Calcitriol modulate post-ischemic TLR signaling pathway in ischemic stroke patients.

BACKGROUND: Neuroinflammation is a significant contributor to post-ischemic neuronal death after stroke, and Toll-Like Receptors (TLRs) are one of the essential mediators in many inflammatory pathways. TLRs activate the nuclear factor kappa ß (NF-kß), which promotes the expression of various pro-inflammatory genes such as interleukin (IL-1ß) and IL-6. 1,25(OH)2D3, also known as calcitriol, is an active form of vitamin D3 that acts as a neurosteroid compound with anti-inflammatory properties. This study aimed to determine the modulatory effects of calcitriol hormone on post-ischemic immunity response. METHODS: Neurological tests and conventional blood factors were evaluated in patients with stroke symptoms upon arrival (n = 38) to confirm the stroke. A blood sample was taken from each stroke patient immediately upon admission and again after 24 h. The experimental group was given 10 µg calcitriol orally. The gene expression levels of TLR4, TLR2, NF-kß, IL-1ß, and IL-6 pro-inflammatory factors were measured using real-time PCR. The protein expression of TLR4 and NF-kß markers was assessed using the flow cytometry technique. RESULTS: TLR4, NF-kß, and pro-inflammatory factors IL-1ß and IL-6 expression increased significantly after an ischemic stroke, and calcitriol could modulate the TLR4/NF-kß signaling pathway 24 h after ischemia. CONCLUSIONS: Calcitriol may be considered a protective reagent after ischemia by reducing the TLR4/NF-kB activation cascade and probably plays a beneficial role in reducing and improving ischemic stroke patients' symptoms. TRIAL REGISTRATION: Iranian Registry of Clinical Trials identifier: IRCT2017012532174N1.

Primordial germ cells can be differentiated by retinoic acid and progesterone induction from embryonic stem cells.

This study aimed to examine the expression of the genes associated with different development stages of primordial germ cells (PGCs) in differentiating mouse embryonic stem cells (mESCs). The cells were cultured in three groups of control, 10-8 M of all-trans retinoic acid and the combination of 10-7 M of Progesterone and retinoic acid for 7, 12, 17, and 22 days. Immunofluorescent and Quantitative RT-PCR were used to evaluate the effect of progesterone on the differentiation of mESCs into primordial germ cells. RA-treated cells exhibited increased expression of Fragilis, Stella, Dazl, Stra8, Sycp3, and Gdf9 genes and decreased expression of Oct4, Mvh genes compared to the non-treated controls. Furthermore, RA in combination with progesterone (RA?P) led to increased expression of Oct4, Fragilis, Stella, Dazl, Sycp3, Gdf9 and decreased expression of Mvh, and Stra8 genes compared to the RA-treated scenario. Immunofluorescence detection of Stella and Mvh showed that the expression levels of the cells treated with RA+P are much higher than those of the other groups. Our project showed that under the influence of the induced factors, mESCs can spontaneously differentiate into germ cells. Also, the combination of RA+P can enhance and accelerate the differentiation of mESCs into germ cells.

Oxytocin improves ischemic stroke by reducing expression of excitatory amino acid transporter 3 in rat MCAO model.

Various molecular mechanisms are activated in neurons during ischemic stroke. Extracellular glutamate secretion into brain tissue causes neurotoxicity and brain damage. Excitatory amino acid transporter 3 (EAAT3) could remove the extracellular glutamate. Neuroprotective activity of oxytocin (OT) in ischemia of various tissues has been reported. This study investigates the neuroprotective effect of OT in an animal model of middle cerebral artery occlusion (MCAO) and the possible role of EAAT3. Transient MCAO was performed as a model of ischemic stroke in male rats and then OT was administrated intra-nasally. Infarct volume was measured by 2, 3, 5-triphenyl tetrazolium chloride staining. Nissl staining method was performed for the evaluation of neuronal cell morphology. Immunohistochemistry assay was performed to analyze the EAAT3 expression in the ischemic region. OT significantly reduced the infarct volume in the cerebral cortex and striatum after ischemia (P< .05). In addition, OT reduces the number of neurons with pyknotic nuclei that are significantly increased in the ischemic region (P< .01) Immunohistochemistry results showed that although EAAT3 expression increased after ischemia, OT therapy increased EAAT3 expression further (P< .05). Therefore, increased EAAT3 expression could be one of the neuroprotective mechanisms of OT after MCAO.

