Micropropagation as Means of Rapid Multiplication of Newly Developed Blackberry and Black Currant Cultivars

Newly developed blackberry cultivar Čačanska bestrna was successfully micropropagated. For black currant, cv Čačanska crna further research should be done to optimize conditions for successful multiplication. Buds from the branches cut during dormancy (end of January) were used as the initial explants and set to develop under laboratory conditions at room temperature. Aseptic culture was established on Murashige and Skoog (MS) medium with BA 2.0, IBA 0.5 and GA3 0.1 mg 1-1. MS media with BA and IBA or NAA and GA3 were used for multiplication phase, whereas medium MS with mineral salts reduced to 1/2, organic complex unchanged according to MS, with 1.0 mg 1-1 IBA, 0.1 mg 1-1 GA3 and 1g 1-1 of active charcoal was used in the rooting phase. Well developed root system and high quality of rooted plants induced a high percentage of acclimatization (100%) of cv Čačanska bestrna under the ‘myst’ system in greenhouse whereas the percentage of acclimatization of cv Čačanska crna was low, 40%

Regular Dog-Walking Improves Physical Capacity in Elderly Patients after Myocardial Infarction

Various positive effects of pet ownership on cardiovascular health are well known. The aim of this prospective and controlled longitudinal study was to determine the effects of everyday dog-walking on physical capacity in elderly patients during the first year after myocardial infarction. Regularly dog-walking for at least 15 minutes three times a day is related to significantly higher work load on the bicycle exercise test (72.5 ± 10.75 versus 67.6 ± 11.6 W, p<0.05) in the »dog-walking« group (N=29, mean age 72.5 years) at 12 months compared to the control group (N=30, mean age 71.7 years). Our results suggest that dogs may help to maintain continuous physical activity in elderly cardiovascular patients promoting their physical capacity. Further researches are needed to confirm this association as well to identify other possible influences of dog ownership on the cardiovascular health and on the outcome in patients after myocardial infarction

