Shengyao Ma, Liya Qin, Xinling Wang, Weiyu Wang, Jinfeng Li, Huaijie Wang, Hanyue Li, Xiaoshan Cai, Yang Yang, Meihua Qu
{"title":"The expression of VISTA on CD4+ T cells associate with poor prognosis and immune status in non-small cell lung cancer patients.","authors":"Shengyao Ma, Liya Qin, Xinling Wang, Weiyu Wang, Jinfeng Li, Huaijie Wang, Hanyue Li, Xiaoshan Cai, Yang Yang, Meihua Qu","doi":"10.17305/bjbms.2021.6531","DOIUrl":"https://doi.org/10.17305/bjbms.2021.6531","url":null,"abstract":"<p><p>Besides the two main histologic types of papillary thyroid carcinoma (PTC), the classical PTC (CL-PTC) and the follicular variant PTC (FV-PTC), several other variants are described. The encapsulated FV-PTC variant was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its similarities to benign lesions. Specific molecular signatures, however, are still unavailable. It is well known that improper DNA repair of dysfunctional telomeres may cause telomere-related genome instability. The mechanisms involved in the damaged telomere repair processing may lead to detrimental outcomes, altering the three-dimensional (3D) nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific 3D nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples, and the telomere length of NIFTP overlaps with that of the FTA histotype. In contrast, there was no association between BRAF expression and telomere length in all tested samples. These preliminary findings reinforce the view that NIFTP is closer to non-malignant thyroid nodules and confirm that PTC features short telomeres.</p>","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":" ","pages":"707-715"},"PeriodicalIF":3.4,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39890609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of cerebrospinal fluid neurofilament light chain levels in multiple sclerosis and non-demyelinating diseases of the central nervous system: clinical and biochemical perspective.","authors":"Burak Arslan, Gökçe Ayhan Arslan, Aslı Tuncer, Rana Karabudak, Aylin Sepici Dinçel","doi":"10.17305/bjbms.2021.7326","DOIUrl":"https://doi.org/10.17305/bjbms.2021.7326","url":null,"abstract":"<p><p>The neurofilament light chain (NfL) is a promising biomarker in the diagnosis, prognosis, and treatment response evaluation of neurological diseases. The aims of this study were to compare the cerebrospinal fluid (CSF) NfL levels in multiple sclerosis (MS) and certain non-demyelinating diseases of the central nervous system (NDCNS); to determine the relationship between clinical and radiological features and CSF NfL levels in patients with MS; and to compare the enzyme-linked immunosorbent assay (ELISA) and single molecule array (SIMOA) methods for NfL measurement using paired CSF and serum samples. We retrospectively analyzed the clinical data and performed NfL measurements in CSF and serum samples of newly diagnosed and treatment-naive patients with CNS diseases evaluated between 1 January 2019 and 1 January 2020. Eligible patients were divided into three groups: MS (n=23), differential diagnosis of MS (n=19), and NDCNS (n=42). First, we compared the CSF NfL levels among the three groups using the previously validated CSF ELISA assay. Next, we evaluated the relationship between CSF NfL levels and the clinical and radiological findings in MS group. Finally, we compared CSF and serum samples from patients of the MS groups (paired serum and CSF samples, n=19) using two different methods (ELISA and SIMOA). The CSF NfL level was the highest in the NDCNS group (1169.64 [535.92-5120.11] pg/mL, p=0.025). There was a strong positive correlation between the number of T2 lesions and CSF NfL level (r=0.786, p<0.001) in the MS group. There was excellent consistency between ELISA and SIMOA for CSF samples, but not for serum samples. Our results indicated that CSF NfL levels may also be used in the management of NDCNS and that SIMOA is the most reliable method for serum NfL determination.</p>","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 5","pages":"699-706"},"PeriodicalIF":3.4,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9129914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vojko Kanic, Gregor Kompara, David Suran, Nina Glavnik Poznic
{"title":"Untangling the relationship between hemoglobin, peak troponin level, and mortality in patients with myocardial infarction.","authors":"Vojko Kanic, Gregor Kompara, David Suran, Nina Glavnik Poznic","doi":"10.17305/bjbms.2021.6744","DOIUrl":"https://doi.org/10.17305/bjbms.2021.6744","url":null,"abstract":"<p><p>Patients with a history of myocardial infarction (MI) and lower admission hemoglobin (aHb) levels have a worse outcome than patients with higher aHb, but lower or similar peaks in enzymatic infarct size. Hemoglobin levels are positively correlated with body surface area (BSA), which is positively correlated with cardiac mass. We hypothesized that patients with lower aHb suffer comparatively greater myocardial injury. We examined the relationships between aHb, and troponin (Tn) normalized to BSA (Tn/BSA) and its association with 30-day mortality. Data from 6055 patients, who were divided into seven groups based on their aHb at 10g/L intervals, were analyzed, and the groups were compared. The relationships between