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Combination of with difenoconazole to control pear black spot and the related synergistic mechanism.Frontiers in Microbiology 2024Pear black spot (PBS) is caused by and causes severe damage worldwide. It is particularly important to screen for synergistic fungicide combinations to address issues...
BACKGROUND
Pear black spot (PBS) is caused by and causes severe damage worldwide. It is particularly important to screen for synergistic fungicide combinations to address issues associated with the low efficacy of biocontrol agents, high dosage requirements and poor sustained effectiveness of chemical fungicides.
METHODS
and studies were performed to determine the efficacy of a treatment for this important disease. Additionally, transcriptomic and metabolomic analyses were performed to determine the main molecular and biochemical mechanisms involved in the interaction.
RESULTS
2_2a has a significant synergistic effect with difenoconazole, causing hyphal entanglement and spore lysis and inhibiting the formation of PBS lesions . In the field, the control effect of the combination was greater than 95%. The pathways associated with the synergistic effect on the mycelia of were divided into two main types: one included glycolysis, oxidative phosphorylation, and MAPK signal transduction, while the other included glycolysis, the TCA cycle, coenzyme A biosynthesis, sterol synthesis, and fatty acid degradation. Both types of pathways jointly affect the cell cycle. The main functions of the key genes and metabolites that have been verified as being affected are glucose synthesis and oxidative respiration, as well as citric acid synthesis, acetyl-CoA synthesis, and sterol synthesis. Both functions involve intracellular pyridine nucleotide metabolism and adenine nucleotide transformation.
CONCLUSION
This study helps to reveal the synergistic mechanisms underlying the combined efficacy of biological and chemical agents, providing a scientific basis for field applications.
PubMed: 38894972
DOI: 10.3389/fmicb.2024.1405039 -
Molecules (Basel, Switzerland) Jun 2024In recent years, there has been increasing attention focused on various products belonging to the imidazopyridine family; this class of heterocyclic compounds shows... (Review)
Review
In recent years, there has been increasing attention focused on various products belonging to the imidazopyridine family; this class of heterocyclic compounds shows unique chemical structure, versatile optical properties, and diverse biological attributes. The broad family of imidazopyridines encompasses different heterocycles, each with its own specific properties and distinct characteristics, making all of them promising for various application fields. In general, this useful category of aromatic heterocycles holds significant promise across various research domains, spanning from material science to pharmaceuticals. The various cores belonging to the imidazopyridine family exhibit unique properties, such as serving as emitters in imaging, ligands for transition metals, showing reversible electrochemical properties, and demonstrating biological activity. Recently, numerous noteworthy advancements have emerged in different technological fields, including optoelectronic devices, sensors, energy conversion, medical applications, and shining emitters for imaging and microscopy. This review intends to provide a state-of-the-art overview of this framework from 1955 to the present day, unveiling different aspects of various applications. This extensive literature survey may guide chemists and researchers in the quest for novel imidazopyridine compounds with enhanced properties and efficiency in different uses.
PubMed: 38893542
DOI: 10.3390/molecules29112668 -
Molecules (Basel, Switzerland) Jun 2024The existing kinase inhibitors for hepatocellular carcinoma (HCC) have conferred survival benefits but are hampered by adverse effects and drug resistance, necessitating...
The existing kinase inhibitors for hepatocellular carcinoma (HCC) have conferred survival benefits but are hampered by adverse effects and drug resistance, necessitating the development of novel agents targeting distinct pathways. To discover potent new anti-HCC compounds, we leveraged scaffold hopping from Sorafenib and introduced morpholine/piperidine moieties to develop ureido-substituted 4-phenylthiazole analogs with optimized physicochemical properties and binding interactions. Notably, compound exhibited potent cytotoxicity against HepG2 cells (IC = 0.62 ± 0.34 μM), significantly exceeding Sorafenib (IC = 1.62 ± 0.27 μM). Mechanistic investigations revealed that compound potently inhibited HCC cell migration and colony formation, and it induced G2/M arrest and early-stage apoptosis. Kinase profiling revealed IGF1R as a key target, which compound potently inhibited (76.84% at 10 μM). Molecular modeling substantiated compound 's strong binding to IGF1R via multiple hydrogen bonds. Computational predictions indicate favorable drug-like properties for compound . These findings provide a promising drug candidate for the treatment of HCC patients.
Topics: Humans; Receptor, IGF Type 1; Cell Proliferation; Hep G2 Cells; Thiazoles; Protein Kinase Inhibitors; Antineoplastic Agents; Apoptosis; Liver Neoplasms; Carcinoma, Hepatocellular; Cell Movement; Structure-Activity Relationship; Molecular Docking Simulation; Receptors, Somatomedin; Molecular Structure; Cell Line, Tumor; Sorafenib; Models, Molecular
PubMed: 38893528
DOI: 10.3390/molecules29112653 -
Molecules (Basel, Switzerland) May 2024A series of iridium(III) triimine complexes incorporating 2,2':6',2″-terpyridine () and 2,6-bis(thiazol-2-yl)pyridine () derivatives were successfully designed and...
