MIR96 Has Good Potential to Differentiate Human Bone Marrow-Derived Mesenchymal Stem Cells into Photoreceptor-Like Cells.

OBJECTIVES: MicroRNAs play an important role in the development and function of neuron cells. Among these, the miRNA known as MIR96 is abundantly expressed in mammalian retina and significantly affects differentiation, maturation, and survival of human photoreceptor cells. In this study, a mimic to miRNA-96 was transfected into human bone marrowderived mesenchymal stem cells to explore the biological functions of MIR96 at differentiation processing. MATERIALS AND METHODS: A mimic to miRNA-96 and a competitive control were transfected into human bone marrow-derived mesenchymal stem cells using Lipofectamine. After 24 and 48 hours, we evaluated changes in expression levels of genes associated with neural progenitor and photoreceptor differentiation (OTX2, NRL, protein kinase C, SLC1A1, and recoverin) by real-time polymerase chain reaction. In addition, we measured expression of mRNA and protein of the CRX gene (neuroretinal progenitor cell marker) and the RHO gene (terminal differentiation marker) using real-time polymerase chain reaction and immunocytochemistry, respectively. RESULTS: Real-time polymerase chain reaction results showed increased levels of RHO and recoverin mRNA after 24 hours in transfected cells. In addition, mRNA levels of OTX2, CRX, NRL, RHO, recoverin, and protein kinase C increased after 48 hours in transfected cells. Immunocytochemistry results confirmed these findings by demonstrating RHO and CRX at both 24 and 48 hours in transfected cells. CONCLUSIONS: Control of the expression of MIR96 can be a good strategy to promote cell differentiation and can be used in cell therapy for retinal degeneration. Our results showed that human bone marrow-derived mesenchymal stem cells can differentiate into photoreceptor cells after transfection with MIR96. These results support therapeutic use of MIR96 in retinal degeneration and suggest human bone marrowderived mesenchymal stem cells as a promising tool for interventions.

The impact of oleuropein on miRNAs regulating cell death signaling pathway in human cervical cancer cells.

Cervical cancer is known as the second most pervasive malignancy in women across the globe. The role played by microRNAs (miRNAs) in the initiation, progression, and metastasis of this cancer has received specific attention. The use of natural compounds leading cancer cells toward apoptosis is a feasible strategy for cancer therapy. Oleuropein, an olive-extracted phenolic substance, displays anticancer properties. Here, it was attempted to assess the role played by oleuropein in cell viability in cervical cancer and changes in the expression of some miRNAs associated with cervical cancer as well as some of their possible target genes selected using bioinformatics analysis. For this purpose, HeLa cell line was exposed to several oleuropein concentrations for 48 and 72 h. After that, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry were employed to assess cell viability and apoptosis, respectively. In addition, to conduct bioinformatics analysis, Cytoscape computer program was used based on STRING database. Furthermore, to examine the role played by oleuropein in the expression of miRNAs of interest as well as their potential target genes, real-time PCR was employed. The findings indicated that oleuropein reduced cell viability through inducing apoptosis. As a result of treatment with oleuropein, miR-34a, miR-125b, and miR-29a showed increased expression levels, whereas miR-181b, miR-221, and miR-16 showed decreased expression levels. Furthermore, oleuropein reduced the expression of the anti-apoptotic genes Bcl-2 and Mcl1, whereas it elevated the expression of the pro-apoptotic Bid, Fas, and TNFRSF10B genes and the p53 tumor suppressor. Our results indicate that the apoptosis induction is a mechanism of action of oleuropein in HeLa cells. Because of its effect on the reflation of the expression of genes and miRNAs effective in the pathogenesis of cervical cancer, oleuropein shows potential as an effective research tool for developing new natural drugs for treating cervical cancer.

Effects of Satureja Bachtiarica Essential Oil in Preventing Seizure in Pentylenetetrazol-Kindled Mice.

