Search

The paper monitors the balance of payments in the Republic of North Macedonia, which determines the amount of the exchange rate through the supply and demand of foreign currency, as well as the impact of the exchange rate on the balance of payments movements. Real exchange rates are essentially equilibrium exchange rates. exchange rate that will keep the balance of payments in balance without taking measures for foreign exchange control, without pronounced inflation and deflationary tendencies and without constant expectation of monetary and foreign exchange reserves.There are several methods by which balance of payments can be established: by devaluation, by currency control and by deflation. When considering the relationship between the national currency exchange rate and the balance of payments of a national economy in terms of their interconnections, one should depart from their causal link of impacts. The exchange rate affects the balance of payments, as well as the balance of payments affects the exchange rate.The first part of the paper elaborates in detail the key activities of the balance of payments adjustment and the exchange rate adjustment, as well as their mutual impact.We use the adjustment mechanism to restore balance once the initial equilibrium has been disturbed. The payment adjustment process takes two different forms. One, under certain conditions, has adjustment factors that automatically contribute to balancing. Second, in the event that automatic adjustment fails to strike a balance, the government adopts a discretionary policy to achieve this goal

Summary. Colorectal cancer (CRC) and prostate cancer (PC) are the most often diagnosed cancers and the main reason for mortality connected to tumor diseases. There is still a shortage of examination of mechanisms including the influence of xanthine oxidase (XO) activity in progressiveness and invasion of the cancers. Therefore, present study investigated the role of XO activity, in correlation to thiobarbituric acid-reactive substances (TBARS) and advanced oxidation protein products (AOPP), as markers of oxidative stress in progression and invasion of human CRC and PC. We took tissue specimens from 30 patients with CRC and 18 patients with PC, in all four clinical stages of the disease. They were divided in 3 groups: cancer tissue, tissue surrounding the tumor and healthy control tissue group. The activity of XO in tumor tissue and tissue adjacent to the tumor was significantly higher when compared to healthy colon tissue. The highest activity of XO was in T2 and T3 tumor stadiums. TBARS and AOPP also showed higher concentration compared to control healthy tissue. There was a positive correlation between XO activity and prostate specific antigen (PSA) levels in PC. Presented results suggest that one of the possible causes of oxidative stress in CRC and PC could be high XO activity. XO may be involved in the malignant transformation, in the progression and invasion of human CRC and PC. XO could represent a theranostic biomarker, whereas using XO inhibitors such as allopurinol, could be a promising adjuvant therapy.

Antioxidant properties of 2-[2-imino-5-nitro-3-(2-oxo-2-phenylethyl)-2,3-dihydro-1H-benzimidazol1-yl]-1-phenylethanone (compound 1) and 2-(4-fluorobenzylidene)-6-(phenylcarbonyl)[1,3]thiazolo[3,2a]benzimidazol-3(2H)-one (compound 2) were evaluated in vitro. Compounds 1 and 2 did not show significant radical scavenging activity. It has been suggested that antioxidant strategies should not be based on direct scavengers but rather on the potentiation of endogenous antioxidant defenses, or on the reduction of the sources of reactive species. Although a direct scavenging mechanism is missing, the assayed compounds (1 and 2) as evidenced inhibitors of xanthine oxidase and dipeptidyl peptidase-4 might act antioxidatively by employing other mechanisms.

A library of 31 butyrylcholinesterase (BChE) and cathepsin B (CatB) inhibitors, was screened in vitro for inhibition of deoxyribonuclease I (DNase I). Compounds 22, 8 and 7 are among the most potent synthetic non-peptide DNase I inhibitors reported up to date. Three 8-hydroxyquinoline analogues inhibited both DNase I and BChE with IC50 values below 35 µM and 50 nM, respectively, while 2 nitroxoline derivatives inhibited DNase I and Cat B endopeptidase activity with IC50 values below 60 µM and 20 µM, respectively. Selected derivatives were screened for various co-target binding affinities at dopamine D2 and D3, histamine H3 and H4 receptors and inhibition of 5-lipoxygenase. Compound 8 bound to the H3 receptor and is highlighted as the most promising multifunctional ligand with a favorable pharmacokinetic profile and one of the most potent non-peptide DNase I inhibitors. The present study demonstrates that 8-hydroxyquinoline is a structural fragment critical for DNase I inhibition in the presented series of compounds. Nasl. z nasl. zaslona. Opis vira z dne 10. 1. 2022. Št. članka: e2021006. Bibliografija: str. 10-11. Abstract. Fund of the Republic of Serbia ARRS