Heat shock protein 27 as a neuroprotective biomarker and a suitable target for stem cell therapy and pharmacotherapy in ischemic stroke.

Ischemic stroke is a major common cause of death and long-term disability worldwide. Several pathophysiological events including excitotoxicity, oxidative/nitrative stress, inflammation, and apoptosis are involved in ischemic injuries. Recently, the molecular mechanisms involved in cerebral ischemia through a focus on a member of small heat shock proteins family, Hsp27, has been developed. Notably, following exposure to ischemia, Hsp27 expression in the brain could be increased rather than the normal condition and it may play an important role in neuroprotection after ischemic stroke. The neuroprotection effects of Hsp27 may arise from its anti-oxidant, anti-inflammatory, anti-apoptotic, and chaperonic properties. Moreover, some therapeutic strategies such as stem cell therapy and pharmacotherapy have been developed with Hsp27 targeting. In this review, we describe the function and structure of Hsp27 and its possible role in neuroprotection after ischemic stroke. Finally, we present current studies in stroke therapy, which focused on Hsp27 targeting.

The protective effect of bone marrow mesenchymal stem cells in a rat model of ischemic stroke via reducing the C-Jun N-terminal kinase expression.

Ischemic stroke is the main cause of disability and mortality worldwide. Apoptosis and inflammation have an important role in ischemic brain injury. Mesenchymal stem cells (MSCs) have protective effects on stroke treatment due to anti-inflammatory properties. The inhibition of the C-Jun N-terminal kinase (JNK) pathway may be one of the molecular mechanisms of the neuroprotective effect of MSCs in ischemic brain injury. Twenty-eight male Wistar rats were divided randomly into 3 groups. Except the sham group, others subjected to transient middle cerebral artery occlusion (tMCAO). Bone marrow MSCs or saline were injected 3 h after tMCAO. Sensorimotor behavioral tests were performed 24 and 72 h after ischemia and reperfusion (I/R). The rats were sacrificed 72 h after I/R and infarct volume was measured by TTC staining. The number of apoptotic neurons and astrocytes in the peri-infarct area was assessed by TUNEL assay. The morphology of cells was checked by Nissl staining, and the expression of p-JNK was detected by immunohistochemistry and Western blot. Behavioral scores were improved and infarct volume was reduced by MSCs 24 h and 72 h after tMCAO. TUNEL assay showed that neuronal apoptosis and astroglial activity in the penumbra region were reduced by MSCs. Also, Nissl staining showed lower neuronal apoptosis in BMSCs-treated rats compared to controls. JNK phosphorylation which was profoundly induced by ischemia was significantly decreased after MSCs treatment. We concluded that anti-apoptotic and anti-inflammatory effects of MSCs therapy after brain ischemia may be associated with the down-regulation of p-JNK.

Differential Expression of HSP90ß in MDA-MB-231 and MCF-7 Cell Lines after Treatment with Doxorubicin.

BACKGROUND: Breast cancer is a complex, heterogeneous disease and one of the most common malignancies in women worldwide. The efficacy of chemotherapy as an important breast cancer treatment option has been severely limited because of the inherent or acquired resistance of cancer cells. The molecular chaperone heat shock protein 90 (HSP90) upregulated in response to cellular stress is required for functions such as conformational maturation, activation and stability in more than 200 client proteins, mostly of the signaling type. In this study, the expression of HSP90 isoforms including HSP90α and HSP90ß in breast cancer cell lines before and after treatment with doxorubicin (DOX) was assessed. MATERIAL AND METHODS: The cell cytotoxicity of DOX in MDA-MB-231 and MCF-7 cell lines was determined using the MTT assay. Immunofluorescence and western blotting techniques were used to determine the expression of HSP90ß in the cell lines before and after DOX treatment. Immunofluorescence was also conducted to ascertain the expression of HSP90α. RESULTS: The MTT assay results showed that the MDA-MB- 231 cells (IC50=14.521 µM) were more sensitive than the MCF-7 cells (IC50=16.3315 µM) to DOX. The immunofluorescence results indicated that the expression of HSP90α in both cell lines decreased after exposure to DOX. The western blot and immunofluorescence analyses showed that HSP90ß expression decreased in the MCF-7 cells but increased in the MDA-MB- 231 cells after DOX treatment. Conclusion: The obtained results suggested that HSP90α and HSP90ß expression levels were reduced in the MCF-7 cells after exposure to DOX. In the MDA-MB-231 cells, HSP90α expression was reduced while HSP90ß was found to be overexpressed following DOX treatment.

