Intraperitoneal injection of mesenchymal stem cells-conditioned media (MSCS-CM) treated monocyte can potentially alleviate motor defects in experimental autoimmune encephalomyelitis female mice; An original experimental study.

INTRODUCTION: Multiple sclerosis (MS), as a destructive pathology of myelin in central nervous system (CNS), causes physical and mental complications. Experimental autoimmune encephalomyelitis (EAE) is laboratory model of MS widely used for CNS-associated inflammatory researches. Cell therapy using macrophage M2 (MPM2) is a cell type with anti-inflammatory characteristics for all inflammatory-based neuropathies. This experimental study investigated the probable therapeutic anti-inflammatory effects of intraperitoneal (IP) injection of MPM2 on alleviation of motor defect in EAE-affected animals. MATERIALS AND METHODS: 24 C57/BL6 female mice were divided into four groups of EAE, EAE + Dexa, EAE + PBS, and EAE + MP2. EAE was induced through deep cervical injection of spinal homogenate of guinea pigs. MPM2 cells were harvested from bone marrow and injected (106cells/ml) in three days of 10, 13 and 16 post-immunizations (p.i). Clinical score (CS), anti-inflammatory cytokines (IL-4, IL-10), pro-inflammatory gene expression (TNF-α, IL-1ß) and histopathological investigations (HE, Nissl and Luxol Fast Blue) were considered. Data were analyzed using SPSS software (v.19) and p < 0.05 was considered significant level. RESULTS: During EAE induction, the mean animal weight was decreased (p < 0.05); besides, following MPM2 injection, the weight gain was applied (p < 0.05) in EAE + MPM2 groups than control. Increased (p < 0.05) levels of CS was found during EAE induction in days 17-28 in EAE animals; besides, CS was decreased (p < 0.05) in EAE + MPM2 group than EAE animals. Also, in days 25-28 of experiment, the CS was decreased (p < 0.05) in EAE + MPM2 than EAE + Dexa. Histopathological assessments revealed low density of cell nuclei in corpus callosum, microscopically. LFB staining also showed considerable decrease in white matter density of corpus callosum in EAE group. Acceleration of white matter density was found in EAE + MPM2 group following cell therapy procedure. Genes expression of TNF-α, IL-1ß along with IL-4 and IL-10 were decreased (p < 0.05) in EAE + MPM2 group. CONCLUSION: IP injection of MPM2 to EAE-affected female mice can potentially reduce the CNS inflammation, neuronal death and myelin destruction. MPM2 cell therapy can improve animal motor defects.

Terminalia chebula attenuates restraint stress-induced memory impairment and synaptic loss in the dentate gyrus of the hippocampus and the basolateral and central nuclei of the amygdala by inhibiting oxidative damage.

Chronic restraint stress induces cognitive abnormalities through changes in synapses and oxidant levels in the amygdala and hippocampus. Given the neuroprotective effects of fruit of Terminalia chebula (Halileh) in different experimental models, the present investigation aimed to address whether Terminalia chebula is able to reduce chronic restraint stress-induced behavioral, synaptic and oxidant markers in the rat model. Thirty-two male Wistar rats were randomly divided into four groups as follows: control (did not receive any treatment and were not exposed to stress), stress (restraint stress for 2 h a day for 14 consecutive days), Terminalia chebula (received 200 mg/kg hydroalcoholic extract of Terminalia chebula), and stress + Terminalia chebula groups (received 200 mg/kg extract of Terminalia chebula twenty minutes before stress) (n = 8 in each group). We used the shuttle box test to assess learning and memory, Golgi-Cox staining to examine dendritic spine density in the dentate gyrus region of the hippocampus and the basolateral and central nuclei of the amygdala, and total antioxidant capacity (TAC) and total oxidant status (TOS) in the brain. The shuttle box test results demonstrated that Terminalia chebula treatment had a profound positive effect on memory parameters, including step-through latency (STL) and time spent in the dark room, when compared to the stress group. Daily oral treatment with Terminalia chebula effectively suppressed the loss of neural spine density in the dentate gyrus region of the hippocampus and the basolateral and central nuclei of the amygdala caused by chronic restraint stress, as demonstrated by Golgi-Cox staining. Additionally, the results indicate that Terminalia chebula significantly reduced the TOS and increased TAC in the brain compared to the stress group. In conclusion, our results suggest that Terminalia chebula improved memory impairment and synaptic loss in the dentate gyrus of the hippocampus and the basolateral and central nuclei of the amygdala induced by restraint stress via inhibiting oxidative damage.

Antiproliferative effects of mesenchymal stem cells carrying Newcastle disease virus and Lactobacillus Casei extract on CT26 Cell line: synergistic effects in cancer therapy.