Herein we report an assessment of 24 1,2,3,4-tetrahydroisoquinoline derivatives for potential DNase I (deoxyribonuclease I) inhibitory properties in vitro. Four of them inhibited DNase I with IC50 values below 200 μM. The most potent was 1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)propan-2-one (2) (IC50 =134.35±11.38 μM) exhibiting slightly better IC50 value compared to three other active compounds, 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]-1-phenylethan-1-one (15) (IC50 =147.51±14.87 μM), 2-[2-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one (18) (IC50 =149.07±2.98 μM) and 2-[6,7-dimethoxy-2-(p-tolyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]cyclohexan-1-one (22) (IC50 =148.31±2.96 μM). Cytotoxicity assessment of the active DNase I inhibitors revealed a lack of toxic effects on the healthy cell lines MRC-5. Molecular docking and molecular dynamics simulations suggest that interactions with Glu 39, His 134, Asn 170, Tyr 211, Asp 251 and His 252 are an important factor for inhibitors affinity toward the DNase I. Observed interactions would be beneficial for the discovery of new active 1,2,3,4-tetrahydroisoquinoline-based inhibitors of DNase I, but might also encourage researchers to further explore and utilize potential therapeutic application of DNase I inhibitors, based on a versatile role of DNase I during apoptotic cell death.

Approved and potent reported dipeptidyl peptidase-4 (DPP-4) inhibitors with gliptin-like structures are classified here according to their structures and mechanisms of the inhibition in three groups: (i) those with pyrrolidine or analogs as P1 fragment with α-aminoacyl linker, (ii) structures with trifluorophenyl moiety or analogs as P1 fragment with β-aminobutanoyl linker, and (iii) DPP-4 inhibitors with pyrimidine-2,4-dione or analogs as P1' fragment. The structure-activity relationship analysis was performed for those whose cocrystallized structures with the enzyme were published. While inhibitors with pyrrolidine and trifluorophenyl moiety or analogs as P1 fragment bind in a similar way in S1, S2 and S2 extensive domains of the enzyme, the binding mode of pyrimidine-2,4-dione derivatives/analogs differs with additional interactions in S1' and S2' pockets. Three general schemes of fragmented gliptins and gliptin-like structures with the enzyme and protein-ligand interaction fingerprints were made, which might be useful in the creation of DPP-4 inhibitor's design strategies.

In this study, seven new 4-oxothiazolidine derivatives were synthesized and assayed, along 7 known derivatives, for inhibitory properties against deoxyribonuclease I (DNase I) and xanthine oxidase (XO) in vitro. Among tested compounds, (5Z)-Ethyl-2-(2-(cyanomethylene)-4-oxothiazolidin-5-yliden)acetate (6) exhibited inhibitory activity against both enzymes (DNase I IC50 = 67.94 ± 5.99 μM; XO IC50 = 98.98 ± 13.47 μM), therefore being the first reported dual inhibitor of DNase I and XO. Observed DNase I inhibition qualifies compound 6 as the most potent small organic DNase I inhibitor reported so far. Derivatives of 2-alkyliden-4-oxothiazolidinone (1) inhibited DNase I below 200 μM, while the other tested 4-oxothiazolidine derivatives remained inactive against both enzymes. The molecular docking and molecular dynamics simulations into the binding sites of DNase I and XO enzyme allowed us to clarify the binding modes of this 4-oxothiazolidine derivative, which might aid future development of dual DNase I and XO.

