A PRELIMINARY STUDY OF THE PALEOLITHIC AND NEOLITHIC CONTRIBUTION THE EUROPEAN MTDNA FLOW IN SHAPING THE GENETIC STRUCTURE OF RECENT BOSNIAN POPULATION

The mitochondrial DNA (mtDNA) polymorphisms in Bosnian human population was analyzed by means of hypervariable segment I and II (HVSI and HVSII) sequencing and restriction fragment-length polymorphism analysis of the mtDNA coding region. The results suggest that shaping the genetic structure of recent Bosnian population likely to be affected by the expansion from the European glacial refuges area at the end of the Last Glacial Maximum (LGM), postglacial expansions from southwestern refuges of Europe, the Italian Peninsula and the dispersion in periods of more recent historical events, from the East European Plain. Especially interesting feature of the Neolithic expansion in this area is the ancient African/South Asian haplogroup N1a with the HVSI variant 16147G, which is almost absent in Europe. The haplotyps HVSI with variant 16147G suggest the colonization of the Northeast Bosnia region by Neolithic communities in the Early Neolithic period of expansion through Europe, as evidenced by the archaeological remains of the Starcevo culture

Investigational Anti SARS-COVID 19 Medication

The newly identified severe acute respiratory syndrome coronavirus-2 (SARS-CoV- 2) that originated in December 2019 in Wuhan, China. By July 2020, the WHO reported over 17 million confirmed cases in over 200 countries around the globe. This review discusses how the COVID-19 pandemic may affect healthy people, structure and replication cycle of SARS- CoV-2; targets and therapeutics SARS- CoV-2 and anti-COVID drugs: strategies and perspectives

Pharmacogenetics- gene and SARS-COVID 19 Medication

An analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes collected from the patients worldwide has identified mutations in the virus that could aid in drug and vaccine development. The researchers found that the virus’s genetic diversity in most countries is similar to what it is globally, suggesting that it was introduced repeatedly by many infected people in each country rather than by a “patient zero.” The genetic analysis found 198 mutations that have occurred more than once. “Mutations in themselves are not a bad thing it is nothing to suggest SARS-CoV-2 is mutating faster or slower than expected. Several factors, including pharmacogenetics, it is possible to contribute to inter-individual variability in drug response. However, till today little is known about the host genetics interaction with infection and COVID-19 progression. To understand the role of host gene, we review the current literature, aggregate readily available genetic resources, and provide some updated analysis relevant to COVID-19 and associated phenotypes

Frequency Distribution and Association of some Morpho- and Physiological Traits in Patients with Lung Diseases in Kosova

The aim of this study was to investigate the distribution of specific phenotypes in patients with lung diseases as well as their eventual association withthe risk of developing lung diseases. For this purpose 2777 patients with lung diseases and 2778 healthy individuals from all over Kosova were examined for the appearance of the following selected phenotypes: ear lobe free (ELF)/ ear lobe attached, normal chin (NC)/cleft chin, tongue roller (TR)/non roller, hand clasping right thumb over (HC)/ hand clasping left thumb over, righthanded (RH)/lefthanded. In addition, the blood group from ABO system and the presence or absence of the Rhesus factor as phenotypical markers were observed. The results obtained show significant differences between control and lung disease patients for NC (P≤0.05) and TR (P≤0.005) as well as for blood groups AB (P≤0.05) and O (P≤0.005). These results point to eventually increased levels of genetic load as a result of the increased homozygosity in some gene loci causing an increased frequency of some recessive phenotypes in patients with lung diseases. Together with the specific associations observed, these preliminary findings could serve as a basis for further in depth investigations with respect to the types of lung diseases, occupational exposure and dietary habits, and thus is expected to contribute to an understanding of predispositions and susceptibility to lung diseases

Epigenetics and treatment of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a disease associated with an impaired autoimmune response; the immune system attacks erroneously own tissues, which leads to inflammation, tissue damage and complement activation. The latter plays a pivotal role in SLE pathology, as complement level is suited as histological marker for disease diagnoses and management. Besides, environmentally factors have been highlighted and their significant contribution for individual genetic predisposition has been pointed out. Here complement factors, their activity and their ability to modify DNA with histone proteins are reviewed; known gene mutations involved in SLE, and new therapeutic approaches suggested for SLE are discussed and summarized, as well

Mucopolysaccharidosis type III (subtype IIIB) diagnosis as a spectrum disorder: A case report from Kosovo

Mucopolysaccharidosis type IIIB (MPS IIIB), also known as Sanfilippo syndrome type B, is a metabolic disease caused by mutations in both alleles of the NAGLU gene encoding for the enzyme α-N-acetylglucosaminidase. A malfunction of this enzyme causes inability to degrade heparan sulfate, which leads to accumulation of glycosaminoglycans in the cells. MPS IIIB is associated with different symptoms such as neurodegeneration, extreme hyperactivity, sleeping problems, aggressive behavior, reduced fear, and cognitive deterioration. The condition is by now not curable. Here we describe a patient with MPS IIIB diagnosed at the age of 5 presenting with communication problems, motor dysfunctions, and speech and sleeping problems. Standard biochemical tests for neurodegenerative disorders and DNA analyses including NAGLU mutation screening were performed. We also did some psychological tests assessing the patient’s communication skills and behavior. The patient was heterozygote for two mutations in the gene NAGLU (Y140C and Ser169fs). Thus, he suffered from MPS IIIB due to two mutations in the disease-causing gene. The patient presented with clear signs and symptoms of MPS IIIB with at least one of the two mutations affecting the α-N-acetylglucosaminidase protein function severely. Here we report the combination of a well-known and previously unreported mutation in the NAGLU gene; this could be dependent on geographical origin of the patient, which needs to be clarified by molecular studies of more MPS IIIB patients from Southeast Europe