Introduction: Epilepsy is a group of chronic neurological disorders characterized by seizures. The present study aimed to investigate the effects of Satureja bachtiarica essential oil in preventing epilepsy. Methods: In this experimental study, 50 mice were randomly assigned to five groups of 10 each. The control group received normal saline plus tween-80 and after 30 min pentylenetetrazol (PTZ). Groups 2 and 3 were treated first with S. bachtiarica essential oil at 50 and 100 mg/kg, respectively and then after 30 min received PTZ. Group 4 received diazepam and 30 min later PTZ. Group 5 received flumazenil and 30 min later PTZ. After the last injection of PTZ, the time of seizure onset, seizure severity and score, the completion time of each seizure (attack episode), and mortality rate in different groups were recorded and compared. Results: The administration of S. bachtiarica essential oil at 50 and 100 mg/kg to PTZ-treated mice caused a significant increase in latency to the first seizure and survival of mice, as well as a significant decrease in the frequency of the head and upper limbs seizure, total body seizures, tonic seizures, and jumping. S. bachtiarica essential oil at 100 mg/kg caused a significant decrease in the head tic frequency. The administration of flumazenil significantly inhibited S. bachtiarica essential oil-induced effects and increased the head and upper limbs seizures, tonic seizures, and jumping. Conclusion: The present study demonstrated that S. bachtiarica essential oil could prevent PTZ-induced seizure and these findings authenticate the traditional claims about the use of S. bachtiarica in treating epilepsy. Highlights: The administration of S. bachtiarica essential oil at 50 and 100 mg/kg to pentylenetetrazol PTZ-treated mice caused a significant increase in latency to the first seizure.• The administration of S. bachtiarica essential oil at 50 and 100 mg/kg to PTZ-treated mice caused a significant decrease in the frequency of the head and upper limbs seizures, total body seizures, tonic seizures, and spin and jump.• The administration of flumazenil significantly inhibited S. bachtiarica essential oil-induced effects and increased the head and upper limbs seizures, tonic seizures, and jumping. Plain Language Summary: Epilepsy is one of the most common disorders of the central nervous system, so that one in every 100 people is suffering from epilepsy globally. Despite the development of antiepileptic drugs, novel strategies are sought out because of drug resistance and the side effects resulting from these drugs at high concentrations. Researchers have focused on plants for certain reasons such as availability, the history of long-term use, being nature-based, and relative safety. In the current study, the effect of the pretreatment with S. bachtiarica essential oil in preventing seizure was studied in the pentylenetetrazol-kindled mice. The injection of 50 and 100 mg/kg of S. bachtiarica essential oil caused a significant increase in latency to the first seizure and survival duration, and a significant decrease in the frequency of the head and upper limbs seizures, tonic seizures, and spin and jump in the pentylenetetrazol-receiving mice.

Chemopreventive effect of spirulina microalgae on an animal model of glioblastoma via down-regulation of PI3K/AKT/mTOR and up-regulation of miR-34a/miR-125B expression.

Recent studies suggest that Spirulina may have great therapeutic benefits due to its antioxidant and anti-inflammatory properties. The primary objective of this study was to evaluate the chemopreventive properties of the Spirulina microalgae (Spi) on the regression and survival of tumor, histopathological features of glioblastoma, and detection of the molecular mechanism of Spi. Tumor viability versus Spi was determined using the MTT assay. In vivo antitumor activity of Spi was studied using the glioblastoma model. After tumor induction, the animals were euthanized, and their brains were removed. Histological evaluation was performed for tumor size and manifestation. The mechanisms of the anticancer effects of Spi were investigated by evaluating the microRNAs and their targets. The results demonstrated that Spi inhibited C6 and U87 cell proliferation and induced cell death. Histopathologic results showed that the administration of Spi could delay the development of tumors and prolonged the survival of tumor-bearing animals. Furthermore, Spi significantly upregulated miR-34a and miR-125b that have a key role in the progression of PI3K/AKT/mTOR pathway. This is the first in vivo report on the chemo-preventive effect of Spi against glioblastoma, suggesting its potential use in the chemoprevention of this cancer and the antiglioma molecular mechanism of Spi.

Retinoic acid and taurine enhance differentiation of the human bone marrow stem cells into cone photoreceptor cells and retinal ganglion cells.

