Biological studies of organoselenium trans-palladium(II) complexes

In this work, two complexes of trans-palladium(II) with organoselenium compounds as their ligands were investigated., PdSe1, [Pd(L1)2Cl2], (L1 = 5- (phenylselanylmethyl) -dihydrofuran-2 (3H) -one)) and PdSe3, [Pd(L3)2Cl2], (L3 =2,2-dimethyl-3-(phenylselanylmethyl)-tetrahydro-2H-pyran). Their antimicrobial and antioxidant activity as well as the effect of the formed biofilm of selected bacteria were studied. Antimicrobial activity was tested by determining the minimum inhibitory concentrations (MIC) and minimum microbicidal concentration (MMC) using the resazurin microdilution plate method The effect of complexes and ligands on formed biofilm of S. aureus ATCC 25923, S. aureus, and P. aeruginosa was determined. The in vitro antioxidant activity of the complex was determined based on the neutralizing capacity of DPPH radicals expressed as EK50. The investigated complexes showed significantly higher antimicrobial activity than the corresponding ligands. The most significant activity was shown on Pseudomonas aeruginosa. Complexes showed a lower effect on tested bacterias formed biofilm than the tested ligands. Complex Pd-Se1 showed a better effect on the tested biofilm of S. aureus, while complex Pd-Se3 showed a significant effect on the tested biofilm of P. aeruginosa. The antioxidant activity of all n organoselenium trans-palladium(II) complexes is significant, with the PdSe1 complex being more active. These complexes have the potential to be further investigated as metallodrugs.The authors are grateful to the Ministry of Education, Science and Technological Development of the Republic of Serbia (Agreement No 451 03 9 2021 14 200378 451 03 68 2021 14 200122 and Agreement No 451 03 68 2021 14 200378 for financial suppor

Synthesis, Characterization and Biological Studies of Organoselenium trans-Palladium(II) Complexes

Background: Over the years, transition metal complexes have exhibited significant antimicrobial and antitumor activity. It all started with cisplatin discovery, but due to the large number of side effects it shows, there is a growing need to find a new metal-based compound with higher selectivity and activity on more tumors. Objectives: Two novel trans-palladium(II) complexes with organoselenium compounds as ligands, [Pd(L1)2Cl2] (L1 = 5-(phenylselanylmethyl)-dihydrofuran-2(3H)-one) and [Pd(L2)2Cl2] (L2 = 2- methyl-5-(phenylselanylmethyl)- tetrahydrofuran) were synthesized, in the text referred to as Pd-Se1 and Pd-Se2. Also, a structurally similar trans-palladium(II) complex, [Pd(L3)2Cl2] (L3= 2,2- dimethyl-3-(phenylselanylmethyl)-tetrahydro-2H-pyran ) was synthesized according to an already published work and is referred to as Pd-Se3. The interaction of synthesized complexes with DNA and bovine serum albumin was observed. Also, antimicrobial activity and in vitro testing, cell viability, and cytotoxic effects of synthesized ligands and complexes on human epithelial colorectal cancer cell line HCT-116 were studied. Molecular docking simulations were performed to understand better the binding modes of the complexes reported in this paper with DNA and BSA, as well as to comprehend their antimicrobial activity. Methods: The interactions of the synthesized complexes with DNA and bovine serum albumin were done using UV-Vis and emission spectral studies as well as docking studies. Antimicrobial activity was tested by determining the minimum inhibitory concentrations (MIC) and minimum microbicidal concentration (MMC) using the resazurin microdilution plate method. Cytotoxic activity on cancer cells was studied by MTT test. Results: The Pd(II) complexes showed a significant binding affinity for calf thymus DNA and bovine serum albumin by UV-Vis and emission spectral studies. The intensity of antimicrobial activity varied with the complexes Pd-Se1 and Pd-Se3, showing significantly higher activity than the corresponding ligand. The most significant activity was shown on Pseudomonas aeruginosa. Under standardized laboratory conditions for in vitro testing, cell viability and cytotoxic effects of synthesized ligands and complexes were studied on human epithelial colorectal cancer cell line HCT-116, where Pd-Se2 showed some significant cytotoxic effects. Conclusion: The newly synthesized complexes have the potential to be further investigated as metallodrugs.Publishe

Antimicrobial, antioxidant and DNA-binding studies of palladium(II) complexes with different chelate ligands containing nitrogen donor atoms

