Assessment of Native Myocardial T1 Mapping for Early Detection of Anthracycline-Induced Cardiotoxicity in Patients with Cancer: a Systematic Review and Meta-analysis.

Anthracycline antibiotic is one of the most effective anti-tumor drugs used to manage certain types of breast cancers, lymphomas, and leukemias. However, anthracyclines induce a dose-dependent cardiotoxicity that may progress to heart failure. Thus, using a sensitive predictor of early cardiac dysfunction in patients treated with anthracyclines can help detect subclinical cardiac dysfunction early and help initiate interventions to protect these patients. Among parameters of myocardial measure, cardiac magnetic resonance (CMR)-measured native myocardial T1 mapping is considered a sensitive and accurate quantitative measure of early subclinical cardiac changes, particularly cardiac inflammation and fibrosis. However, to understand the quality and the validity of the current evidence supporting the use of these measures in patients treated with anthracyclines, we aimed to conduct a systematic review of clinical studies of this measure to detect early myocardial changes in cancer patients treated with anthracyclines. The primary outcome was the level of native T1 mapping. We performed fixed-effects meta-analyses and assessed certainty in effect estimates. Of the 1780 publications reviewed (till 2022), 23 were retrieved, and 9 articles met the inclusion criteria. Our study showed that exposure to anthracycline was associated with a significant elevation of native myocardial T1 mapping from baseline (95% CI 0.1121 to 0.5802; p = 0.0037) as well as compared to healthy control patients (95% CI 0.2925 to 0.7448; p < 0.0001). No significant publication bias was noted on the assessment of the funnel plot and Egger's test. According to the Q test, there was no significant heterogeneity in the included studies (I2 = 0.0000% versus healthy controls and I2 = 14.0666% versus baseline). Overall, our study suggests that native myocardial T1 mapping is useful for detecting anthracycline-induced cardiotoxicity in patients with cancer.

Isolation, screening and characterization of phage.

Bacterial resistance threatens public health due to a lack of novel antibacterial classes since the 21st century. Bacteriophages, the most ubiquitous microorganism on Earth and natural predators of bacteria, have the potential to save the world from the post-antibiotic era. Therefore, phage isolation and characterization are in high demand to find suitable phages for therapeutic and bacterial control applications. The chapter presents brief guidance supported by recommendations on the isolation of phages, and initial screening of phage antimicrobial efficacy, in addition to, conducting comprehensive characterization addressing morphological, biological, genomic, and taxonomic features.

A Comprehensive Review on the Biological, Agricultural and Pharmaceutical Properties of Secondary Metabolites Based-Plant Origin.

Natural products are compounds produced by living organisms and can be divided into two main categories: primary (PMs) and secondary metabolites (SMs). Plant PMs are crucial for plant growth and reproduction since they are directly involved in living cell processes, whereas plant SMs are organic substances directly involved in plant defense and resistance. SMs are divided into three main groups: terpenoids, phenolics and nitrogen-containing compounds. The SMs contain a variety of biological capabilities that can be used as flavoring agents, food additives, plant-disease control, strengthen plant defenses against herbivores and, additionally, it can help plant cells to be better adapted to the physiological stress response. The current review is mainly focusing on certain key elements related to the significance, biosynthesis, classification, biochemical characterization and medical/pharmaceutical uses of the major categories of plant SMs. In addition, the usefulness of SMs in controlling plant diseases, boosting plant resistance and as potential natural, safe, eco-friendly substitutes for chemosynthetic pesticides were also reported in this review.

Estimation of genotoxicity, apoptosis and oxidative stress induction by TiO2 nanoparticles and acrylamide subacute oral coadministration in mice.

