Genetically Engineered Mesenchymal Stem Cell Therapy Against Murine Experimental Autoimmune Encephalomyelitis.

We used recombinant interleukin 23 receptor (RIL-23R)-engineered mesenchymal stem cells (MSCs) to study its therapeutic role in enhancing inflammation of nervous tissue in the mouse model (EAE) of multiple sclerosis (MS). Recombinant IL-23 receptor construct was designed to enter MSCs. The bioactivity of the constructs was assessed by the co-culture of MSCs/CD4 + T cells. The EAE model was induced in mice. After cell transplantation, clinical scores were evaluated, and tissue demyelination was measured by Luxol fast blue staining. The transfection of RIL-23R mRNA improved MSC properties significantly to the inflamed regions of EAE mice, and it performed an increased suppressive function on the T lymphocyte proliferation. Furthermore, in vivo therapy with RIL-23R MSCs in EAE mice showed an enhanced therapeutic action than MSCs, proven by improved myelination and a reduction in the penetration of inflammatory cells into the white matter. Our targeted transplantation procedure of modified MSC can be applied to improve the effectiveness of cellular therapy for multiple sclerosis and other autoimmune disorders.

Genetically Engineered Adipose Mesenchymal Stem Cells Using HIV-Based Lentiviral Vectors as Gene Therapy for Autoimmune Diseases.

The immunomodulatory and self-renewable features of human adipose-derived mesenchymal stem cells (hAD-MSCs) mark their importance in regenerative medicine. Interleukin (IL)-23 as a proinflammatory cytokine suppresses T regulatory cells and promotes the response of T helper 17 and T helper 1 cells. This pathway initiates inflammation and immunosuppression in several autoimmune diseases. The current study aimed at producing recombinant IL-23 decoy receptor (RIL-23R) using hAD-MSCs as a good candidate for ex vivo cell-based gene therapy purposes to reduce inflammation in autoimmune diseases. hAD-MSCs was isolated from lipoaspirate and then characterized by differentiation. RIL-23R was designed and cloned into a pCDH813A-1 lentiviral vector. The transduction of hAD-MSCs was performed at multiplicity of infection = 50 with pCDH-EFI α-RIL-23R-PGK copGFP. Expressions of RIL-23R and octamer-binding transcription factor 4 (OCT-4) were determined by real-time polymerase chain reaction. Self-renewing properties were assayed with OCT-4. Bioactivity of the designed RIL-23R was evaluated by IL-17 and IL-10 expression of mouse splenocytes. The results showed that the transducted hAD-MSCs/RIL-23R, expressing IL-23 decoy receptor, can provide a useful approach for a basic research on cell-based gene therapy for autoimmune disorders.

The Human IL-23 Decoy Receptor Inhibits T-Cells Producing IL-17 by Genetically Engineered Mesenchymal Stem Cells.

The immunomodulatory and self-renewable features of human adipose mesenchymal stem cells (hAD-MSCs) mark their importance in regenerative medicine. Interleukin 23 (IL- 23) as a proinflammatory cytokine suppresses T regulatory cells (Treg) and promotes the response of T helper 17 (Th17) and T helper 1 (Th1) cells. This pathway starts inflammation and immunosuppression in several autoimmune diseases. The current study for producing recombinant IL- 23 decoy receptor (RIL- 23R) using hAD-MSCs as a good candidate for ex vivo cell-based gene therapy purposes reducing inflammation in autoimmune diseases. hAD-MSCs was isolated from lipoaspirate and then characterized by differentiation. RIL- 23R was designed and cloned into a pCDH-813A- 1 lentiviral vector. The transduction of hAD-MSCs was performed at MOI (multiplicity of infection) = 50 with pCDH- EFI α- RIL- 23R- PGK copGFP. Expressions of RIL- 23R and octamer-binding transcription factor 4 (OCT- 4) were determined by real-time polymerase chain reaction (real time-PCR). Self-renewing properties were assayed with OCT- 4. Bioactivity of the designed RIL- 23R was evaluated by IL- 17 and IL- 10 expression of mouse splenocytes. Cell differentiation confirmed the true isolation of hAD-MSCs from lipoaspirate. Restriction of the enzyme digestion and sequencing verified the successful cloning of RIL- 23R in the CD813A-1 lentiviral vector. The green fluorescent protein (GFP) positive transduction rate was up to 90%, and real-time PCR showed the expression level of RIL-23R. Oct-4 had a similar expression pattern with nontransduced hAD-MSCs and transduced hAD-MSCs/ RIL-23R indicating that lentiviral vector did not affect hAD-MSCs characteristics. Downregulation of IL-17 and upregulation of IL-10 showed the correct activity of the engineered hAD-MSCs. The results showed that the transduced hAD-MSCs/ RIL- 23R, expressing IL-23 decoy receptor, can give a useful approach for a basic research on cell-based gene therapy for autoimmune disorders.