Prenatal exposure to diesel exhaust particles causes anxiety, spatial memory disorders with alters expression of hippocampal pro-inflammatory cytokines and NMDA receptor subunits in adult male mice offspring.

Air pollution by Diesel exhaust (DE) consists of gaseous compounds and diesel exhaust particles (DEPs). Previous studies show associations between prenatal exposure to diesel exhaust affects the central nervous system (CNS). However, there was not reported that these effects were caused by gaseous compounds, diesel exhaust particles, or both. A limited number of studies in rodent models have shown that exposure to DEPs can result in CNS. Here, we explored the effects of prenatal exposure to DEPs on anxiety and learning and memory in NMRI mice male offspring. Three groups of pregnant mice were exposed to 350-400 µg DEPs/m3 for 2, 4 and 6 h daily in a closed system room. We examined anxiety and learning and memory in 8-to-9-week-old male offspring using the Elevated plus maze and Morris water maze (MWM) test. Hippocampi were isolated after the behavioral tests and measured pro-inflammatory cytokines and N-methyl-D-aspartate (NMDA) receptor expression by quantitative RT-PCR analysis. Mice exposed to DEPs in utero showed deficits in the Elevated plus maze and Morris water maze test. In addition, DEPs exposed mice exhibited decreased hippocampal NR2A and NR3B expression. Taken together, our data suggest that maternal DEP exposure is associated with anxiety, disrupts learning and memory and reduction hippocampal NR2A and NR3B expression in male offspring.

The regulatory role of Toll-like receptors after ischemic stroke: neurosteroids as TLR modulators with the focus on TLR2/4.

Ischemic stroke is the most common cerebrovascular disease and considered as a worldwide leading cause of death. After cerebral ischemia, different pathophysiological processes including neuroinflammation, invasion and aggregation of inflammatory cells and up-regulation of cytokines occur simultaneously. In this respect, Toll-like receptors (TLRs) are the first identified important mediators for the activation of the innate immune system and are widely expressed in glial cells and neurons following brain trauma. TLRs are also able to interact with endogenous and exogenous molecules released during ischemia and can increase tissue damage. Particularly, TLR2 and TLR4 activate different downstream inflammatory signaling pathways. In addition, TLR signaling can alternatively play a role for endogenous neuroprotection. In this review, the gene and protein structures, common genetic polymorphisms of TLR2 and TLR4, TLR-related molecular pathways and their putative role after ischemic stroke are delineated. Furthermore, the relationship between neurosteroids and TLRs as neuroprotective mechanism is highlighted in the context of brain ischemia.

The combination of retinoic acid and estrogen can increase germ cells genes expression in mouse embryonic stem cells derived primordial germ cells.

Generation of germ cells from embryonic stem cells in vitro could have great application for treating infertility. The temporal expression profile of several genes was expressed at different stages of germ cell development and examined in differentiation the mouse embryonic stem cells. Cells were treated in three groups of control, with 10-8 M of all-trans retinoic acid and the combination of 10-9 M of 17ß-Estradiol and retinoic acid for 7, 12, 17 or 22 days. Quantitative RT-PCR and Immunofluorescent were used to investigate the possible inductive effects of estrogen on mouse embryonic stem cell-derived primordial germ cells. mRNA expression of Oct4 and Dazl were downregulated in embryonic stem cells by the retinoic acid group, whereas Mvh transcription was reduced by retinoic acid and estrogen group in these cells compared to the control group. But, retinoic acid with estrogen group-treated cells exhibited increased mRNA expression of Stra8, Fragilis, Sycp3, GDF9, and Stella compared to untreated controls. The expression of Stella and Mvh proteins were remarkably increased in cell colonies. This study shows that estrogen affects the expression of specific markers of primordial germ cells. Also, estrogen and retinoic acid speed up and increase the level of expression of specific markers.