A genotyping assay for missense mutation in WISP3 gene associated with childhood onset pseudorheumatoid arthropathy

Introduction: Progressive pseudorheumatoid dysplasia (PPD) is an autosomal recessive genetic disorder reported to be caused by gene alterations of the Wnt1-inducible signaling pathway protein 3 corresponding gene (WISP3) located on chromosome position 6q22.  Up to date, there is only a handful of WISP3 mutations identified in Europe, whereas most mutations are identified in Asia and Middle East.  According to our knowledge, this is the first report of genetic dissection of WISP3 associated with spondyloepiphyseal dysplasia tarda from Bosnia and Herzegovina. Based on clinical examination findings (general manifestations, physical examination, characteristics of their bones on X-ray and laboratory results), an index patient was directed to WISP3 genotyping for confirmation of suspected diagnosis of PPD.Methods: DNA was extracted from peripheral blood leukocytes. All 5 exons and their exon-intron boundaries of the WISP3 gene were amplified by polymerase chain reaction (PCR) and sequenced by Sanger method. Segregation analysis was done to confirm the familial carrier status.Results: A missense mutation (C223G) - homozygous T to G transition at c.667 in exon 4 was identified in index patient. This mutation changed codon CAG to TAG and resulted in a subsequent change of the cysteine to glycine codon. Same mutation was observed in both parents in heterozygous form confirming the familial segregation.Conclusion: Due to its nature, the identified mutation C223G in exon 4 in WISP3 gene is the most probably causative for PPD in described patient. Here we describe the PCR based method for genotyping of specific mutation in WISP3 gene. The identification of this mutation might be a valuable addition to a regional databases on rare genetic variant although a functional analysis should be performed to explain its pathological effect

Genotoxicity Evaluation of Dipotassium -Trioxohydroxytetrafluorotriborate, K2(B3O3F4OH), in Human Lymphocyte Cultures and Mice Reticulocytes

ABSTRACT Genotoxic effects of inorganic molecule dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH), a promising new therapeutic for the epidermal changes treatment, have been evaluated. In vitro analysis included evaluation of genotoxic and cytotoxic potential of K2(B3O3F4OH) in concentrations of 0.01, 0.02, 0.05 and 0.06 mg/mL applying cytokinesis-block micronucleus cytome assay in human lymphocyte culture. With the increase of concentration the frequency of micronuclei elevated but the differences were not significant. Also, there were no significant differences among the frequencies of nuclear buds and nucleoplasmic bridges between controls and treated cultures. Nuclear division index and nuclear division cytotoxycity index values did not reveal significant cytotoxic effect of K2(B3O3F4OH). In vivo genotoxic effects were analyzed on BALB/c mice applying reticulocytes micronucleus assay. K2(B3O3F4OH) was administrated intraperitoneally in final concentrations of 10, 20, 50 and 55 mg/kg. Significant decrease of reticulocytes ratio and increase of micronuclei frequencies against pre-treatments were found for both sampling periods of 48 and 72 hours of the highest applied concentration. This study confirmed that K2(B3O3F4OH) is not genotoxic in tested concentrations in vitro as well as in concentrations lower than 55 mg/kg in vivo. This study presents a reliable basis for further pre-clinical and potential clinical investigations

An intricate rewiring of cancer metabolism via alternative splicing

All human genes undergo alternative splicing leading to the diversity of the proteins. However, in some cases, abnormal regulation of alternative splicing can result in diseases that trigger defects in metabolism, reduced apoptosis, increased proliferation, and progression in almost all tumor types. Metabolic dysregulations and immune dysfunctions are crucial factors in cancer. In this respect, alternative splicing in tumors could be a potential target for therapeutic cancer strategies. Dysregulation of alternative splicing during mRNA maturation promotes carcinogenesis and drug resistance in many cancer types. Alternative splicing (changing the target mRNA 3'UTR binding site) can result in a protein with altered drug affinity, ultimately leading to drug resistance.. Here, we will highlight the function of various alternative splicing factors, how it regulates the reprogramming of cancer cell metabolism, and their contribution to tumor initiation and proliferation. Also, we will discuss emerging therapeutics for treating tumors via abnormal alternative splicing. Finally, we will discuss the challenges associated with these therapeutic strategies for clinical applications

Ribosome-Directed Therapies in Cancer

The human ribosomes are the cellular machines that participate in protein synthesis, which is deeply affected during cancer transformation by different oncoproteins and is shown to provide cancer cell proliferation and therefore biomass. Cancer diseases are associated with an increase in ribosome biogenesis and mutation of ribosomal proteins. The ribosome represents an attractive anti-cancer therapy target and several strategies are used to identify specific drugs. Here we review the role of different drugs that may decrease ribosome biogenesis and cancer cell proliferation