Degeneration and apoptotic death of the photoreceptor cell-layer of retina are a major cause of irreversible blindness in the development era. The stem cell replacement therapy is one of the strategies for the retinal repairing. In addition, exogenous signals critically contribute to the direction of lineage decisions that causes the fate-restricted photoreceptor progenitors from stem cell progeny in culture. It has been found that epidermal growth factor (EGF), taurine, and retinoic acid (RA) initially act in the instructive as well as lineage-restricted way in the progenitor lineage for producing neuroretinal cells or photoreceptor like cells from stem cell. The study aims to investigate the effect of RA and taurine in differentiation of the human bone marrow stem cell into cone photoreceptors cells and retinal ganglion cells. Mesenchymal stem cell was derived from human bone marrow of the term delivery. Therefore, the cultured cells have been treated with Dulbecco's modified Eagle's medium (DMEM)/high glucose (H+ ). After the four-cell passage, basal medium was replaced with DMEM/F12 complemented with 50 µmol/L taurine, RA (1 µM) and EGF (1 µg/ml). Subsequently cellular change morphology was detected following 7 and 14 days. Then, gene expression of neuroretinal and photoreceptor cell biomarkers (CRX, OTX2, PKC-α, recoverin, and Rho) were examined by quantitative polymerase chain reaction (Q-PCR). Also, cells were cultured, fixed, and then immunocytochemical analyzed. Primary antibodies included CRX and Rho. Cellular morphology demonstrated spindle elongated morphology. Taurine alone and combination of RA upregulate neuroretinal and photoreceptor cell biomarkers in messenger RNA and protein levels but along with EGF have not significant effect. Our data showed that taurine combination with RA can differentiate bone marrow mesenchymal stem cells into neuroretinal or photoreceptor like cells in vitro that can offer an attractive treatment ground for transplantation in the cell-replacement therapy for some forms of the retinal degeneration.

Prediction and analysis of microRNAs involved in COVID-19 inflammatory processes associated with the NF-kB and JAK/STAT signaling pathways.

COVID-19 is the cause of a pandemic associated with substantial morbidity and mortality. As yet, there is no available approved drug to eradicate the virus. In this review article, we present an alternative study area that may contribute to the development of therapeutic targets for COVID-19. Growing evidence is revealing further pathophysiological mechanisms of COVID-19 related to the disregulation of inflammation pathways that seem to play a critical role toward COVID-19 complications. The NF-kB and JAK/STAT signaling pathways are highly activated in acute inflammation, and the excessive activity of these pathways in COVID-19 patients likely exacerbates the inflammatory responses of the host. A group of non-coding RNAs (miRNAs) manage certain features of the inflammatory process. In this study, we discuss recent advances in our understanding of miRNAs and their connection to inflammatory responses. Additionally, we consider the link between perturbations in miRNA levels and the onset of COVID-19 disease. Furthermore, previous studies published in the online databases, namely web of science, MEDLINE (PubMed), and Scopus, were reviewed for the potential role of miRNAs in the inflammatory manifestations of COVID-19. Moreover, we disclosed the interactions of inflammatory genes using STRING DB and designed interactions between miRNAs and target genes using Cityscape software. Several miRNAs, particularly miR-9, miR-98, miR-223, and miR-214, play crucial roles in the regulation of NF-kB and JAK-STAT signaling pathways as inflammatory regulators. Therefore, this group of miRNAs that mitigate inflammatory pathways can be further regarded as potential targets for far-reaching-therapeutic strategies in COVID-19 diseases.

Neuroprotective effect of herniarin following transient focal cerebral ischemia in rats.

Ischemic stroke is a devastating central nervous disease. Despite extensive research in to this area, few innovative neuroprotective treatments have been presented. 7-methoxycoumarin, also known as herniarin, is a common natural coumarin in several plant species. This project examined the effects of the herniarin in rats subjected to the middle cerebral artery occlusion (MCAO). Herniarin at doses of 10 and 20 mg/kg was administered through intraperitoneal injection for 7 days before MCAO induction. Rats were subjected to a 30 min MCAO and a subsequent 24 h' reperfusion. 24 h after the termination of MCAO, neurologic outcome, volume of brain infarction, level of interleukin-1ß (IL-1ß) and tumor necrosis factor alpha (TNF-α), as inflammatory markers, and oxidative stress markers including levels of total thiol, malondialdehyde (MDA), and superoxide dismutase (SOD) activity were estimated. Herniarin administration decreased the MCAO-induced infarct volume and neurological deficits. Moreover, pretreatment with herniarin significantly decreased the levels of MDA while simultaneously increasing the level of total thiol and SOD activity in the brain tissues of MCAO rats. Moreover, herniarin pretreatment decreased the levels of IL-1ß and TNF-α in the brain tissues of MCAO rats. These results suggest that herniarin presents beneficial effects against ischemic stroke, partly through the inhibition of oxidative stress and inflammation.

