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In silico based exploration of natural and synthetic antidiabetic compounds: A comprehensive review of computational approaches
Background and purpose: Diabetes mellitus type 2 is a global health issue marked by hyperglycemia and metabolic dysfunction. Despite progress, discovering safe and effective antidiabetic agents remains crucial. This review highlights integrated In Silico, In Vitro, and in vivo methods for identifying novel antidiabetic compounds from natural and synthetic origins. Experimental approach: Computational tools including molecular docking, molecular dynamics, and ADMET prediction identified inhibitors targeting DPP-IV, α-glucosidase, and PPAR. Promising compounds underwent in vitro enzymatic and cellular assays, followed by in vivo efficacy tests in diabetic animal models assessing glucose levels, biochemical markers, and tissue histopathology. Key results: Integrated computational and experimental approaches effectively pinpointed compounds with strong target binding, enzyme inhibition, and positive cellular effects. In vivo data showed significant glucose reduction, enhanced insulin response, and pancreatic protection. ADMET analysis further supported their drug-likeness and safety profiles. Conclusion: Combining computational screening with biological validations forms a cost-effective pipeline for antidiabetic drug discovery. Multi-disciplinary integration increases lead identification success, guiding future refinement of in silico models and expanded in vivo studies to accelerate novel diabetes therapeutic development
Insights into drug resistance in Leishmania: Mechanisms, therapeutics, and clinical case studies
Background and purpose: Leishmaniasis, a neglected tropical disease caused by the protozoan parasite Leishmania, remains a significant public health concern in endemic regions. The disease manifests in various forms, including cutaneous, mucocutaneous, and visceral leishmaniasis, each associated with specific Leishmania species and influenced by host immune responses. Over the past few decades, treatment for leishmaniasis has relied on a limited range of drugs, including pentavalent antimonials, amphotericin B formulations, miltefosine, and paromomycin. However, widespread drug resistance, particularly in visceral leishmaniasis, has severely compromised treatment efficacy, leading to rising cases of treatment failure. This review aims to provide a comprehensive understanding of the mechanisms underlying drug resistance in leishmaniasis and to highlight the factors that contribute to its development. Experimental approach: The study synthesizes existing literature on resistance mechanisms among anti-leishmanial drugs, focusing on changes in parasite uptake and efflux, intracellular sequestration, and modulation of stress responses. It also examines the impact of environmental factors, such as arsenic exposure in endemic regions, and reviews recent molecular and genomic studies that have identified resistance-associated markers. Conclusion: The review underscores the urgent need for innovative therapeutic strategies and highlights the importance of an integrated approach to combat drug resistance through enhanced surveillance, molecular insights, and global collaboration
Hypotension and antiphlogistic potential of empagliflozin ocular film: swelling and release kinetics
Background and Purpose: Empagliflozin (EMP) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor used for the management of type 2 diabetes mellitus. The danger of glaucoma in type 2 diabetes mellitus patients is known to be reduced using SGLT2 inhibitors. Empagliflozin is also believed to reduce the level of inflammatory markers. The present work has been undertaken for monitoring intraocular pressure and anti-inflammatory activity using the empagliflozin ocular film formulation. The effect of colloidal silicon dioxide upon the dynamics of swelling and drug release performance was also studied. Experimental Approach: Hydroxypropyl methylcellulose-based ocular film of empagliflozin was prepared, including silicon dioxide in different ratios as 1:0.00, 1:0.01, 1:0.02, 1:0.04, and 1:0.06 (namely, EMA0, EMA1, EMA2, EMA3 and EMA4, respectively) using casting and solvent evaporation. Swelling and drug release studies of the films were conducted in phosphate buffer solution (pH 7.4), and the kinetic mechanisms of swelling and drug release were evaluated. Intraocular pressure was measured after application of the film in the normotensive rabbit eye. Moreover, the anti-inflammatory effect was assessed using a rabbit ocular carrageenan-induced inflammation model. Key Results: Swelling behaviour followed Fickian mechanism in the order: EMA
The most common toxinotypes of the bacterium Clostridium perfringens in small ruminants and their resistance to antibiotics