Acrylamide is used in the industry and can be a by-product of high-temperature food processing which has toxic potential in various tissues, and titanium dioxide nanoparticles (TiO2NPs) are widely used in toothpaste, sweets, food perseveration, chewing gum and medicines. Consequently, humans are daily exposed to large amounts of acrylamide and TiO2NPs mainly through food intake. However, limited studies are available on the effect of simultaneously intake of acrylamide and TiO2NPs on the integrity of genomic DNA and the induction of apoptosis in brain tissues. Therefore, this study estimated the influence of acrylamide coadministration on TiO2NPs induced genomic instability and oxidative stress in the brain tissues of mice. To achieve this, mice were orally administrated acrylamide (3 mg/kg b.w) or/and TiO2NPs (5 mg/kg b.w) for two successive weeks (5 days per week). The comet assay results showed that concurrent oral administration of acrylamide and TiO2NPs strongly induced single- and double stranded DNA breaks, and that the level of reactive oxygen species (ROS) was also highly elevated within neural cells after simultaneous oral intake of acrylamide and TiO2NPs compared to those observed after administration of acrylamide or/TiO2NPs alone. Moreover, oral co-administration of acrylamide with TiO2NPs increased apoptotic DNA damage to neurons by upregulating the expression levels of P53, TNF-α, IL-6 and Presenillin-1 genes compared to groups administered TiO2NPs. Therefore, from these results, the present study concluded that coadministration of acrylamide renders TiO2NPs more genotoxic and motivates apoptotic DNA damage and oxidative stress induced by TiO2NPs in brain cells, and thus it is recommended to avoid concurrent oral acrylamide administration with TiO2NPs.

Biochemical Characterization of New Gemifloxacin Schiff Base (GMFX-o-phdn) Metal Complexes and Evaluation of Their Antimicrobial Activity against Some Phyto- or Human Pathogens.

Four novel ligand-metal complexes were synthesized through the reaction of Fe(III), pleaseCo(II), Zn(II), and Zr(IV) with Schiff base gemifloxacin reacted with ortho-phenylenediamine (GMFX-o-phdn) to investigate their biological activities. Elemental analysis, FT-IR, 1H NMR, UV-visible, molar conductance, melting points, magnetic susceptibility, and thermal analyses have been carried out for insuring the chelation process. The antimicrobial activity was carried out against Monilinia fructicola, Aspergillus flavus, Penicillium italicum, Botrytis cinerea, Escherichia coli, Bacillus cereus, Pseudomonas fluorescens, and P. aeruginosa. The radical scavenging activity (RSA%) was in vitro evaluated using ABTS method. FT-IR spectra indicated that GMFX-o-phdn chelated with metal ions as a tetradentate through oxygen of carboxylate group and nitrogen of azomethine group. The data of infrared, 1H NMR, and molar conductivity indicate that GMFX-o-phdn reacted as neutral tetra dentate ligand (N2O2) with metal ions through the two oxygen atoms of the carboxylic group (oxygen containing negative charge) and two nitrogen atoms of azomethine group (each nitrogen containing a lone pair of electrons) (the absent of peak corresponding to ν(COOH) at 1715 cm-1, the shift of azomethine group peak from 1633 cm-1 to around 1570 cm-1, the signal at 11 ppm of COOH and the presence of the chloride ions outside the complex sphere). Thermal analyses (TG-DTG/DTA) exhibited that the decaying of the metal complexes exists in three steps with the final residue metal oxide. The obtained data from DTA curves reflect that the degradation processes were exothermic or endothermic. Results showed that some of the studied complexes exhibited promising antifungal activity against most of the tested fungal pathogens, whereas they showed higher antibacterial activity against E. coli and B. cereus and low activity against P. fluorescens and P. aeruginosa. In addition, GMFX-o-phdn and its metal complexes showed strong antioxidant effect. In particular, the parent ligand and Fe(III) complex showed greater antioxidant capacity at low tested concentrations than that of other metal complexes where their IC50 were 169.7 and 164.6 µg/mL, respectively.

Erratum: Elshafie et al. Biological and Spectroscopic Investigations of New Tenoxicam and 1.10-Phenthroline Metal Complexes. Molecules 2020, 25, 1027.

The authors of this paper [...].

Biochemical Characterization, Phytotoxic Effect and Antimicrobial Activity against Some Phytopathogens of New Gemifloxacin Schiff Base Metal Complexes.