A series of iridium(III) triimine complexes incorporating 2,2':6',2″-terpyridine () and 2,6-bis(thiazol-2-yl)pyridine () derivatives were successfully designed and synthesized to investigate the impact of the peripheral rings (pyridine, thiazole) and substituents (thiophene, bithiophene, EDOT) attached to the triimine skeleton on their photophysical properties. The Ir(III) complexes were fully characterized using IR, H, elemental analysis and single crystal X-ray analysis. Their thermal properties were evaluated using TGA measurements. Photoluminescence spectra of [IrClL] were investigated in solution at 298 and 77 K. The experimental studies were accompanied by DFT/TDDFT calculations. The photophysical properties of the synthesized triimine ligands and Ir(III) complexes were studied in detail by electronic absorption and emission. In solution, they exhibited photoluminescence quantum yields ranging from 1.27% to 5.30% depending on the chemical structure. The experimental research included DFT/TDDFT calculations. The photophysical properties of the synthesized triimine ligands and Ir(III) complexes were conducted using electronic absorption and emission techniques. In solution, they displayed photoluminescence quantum yields ranging from 1.27% to 5.30% depending on the chemical structure.
PubMed: 38893372
DOI: 10.3390/molecules29112496 -
Molecules (Basel, Switzerland) May 2024The use of z-drugs has increased worldwide since its introduction. Although the prescribing patterns of hypnotics differ among countries, zolpidem is the most widely...
Development and Validation of a Sonication-Assisted Dispersive Liquid-Liquid Microextraction Procedure and an HPLC-PDA Method for Quantitative Determination of Zolpidem in Human Plasma and Its Application to Forensic Samples.
The use of z-drugs has increased worldwide since its introduction. Although the prescribing patterns of hypnotics differ among countries, zolpidem is the most widely used z-drug in the world. Zolpidem may be involved in poisoning and deaths. A simple and fast HPLC-PDA method was developed and validated. Zolpidem and the internal standard chloramphenicol were extracted from plasma using a sonication-assisted dispersive liquid-liquid microextraction procedure. The method was validated including selectivity, linearity, precision, accuracy, and recovery. The calibration range (0.15-0.6 µg/mL) covers therapeutic and toxic levels of zolpidem in plasma. The limit of quantification was set at 0.15 µg/mL. Intra- and interday accuracy and precision values were lower than 15% at the concentration levels studied. Excellent recovery results were obtained for all concentrations. The proposed method was successfully applied to ten real postmortem plasma samples. In our series, multiple substances (alcohol and/or other drugs) were detected in most cases of death involving zolpidem. Our analytical method is suitable for routine toxicological analysis.
Topics: Zolpidem; Humans; Liquid Phase Microextraction; Chromatography, High Pressure Liquid; Sonication; Reproducibility of Results; Hypnotics and Sedatives; Limit of Detection; Pyridines
PubMed: 38893365
DOI: 10.3390/molecules29112490 -
Cancers Jun 2024The authors would like to make a correction to the previous article [...].
The authors would like to make a correction to the previous article [...].
PubMed: 38893284
DOI: 10.3390/cancers16112151 -
Nutrients May 2024Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (Soloways) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized...
Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B vitamin supplements (methylfolate, pyridoxal-5'-phosphate, and methylcobalamin) on homocysteine and lipid levels, potentially guiding personalized CVD risk management. In a randomized, double-blind, placebo-controlled trial, 54 patients aged 40-75 with elevated homocysteine and moderate LDL-C levels were divided based on MTHFR, MTR, and MTRR genetic polymorphisms. Over six months, they received either a combination of methylfolate, P5P, and methylcobalamin, or a placebo. At the 6 months follow-up, the treatment group demonstrated a significant reduction in homocysteine levels by 30.0% (95% CI: -39.7% to -20.3%) and LDL-C by 7.5% (95% CI: -10.3% to -4.7%), compared to the placebo ( < 0.01 for all). In the subgroup analysis, Homozygous Minor Allele Carriers showed a more significant reduction in homocysteine levels (48.3%, 95% CI: -62.3% to -34.3%, < 0.01) compared to mixed allele carriers (18.6%, 95% CI: -25.6% to -11.6%, < 0.01), with a notable intergroup difference (29.7%, 95% CI: -50.7% to -8.7%, < 0.01). LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: -15.8% to -7.8%, < 0.01) and 4.8% in mixed allele carriers (95% CI: -6.8% to -2.8%, < 0.01), with a significant between-group difference (7.0%, 95% CI: -13.0% to -1.0%, < 0.01). Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR, MTR, and MTRR polymorphisms, particularly with homozygous minor allele polymorphisms.
Topics: Humans; Middle Aged; Homocysteine; Female; Male; Dietary Supplements; Methylenetetrahydrofolate Reductase (NADPH2); Double-Blind Method; 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Cholesterol, LDL; Aged; Vitamin B 12; Pyridoxal Phosphate; Adult; Ferredoxin-NADP Reductase; Tetrahydrofolates; Polymorphism, Genetic; Vitamin B Complex
PubMed: 38892484
DOI: 10.3390/nu16111550 -
International Journal of Molecular... Jun 2024Phenotypic susceptibility testing of the complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing...