News about the process of dyeing a polyamide yarn with unconventional direct textile dye, which is conventional for dyeing cotton yarns have described in this study. An attempt to polyamide yarn dyeing with this type of dye in laboratory is done in order to create realistic possibilities for application in industrial conditions. Polyamide is a chemical fiber obtained from synthetically produced polymers, while direct dyes are sulphonated azo compounds: derived from benzidine and his derivates or type of amine diaminostylene and others. In the experiment, the samples of polyamide yarn with linear density of 6,6 tex (units for fineness) has used. The yarn has dyed with a direct dye of a specific structure that has a predisposition to connect to this fiber. Dyeing time with continuous mixing was 5, 10, 15, 25 and 40 minutes. Also, in dyeing solution, to achieve a certain pH solution, acetic acid is added. The applied dye is marked like a C.I. Direct Brown 2 (azo-dye). The constant bulk of solution is contained concentrations of dye 10, 30, 50, 70 and 100 mg/dm3. Samples were dyed at a temperature of 90 °C. The spectrophotometer (Cary 100 Conc UV-VIS, Varian) was used to measure the adsorption of aqueous dyed solutions and to calculate an unknown dye concentration in the solution based on the calibration curve. The degree of dye exhaustion and the amount of adsorbed dye were calculated. The degree of exhaustion at all concentrations, for different dyeing time after 40 min was 80 %. The time of length of contact between the absorbent and the adsorbent, for different concentrations of used dye, results in a higher degree of exhaustion. Noticeable is continuity in the changes in the amount of adsorbate on the adsorbent with the increase of the initial concentration and time, i.e. a bigger amount of dye in the solution or longer dyeing time contribute a higher amount of adsorbed dye per unit mass of the adsorbent. Freundlich's model in the form of nonlinear or linear isotherms proved to be the most effective in the simulating the polyamide dyeing. High functionality of the variables was detected, the coefficient of determination was 0,95. Dyeing of polyamide with direct dye expands the dye spectrum that can be dyed the polyamide yarns. Dyeing of the yarn at a higher temperature gives better results than dyeing at a lower temperature. The results of this research with achieved efficiency indicate the possibility of a different approach in the dyeing the polyamide yarn with direct dyes, in order to further development of the industrial process. For better results, it necessary to carefully select the compistion of the bath and the method od dyeing, to elaborate the phase of dyeing to achieve good dyeing of fiber. It has been shown that dzeing at a higher temperature increases adsorption of dye. It has been determined that dyeing - adsorption depends on the contact time and the initial dye concentration.

The new knowledge through a concrete scientific study of the dyeing process of polyamide filament yarns (nylon yarn) with anionic dye in slightly acidic medium without any other additives (electrolyte, yeast, equalizer, etc.) in order to transfer the process in industrial conditions have investigated in this study. Generally, polyamide fibers (nylon, PA) have a different but similar chemical composition, depending on the base materials used for their synthesis. Anionic dye is usually used for dyeing cellulosic materials, but in special cases it can also be used for dyeing other textile raw materials. In this study, samples of polyamide filament yarn of linear density of 151 Nm have dyed with anionic dye at a temperature of 95 °C. Acetic acid was added in the dyeing solution to adjust the pH of the medium. The used dye is marked like C.I. Direct Red 1. The used dye concentrations for dyeing the samples were 5, 10, 15 and 20 mg/dm3, while the time of the dyeing process were 5, 10, 15, 25 and 40 minutes. At the end of dyeing, the absorbance measuring at the maximum wavelength (520 nm) was performed using a spectrophotometer (Cary 100 Conc UV-VIS, Varian). From the results, the degree of exhaustion dye and the amount adsorbed dye are obtained. The degree of dye exhaustion compared to initial dye concentration for different dyeing time, after 40 min was 70 %. The influence of the contact length between adsorbate (dye) and absorbent (polyamide yarn) on dye is evident i.e. a longer time contributes to a bigger degree of exhaustion. Changing the adsorbed amount of adsorbate on the adsorbent for different initial concentrations and dyeing time shows continuity in changes during initial concentration and time growth, i.e. a bigger amount of dye in the solution or longer dyeing time cause a bigger amount of adsorbed dye per unit mass of the adsorbent. Isotherms of adsorption are of big importance for the study of the dyeing process, so more of them were used in this study, but thee isothermal Halsey model was the most effective for clarifying process of dyeing. High functionality of the variables was detected with Halsey model (coefficient of determination=0,995). The process of dyeing polyamides with used dye solves the problem of large quantities of electrolytes and surfactants in wastewater after dyeing. The results show that the addition of acetic acid in solution, gives a bigger dye adsorption to the fiber. For better results, it is necessary to carefully select to the appropriate of the bath (appropriate acid, mineral-organic, some additives, etc.), the temperature-time regime od dyeing process, as well as the dyeing stage itself. For better results, it is necessary to carefully select the appropriate composition of the bath (appropriate acid, mineral-organic, some additives, etc.), the temperature-time regime of the dyeing process, as well as the dyeing phase.