The antimicrobial and antioxidant activities, as well as the DNA-binding of four square-planar Pd(II) complexes, [Pd(terpy)Cl]+ (C1), [Pd(en)Cl2] (C2), [Pd(DMEAImiPr)Cl2] (C3) and [Pd(dach)Cl2] (C4) (terpy = 2,2′:6′,2′′- -terpyridine, en = ethylenediamine, dach = trans-1,2-diaminocyclohexane and DMEAImiPr = N2-((1,3-dihydro-1,3-diisopropyl-4,5-dimethyl)-2H-imidazol-2- ylidene)-N1,N1-dimethyl-1,2-ethanediamine are reported. The antimicrobial activities of the Pd(II) complexes with the appropriate ligands were tested using the microdilution method against 18 strains of microorganisms, whereby the minimal inhibitory concentration (MIC) and the minimal microbicidal concentration (MMC) were determined. The antibiofilm activity of [Pd(terpy)Cl]+ and the corresponding ligand were determined on a formed biofilm. The intensity of antimicrobial activity varied depending on the type of microorganism and the tested compound. The C1 complex with the corresponding ligand demonstrated significantly greater overall antimicrobial activity than C2, C3 and C4. The antibacterial activity of the C1 complex was better than its antifungal activity that was overall greater than that of the positive control, fluconazole. The greatest sensitivity for C1 and L1 was with Penicillium italicum (MIC < 0.49 μg mL-1) among the fungi, and with Proteus mirabilis ATCC 12453 (MIC = 0.98 μg mL-1) among the tested bacteria. The tested compounds show low and moderate antibiofilm activity. The complexes showed weak antioxidant properties when tested using the DPPH (1,1-diphenyl-2- -picrylhydrazyl) method. The interaction of the metal complexes C1–C4 with calf thymus DNA (CT-DNA) was further examined by absorption (UV–Vis) and emission spectral studies (EthBr displacement studies). Overall, the investigated complexes exhibited good DNA interaction ability.Publishe

Heart and Vessels / Prevalence of early repolarization syndrome and long-term clinical outcome in patients with the diagnosis of idiopathic ventricular fibrillation

Idiopathic ventricular fibrillation (IVF) is diagnosed in up to 14% of sudden cardiac death (SCD) survivors. Early repolarization syndrome (ERS) in patients with ventricular tachyarrhythmia is characterized by an elevated J-point in inferior and/or antero-lateral leads. Our objectives were to determine the prevalence of ERS in IVF patients, and to evaluate potential differences in clinical outcome. Out of 3,552 implantable cardioverter defibrillator (ICD) carriers, 758 SCD survivors were retrospectively identified from the databases of the Medical Universities of Vienna and Innsbruck within the last three decades. Early repolarization pattern (ERP) was classified either as "notching" or "slurring". Endpoints were defined as appropriate ICD therapies for ventricular tachyarrhythmia, either anti-tachycardia pacing or shock, and all-cause mortality. After exclusion of recognized reasons for SCD, 50 patients were assigned to the diagnosis of IVF (6.6%). An ERP was identified in 10 patients, most of them with notching (n=8). After a mean follow-up of 11.26.7 years (539.3 patient years), appropriate ICD therapies were found in 50% of ERS and 43% of IVF patients without ERP (p=0.732). In ERS patients, all ICD therapies were found in patients with notching pattern. Similarly, incidence of inappropriate ICD therapies, and all-cause mortality was comparable (30% vs. 23%, p=0.707; 10% vs. 5%, p=0.496, respectively). In 758 SCD survivors, we found a low prevalence of IVF and ERS. Similar event rates were reported concerning all-cause mortality and ICD therapies for ventricular tachyarrhythmia after long-term follow-up in this cohort.(VLID)364364

The Influence of Different Types of Physical Activity on The Redox Status of Scuba Divers

The effect of scuba diving on ROS production and oxidative stress compared to that of other recreational activities is still poorly understood. The aim of this study was to assess the influence of different types of physical activity on the redox status of scuba divers by testing the pro- and anti-oxidative parameters immediately before and after different types of physical load. The prevalence study included 10 professional police divers. All examinees were male, 32 ± 5.1 years of age, well-trained, and with a minimum of five to a maximum of 20 years of diving experience. The study was divided into three experimental protocols: 1) an exercise test (at atmospheric pressure), 2) an at sea dive (30 meters for 30 minutes), and 3) a dive into river current (10 meters for 30 minutes). Immediately before and after the load test of the divers at atmospheric pressure and immediately before and after the dive, blood samples were taken to determine the values of the following pro-oxidant markers: O2−, H2O2, NO2− and TBARS, as well as antioxidant enzymes (SOD and CAT). A comparison of the results before and after physical activity for all three protocols revealed a significant increase in values for NO2−, O2−, H2O2 and CAT after physical activity. It can be concluded that the values of all oxidative stress markers depend on the season of the year in which the research is conducted or on the frequency of dives and degree of physical exertion during this period of the year

The influence of different types of physical activity on the redox status of scuba divers