Neuroprotective effect of wild lowbush blueberry (Vaccinium angustifolium) on global cerebral ischemia/reperfusion injury in rats: Downregulation of iNOS/TNF-α and upregulation of miR-146a/miR-21 expression.

This study aims to investigate the neuroprotective effect of wild lowbush blueberry on CIRI in rats. Accordingly, CIRI and reperfusion were induced in rats for 60 min and 24 h, respectively. Then, the mechanisms of the neuroprotective effects of BBE were investigated in the injury through evaluating miR-146a, miR-21, and their targets in a CIRI rat model. After that, the BBE (30, 60, and 120 mg/kg b.wt) was intraperitoneally injected for 14 days, then CIRI was induced by BCCAO for 60 min for ischemic stroke and reperfusion for 24 h. Several parameters including the oxidative stress levels in the hippocampus and serum were measured 24 h after the CIRI. The findings showed that the BBE significantly decreased the levels of malondialdehyde (MDA) and nitric oxide (NO) and increased ferric ion reducing antioxidant power (FRAP) levels in the hippocampus and serum following the stroke. The BBE also maximized the miR-146a and miR-21 expressions and moderated iNOS and TNF-α expressions in the hippocampus. Likewise, the BBE enlarged the CA1 and CA3 domains of the post-stroke pyramidal cell layers of the hippocampus. Overall, the results revealed that BBE had potent neuroprotective efficacy against CIRI via the effective modulation of neuroinflammatory cascades and protected neurons against ischemic death.

Protective Effect of Capparis spinosa Extract against Focal Cerebral Ischemia-reperfusion Injury in Rats.

BACKGROUND: Ischemic stroke is a serious public health problem. Despite extensive researches focusing on the area, little is known about novel treatments. OBJECTIVE: In this study, we aimed to investigate the effects of Capparis spinosa (C. spinosa) extract in the middle cerebral artery occlusion (MCAO) model of ischemic stroke. METHODS: Wistar rats underwent 30-min MCAO-induced brain ischemia followed by 24 h of reperfusion. C. spinose was administrated orally once a day for 7 days before the induction of MCAO. The neurologic outcome, infarct volume (TTC staining), histological examination, and markers of oxidative stress, including total thiol content, and malondialdehyde (MDA) levels, were measured 24hr. after the termination of MCAO. RESULTS: Pretreatment with C. spinosa reduced neurological deficit score, histopathological alterations, and infarct volume in treated groups compared to the stroke group. Furthermore, pretreatment with C. spinosa extract significantly reduced the level of MDA with concomitant increases in the levels of thiol in the brain tissues compared to the stroke group. CONCLUSION: Our study demonstrates that C. spinosa extract effectively protects MCAO injury through the attenuation or the suppression of the oxidative stress.

Prediction and interpretation of rare missense variant in OTOG associated with hearing loss.

OTOG encodes for otogelin, a component of the tectorial membrane. This gene is associated with nonprogressive mild-to-moderate hearing loss. However, no studies have yet identified the association between OTOG variation and severe-to-profound hearing loss. Therefore, to address this issue, a family-based whole-exome sequencing strategy (WES) was carried out. Two unrelated Iranian families with non-syndromic hearing loss were identified, and WES was conducted on one selected candidate from each family. As a result, a rare homozygous missense variant, OTOG (c.C2383T:p.R795C), was detected in both of the subjected probands, and segregation analysis confirmed the c.C2383T variant in seven cases of severe-to-profound hearing loss. Additionally, the results from the protein modeling demonstrated that the altered position of a few disulfide bonds in the TIL domain may have a deleterious impact on protein stability and normal functionality. In conclusion, it seems that the homozygosity of the OTOG c.C2383T mutation sheds light on hearing loss pathobiology. Nevertheless, further studies are required to unravel the precise function of OTOG mutation, which is potentially associated with severe-to-profound hearing loss.