Deoxyribonuclease I (DNase I) inhibitory properties of two 1-(pyrrolidin-2-yl)propan-2-one derivatives were examined in vitro. Determined IC50 values of 1-[1-(4-methoxyphenyl)pyrrolidin-2-yl]propan-2-one (1) (192.13±16.95 μM) and 1-[1-(3,4,5-trimethoxyphenyl)pyrrolidin-2-yl]propan-2-one (2) (132.62±9.92 μM) exceed IC50 value of crystal violet, used as a positive control, 1.89- and 2.73-times, respectively. Compounds are predicted to be nontoxic and to have favorable pharmacokinetic profiles, with high gastrointestinal absorption and blood-brain barrier permeability. Molecular docking and molecular dynamics simulations suggest that interactions with Glu 39, Glu 78, Arg 111, Pro 137, Asp 251 and His 252 are an important factor for inhibitors affinity toward the DNase I. Determined inhibitory properties along with predicted ADMET profiles and observed interactions would be beneficial for the discovery of new active 1-(pyrrolidin-2-yl)propan-2-one-based inhibitors of DNase I. Supporting information: [https://cer.ihtm.bg.ac.rs/handle/123456789/4499] Animation of molecular dynamics simulations - Inhibitor 1/DNase I: [https://cer.ihtm.bg.ac.rs/handle/123456789/4500] Animation of molecular dynamics simulations - Inhibitor 2/DNase I: [https://cer.ihtm.bg.ac.rs/handle/123456789/4501]

Xanthine oxidase (XO) is a versatile metalloflavoprotein enzyme that is best known for its rate-limiting role in the purine degradation pathway. Therapeutic inhibition of XO is based on its role in a variety of diseases that is attributed either to the hyperproduction of uric acid, or the hyperproduction of reactive oxygen species. Herein, we report the assessment of XO inhibitory properties of 24 1,2,3,4-tetrahydroisoquinoline derivatives, among which compound 16 exhibited IC50 value of 135.72 ± 2.71 µM. The interaction of compound 16 with XO enzyme was simulated using the Site Finder module, molecular docking and molecular dynamics. Molecular modeling suggests that interactions with Met 1038, Gln 1040, Thr 1077, Gln 1194 and Val 1259 are an important factor for inhibitor affinity toward the XO enzyme. Our proposed binding model might be beneficial for the discovery of new active 1,2,3,4-tetrahydroisoquinoline-based inhibitors of XO enzyme.

Multiple-targeting compounds might reduce complex polypharmacy of multifactorial diseases, such as diabetes, and contribute to the greater therapeutic success. Targeting reactive oxygen species-producing enzymes, as xanthine oxidase (XO), might suppress progression of diabetes-associated vascular complications. In this study a small series of benzimidazole derivatives (1–9) was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4) and XO. One 1,3-disubstituted-benzimidazole-2-imine (5) and 1,3-thiazolo[3,2-a]benzimidazolone derivative (8) were shown as effective dual DPP-4 and XO inhibitors, with IC50 values lower than 200 μM, and predicted binding modes with both target enzymes. Both selected dual inhibitors (compounds 5 and 8) did not show cytotoxicity to a greater extent on Caco-2 cells even at concentration of 250 μM. These structures represent new non-purine scaffolds bearing two therapeutic functionalities, being DPP-4 and XO inhibitors, more favorable in comparison to DPP-4 inhibitors with DPP-4 as a single target due to pleiotropic effects of XO inhibition.

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease frequently accompanied by urothelial carcinoma (UC). In light of the increased UC incidence and the markers observed in BEN patients with developed UC, the aim of the current case&ndash, control study is to assess survivin, p53 protein, growth factors and receptors (VEGF, VEGFR1, IGF I, IGF-1R and IGFBP5), tumor marker (TF)/CD142, circulating soluble Fas receptor and neopterin, as potentially predictive markers for UC in patients with BEN (52 patients), compared to healthy, age-matched subjects (40). A threefold increase was registered in both circulating and urinary survivin level in BEN patients. Especially noticeable was the ratio of U survivin/U Cr level five times the ratio of BEN patients associated with standard renal markers in multivariate regression models. The concentrations of VEGF, VEGFR1, (TF)/CD142, (sFas) were not significantly different in BEN patients, while urinary/plasma level demonstrated a significant decrease for VEGF. The levels of IGF I, IGFBP5 and IGF-1R were significantly reduced in the urine of BEN patients. Plasma concentration of neopterin was significantly higher, while urinary neopterin value was significantly lower in BEN patients compared to healthy controls, which reflected a significantly lower urine/plasma ratio and low local predictive value. As BEN is a slow-progressing chronic kidney disease, early detection of survivin may be proposed as potential predictor for malignant alteration and screening tool in BEN patients without the diagnosis of UC.

