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Future Medicinal Chemistry Jul 2024This study aimed to enhance the aqueous dissolution of SRPK inhibitor -(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340). A complex with...
This study aimed to enhance the aqueous dissolution of SRPK inhibitor -(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340). A complex with -sulfonic calix[6]arene (Host) and SRPIN340 (Guest) was prepared, studied via H nuclear magnetic resonance (NMR) and theoretical calculations and biologically evaluated on cancer cell lines. The 1:1 host (H)/guest (G) complex significantly enhanced the aqueous dissolution of SRPIN340, achieving 64.8% water solubility as determined by H NMR quantification analysis. The H/G complex reduced cell viability by 75% for HL60, ∼50% for Nalm6 and Jurkat, and ∼30% for B16F10 cells. It exhibited greater cytotoxicity than free SRPIN340 against Jurkat and B16F10 cells. Theoretical studies indicated hydrogen bond stabilization of the complex, suggesting broader applicability of SRPIN340 across diverse biological systems.
PubMed: 38949866
DOI: 10.1080/17568919.2024.2366690 -
Future Medicinal Chemistry Jul 2024: To synthesize new hybrid cinnamic acids (, and ) and ester derivatives (, and ) and investigate their anti-breast cancer activities. Compounds were evaluated ()...
: To synthesize new hybrid cinnamic acids (, and ) and ester derivatives (, and ) and investigate their anti-breast cancer activities. Compounds were evaluated () for their cytotoxic activities against the MCF-7 cell line. A flow cytometry examination was performed. Protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), topoisomerase II and caspase-9 were measured by qRT-PCR. Molecular docking studies were conducted. : Several components were discovered to be active, mainly component , which induced arrest in the cell cycle at phase S, greatly decreased the expression of Nrf2 and topoisomerase II; and upregulated the expression of caspase-9. The newly thiohydantoin-cinnamic acid hybrids can contribute to creating promising candidates for cancer drugs.
PubMed: 38949859
DOI: 10.1080/17568919.2024.2366694 -
Angewandte Chemie (International Ed. in... Jul 2024The diterpene synthase AfAS was identified from Aspergillus fumigatiaffinis. Its amino acid sequence and - according to a structural model - active site architecture are...
The diterpene synthase AfAS was identified from Aspergillus fumigatiaffinis. Its amino acid sequence and - according to a structural model - active site architecture are highly similar to those of the fusicocca-2,10(14)-diene synthase PaFS, but AfAS produces a structurally much more complex diterpene with a novel 6-5-5-5 tetracyclic skeleton called asperfumene. The cyclisation mechanism of AfAS was elucidated through isotopic labelling experiments and DFT calculations. The reaction cascade proceeds in its initial steps through similar intermediates as for the PaFS cascade, but then diverges through an unusual vicinal deprotonation-reprotonation process that triggers a skeletal rearrangement at the entrance to the steps leading to the unique asperfumene skeleton. The structural model revealed only one major difference between the active sites: The PaFS residue F65 is substituted by I65 in AfAS. Intriguingly, site-directed mutagenesis experiments with both diterpene synthases revealed that position 65 serves as a bidirectional functional switch for the biosynthesis of tetracyclic asperfumene versus structurally less complex diterpenes.
PubMed: 38949843
DOI: 10.1002/anie.202407895 -
Dental and Medical Problems 2024Despite the superiority of glass-ionomer cements (GICs) over composites in treating white spot lesions (WSLs), there is still a concern about their preventive and...
BACKGROUND
Despite the superiority of glass-ionomer cements (GICs) over composites in treating white spot lesions (WSLs), there is still a concern about their preventive and antibacterial properties. Efforts have been made to improve the strength of their bond to demineralized enamel, fluoride release and antibacterial properties by adding nanoparticles of chitosan, which seems to be a promising method.
