Explore the vast range of titles available.

Recently, intensive scientific efforts have been directed to investigate the role of small non-coding RNA (miRs) in different renal diseases. Extracellular vesicles (EVs) are small secretory vesicles released from almost all mammalian cells. EVs-miRs cargo plays a significant role in regulating various aspects of the biological machinery of the recipient cells. EVs-miRs may play an essential role in promoting cellular regenerative functions. miRs contained within the EVs fractions are capable of preserving their function throughout their journey from the cell of origin to the host cells. Our review discusses the role of EVs-miRs in different renal diseases as a novel approach to managing particular renal injuries. We have tried to simplify the possible modulatory impact of miRs at ultrastructural cellular pathological signalling,demonstrating both hazardous and beneficial subtypes based on published research. Further investigations are still needed in this regard, as miRs may have dual effects, as EVs-miR-23a could attenuate renal fibrosis through the activation of Akt and the inhibition of FoxO1 signalling. We have found that EVs-miR-23a was upregulated by hypoxia-inducible factor (HIF-1a) in hypoxic TECs and activated macrophages to accelerate the renal inflammatory cytokine storm and promote interstitial fibrosis.

Background: Liver inflammation and fibrosis are directly associated with non-alcoholic fatty liver disease (NAFLD). Dysregulation of the potent pro-inflammatory cytokine interleukin-1 beta (IL-1β), inducible nitric oxide synthase (iNOS), and tissue leukocyte infiltration (CD45 +ve) are connected with multiorgan injury and fibrosis. We investigated whether the induction of NAFLD can cause dysregulation in the hepatic IL-1β/iNOS and IL-1β/CD45 axes of inflammation and fibrosis, as well as in endogenous metabolites (lipids, glucose, and insulin) and apoptosis, in the presence and absence of the flavonoid quercetin. Methods: The model group of rats was fed with a high-fat and high-carbohydrate diet (HFCD) for 4 weeks. The protective group of rats was given both quercetin (50 mg/kg) and HFCD for 4 weeks. All rats were sacrificed on day 29. Results: NAFLD was induced in rats as demonstrated by dyslipidemia, hyperglycemia, insulin resistance, liver inflammation, and elevation of liver injury enzymes. NAFLD was also associated with the upregulation of hepatic IL-1β, iNOS, CD45, and apoptosis (p53). Biomarkers of fibrosis (TIMP-1 and α-SMA) were also elevated, and fibrosis was confirmed in the model group by increased collagen deposition and elevated stages of fibrosis score (Stage 1 to 2 of Brunt’s NASH classification). All these parameters were significantly (p < 0.01) modulated by quercetin treatment. Additionally, a significant (p < 0.001) correlation between IL-1β and hepatic injury parameters was observed. Conclusions: These findings suggest a potential association between NAFLD and the IL-1β/iNOS and IL-1β/CD45 axes of liver injury and fibrosis, as well as dyslipidemia, glycemia, and apoptosis, with quercetin exhibiting beneficial hepatic pleiotropic effects.

Background Among the several disorders induced by sepsis, acute kidney injury (AKI) represents the most important economic burden problem that is associated with high mortality and morbidity rates. The aim of this study was to investigate the anti-inflammatory effects of ghrelin in sepsis-induced AKI and the possible role of vagus nerve. Methods Five groups were included: sham, cecal ligation and puncture (CLP), CLP–ghrelin, CLP–vagotomy and CLP–vagotomy–ghrelin group. Results Ghrelin treatment immediately after induction of CLP, significantly improved renal Glomerular filtration rate (GFR), serum creatinine, BUN and renal necrosis score as compared to the unprotected CLP group. In addition, ghrelin significantly decreased renal TNF alpha (111.5 ± 10.35 vs. 291.8 ± 15.8 pg/mg ptn), VCAM1 (6.28 ± 1.7 vs. 12.9 ± 1.2 µ/g ptn) and MPO (0.95 ± 0.13 vs. 2.5 ± 0.4 µ/g ptn) without significant increase in renal IL-10. Those effects were abolished by vagotomy. Conclusion We concluded that ghrelin could represent new therapeutic window in early treatment of sepsis-induced AKI and this could be mainly due to its anti-inflammatory effects.

