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R. Hadziselimovic

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This document presents strategic guidelines and a development framework aimed at enhancing higher education programs in biotechnology within Bosnia and Herzegovina. It emphasizes the importance of aligning academic curricula, research capacities, and innovation ecosystems with global sustainable development goals (SDGs) and emerging scientific trends. Drawing on insights from the 2025 scientific-expert symposium "Next-Generation Biotechnologists – Skills of Future Educators," this work outlines key recommendations for modernizing educational approaches, strengthening interdisciplinary collaboration, and fostering the next generation of biotechnologists equipped to meet societal and technological challenges. The framework is intended for academic institutions, policymakers, and stakeholders committed to advancing biotechnology education and innovation in the region.

In the early stages of research on the genetics of human morphological traits, particular attention was given to the details of the physical complexities of the face. In this field, prominent focus was placed on the characteristics of the auricle, especially the types of the earlobe (lobulus auriculae). This paper presents the first data on the previously undescribed possibility of inheriting the ossified granules of the antihelix. Based on genealogical analysis of the presence/absence of the granule across five successive generations of a Bosnian family, evidence is provided for the autosomal recessive inheritance of this dimorphism.

G. Temaj, Sarmistha Saha, S. Chichiarelli, Pelin Telkoparan-Akillilar, Nexhibe Nuhii, R. Hadziselimovic, Luciano Saso

Polyploid giant cancer cells (PGCCs) are characterized by enlarged nuclei, association with tumors, and resistance to treatment, contributing significantly to cellular heterogeneity. These cells arise from endoreplication and cell fusion, often triggered by stressors such as radiation and chemotherapy. PGCCs exhibit chromosomal instability and aneuploidy, leading to poor prognosis in various cancers. Key features include the ability to produce progeny cells via amitotic division and the expression of cancer stem cell markers. PGCC formation and function involve signaling pathways like cell fusion (GCM1/syncytin-1), cell cycle control, stress response, and EMT. Understanding these pathways is crucial for identifying therapeutic targets. Current therapeutic strategies targeting PGCCs involve drugs like azacitidine, decitabine, and zoledronic acid, as well as DNMT inhibitors in combination therapies. These approaches aim to reverse drug resistance and enhance antitumor efficacy. Furthermore, microRNAs (miRNAs) are pivotal in regulating gene expression and influencing the cell cycle, proliferation, and apoptosis. Cataloging miRNAs and understanding their function is critical for developing potential cancer treatments. Researchers are exploring miRNA-based modulation of signaling pathways to block tumor growth. This review highlights the complex biology of PGCCs and emphasizes the need for targeted therapies to improve cancer treatment outcomes.

E. Behluli, S. Xharra, H. Nefic, R. Hadziselimovic, G. Temaj

The chemical reactive molecule ROS (Reactive Oxygen Species) is a product of normal cellular metabolism. ROS plays a pivotal role in a wide range of biological processes, including aging, cancer and neurodegenerative diseases. Recent studies have shown that ROS can also affect the ribosomes – molecular machines responsible for protein synthesis.  ROS leads to errors in protein synthesis and the production of misfolded proteins, causing damage to ribosomes. However, it has also been suggested that ROS is implicated in the regulation of the ribosome activity under certain conditions. The aim of this paper is to review current knowledge regarding the effects of ROS on ribosomes, with a focus on the mechanisms by which ROS can cause damage to ribosomes and the potential role of ROS in regulating ribosome activity.

G. Temaj, S. Chichiarelli, Sarmistha Saha, Pelin Telkoparan-Akillilar, Nexhibe Nuhii, R. Hadziselimovic, Luciano Saso

Leukemia represents the most prevalent malignancy in children, constituting 30% of childhood cancer cases, with acute lymphoblastic leukemia (ALL) being particularly heterogeneous. This paper explores the role of alternative splicing in leukemia, highlighting its significance in cancer development and progression. Aberrant splicing is often driven by mutations in splicing-factor genes, which can lead to the production of variant proteins that contribute to oncogenesis. The spliceosome, a complex of small nuclear RNAs and proteins, facilitates RNA splicing, a process critical for generating diverse mRNA and protein products from single genes. Mutations in splicing factors, such as U2AF1, SF3B1, SRSF2, ZRSR2, and HNRNPH1, are frequently observed across various hematological malignancies and are associated with poor prognosis and treatment resistance. This research underscores the necessity of understanding the mechanisms of RNA splicing dysregulation in order to develop targeted therapies to correct these aberrant processes, thereby improving outcomes for patients with leukemia and related disorders.

This research work presents a comprehensive overview of four traits related to the head, with the aim of assessing the statistical phenotypic association among them. The traits examined in this study encompass earlobe type, tongue rugosity, cleft chin and tongue rolling. The primary objective was to investigate the potential associations between these traits and understand their interrelationships. The study focused on examining specific traits in a diverse group of 7431 unrelated individuals, where the genders were almost evenly distributed. To facilitate a comprehensive analysis, three distinct groups were created for each characteristic, comprising the total population, as well as male and female subsets. The selection of subjects was carefully done to ensure a fair representation across different geographical regions within Bosnia and Herzegovina, thereby accurately reflecting the nation's national and ethnic diversity. The association among these traits was assessed for statistical significance using the Chi-squared test, with Fisher's exact test used as a supplementary method to examine the connection between each pair of observed traits. Additionally, the Chi-squared test was applied to examine gender-based differences in the frequencies of the phenotypic characteristics of the head. Following traits were shown to have a statistically significant association: tongue rugosity - tongue rolling, tongue rugosity – earlobe type, cleft chin – earlobe type, cleft chin – tongue rolling and earlobe type – tongue rolling. Investigation into the variations in the frequencies of observed phenotypic traits of the head, with respect to gender, revealed statistically significant results for every trait examined.