OBJECTIVES
The aim of the present study was to assess the antibacterial effect, the microshear bond strength (μSBS) to enamel at the WSL area, and the fluoride and nano-chitosan release after modifying the polyacrylic acid liquid phase of a traditional GIC with different nano-chitosan volumes.
MATERIAL AND METHODS
A total of 120 samples were prepared, and then divided into 4 groups (n = 30): G1 - non-modified GIC, which served as a control group, while G2, G3 and G4 were modified with different nano-chitosan volumes (50%, 100% and 150%, respectively). Microshear bond strength was assessed using a universal testing machine (UTM) after storage in distilled water for 24 h. Fluoride and nanochitosan release was measured with the use of spectrophotometers at different time points (initially, and at 1 h, 24 h, 48 h, 72 h, 1 week, 2 weeks, 3 weeks, and 6 weeks) after storage in distilled water. The antibacterial effect against the Streptococcus aureus strain was assessed with the agar diffusion test. The data was statistically analyzed.
RESULTS
After 24-hour storage, G2 recorded a slight, yet non-significant, increase in the μSBS values (4.1 ±0.94 MPa) as compared to G1 (3.9 ±1.30 MPa). With regard to fluoride release, the amount recorded for G1 was significantly greater at the end of the 24-hour storage period (0.70 ±0.30 μmf/cm2) than modified nano-chitosan GIC groups; G1 was followed by G4 (0.54 ±0.34 μmf/cm2). The highest amount of nano-chitosan release after 24-hour storage was noted for G3 (0.85 ±0.00 μmf/cm2). The highest inhibition zone value was recorded for G2.
CONCLUSIONS
Glass-ionomer cement modified with 50% nano-chitosan was shown to positively affect μSBS and the antibacterial effect, while modification with 150% nano-chitosan significantly increased fluoride release.
Topics: Chitosan; Anti-Bacterial Agents; Glass Ionomer Cements; Dental Caries; In Vitro Techniques; Fluorides; Humans; Nanoparticles; Shear Strength; Dental Enamel; Materials Testing; Dental Bonding
PubMed: 38949834
DOI: 10.17219/dmp/158835 -
Bulletin of Environmental Contamination... Jun 2024Microplastics (MPs) pollution is a profound problem around the world yet it's study on the effect on zooplankton including copepods are very limited. The study was...
Microplastics (MPs) pollution is a profound problem around the world yet it's study on the effect on zooplankton including copepods are very limited. The study was conducted between January 2021 and January 2022 in the Lower Meghna Estuary to investigate MPs ingestion in two different family of copepod: Calanoid and Cyclopoid. A method of acid digestion along with Scanning Electron Microscope (SEM) was used to identify MPs ingested by copepods from the conducted area. However, three types of MPs namely fiber, fragment and foam were extracted from this copepod biomass. Fibers represent highest (> 50%) of the ingested MPs from both group of copepod that exceed fragments and foams in all sampling stations. The overall ingestion rate of Calanoid was found higher (0.084 ± 0.002 particles/individual) compared to the Cyclopoid group (0.077 ± 0.001 particles/individual). The results of the study have effectively illustrated that copepod, obtained from multiple sampling sites within the Lower Meghna Estuary, display a propensity to ingest MPs and subsequently endangering the food security of seafood industry.
Topics: Copepoda; Animals; Microplastics; Water Pollutants, Chemical; Environmental Monitoring; Estuaries; Bangladesh; Eating
PubMed: 38949743
DOI: 10.1007/s00128-024-03919-5 -
Tropical Animal Health and Production Jun 2024This study aimed to evaluate and analyze the effects of a flushing diet containing Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) from Lemuru (Sardinella sp)...
The benefits of flushing with Lemuru fish oil as a source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on the performance of reproductive parameters in Garut ewes.