String of Fe(III), Cu(II), Zn(II) and Zr(IV) complexes were synthesized with tetradentateamino Schiff base ligand derived by condensation of ethylene diamine with gemifloxacin. The novel Schiff base (4E,4'E)-4,4'-(ethane-1,2-diyldiazanylylidene)bis{7-[(4Z)-3-(aminomethyl)-4-(methoxyimino)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid} (GMFX-en) and its metal complexes were identified and confirmed by elemental analyses, FT-IR, UV/VIS, 1 H-NMR spectra, magnetic susceptibility, conductometric measurements and thermal analyses. The FT-IR spectral data showed the chelation behavior of GMFX-en toward the metal ions through oxygen of carboxylate group and nitrogen of azomethine group. In the light of all spectral data, these complexes presumably have octahedral geometry configurations. Thermal analysis specified that the decaying of the metal complexes exist in two or three steps with the final residue metal oxides. Antimicrobial activity of the new prepared metal complexes was screened against some common phytopathogens and their mode of action has been also discussed. The potential phytotoxic effectiveness of the new complexes was furthermore inspected on two commonly experimental plants. The complexes showed significant antimicrobial and phytotoxic effects against the majority of tested phytopathogens and the two tested plants, respectively. The potential antimicrobial activity of the complexes proved their possibility to be used successfully in agropharmacutical industry to control many serious phytopathogens. The phytotoxicity of the studied complexes also indicated their possibility as potential bio-based herbicides alternatives to weed control in crop fields.

Meloxicam and Study of Their Antimicrobial Effects against Phyto- and Human Pathogens.

Recently, the design of new biological metal-ligand complexes has gained a special interest all over the world. In this research, new series of mixed ligand complexes from meloxicam (H2mel) and glycine (Gly) were synthesized. Structures of the compounds were investigated employing elemental analyses, infrared, electronic absorption, 1H NMR, thermal analyses, effective magnetic moment and conductivity. The estimated molar conductivity of the compounds in 1 × 10-3 M DMF solution indicates the non-electrolyte existence of the examined complexes. Additionally, the effective magnetic moment values refer to the complexes found as octahedral molecular geometry. The data of the infrared spectra showed the chelation of H2mel and Gly with metal ions from amide oxygen and nitrogen of the thyizol groups of H2mel and through nitrogen of the amide group and oxygen of the carboxylic group for Gly. Thermal analyses indicated that the new complexes have good thermal stability and initially lose hydration water molecules followed by coordinated water molecules, Gly and H2mel. The kinetic parameters were calculated graphically using Coats-Redfern and Horowitz-Metzeger methods at n = 1 and n ≠ 1. The density functional theory (DFT) calculations were performed at B3LYP levels. The optimized geometry of the ligand and its complexes were obtained based on the optimized structures. The data indicated that the complexes are soft with η value in the range 0.114 to 0.086, while η = 0.140 for free H2mel. The new prepared complexes were investigated as antibacterial and antifungal agents against some phyto- and human pathogens and the minimum inhibitory concentration (MIC) data showed that complex (A) has the lowest MIC for Listeria and E. coli (10.8 µg/mL).

Biological and Spectroscopic Investigations of New Tenoxicam and 1.10-Phenthroline Metal Complexes.

In the present work, tenoxicam (H2Ten) reacted with Mn(II), Co(II), Ni(II), Cu(II) and Zn (II) ions in the presence of 1.10-phenthroline (Phen), forming new mixed ligand metal complexes. The properties of the formed complexes were depicted by elemental analyses, infrared, electronic spectra, proton nuclear magnetic resonance (1H NMR), mass spectrometry, thermogravimetric (TGA) and differential thermogravimetric (DTG) analysis, molar conductance and magnetic moment. IR spectra demonstrated that H2Ten acted as a neutral bidentate ligand, coordinated to the metal ions via the pyridine-N and carbonyl group of the amide moiety, and Phen through the nitrogen atoms. Kinetic thermodynamics parameters activation energy (E*), enthalpy of activation (ΔH*), entropy of activation (ΔS*), Gibbs, free energy (ΔG*) associated to the complexes have been evaluated. Antibacterial screening of the compounds was carried out in vitro against Clavibacter michiganensis, Xanthomonas campestris and Bacillus megaterium. Antifungal activity was performed in vitro against Monilinia fructicola, Penicillium digitatum and Colletotrichum acutatum. The possible phytotoxic effect of the studied compounds was also investigated on Solanum lycopersicum (tomatoes) and Lepidium sativum (garden cress) seeds. The anticancer activity was screened against cell cultures of HCT-116 (human colorectal carcinoma), HepG2 (human hepatocellular carcinoma) and MCF-7 (human breast adenocarcinoma).

