Activation of BDNF- and VEGF-mediated Neuroprotection by Treadmill Exercise Training in Experimental Stroke.

Early treatment of ischemic stroke is one of the most effective ways to reduce brains' cell death and promote functional recovery. This study was designed to examine the effect of aerobic exercise on post ischemia/reperfusion injury on concentration and expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) after inducing a neuronal loss in CA1 region of hippocampus in Male Wistar rats. Three experimental groups including sham(S), ischemia/reperfusion-control (IRC) and ischemia/reperfusion exercise (IRE) were used for this purpose. The rats in the IRE group received a bilateral carotid artery occlusion treatment. They ran for 45 minutes on a treadmill five days per week for eight consecutive weeks. Cresyl violet (Nissl), Hematoxylin (H & E) and Eosin staining procedure were used to determine the extent of damage. A ladder rung walking task was used to assess the functional impairments and recovery after the ischemic lesion. ELISA and immunohistochemistry method were employed to measure BDNF and VEGF protein expressions. The result showed that the brain ischemia/reperfusion condition increased the cell death in hippocampal CA1 neurons and impaired motor performance on the ladder rung task whereas the aerobic exercise program significantly decreased the brain cell's death and improved motor skill performance. It was concluded that ischemic brain lesion decreased the BDNF and VEGF expression. It seems that the aerobic exercise following the ischemia/reperfusion potentially promotes neuroprotective mechanisms and neuronal repair and survival mediated partly by BDNF and other pathways.

Curcumin delivery by modified biosourced carbon-based nanoparticles.

Aim: To prepare a novel hybrid system for the controlled release and delivery of curcumin (CUR). Methods: A method for the ultrasound-assisted fabrication of protein-modified nanosized graphene oxide-like carbon-based nanoparticles (CBNPs) was developed. After being modified with bovine serum albumin (BSA), CUR was loaded onto the synthesized hybrid (labeled CBNPs@BSA-CUR). The structure and properties of the synthesized nanoparticles were elucidated using transmission electron microscopy (TEM), atomic force microscopy (AFM), ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR) and x-ray photoelectron spectroscopy (XPS) methods. Results: CBNPs@BSA-CUR showed pH sensitivity and were calculated as controlled CUR release behavior. The drug-free system exhibited good biocompatibility and was nontoxic. However, CBNPs@BSA-CUR showed acceptable antiproliferative ability against MCF-7 breast cancer cells. Conclusion: CBNPs@BSA-CUR could be considered a highly promising nontoxic nanocarrier for the delivery of CUR with good biosafety.

Anticancer effects of bifidobacteria on colon cancer cell lines.

BACKGROUND: Colorectal cancer (CRC), with a growing incidence trend worldwide, is resistant to apoptosis and has uncontrolled proliferation. It is recently reported that probiotic microorganisms exert anticancer effects. The genus Bifidobacterium, one of the dominant bacterial populations in the gastrointestinal tract, has received increasing attention because of widespread interest in using it as health-promoting microorganisms. Therefore, the present study aimed to assess the apoptotic effects of some bifidobacteria species on colon cancer cell lines. METHODS: The cytotoxicity evaluations performed using MTT assay and FACS-flow cytometry tests. Also, the effects of five species of bifidobacteria secretion metabolites on the expression level of anti- or pro-apoptotic genes including BAD, Bcl-2, Caspase-3, Caspase-8, Caspase-9, and Fas-R studied by real-time polymerase chain reaction (RT-PCR) method. RESULTS: The cell-free supernatant of all studied bifidobacteria significantly decreased the survival rates of colon cancer cells compared with control groups. Flow cytometric and RT-PCR results indicated that apoptosis is induced by bifidobacteria secretion metabolites and the mechanism for the action of bifidobacteria species in CRC prevention could be down-regulation and up-regulation of anti-apoptotic and, pro-apoptotic genes. CONCLUSIONS: In the present study, different bifidobacteria species showed anticancer activity on colorectal cancer cells through down-regulation and up-regulation of anti-apoptotic and pro-apoptotic genes. However, further studies are required to clarify the exact mechanism of apoptosis induction by bifidobacteria species.

Evaluation of STAT3 decoy oligodeoxynucleotides' synergistic effects on radiation and/or chemotherapy in metastatic breast cancer cell line.