aHb and Tn/BSA and between Tn/BSA and 30-day mortality were assessed. Patients with higher aHb levels had greater BSA (p<0.0001). A negative relationship between aHb and log10Tn/BSA was observed in the entire group, and in men and women separately (p<0.0001, p<0.0001, and p=0.013, respectively). The log10Tn/BSA value was associated with 30-day mortality in the entire group, and in men and women separately (p<0.0001, p=0.014, and p<0.0001, respectively). Our finding suggests that a similar peak Tn value in patients with lower aHb means comparatively greater myocardial injury relative to cardiac mass. This hypothesis helps to explain the worse outcomes in patients with lower aHb. According to our findings, troponin should be indexed to BSA to provide comparable information on cardiac injury relative to cardiac mass. Whether this relationship is causal remains to be clarified.</p>","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":" ","pages":"791-797"},"PeriodicalIF":3.4,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39932580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emana Sheikh, Tony Tran, Semir Vranic, Arkene Levy, R Daniel Bonfil
{"title":"Role and significance of c-KIT receptor tyrosine kinase in cancer: A review.","authors":"Emana Sheikh, Tony Tran, Semir Vranic, Arkene Levy, R Daniel Bonfil","doi":"10.17305/bjbms.2021.7399","DOIUrl":"10.17305/bjbms.2021.7399","url":null,"abstract":"<p><p>c-kit is a classical proto-oncogene that encodes a receptor tyrosine kinase (RTK) that responds to stem cell factor (SCF). C-KIT signaling is a critical regulator of cell proliferation, survival, and migration and is implicated in several physiological processes, including pigmentation, hematopoiesis and gut movement. Accumulating evidence suggests that dysregulated c-KIT function, caused by either overexpression or mutations in c-kit, promotes tumor development and progression in various human cancers. In this review, we discuss the most important structural and biological features of c-KIT, as well as insights into the activation of intracellular signaling pathways following SCF binding to this RTK. We then illustrate how different c-kit alterations are associated with specific human cancers and describe recent studies that highlight the contribution of c-KIT to cancer stemness, epithelial-mesenchymal transition and progression to metastatic disease in different experimental models. The impact of tyrosine kinase inhibitors in treating c-KIT-positive tumors and limitations due to their propensity to develop drug resistance are summarized. Finally, we appraise the potential of novel therapeutic approaches targeting c-KIT more selectively while minimizing toxicity to normal tissue.</p>","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 1","pages":"683-698"},"PeriodicalIF":3.1,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47222621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic risk factors in melanoma etiopathogenesis and the role of genetic counseling: A concise review.","authors":"Nikola Serman, Semir Vranic, Mislav Glibo, Ljiljana Serman, Zrinka Bukvic Mokos","doi":"10.17305/bjbms.2021.7378","DOIUrl":"10.17305/bjbms.2021.7378","url":null,"abstract":"<p><p>Melanoma is a highly aggressive cancer originating from melanocytes. Its etiopathogenesis is strongly related to genetic, epigenetic, and environmental factors. Melanomas encountered in clinical practice are predominantly sporadic, whereas hereditary melanomas account for approximately 10% of the cases. Hereditary melanomas mainly develop due to mutations in the CDKN2A gene, which encodes two tumor suppressor proteins involved in the cell cycle regulation. CDKN2A, along with CDK4, TERT, and POT1 genes, is a high-risk gene for melanoma. Among the genes that carry a moderate risk are MC1R and MITF, whose protein products are involved in melanin synthesis. The environment also contributes to the development of melanoma. Patients at risk of melanoma should be offered genetic counseling to discuss genetic testing options and the importance of skin UV protection, avoidance of sun exposure, and regular preventive dermatological examinations. Although cancer screening cannot prevent the development of the disease, it allows for early diagnosis when the survival rate is the highest.</p>","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 1","pages":"673-682"},"PeriodicalIF":3.4,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47732799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Timur Cerić, Emir Sokolović, Berisa Hasanbegović, Anes Pašić, Zdenka Gojković, Jelena Vladičić Mašić, Nikolina Dukić, Inga Marijanović, Alma Mekić Abazović, Ibrahim Šišić, Dijana Koprić, Mustafa Hammami, Senad Bajramović, Taib Delić, Semir Bešlija
