: </strong>miR-770-5p expression was significantly downregulated in trastuzumab-resistant BT-474 and SK-BR-3 cells. Overexpression of miR-770-5p sensitized the resistant cells to trastuzumab, as evidenced by reduced cell proliferation and increased cell viability. Additionally, in resistant cells, increased expression and activation of EGFR and IGF1R were observed. However, miR-770-5p overexpression resulted in decreased phosphorylation of AKT and ERK, indicating its suppressive role in EGFR/HER2 signaling. Furthermore, miR-770-5p downregulated the expression of IGF1R and mTOR, suggesting its involvement in regulating the escape signaling mediated by IGF1R in resistance.</p><p><strong>Conclusion: </strong>In conclusion, our findings demonstrate the critical role of miR-770-5p in regulating bidirectional crosstalk and overcoming trastuzumab resistance in breast cancer cells. These results highlight the potential of miR-770-5p as a therapeutic target to improve the efficacy of targeted therapies and address resistance mechanisms in breast cancer.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"48 2","pages":"153-162"},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Deep learning in bioinformatics.","authors":"Malik Yousef, Jens Allmer","doi":"10.55730/1300-0152.2671","DOIUrl":"https://doi.org/10.55730/1300-0152.2671","url":null,"abstract":"<p><p>Deep learning is a powerful machine learning technique that can learn from large amounts of data using multiple layers of artificial neural networks. This paper reviews some applications of deep learning in bioinformatics, a field that deals with analyzing and interpreting biological data. We first introduce the basic concepts of deep learning and then survey the recent advances and challenges of applying deep learning to various bioinformatics problems, such as genome sequencing, gene expression analysis, protein structure prediction, drug discovery, and disease diagnosis. We also discuss future directions and opportunities for deep learning in bioinformatics. We aim to provide an overview of deep learning so that bioinformaticians applying deep learning models can consider all critical technical and ethical aspects. Thus, our target audience is biomedical informatics researchers who use deep learning models for inference. This review will inspire more bioinformatics researchers to adopt deep-learning methods for their research questions while considering fairness, potential biases, explainability, and accountability.</p>","PeriodicalId":94363,"journal":{"name":"Turkish journal of biology = Turk biyoloji dergisi","volume":"47 6","pages":"366-382"},"PeriodicalIF":0.0,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11045206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}