Lipoprotein lipase gene polymorphisms as risk factors for stroke: a computational and meta-analysis.

OBJECTIVES: Stroke is the most common neurological disorder and genetic susceptibility has an important role in its etiology. Polymorphism in several genes such as lipoprotein lipase (LPL) is propounded as a risk for stroke. This meta-analysis investigated the association of rs285 and rs320 LPL polymorphism with stroke risk. MATERIALS AND METHODS: We searched PubMed, Clarivate Analytics Web of Science, Google Scholar, and Science Direct databases for appropriate studies. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of this association. Also, the effects of four common polymorphisms (rs268, rs285, rs320, and rs328) on the molecular aspects of LPL were evaluated by in silico tools. Five studies were included in meta-analysis after screening. RESULTS: Our data indicated that rs320 significantly decreased the risk of stroke (G vs. T: OR= 0.64, 95%CI=0.54-0.76; GG vs. TT: OR=0.47, 95%CI=0.29-0.75; TG vs. TT: OR=0.65, 95%CI=0.53-0.80; TG+GG vs. TT: OR=0.62, 95%CI=0.51-0.75; GG vs. TT+TG: OR=0.51, 95%CI=0.32-0.82). Moreover, a significant association between rs285 and diminution of stroke risk was seen (P- vs. P+: OR=0.72, 95%CI=0.58-0.91; P-P- vs. P+P+: OR=0.50, 95%CI=0.31-0.82; P+P-+P-P- vs. P+P+: OR=0.72, 95%CI=0.53-0.96; P-P- vs. P+P++P+P-: OR=0.581, 95%CI=0.369-0.916). Also, the same results were observed after stratifying, without any publication bias (PEgger>0.05). Furthermore, computational analysis revealed that rs268 and rs328 may affect the protein structure (prediction: non-neutral; score=19; expected accuracy=59%) while rs320 could affect the RNA structure (distance=0.2264, P-value=0.0534; P<0.2 is significant). CONCLUSION: This meta-analysis indicated that risk of stroke was decreased in rs320 and rs285 polymorphisms in the LPL gene.

Collagen-coated nano-electrospun PCL seeded with human endometrial stem cells for skin tissue engineering applications.

Human endometrial stem cells (hEnSCs) are known as an attractive source of stem cells for regenerative medicine. hEnSCs are easily isolated and are capable of repairing uterine through their strong ability of creating new capillaries. In this study, a three-dimensional (3D) nanofibrous polycaprolactone (PCL)/collagen scaffold was fabricated and characterized in order to be applied as a new approach for skin reconstruction. Furthermore, the behavior of hEnSCs on this scaffold was investigated. First, a PCL 3D scaffold was constructed using electrospinning technique. Plasma treated and PCL was grafted by collagen. The constructs were characterized for mechanical and structural properties. Cell attachment, proliferation, viability, and differentiation of hEnSCs were assessed after being seeded on PCL and PCL/collagen scaffolds using scanning electron microscopy, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and real-time polymerase chain reaction tests. The results showed higher wettability for the PCL/collagen scaffold with desirable mechanical and structural characteristics compared to PCL and collagen alone. The attachment and proliferation rates of hEnSCs on the PCL/collagen scaffold were higher compared to those on the bare PCL. Hence, hEnSCs are newly discovered stem cell source for skin tissue engineering in vitro, particularly when developed on PCL/collagen nanofiber scaffolds. Therefore, application of hEnSCs for skin regeneration is a novel therapeutic approach for temporary skin substitute. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1578-1586, 2018.

Neuroprotective Effects of Oxytocin Hormone after an Experimental Stroke Model and the Possible Role of Calpain-1.