{"title":"The Oncology Association of Bosnia and Herzegovina's recommendations for fertility preservation in oncologic patients.","authors":"Timur Cerić, Emir Sokolović, Berisa Hasanbegović, Anes Pašić, Zdenka Gojković, Jelena Vladičić Mašić, Nikolina Dukić, Inga Marijanović, Alma Mekić Abazović, Ibrahim Šišić, Dijana Koprić, Mustafa Hammami, Senad Bajramović, Taib Delić, Semir Bešlija","doi":"10.17305/bjbms.2021.6977","DOIUrl":"10.17305/bjbms.2021.6977","url":null,"abstract":"<p><p>Malignancy is one of the major public health problems in Bosnia and Herzegovina. Along with breakthroughs in specific oncological therapy, improving the quality of life of cancer patients and management of therapy-induced side effects need to be recognized as a priority in the comprehensive cancer patient care. Fertility loss after cancer treatment is a field requiring special attention due to its various consequences on patients themselves. Although oncofertility is well-recognized area of oncology, low- to middle-income countries are facing issues with its implementation in everyday practice. Increased awareness about fertility preservation is of high priority for all specialists who participate in the medical care of cancer patients. The absence of a systemic solution and lack of expertise led to the founding of Fertility Preservation Working Group of the Oncology Association of Bosnia and Herzegovina. We have made recommendationsas an expert consensus with the ultimate goal of making the first step towards enhancement of oncofertility implementation in Bosnia and Herzegovina.</p>","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 1","pages":"646-650"},"PeriodicalIF":3.4,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48638435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Refat M Nimer, Omar F Khabour, Samer F Swedan, Hassan M Kofahi
{"title":"The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization.","authors":"Refat M Nimer, Omar F Khabour, Samer F Swedan, Hassan M Kofahi","doi":"10.17305/bjbms.2021.7009","DOIUrl":"10.17305/bjbms.2021.7009","url":null,"abstract":"<p><p>The COVID-19 pandemic has caused a global public health emergency. Nutritional status is suggested to be related to the severity of COVID-19 infection. Herein, we aimed to explore the impact of using vitamin and mineral supplements prior to COVID-19 infection on disease severity and hospitalization. In addition, the prior use of aspirin as an anticoagulant on the disease severity was investigated. A cross-sectional, self-administered survey was conducted between March and July 2021. Recovered COVID-19 individuals (age ≥ 18 years, n = 2148) were recruited in the study. A multivariate logistic regression was used to evaluate the associations of supplements and aspirin use with COVID-19 disease severity and hospitalization status. Among the participants, 12.1% reported symptoms consistent with severe COVID-19, and 10.2% were hospitalized due to COVID-19. After adjustment for confounding variables (age, gender, BMI, cigarette smoking status, and the number of comorbidities), the multivariate logistic regression model showed that the consumption of vitamin D supplements prior to COVID-19 infection was associated with a significant decrease in disease severity (OR = 0.68, 95% CI 0.50 - 0.92; P = 0.01), and a lower risk of hospitalization (OR = 0.64, 95% CI 0.45 - 0.89; P = 0.01). On the other hand, there were no significant differences in the frequencies of severe illness and hospitalizations with the consumption of vitamin A, folic acid, vitamin B12, vitamin B complex, vitamin C, zinc, iron, selenium, calcium, magnesium, omega 3, and aspirin before COVID-19 infection. Among the investigated nutrients, the use of vitamin D prior to COVID-19 infection was associated with reduced disease severity and hospitalization. However, more studies are required to confirm this finding.</p>","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 1","pages":"826-832"},"PeriodicalIF":3.1,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43284336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yipeng Xu, Gabriela Pachnikova, He Wang, Yaoyao Wu, Dorothea Przybilla, Reinhold Schäfer, Zihao Chen, Shaoxing Zhu, Ulrich Keilholz
{"title":"IC50: an unsuitable measure for large-sized prostate cancer spheroids in drug sensitivity evaluation.","authors":"Yipeng Xu, Gabriela Pachnikova, He Wang, Yaoyao Wu, Dorothea Przybilla, Reinhold Schäfer, Zihao Chen, Shaoxing Zhu, Ulrich Keilholz","doi":"10.17305/bjbms.2022.7279","DOIUrl":"https://doi.org/10.17305/bjbms.2022.7279","url":null,"abstract":"<p><p>Preclinical models of tumors have the potential to become valuable tools for commercial drug research and development, and 3D culture systems are gaining traction in this area, particularly in prostate cancer (PCa) research. However, nearly all 3D drug design and screening assessments are based on 2D experiments, suggesting limitations of 3D drug testing. To simulate the natural response of human cells to the drug, we detected the half-maximal inhibitory concentration (IC50) changes of 2D/3D LNCaP cells in the drug docetaxel, as well as the sensitivity of different morphologies of 2D/3D LNCaP to docetaxel treatment. In contrast to 2D LNCaP cells, the evaluation of LNCaP spheroids' susceptibility to treatment was more complicated; the fitness of IC50 curves of 2D and 3D tumor cell preclinical models differs significantly. IC50 curves were unsuitable for large-sized LNCaP spheroids. More evaluation indexes (such as max inhibition) and experiments (such as spheroids formation) should be explored and performed to evaluate the susceptibility systematically.