Infection with the bacterium C. perfringens in sheep and goat herds leads to considerable losses. The most common diseases in small ruminants caused by this bacterium are pulpy kidney disease, enterotoxaemia, yellow lamb disease, and necrotic enteritis. C. perfringens is widely distributed in the environment and is part of the intestinal microbiota of humans and animals. When physiological conditions in the body change, it begins to produce toxins that lead to various pathological changes. Depending on the toxins it produces, it is classified into seven types (A–G), defined based on the presence of genes encoding the CPA toxin (all types), CPB toxin (type B and type C), ETX toxin (type B and D), ITX toxin (type E), CPE toxin (type F) and NetB toxin (type G). Strains A and D are most commonly associated with enterotoxaemia in small ruminants. According to the available literature, C. perfringens toxinotype A is most frequently isolated in small ruminant herds. In addition to toxin genes, antibiotic resistance genes also play an important role in bacterial survival. Of the genetic determinants of antimicrobial resistance discovered to date, most are associated with the following antimicrobial drugs: bacitracin (bcrR gene), tetracyclines (tet genes), macrolides (erm genes), lincosamides (erm and lnu genes), streptogramins (erm genes) and chloramphenicol (cat genes). Due to sudden death after the onset of symptoms and the economic unprofitability, very few results are available on antibiotic resistance of C. perfringens in small ruminants. Therefore, it has proven to be more economical and effective to work on prevention than on treatment. Since there is no vaccine against enterotoxaemia in Croatia, prevention of the disease is difficult
Preliminary analysis of cattle deaths suspected to be an adverse reaction of vaccination against lumpy skin disease in Croatia
Vaccination against lumpy skin disease was carried out in Croatia during 2016 and 2017 to prevent this emerging viral disease from causing significant damage to the cattle population. Two unauthorised live vaccines were used for immunoprophylaxis, and adverse reactions in cattle were expected. Adverse events were monitored and 14 selected reported cases of deaths were analysed using the available necropsy results. The cases analysed were classified as probable, possible, inconclusive, or unlikely to be caused by vaccination, primarily based on results of post-mortem examination, taking into consideration factors that contributed to or resulted in death or euthanasia. Most cases were classified as possibly caused by vaccination due to subcutaneous oedema of varying consistency (at the injection site) and intramuscular haemorrhage, in some cases leading to purulent and necrotic processes. These processes eventually led to fatal purulent bronchopneumonia, pulmonary emphysema, septic conditions, or euthanasia. In the remaining cases, necropsy results were unable to be linked to vaccination or the findings were inconclusive due to the presence of other factors, such as Klebsiella infection. It can be assumed that neither vaccine had a direct connection with animal deaths, but they may have contributed to the fatal outcomes due to the complications of severe local reactions and general impact on the immune system
ANALYSIS OF THE FUNCTIONS OF HUMAN RESOURCE MANAGEMENT IN FOREIGN-OWNED AND DOMESTICALLY OWNED PRIVATE COMPANIES
Istraživanje analizira funkcija upravljanja ljudskim resursima (ULJR) u privatnim poduzećima u Republici Hrvatskoj u stranom i domaćem vlasništvu na uzorku od 130 velikih i srednje velikih poduzeća. Ključna područja predmetnog istraživanja uključuju analizu razvijenosti pojedinih podfunkcija ULJR-a, analizu kvalitete realizacije pojedine aktivnosti unutar specifične podfunkcije ULJR-a, važnost pojedine podfunkcije ULJR-a za uspješnost poslovanja poduzeća te osobno zadovoljstvo menadžera ULJR-a razvojem pojedine podfunkcije ULJR-a. Cilj je rada pokazati kako se kvaliteta funkcije ULJR-a u hrvatskim poduzećima razlikuje s obzirom na podrijetlo vlasništva poduzeća. Analizirani i statistički obrađeni podaci, prikupljeni anketnim upitnikom ispitivanih menadžera ljudskih resursa, pokazuju određene sličnosti, ali ipak i niz razlika u funkciji ULJR-a u poduzećima u stranom i domaćem vlasništvu u Republici Hrvatskoj. Zaključuje se da je stupanj razvijenosti pojedinih podfunkcija ULJR-a, kvaliteta realizacije pojedine aktivnosti unutar specifične podfunkcije ULJR-a, stupanj važnosti pojedine podfunkcije ULJR-a, kao i stupanj zadovoljstva menadžera za LJR razvojem podfunkcija ULJR-a veći pri privatnim poduzećima u stranom vlasništvu u odnosu na privatna poduzeća u domaćem vlasništvu.The study analyses the function of human resource management (HRM) in private companies in the Republic of Croatia, including both