Oleuropein reduces cisplatin resistance in ovarian cancer by targeting apoptotic pathway regulators.

AIMS: Despite many attempts to treat ovarian cancer, 13,940 individuals perish annually due to this disease worldwide. Chemotherapy is the main approach to ovarian cancer treatment, but the development of drug resistance is a major obstacle to the successful treatment. Oleuropein is a phenolic ingredient with anticancer characteristics. This study was aimed at investigating the effect of oleuropein on cell viability, cisplatin resistance, and apoptosis, as well as the expression levels of miR-34a, miR-125b, miR16, miR-21, and some of their potential target genes in ovarian cancer cells. MAIN METHODS: A2780S and A2780/CP cell lines were exposed to different concentrations of oleuropein alone or in combination with cisplatin for 48 h and 72 h. After that, the cell viability and apoptosis were evaluated using MTT assay and flow cytometry, respectively. Bioinformatics analyses were conducted using STRING database and Cytoscape software. The effect of oleuropein and/or cisplatin on the expression of miRNAs and target genes was assessed via Real-time PCR. KEY FINDINGS: Upon treatment with oleuropein, the expression of P21, P53, and TNFRSF10B increased while that of Bcl-2 and Mcl1 decreased. Moreover, this is the 1st report of a significant decrease in the expression of miR-21 and increase in the expression of miR-34a, miR-125b, and miR16 by oleuropein and/or cisplatin in ovarian cancer cells. SIGNIFICANCE: Altogether, these data revealed that oleuropein regulated the expression of the above-mentioned miRNAs in ovarian cancer cells, which potentially resulted in apoptosis induction, cell proliferation inhibition, and cisplatin resistance decline in ovarian cancer cells. To confirm the results of this study, it is suggested that similar experiments be performed in animal models of ovarian cancer.

Therapeutic Potential of Saffron (Crocus sativus L.) in Ischemia Stroke.

Stroke is the second leading cause of death and a main cause of disability worldwide. The majority (approximately 80%) of strokes are ischemic. Saffron (Crocus sativus L.) has been considered for medicinal purposes since ancient times. Pharmacological effects of saffron are attributed to the presence of crocin, crocetin, picrocrocin, and safranal. In the present review, we summarized the reported neuroprotective effects of saffron and its active constituents against cerebral ischemia stroke. Saffron and its components exert its beneficial effects as an antioxidant, anti-inflammatory, and antiapoptotic agent though inhibition of biochemical, inflammatory, and oxidative stress markers. Taken together, this review indicates that saffron and its ingredients could be a potent candidate in the process of new drug production for the treatment of ischemia stroke.

Regenerative Medicine Approaches in COVID-19 Pneumonia.

Regenerative medicine (RM) is an interdisciplinary field that uses different approaches to accelerate the repair and regeneration or replace damaged or diseased human cells or tissues to achieve normal tissue function. These approaches include the stimulation of the body's own repair processes, transplantation of progenitor cells, stem cells, or tissues, as well as the use of cells and exosomes as delivery-vehicles for cytokines, genes, or other therapeutic agents. COVID-19 pneumonia is a specific disease consistent with diffuse alveolar damage resulting in severe hypoxemia. Therefore, the most serious cause of death from COVID-19 is lung dysfunction. Here, we consider RM approaches to cure COVID-19 pneumonia based on what RM has so far used to treat lung diseases, injuries, or pneumonia induced by other pathogens. These approaches include stem and progenitor cell transplantation, stem cell-derived exosomes, and microRNAs therapy.

Tumor-resident adenosine-producing mesenchymal stem cells as a potential target for cancer treatment.

