Plasma gelsolin (pGSN) correlates with clinical improvement in septic patients. We aimed to investigate pGSN levels as a diagnostic and prognostic marker of neonatal late-onset-sepsis (LOS). A ...case-control study was done on 184 neonates (92 with LOS and 92 controls). All participants were subjected to detailed history taking, full clinical evaluation, sepsis workup, and pGSN enzyme-linked immunosorbent-assay measurement. We detected significantly lower pGSN level among cases compared to controls (90.63 ± 20.64 vs 451.83 ± 209.59). It was significantly related to the severity of sepsis and mortality, with significantly lower values among cases with septic shock and multiorgan failure and non-survivors. Follow-up pGSN significantly increased after sepsis improvement in survivors compared to admission values. pGSN might be a reliable diagnostic and prognostic marker for LOS.
Microplastics (MPs) pollution is a newly emerging environmental issue. MPs can accumulate within animals and humans, which can pose a serious health threat. Petroleum-based polyethylene (PE) is one ...of the most popular plastics. Accordingly, its exposure rates have steadily increased over the years. This study aimed to analyze the effects of PE-MPs on the hematological system of albino rats and the epigenetic effect. Five groups of adult male eight-weeks-old rats received either distilled water, corn oil, 3.75 mg/kg PE-MPs, 15 mg/kg PE-MPs, or 60 mg/kg of PE-MPs, daily by oral gavage for 35 days. PE-MPs significantly increased the body weights of the rats and lipid peroxidation, with concomitant reduction of superoxide dismutase activity and depletion of reduced glutathione, thus adversely affecting oxidants/antioxidants balance. Moreover, PE-MPs increased the % of abnormal RBCs, irregular cells, tear drop cells, Schistocyte cells, and folded cells. The genotoxic effects on DNA were evident by increased DNA damage, confirmed by the comet assay, in addition to increased DNA methylation. The effects of PE-MPs have been shown to be dose correlated. In conclusion, this study provides evidence of dose-related PE-MPs-induced hematological, genotoxic, and epigenetic effects in mammals, and thus emphasizes the potentially hazardous health effects of environmental PE-MPs.
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•Rat PE-MPs exposure induced weight gain, oxidative stress, RBCs abnormalities.•PE-MPs exposure was associated with dose-related DNA genotoxic effects in rats.•PE-MPs induced DNA epigenetic toxicity evidenced by increased DNA methylation.•PE-MPs effects were significantly correlated with PE-MPs dose.•The first study reports PE-MPs epigenetic effects in mammals.
In Saudi Arabia,
(L.) has been traditionally used to treat a variety of diseases. This study aimed to investigate the crude methanolic extract of
(L.) phytochemical, chemical composition, and ...antibacterial activity. Phytochemical analysis revealed the presence of tannins, poly-tannins, steroids, alkaloids, essential oils, terpenoids, and flavonoids. The presence of functional groups such as -COOH, -OH, -C=O, and CH
was revealed via FTIR spectroscopy.
C and
H NMR (nuclear magnetic resonance) were used to determine the types and number of protons (hydrogen atoms) and their electronic states. Using an agar well diffusion assay, methanolic extract of
(L.) inhibited the growth of some foodborne pathogenic bacteria in zones ranging from 8 to 25 mm in diameter. The minimum inhibitory concentration (MIC) for
was 12.5 mg/mL, whereas it was 25 mg/mL for
,
, and
. The time-kill assay revealed a sharp decline in
and
after 2 h at a concentration of 150 mg/mL, while
and
showed a gradual decline with constant concentrations of 75 to 150 mg/mL. The minimum bactericide concentration (MBC) value for
,
, and
was 50 mg/mL, while it was 25 mg/mL for
. In conclusion, our study revealed that
(L.) methanolic extract has a significant antibacterial effect, suggesting that it could be used to treat various foodborne pathogens.
