Seda Cetinkaya Karabekir, Burcu Gultekin, Hasan Basri Savas
et al.
Diabetes mellitus (DM) is associated with vascular complications that increase morbidity and mortality. Natural antioxidants play a vital role in reducing diabetes-related damage. This study investigated the protective effects of the phenolic monoterpene carvacrol (CAR) against diabetic complications. Thirty-two male Wistar Albino rats (4 months, 250–300 g) were divided into four groups: control, DM, DM + DMSO, and DM + CAR. Type 1 diabetes was induced via intraperitoneal injection of 50 mg/kg streptozotocin (STZ). The DM + CAR group received 20 mg/kg CAR daily for four weeks. Body weight and blood glucose levels were regularly monitored. At the end of the study, aortic tissues were examined using hematoxylin–eosin (H&E), Verhoeff–Van Gieson, and immunohistochemical staining, while cardiac tissues were analyzed with H&E and Masson’s trichrome. Serum levels of ischemia-modified albumin (IMA), cholesterol (CHOL), triglycerides (TG), and high-density lipoprotein (HDL) were measured. In the DM group, IMA and CHOL levels were increased (<i>p</i> = 0.0208 and <i>p</i> = 0.0207, respectively), apoptosis was elevated (caspase-3 expression, <i>p</i> = 0.0001), and marked tissue damage was observed. In contrast, in the DM + CAR group, IMA levels (<i>p</i> = 0.0228) and caspase-3 expression (<i>p</i> = 0.0457) were reduced, and notable improvements were detected in vascular and cardiac tissues. These results suggest that CAR protects against diabetic complications by modulating oxidative stress, inhibiting apoptosis, and preventing tissue injury.
The capacity to sense and respond to cellular energy stress is an important factor in tumorigenesis. We aimed to investigate the proliferation patterns of KRAS-mutant NSCLC cell lines (A549, Calu-1, H2009) under high (HG) and low glucose (LG) conditions w/wo DCA, which alters metabolic pathways and promotes oxidative phosphorylation.
S. Yu. Shchyogolev, G. L. Burygin, L. A. Dykman
et al.
We report the results of taxonomic studies on members of the family Micrococcaceae that, according to the 16S rRNA, internal transcribed spacer 1 (ITS1), average nucleotide identity (ANI), and average amino acid identity (AAI) tests, are related to Kocuria rosea strain RCAM04488, a plant-growth-promoting rhizobacterium (PGPR) isolated from the rhizosphere of potato (Solanum tuberosum L.). In these studies, we used whole-genome phylogenetic tests and pangenomic analysis. According to the ANI > 95 % criterion, several known members of K. salina, K. polaris, and K. rosea (including K. rosea type strain ATCC 186T) that are related most closely to isolate RCAM04488 in the ITS1 test should be assigned to the same species with appropriate strain verification. However, these strains were isolated from strongly contrasting ecological and geographical habitats, which could not but affect their genotypes and phenotypes and which should be taken into account in evaluation of their systematic position. This contradiction was resolved by a pangenomic analysis, which showed that the strains differed strongly in the number of accessory and strain-specific genes determining their individuality and possibly their potential for adaptation to different ecological niches. Similar results were obtained in a full-scale AAI test against the UniProt database (about 250 million records), by using the AAI-profiler program and the proteome of K. rosea strain ATCC 186T as a query. According to the AAI > 65 % criterion, members of the genus Arthrobacter and several other genera belonging to the class Actinomycetes, with a very wide geographical and ecological range of sources of isolation, should be placed into the same genus as Kocuria. Within the paradigm with vertically inherited phylogenetic markers, this could be regarded as a signal for their following taxonomic reclassification. An important factor in this case may be the detailing of the gene composition of the strains and the taxonomic ratios resulting from analysis of the pangenomes of the corresponding clades.
Summary: Hen egg white lysozyme (HEWL) was exploited for the synthesis of β-amino carbonyl compounds through a direct and three-component Mannich reaction in aqueous, confirming high chemoselectivity toward imine. In order to further extend the applications of the enzyme, HEWL was encapsulated using a metal-organic framework (MOF). The reactivity, stereoselectivity, and reusability of the encapsulated enzyme were investigated. The reaction was significantly enhanced as compared to the non-encapsulated enzyme. A mutated version of the enzyme, containing Asp52Ala (D52A), lacking important catalytical residue, has lost the bacterial site activity against Micrococcus luteus (M. luteus) while the D52A variant displayed an increased rate of the Mannich reaction, indicating a different catalytical residue involved in the promiscuous reaction. Based on site-directed mutagenesis, molecular docking, and molecular dynamic studies, it was proposed that π-stacking, H-bond interactions, and the presence of water in the active site may play crucial roles in the mechanism of the reaction.
Samuel C. Ugbaja, Sphamandla E. Mtambo, Aganze G. Mushebenge
et al.