</p>","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 4","pages":"580-592"},"PeriodicalIF":3.4,"publicationDate":"2022-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9392968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10643734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulatory aspects of biological medicines in Bosnia and Herzegovina.","authors":"Biljana Tubić, Saša Jungić","doi":"10.17305/bjbms.2021.6910","DOIUrl":"10.17305/bjbms.2021.6910","url":null,"abstract":"<p><p>The use of the biological medicines, also called \"biologics,\" has contributed to the progress of the treatment of many chronic diseases, such as cancer, rheumatoid arthritis, Crohn's disease, multiple sclerosis, and psoriasis. However, biologicals are expensive for healthcare systems in several countries. Their availability has been a global issue, which has affected many patients that suffer from various diseases. A biosimilar medicine, also called \"biosimilar,\" is a medicine with similar characteristics in terms of quality, biological activity, safety, and efficacy as the approved original biological medicine, known as \"originator biologic.\" Biosimilars generate competition within the market because they lower the prices of biologics and thus allow for an increase in patient access. However, there are barriers when it comes to the acceptability rate of biosimilars and how interchangeable they are with the originator biologic. In this review, we present a national regulatory framework for biologics along with its limitations, a system of monitoring the safety profile of biologics, the guideline for interchangeability, and a list of approved and available biologics in Bosnia and Herzegovina. Additionally, recommendations were made here in order to provide opportunities for greater acceptance of biosimilars and better access to biologics. These recommendations include, but are not limited to, strengthening the national regulatory framework for biologics, capacity building, increasing awareness among healthcare providers for reporting adverse drug events and active pharmacovigilance, and better definitions of interchangeability. Finally, awareness among healthcare providers regarding biosimilars and biologics should be raised through continuous education and workshops, and by including this important topic in the graduate and postgraduate curriculum programs in the country.</p>","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":"22 1","pages":"511-522"},"PeriodicalIF":3.1,"publicationDate":"2022-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9392977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49184656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vedrana Mužić Radović, Paula Bunoza, Tihana Marić, Marta Himelreich-Perić, Floriana Bulić-Jakuš, Marta Takahashi, Gordana Jurić-Lekić, Nino Sinčić, Davor Ježek, Ana Katušić-Bojanac
{"title":"Global DNA methylation and chondrogenesis of rat limb buds in a three-dimensional organ culture system.","authors":"Vedrana Mužić Radović, Paula Bunoza, Tihana Marić, Marta Himelreich-Perić, Floriana Bulić-Jakuš, Marta Takahashi, Gordana Jurić-Lekić, Nino Sinčić, Davor Ježek, Ana Katušić-Bojanac","doi":"10.17305/bjbms.2021.6584","DOIUrl":"https://doi.org/10.17305/bjbms.2021.6584","url":null,"abstract":"<p><p>Although DNA methylation epigenetically regulates development, data on global DNA methylation during development of limb buds (LBs) are scarce. We aimed to investigate the global DNA methylation developmental dynamics in rat LBs cultivated in a serum-supplemented (SS) and in chemically defined serum- and protein-free (SF) three-dimensional organ culture. Fischer rat front- and hind-LBs at 13th and 14th gestation days (GD) were cultivated at the air-liquid interface in Eagle's Minimal Essential Medium (MEM) or MEM with 50% rat serum for 14 days, as SF and SS conditions, respectively. The methylation of repetitive DNA sequences (SINE rat ID elements) was assessed by pyrosequencing. Development was evaluated by light microscopy and extracellular matrix glycosaminoglycans staining by Safranin O. Upon isolation, weak Safranin O staining was present only in more developed GD14 front-LBs. Chondrogenesis proceeded well in all cultures towards day 14, except in the SF-cultivated GD13 hind-LBs, where Safranin O staining was almost absent on day 3. That was associated with a higher percentage of DNA methylation than in SF-cultivated GD13 front-LBs on day three. In SF-cultivated front-LBs, a significant methylation increase between the 3rd and 14th day was detected. In SS-cultivated GD13 front-LBs, methylation increased significantly on day three and then decreased. In older GD14 SS-cultivated LBs, there was no increase of DNA methylation, but they were significantly hypomethylated relative to the SS-cultivated GD13 at days 3 and 14. We confirmed that the global DNA methylation increase is associated with less developed limb organ primordia that strive towards differentiation in vitro, which is of importance for regenerative medicine strategies.</p>","PeriodicalId":9147,"journal":{"name":"Bosnian journal of basic medical sciences","volume":" ","pages":"560-568"},"PeriodicalIF":3.4,"publicationDate":"2022-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9392980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39637871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}