The development of new therapies based on tumor biology is one of the main topics in cancer treatment. In this regard, investigating the microenvironment and cellular composition of the tumor is of particular interest. Mesenchymal stem cells (MSCs) are a major group of cells in the tumor tissue and play a critical role in tumor growth and development. Investigating the mechanisms by which MSCs influence tumor growth and progression is very useful in establishing new therapeutic approaches. MSCs have some immunological capacities, including anti-inflammatory, immune-regulatory, and immune-suppressive abilities, which help the tumor growth in the inflammatory condition. They can suppress the proliferation and activation of CD4 + T cells and direct them toward the regulatory phenotype through the release of some factors such as indoleamine 2,3-dioxygenase, prostaglandin E2, and HO-1, PD-1 ligands (PD-L1 and PD-L2) and promote tolerance and apoptosis. Besides, these cells are able to produce adenosine. Adenosine has a key role in controlling the immune system by signaling through receptors located on the surface of immune cells. It plays a very essential role in tumor growth and progression. In the present review, we investigate and introduce adenosine-producing mesenchymal stem cells as a potential target for cancer treatment.

Novel MYO15A variants are associated with hearing loss in the two Iranian pedigrees.

BACKGROUND: Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods. METHODS: This study was a report on a research study of two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families. RESULTS: The results of WES data analysis to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) disease-causing variants was reported in the present study. Initial analysis identified two novel variants of MYO15A i.e. c.T6442A:p.W2148R and c.10504dupT:p.C3502Lfs*15 correspondingly which were later confirmed by Sanger validations and segregation analyses. According to online prediction tools, both identified variants seemed to have damaging effects. CONCLUSION: In this study, whole exome sequencing were used as a first approach strategy to identify the two novel variants in MYO15A in two Iranian families with ARNSHL.

Hydroalcoholic Extract of Anchusa Italica Protects Global Cerebral Ischemia-Reperfusion Injury Via a Nitrergic Mechanism.

INTRODUCTION: In stroke models, Inducible Nitric Oxide Synthase (iNOS) expression initiates cellular toxicity due to excessive Nitric Oxide (NO) generation. Anchusa italica is a medicinal herb with anti-inflammatory, antioxidant and neuroprotective properties. This study evaluated the antioxidant activity and NOS mRNA expression of the Hydroalcoholic Extract Of Anchusa Italica (HEAI) in an experimental stroke model in rats. METHODS: The stroke model was induced by bilateral occlusion of both common carotid arteries for 60 min. Twenty-four hours after surgery, HEAI (50 and 100 mg/kg i.p.) was injected daily for 10 consecutive days. mRNA expression levels of NOS subtypes and hippocampal Brain-Derived Neurotrophic Factor (BDNF) were studied using real-time PCR. Besides, hippocampal tissue plus serum concentrations of NO and Malondialdehyde (MDA) were measured. RESULTS: HEAI decreased MDA in both serum and hippocampal tissue and also reduced serum NO levels. Additionally, in the HEAI-treated groups, a down-regulation of iNOS mRNA expression, and an up-regulation of BDNF mRNA expression were observed. CONCLUSION: The results indicated that the administration of HEAI even after the onset of ischemia protects the brain from free radical injury and inflammation via a down-regulation of iNOS expression inhibiting NO production and an up-regulation of BDNF mRNA.

Therapeutic Effects of Oleuropein in Improving Seizure, Oxidative Stress and Cognitive Disorder in Pentylenetetrazole Kindling Model of Epilepsy in Mice.

Prolonged epileptic seizures are the cause of neuronal death and brain damage. Lesions in different regions of the brain can lead to memory loss and cognitive disorders. It is therefore essential to seek out new neuroprotective drugs. Our aim was to investigate the therapeutic effects of oleuropein in improving seizure, oxidative stress, and cognitive disorder in pentylenetetrazole (PTZ) kindling model of epilepsy in mice. Mice were randomized to four groups; negative control group intraperitoneally receiving PTZ for 10 days, oleuropein group receiving oleuropein (20 mg/kg) 30 min before PTZ administration, positive control group receiving diazepam 30 min before PTZ administration and flumazenil group receiving flumazenil and then oleuropein 30 min before PTZ administration. Epilepsy severity was investigated after final administration of PTZ. Then hippocampal tissues were removed and stored at -70 °C until measurements of the interleukin-1 (IL-1) and glutamate transporter 1 (GLT-1) gene expression were conducted. Oleuropein treatment caused a significant increase in seizure latency and a significant decrease in total frequencies of head ticks, head and upper limbs seizures, the whole body seizures, frequent spinning and jumping and tonic seizures in PTZ receiving mice. IL-1 expression decreased in oleuropein group and GLT-1 levels did not change significantly in this group. Oleuropein treatment caused significant improvement of passive avoidance memory in PTZ receiving mice in shuttle box. Oleuropein can decrease PTZ-induced seizures and memory disorders due to its antioxidant and anti-inflammatory properties and is thus recommended to be used for production of anti-epileptic drugs.

