Synthesis, characterization, PXRD studies, and theoretical calculation of the effect of gamma irradiation and antimicrobial studies on novel Pd(II), Cu(II), and Cu(I) complexes.

The main objective of this study is to synthesize and characterize of a new three complexes of Pd (II), Cu (II), and Cu (I) metal ions with novel ligand ((Z)-2-(phenylamino)-N'-(thiophen-2-ylmethylene)acetohydrazide) H2LB. The structural composition of new compounds was assessed using several analytical techniques including FT-IR, 1H-NMR, electronic spectra, powder X-ray diffraction, and thermal behavior analysis. The Gaussian09 program employed the Density Functional Theory (DFT) approach to optimize the geometry of all synthesized compounds, therefore obtaining the most favorable structures and crucial parameters. An investigation was conducted to examine the impact of γ-irradiation on ligands and complexes. Before and after γ-irradiation, the antimicrobial efficiency was investigated for the activity of ligands and their chelates. The Cu(I) complex demonstrated enhanced antibacterial activity after irradiation, as well as other standard medications such as ampicillin and gentamicin. Similarly, the Cu(I) complex exhibited superior activity against antifungal species relative to the standard drug Nystatin. The docking investigation utilized the target location of the topoisomerase enzyme (2xct) chain A.

Antimicrobial screening involving Helicobacter pylori of nano-therapeutic compounds based on the amoxicillin antibiotic drug.

Nano-structure Cu(II) complex [Cu(AMAB)2 ]Cl2 with Schiff base (AMAB) derived from the condensation between 4-(dimethylamino)benzaldehyde and amoxicillin trihydrate was prepared. (AMAB) Schiff base and its Cu(II) complex were identified and confirmed by different physicochemical techniques. The Schiff base (AMAB) was coordinated to copper ion through carbonyl oxygen and imine nitrogen donor sites. X-ray powder diffraction shows a cubic crystal system of the Cu(II) complex. The density functional theory was used to optimize the structure geometries of the investigated compounds. The molecular docking of the active amino acids of the investigated proteins' interactions with the tested compounds was evaluated. The bactericidal or bacteriostatic effect of the compounds was screened against some bacterial strains. The activity of Cu-chelate against Gram-negative bacteria was mainly more effective than its (AMAB) ligand and vice versa in the case of Gram-positive bacteria. The biological activity of the prepared compounds with biomolecules calf thymus DNA (CT-DNA) was determined by electronic absorption spectra and DNA gel electrophoresis technique. All studies revealed that the Cu-chelate derivative exhibited better binding affinity to both CT-DNA than the AMAB and amoxicillin itself. The anti-inflammatory effect of the designed compounds was determined by testing their protein denaturation inhibitory activity spectrophotometrically. All obtained data supported that the designed nano-Cu(II) complex with Schiff base (AMAB) is a potent bactericide against H. pylori, and exhibits anti-inflammatory activity. The dual inhibition effects of the designed compound represent a modern therapeutic approach with extended spectrum of action. Therefore, it can act as good drug target in antimicrobial and anti-inflammtory therapies. Finally, H. pylori resistance to amoxicillin is absent or rare in many countries, thus amoxicillin nanoparticles may be beneficial for countries where amoxicillin resistance is reported.

Effect of exercise training with laser phototherapy on homeostasis balance resistant to hypercoagulability in seniors with obesity: a randomized trial.

The prevalence of obesity has increased the incidence of obesity-related coagulation disorders. The current study assessed the effectiveness of combined aerobic exercise and laser phototherapy on the coagulation profile and body measurements in older adults with obesity compared to aerobic exercise alone, which has not been adequately explored. We included 76 obese people (50% women and 50% men) with a mean age of 67.83 ± 4.84 years and a body mass index of 34.55 ± 2.67 kg/m2. The participants were randomly assigned to the experimental group (which received aerobic training with laser phototherapy) and the control group (which received aerobic training alone) for three months. From the baseline to the final analysis, the absolute changes in specific coagulation biomarker levels (fibrinogen, fibrin fragment D, prothrombin time, Kaolin-Cephalin Coagulation Time), and contributing parameters (C-reactive protein and total cholesterol), were assessed. In comparison to the control group, the experimental group showed significant improvements in all evaluated measures (p < 0.001). So, in comparison to aerobic exercise alone, combined aerobic exercise and laser phototherapy had superior positive effects on coagulation biomarkers and decreased the risk of thromboembolism throughout a three-month intervention period in senior obese persons. Therefore, we suggest adopting laser phototherapy for individuals with a greater risk of hypercoagulability.The research was entered into the database of clinical trials under the identification NCT04503317.

