Search

Introduction: Administration of high doses of acetaminophen (APAP) results in liver injury. Oxidative stress and iron overload play roles in the pathogenesis of APAP-induced hepatotoxicity. The present study assessed the potential hepatoprotective effects of phytic acid (PA), a natural antioxidant and iron chelator, on APAP-induced hepatotoxicity and the possible underlying mechanism through its effects on CYP2E1 gene expression, iron homeostasis, oxidative stress, and SIRT-1 expression levels. Methods: Twenty-four adult male albino mice were used in this study. Mice were divided into four groups (six mice in each group): control, APAP-treated, PAtreated and APAP + PA-treated groups. Liver function tests, serum and liver tissue iron load were evaluated in all the study groups. Hepatic tissue homogenates were used to detect oxidative stress markers, including malondialdehyde (MDA) and reduced glutathione (GSH). Histological hepatic evaluation and immunohistochemistry of SIRT-1 were performed. Quantitative real-time PCR was used for the assessment of CYP2E1 and SIRT-1 gene expressions. APAPinduced biochemical and structural hepatic changes were reported. Results: PA administration showed beneficial effects on APAP-induced hepatotoxicity through improvements in liver functions, decreased CYP2E1 gene expression, decreased serum and liver iron load, decreased MDA, increased GSH, increased SIRT-1 expression level and improvement in hepatic architecture. Conclusion: Conclusively, PA can be considered a potential compound that can attenuate acetaminophen-induced hepatotoxicity through its role as an iron chelator and antioxidant, as well as the up-regulation of SIRT-1 and downregulation of CYP2E1. [ABSTRACT FROM AUTHOR]

Background. Malaria has been appraised as a significant vector-borne parasitic disease with grave morbidity and high-rate mortality. Several challenges have been confronting the efficient diagnosis and treatment of malaria. Method. Google Scholar, PubMed, Web of Science, and the Egyptian Knowledge Bank (EKB) were all used to gather articles. Results. Diverse biochemical and physiological indices can mirror complicated malaria e.g., hypoglycemia, dyslipidemia, elevated renal and hepatic functions in addition to the lower antioxidant capacity that does not only destroy the parasite but also induces endothelial damage. Multiple trials have been conducted to improve recent points of care in malaria involving biosensors, lap on-chip, and microdevices technology. Regarding recent therapeutic trials, chemical falcipain inhibitors and plant extracts with anti-plasmodial activities are presented. Moreover, antimalaria nano-medicine and the emergence of nanocarrier (either active or passive) in drug transportation are promising. The combination therapeutic trials e.g., amodiaquine + artemether + lumefantrine are presented to safely counterbalance the emerging drug resistance in addition to the Tafenoquine as a new anti-relapse therapy. Conclusion. Recognizing the pathophysiology indices potentiate diagnosis of malaria. The new points of care can smartly manipulate the biochemical and hematological alterations for a more sensitive and specific diagnosis of malaria. Nano-medicine appeared promising. Chemical and plant extracts remain points of research. [ABSTRACT FROM AUTHOR]

Objective(s): The process of vascular formation, also known as angiogenesis, primarily relies on endothelial cell proliferation, migration, and invasion. In recent years, it has been discovered that synthetic cannabinoids (SCs) may potentially impact angiogenic processes within the body. We evaluated the impact of the synthetic cannabinoid (R)-5-Fluoro-ADB on the proliferation rate and angiogenesis in Human Cerebral Microvascular Endothelial Cells (hBMECs). Materials and Methods: hBMECs were treated with (R)-5-Fluoro-ADB and investigated for cell viability, migration rate, and tube-like structure formation. Furthermore, angiogenic-related proteins including Angopoitein-1 and -2, and Vascular Endothelial Growth Factors (VEGF) were examined on mRNA and protein levels. Results: The results showed a notable rise in the rate of proliferation (P-value<0.0001) of HBMECs induced by (R)-5-Fluoro-ADB. The angiogenic capacity of HBMECs was also enhanced between 0.001 µM to 1 µM (R)-5-Fluoro-ADB. Moreover, an increase in the levels of ANG-1, ANG-2, and VEGF mRNA and protein, as well as elevated phosphorylation rate of GSK-3ß, were observed across various concentrations of (R)-5-Fluoro-ADB. Conclusion: Our results suggest an innovative approach in pharmacology for addressing a range of conditions linked to angiogenesis. This approach involves precise targeting of both cannabinoid receptors type-1 and -2. To achieve this, specific agonists or antagonists of these receptors could be employed based on the particular characteristics of the diseases in question. [ABSTRACT FROM AUTHOR]

Detailed knowledge on the formation of new aerosol particles in the atmosphere from precursor gases, and their subsequent growth, commonly known as new particle formation (NPF) events, is one of the largest challenges in atmospheric aerosol science. High pre-existing particle loadings are expected to suppress the formation of new atmospheric aerosol particles due to high coagulation and condensation (CS) sinks. However, NPF events are regularly observed in conditions with high concentrations of pre-existing particles and even during intense desert dust intrusions that imply discrepancies between the observations and theory. In this study, we present a multi-site analysis of the occurrence of NPF events under the presence of desert dust particles in dust-influenced areas. Characterization of NPF events at five different locations highly influenced by desert dust outbreaks was done under dusty and non-dusty conditions using continuous measurements of aerosol size distribution in both fine and coarse size fractions. Contrary to common thought, our results show that the occurrence of NPF events is highly frequent during desert dust outbreaks, showing that NPF event frequencies during dusty conditions are similar to those observed during non-dusty conditions. Furthermore, our results show that NPF events also occur during intense desert dust outbreaks at all the studied sites, even at remote sites where the amounts of precursor vapours are expected to be low. Our results show that the condensation sink associated with coarse particles (CS C) represents up to the 60 % of the total CS during dusty conditions, which highlights the importance of considering coarse-fraction particles for NPF studies in desert-dust-influenced areas. However, we did not find a clear pattern of the effect of desert dust outbreaks on the strength of NPF events, with differences from site to site. The particle growth rate (GR) did not present a clear dependence on the CS during dusty and non-dusty conditions. This result, together with the fact that desert dust has different effects on the growth and formation rates at each site, suggests different formation and growth mechanisms at each site between dusty and non-dusty conditions, probably due to differences in precursor vapours' origins and concentrations as well as changes in the oxidative capacity of pre-existing particles and their effectiveness acting as CS. Further investigation based on multiplatform measurement campaigns and chamber experiments with state-of-the-art gaseous and particulate physical and chemical properties measurements is needed to better understand the role of catalyst components present in desert dust particles in NPF. Finally, our results reveal a significant impact of NPF events on the cloud condensation nuclei (CCN) budget during desert dust outbreaks at the studied sites. Therefore, since desert dust contributes to a major fraction of the global aerosol mass load, and since there is a foreseeable increase in the frequency, duration and intensity of desert dust episodes due to climate change, it is imperative to improve our understanding of the effect of desert dust outbreaks on NPF and the CCN budget for better climate change prediction. [ABSTRACT FROM AUTHOR]