Upregulation of heme oxygenase 1 (HO-1) attenuates kidney damage, oxidative stress and inflammatory reaction during renal ischemia/reperfusion injury

Objectives: The current work investigated the effect of Wharton jelly mesenchymal stem cells (WJ-MSCs) pretreated with all-trans-retinoic acid (ATRA) on renal ischemia in rats and the possible role of oxidative stress, apoptotic and Wnt/β-Catenin signaling pathways, and inflammatory cytokines in their effects. Methods: The study included 90 male Sprague Dawley rats that were allocated to five groups (n = 18 rats): (I) Sham-operated group (right nephrectomy was performed); (II) Ischemia/reperfusion injury (IRI) group, a sham group with 45-min renal ischemia on the left kidney; (III) ATRA group, an ischemic group with an intravenous (i.v.) administration of ATRA 10 µM, 10 min post-surgery); (IV) WJ-MSCs group, an IRI group with an i.v. administration of 150 µL containing 7 × 10⁶ WJ-MSCs, 10 min post-surgery; (V) WJ-MSCs + ATRA group, an IRI group with an i.v. administration of 150 µL of 7 × 10⁶ WJ-MSCs pretreated with 10 µM ATRA. At the end of the experiments, serum creatinine, BUN micro-albuminuria (MAU), urinary protein, markers of redox state in the left kidney (MDA, CAT, SOD, and GSH), and the expression of Bax, IL-6, HIF-1α, Wnt7B, and β-catenin genes at the level of mRNA as well as for immunohistochemistry for NFkB and β-Catenin markers were analyzed. Results: The current study found that 45-min of renal ischemia resulted in significant impairment of kidney function (evidenced by the increase in serum creatinine, BUN, and urinary proteins) and deterioration of the kidney morphology, which was associated with a significant increase in redox state (evidenced by an increase in MDA and a decrease in GSH, SOD, and CAT), and a significant increase in inflammatory and apoptotic processes (evidenced by an increase in Bax and IL-6, NFkB, Wnt7B, β-catenin and HIF-1α) in kidney tissues (p < 0.05). On the other hand, treatment with ATRA, WJ-MSCs, or a combination of both, caused significant improvement in kidney function and morphology, which was associated with significant attenuation of oxidative stress, apoptotic markers, and inflammatory cytokines (IL6 and NFkB) with the upregulation of HIF-1α and β-catenin in kidney tissues (p < 0.05). Moreover, the renoprotective effect of WJ-MSCs pretreated with ATRA was more potent than WJ-MSCs alone. Conclusions: It is concluded that preconditioning of WJ-MSCs with ATRA may enhance their renoprotective effect. This effect could be due to the upregulation of the beta-catenin/Wnt pathway and attenuation of apoptosis, inflammation, and oxidative stress.

In response to the global COVID-19 epidemic, the United Arab Emirates (UAE) government is taking precautionary action to mitigate the spread of the virus. The aim of this study was to evaluate the knowledge and practices toward COVID-19 among the general public in the UAE during the current outbreak. A cross-sectional online survey of 1356 respondents in the UAE was conducted during the epidemic outbreak between 9^th to 24^th June-2020. The questionnaire consisted of three sections: Socio-demographic, knowledge, practices. Independent-samples t-test, one-way analysis of variance (ANOVA), chi-square and binary logistic regression was used. A p-value of (p < 0.05) was considered statistically significant. The total correct score of knowledge and practice questions was high 85% and 90%, respectively. Male’s sex, other marital status, and illiterate/primary educational levels had a lower level of knowledge and practices than others. Participants aged 18–29 had little higher knowledge than other ages but had a lower level in practices, people who live in Abu Dhabi had better knowledge and practices than other emirates, employed people had a lower level of knowledge but higher in practices. Binary logistic regression analysis presented that females, 18–29 years, and married participants significantly associated with a higher score of knowledge, while female, over 30 years old, the martial status of singles, college-level and higher, unemployed, were significantly associated with high mean practices score. This study provided a full screening of the knowledge and practices among a sample of residents in The UAE toward COVID-19, continuing to implement the health education programs pursued by the UAE is highly important to maintain the appropriate level of awareness among the public.