Bone marrow stromal cell-conditioned medium regenerates injured sciatic nerve by increasing expression of MPZ and NGF and decreasing apoptosis.

Objectives: Despite the many benefits of mesenchymal stem cell (MSC) transplantation for tissue regeneration, there are some limitations to using them, including the high costs, applying invasive procedures, the possibility of transplant rejection, and cell malignancy. This study aimed to investigate the effect of secretions of bone marrow stromal cells (BMSCs) with the cell-free strategy on damaged sciatic nerve with an emphasis on the role of apoptosis and the expression of myelin protein zero (MPZ) and nerve growth factor (NGF) proteins. Materials and Methods: BMSCs were cultured and a 25-fold concentrated conditioned medium (CM) from the cells was provided. After creating a crush injury in the left sciatic nerve of male rats, BMSCs or CM were injected into the injured site of the nerve. Four weeks later, the expression of MPZ, NGF, Bax, and Bcl-2 proteins in the sciatic nerve and histological parameters of the sciatic nerve and gastrocnemius muscle were assessed. Results: The results demonstrated that injection of CM decreased apoptosis and increased expression of MPZ and NGF proteins, improving remyelination and regeneration of the sciatic nerve almost as much as the transplantation of the BMSCs themselves compared to the control group. Conclusion: The results suggest that BMSC secretions may improve remyelination and regeneration of damaged sciatic nerve by increasing the expression of MPZ and NGF and decreasing apoptosis.

Therapeutic Effects Of Combined and Chronic Treatment of Tat-GluA23y and D-Serine on Cognitive Dysfunction in Postmenopausal Rats.

BACKGROUND: The incidence of Alzheimer's disease (AD) in female gender compared with male has been addressed as a health concern, particularly in menopausal age. We here hypothesized that co-administration of NMDARs agonist (D-serine) and AMPARs endocytosis inhibitor (Tat-GluA23y) might be a potential target for alleviating memory impairment in sporadic Alzheimer model of rats. METHODS: Forty-eight female Wistar rats weighing 200-220 randomly divided into six groups. One month later, ovariectomized rats underwent stereotaxic surgery and were cannulated into the brain lateral ventricles. Streptozotocin was injected (3 mg/kg), then animals received the related treatments until the day 51, which experienced acquisition of spatial memory in Morris Water Maze test. Finally, the level of phosphorylated cAMP response element binding protein (CREB) in the hippocampus was measured by Western blotting. RESULTS: Co-administration of D-serine and GluA23y significantly enhanced the acquisition and retrieval of impaired spatial memory in ovariectomized rats with AD (p < .001). Compared to Glu-A 23, D-serine caused more improvement in the mentioned parameters above, however, these values for both groups were still significantly different from the control group (P < .05). CONCLUSION: Simultaneous treatment with D-serine and GluA23y synergistically improved STZ induced spatial memory impairment in OVX rat, probably partly via increase in phosphorylated CREB protein.

Potential anti-inflammatory effect of Lamium album extract through caspase-3 and cyclooxygenase-2 genes expression in a rat model of middle cerebral artery occlusion.

INTRODUCTION: Stroke is one of the most common causes of death worldwide. Inflammation and apoptosis play an important role in the cascade of ischemic stroke.

Protective Effect of the Viola spathulata Extract on NCX3 Gene Expression in an Animal Model of Cerebral Ischemia.

