Shaker, O., H. Mahfouz, A. Salama, and E. Medhat, "Long Non-Coding HULC and miRNA-372 as Diagnostic Biomarkers in Hepatocellular Carcinoma.", Reports of biochemistry & molecular biology, vol. 9, issue 2, pp. 230-240, 2020. Abstract

Background: We aimed to evaluate the effectiveness of Highly Upregulated in Liver Cancer (HULC) and microRNA-372 (miR-372) as biochemical markers in Hepatocellular carcinoma (HCC) and HCV-infected patients.

Methods: The present study was conducted on 100 Egyptian individuals divided into 3 groups, 40 patients with HCC and HCV infection, 40 patients only HCV-infected, and 20 individuals as normal controls. They were subject to full history taking, full clinical and laboratory examination, and assessment of HULC and miR-372 levels by real-time PCR.

Results: A statistically significant difference was found with p< 0.05 between HCC and each of HCV and control groups as regards HULC level with high mean among HCC followed by HCV patients. Our results also show a statistically significant difference with p< 0.05 between each of HCC and HCV compared to control as regards miR-372 level with low mean among HCC patients.

Conclusion: HULC could be considered as a potential non-invasive marker for detection and early diagnosis of HCC. Also, it may play an important role in the early prophylaxis and control measures to reduce the incidence of HCC. However, miR-372 cannot be considered as a reliable marker as HULC for early detection of HCC especially in HCV patients.

Saad El-Din, S., L. Rashed, E. Medhat, B. E. Aboulhoda, A. D. Badawy, A. M. Shamseldeen, and M. Abdelgwad, "Active form of vitamin D analogue mitigates neurodegenerative changes in Alzheimer's disease in rats by targeting Keap1/Nrf2 and MAPK-38p/ERK signaling pathways.", Steroids, vol. 156, pp. 108586, 2020. Abstract

BACKGROUND: The nuclear factor erythroid2-related factor2 (Nrf2), a chief transcriptional regulator of antioxidant response element (ARE), is considered a promising target for the prevention of Alzheimer's disease (AD). Vitamin D has been recognized to have a crucial role in improving AD cognitive functions. The present study was conducted to evaluate the effects of active vitamin D analogue, Maxacalcitol, on Keap1-Nrf2 signaling pathway in experimental Alzheimer's disease in rats.

MATERIALS AND METHODS: The study was conducted on thirty female white albino rats divided equally into 3 groups: control group, Alzheimer group induced by Lipopolysaccharide and Alzheimer group treated with active vitamin D3 analogue, Maxacalcitol. The following parameters were assessed in rat brain tissues: Gene expression of Nrf2, Keap1 and MAF by RT-PCR, protein levels of phosphorylated MAPK-38p and ERK1/2 by Western Blot Technique, estimation of HO-1, Amyloid β, p-Tau levels and serum levels of TNFα, IL-10 and total 25-hydroxyvitamin D, serum calcium levels, GSH and MDA levels were also estimated in addition to cognitive function tests and histo-pathological examination of rat brain tissues.

RESULTS: In Alzheimer group, there was a significant deficit in cognition along with down-regulation of gene expression of Nrf2 and the protein levels of its downstream antioxidant effectors (HO-1 and GSH) with increased levels of the lipid peroxidation biomarker MDA. Also, there was increased neuro-inflammation as evidenced by increased levels of TNFα and decreased levels of IL-10. Moreover, there were increased amyloid β load and enhanced levels of phosphorylation of MAPK-38 and ERK1/2 leading to hyperphosphorylation of Tau protein. In addition, there were decreased serum levels of both total 25-hydroxyvitamin D and calcium. Treatment with vitamin D3 analogue, Maxacalcitol significantly improved cognitive dysfunction and histopathological picture of the brains of Alzheimer rats. Also, Vitamin D analogue significantly increased expression of Nrf2 and its downstream effectors (HO-1 and GSH), improved serum levels of total 25-hydroxyvitamin D and calcium, decreased neuro-inflammation and Amyloid β load as well as hyperphosphorylation of MAPK-38, ERK1/2 and tau proteins were also observed. Therefore, these data suggest that vitamin D analogue, Maxacalcitol could be used as a therapeutic agent in treatment of Alzheimer disease.

Medhat, E., L. Rashed, M. Abdelgwad, B. E. Aboulhoda, M. M. Khalifa, and S. Saad El-Din, "Exercise enhances the effectiveness of vitamin D therapy in rats with Alzheimer's disease: emphasis on oxidative stress and inflammation.", Metabolic brain disease, vol. 35, issue 1, pp. 111-120, 2020. Abstract