© 2017, University of Kragujevac, Faculty of Science. All rights reserved. The effect of scuba diving on ROS production and oxidative stress compared to that of other recreational activities is still poorly understood. The aim of this study was to assess the influence of different types of physical activity on the redox status of scuba divers by testing the pro- and anti-oxidative parameters immediately before and after different types of physical load. The prevalence study included 10 professional police divers. All examinees were male, 32 ± 5.1 years of age, well-trained, and with a minimum of five to a maximum of 20 years of diving experience. The study was divided into three experimental protocols: 1) an exercise test (at atmospheric pressure), 2) an at sea dive (30 meters for 30 minutes), and 3) a dive into river current (10 meters for 30 minutes). Immediately before and after the load test of the divers at atmospheric pressure and immediately before and after the dive, blood samples were taken to determine the values of the following pro-oxidant markers: O2-, H2O2, NO2- and TBARS, as well as antioxidant enzymes (SOD and CAT). A comparison of the results before and after physical activity for all three protocols revealed a significant increase in values for NO2-, O2-, H2O2 and CAT after physical activity. It can be concluded that the values of all oxidative stress markers depend on the season of the year in which the research is conducted or on the frequency of dives and degree of physical exertion during this period of the year

The role of TERT-CLPTM1L SNPs, hTERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma

The aim of this study was to assess TERT-CLPTM1L single-nucleotide polymorphisms (SNPs) (rs402710 C/T in the CLPTM1L gene; rs2736100 A/C and rs2736098 G/A in the TERT gene) as risk factors for development of oral squamous cell carcinoma (OSCC), and to investigate the relationship between the analyzed polymorphisms, relative telomere length (RTL), telomerase expression and clinicopathologic characteristics of OSCC in a Serbian population. Paraffin-embedded tumor samples and buccal swabs from cancer-free controls were genotyped using PCR-RFLP, while tumor RTL values and telomerase expression were estimated by real-time PCR and immunohistochemistry, respectively. CLPTM1L rs402710 and TERT rs2736100 polymorphisms were associated with a significantly increased risk of OSCC, and TERT rs2736098 with a significantly decreased risk. No significant association was found between TERT-CLPTM1L polymorphisms, tumor RTL values, telomerase expression, and clinicopathologic features, although a trend towards longer telomeres was evident in telomerase-positive samples and less advanced tumors. Kaplan-Meier survival analysis showed that patients with longer telomeres in their tumors had significantly better overall survival than patients with shorter telomeres. Our research seems to provide strong evidence for an association between CLPTMIL rs402710C/T and TERT rs2736100A/C SNPs and the risk of OSSC, and suggests that higher tumor RTL values and positive hTERT expression may be applicable as early prognostic markers

Markers of Epithelial–Mesenchymal Transition and Mucinous Histology Are Significant Predictors of Disease Severity and Tumor Characteristics in Early-Onset Colorectal Cancer

Approximately 20% of patients with colorectal cancer (CRC) are diagnosed with a mucinous subtype of this tumor, have a worse prognosis, and often show resistance to available therapies. Molecules from the mucin family are involved in the regulation of epithelial–mesenchymal transition (EMT), which significantly determines the cancer aggressiveness. This study aimed to examine the diagnostic and prognostic significance of mucinous histology and EMT markers in patients with early-onset CRC and their association with disease severity and tumor characteristics. This study included tumor tissue samples from 106 patients diagnosed with CRC before the age of 45, 53 with mucinous and 53 with non-mucinous tumors. The EMT status was determined by immunohistochemical analysis of E-cadherin and Vimentin in tissue sections. Mucinous tumors had significantly higher Mucin-1 (p p = 0.043) scores; they were significantly less differentiated (p = 0.007), more advanced (p = 0.027), and predominately affected right the colon (p = 0.039) compared to non-mucinous tumors. Epithelial tumors were significantly better differentiated (p = 0.034) and with less prominent tumor budding (p p = 0.006) and budding (p = 0.001), respectively. Mucinous histology and EMT markers are significant predictors of disease severity and tumor characteristics in early-onset colorectal cancer

Putative application of Najas marina L. extracts as a source of bioactive compounds and their antioxidant, antimicrobial, antibiofilm, and genotoxic properties

In this research paper, the total phenols (TP), flavonoids (TF), and tannins (TT) content in the acetone and ethyl acetate extracts of Najas marina L. and the identification and quantification of phenolic acids and flavonoids from the ethyl acetate extract were performed. Antioxidant, antimicrobial, and antibiofilm properties of the mentioned extracts were investigated in vitro. The genotoxic potential was analyzed in cultured human peripheral blood lymphocytes (PBL). The TP and TF content was higher in the ethyl acetate extract, dominated by quercetin (172.4 μg mg−1) and ferulic acid (22.74 μg mg−1), while the TT content was slightly higher in the acetone extract. Both extracts tested showed limited antioxidant effects compared to ascorbic acid. The strongest antibacterial activity was observed with Gram-positive bacteria, particularly Staphylococcus aureus (MIC and MMC at 0.31 mg ml−1) and S. aureus ATCC 25923 (MIC at <0.02 mg ml−1), while antifungal activity was limited. Both extracts tested showed better activity on preformed biofilms. Acetone extract had no genotoxic activity but showed significant genoprotective activity against mitomycin C-induced DNA damage in cultured PBLs. Results of our research demonstrate the potential for the development of plant-based antibacterial and biofilm agents.Publishe