Ethnic difference in brain weight of 17-20 year-old males in Northern Iran / Diferencias étnicas en el peso del cerebro en hombres de 17 a 20 años de edad del norte de Irán

Cranial capacity and brain weight are important measurements in the study of racial/ethnic differences. Using linear (Lee­Pearson's) formula, brain weight and cranial capacity were estimated in 398 normal 17 to 20-year-old males (200 native Fars and 198 Turkman) males in Northern Iran. The dimensions of the head measured with spreading caliper and auricular head spanner. The mean±S.D of brain weight and cranial capacity in native Fars males were 1343.45±102.37 cm3, and 1390.47±105.95 g, and that of Turkmans were 1163.02±115.76 cm3 and 1203.73±119.81 g, respectively. Cerebral Index was 3.40 ±0.37 % and 2.52 ±0.37 % in Native Fars and Turkmans, respectively and cerebral quotient was higher in Turkmans (8.34) than Native Fars males (7.95). This study showed, the effect of ethnic factor influences the brain weight of 17-20 year-old males in Northern Iran.

La capacidad craneal y el peso del cerebro son mediciones importantes en el estudio de las diferentes etnias. Se estimó el peso del cerebro y la capacidad craneal usando la fórmula lineal de Lee-Pearson, en 398 hombres de 17 a 20 años de edad (200 nativos Fars y 198 Turcomanos) en el norte de Irán. Las dimensiones de la cabeza se midieron con caliper deslizante y con una llave de Todd, para la medición auricular. La media ± D.S. del peso del cerebro y la capacidad craneal en hombres nativos Fars fue de 1343,45±102,37 cm3, y 1390,47±105,95 g, y la de los turcomanos fue de 1163,02±115,76 cm3 y 1203,73 ± 119,81 g, respectivamente. El índice cerebral fue de 3,40± 0,37 % y 2,52 ± 0,37 % en nativos Fars y turcomanos, respectivamente, y el cociente cerebral fue mayor en los turcomanos (8,34) que en los hombres Fars (7.95). Este estudio demostró que el efecto del factor étnico influye en el peso del cerebro en hombres de 17-20 años del norte de Irán.

Effects of Repeated Administration of 3,4-methylenedioxymethamphetamine (MDMA) on Avoidance Memory and Cell Density in Rats' Hippocampus.

INTRODUCTION: MDMA or ecstasy is a derivative of amphetamines used mostly by young people worldwide. Although the acute effects of this drug are known, the effect of chronic administration is not well studied. Therefor the aim of this study was to determine the effects of repeated (long term) administration of MDMA on rats' memory and their hippocampal cell density. METHOD: Young adult male Wistar rats 200 ± 20 g served as subjects. The rats were randomly distributed into three MDMA treated groups (3×2.5 mg/kg, 3×5 mg/kg, 3×10 mg/kg) and one control-saline group. All animals received MDMA intraperitoneally (3h apart; a challenge) 7th day of every week for consecutive 4 weeks. Animals were trained before and were tested after injections for their memory status using the standards passive avoidance method. Finally, 24hr after the memory test, rats were sacrificed and after tissue operations, the hippocampal astrocytes and neurons were counted. RESULTS: Results showed that the number of neurons in all experimental groups was lower than the control-saline group. The most decreased number of neurons was shown in 5 mg/kg MDMA group compared to control-saline in all the regions of hippocampus. Also we found that repeated administration of MDMA reduced the number of hippocampal astrocytes. DISCUSSION: It is concluded that repeated administration of MDMA can reduce density of neurons and astrocytes and this decrease is not dose dependence.

The effect of leukemia inhibitory factor and coculture on the in vitro maturation and ultrastructure of vitrified and nonvitrified isolated mouse preantral follicles.

OBJECTIVE: To develop a system for in vitro maturation of preantral follicles isolated from vitrified and nonvitrified mouse ovaries by leukemia inhibitory factor (LIF) and coculture with cumulus cells. DESIGN: Experimental study. SETTING: University-based research laboratory. ANIMAL(S): Twelve- to 14-day-old National Medical Research Institute female mice. INTERVENTION(S): Vitrification of mouse ovaries and in vitro maturation of follicles. MAIN OUTCOME MEASURE(S): The growth, maturation, steroidogenesis, alkaline phosphatase activity, and ultrastructure of preantral follicles derived from vitrified and nonvitrified mouse ovaries and the developmental capacity of embryos obtained from metaphase II to blastocyst stage. RESULT(S): The follicular diameters were increased in the presence of LIF in the simple culture, coculture, and vitrified coculture groups. The survival and developmental rates of follicles were not significantly different between groups. The E(2) production was increased in all groups during the culture period. Alkaline phosphatase activity was observed in the follicles of cryosectioned slices and cultured preantral follicles. There was no remarkable change in ultrastructural maturation features of cultured follicles. CONCLUSION(S): LIF alone or in combination with the coculture system increased the growth of cultured preantral follicles but had no effect on their maturation; the ultrastructure, growth, and maturation of vitrified follicles were the same in the cultured groups and in the controls.