Alzheimer's disease (AD) is characterized by gradual loss of memory and cognitive functions which can affect anyone. Authors declared that there is a link between vitamin D and brain function. It has been proven that vitamin D plays an important role in improving AD cognitive functions. Researchers have found that exercise has many beneficial effects on humans. In addition to cardioprotection, it has been demonstrated that exercise provides an effective improvement in different brain functions. So in our study, we aimed to evaluate the effect of each of vitamin D and/ or exercise on AD and if they could be used as a potential line for treating AD. This study was conducted on fifty female white albino rats divided equally into 5 groups: control group, Alzheimer group induced by Lipopolysaccharide, Alzheimer group treated with vitamin D, Alzheimer group treated with exercise and Alzheimer group treated with both vitamin D and exercise. The following parameters were assessed in rat brain tissues: acetylcholine esterase (AChE) activity, levels of amyloid β 42 and tau proteins, dopamine brain neurotransmitter, BDNF and NGF by ELISA. Serum levels of IL-6 and IL-10 were assessed by ELISA. MDA, GSH and vitamin D levels were also estimated in addition to cognitive function tests and histopathological examination of rat brain tissues. In Alzheimer group, there was a significant increase in the proinflammatory cytokine IL-6, the lipid peroxidation marker MDA, amyloid β and tau proteins levels. In addition to a significant increase in time consumed in T-maze test. Alzheimer group also showed a significant decrease in the anti-inflammatory cytokine IL-10, the anti-oxidative stress biomarker GSH, the neurotransmitters AChE and dopamine, and the growth factors BDNF and NGF as well as serum vitamin D levels. Treatment with either vitamin D or exercise significantly improved cognitive dysfunction and the histopathological picture of the brains of Alzheimer's rats with the best results in combined vitamin D and exercise treated group. The treated groups, especially combined vitamin D and exercise group, showed a significant decrease in IL-6, MDA, amyloid β and tau proteins levels, but on the other hand they showed a significant increase in IL-10, GSH, AChE, dopamine, BDNF and NGF. These data suggest that combined vitamin D and exercise could be considered as a potential and effective line for treating AD.

Megeed, E. M. A. A. E., P. D. M. A. - E. A. Wassef, D. S. F. Hassan, P. D. S. Mahfouz, and D. W. I. Ali, Effect of Mesenchymal Stem Cells on Cisplatin Induced Nephrotoxicity in Albino Rats:Possible Role of Melatonin, , Giza, Cairo univ, 2016. Abstract

Background: Cisplatin is one of the most effective and potent anticancer drugs. It is used in the treatment of a wide variety of both pediatric and adult malignancies. However, the chemotherapeutic use of cisplatin is limited by its serious side effects such as nephrotoxicity. Bone marrow derived mesenchymal stem cells (MSCs) have shown great potential in cell therapy of solid organs. Melatonin and its metabolites possess free-radical scavenging activity and it has been shown that they protect against cisplatin toxicity. So we designed this work to evaluate the effect of MSCs and melatonin on cisplatin induced nephrotoxicity and to study the effect of melatonin on MSCs proliferation.
Methods: This work included: in vivo study and in vitro study. The in vivo study included sixty rats which were divided equally into six groups: healthy control group, nephrotoxicity group induced by cisplatin, nephrotoxicity group received melatonin only, nephrotoxicity group received MSCs only, nephrotoxicity group received both MSCs and melatonin, nephrotoxicity group received MSCs pretreated with melatonin. Histopathological examination, gene expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), caspase 3 and beclin genes by real time reverse transcription-polymerase chain reaction (RT-PCR) in rat kidney tissue, tissue nuclear factor erythroid 2-related factor 2 (Nrf2) protein by western blot technique, serum levels of tumor necrosis factor alpha (TNF α) and interleukin-10 (IL-10) by ELISA, serum levels of urea, creatinine, malondialdehyde (MDA) and glutathione (GSH) by colorimetry were performed in all groups. The in vitro study included two groups of cells, the first group included MSCs and the second one included MSCs treated with melatonin. Gene expression of BCL2 associated X protein (BAX) and B cell lymphoma 2 (BCL2) and cell proliferation assay were performed for the two in vitro groups.
Results: Histopathological examination of kidney tissue from rats which received cisplatin only, revealed the occurrence of nephrotoxicity. Administration of MSCs after induction of experimental nephrotoxicity slightly improved the histopathological picture with residual pathology while administration of melatonin, MSCs together with melatonin and MSCs pretreated with melatonin showed much more improvement of the histopathological picture specially the group of MSCs pretreated with melatonin. Gene expression in rat kidney tissue demonstrated that NFκB and caspase 3 were downregulated in all treated groups with more suppressive effect in the groups treated with MSCs together with melatonin and MSCs pretreated with melatonin specially the pretreated one. Beclin gene expression and Nrf2 protein levels were increased in all treated groups specially in the groups treated with MSCs together with melatonin and MSCs pretreated with melatonin. Serum levels of TNF α and MDA were decreased and those of IL-10 and GSH were increased in all treated groups specially the groups treated with MSCs together with melatonin and MSCs pretreated with melatonin. The melatonin treated MSCs showed significant increase in the proliferation rate and BCL2 gene expression and a significant decrease in BAX gene expression.
Conclusion: Administration of MSCs, melatonin, MSCs together with melatonin and MSCs pretreated with melatonin improves nephrotoxicity with marked improvement achieved by the MSCs pretreated with melatonin as evidenced by histopathological examination and selected biochemical markers of inflammation, apoptosis, autophagy and oxidative stress.
Key words: nephrotoxicity, cisplatin, MSCs, melatonin.

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