Phenotypic susceptibility testing of the complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing (WGS) and data analysis pipelines can assist in predicting resistance to antimicrobials used in the treatment of tuberculosis (TB). This study compared phenotypic susceptibility testing results and WGS-based predictions of antimicrobial resistance (AMR) to four first-line antimicrobials-isoniazid, rifampin, ethambutol, and pyrazinamide-for MTBC isolates tested between the years 2018-2022. For this 5-year retrospective analysis, the WGS sensitivity for predicting resistance for isoniazid, rifampin, ethambutol, and pyrazinamide using Mykrobe was 86.7%, 100.0%, 100.0%, and 47.8%, respectively, and the specificity was 99.4%, 99.5%, 98.7%, and 99.9%, respectively. The predictive values improved slightly using Mykrobe corrections applied using TB Profiler, i.e., the WGS sensitivity for isoniazid, rifampin, ethambutol, and pyrazinamide was 92.31%, 100%, 100%, and 57.78%, respectively, and the specificity was 99.63%. 99.45%, 98.93%, and 99.93%, respectively. The utilization of WGS-based testing addresses concerns regarding test turnaround time and enables analysis for MTBC member identification, antimicrobial resistance prediction, detection of mixed cultures, and strain genotyping, all through a single laboratory test. WGS enables rapid resistance detection compared to traditional phenotypic susceptibility testing methods using the WHO TB mutation catalog, providing an insight into lesser-known mutations, which should be added to prediction databases as high-confidence mutations are recognized. The WGS-based methods can support TB elimination efforts in Canada and globally by ensuring the early start of appropriate treatment, rapidly limiting the spread of TB outbreaks.
Topics: Whole Genome Sequencing; Mycobacterium tuberculosis; Antitubercular Agents; Humans; Microbial Sensitivity Tests; Retrospective Studies; Drug Resistance, Bacterial; Genome, Bacterial; Ethambutol; Isoniazid; Pyrazinamide; Tuberculosis; Rifampin
PubMed: 38892433
DOI: 10.3390/ijms25116245 -
International Journal of Molecular... May 2024Diarrhoea remains an important public health concern, particularly in developing countries, and has become difficult to treat because of antibacterial resistance. The...
Diarrhoea remains an important public health concern, particularly in developing countries, and has become difficult to treat because of antibacterial resistance. The development of synergistic antimicrobial agents appears to be a promising alternative treatment against diarrhoeic infections. In this study, the combined effect of tetracycline together with either nitroxoline, sanguinarine, or zinc pyrithione (representing various classes of plant-based compounds) was evaluated in vitro against selected diarrhoeic bacteria (, , , , , and ). The chequerboard method in 96-well microtiter plates was used to determine the sum of the fractional inhibitory concentration indices (FICIs). Three independent experiments were performed per combination, each in triplicate. It was observed that the combination of tetracycline with either nitroxoline, sanguinarine, or zinc pyrithione produced synergistic effects against most of the pathogenic bacteria tested, with FICI values ranging from 0.086 to 0.5. Tetracycline-nitroxoline combinations produced the greatest synergistic action against at a FICI value of 0.086. The combinations of the agents tested in this study can thus be used for the development of new anti-diarrhoeic medications. However, studies focusing on their in vivo anti-diarrhoeic activity and safety are required before any consideration for utilization in human medicine.
Topics: Drug Synergism; Tetracycline; Anti-Bacterial Agents; Microbial Sensitivity Tests; Alkaloids; Bacteria; Diarrhea; Humans; Pyridines; Nitroquinolines; Organometallic Compounds
PubMed: 38892226
DOI: 10.3390/ijms25116038 -
International Journal of Molecular... May 2024N-methylpyridinium (NMP) is produced through the pyrolysis of trigonelline during the coffee bean roasting process. Preliminary studies suggest that NMP may have health...
N-methylpyridinium (NMP) is produced through the pyrolysis of trigonelline during the coffee bean roasting process. Preliminary studies suggest that NMP may have health benefits, thanks to its antioxidant properties. Based on this background, the aim of this study was to evaluate whether NMP could have a protective effect against LPS-induced neuroinflammation in human glioblastoma cells (U87MG). With this aim, U87MG cells were pre-treated with NMP (0.5 μM) for 1 h and then exposed to LPS (1 μg/mL) for 24 h. Our findings show that NMP attenuates LPS-induced neuroinflammation by reducing the expression of pro-inflammatory cytokines, such as IL-1β, TNF-α and IL-6, through the inhibition of the NF-κB signaling pathway, which is critical in regulating inflammatory responses. NMP is able to suppress the activation of the NF-κB signaling pathway, suggesting its potential in preventing neuroinflammatory conditions. These outcomes support the notion that regular consumption of NMP, possibly through coffee consumption, may offer protection against neuroinflammatory states implicated in neurological disorders.
Topics: Humans; Lipopolysaccharides; Neuroprotective Agents; NF-kappa B; Neuroinflammatory Diseases; Signal Transduction; Pyridinium Compounds; Cell Line, Tumor; Cytokines
PubMed: 38892185
DOI: 10.3390/ijms25116000