BACKGROUND: Different mechanisms will be activated during ischemic stroke. Calpain proteases play a pivotal role in neuronal death after ischemia damage through apoptosis. Anti-apoptotic activities of the oxytocin (OT) in different ischemic tissues were reported in previous studies. Recently, a limited number of studies have noted the protective effects of OT in the brain. In the present study, the neuroprotective potential of OT in an animal model of transient middle cerebral artery occlusion (tMCAO) and the possible role of calpain-1 in the penumbra region were assessed. METHODS: Adult male Wistar rats underwent 1 hour of tMCAO and were treated with nasal administration of OT. After 24 hours of reperfusion, infarct size was evaluated by triphenyltetrazolium chloride. Immunohistochemical staining and Western blotting were used to examine the expression of calpain-1. Nissl staining was performed for brain tissue morphology evaluation. RESULTS: OT reduced the infarct volume of the cerebral cortex and striatum compared with the ischemia control group significantly (P < .05). Calpain-1 overexpression, which was caused by ischemia, decreased after OT administration (P < .05). The number of pyknotic nuclei in neurons increased dramatically in the ischemic area and OT attenuated the apoptosis of neurons in the penumbra region (P < .01). CONCLUSION: We provided evidence for the neuroprotective role of OT after tMCAO through calpain-1 attenuation.

Comparison of the effects of progesterone and 17 ß-estradiol on Schwann cell markers expression in rat adipose-derived stem cells.

Steroids promote the myelination and regeneration in the peripheral nervous system. Whereas, little is known about the inducing effects by which the hormones exert their effects on Schwann cells differentiation. This could be revealed by the expression of Schwann cell markers in adipose-derived stem cells (ADSCs). The purpose of this study was to present the effects of progesterone and 17 ß-estradiol on the Schwann cell markers in rat ADSCs. The mesenchymal stem cell markers (CD73, and CD90) were assayed by flow cytometry. Rat ADSCs were sequentially treated with ß-mercaptoethanol, and all-trans-retinoic acid, followed by a mixture of basic fibrobroblast growth factor, platelet-derived growth factor, forskolin and heregulin. In experimental groups, forskolin and heregulin were substituted by progesterone and 17 ß-estradiol. After induction, the expression of Schwann cell markers P0, and S-100 and the cellular immunocytochemical staining positive rate of anti-S100 and anti-glial fibrillary acidic protein (GFAP) antibodies were compared in the experimental and control groups. Progesterone and 17 ß-estradiol triggered P0 and S-100 genes expression and induced a cellular immunocytochemical staining positive rate of S-100 and GFAP in rats ADSCs. Progesterone induced these changes stronger than 17 ß-estradiol. Thus, progesterone may induce rat ADSCs toward Schwann-like cells by expression of Schwann cell markers and is more potent than 17 ß-estradiol in the expression of these markers.

Protective effect of alcoholic extract of garden cress seeds on the histopathological changes of the ventral prostate in streptozotocin diabetic rats / Efecto protectivo de extracto alcohólico de garden cress seeds en los cambios histopatológicos de la próstata ventral en ratas diabéticas por streptozotocina

Diabetes mellitus is a common serious metabolic illness occurring worldwide that may lead to male infertility. Various plants have been used in the treatment of diabetes. In this study, the effect of garden cress (Lepidium sativum) seed extract on fasting blood sugar is assessed for its protective effect on histopathological changes in the ventral prostate gland of streptozotocine-induced diabetic rats. Fifty adult male Wistar rats were randomly selected into five groups. Group 1 was the control placebo group where rats received only 0.1 mL normal saline via gastric gavages. Rats in Group 2 received an intraperitoneal injection of STZ 60 mg/kg body weight and those with FBS >250 mg/dL were considered diabetic. In Group 3, diabetic rats received insulin (3 U/100 g body weight) while in Groups 4 and 5 diabetic rats received 0.1 ml of 200 and 400 mg/kg respectively of an ethanol extract of Lepidium sativum seeds by gavage daily. The prostate was removed and weighed before transfer to Bouin’s solution for histological studies. Administration of the 200 and 400 mg/kg doses of Lepidium sativum seed extract increased epithelium height and decreased interstitial volume density and fibromuscular thickness of the prostate significantly. Also, the volume density of the epithelium, fibro muscular, lumen, and interstitial tissues were changed significantly. The results suggest that Lepidium sativum seed extract has beneficial effects as a protective agent against the detrimental effects of diabetes on the reproductive system of diabetic male rats.