BACKGROUND AND AIMS: Colorectal Cancer (CRC) is a frequent malignancy with a high mortality rate. Specific inherited and environmental influences can affect CRC. Oncolytic viruses and bacteria in treating CRC are one of the innovative therapeutic options. This study aims to determine whether mesenchymal stem cells (MSCs) infected with the Newcastle Disease Virus (NDV) in combination with Lactobacillus casei extract (L. casei) have a synergistic effects on CRC cell line growth. MATERIALS AND METHODS: MSCs taken from the bone marrow of BALB/c mice and were infected with the 20 MOI of NDV. Then, using the CT26 cell line in various groups as a single and combined treatment, the anticancer potential of MSCs containing the NDV and L. casei extract was examined. The evaluations considered the CT26 survival and the rate at which LDH, ROS, and levels of caspases eight and nine were produced following various treatments. RESULTS: NDV, MSCs-NDV, and L. casei in alone or combined treatment significantly increased apoptosis percent, LDH, and ROS production compared with the control group (P˂0.05). Also, NDV, in free or capsulated in MSCs, had anticancer effects, but in capsulated form, it had a delay compared with free NDV. The findings proved that L. casei primarily stimulates the extrinsic pathway, while NDV therapy promotes apoptosis through the activation of both intrinsic and extrinsic apoptosis pathways. CONCLUSIONS: The results suggest that MSCs carrying oncolytic NDV in combination with L. casei extract as a potentially effective strategy for cancer immunotherapy by promoting the generation of LDH, ROS, and apoptosis in the microenvironment of the CT26 cell line.

Comprehensive Assessment of Multiple Sclerosis: From Immunotherapy and Immunopathogenesis to Predictive Biomarkers.

Background & Objective: Multiple sclerosis (MS) is an inflammatory neurological disorder that affects the central nervous system (CNS) and causes individuals to experience a variety of cognitive and physical problems. As proven by two decades of clinical experience with immunomodulatory therapies for MS, the disease progresses and relapses through several immunological pathways. New medicines aimed at remyelination and neurodegeneration are being developed; however, they need stronger evidence before being introduced into routine clinical care. The purpose of this study was a thorough assessment of MS immunopathology and predictive biomarkers. Methods: Immunotherapy, immunopathogenesis, and prognostic biomarkers were all parts of the search method. Only publications in English were considered for inclusion in the study. For that purpose, we went through the current state of knowledge around MS immunopathology and related biomarkers. Immunology, as well as the identification of increased inflammation as an important component of neurodegeneration, shaped our understanding of this disease aetiology. The relevant sources examined covered the years 2015-2021. Conclusion: We found biomarkers in the cerebrospinal fluid and blood that might be used for the prediction and diagnosis of MS, as well as for measuring treatment response and adverse effects. Many variables, including the role of some infectious organisms and the impact of environmental and social factors, might contribute to the immunological dysfunctions seen in MS. Patients with MS may benefit from better therapy options if a better understanding of MS biomarkers and immune response mechanisms would be obtained.

Oncolytic Viruses and Cancer, Do You Know the Main Mechanism?

The global rate of cancer has increased in recent years, and cancer is still a threat to human health. Recent developments in cancer treatment have yielded the understanding that viruses have a high potential in cancer treatment. Using oncolytic viruses (OVs) is a promising approach in the treatment of malignant tumors. OVs can achieve their targeted treatment effects through selective cell death and induction of specific antitumor immunity. Targeting tumors and the mechanism for killing cancer cells are among the critical roles of OVs. Therefore, evaluating OVs and understanding their precise mechanisms of action can be beneficial in cancer therapy. This review study aimed to evaluate OVs and the mechanisms of their effects on cancer cells.

Therapeutic Potential of Nanoparticle-loaded Hydroxyurea on Proliferation of Human Breast Adenocarcinoma Cell Line.

Although Hydroxyurea is one of the most widely used drugs in treating breast cancer, the use of it leads to some side effects. Hence, in order to reduce complications of treatment and increase its efficiency, drug delivery has been attracted more attention. Present study included three stages. The first stage was involved in the synthesis of nanoparticles-loaded Hydroxyurea that its characteristics were evaluated by using scanning electron microscopy and Zetasizer system. In the second stage, cultured MCF-7 cells were undergone treatments by Hydroxyurea and Nanoparticles-loaded Hydroxyurea in various concentrations. In the third stage, the MCF-7 was treated by IC50 of Hydroxyurea and nanoparticles-loaded Hydroxyurea which are in combination with radiation and hyperthermia. Afterward, the viable of cell, apoptosis, and levels of caspase-8 and-9 proteins were assessed. The average size and the potential surface of nanoparticles and nanoparticles-loaded Hydroxyurea were 26 nm, 48 nm, 3.86 mV, and -29.3 mV, respectively. Results of MTT assay and apoptosis represented that the percentage of cytotoxicity in the treated groups by in combination group and nanoparticles-loaded Hydroxyurea was significantly increased in comparison with Hydroxyurea. This increase was dependent on the concentration of nanoparticles-loaded Hydroxyurea. Nevertheless, the activity of caspase-8 shows any significant changes, the activity of caspase-9 was significantly increased in the control and treatment groups. We concluded that nanoparticles-loaded Hydroxyurea and it in combination with radiation and hyperthermia induces mitochondrial-dependent apoptosis by down-regulation of caspase-8 and up-regulation of caspase-9 expressions and have higher toxicity effect on MCF-7 cells in comparison with pure Hydroxyurea.