foreign and domestically owned companies, based on a sample of 130 large and medium-sized enterprises. The core areas of the research include analysing the development of individual HRM sub-functions, analysing the quality of the implementation of individual activities within a particular HRM sub-function, the importance of individual HRM sub-functions for the business success of the company and the personal satisfaction of HRM managers with the development of individual HRM sub-functions. The aim of this paper is to show how the quality of the HRM function in Croatian companies varies depending on the origin of the company owners. The analysed and statistically processed data, which were collected through a questionnaire from the interviewed HRM managers, reveal both similarities and differences in the HRM function in foreign-owned and domestically owned companies in the Republic of Croatia. It is concluded that the degree of development of individual HRM sub-functions, the quality of implementation of individual activities within a particular HRM sub-function, the degree of importance of individual HRM sub-functions, and the degree of HR managers' satisfaction with the development of HRM sub-functions are higher in foreign-owned private companies than in domestically owned private companies
The genus Carex (Cyperaceae) in Kosovo
This study presents the first verified checklist of Carex taxa in Kosovo, based on field surveys (2022–2024), herbarium revisions and literature analyses. We recorded 52 species, including 19 subspecies and 1 variety, as well as 2 hybrids. Among them are 15 taxa newly reported for the flora of Kosovo. Most of the records come from the Sharri Mountains and the Albanian Alps of Kosovo, both national parks, although significant populations occur throughout the country. Several taxa are restricted to single localities, emphasising the urgent need for conservation efforts. These results refine the taxonomy and distribution of Carex in Kosovo and provide an important basis for future molecular and conservation studies in the Balkans
Influence of Annealing Temperature on Microstructure and Properties of 6061 Aluminum Alloy for Chinese Alu-minum Bow and Arrow
Aluminum alloy has excellent elasticity, strength, and toughness. As a kind of high-strength alloy, 6061 aluminum alloy has excellent mechanical and pro-cessing properties, so it is widely used in the development of Chinese inverted arch arrows. In this paper, the effect of annealing temperature on the mechanical properties of 6061 aluminum alloy was studied. The microstructure, hardness, and tensile properties of the experimental aluminum alloy after different anneal-ing temperatures were analyzed. The effect of annealing temperature on the mi-crostructure, hardness, strength, elongation, and reduction of area of the alloy was clarified. It was found that when the annealing temperature is 580 °C, its mechan-ical properties are the best, making it more suitable for the development of Chinese inverted arch arrows
Barbara Ćuk (ur.), Tko su te filozofkinje?: Svezak II. Zagreb: Fakultet filozofije i religijskih znanosti, 2024.
CARBON STOCK EVALUATION IN NATIVE AND EXOTIC TREE SPECIES USING MULTIPLE ALLOMETRIC EQUATIONS: INSIGHTS FROM INDIA’S GREENEST UNIVERSITY
Understanding the dynamics of tree carbon stock in urban green spaces is critical for sustainable ecosystem management and climate change mitigation. This study evaluates carbon stock in native and exotic tree species at India’s greenest university (Maharshi Dayanand University) using four different allometric equations. A total of 5742 trees (22.81 trees/ha) were analysed, representing 56 species from 28 families. Tree parameters showed substantial variation. Diameter at breast height (DBH) ranged from 10.21 cm (Citrus limon) to 24.29 cm (Ficus benghalensis), with an average of 16 cm. Basal area (BA) ranged from 0.008 m²/tree to 0.046 m²/tree, with an average of 0.020 m²/tree. Biomass ranged from 20.22 kg/tree (Pterospermum acerifolium) to 194.82 kg/tree (Casuarina equisetifolia), with an average of 70.35 kg/tree, totalling 403.95 Mg. In comparison, the mean total carbon (TC) was 35.17 kg/tree, giving a total of 201.97 Mg and 0.80 Mg/ha. The dominant families, Fabaceae (112.31 kg/ha) and Moraceae (146.02 kg/ha) contributed significantly to carbon storage, while families like Lauraceae (0.19 kg/ha) and Moringaceae (0.34 kg/ha) showed minimal contributions. Equation A [AGB = exp (−2.409 + 0.9522 ln (D2 H ρ))] gave the maximum values of carbon stock. Statistical analysis revealed significant variation between equations (one-way repeated measures ANOVA, p 0.6). Native trees showed greater carbon stocks. These findings highlight the superior carbon storage of native trees and the role of allometric equations in precise carbon estimation, aiding urban carbon management