Novel spectrophotometric methods for the determination of Leflunomide and Diacerein in binary mixtures.

Two novel spectrophotometric methods were presented in this work using ethanol as a solvent. The first method was the ratio difference spectrophotometric method [RDSM], in which the amplitude difference between two selected wavelengths on the ratio spectra were recorded and used for estimation of each of Leflunomide LEF in mixture with its alkaline induced degradate DEG and also for Diacerein DIA determination in mixture with Aceclofenac ACEC without interference from the other component in the mixture. The second method is the ratio subtraction coupled with constant multiplication [RS-CM], where LEF was determined in its mixture with its alkaline degradate DEG at 261 nm which is considered as a stability indicating assay. In addition to simultaneous determination of Diacerein DIA and Aceclofenac ACEC in their mixtures at 257 and 277 nm, respectively, by the second method without previous separation. Linearity was shown over the concentration range of [1.5-15 µg/ml] for LEF, [1-11 µg/ml] for DIA and [2.5-25 µg/ml] for ACEC, by both proposed methods. Leflunomide was found to be completely degraded when subjected to alkaline degradation producing one alkaline product. Validation of the suggested methods was conducted according to ICH guidelines, concerning precision, accuracy, repeatability. The suggested spectrophotometric methods were statistically compared to reference methods showing no significant difference. The suggested spectrophotometric methods are considered to be simple, sensitive and could be easily applied in quality control laboratories instead of LC methods.

Carotid Doppler ultrasonography as a screening tool of early atherosclerotic changes in children and young adults with ß-thalassemia major.

PURPOSE: ß-thalassemia major (ß-TM) patients had an increased incidence of cardiovascular complications secondary to iron overload. They showed early carotid atherosclerosis as showed by increased carotid intima media thickness (CIMT) that may occur early even when significant iron overload is absent. We aimed to test the diagnostic performance of CIMT measurement by Doppler ultrasonography as a structural indicator for premature atherosclerosis in ß-TM patients. METHODS: Case-control study included 42 ß-TM patients (24 males and 18 females) aged from 3 to 30 years and 36 age- and sex-matched healthy controls. Carotid Duplex was used for measurement of CIMT in all subjects. RESULTS: The frequency of abnormal CIMT among patients was 19%. Mean CIMT of right anterior wall was 0.8 ± 0.16 (range 0.5-1.2) mm, of right posterior wall was 0.80 ± 0.17 (range 0.5-1.2), of right lateral wall was 0.8 ± 0.17 (range 0.5-1.1) mm. CIMT of left anterior wall ranged from 0.5 to 1.2 with mean 0.81 ± 0.17, CIMT of left posterior wall ranged from 0.5 to 1.1 with mean 0.80 ± 0.17 mm. Mean CIMT of left lateral wall was 0.81 ± 0.18 mm (range 0.5-1.2). CIMT of right anterior, right posterior and left anterior walls were thicker in patients compared to controls (P = 0.003, 0.015, < 0.001, respectively). There was no observable difference in CIMT between males and females, splenectomised and non-splenectomised, or well and poorly chelated subgroups (P > 0.05). CIMT of right lateral wall correlated with the disease duration (r = 0.3, P = 0.04). CONCLUSIONS: Carotid ultrasound was a useful tool to detect subclinical atherosclerosis thorough CIMT evaluation in B-thalassemia major patients. B-thalassemia major children proved to have an increased CIMT regardless the state of iron overload.