Evaluation of the protective and therapeutic effects of Pistacia atlantica gum aqueous extract on cellular and pathological aspects of experimental asthma in Balb/c mice.

OBJECTIVE: The purpose of this study was to investigate the protective and therapeutic effects of aqueous extract of P. atlantica gum on an experimental asthma in BALB/c mice. MATERIALS AND METHODS: Aqueous extract of dried and milled P. atlantica gum was assemble and evaluate by GC-MS. In order to investigate the effect of P. atlantica gum extract on cellular and pathological aspects of asthma, 60 BALB/c mice were divided into six groups as: negative control, asthmatic group, asthmatic group receiving dexamethasone (1mg/kg; intraperitoneal (IP)) and three asthmatic groups receiving different concentrations of the extract (100, 200 and 400 mg/kg, orally) from the beginning of the study and continued for 84 days. The examined parameters included cell population, IgE antibody production, levels of IL-4, IL-5, TGF-ß, INF-γ, IL-10, and IL-17 cytokines, and lung tissue damage. RESULTS: Regardless of the dose, aqueous extract of P. atlantica gum, caused significant decrease in the number of BALF eosinophilic cells and levels of anti-ovalbumin IgE, IL-4, IL-5 and IL-17 cytokine levels, as well as pathologic damage of the lung tissue. In addition, the amount of anti-inflammatory IL-10, TGF-ß, and INF-γ Th1 cytokines significantly increased in the extract-treated groups compared to the asthmatic and dexamethasone-treated groups. Moreover, IFN-γ/IL-4 ratio significantly increased in a dose-dependent manner compared to the un-treated asthma group. CONCLUSION: The aqueous extract of P. atlantica gum can be considered as a potent anti-inflammatory and immunomodulatory compound and may be used as a natural compound for treatment of immune system disorders.

A Rare Case of Takayasu's Arteritis with Aortic Arch Branching Pattern Variation in a Young Female.

Takayasu's arteritis, formerly known as "pulseless disease", is a chronic inflammatory disease which affects the aorta and its main branches. The prevalence of this disease is higher in Asian countries and among young women. Depending on the progress of the disease, the symptoms and prognosis of the disease is different. Herein, we report the case of a 31-year-old woman with Takayasu's arteritis in the Iranian population. In this case, the size of the aorta and the main branches increased and the large artery walls were thickened. Narrowing of the right and left subclavian artery, carotid artery and left vertebral artery were obvious in these patients. In addition, an anatomic variation was observed in the aortic arch branches. In this patient, the left vertebral artery was branched directly from the aortic arch instead of the left subclavian artery. Hepatomegaly and splenomegaly, indicating a chronic inflammatory disease, were also observed in this case.

Magnetic Resonance Angiographic Study of Anatomic Variations of the Circle of Willis in a Population in Tehran.

BACKGROUND AND OBJECTIVES: The circle of Willis, an anastomotic polygon at the base of the brain, forms an important collateral network to maintain cerebral blood perfusion. The aim of this study was to investigate different anatomic variations of the circle of Willis and their prevalence. METHODS: This cross-sectional study was conducted on 525 healthy participants including 205 men and 320 women. The mean age of the patients was 51.5 years. Three-dimensional time-of-flight magnetic resonance angiography (3D-TOF MRA) technique was used. Vascular variations in the anterior and posterior parts of the circle were evaluated. RESULTS: The findings show that the complete circle of Willis was visible in a small number of patients. The circle of Willis had a complete vascular structure in 20.9% of the patients. The anterior part of the circle of Willis had a complete structure in 80.95% of the cases, while the posterior part had a complete structure in 20.95% of the cases. CONCLUSION: We observed wide variations in the circle of Willis configuration in our study. Similar to other studies, most variations are related to the posterior part of the circle of Willis. Absence of bilateral posterior communicating artery variation is more common than other types of variations in this population.

Anatomical Variations in Aortic Arch Branching Pattern.

BACKGROUND: The branch anatomy of the aortic arch varies widely between individuals. These are likely due to alterations in the development of aortic arch arteries during the embryonic period. The purpose of this study is to determine the frequency of the aortic arch branch variations in the local population and provide useful data to intervention radiologists, neck and thoracic surgeons. METHODS: In this study, branching pattern of the aortic arch in 226 patients was retrospectively evaluated by MR angiography. MRA performed on a high field 3 Tesla MRI scanner using 3D flash sequence. RESULTS: The normal aortic arch branching pattern was observed in 192 patients (84.9%). Also, three variations of the aortic arch branching pattern were observed. The aortic arch in 12.4% of the patients had two arterial branches. In 0.9% of cases, the left vertebral artery originated directly from the aortic arch. In 1.8% of cases, the right subclavian artery originated as the fourth aortic arch branch. CONCLUSION: Although the number of cases with aortic arch branches variation in our study is similar to other studies, the Bovine aortic arch variation is more common than other variations of aortic arch branches.