Globally, hepatocellular carcinoma (HCC) presents a clinical and financial burden, as it is often diagnosed at a later stage. Cisplatin is one of the most commonly used chemotherapeutics for treating various types of solid tumours; however, it is a double-edged sword due to its cytotoxic effects. Consequently, we hypothesized that combining cisplatin with melatonin could be effective in treating HCC. Additionally, melatonin may mitigate the severe adverse effects of cisplatin on normal cells through its cellular protection, immunomodulation, and antioxidant activities. Forty male adult Wistar rats were randomly divided into five groups: Group 1( n =  8), negative control group. HCC was induced in 32 rats with diethyl nitrosamine and carbon tetrachloride injection. Following induction, rats were divided into group 2 (HCC): diseased control; group 3 (HCC-Cis): HCC rats received cisplatin (2.5 mg/kg I.P. once every week for 3 weeks); group 4 (HCC-Melatonin): HCC rats received melatonin in drinking water (20 mg/L for 3 weeks); and group 5 (HCC-Cis-Melatonin; Combined therapy): the HCC rats received both cisplatin and melatonin . HCC group revealed significant elevation in ALT, AST, and AFP associated with increased TNF-α and MDA levels. Hepatic tissue exhibited a significant increase in VEGF, MDM2, COX-2, and miR-155, and a decrease in caspase-3 associated with hepatic damage, ballooning of hepatocytes, and increased BCL-2 and CD68 immunostaining. Although cisplatin was able to induce HCC apoptosis by COX-2 and MDM2/p53/ miR-155 modulation, it aggravated normal hepatocytic damage that was improved by the antioxidant and anti-inflammatory effects of melatonin. In conclusion, melatonin and cisplatin co-administration may be a viable strategy to preserve liver function by shielding healthy hepatocytes from the cytotoxic effects of cisplatin.

Liver fibrosis is a hallmark of thioacetamide (TAA) intoxications. MicroRNAs (miRs), such as miR-155, have been implied in the pathogenesis of liver disease, and regulated by the antioxidant and anti-inflammatory compound resveratrol (RES). The link between reactive oxygen species (ROS), tumour suppressor p53 (p53), and liver fibrosis-during the pathogenesis of TAA-induced liver injury-associated with miR-155 dysregulation with and without RES incorporation has not been previously studied. Therefore, one group of rats received TAA injections of 200 mg/kg; twice a week at the beginning of week 3 for 8 weeks (TAA group; or model group), whereas the protective group was pretreated daily with RES suspension (20 mg/kg; orally) for the first two weeks and subsequently sustained on receiving both RES and TAA until being sacrificed at the 10th week. Liver injuries developed in the model group were confirmed by a significant (p < 0.0001) elevation of hepatic tissue levels of miR-155, ROS, p53, and the profibrogenic biomarkers: tissue inhibitor of metalloproteinases-1 and α-smooth muscle actin, as well as collagen deposition (fibrosis). All these parameters were significantly (p ≤ 0.0234) protected by resveratrol (RES + TAA). In addition, we observed a significant (p < 0.0001) correlation between ROS/p53 axis mediated liver fibrosis and miR-155. Thus, TAA intoxication induced miR-155 imbalance and ROS/p53-mediated liver fibrosis, with resveratrol, conversely displaying beneficial hepatic pleiotropic effects for a period of 10 weeks.

Background The angiotensin-converting enzyme-2 (ACE2) is recognized to be the fundamental receptor of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), responsible for the worldwide Coronavirus Disease-2019 (COVID-19) epidemic. However, genetic differences between people besides racial considerations and their relation to disease susceptibility are still not fully elucidated. Main body To uncover the role of ACE2 in COVID-19 infection, we reviewed the published studies that explore the association of COVID-19 with the functional characteristics of ACE2 and its genetic variations. Notably, emerging studies tried to determine whether the ACE2 variants and/or expression could be associated with SARS-CoV/SARS-CoV2 have conflicting results. Some researchers investigated the potential of \"population-specific\" ACE2 genetic variations to impact the SARS-CoV2 vulnerability and suggested no ethnicity enrichment for ACE2 polymorphisms that could influence SARS-CoV2 S-protein binding. At the same time, some studies use data mining to predict several ACE2 variants that could enhance or decline susceptibility to SARS-CoV. On the other hand, fewer studies revealed an association of ACE2 expression with COVID-19 outcome reporting higher expression levels of ACE2 in East Asians. Conclusions ACE2 gene variants and expression may modify the deleterious consequences of SARS-CoV2 to the host cells. It is worth noting that apart from the differences in gene expression and the genetic variations of ACE2, many other environmental and/or genetic factors could modify the disease outcome, including the genes for the innate and the adaptive immune response.

