Exosomes Derived from Heat-shocked Tumor Cells Promote In vitro Maturation of Bone Marrow-derived Dendritic Cells.

Dendritic cells (DCs), professional antigen-presenting cells that process and deliver antigens using MHC II/I molecules, can be enhanced in numerous ways.  Exosomes derived from heat-shocked tumor cells (HS-TEXs) contain high amounts of heat-shock proteins (HSPs). HSPs, as chaperons, can induce DC maturation. This study aimed to investigate whether HS-TEXs can promote DC maturation. To generate DC, bone marrow-derived cells were treated with Interleukin-4 and GM-CSF. Exosomes were isolated from heat-treated CT-26 cells. The expression level of HSP in exosomes was checked by western blot and the increase in the expression of this protein was observed. Then, HS-TEXs were co-cultured with iDCs to determine DC maturity, and then DCs were co-cultured with lymphocytes to determine DC activity. Our results showed that  DCs treated with HS-TEXs express high levels of molecules involved in DC maturation and function including MHCII, CD40, CD83, and CD86. HS-TEXs caused phenotypic and functional maturation of DCs. In addition, flow cytometric results reflected a higher proliferative response of lymphocytes in the iDC / Tex + HSP group. HS-TEXs could be used as a strategy to improve DC maturation and activation.

MicroRNA-122 Is More Effective than Rapamycin in Inhibition of Epithelial-mesenchymal Transition and mTOR Signaling Pathway in Triple Negative Breast Cancer.

The fundamental mechanism responsible for the aggressiveness of metastatic cancers such as triple-negative breast cancer (TNBC) is the epithelial-mesenchymal transition (EMT). In cancer microenvironments, the Phosphoinositide 3-kinases (PI3K)-Akt- mammalian target of rapamycin (mTOR) signaling pathway plays a critical role in regulating the EMT mechanism. The current study focuses on the impacts of rapamycin, a newly retargeted chemotherapeutic agent against mTOR, and MicroRNA (miR)-122 on the aggressive behavior of TNBC.  The half-maximal inhibitory concentration (IC50) of rapamycin on 4T1 cells was determined using an MTT assay. Also, miR-122 was transiently transfected into 4T1 cells to study its effect on the pathway. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess the expression level of central mTOR and EMT-related cascade genes. Moreover, cell mobility and migration were evaluated using scratch and migration assays, respectively. Both rapamycin and miR-122 significantly decreased the expression levels of PI3K, AKT, and mTOR, as well as ZeB1 and Snail genes. However, no significant change was observed in Twist gene expression. Furthermore, scratch and migration assays revealed that the migration of 4T1 cells was markedly reduced, especially following miR-122 induction. Our experimental findings and gene enrichment studies indicated that miR-122 mainly operates on multiple metabolic pathways, as well as EMT and mTOR, while rapamycin has restricted targets in cancer cells.  Consequently, miR-122 can be considered a potential cancer microRNA therapy option, which can be validated in the future in animal studies to demonstrate its efficacy in cancer control.

Aripiprazole for prevention of delirium in the neurosurgical intensive care unit: a double-blind, randomized, placebo-controlled study.

PURPOSE: Delirium is reported in over 50% of critically ill ICU patients, and is associated with increased mortality and long-term cognitive consequences. Prevention and early management of delirium are essential components of ICU care. However, pharmacological interventions have not been effective in delirium prevention. This study investigated the effect of aripiprazole in the prevention of delirium in a neurosurgical intensive care unit. METHODS: In this prospective, randomized placebo-controlled small clinical trial, 53 patients, 18 to 80 years old, were randomized to receive enteric aripiprazole (15 mg) or placebo for up to 7 days. Delirium, detected by the Confusion Assessment Method-ICU, ICU events, laboratory studies, aripiprazole safety, time to delirium onset, delirium-free days, delirium prevalence during follow-up and ICU length of stay were recorded. RESULTS: Forty patients with similar baseline characteristics, including age, sex, neurosurgery types and APACHE II scores, completed the study. Delirium incidence and the mean days to its onset were 20% vs. 55% (p = 0.022) and 2.17 ± 0.41 vs. 2.09 ± 0.30 (p = 0.076) in the aripiprazole and placebo groups, respectively. The mean number of delirium-free days were: 5.6 (95%CI, 4.6-6.5) and 4.3 (95%CI, 3.2-5.4), in aripiprazole and placebo groups, respectively (p = 0.111). The prevalence of delirium during the follow-up was significantly lower in the aripiprazole group (p = 0.018). Serious aripiprazole adverse reactions were not observed. CONCLUSIONS: Aripiprazole can reduce the incidence of delirium in the neurosurgical ICU. Studies with larger sample size in diverse ICU settings and longer follow-up are needed to confirm our findings.

Feasibility and Data Quality of the National Spinal Cord Injury Registry of Iran (NSCIR-IR): A Pilot Study.