This study aimed to evaluate and analyze the effects of a flushing diet containing Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) from Lemuru (Sardinella sp) fish oil on the reproductive performance parameters of Garut ewes. Forty (n = 40) primiparous Garut ewes aged 12-14 months with an average body weight of 28.92 ± 4.94 kg were assigned into four experimental treatment groups. The experimental diets contained roughage: concentrate (30:70%) designated as control concentrate (CNT), flushing concentrate with 6% palm oil (PO), flushing concentrate with 3% palm oil mixed with 3% lemuru oil as DHA and EPA sources (PFO), and flushing concentrate with the addition of 6% lemuru oil (FO). Treatment animals were fed two weeks before and after conception and parturition (8 weeks of total flushing treatment). The addition of fish oil at either 3% (PFO) or 6% (FO) resulted in significantly higher reproductive performance of ewes by increasing the litter size, as reflected by the birth of multiple kids (P < 0.05) compared to CNT and PO. Adding fish oil (PFO and FO) also maintains gestation, resulting in increased lamb yield, especially in the FO treatment, which yields the highest lamb yield (0% single lamb birth). The lamb male ratio was also higher with fish oil supplementation (PFO and PO) (P < 0.05). This research revealed a positive effect of 6% Lemuru oil on decreasing embryo loss and increasing the proportion of twin births. These findings thus support the hypothesis that ration flushing with double the required DHA and EPA from 6% Lemuru fish oil (FO) resulted in significantly higher reproductive performance in Garut sheep.
Topics: Animals; Female; Eicosapentaenoic Acid; Docosahexaenoic Acids; Fish Oils; Animal Feed; Dietary Supplements; Reproduction; Diet; Sheep, Domestic; Pregnancy
PubMed: 38949740
DOI: 10.1007/s11250-024-04060-5 -
Environmental Science and Pollution... Jun 2024To maximize the efficiency of biomass waste utilization and waste management, a novel acid-modified magnetic biomass spent coffee grounds (NiFeO/SCG) was obtained by...
To maximize the efficiency of biomass waste utilization and waste management, a novel acid-modified magnetic biomass spent coffee grounds (NiFeO/SCG) was obtained by pyrolysis at 473 K and co-precipitation methods and employed to eliminate bivalent mercury (Hg(II)) in water bodies. The prepared NiFeO/SCG adsorbent exhibits remarkable magnetism with a strength of 45.78 emu/g and can easily be separated from water via a magnetic force. The adsorption of Hg(II) over the NiFeO/SCG has an optimal conditions of pH = 8, T = 39 ℃, and dosage of 0.055 g/L, and the maximal adsorption capacity for Hg(II) is 167.44 mg/g via Response Surface Methodology optimization. The removal of Hg(II) over NiFeO/SCG primarily involves ion exchange, electrostatic attraction, and chelation; conforms to the pseudo-second-order kinetic and Langmuir models; and is an endothermic reaction. Additionally, the magnetic biomass NiFeO/SCG has good regeneration capability and stability. The application research reveal that inorganic salt ions, nitrogen fertilizer urea, humus, and other contaminants in different actual water bodies (river water, lake water, and the effluent of sewage treatment plant) have little effect on the adsorption of Hg(II) over the NiFeO/SCG. The prepared adsorbent NiFeO/SCG has practical application value for removing Hg(II) from water bodies.
PubMed: 38949731
DOI: 10.1007/s11356-024-34058-3 -
Methods in Molecular Biology (Clifton,... 2024Antimicrobial resistance (AMR) poses a serious threat to global health, potentially causing 10 million deaths per year globally by 2050. To tackle AMR, researchers from...