Imidacloprid (IMI) is a commonly used new-generation pesticide that has numerous harmful effects on non-targeted organisms, including animals. This study analysed both the adverse effects on the ...pancreas following oral consumption of imidacloprid neonicotinoids (45 mg/kg daily for 30 days) and the potential protective effects of lycopene (LYC) administration (10 mg/kg/day for 30 days) with IMI exposure in male Sprague–Dawley rats. The apoptotic, pyroptotic, inflammatory, oxidative stress, and endoplasmic reticulum stress biomarkers were evaluated, along with the histopathological alterations. Upon IMI administration, noticeable changes were observed in pancreatic histopathology. Additionally, elevated oxidative/endoplasmic reticulum-associated stress biomarkers, inflammatory, pyroptotic, and apoptotic biomarkers were also observed following IMI administration. LYC effectively reversed these alterations by reducing oxidative stress markers (e.g., MDA) and enhancing antioxidant enzymes (SOD, CAT). It downregulated ER stress markers (IRE1α, XBP1, CHOP), decreased pro-inflammatory cytokines (TNF-α, IL-1β), and suppressed pyroptotic (NLRP3, caspase-1) along with apoptotic markers (Bax, cleaved caspase-3). It also improved the histopathological and ultrastructure alterations brought on by IMI toxicity.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles. Prior to the development of these characteristic pathological ...hallmarks of AD, anterograde axonal transport is impaired. However, the key proteins that initiate these intracellular impairments remain elusive. The collapsin response mediator protein-2 (CRMP-2) plays an integral role in kinesin-1-dependent axonal transport and there is evidence that phosphorylation of CRMP-2 releases kinesin-1. Here, we tested the hypothesis that amyloid-beta (Aβ)-dependent phosphorylation of CRMP-2 disrupts its association with the kinesin-1 (an anterograde axonal motor transport protein) in AD. We found that brain sections and lysates from AD patients demonstrated elevated phosphorylation of CRMP-2 at the T555 site. Additionally, in the transgenic Tg2576 mouse model of familial AD (FAD) that exhibits Aβ accumulation in the brain with age, we found substantial co-localization of pT555CRMP-2 and dystrophic neurites. In SH-SY5Y differentiated neuronal cultures, Aβ-dependent phosphorylation of CRMP-2 at the T555 site was also elevated and this reduced the CRMP-2 association with kinesin-1. The overexpression of an unphosphorylatable form of CRMP-2 in neurons promoted the re-establishment of CRMP-2-kinesin association and axon elongation. These data suggest that Aβ-dependent phosphorylation of CRMP-2 at the T555 site may directly impair anterograde axonal transport protein function, leading to neuronal defects.
Alzheimer’s disease (AD) is one of the most prevalent severe neurological disorders afflicting our aged population. Cognitive decline, a major symptom exhibited by AD patients, is associated with ...neuritic dystrophy, a degenerative growth state of neurites. The molecular mechanisms governing neuritic dystrophy remain unclear. Mounting evidence indicates that the AD-causative agent, β-amyloid protein (Aβ), induces neuritic dystrophy. Indeed, neuritic dystrophy is commonly found decorating Aβ-rich amyloid plaques (APs) in the AD brain. Furthermore, disruption and degeneration of the neuronal microtubule system in neurons forming dystrophic neurites may occur as a consequence of Aβ-mediated downstream signaling. This review defines potential molecular pathways, which may be modulated subsequent to Aβ-dependent interactions with the neuronal membrane as a consequence of increasing amyloid burden in the brain.
Brain natriuretic peptide (BNP) is synthesized in the cardiac ventricles and released in response to volume or pressure load. The aim of the study was to determine whether plasma level of N-terminal ...pro BNP (NT-pro BNP) can distinguish between cardiac and pulmonary disease (PD) among neonates with respiratory distress (RD).