Since the outbreak of SARS-CoV-2 virus more than 12,500,000 cases have been reported worldwide. Patients suffering from diabetes and other comorbidities are particularly susceptible to severe forms of the COVID-19, which might result in chronic complications following recovery. Dipeptidyl peptidase-4 inhibitors exert beneficial effects in prevention/treatment of pulmonary fibrosis, heart, and kidney injury, and since they may be a long-term consequence caused by COVID-19, it is reasonable to expect that DPP-4 inhibitors might be beneficial in alleviating long-term consequences of COVID-19. With that in mind, we would like to voice our concerns over chronic implications following recovery from COVID-19, especially not only in diabetic but also in non-diabetic patients, and to indicate that some preventive measures could be undertaken by application of DPP-4 inhibitors. Nasl. z nasl. zaslona. Opis vira z dne 14. 8. 2020. Št. članka 1185. Abstract. Bibliografija: str. 10-11. Ministry of Education, Science and Technological Development of the Republic of Serbia; Serbian Academy of Sciences and Arts, branch in Nis Faculty of Medicine of the University of Niš ARRS

PURPOSE: Our aim was to evaluate the frequency and SNP-SNP interactions between factor V Leiden (FVL) G1691A, prothrombin G20210A mutation, and C677T MTHFR and PAI-1 4G/5G gene polymorphisms in female IVF patients with unexplained infertility (UI) by using a multifactor dimensionality reduction (MDR) model analysis. METHODS: A total of 225 subjects were enrolled in the study. There were 105 females in UI group and 120 healthy controls. Designated SNPs were determined by using allele-specific PCR methods. The difference in thrombophilia prevalence was assessed by a chi-square test and logistic regression analysis. Four-locus SNP interaction model was tested using the MDR approach. A ten-fold cross-validation consistency (CVC) and permutation testing were performed. RESULTS: There was a significant difference of MTHFR C677T polymorphism frequency between the groups. Significantly less UI patients had MTHFR CC genotype (p = 0.005), while the risk allele T was more frequent (OR = 1.83, p = 0.0018). Logistic regression determined a significant association only for MTHFR C677T in our patients (TT genotype OR = 2.99). The MDR analysis confirmed the significance of a single-locus model for MTHFR C677T polymorphism (p = 0.015; OR = 2.93). However, the best, significant predictive model was the two-locus model comprising MTHFR C677T and FVL (CVC = 10/10, testing accuracy = 60.95%, p = 0.013; OR = 3.02). CONCLUSION: The MTHFR C677T polymorphism was significantly associated with UI, with minor allele T being more frequent. Additionally, there was a significantly increased presence of MTHFR C677T with FVL mutation in these patients. Therefore, MTHFR and its interaction with FVL should be recognized as contributing factors in the pathogenesis of infertility.

Since the outbreak of SARS-CoV-2 virus more than 2 800 000 cases have been reported worldwide. Patients suffering from diabetes and other comorbidities are particularly susceptible to severe forms of the COVID-19, which might result in chronic complications following recovery. Dipeptidyl peptidase-4 inhibitors exert beneficial effects in the prevention/treatment of pulmonary fibrosis, heart, and kidney injury, and since they may be a long-term consequence caused by COVID-19, it is reasonable to expect that DPP-4 inhibitors might be beneficial in alleviating long-term consequences of COVID-19. With that in mind, we would like to voice our concerns over chronic implications following recovery from COVID-19 especially in diabetic, but also in non-diabetic patients, and to indicate that some preventive measures could be undertaken by application of DPP-4 inhibitors.

Balkan endemic nephropathy (BEN) represents a chronic tubulointerstitial nephropathy which is followed by the progression of kidney fibrosis to end-stage kidney failure. The critical involvement of poisons in food (aristolochic acid (AA), ochratoxin, and heavy metals) and selenium deficiency are among nutritive factors which contribute to the pathogenesis of BEN, due to reactive oxygen species (ROS) liberation and/or decreased antioxidative defence system. The aim of the study is to distinguish a possible systemic and local origin of ROS through the measurement of xanthine oxidase (XO) activity in urine and plasma, along with the determination of the oxidative changes in lipids and proteins. The study included 50 patients with BEN and 38 control healthy subjects. We noted increased levels of both thiobarbituric acid-reactive substances (TBARS) and advanced oxidation protein products (AOPPs) in the plasma of patients with BEN, compared to the control group (p<0.001). The urinary levels of AOPPs were higher in patients with BEN in comparison to the control (p<0.001). The specific activity of XO was significantly lower in plasma and urine in BEN samples, compared to controls (p<0.005). Based on these results, we hypothesize that XO might not be considered a direct systemic or local contributor to ROS production in BEN, most probably because of the diminished kidney functional tissue mass and/or AA-induced changes in purine nucleotide conformation. The increased AOPP and TBARS level in both plasma and urine in BEN may predict ROS systemic liberation with toxic local effects.