The nephrotoxicity of cisplatin (CIS) is a significant complication that challenges its clinical applicability. The epithelial to mesenchymal transition (EMT) may be included in the pathogenesis of CIS-evoked nephrotoxicity. Therefore, the current study aimed to evaluate, for the first time, the possible protective effect of AZL and/or AT-MSCs against CIS-induced EMT in rats on molecular bases. Fifty-four healthy Wistar male albino rats were used in this study. Different biochemical markers of kidney function as well as oxidative stress parameters were investigated. Additionally, renal histopathological study was performed. The expression of EMT-related proteins and genes was evaluated by western blotting and qRT-PCR. CIS markedly increased SCr, BUN, uric acid and renal MDA levels, with concomitant decrease in serum total protein, renal GSH level and SOD activity. Furthermore, it suppressed the expression of Cdh1 gene, increased the α-SMA, Acta2, Cdh2 and Vim genes expression, down regulated the expression of E-cad protein and up-regulated the α-SMA, TGF-β1, p-Smad2/3 and Snail proteins expression. Kidney tissues showed severe histopathological alterations and extensive collagen accumulation. Conversely, the treatment with either AZL or AT-MSCs significantly attenuated these alterations caused by CIS. Interestingly, the combined therapy of AZL and AT-MSCs has a superior ameliorative effect than AT-MSCs alone. In conclusion, this study, for the first time, revealed that AZL and/ or AT-MSCs successfully ameliorated the CIS-induced EMT via the inhibition of oxidative stress and TGF-β/Smad signaling pathway. Intriguingly, AZL enhanced the effect of AT-MSCs making them promising agents for kidney protection against CIS-induced EMT.

Alzheimer’s disease (AD)is an age-related neurodegenerative disease characterized by memory decline and cognitive impairment .AD is common in people aged > 65 years, though most of AD cases are sporadic, which accounts for 95%, and 1–5% of AD is caused by familial causes . The causes of AD are aging, environmental toxins, and cardiometabolic factors that induce the degeneration of cholinergic neurons. It has been shown that the metabolic syndrome which is a clustering of dissimilar constituents including insulin resistance (IR), glucose intolerance, visceral obesity, hypertension, and dyslipidemia is implicated in the pathogenesis of AD. Metabolic syndrome disapprovingly affects cognitive function and the development in AD by inducing the development of oxidative stress, neuroinflammation, and brain IR. These changes, together with brain IR, impair cerebrovascular reactivity causing cognitive impairment and dementia. Nevertheless, the fundamental mechanism by which metabolic syndrome persuades AD risk is not entirely explicated. Accordingly, this review aims to discuss the connotation between metabolic syndrome and AD. In conclusion, metabolic syndrome is regarded as a possible risk factor for the initiation of AD neuropathology by diverse signaling pathways such as brain IR, activation of inflammatory signaling pathways, neuroinflammation, defective proteostasis, and dysregulation of lipid mediators.

Despite its clinical value, cisplatin (CISP) is complicated by marked hepatotoxicity via inducing oxidative stress, inflammatory, and apoptotic pathways. This study aims to explore the protective impact of azilsartan (AZIL), an antihypertensive drug, in addition to adipose tissue-derived mesenchymal stem cells (AD-MSCs) on CISP-induced hepatotoxicity. After characterization and labeling of AD-MSCs by PKH26 dye, 54 Wistar male albino rats were randomly divided into nine groups: I (CONT), II (AZIL.H), III (CISP), IV (CISPAZIL.L), V (CISPAZIL.H), VI (CISPAD-MSCs), VII (CISPAZIL.LAD-MSCs), VIII (CISPAZIL.HAD-MSCs), and IX (CISPVITA C). Serum alanine aminotransferase (ALT), alanine aminotransferase (AST), and albumin levels were determined. Assessment of reactive oxygen species, malondialdehyde, and glutathione contents, and superoxide dismutase activity and histopathological evaluations were done on hepatic tissue. Quantitative real-time PCR was utilized to estimate the expression of TNF-α and IL-6 genes. Cell homing of labeled AD-MSCs to the liver tissues was investigated. Hepatic expression of JNK1/2, ERK1/2, p38, Bax, Bcl-2, and cleaved caspase-3 proteins was investigated by western blot analysis. CISP elevated serum ALT and AST activities, reduced albumin level, and remarkably changed the hepatic architecture. It increased the expression TNF-α and IL-6 genes, raised the expression of JNK1/2, ERK1/2, p38, Bax, and cleaved caspase-3 proteins, and diminished the Bcl-2 protein. By contrast, treatment of animals with either AZIL or AD-MSCs dramatically reduced the effects of CISP injection. Moreover, treatment with combination therapy (AZIL.L or HAD-MSCs) considerably mitigated all previously mentioned alterations superior to AZIL or AD-MSCs alone, which might be attributed to the AZIL-enhanced homing ability of AD-MSCs into the injured liver tissue. In conclusion, the present findings demonstrated that AZIL improves the hepatoprotective potential of AD-MSCs against CISP-induced hepatotoxicity by modulating oxidative stress, mitogen-activated protein kinase, and apoptotic pathways.

Fibrosis is a pathological condition attributed to an inappropriate deposition of extracellular matrix that promotes scarring and dysfunction of the implicated organ or tissue. Moreover, fibrosis encompasses an enormous range of organs and tissues, each with a distinct molecular basis. Yet, two factors are discussed: the critical function of transforming growth factor-beta (TGF-β) and the participation of the inflammatory cascade, which is required to initiate fibrotic destruction. Epithelial to mesenchymal transition (EMT), the most prevalent cellular program underlying fibrosis, is regulated by TGF-β, as well as other cytokines. EMT has been widely investigated, although it has not yet been adequately examined as a potential treatment option for fibrosis. A better knowledge of the linkages between fibrosis and EMT may provide an option for the establishment of a highly useful anti-fibrotic treatment. Thus, we provide a general overview of EMT; summarize the significance of TGF-β/Smad signaling cascade in EMT induction, the correlation between both EMT and renal fibrosis and the promising treatment strategies targeting fibrosis induced by EMT.

Fibrosis is a pathological condition attributed to an inappropriate deposition of extracellular matrix that promotes scar and a dysfunction of the implicated organ or tissue. Moreover, fibrosis encompasses an enormous range of organs and tissues, each with a distinct molecular basis. Yet, two factors are discussed: the critical function of transforming growth factor-beta (TGF-β) and the participation of the inflammatory cascade, which is required to initiate fibrotic destruction. Epithelial to mesenchymal transition (EMT), the most prevalent cellular program underlying fibrosis is regulated by TGF-β, as well as other cytokines. EMT has been widely investigated, although it has not yet been adequately examined as a potential treatment option for fibrosis. A better knowledge of the linkages between fibrosis and EMT may provide an option for the establishment of a highly useful anti-fibrotic treatment. Thus, we provide a general overview of EMT; summarize the significance of TGF-β/Smad signaling cascade in EMT induction, the correlation among both EMT and renal fibrosis and the promising treatment strategies targeting fibrosis induced by EMT.