Antitumor and Antibacterial Activity of Ni(II), Cu(II), Ag(I), and Hg(II) Complexes with Ligand Derived from Thiosemicarbazones: Characterization and Theoretical Studies.

Four new complexes (Ni2+, Cu2+, Ag+, and Hg2+) were prepared from the ligand N-(4-chlorophenyl)-2-(phenylglycyl)hydrazine-1-carbothioamide (H2L). Analytical and spectroscopic techniques were used to clarify the structural composition of the new chelates. In addition, all chelates were tested against bacterial strains and the HepG2 cell line to determine their antiseptic and carcinogenic properties. The Ni(II) complex was preferable to the other chelates. Molecular optimization revealed that H2L had the highest reactivity, followed by Hg-chelate, Ag-chelate, Ni-chelate, and Cu-chelate. Moreover, molecular docking was investigated against two different proteins: the ribosyltransferase enzyme (code: 3GEY) and the EGFR tyrosine kinase receptor (code: 1m17).

The RND Efflux Pump Gene Expression in the Biofilm Formation of Acinetobacter baumannii.

Multidrug resistant (MDR) Acinetobacter baumannii is a critical opportunistic pathogen in healthcare-associated infections (HAI). This is attributed to several factors, including its ability to develop biofilms that can enhance antimicrobial resistance (AMR) in addition to creating an environment for horizontal transfer of antibiotic resistance genes. The role of the efflux pump in biofilm formation is important for studies on alternative treatments for biofilms. One of the significant efflux pump families is the RND efflux pump family, which is common in Gram negative bacteria. The aim is to study the role of the RND efflux pump in biofilm formation by A. baumannii. The biofilm formation potential of thirty-four MDR A. baumannii isolates was evaluated by crystal violet assays. The effect of efflux pump inhibition and activation was studied using the efflux pump inhibitor carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and the RND efflux pump substrate levofloxacin (at sub-MIC), respectively. The isolates were genotypically grouped by enterobacterial repetitive intergenic consensus (ERIC) typing and the expression of adeABC, adeFGH, and adeIJK efflux pump genes was measured by qPCR. Overall, 88.2% (30/34) of isolates were biofilm producers (the phenotype was variable including strong and weak producers). Efflux pump inhibition by CCCP reduced the biofilm formation significantly (p < 0.05) in 17.6% (6/34) of some isolates, whereas sub-MICs of the substrate levofloxacin increased biofilm formation in 20.5% (7/34) of other isolates. Overexpression of the three RND efflux pump genes was detected in five out of eleven selected isolates for qPCR with remarkable overexpression in the adeJ gene. No correlation was detected between the biofilm phenotype pattern and the RND efflux pump gene expression in biofilm cells relative to planktonic cells. In conclusion, the role of the RND efflux pumps AdeABC, AdeFGH, and AdeIJK in biofilm formation does not appear to be pivotal and the expression differs according to the genetic background of each strain. Thus, these pumps may not be a promising target for biofilm inhibition.

Synthesis, Characterization, PXRD Studies, Theoretical Calculation, and Antitumor Potency Studies of a Novel N,O-Multidentate Chelating Ligand and Its Zr(IV), V(IV), Ru(III), and Cd(II) Complexes.

A new series of Zr(IV), V(IV), Ru(III), and Cd(II) complexes with the ligand N-((5-hydroxy-4-oxo-4H-pyran-3-yl)methylene)-2-(p-tolylamino)acetohydrazide (H2L) have been prepared. FT-IR, 1H-NMR, electronic spectra, powder X-ray, and thermal behavior methods were applied to elucidate the structural composition of new compounds. Geometry optimization for all synthesized compounds was conducted using the Gaussian09 program via the DFT method, to obtain optimal structures and essential parameters. Moreover, the antibacterial and antitumor activity of the ligand and its complexes were studied, where the Cd(II) complex acquires probably the best antibacterial activity followed by the Ru(III) complex towards bacterial species than others when using ampicillin and gentamicin were used as standard drugs. The complexes exhibited interestingly antitumor potential against the MCF-7 breast cancer cell line. The cytotoxicity of the new complexes has been arranged to follow the order: Ru(III) complex > Cd(II) complex > Zr(IV) complex > V(IV) complex > ligand. Molecular docking was performed on the active site of ribosyltransferase and obtained good results. Structure-based molecular docking is used to identify a potential therapeutic inhibitor for NUDT5.