Abnormal conduction and improper electrical impulse propagation are common in heart after myocardial infarction (MI). The scar tissue is non-conductive therefore the electrical communication between adjacent cardiomyocytes is disrupted. In the current study, we synthesized and characterized a conductive biodegradable scaffold by incorporating graphene oxide gold nanosheets (GO-Au) into a clinically approved natural polymer chitosan (CS). Inclusion of GO-Au nanosheets in CS scaffold displayed two fold increase in electrical conductivity. The scaffold exhibited excellent porous architecture with desired swelling and controlled degradation properties. It also supported cell attachment and growth with no signs of discrete cytotoxicity. In a rat model of MI, in vivo as well as in isolated heart, the scaffold after 5 weeks of implantation showed a significant improvement in QRS interval which was associated with enhanced conduction velocity and contractility in the infarct zone by increasing connexin 43 levels. These results corroborate that implantation of novel conductive polymeric scaffold in the infarcted heart improved the cardiac contractility and restored ventricular function. Therefore, our approach may be useful in planning future strategies to construct clinically relevant conductive polymer patches for cardiac patients with conduction defects.

The angiotensin-converting enzyme-2 (ACE2) is recognized to be the fundamental receptor of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), responsible for the worldwide Coronavirus Disease-2019 (COVID-19) epidemic. However, genetic differences between people besides racial considerations and their relation to disease susceptibility are still not fully elucidated. ACE2 gene variants and expression may modify the deleterious consequences of SARS-CoV2 to the host cells. It is worth noting that apart from the differences in gene expression and the genetic variations of ACE2, many other environmental and/or genetic factors could modify the disease outcome, including the genes for the innate and the adaptive immune response.

There have been concerns about the potential health risks posed by microplastics (MP). The detection of MP in a variety of food products revealed that humans are ingesting MP. Nevertheless, there is a paucity of data about their impacts, as well as their uptake, on intestinal barrier integrity. This study examined the toxic effects of oral administration of two doses of polyethylene microplastics (PE-MP) (3.75 or 15 mg/kg/day for 5 weeks; mean particle size: 4.0–6.0 µm) on the intestinal barrier integrity in rats. Moreover, the effect of melatonin treatment with MP exposure was also assessed. The PE-MP particle uptake, histopathological changes, Alcian blue staining, Muc2 mRNA, proinflammatory cytokines (IL-1β and TNF-α), and cleaved caspase-3, as well as tight junction proteins (claudin-1, myosin light-chain kinase (MLCK), occludin, and zonula occludens-1 (ZO-1)) were assessed. Oral administration of PE-MP resulted in apparent jejunal histopathological alterations; significantly decreased mucin secretion, occludin, ZO-1, and claudin-1 expression; and significantly upregulated MLCK mRNA, IL-1β concentration, and cleaved caspase-3 expression. Melatonin reversed these altered parameters and improved the PE-MP-induced histopathological and ultrastructure changes. This study highlighted the PE-MP’s toxic effect on intestinal barrier integrity and revealed the protective effect of melatonin.

BackgroundDementia is a pressing problem for families and society. In 2019, a total of 57.4 million people worldwide were estimated to be living with dementia, and this number will almost double every 20 years, especially in Africa and the Middle East. This study aimed to investigate knowledge about dementia among the Egyptian population. A cross-sectional online survey was conducted among a sample of adult Egyptians using a socio-demographics data sheet and a designed dementia knowledge questionnaire.ResultsNearly one-third (33.4%) had a poor knowledge score. The items most often answered incorrectly were the sudden onset of cognitive problems as characteristic of dementia (59.3%). The highest percentage of good knowledge was in the manifestations and prevention domains (62.20% and 67.18%, respectively). On the other hand, the lowest rate of good knowledge was in the treatment and life impact domains (35.23% and 25.70%, respectively). Not working in the medical field (OR 2.656, 95% CI: 1.504–4.688, p < 0.001), had no contact with dementia patients (OR 1.910, 95% CI: 1.229–2.970, p = 0.004), no previous knowledge on dementia (OR 3.184, 95% CI: 1.797–5.642, p < 0.001), or never heard about dementia \"Marad Alkharaf\" (OR 6.385, 95% CI: 4.127–9.878, p < 0.001) were significantly associated with poorer dementia knowledge.ConclusionThe findings of our study indicated variable levels of knowledge of dementia among Egyptians. Our recommendation is to encourage conducting campaigns for raising public awareness about dementia and through media that has an important and widespread effect in reaching the Egyptian population.