Molecular Mechanisms of miR-214 Involved in Cancer and Drug Resistance.

As a transcriptional regulation element, the microRNA plays a crucial role in many aspects of molecular biological processes, like cellular metabolism, cell division, cell death, cell movement, intracellular signaling, and immunity. Previous studies suggested that microRNA-214 (miR-214) is probably a valuable cancer marker. In this study, a brief updated overview of the vital dual role of miR-214 in cancer as a tumor suppressor or oncogene was provided. We also examined target genes and signaling pathways related to the dysregulation of miR-214 reported in previous experimental research on various human diseases. To highlight the critical function of miR-214 in the prognostic, diagnostic, and pathogenesis of cancer diseases, we focused on the probable clinical biomarker and drug resistance function of miR-214. The current research provides a comprehensive perspective of the regulatory mechanisms governed by miR-214 in human disease pathogenesis and a list of probable candidates for future study.

Apelin signalling in the periaqueductal grey matter alleviates capsaicin-evoked pulpal nocifensive behaviour and capsaicin-induced spatial learning and memory impairments in rat.

AIM: Pulpal pain is a common orofacial health issue that has been linked to cognitive impairment. Because of its prominent role in pain modulation and cognitive impairment, apelin (Apl) is regarded as a promising target for clinical pain management. The role of Apl in orofacial pain, however, is unknown. The purpose of this study was to determine the effects of intra-periaqueductal grey matter (PAG) administrations of Apl-13 on capsaicin-evoked pulpal nocifensive behaviour and capsaicin-induced spatial learning and memory impairments in rats. METHODOLOGY: Forty-nine male Wistar rats (200-250 g) were randomly divided into seven groups (n = 7 per group). The groups included: untreated intact, capsaicin (Caps) only, three Caps+Apl groups that received different dosages of intra-PAG injection of Apl-13 (1, 2 and 3 µg/rat) 20 min prior to capsaicin application, and two Apl+antagonist groups that received Apl receptor antagonist or naloxone (a µ opioid receptor) 20 min before Apl injection. Learning and memory were assessed using the Morris water maze test. One-way analysis of variance followed by Tukey post hoc tests was used for statistical analysis. RESULTS: Intra-PAG administration of Apl-13 significantly reduced the capsaicin-induced nocifensive behaviour (p < .01). This antinociception effect was inhibited by F13A and naloxone. Apl-13 inhibited nociception-induced learning and memory deficits (p < .01). The cognitive effects were also blocked by pre-treatment administration of F13A (3 µg/rat). CONCLUSIONS: These findings indicated that Apl-13, via Apl receptors (AR or APJ) and µ opioid receptors, alleviated capsaicin-induced dental nocifensive behaviour and protected against nociception-induced learning and memory impairments. As a result of our findings, Apl appears to be a promising analgesic option for further research in orofacial pain models and clinical trials.

A high dose of estrogen can improve renal ischemia-reperfusion-induced pulmonary injury in ovariectomized female rats.

Renal ischemia-reperfusion injury (RIRI) as a pathological process induces remote organ injury such as lung complications and it is regulated in a hormone-dependent manner. This study investigates the effect of estrogen on RIR-induced pulmonary injury in ovariectomized (OV) rats. A total of 60 female Wistar rats were divided into six groups: (i) intact sham, (ii) OV sham, (iii) OV sham + estradiol valerate (E), (iv) intact ischemia, (v) OV ischemia, and (vi) OV ischemia + E. Bilateral ischemia was performed for 45 min in all groups except sham. Before the ischemia, OV groups received an intramuscular (i.m.) injection of E. After reperfusion, blood samples were collected for serum analysis and kidney and lung tissue were separated for pathological experiment and malondialdehyde (MDA) and nitrite measurement. The left lung was weighed to measure pulmonary edema. Estrogen deficiency caused a greater increase in blood urea nitrogen and creatinine levels during IRI. Ischemia reduced nitrite of serum and lung tissue. The increased level of MDA during ischemia, returned to normal levels via estrogen injection. The severity of renal and lung damage in ischemic groups increased significantly, and estrogen improved this injury. Estrogen as an antioxidant agent can reduce oxidative stress and may improve renal function and ameliorating lung damage caused by RIR.

The influence of renal ischemia-reperfusion injury on remote organs: The histological brain changes in male and female rats.