BACKGROUND: Spinal cord injury (SCI) is one of the most disabling consequences of trauma with unparalleled economic, social, and personal burden. Any attempt aimed at improving quality of care should be based on comprehensive and reliable data. This pilot investigation studied the feasibility of implementing the National Spinal Cord and Column Injury Registry of Iran (NSCIR-IR) and scrutinized the quality of the registered data. METHODS: From October 2015 to May 2016, over an 8-month period, 65 eligible trauma patients who were admitted to hospitals in three academic centers in mainland Iran were included in this pilot study. Certified registered nurses and neurosurgeons were in charge of data collection, quality verification, and registration. RESULTS: Sixty-five patients with vertebral column fracture dislocations were registered in the study, of whom 14 (21.5%) patients had evidence of SCI. Mechanisms of injury included mechanical falls in 30 patients (46.2%) and motor vehicle accidents in 29 (44.6%). The case identification rate i.e. clinical and radiographic confirmation of spine and SCI, ranged from 10.0% to 88.9% in different registry centers. The completion rate of all data items was 100%, except for five data elements in patients who could not provide clinical information because of their medical status. Consistency i.e. identification of the same elements by all the registrars, was 100% and accuracy of identification of the same pathology ranged from 66.6% to 100%. CONCLUSIONS: Our pilot study showed both the feasibility and acceptable data quality of the NSCIR-IR. However, effective and successful implementation of NSCIR-IR data use requires some modifications such as presence of a dedicated registrar in each center, verification of data by a neurosurgeon, and continuous assessment of patients' neurological status and complications.

Intradiploic dermoid cyst: a rare cause of intracranial hypertension.

In this study, we report a rare case of intradiploic dermoid cyst in a patient who developed rapid symptoms of intracranial hypertension (ICH) that mimicked Pseudotumor cerebri syndrome clinically. A 25-year-old female presented with a history of headache, nausea, vertigo and blurred vision in the past 4 months. Images revealed a small supratentorial extradural intradiploic tumor. A midline occipital craniotomy was performed and total removal of the dermoid cyst was accomplished. Present case demonstrated that dermoid cysts can be considered an exceptionally rare basic cause of ICH.

Variations in the Anatomy of the Willis' circle: A 3-year cross-sectional study from Iran (2006-2009). Are the distributions of variations of circle of Willis different in different populations? Result of an anatomical study and review of literature.

BACKGROUND: It is not well known whether the distributions of variations of circle of Willis (CW) are different in different populations. Previous studies have indicated: (a) The variations of the structure of the CW in different populations and ethnic and (b) some correlation between those congenital anatomical variations and possible cerebrovascular diseases. The frequency of such anatomical variations has not been evaluated sufficiently in the Iranian population. The aim of this study is to find the variations of the anatomy of the vessels in the CW in sample population of Iranian people and compare it with other available studies in the literature, providing a new grouping for variations. METHODS: Samples were obtained from 200 autopsies in different ages, all retrieved in the department of Forensic Medicine, Tehran university of Medical Sciences after achieving permission from the Department of Ethics and Medico-legal Sciences. The CW was examined directly, using magnification, at the base of the brain. The cerebral vessels were observed for their configuration and their calibers were measured directly. Variations were noted and grouped into different categories. RESULTS: Out of the 200 specimens examined, 69 (34.5%) were compatible with the typical anatomy of the CW. In the remaining 65.5% of the specimens, there were variations in the CW. Hypoplasia of the posterior communicating arteries was the most common variation in our study. One of the autopsies showed the presence of an aneurysm (0.5%). CONCLUSION: The anatomical variations found in our study were not significantly different from those reported in the literature. Based on the available data; (a) there is no evidence that the distribution of the variations of the anatomy of the CW is different in various societies and (b) the prevalence of the congenital aneurysmal changes in this region is not low in the Iranian population.

Induction of humoral and cellular immunity against latent HSV-1 infections by DNA immunization in BALB/c mice.

Previously, we have reported that the injection of an expression vector containing Herpes simplex virus (HSV) Glycoprotein D-1 (gD-1) generated a significant antibody response in mice and protected them against HSV lethal challenge. We tested its potential to induce antibody and cell mediated immune responses in latently infected mice. Positive control group (KOS) and HSV gD-1 vaccinated mice demonstrated protection against a lethal ocularly challenge of 10(5.5) plaque-forming units (pfu)/eye of wild HSV-1 versus negative control groups. For neutralizing antibody titers, delayed-type hypersensitivity (DTH), lymphocyte proliferation responses, clinical evaluation and survival following lethal challenge, no considerable difference was observed between mice vaccinated with DNA plasmid and those vaccinated with KOS. KOS-vaccinated mice demonstrated the ability to completely prevent latency whereas DNA vaccinated group showed some degree of protection and displayed less latency than negative control groups and had considerably high levels of IFN-gamma and strong CTL responses versus negative control groups. It can be concluded that although immunization with the DNA vaccine is more effective in both protecting mice and induction of immune response, however it could not completely block the latent infection in sensory nerves.