Antimicrobial resistance (AMR) poses a serious threat to global health, potentially causing 10 million deaths per year globally by 2050. To tackle AMR, researchers from all around the world have generated a selection of various formulated (viz. nanoparticulate, liposomal) therapeutic combinations to be evaluated for new antimicrobial drug discovery. To meet the urgent need for accelerating new antibacterial drug development, we need rapid but reliable whole-cell assay methods and models to test formulated therapeutic combinations against several pathogens in different in vitro conditions as models of actual infections.Over the past two decades, high-throughput spot-culture growth inhibition assay (HT-SPOTi) has been demonstrated to be a gold-standard drug susceptibility method for evaluating novel chemotherapeutic entities and existing drugs against various microbes of global concern. Our modified HT-SPOTi method serves the purpose of evaluating drug combinations against Gram-positive/negative microorganisms as well as acid-fast bacilli. The newly developed and modified HT-SPOTi assay builds upon the limitations of our previously published method to incorporate antimicrobial susceptibility testing with formulated therapeutic combinations. The modified HT-SPOTi is compared with a range of other antimicrobial susceptibility testing methods and validated using a library of existing antibiotics as well as formulated therapeutic combinations. The modified HT-SPOTi assay can serve as an efficient and reliable high-throughput drug screening platform to discover new potential antimicrobial molecules, including as part of therapeutic formulations.This chapter describes the generation of drug susceptibility profile for formulated therapeutic combinations using modified HT-SPOTi in a semi-automated system.
Topics: Microbial Sensitivity Tests; Anti-Bacterial Agents; High-Throughput Screening Assays; Humans; Bacteria
PubMed: 38949698
DOI: 10.1007/978-1-0716-3981-8_4 -
Neurotoxicity Research Jun 2024Nonketotic hyperglycinemia (NKH) is an inherited disorder of amino acid metabolism biochemically characterized by the accumulation of glycine (Gly) predominantly in the... (Review)
Review
Nonketotic hyperglycinemia (NKH) is an inherited disorder of amino acid metabolism biochemically characterized by the accumulation of glycine (Gly) predominantly in the brain. Affected patients usually manifest with neurological symptoms including hypotonia, seizures, epilepsy, lethargy, and coma, the pathophysiology of which is still not completely understood. Treatment is limited and based on lowering Gly levels aiming to reduce overstimulation of N-methyl-D-aspartate (NMDA) receptors. Mounting in vitro and in vivo animal and human evidence have recently suggested that excitotoxicity, oxidative stress, and bioenergetics disruption induced by Gly are relevant mechanisms involved in the neuropathology of NKH. This brief review gives emphasis to the deleterious effects of Gly in the brain of patients and animal models of NKH that may offer perspectives for the development of novel adjuvant treatments for this disorder.
Topics: Hyperglycinemia, Nonketotic; Animals; Humans; Oxidative Stress; Energy Metabolism; Glycine; Brain
PubMed: 38949693
DOI: 10.1007/s12640-024-00711-5 -
Mikrochimica Acta Jun 2024A pico-injection-aided digital droplet detection platform is presented that integrates loop-mediated isothermal amplification (LAMP) with molecular beacons (MBs) for...
A pico-injection-aided digital droplet detection platform is presented that integrates loop-mediated isothermal amplification (LAMP) with molecular beacons (MBs) for the ultrasensitive and quantitative identification of pathogens, leveraging the sequence-specific detection capabilities of MBs. The microfluidic device contained three distinct functional units including droplet generation, pico-injection, and droplet counting. Utilizing a pico-injector, MBs are introduced into each droplet to specifically identify LAMP amplification products, thereby overcoming issues related to temperature incompatibility. Our methodology has been validated through the quantitative detection of Escherichia coli, achieving a detection limit as low as 9 copies/μL in a model plasmid containing the malB gene and 3 CFU/μL in a spiked milk sample. The total analysis time was less than 1.5 h. The sensitivity and robustness of this platform further demonstrated the potential for rapid pathogen detection and diagnosis, particularly when integrated with cutting-edge microfluidic technologies.
Topics: Nucleic Acid Amplification Techniques; Escherichia coli; Limit of Detection; Milk; Animals; Molecular Diagnostic Techniques; Microfluidic Analytical Techniques; DNA, Bacterial
PubMed: 38949666
DOI: 10.1007/s00604-024-06509-8