Resistance to radiotherapy and chemotherapy has been a major problem of conventional cancer therapies, which consequently leads to cancer relapse and cancer-related death. It is known that cancer stem cells (CSCs) play a key role in therapy resistance and CSC-based targeted therapies have been considered as a powerful tool for cancer treatment. In the current study, we investigated the synergistic effects of suppressing signal transducer and activator of transcription (STAT3) function by decoy ODNs on X-irradiation (XI) and methotrexate (MTX) exposure as a combinational therapy in triple-negative breast cancer (TNBC) MDA-MB-231 cells. Lipofectamine 2000® was used as a transfecting agent and the cells treated with Scramble ODNs (SCR) and decoy ODNs were subjected to irradiation with 2 Gy at single/fractionated (XI group) doses, different concentration of MTX group, and X-irradiation-methotrexate (XI/MTX group). Synergistic effects of STAT3 SCR and decoy ODNs on cells were investigated by cell viability (MTT), cell cycle profile, apoptosis rate, migration, and invasion assays. Statistical analysis of obtained data showed that STAT3 decoy ODNs significantly decreased the cell viability, arrested the growth at G0/G1 phase, increased apoptosis rate, and reduced migrated and invaded cells through transwell membrane, in XI, MTX, and XI/MTX exposed groups. Since STAT3 is a master transcription factor in breast cancer cells stemness, aggressiveness, TNBC's heterogeneity, and therapy resistance; therefore, inhibition of this transcription factor by decoy ODNs could increase antitumor efficiencies of XI and MTX exposure strategies. Accordingly, this method could have the potential to increase the efficiency of combination therapies.

Anticancer effect of X-Ray triggered methotrexate conjugated albumin coated bismuth sulfide nanoparticles on SW480 colon cancer cell line.

The application of nanoparticles (NPs) as radio-sensitizers and carriers has opened up a new horizon to overcome the limitations of chemo and radiotherapy. In this study, bovine serum albumin-coated Bi2S3 NPs (Bi2S3@BSA NPs) were synthesized and evaluated in terms of their ability to be used as a radio-sensitizer and carrier for methotrexate (MTX). Physicochemical properties of MTX conjugated Bi2S3@BSA NPs (Bi2S3@BSA-MTX NPs) were characterized by DLS, TEM, FTIR, UV/Vis, and XRD analyses. After the evaluation of cellular uptake and intracellular localization, the cytotoxicity of the combination of Bi2S3@BSA-MTX NPs and X-Ray radiation was analyzed against the SW480 cell line. The synthesized NPs exhibited spherical-like shapes and homogenous morphology, possessing a hydrodynamic diameter of 140.2 ± 5.71 nm (mean ± SD) and zeta potential of -25 mV. Also, the release study showed that the release of MTX is faster and higher in the presence of the proteinase K enzyme than the absence of the enzyme. The results of in-vitro chemo-radiation therapy indicated that the viability of treated cells with Bi2S3@BSA-MTX NPs is significantly lower than the cells treated with Bi2S3@BSA NPs. Furthermore, cells treated with Bi2S3@BSA-MTX NPs showed a lower degree of viability when combined with X-Ray radiation in comparison with the absence of irradiation, which confirmed the ability of the Bi2S3@BSA-MTX NPs as radio-sensitizer.

Exogenous adenosine facilitates neuroprotection and functional recovery following cerebral ischemia in rats.

INTRODUCTION & OBJECTIVE: Cerebral ischemia causes physiological and biochemical cellular changes that ultimately result in structural and functional damage to hippocampal neurons. Ischemia also raises endogenous adenosine release that in turn has neuroprotective effects. The purpose of this study was to evaluate the effect of exogenous adenosine on mitigating neuronal lesions to the CA1 region of hippocampus and A2A protein expression following cerebral I/R in rats. METHODS: Male Wistar rats were randomly assigned to three experimental groups (sham, ischemia + control, and ischemia + adenosine). A daily dose of adenosine (0.1 mg/ml/kg, i.p.) was administered starting 24 h post-ischemia for 7 days. Ischemia was induced by occlusion of both common carotid arteries for 45 min. Cresyl violet and Hematoxylin Eosin staining were used to assess lesion extent and location. To investigate the expression and protein levels, immunohistochemistry and enzyme-linked immunosorbent assay method was used. RESULTS: The cerebral ischemia caused neuronal loss in the CA1 region and reduced sensorimotor functions in lesion animals. Injection of adenosine significantly diminished cell death and improved sensorimotor functional recovery. Moreover, the expression and concentration of A2A protein was significantly greater in the adenosine group compared to the ischemia group. CONCLUSION: This study showed that the administration of exogenous adenosine promotes protection against cell death and supports functional recovery following ischemic injury.