Molecular Docking, DFT Calculations, Effect of High Energetic Ionizing Radiation, and Biological Evaluation of Some Novel Metal (II) Heteroleptic Complexes Bearing the Thiosemicarbazone Ligand.

New Pb(II), Mn(II), Hg(II), and Zn(II) complexes, derived from 4-(4-chlorophenyl)-1-(2-(phenylamino)acetyl)thiosemicarbazone, were synthesized. The compounds with general formulas, [Pb(H2L)2(OAc)2]ETOH.H2O, [Mn(H2L)(HL)]Cl, [Hg2(H2L)(OH)SO4], and [Zn(H2L)(HL)]Cl, were characterized by physicochemical and theoretical studies. X-ray diffraction studies showed a decrease in the crystalline size of compounds that were exposed to gamma irradiation (γ-irradiation). Thermal studies of the synthesized complexes showed thermal stability of the Mn(II) and Pb(II) complexes after γ-irradiation compared to those before γ-irradiation, while no changes in the Zn(II) and Hg(II) complexes were observed. The optimized geometric structures of the ligand and metal complexes are discussed regarding density functional theory calculations (DFT). The antimicrobial activities of the ligand and metal complexes against several bacterial and fungal stains were screened before and after irradiation. The Hg(II) complex has shown excellent antibacterial activity before and after γ-irradiation. In vitro cytotoxicity screening of the ligand and the Mn(II) and Zn(II) complexes before and after γ-irradiation disclosed that both the ligand and Mn(II) complex exhibited higher activity against human liver (Hep-G2) than Zn(II). Molecular docking was performed on the active site of MK-2 and showed good results.

Co-Existence of Carbapenemase-Encoding Genes in Acinetobacter baumannii from Cancer Patients.

INTRODUCTION: Acinetobacter baumannii is an opportunistic pathogen, which can acquire new resistance genes. Infections by carbapenem-resistant A. baumannii (CRAB) in cancer patients cause high mortality. METHODS: CRAB isolates from cancer patients were screened for carbapenemase-encoding genes that belong to Ambler classes (A), (B), and (D), followed by genotypic characterization by enterobacterial-repetitive-Intergenic-consensus-polymerase chain reaction (ERIC-PCR) and multilocus-sequence-typing (MLST). RESULTS: A total of 94.1% of CRAB isolates co-harbored more than one carbapenemase-encoding gene. The genes blaNDM, blaOXA-23-like, and blaKPC showed the highest prevalence, with rates of 23 (67.7%), 19 (55.9%), and 17 (50%), respectively. ERIC-PCR revealed 19 patterns (grouped into 9 clusters). MLST analysis identified different sequence types (STs) (ST-268, ST-195, ST-1114, and ST-1632) that belong to the highly resistant easily spreadable International clone II (IC II). Genotype diversity indicated the dissemination of carbapenem-hydrolyzing, ß-lactamase-encoding genes among genetically unrelated isolates. We observed a high prevalence of metallo-ß-lactamase (MBL)-encoding genes (including the highly-resistant blaNDM gene that is capable of horizontal gene transfer) and of isolates harboring multiple carbapenemase-encoding genes from different classes. CONCLUSION: The findings are alarming and call for measures to prevent and control the spread of MBL-encoding genes among bacteria causing infections in cancer patients and other immunocompromised patient populations.

In vitro knock-out of miR-155 suppresses leukemic and HCV virus loads in pediatric HCV-4-associated acute lymphoid leukemia: A promising target therapy.

Hepatitis C virus (HCV) infection is a major public health problem, having a high prevalence in Egypt. Leukemia and lymphoma have been associated with HCV infection. MicroRNA-155 (miR-155) has been reported to play a regulatory role in cancer, inflammation, and immune response to infection. The expression level of miR-155 in HCV viremic patients is controversial; although high miR-155 levels were demonstrated in HCV genotypes 1,2, and 3, low levels of miR-155 were detected in Egyptian patients with HCV genotype 4. Several studies have investigated the correlation between the levels of miRNA-155 and the replication of HCV, others have evaluated miRNA-155 as a prognostic biomarker in different types of cancer. No studies have investigated the impact of miRNA-155 knockdown on HCV pediatric patients associated with childhood acute lymphoblastic leukemia (ALL). We knocked-out the miR_155a in cultured polymorphonuclear cells (PBMCs) obtained from 60 children with ALL; 30 were associated with HCV-4 infection and 30 were HCV negative. The miR_155a, HCV viral load, and cell proliferation werre assessed in treated and untreated cells using TaqMan assay quantitative polymerase chain reaction. We found that miRNA-155 was significantly upregulated by seven folds in the HCV-4 associated ALL group; while being linked to high HCV viral load and leukemic burden, miR_155a knock-out can improve the disease outcome. We conclude that miR-155 is a critical miRNA that is considered a therapeutic target in pediatric HCV leukemic patients.