Morphological Evaluation of Head in Turkman Males in Gorgan-North of Iran / Evaluación Morfológica de la Cabeza en Hombres Turcos en Gorgan del Norte de Irán

Cephalometry or measurement of human head is used in identification, forensic medicine, plastic surgery, orthodontics, archeology and examine the differences between races and ethnicities. This descriptive investigation was undertaken on 198 young Turkman males to determine the cephalic index and head phenotype among them in Gorgan, North of Iran. In this study cephalic index was determined by classic cephalometric method. Mean and standard deviation of cephalic index was 80.4 + 4. Based on the cephalic index, the head shape of 42.4% of individuals were brachycephalic, 7.6% hyperbrachycephalic, 40.9% mesocephalic and 8.1% dolicocephalic. This research showed that Turkman individuals have typical brachycephalic phenotype. In comparison to other studies, we can conclude that the ethnic factor has an effective role on head phenotype in North of Iran.

La cefalometría o mediciones de la cabeza humana son usadas en identificación, Medicina Forense, Cirugía Plástica, Ortodoncia, Arqueología y tiene la finalidad de examinar las diferencias entre razas y etnias. Esta investigación descriptiva fue realizada en 198 hombres jóvenes turcos en Gorgan, Norte de Irán, para determinar el índice cefálico y el fenotipo de la cabeza. El índice cefálico fue determinado por el método de cefalometría clásica. La media y desviación estándar del índice cefálico fue de 80.4 + 4. Basado en el índice cefálico, la forma de la cabeza era braquicefálica en el 42.4%, hiperbraquicefálica en el 7.6%, mesocefálica en el 40.9% y dolicocefálica en el 8,1% de los individuos. Esta invetigación mostró que los individuos turcos presentan un típico fenotipo braquicefálico. En comparación con otros estudios, podemos concluir que el factor étnico tiene un efectivo rol en el fenotipo cefálico en el Norte de Irán.

Estimation of Cranial Capacity in 17-20 Years Old in South East of Caspian Sea Border (North of Iran) / Estimación de la Capacidad Craniana en Individuos entre 17-20 Años de Edad del Sureste del Borde Costero del Mar Caspio (Norte de Irán)

It is natural that there is close relationship between cranial capacity, and the size of brain, several studies have estimated the cranial capacity which indirectly reflects the brain volume in different countries. In the present study cranial capacity has been estimated in Turkmans and native Fars17-20 years old groups in North of Iran. This study was carried out on 808 normal 17-20 years old (male 398, female 410) in Turkman and native Fars groups in South-East of Caspian Sea border (North of IRAN). By using linear dimensions of the head. The mean and SD of cranial capacity in Turkmans males and females were 1420.6±85 ml and 1227.2±120 ml, respectively. The mean and SD of cranial capacity in native Fars male and females were 1369±142ml, 1215.8±125ml, respectively, this difference was significant (P<0.05). This investigation was shown that the cranial capacity is higher in male than female, also racial factor can affect on cranial capacity.

Es natural que exista una relación entre la capacidad craneana y el tamaño del cerebro. Numerosos estudios realizados en diferentes países, han estimado la capacidad craneana con lo cual han determinado indirectamente el volumen del cerebro. En este estudio ha sido estimada la capacidad craneana, en individuos pertenecientes a grupos del Norte de Irán, Turcomanos y Fars nativos. El estudio fue realizado en 808 individuos (398 hombres y 410 mujeres), normales, entre 17-20 de edad pertenecientes a grupos del Norte de Irán, Turcomanos y Fars nativos del Sureste del borde costero del Mar Caspio (Norte de Irán). Para la estimación de la capacidad craniana se utilizaron las dimensiones lineares de la cabeza. La media y SD de la capacidad craneana en Turcomanos hombres y mujeres, fue de 1420.6±85 ml y 1227.2±120 ml, respectivamente. La media y SD de la capacidad craneana en nativos Fars, hombres y mujeres, fue de 1369±142ml, 1215.8±125ml, respectivamente. Las diferencias fueron estadísticamente significativas (p<0.05). La investigación demostró que la capacidad craneana es mayor en los hombres que en las mujeres pudiendo además, influir en la capacidad craneana factores raciales.