La diabetes mellitus es una enfermedad metabólica común y grave que ocurre en todo el mundo y que puede conducir a la infertilidad masculina. Se han utilizado varias plantas en el tratamiento de la diabetes. En este estudio se evalúa el efecto del extracto de semilla de Lepidium sativum sobre los niveles de azúcar en sangre, en ayunas, por su efecto protector sobre los cambios histopatológicos en la próstata ventral, de ratas diabéticas inducidas por estreptozotocina (STZ). Cincuenta ratas Wistar adultas fueron divididas aleatoriamente en cinco grupos. El grupo 1 fue el grupo placebo, de control, en el que las ratas recibieron sólo 0,1 ml de solución salina normal mediante sondas gástricas. Las ratas del grupo 2 recibieron una inyección intraperitoneal de 60 mg / kg de peso corporal de STZ y aquellas con FBS> 250 mg / dl se consideraron diabéticas. En el grupo 3, las ratas diabéticas recibieron insulina (3 U / 100 g de peso corporal) mientras que en los grupos 4 y 5 las ratas diabéticas recibieron 0,1 ml de 200 y 400 mg / kg respectivamente de un extracto etanólico de semillas de Lepidium sativum por gavage diariamente. La próstata se retiró y se pesó antes de transferir a una solución de Bouin para realizar estudios histológicos. La administración de las dosis de 200 y 400 mg / kg de extracto de semilla de Lepidium sativum aumentó la altura del epitelio y disminuyó la densidad volumétrica intersticial y el espesor fibromuscular de la próstata, significativamente. Además, la densidad volumétrica del epitelio fibromuscular, del lumen y el intersticio de los tejidos sufrieron modificaciones significativas. Los resultados sugieren que el extracto de semilla de Lepidium sativum posee efectos beneficiosos como agente protector contra los efectos perjudiciales de la diabetes en el sistema reproductivo de las ratas macho diabéticas.

Protective effect of Lepidium sativum seed extract on histopathology and morphology of epididymis in diabetic rat model / Efecto protector de extracto de semilla Lepidium sativum sobre la histopatología y morfología del epidídimo en modelo de rata diabética

Diabetes mellitus is a frequent and serious metabolic illness all over the world and plants have been a desirable source of medicine recently. Diabetes has unpleasant effect on male reproductive system and it may lead to male infertility. It causes erectile dysfunction and reduces ejaculate volume by affecting the health of small blood vessels and the small nerves that control ejaculation and also decreases libido by decreasing testosterone levels. Current study evaluated the possible protective efficiency of Lepidium sativum (Garden cress) seed extract on fasting blood sugar (FBS) and then assessed histopathological change of epididymis in streptozotocine (STZ)-induced diabetic rats. We randomly categorized 50 adult male Wistar rats into five groups (each 10 rats). Group 1 was control placebo group receiving only 0.1 ml normal saline via gastric gavages, Group 2 as control diabetic rats received an intraperitoneal (IP) injection of STZ 60 mg/kg body weight. Rats with FBS >250 mg/dl were considered as diabetic. Group 3 were diabetic rats receiving insulin in dose 3U/100 g body weight and Groups 4 and 5 were diabetic rats that received 0.1 cc of 200 and 400 mg/kg, ethanol extract of Lepidium sativum seed by gavages daily. One day after the last gavages, rats were anesthetized by chloroform. Epididymis duct was removed from abdomen and weighed with a digital scale. Afterwards, samples were putted in Bouin's solution for histological measurement. Administration of 200 and 400 mg/ml doses of Lepidium sativum seed extract increased epithelium height and decreased interstitial volume density and fibro muscular thickness significantly. Also, volume density of epithelium, fibro muscular, lumen and interstitial decreased significantly. Tubular and lumen diameter did not change significantly in different groups. It appears Lepidium sativum seed extract is a beneficial protective supplementary agent against adverse effects of diabetes on male reproductive system.