The use of vaccinations and antiviral medications have gained popularity in the therapeutic management of avian influenza H7N9 virus lately. Antiviral medicines are more popular due to being readily available. The presence of the neuraminidase protein in the avian influenza H7N9 virus and its critical role in the cleavage of sialic acid have made it a target drug in the development of influenza virus drugs. Generally, the neuraminidase proteins have common conserved amino acid residues and any mutation that occurs around or within these conserved residues affects the susceptibility and replicability of the influenza H7N9 virus. Herein, we investigated the interatomic and intermolecular dynamic impacts of the experimentally reported E119V mutation on the oseltamivir resistance of the influenza H7N9 virus. We extensively employed molecular dynamic (MD) simulations and subsequent post-MD analyses to investigate the binding mechanisms of oseltamivir-neuraminidase wildtype and E119V mutant complexes. The results revealed that the oseltamivir-wildtype complex was more thermodynamically stable than the oseltamivir-E119V mutant complex. Oseltamivir exhibited a greater binding affinity for wildtype (−15.46 ± 0.23 kcal/mol) relative to the E119V mutant (−11.72 ± 0.21 kcal/mol). The decrease in binding affinity (−3.74 kcal/mol) was consistent with RMSD, RMSF, SASA, PCA, and hydrogen bonding profiles, confirming that the E119V mutation conferred lower conformational stability and weaker protein–ligand interactions. The findings of this oseltamivir-E119V mutation may further assist in the design of compounds to overcome E119V mutation in the treatment of influenza H7N9 virus patients.
Md Abdul Awal, Suza Mohammad Nur, Ali Khalaf Al Khalaf
et al.
Ubiquitin-like containing plant homeodomain Ring Finger 1 (UHRF1) protein is recognized as a cell-cycle-regulated multidomain protein. UHRF1 importantly manifests the maintenance of DNA methylation mediated by the interaction between its SRA (SET and RING associated) domain and DNA methyltransferase-1 (DNMT1)-like epigenetic modulators. However, overexpression of UHRF1 epigenetically responds to the aberrant global methylation and promotes tumorigenesis. To date, no potential molecular inhibitor has been studied against the SRA domain. Therefore, this study focused on identifying the active natural drug-like candidates against the SRA domain. A comprehensive set of in silico approaches including molecular docking, molecular dynamics (MD) simulation, and toxicity analysis was performed to identify potential candidates. A dataset of 709 natural compounds was screened through molecular docking where chicoric acid and nystose have been found showing higher binding affinities to the SRA domain. The MD simulations also showed the protein ligand interaction stability of and in silico toxicity analysis has also showed chicoric acid as a safe and nontoxic drug. In addition, chicoric acid possessed a longer interaction time and higher LD50 of 5000 mg/kg. Moreover, the global methylation level (%5 mC) has been assessed after chicoric acid treatment was in the colorectal cancer cell line (HCT116) at different doses. The result showed that 7.5 µM chicoric acid treatment reduced methylation levels significantly. Thus, the study found chicoric acid can become a possible epidrug-like inhibitor against the SRA domain of UHRF1 protein.
Nagwa Mohamed Assem, Amany Ibrahim Mohammed, Hamed Mohamed Abdel Barry
et al.
Abstract Background Hepatitis C virus (HCV) may induce extrahepatic manifestations as acute or chronic renal dysfunction. The aim was to evaluate the diagnostic role of some biomarkers as cystatin C, cryoglobulins, rheumatoid factor (RF), and complement C3 for extrahepatic renal affection in newly diagnosed patients with HCV infection. Methods Blood and urine were collected from randomized individuals screened for new HCV infection (n=400). The studied populations were divided into 3 groups: control group I: thirty healthy individuals not suffering from either liver or kidney diseases, group IIa: thirty HCV patients who have positive HCV antibody test but showed negative PCR test, and group IIb: thirty HCV patients who showed positive results for both HCV antibody and PCR tests. Results In HCV group IIb, levels of serum total bilirubin, AST and ALT, and urine albumin/creatinine ratio were increased whereas serum albumin and creatinine clearance were decreased versus other groups. However, the levels of blood urea nitrogen and serum creatinine were still within the normal range in all groups. In HCV group IIb, cystatin C, cryoglobulins, and RF levels were increased; meanwhile, serum creatinine/cystatin C ratio and complement 3 levels were decreased compared to the other groups. HCV-infected patients significantly had higher serum cystatin C (>1.24 mg/L, P<0.001) and lower creatinine/cystatin C ratio (<70.1μMol/mg, P=0.002), and cystatin C was significantly correlated with liver and kidney parameters. Conclusion High serum cystatin C and low creatinine/cystatin C ratio may be early indicators of mild renal dysfunction with normal serum levels of creatinine in HCV-infected individuals.
Surgery, Diseases of the digestive system. Gastroenterology