INTRODUCTION: Brain tissue was adversely affected by renal ischemia-reperfusion injury (renal IRI) in several studies. Moreover, we are awareness that kidney diseases are gender dependent, but there is not enough evidence of the impact of gender on renal IRI-induced brain injury. Hence, this study was designed to investigate gender differences in renal IRI-induced brain tissue injury in adult rats. MATERIALS AND METHODS: Forty Wistar rats (four groups) include two main groups (20 male and 20 female). Each of them was divided into two subgroups including 1 and 2: male and female sham-operated groups and 3and 4: male and female ischemia (ISC) groups were exposed to renal ischemia for 45 min and then 24 h reperfusion (male and female ISC 24 h). Sham groups were exposed to surgery without ischemia process. After reperfusion time, blood samples were obtained for the renal function measurements. The kidney and brain were removed and were fixed in a 10% formalin solution for pathological assessment. The left kidney was used to measure malondialdehyde (MDA) and nitrite. RESULTS: Renal IRI increased significantly levels of creatinine, blood urea nitrogen, kidney weight, and damage score in both genders (P < 0.05). Furthermore, brain injuries were significantly higher following 24 h of reperfusion in male and female groups. Serum nitrite level and MDA concentration of female rats decreased significantly in ISC 24 h group (P < 0.05) but not in male rats. CONCLUSION: The brain tissue of both genders, male and female, is affected by renal IRI as a remote organ. Female sex hormones may indicate a protective role against IR by the nitric oxide pathway and antioxidant signaling.

Cisplatin-Induced Nephrotoxicity; Protective Supplements and Gender Differences

Cisplatin (CDDP) has been widely used as a chemotherapeutic agent for solid tumors. The most common side effect of CDDP is nephrotoxicity, and many efforts have been made in the laboratory and the clinic to employ candidate adjuvants to CDDP to minimize this adverse influence. Many synthetic and herbal antioxidants as well as trace elements have been investigated for this purpose in recent years and a variety of positive and negative results have been yielded. However, no definitive supplement has so far been proposed to prevent CDDP-induced nephrotoxicity; however, this condition is gender related and the sex hormone estrogen may protect the kidney against CDDP damage. In this review, the results of research related to the effect of different synthetic and herbal antioxidants supplements are presented and discussed with suggestions included for future work.

Role of Mas receptor in renal blood flow response to angiotensin-(1-7) in ovariectomized estradiol treated rats.

The angiotensin 1-7 (Ang 1-7), is abundantly produced in kidneys and antagonizes the function of angiotensin II through Mas receptor (MasR) or other unknown mechanisms. In the current study, the role of MasR and steroid hormone estrogen on renal blood flow response to Ang 1-7 administration was investigated in ovariectomized (OV) female rats. OV female Wistar-rats received estradiol (500 µg/kg/week) or vehicle for two weeks. In the day of the experiment, the animals were anesthetized, cannulated, and the responses including mean arterial pressure, renal blood flow (RBF), and renal vascular resistance at the constant level of renal perfusion pressure to graded infusion of Ang 1-7 at 0, 100 and 300 ng/kg/min were determined in OV and OV estradiol-treated (OVE) rats, treated with vehicle or MasR antagonist; A779. RBF response to Ang 1-7 infusion increased dose-dependently in vehicle (Pdose <0.001) and A779-treated (Pdose <0.01) animals. However, when MasR was blocked, the RBF response to Ang 1-7 significantly increased in OV animals compared with OVE rats (P<0.05). When estradiol was limited by ovariectomy, A779 increased RBF response to Ang 1-7 administration, while this response was attenuated in OVE animals.

Cisplatin-induced nephrotoxicity alters blood pressure response to angiotensin II administration in rats.

BACKGROUND: Cisplatin (CP) is an effective chemotherapeutic drug used in the clinic, which is accompanied with nephrotoxicity. CP may also disturb hemodynamics of the circulation system. We have tested the role of CP in mean arterial pressure (MAP) response to graded angiotensin (Ang) II infusion in rats. MATERIALS AND METHODS: Male and female rats were treated with CP (2.5 mg/kg/day) for a period of 1-week and compared with the vehicle-treated animals. The blood pressure response to Ang II (100-1000 ng/kg/min) was determined under the anesthesia condition. Endothelial permeability of aorta was measured according to the Evans blue uptake. The kidney tissue was also subjected to histological investigation. RESULTS: Significant increase in serum levels of blood urea nitrogen and creatinine and pathological findings in CP-treated rats verified CP-induced nephrotoxicity. Significant difference in percentage of change in MAP response to Ang II between male and female rats was detected in vehicle-treated groups (P < 0.05) while in CP-treated animals this response difference was not observed. The groups were not significantly different with regard to the endothelial permeability of aorta while the serum level of nitrite in male rats increased significantly following administration of CP (P < 0.05). CONCLUSION: It seems the different response in percentage of change of MAP to graded Ang II infusion between male and female indicates the effect of CP on renin Ang system parameters.

Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7 after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats.

Background. The accompanied role of Mas receptor (MasR), bradykinin (BK), and female sex hormone on renal blood flow (RBF) response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779) and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats. Methods. Ovariectomized Wistar rats received estradiol (OVE) or vehicle (OV) for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP), RBF, and renal vascular resistance (RVR) responses to Ang 1-7 (0, 100, and 300 ng kg(-1) min(-1)) were determined. Results. Percentage change of RBF (%RBF) in response to Ang1-7 infusion increased in a dose-dependent manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1-7 in OVE group was greater than OV group significantly (P < 0.05). Infusion of 300 ng kg(-1) min(-1) Ang 1-7 increased RBF by 6.9 ± 1.9% in OVE group versus 0.9 ± 1.8% in OV group. However when MasR was blocked, %RBF response to Ang 1-7 in OV group was greater than OVE group insignificantly. Conclusion. Coadministration of BK and A779 compared to BK alone increased RBF response to Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol treated rats.

Protective effect of pomegranate flower extract against gentamicin-induced renal toxicity in male rats.

INTRODUCTION: Gentamicin (GM) as an antibiotic is used in clinic. However, its administration is limited by side effects such as nephrotoxicity. Herbal extracts could be used in therapeutic approaches. OBJECTIVES: The present study was planned to investigate whether pomegranate flower extract (PFE) could ameliorate GM-induced renal toxicity in male rats. MATERIALS AND METHODS: Twenty eight male Wistar rats were divided into 5 groups. Groups 1 and 2 respectively received PFE 25 and 50 mg/kg for 9 days. Groups 3, 4 and 5 received saline, PFE 25 mg/kg, and PFE 50 mg/kg for 9 days, respectively, and GM (100 mg/kg/day) was administered from day 3 on. Blood samples were obtained, and after sacrificing the animals, the kidneys were removed for histopathology investigations. RESULTS: GM alone increased the serum levels of creatinine (Cr) and blood urea nitrogen (BUN), and tissue damage and kidney weight (P < 0.05). However, administration of low dose of PFE accompanied with GM decreased these markers significantly (P < 0.05). Low dose of PFE also ameliorated weight loss induced by GM (P < 0.05). CONCLUSION: It is concluded that PFE 25 mg/kg is the effective dose to ameliorate nephrotoxicity induced by GM.

Effect of pomegranate flower extract on cisplatin-induced nephrotoxicity in rats.

BACKGROUND: Chemotherapy with cisplatin (CP) is accompanied with nephrotoxicity. OBJECTIVES: In the current study, pomegranate flower extract (PFE) has been evaluated as an antioxidant agent against CP-induced-renal toxicity. MATERIALS AND METHODS: Thirty two male Wistar rats were divided into five groups (6-8 in each group). The animals in groups 1 to 3 received PFE (25 mg/kg), PFE (50 mg/kg), and placebo (saline), respectively for 9 days, and onset of the day 3, they also received CP (2.5 mg/kg/day). Groups 4 and 5 were treated with PFE (25 and 50 mg/kg/day) for 9 days. Finally, the animals were sacrificed at day 9 after collecting blood samples. Kidneys were removed, weighted, and underwent histopathological investigation. RESULTS: The mean serum level of creatinine in group 3 (treated with CP and placebo) increased significantly (p<0.05), but the value decreased significantly (p<0.05) in group 1. Kidney weight in group 1 was lower than KW in groups 2 and 3, however it was significant when compared with group 2 (p<0.05). The serum nitrite level in group 2 was non-significantly lower than that in other groups, and no significant changes were observed in serum levels of malondialdehyde (MDA). Tissue level of nitrite was significantly decreased in the positive control and high dose of PFE plus CP-treated groups (p<0.05). Among CP-treated groups, low dose of PFE significantly improved kidney nitrite level (p<0.05). The results from histopathological staining indicated less tissue damage in group 1 when compared with group 3. CONCLUSIONS: It seems that low dose of PFE plays a protective role against CP-induced renal toxicity in rats.