La diabetes mellitus es una enfermedad metabólica frecuente y grave que afecta a los hombres en todo el mundo. Recientemente, las plantas han sido una fuente deseable de medicina para este tipo de enfermedad. La diabetes tiene un efecto perjudicial en el sistema reproductivo masculino y puede conducir a la infertilidad. Causa disfunción eréctil y reduce el volumen de la eyaculación al afectar los pequeños vasos sanguíneos y los nervios que controlan la eyaculación. También disminuye la libido reduciendo los niveles de testosterona. El presente estudio evaluó la posible eficacia protectora del extracto de semilla de Lepidium sativum en la glucemia en ayunas y también se evaluó el cambio histopatológico del epidídimo en ratas diabéticas inducidas por estreptozotocina (STZ). Se dividieron aleatoriamente 50 ratas Wistar macho adultas en cinco grupos de 10 ratas cada uno. El grupo 1 recibió 0,1 ml de solución salina normal a través de los gavajes gástricos, el grupo 2 de ratas diabéticas control recibió una inyección intraperitoneal (IP) de STZ 60 mg / kg de peso corporal. Las ratas con FBS> 250 mg / dl se consideraron como diabéticas. El Grupo 3 eran ratas diabéticas que recibieron insulina en dosis de 3 U/ 100 g de peso corporal y los Grupos 4 y 5 estaban compuestos por ratas diabéticas que recibieron 0,1 cc con 200 y 400 mg / kg, de extracto de etanol de semillas de Lepidium sativum por gavajes diarios. Un día después de los últimos gavages, las ratas fueron anestesiadas con cloroformo. Se extrajo el epidídimo y se pesó con una pesa digital. Posteriormente, las muestras se pusieron en solución de Bouin para el estudio histológico. La administración de dosis de 200 y 400 mg / ml de extracto de semilla Lepidium sativum aumentó la altura del epitelio y disminuyó significativamente la densidad volumétrica intersticial y el grosor fibromuscular. Además, la densidad volumétrica del epitelio fibromuscular, lumen e intersticio disminuyeron significativamente. El diámetro tubular y el lumen no cambiaron significativamente en los diferentes grupos. El extracto de semilla de Lepidium sativum es un agente complementario beneficioso protector contra los efectos adversos de la diabetes en el sistema reproductor masculino.

Comparing Apoptosis and Necrosis Effects of Arctium Lappa Root Extract and Doxorubicin on MCF7 and MDA-MB-231 Cell Lines

Objective: Breast cancer is a heterogeneous disease and very common malignancy in women worldwide. The efficacy of chemotherapy as an important part of breast cancer treatment is limited due to its side effects. While pharmaceutical companies are looking for better chemicals, research on traditional medicines that generally have fewer side effects is quite interesting. In this study, apoptosis and necrosis effect of Arctium lappa and doxorubicin was compared in MCF7, and MDA-MB-231 cell lines. Materials and Methods: MCF7 and MDA-MB-231 cells were cultured in RPMI 1640 containing 10% FBS and 100 U/ml penicillin/streptomycin. MTT assay and an annexin V/propidium iodide (AV/PI) kit were used respectively to compare the survival rate and apoptotic effects of different concentrations of doxorubicin and Arctium lappa root extract on MDA-MB-231 and MCF7 cells. Results: Arctium lappa root extract was able to reduce cell viability of the two cell lines in a dose and time dependent manner similar to doxorubicin. Flow cytometry results showed that similar to doxorubicin, Arctium Lappa root extract had a dose and time dependent apoptosis effect on both cell lines. 10µg/mL of Arctium lappa root extract and 5 µM of doxorubicin showed the highest anti-proliferative and apoptosis effect in MCF7 and MDA231 cells. Conclusion: The MCF7 (ER/PR-) and MDA-MB-231 (ER/PR+) cell lines represent two major breast cancer subtypes. The similar anti-proliferative and apoptotic effects of Arctium lappa root extract and doxorubicin (which is a conventional chemotherapy drug) on two different breast cancer cell lines strongly suggests its anticancer effects and further studies.

Learning styles and strategies preferences of Iranian medical students in gross anatomy courses and their correlations with gender.