RETROSPECTIVE ANALYSIS ABOUT THE INJURIES IN KINESIOLOGY STUDENTS – COMPARISON OF TWO STUDY PROGRAMS

Glavni cilj ovog istraživanja bio je utvrditi postoji li razlika u učestalosti i specifičnosti ozljeđivanja studenata Kineziološkog fakulteta koji su studirali prema starom (integriranom četverogodišnjem) i onih koji studiraju prema novom petogodišnjem (3+2) programu studija. Istraživanje je provedeno na uzorku od 77 ispitanika (36 studentica i 41 studenta) Kineziološkog fakulteta Sveučilišta u Zagrebu koji studiraju prema novom, petogodišnjem programu studija. Studenti su na kraju osmog semestra ispunili posebni anketni upitnik. Njihovi su rezultati uspoređeni s onima dobivenim na studentima koji su studirali prema starom studijskom programu. Prema rezultatima, učestalost ozljeđivanja studenata Kineziološkog fakulteta koji su studirali prema novom ili starom programu studija vrlo je visoka. U prosjeku svaki se anketirani student ozlijedio barem jedan put u četiri godine studija. Pri tome prevladavaju ozljede zglobova, pogotovo donjih ekstremiteta, a studenti se češće ozljeđuju od studentica. Distribucija ozljeda po godinama studija kod studenata koji su studirali prema starom ili prema novom programu studija vrlo je slična, a rizik ozljeđivanja se u obama generacijama znatno smanjuje tek na četvrtoj godini, što je najvjerojatnije odraz smanjenja broja obveznih praktičnih predmeta. Uvođenje novog programa, dovelo je do znatnog smanjenja rizika ozljeđivanja studenata na sportskoj gimnastici uz istovremeno povećanje rizika ozljeđivanja na rukometu. Osim toga, ozljede koje su pretrpjeli studenti novije generacije lakše su naravi te znatno ne utjeću na tijek njihova studiranja. Nadalje, studenti novije generacije u većem se omjeru ozljeđuju na nastavi, dok su se oni koji su studirali prema starom programu češće ozljeđivali tijekom samostalnog pripremanja ispita. Dva puta dokazana visoka učestalost ozljeđivanja studenata Kineziološkog fakulteta ukazuje na potrebu za uvođenjem određenih promjena u novom programu studija (3+2). U tom smislu vrijedilo bi pokušati sa dodatnim smanjenjem broja studenata po grupi, pogotovo na vježbama, kada se studenti najčešće i ozljeđuju. Osim toga, dodatno povećanje broja predavaonica i sportskih dvorana (terena), u smislu jutarnjeg rasporeda nastave moglo bi spriječiti nakupljanje umora tijekom dugih radnih dana te indirektno smanjiti utjecaj umora na mogućnost ozljede studenataThe main goal of this study was to search for possible differences in frequency and specificity of injuries between the Kinesiology students who attended the Faculty of Kinesiology, University of Zagreb according to the old study program (4 years), and those who are attending the new study program (5 years). The sample was composed of 77 students (36 female and 41 male) attending the new study program, who were compared to the previously studied sample. They filled up a questionnaire at the end of their eight semester. Their results where than compared with those of the students who attended the old study program. The results showed a high injury rate in both samples. In average, every examinee suffered at least one injury during his/her study. Mostly, they injured their lower extremities, and the male students where injured more often. The injury risk in both generations decreased only in the 4th study year, probably because of less compulsory practical subjects. The implementation of the new study program resulted in a biggest injury risk during team handball, and smaller risk during sport gymnastics. Besides, the injuries sustained by the students who attended the new study program, were less serious with much lower implications for the regularity of their study. Further, numerous students attending the new study program suffered an injury during the classes, while the ones attending the old study program where mostly injured when preparing the exam. Since the injury rate was very high in both groups, there is a need to introduce some changes in the new study program in order to decrease the injury risk of Kinesiology students. An additional reduction in number of students per group, especially for the practical classes, may be helpful. Besides, a bigger number of classrooms as well as sport halls may implicate a morning schedule, giving the students more time to rest before their afternoon practice, eventually leading to a smaller number of injuries due to fatigu

Regular Dog-Walking Improves Physical Capacity in Elderly Patients after Myocardial Infarction

Various positive effects of pet ownership on cardiovascular health are well known. The aim of this prospective and controlled longitudinal study was to determine the effects of everyday dog-walking on physical capacity in elderly patients during the first year after myocardial infarction. Regularly dog-walking for at least 15 minutes three times a day is related to significantly higher work load on the bicycle exercise test (72.5 ± 10.75 versus 67.6 ± 11.6 W, p<0.05) in the »dog-walking« group (N=29, mean age 72.5 years) at 12 months compared to the control group (N=30, mean age 71.7 years). Our results suggest that dogs may help to maintain continuous physical activity in elderly cardiovascular patients promoting their physical capacity. Further researches are needed to confirm this association as well to identify other possible influences of dog ownership on the cardiovascular health and on the outcome in patients after myocardial infarction

Regular Dog-Walking Improves Physical Capacity in Elderly Patients after Myocardial Infarction

Various positive effects of pet ownership on cardiovascular health are well known. The aim of this prospective and controlled longitudinal study was to determine the effects of everyday dog-walking on physical capacity in elderly patients during the first year after myocardial infarction. Regularly dog-walking for at least 15 minutes three times a day is related to significantly higher work load on the bicycle exercise test (72.5 ± 10.75 versus 67.6 ± 11.6 W, p<0.05) in the »dog-walking« group (N=29, mean age 72.5 years) at 12 months compared to the control group (N=30, mean age 71.7 years). Our results suggest that dogs may help to maintain continuous physical activity in elderly cardiovascular patients promoting their physical capacity. Further researches are needed to confirm this association as well to identify other possible influences of dog ownership on the cardiovascular health and on the outcome in patients after myocardial infarction

Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies. Development of the chemoresistance in the PDAC is one of the key contributors to the poor survival outcomes and the major reason for urgent development of novel pharmacological approaches in a treatment of PDAC. Systematically tailored combination therapy holds the promise for advancing the treatment of PDAC. However, the number of possible combinations of pharmacological agents is too large to be explored experimentally. In respect to the many epigenetic alterations in PDAC, epigenetic drugs including histone deacetylase inhibitors (HDACi) could be seen as the game changers especially in combined therapy settings. In this work, we explored a possibility of using drug-sensitivity data together with the basal gene expression of pancreatic cell lines to predict combinatorial options available for HDACi. Developed bioinformatics screening protocol for predictions of synergistic drug combinations in PDAC identified the sphingolipid signaling pathway with associated downstream effectors as a promising novel targets for future development of multi-target therapeutics or combined therapy with HDACi. Through the experimental validation, we have characterized novel synergism between HDACi and a Rho-associated protein kinase (ROCK) inhibitor RKI-1447, and between HDACi and a sphingosine 1-phosphate (S1P) receptor agonist fingolimod

Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention

The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death programs. Over the last three decades, an increasing number of synthetic and naturally derived compounds, such as dietary-derived products, have been demonstrated to act as HDACi and have provided biological and molecular insights with regard to the role of HDAC in cancer. The first part of this review is focused on the biological roles of the Zinc-dependent HDAC family in malignant diseases. Accordingly, the small-molecules and natural products such as HDACi are described in terms of cancer therapy and chemoprevention. Furthermore, structural considerations are included to improve the HDACi selectivity and combinatory potential with other specific targeting agents in bifunctional inhibitors and proteolysis targeting chimeras. Additionally, clinical trials that combine HDACi with current therapies are discussed, which may open new avenues in terms of the feasibility of HDACi’s future clinical applications in precision cancer therapies

Epigenetic drug discovery: fragment-based drug design of novel 1-benzhydryl-piperazine derivatives as selective histone deacetylase 6 inhibitors

Selective histone deacetylase 6 (HDAC6) inhibition with small molecules is regarded as a rational strategy to develop safer anti-cancer drugs compared to non-selective HDAC inhibitors1. To date, structural motifs that are important for HDAC inhibitory activity and selectivity are defined as: surface recognition group (CAP group), aliphatic or aromatic linker and zinc-binding group (ZBG). Herein, we describe a comprehensive protocol for the computational fragment search of novel surface-recognition (CAP) groups aimed to design selective Histone Deacetylase 6 (HDAC6) inhibitors (Figure 1)2. Identified heterocyclic CAP group, 1-benzhydryl piperazine was employed to synthesize novel HDAC inhibitors with small structural perturbations in the hydrocarbon linker. Enzymatic in vitro HDAC screening identified two selective HDAC6 inhibitors (6b, IC50 = 186 nM and 9b, IC50 = 31 nM), as well as two non-selective nanomolar HDAC inhibitors (7b and 8b). The influence of linker chemistry of synthesized inhibitors on HDAC6 potency was studied using structure-based molecular modelling. References 1. J. Amengual, J. Lue, H. Ma, R. Lichtenstein, B. Shah, S. Cremers, S. Jones, A. Sawas, The Oncologist, 2021, 26(3), 184 e366. 2. D. Ruzic, M. Petkovic, D. Agbaba, A. Ganesan, K. Nikolic, Mol. Inform., 2019, 38(5), 1800083. Acknowledgments The authors acknowledge a Ministry of Education, Science and Technological Development of the Republic of Serbia Faculty of Pharmacy project (451-03-68/2022- 14/200161).8th Conference of Young Chemists of Serbia 29th October 2022 University of Belgrade, Faculty of Chemistry Book of Abstracts M32 DRuzic Abstracts_8 CYCS BGD 202