A novel primer set for improved direct gene sequencing of human bocavirus genotype-1 from clinical samples.

Human bocavirus genotype (HBoV-1) is a parvovirus associated with respiratory tract infections in children with different degrees of severity. The current study intended to improve the direct gene sequencing of the HBoV-1 using a newly developed primer set. Screening the presence of human bocavirus infection among in-patients children suffering from lower respiratory tract infections was another aim of the current study. Nasopharyngeal swab samples from in-patients children suffering from lower respiratory tract infections were examined. The real-time polymerase chain reaction was used for the initial screening as a highly sensitive method to detect the HBoV. Genotyping of real-time positive samples was attempted by direct sequencing of PCR amplicons using NP, VP1/2 and the newly developed VP/NC primers. HBoV-1 was present in 56.8% of the examined children. The newly developed primer set successfully amplified all real-time PCR positive samples, however, the other primer pairs did not reliably detect real-time PCR positive samples. The gene sequences of the detected HBoV-1 showed conserved sequences to each other with a low rate of discrepancies. The high rate of infection and the similarity between the detected strains strongly suggest nosocomial infections.

Complex formation equilibria of binary and ternary complexes involving 3,3-bis(1-methylimidazol-2yl)propionic acid and bio-relevant ligands as 1-aminocyclopropane carboxylic acid with reference to plant hormone.

The formation equilibria for the binary complexes of Cu(II) with 1-aminocyclopropane carboxylic acid (ACC) and 3,3-bis(1-methylimidazol-2-yl)propionic acid (BIMP) were investigated. ACC and BIMP form the complexes 110, 120 and 11-1. The ternary complexes of Cu(II) with BIMP and biorelevant ligands as some selected amino acids, peptides and DNA constituents are formed in a stepwise mechanism. The stability constants of the complexes formed were determined and their distribution diagrams were evaluated. The kinetics of hydrolysis of glycine methyl ester in presence of [Cu(BIMP)](+) was investigated by pH-stat technique and the mechanism was discussed.

Speciation studies of diorganotin(IV) complexes with 3,3-bis(1-methylimidazol-2-yl)propionate--displacement reaction by DNA constituents.

The interaction of 3,3-bis(1-methylimidazol-2-yl)propionate (BIMP) with dimethyltin(IV) dichloride (DMT), dibutyltin(IV) dichloride (DBT), and diphenyltin(IV) dichloride (DPT) is investigated at 25°C and 0.1 M ionic strength in water for dimethyltin(IV), and in a 50% dioxane-water mixture for dibutyltin(IV) and diphenyltin(IV). The stepwise formation constants of the 1 : 1 and 1 : 2 complexes formed in solution are calculated from potentiometric measurements using the nonlinear least-square program MINIQUAD-75. The concentration distribution of the various complex species is evaluated as a function of pH. Displacement reactions of the coordinated 3,3-bis(1-methylimidazol-2-yl)propionate by inosine and inosine-5'-monophosphate are investigated from calculations based upon equilibrium properties.

Thermodynamics of the interaction of ruthenium(III) polyaminecarboxylate complexes with bio-relevant ligands. Deactivation of the complexes as NO scavengers by thiol ligands.

The acid-base and complex-formation equilibria of [Ru(H(2)dtpa)(H(2)O)], where dtpa = diethylenetriaminepentaacetate, with a series of bio-relevant ligands having various functional groups, viz. thiol, amine, imidazole and carboxylate, were investigated using potentiometric and spectrophotometric techniques. The pK(a) values for [Ru(H(2)dtpa)(H(2)O)] were found to be 2.28 and 3.48 for the uncoordinated carboxylic acid groups and 8.83 for the coordinated water molecule. The complexes formed are of 1:1 stoichiometry and their formation-constants were determined. The effect of dioxane on the acid-base and complex-formation equilibria of the Ru(III) complex was studied. The displacement reaction of coordinated NO by the investigated ligands showed that thiols can compete with NO in their reaction with [Ru(III)(dtpa)(H(2)O)](2-). The results reveal that the Ru(III) complex is deactivated as a NO scavenger by thiolate ligands.