The study included 48 term neonates in the first month of life with signs of RD. They were recruited from Neonatal Intensive Care Unit of Al-Galaa Teaching Hospital. Twenty-six healthy neonates were included as a control group. The degree of RD was assessed using Silverman-Anderson score. Chest X-ray, echocardiography, and laboratory measurement of NT-pro BNP were performed.
According to the underlying disease, neonates with RD were divided into 28 neonates with PD and 20 neonates with congenital heart disease (CHD). Regardless the etiology of RD, NT-pro BNP was significantly higher in the RD group than in the control (
= 0.001). There was a significant difference between and within the three groups regarding NT-pro BNP (
= 0.001). NT-pro BNP was significantly higher in the CHD group than in the PD group (
= 0.001). There was a significant difference between and within RD subgroups. The NT-pro BNP is a very useful test for identification of CHD in neonates with RD. Area under the receiver operating characteristic curve for CHD was 0.857 (
= 0.01), sensitivity 66%, specificity 85%, and cutoff point was 24.5 pg/mL. The area under the curve for PD was 0.646 (
= 0.1) with poor sensitivity and specificity, indicating that NT-pro BNP is a poor test for identification of PD in neonates with RD.
Term neonates with RD have increased plasma levels of NT-pro BNP. NT-pro BNP is a very good test for identification of CHD in neonates with RD, in comparison with PD. Therefore, plasma NT-pro BNP can be used to differentiate between cardiac and pulmonary cause of RD.
Background/aim: Motor dysfunction is one of the major byproducts of stroke; however, another domain that is severely affected yet mostly neglected is cognition. It is not certain yet whether a ...relationship between cognitive impairment (attention) and upper-limb motor impairment is present. The aim of our study was to investigate the correlation between attention deficits with upper limb motor dysfunction after stroke. Material and methods: Sixty stroke survivors were recruited in this correlational study. Upper limb motor function was evaluated by the Upper Limb Functional Index (ULFI). Attention deficits were evaluated by the Mini Mental State Examination (MMSE). For correlation, data were imported into Statistical Package for the Social Sciences (SPSS version 20.0). A result was considered statistically significant when p was <0.05. Chi-Square testΧ² was used to test the association variables for categorical data. Results: There was significant correlation between Mini Mental State Examination with motor functions MMSE with ULFI (r=.295*, p=.022). Conclusion: There is a significant correlation between attention deficits and motor dysfunction of the upper extremities in patients after stroke.
This study provides a comprehensive computational exploration of the inhibitory activity and metabolic pathways of 8-methoxypsoralen (8-MP), a furocoumarin derivative used for treating various skin ...disorders, on cytochrome P450 (P450). Employing quantum chemical DFT calculations, molecular docking, and molecular dynamics (MD) simulations analyses, the biotransformation mechanisms and the active site binding profile of 8-MP in CYP1B1 were investigated. Three plausible inactivation mechanisms were minutely scrutinized. Further analysis explored the formation of reactive metabolites in subsequent P450 metabolic processes, including covalent adduct formation through nucleophilic addition to the epoxide, 8-MP epoxide hydrolysis, and non-CYP-catalyzed epoxide ring opening. Special attention was paid to the catalytic effect of residue Phe268 on the mechanism-based inactivation (MBI) of P450 by 8-MP. Energetic profiles and facilitating conditions revealed a slight preference for the C4'=C5' epoxidation pathway, while recognizing a potential kinetic competition with the 8-OMe demethylation pathway due to comparable energy demands. The formation of covalent adducts via nucleophilic addition, particularly by phenylalanine, and the generation of potentially harmful reactive metabolites through autocatalyzed ring cleavage are likely to contribute significantly to P450 metabolism of 8-MP. Our findings highlight the key role of Phe268 in retaining 8-MP within the active site of CYP1B1, thereby facilitating initial oxygen addition transition states. This research offers crucial molecular-level insights that may guide the early stages of drug discovery and risk assessment related to the use of 8-MP.
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