The learning approaches can help anatomy teachers design a suitable curriculum in harmony with their students' learning styles. The research objective is to evaluate gross anatomy learning styles and strategies preferences of Iranian medical students at Kashan University of Medical Sciences (KAUMS). This cross-sectional questionnaire-based study was carried out on 237 Iranian medical students. The students answered questions on approaches to learning anatomy and expressed opinions about learning anatomy in medical curriculum. The data were analyzed to disclose statistically significant differences between male and female students. Iranian male and female students were interested in learning anatomy using notes, plastic models, pictures and diagrams, clinical context, dissection and prosection of cadavers; however, they rarely used cross-sectional images and web-based resources. Both groups of medical students used region and system in learning anatomy. However, there existed some striking differences, particularly in having difficulty in studying anatomy using cadaveric specimens, using books alone, and learning it in small groups. Male students were less interested in learning with cadavers than female counterparts. However, female students were more interested in learning anatomy in small groups. This study suggests that instructors should design gross anatomy curriculum based on limitations of using dissection of cadaver in Iranian universities, emphasis on the applied anatomy, and learning of gross anatomy in small groups.

Cultural acceptability and personal willingness of Iranian students toward cadaveric donation.

Cadaver dissection stands as a crucial component in medical curricula around the world, although computer-based multimedia programs have been introduced in order to replace the need for cadaver donations. Due to a decrease in the number of unclaimed bodies and rather few donations, there is an insufficient number of cadavers for anatomical studies in Iran. This study was carried out to evaluate medical students' awareness and willingness regarding body donation in Kashan University of Medical Sciences, Iran. In this study, a questionnaire was designed to focus on the cultural acceptability and personal willingness to donate one's body after death. Students from the university's anatomy classes (n = 331) participated in this study. Seventy-seven percent of the students expressed their agreement toward the idea of utilizing body donation services, though only 25.4% of participants were willing to donate their own bodies. None of the demographic factors were associated with cultural acceptability or personal willingness towards body donation. These findings indicated that besides "payment", other factors were associated with students' willingness to become donors. All factors of awareness except "previous awareness of organization" were associated with cultural acceptability. In this study, students suggested that encouraging people to register for body donation using mass media (25.6%) and teaching students to respect cadavers in the dissection environment (24.8%) were the best solutions for addressing the lack of cadavers. These findings indicated that a lack of awareness about body donation might be the main factor responsible for unwillingness towards body donation; therefore, improving the public's awareness and addressing the willingness of students regarding body donation may help overcome the current lack of donated cadavers. Anat Sci Educ 10: 120-126. © 2016 American Association of Anatomists.

Gonadal steroids block the calpain-1-dependent intrinsic pathway of apoptosis in an experimental rat stroke model.

OBJECTIVES: Apoptosis plays an important role in the progression of the ischemic penumbra after reperfusion. Estrogen and progesterone have neuroprotective effects against ischemic brain damage, however the exact mechanisms of neuroprotection and signaling pathways is not completely understood. In this study, we investigated the possible regulatory effects of a combined steroid treatment on extrinsic and intrinsic apoptotic signaling pathways after cerebral ischemia. METHODS: Adult male Wistar rats were subjected to transient middle cerebral artery occlusion (tMCAO) using an intraluminal filament technique for 1 h followed by 23 h reperfusion. Estrogen and progesterone were immediately injected after tMCAO subcutaneously. Sensorimotor functional tests and the infarct volume were evaluated 24 h after ischemia. Protein expression of calpain-1 and Fas receptor (FasR), key members of intrinsic and extrinsic apoptosis, were determined in the penumbra region of the ischemic brain using western blot analysis, immunohistochemistry, and TUNEL staining. RESULTS: Neurological deficits and infarct volume were significantly reduced following hormone therapy. Calpain-1 up-regulation and caspase-3 activation were apparent 24 h after ischemia in the peri-infarct area of the cerebral cortex. Steroid hormone treatment reduced infarct pathology and attenuated the induction of both proteases. FasR protein levels were not affected by ischemia and hormone application. CONCLUSION: We conclude that a combined steroid treatment inhibits ischemia-induced neuronal apoptosis through the regulation of intrinsic pathways.

A brachioulnoradial artery: a short report.

Variations in the number and/or course of the arteries of the upper limb have clinical and surgical significance. During routine dissection of the left upper limb of a 50-year-old male cadaver, a brachial artery was noted that bifurcated into superficial and deep branches in the middle arm. The ulnar and radial arteries had a high origin from the superficial branch and proceeded superficially in the forearm, but had a normal termination in the hand. The common interosseous artery was termination of the deep branch. This report is a rare variation in arteries of upper limb and was not additional vessels.