Effect of human umbilical cord blood-mesenchymal stem cells on cisplatin-induced nephrotoxicity in rats.

BACKGROUND: Cisplatin-containing regimen is an effective treatment for several malignancies. However, cisplatin is an important cause of nephrotoxicity. So, many trials were performed to transplant stem cells systemically or locally to control cisplatin-induced nephrotoxicity. Stem cell therapeutic effect may be dependent on the regulation of inflammation and oxidant stress. AIM: To investigate the effect of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) on the histological structure, the oxidant stress, and the inflammatory gene expression in an experimental model of cisplatin-induced nephrotoxicity in rats. METHOD: The rats were divided into 6 equal groups (each of 10 rats): Group I included normal rats that received no treatment. Group II included healthy rats that received IV hUCB-MSCs. Group III included untreated cisplatin-induced nephrotoxic rats. Group IV included cisplatin-induced nephrotoxic rats that received magnesium (Mg) injections after injury. Group V was injected with hUCB-MSCs after injury. Group VI received both Mg and hUCB-MSCs after injury. In tissue homogenates, reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) activities were measured. Quantitative real-time-polymerase chain reaction (qRT-PCR) was performed to assess iNOS, TLR4, and NF-kB gene expression. Hematoxylin and eosin (H&E) staining was performed to study the histological structure of the kidney. Immunohistochemical staining of iNOS and NF-κB was performed, as well. RESULTS: Disturbed kidney functions, oxidative status, and histological structure were seen in the rats that received cisplatin. Treated groups showed improvements in kidney functions, oxidative status, and histological structure, particularly in the combined treatment group. CONCLUSION: In the cisplatin-induced nephrotoxicity model, hUCB-MSCs could improve the functional and morphological kidney structure by modulation of oxidative and inflammatory status.

Interplay of LncRNA TUG1 and TGF-ß/P53 Expression in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent and deadly cancers worldwide. It is still necessary to further define the mechanisms and explore the therapeutic targets of CRC. Long non-coding RNA taurine upregulated gene 1 (LncRNA TUG1) was initially discovered as a transcript upregulated by taurine and is observed to be expressed in numerous human cancers. The Study Aim: This article was to explore the correlation between transforming growth factor-beta (TGF-ß)/tumor protein 53 (P53) signaling mechanisms as regulators for LncRNA TUG1 in Egyptian patients with CRC. SUBJECTS AND METHODS: Immunohistochemical (IHC) staining was achieved to study TGF-ß and P53 expression in CRC specimens vs. normal colonic specimens and quantitative real-time PCR (qRT-PCR) was used to analyze LncRNA TUG1, TGF-ß, and P53 relative gene expression in 96 tissue specimens (neoplastic specimens and the corresponding adjacent non-neoplastic specimens). RESULTS: The expressions of LncRNA TUG1, TGF-ß, and P53 were overexpressed significantly in CRC specimens as opposed to the matched neighboring non-neoplastic specimens (P<0.001), also LncRNA TUG1 was significantly positively correlated to the expression of TGF-ß and P53 (r=0.89, 0.91 respectively, P<0.001). CONCLUSION: These findings reveal that LncRNA TUG1 may be a molecular component in the TGF-ß/P53 signaling pathway, and LncRNA TUG1 could function as a CRC possible oncogene. LncRNA TUG1 may serve as a potential oncogene for CRC. The TGF-ß/P53/LncRNA TUG1 interactions may be employed as potential targets for CRC diagnosis, prognostic evaluation, and cure.

Morphological, ultrastructural, and biochemical changes induced by sodium fluoride in the tongue of adult male albino rat and the ameliorative effect of resveratrol.

Little knowledge is available about the effects of fluoride exposure on the tongue. This study evaluated the effects of sodium fluoride (NaF) on the tongue ultrastructure and detected the ameliorative effects of resveratrol. Forty adult albino rats were separated into 4 groups: the control group was given a balanced diet and purified water. The NaF treated group: received 10 mg/kg/d dissolved in 2.5 ml distilled water once daily for 30 days orally. The NaF+resveratrol group: received NaF 10 mg/kg/d orally together with resveratrol in a dose of 30 mg/kg daily for 30 days. The resveratrol group was subjected to resveratrol in a dose of 30 mg/kg/d by oral gavage for 30 days. Sections were stained with hematoxylin & eosin, and Masson's trichrome. Tumor necrosis factor α immunohistochemical study and electron microscopic examinations were done. The oxidative stress markers malondialdehyde, antioxidant reduced glutathione, and the total antioxidant capacity were measured. The NaF group revealed ulceration, necrotic muscle fibers, distorted papillae and a significant increase in malondialdehyde level, and a significant decrease in glutathione and the total antioxidant levels. In the NaF+resveratrol group, pathological changes were less, and the oxidant levels were decreased by the administration of resveratrol with NaF. In conclusion, NaF adversely affects the ultrastructure of the adult rat tongue and resveratrol can ameliorate this effect.

Maternal exposure to the environmental pollutant "BDE-47" impairs the postnatal development of rat cerebellar cortex by modulating neuronal proliferation, synaptogenesis, NGF and BDNF pathways.

2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is an environmental contaminant that crosses the blood placental barrier and interferes with the homeostasis of fetal thyroid hormones. AIM OF WORK: This study was designed to investigate the perinatal effect of BDE-47 exposure on the postnatal development of the rat cerebellar cortex. MATERIALS AND METHODS: This study was carried out on 20 pregnant rats and 36 of their offspring. The pregnant rats were divided equally into control and BDE-47 treated mother groups; supplemented orally with BDE-47 (0.2 mg/kg/day from day 8 of gestation until the day of weaning). The offspring of both mother groups were subdivided, according to their developmental age, into three subgroups; PND14, PND21and PND42. SerumT3, T4 and TSH were assessed for dams and their offspring. Testing the motor coordination of the offspring via the rotarod test was conducted. Sections of the cerebellar cortex from offspring subgroups were stained with hematoxylin and eosin alongside immunohistochemical reactions and optical density of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), proliferating cell nuclear antigen (PCNA) and synaptophysin (SYN). Also, the thickness of different layers of the cerebellar cortex was histomorphometrically measured. RESULTS: BDE-47 treated mothers and their offspring subgroups showed a significant decrease in the serum free T3, T4 and increased TSH. The BDE-47 offspring displayed incoordination of the motor activity together with disturbed cytoarchitecture of the cerebellar cortical layers, and impaired migration of its germinative neuronal zones, particularly on PND14 and PND21. Moreover, these offspring displayed a decrease of the immune-expression and optical density of NGF, BDNF in the cerebellar cortical layers with impaired proliferation, and synaptogenesis. CONCLUSION: Maternal exposure to BDE-47 during pregnancy and lactation effectuated a potential deleterious retarding effect on the postnatal development of the rat cerebellar cortex mostly via modulating neuronal proliferation, synaptogenesis, NGF and BDNF pathways secondary to its hypothyroid effect.