V. Graiqevci-Uka, E. Behluli, R. Hadziselimovic, Thomas Liehr, G. Temaj

Introduction: Acute lymphoblastic leukemia (ALL) is the most frequent pediatric leukemia; it can be defined according to chromosomic and genomic data. Cytogenetic analyses and determination of chromosomal numbers (such as hypo- or hyperdiploidy) and/or specific chromosomal rearrangements are basic for ALL classification and treatment. Even though cure rates of childhood ALL are at ~95%, pharmacogenetic aspects are of raising importance. Material and Methods: We have analyzed the literature for ALL subtypes, corresponding therapy options, and pharmacogenetic implications. Results: Data for ALL subtypes such as B-ALL, T-ALL, Ph-like ALL, DS-ALL, ETP-ALL, BCR-ABL1-like ALL are presented here. The gene polymorphism which lead to metabolizability of 6-MP are ITPA variants (94C>A) and IVS2+21A>C, in conjunction with TPMT (238G>C, TPMT*3B 460G>A and *3C 719A>G and NUDT15 (415C>T). For methotrexate metabolism gene polymorphisms are found for gene MTHFR as C677T and A1298C. Conclusion: In the last decade in many hospital laboratories, pharmacogenetic aspects gain more and more importance. Application of many molecular biology methods provided progress in treatment and diagnosis of ALL patients. Combination therapy is proposed as an alternative to single drug treatments.

G. Temaj, S. Chichiarelli, Pelin Telkoparan-Akillilar, Sarmistha Saha, Nexhibe Nuhii, R. Hadziselimovic, Luciano Saso

The tumor suppressor proteins are key transcription factors involved in the regulation of various cellular processes, such as apoptosis, DNA repair, cell cycle, senescence, and metabolism. The tumor suppressor protein p53 responds to different type of stress signaling, such as hypoxia, DNA damage, nutrient deprivation, oncogene activation, by activating or repressing the expression of different genes that target processes mentioned earlier. p53 has the ability to modulate the activity of many other proteins and signaling pathway through protein-protein interaction, post-translational modifications, or non-coding RNAs. In many cancers the p53 is found to be mutated or inactivated, resulting in the loss of its tumor suppressor function and acquisition of new oncogenic properties. The tumor suppressor protein p53 also plays a role in the development of other metabolic disorders such as diabetes, obesity, and fatty liver disease. In this review, we will summarize the current data and knowledge on the molecular mechanisms and the functions of p53 in different pathways and processes at the cellular level and discuss the its implications for human health and disease.

Abdurahim Kalajdžić, N. Pojskić, A. Ahmić, Merima Miralem, Lejla Lasić, M. Dzehverovic, Belma Jusić, A. Pilav, L. Pojskić et al.

ABSTRACT Population genetic studies have shown that the Bosnian-Herzegovinian (B&H) population is a part of the European gene pool, but there has been limited information on the genetic structure of ancient B&H populations. This study aimed to determine the frequency and distribution of mitochondrial DNA (mtDNA) haplogroups for a medieval Bosnian population. Thirty-four samples, excavated from medieval necropolises located within the borders of medieval Bosnia, were analyzed. Sequencing of the mtDNA hypervariable segment 1 (HVS1) region and RFLP analysis were performed for haplogroup determination. All 32 samples were identified as haplogroup H, with subhaplogroups H2a and H5 in 30 and 2 samples, respectively. The frequency of the H haplogroup was significantly different between the studied samples and previous studies of contemporary B&H populations, where the H haplogroup frequency was approximately half that of the ancient population studied here. A significant difference in H haplogroup frequency compared with other medieval populations outside of Bosnia was also observed: the ancient B&H population is most similar to ancient Italians. These results provide insight into the mitochondrial landscape of populations that inhabited the territory of present-day Bosnia and Herzegovina in the Middle Ages. Our study reveals that inhabitants of medieval Bosnia carried genetic lineages that exist today in B&H populations, suggesting continuity of mtDNA haplogroups over a long period of time, regardless of various historical demographic events that shaped the genetic structure of the modern B&H population.

G. Temaj, S. Chichiarelli, Pelin Telkoparan-Akillilar, Sarmistha Saha, Nexhibe Nuhii, R. Hadziselimovic, Luciano Saso

It is known that more than 10% of genetic diseases are caused by a mutation in protein-coding mRNA (premature termination codon; PTC). mRNAs with an early stop codon are degraded by the cellular surveillance process known as nonsense-mediated mRNA decay (NMD), which prevents the synthesis of C-terminally truncated proteins. Up-frameshift-1 (UPF1) has been reported to be involved in the downregulation of various cancers, and low expression of UPF1 was shown to correlate with poor prognosis. It is known that UPF1 is a master regulator of nonsense-mediated mRNA decay (NMD). UPF1 may also function as an E3 ligase and degrade target proteins without using mRNA decay mechanisms. Increasing evidence indicates that UPF1 could serve as a good biomarker for cancer diagnosis and treatment for future therapeutic applications. Long non-coding RNAs (lncRNAs) have the ability to bind different proteins and regulate gene expression; this role in cancer cells has already been identified by different studies. This article provides an overview of the aberrant expression of UPF1, its functional properties, and molecular processes during cancer for clinical applications in cancer. We also discussed the interactions of lncRNA with UPF1 for cell growth during tumorigenesis.

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