The effect of oleuropein on apoptotic pathway regulators in breast cancer cells.

In spite of advancements in breast cancer therapy, this disease is still one of the significant causes of women fatalities globally. Dysregulation of miRNA plays a pivotal role in the initiation and progression of cancer. Therefore, the administration of herbal compounds with anticancer effects through controlling microRNA expression can be considered as a promising therapy for cancer. Oleuropein is the most prevalent phenolic compound in olive. Given its domestic consumption, low cost, and nontoxicity for human beings, oleuropein can be used in combination with the standard chemotherapy drugs. To this end, we examined the effect of oleuropein on two breast cancer cell lines (MCF7 and MDA-MB-231). Our findings revealed that oleuropein significantly decreased cell viability in a dose- and time-dependent manner, while it increased the apoptosis in MCF7 and MDA-MB-231 cells. In the presence of oleuropein, the expression levels of miR-125b, miR-16, miR-34a, p53, p21, and TNFRS10B increased, while that of bcl-2, mcl1, miR-221, miR-29a and miR-21 decreased. The findings pointed out that oeluropein may induce apoptosis via not only increasing the expression of pro-apoptotic genes and tumor suppressor miRNAs, but also decreasing the expression of anti-apoptotic genes and oncomiR. Consequently, oleuropein can be regarded as a suitable herbal medication for cancer therapy.

MicroRNAs in Noise-Induced Hearing Loss and their Regulation by Oxidative Stress and Inflammation.

Noise exposure (NE) has been recognized as one of the causes of sensorineural hearing loss (SNHL), which can bring about irreversible damage to sensory hair cells in the cochlea, through the launch of oxidative stress pathways and inflammation. Accordingly, determining the molecular mechanism involved in regulating hair cell apoptosis via NE is essential to prevent hair cell damage. However, the role of microRNAs (miRNAs) in the degeneration of sensory cells of the cochlea during NE has not been so far uncovered. Thus, the main purpose of this study was to demonstrate the regulatory role of miRNAs in the oxidative stress pathway and inflammation induced by NE. In this respect, articles related to noise-induced hearing loss (NIHL), oxidative stress, inflammation, and miRNA from various databases of Directory of Open Access Journals (DOAJ), Google Scholar, PubMed; Library, Information Science & Technology Abstracts (LISTA), and Web of Science were searched and retrieved. The findings revealed that several studies had suggested that up-regulation of miR-1229-5p, miR-451a, 185-5p, 186 and down-regulation of miRNA-96/182/183 and miR-30b were involved in oxidative stress and inflammation which could be used as biomarkers for NIHL. There was also a close relationship between NIHL and miRNAs, but further research is required to prove a causal association between miRNA alterations and NE, and also to determine miRNAs as biomarkers indicating responses to NE.

A Review on Stem Cell Therapy for Neuropathic Pain.

Neuropathic pain is a complex, chronic pain state that is heterogeneous in nature and caused by the consequence of a lesion or disease affecting the somatosensory system. Current medications give a long-lasting pain relief only in a limited percentage of patients also associated with numerous side effects. Stem cell transplantation is one of the attractive therapeutic platforms for the treatment of a variety of diseases, such as neuropathic pain. Here, the authors review the therapeutic effects of stem cell transplantation of different origin and species in different models of neuropathic pain disorders. Stem cell transplantation could alleviate the neuropathic pain; indeed, stem cells are the source of cells, which differentiate into a variety of cell types and lead trophic factors to migrate to the lesion site opposing the effects of damage. In conclusion, this review suggests that stem cell therapy can be a novel approach for the treatment of neuropathic pain.