Introduction: Viola plant has been used traditionally to treat neurological disorders. We aimed at determining whether pretreatment with Viola spathulata extract can alleviate the severity of ischemic-reperfusion damages and exert its protective effects through the regulation of a sodium/calcium exchanger (NCX3) gene expression in a rat brain. Methods: Male Wistar rats were divided into two main groups: one main group for evaluating Neurologic Deficit Score (NDS) and Infarct Volume (IV) and the other group for the evaluation of NCX3 gene expression in the brain tissue. The latter group was subdivided into the intact, control (vehicle), sham, V5, and V10. The vehicle (control) subgroup received Dimethyl Sulfoxide (DMSO), and V5 and V10 subgroups received V. spathulata extract at the doses of 5 and 10 mg/kg (IP), respectively, for 7 days. After pretreatment, we carried out Middle Cerebral Artery Occlusion (MCAO) for 60 min. Results: In the V5 and V10 subgroups, NDS and IV significantly decreased. MCAO upregulated NCX3 gene expression in the core, penumbra, and subcortical regions compared with the intact subgroup. The V5 subgroup significantly downregulated the NCX3 gene expression level in the core compared with the control subgroup. The V10 subgroup showed downregulation of the NCX3 gene expression level in the core, penumbra, and subcortex compared with the control subgroup. Conclusion: V. spathulata extract may have a neuroprotective role against MCAO-induced ischemic brain damage, possibly by preventing the alteration of NCX3 gene expression level. Highlights: MCAO results Infarct Volume (IV) and Neurologic Deficit Score (NDS);MCAO upregulated NCX3 gene expression in brain tissues;Viola spathulata extract pretreatment decreased IV and NDS in brain ischemia;Viola spathulata pretreatment downregulated NCX3 gene expression in brain tissues. Plain Language Summary: Stroke is the second leading cause of death and long term disability. Recently it has been reported that herbal extracts have protective role in ischemia injury. In Iranian traditional medicine Viola plant has a long history to treat disorders such as cancer. So we designed an animal study to investigate Viola plant extract in brain ischemia injury. Viola spathulata extract was administrated to rats for seven days, then animal model of brain ischemia was operated on them and some behavioral, histological and molecular factors were analyzed. Our findings showed that Viola spathulata extract improved behavioral disability, decreased infarct volume in brain tissue, and modulate Sodium/Calcium exchanger 3 gene expression. It could be concluded that Viola spathulata has the neuroprotective effect in animal stroke model and is a good candidate for nutritional supplements, although further studies are needed.

The Importance of Happy Hypoxemia in COVID-19.

BACKGROUND: Nowadays, the new coronavirus (SARS-CoV-2) and its complications are one of the main concerns of the world. One of the most severe complications of COVID-19 is hypoxemia. OBJECTIVES: This study aimed to assess the importance of happy hypoxemia in COVID-19. METHODS: We systematically searched web of science, PubMed, and Google scholar databases to find articles related to COVID-19 and happy hypoxemia. RESULTS: COVID-19 causes a type of hypoxemia named silent (happy) hypoxemia, which has an atypical clinical presentation. This type of hypoxemia has not been noted before in viral pneumonia, and there is no specific treatment for this serious complication. Patients with silent hypoxemia may develop severe hypoxemia without dyspnea and with near-normal lung compliance. These patients are awake, calm, and responsive. Although their lungs are not oxygenated efficiently, they are alert and cooperative. Their condition may be deteriorated rapidly without warning and causes death. CONCLUSIONS: According to the findings, paying attention to happy hypoxemia is important for improving the health status of COVID-19 patients.

Enriched environment effect on lipopolysaccharide-induced spatial learning, memory impairment and hippocampal inflammatory cytokine levels in male rats.

Neuro-inflammation is responsible for cognitive impairments and neurodegenerative diseases such as Alzheimer's disease. In this study, we aimed to investigate the enriched environment (EE) effect on learning and memory impairment as well as on pro-inflammatory cytokines changes induced by lipopolysaccharide (LPS). LPS injection (1 mg/kg/i.p, days 1, 3, 5, and 7) was used to develop the animal model of neuro-inflammation. Twenty-eight male Wistar rats were used in the experiment and randomly divided into 4 groups: 1) sham (S), 2) sham + enriched environment (SE), 3) LPS (L), and 4) LPS + EE (LE). Two different housing conditions, including standard environment (SE) and enriched environment, were used. The Morris Water Maze (MWM) test was used to examine animals learning and memory. IL-1ß, IL-10, and TNF-α levels were measured in the brain using ELISA. We found that LPS significantly impaired learning and memory (p < 0.05) in the MWM task, but EE could significantly improve learning and memory impairment (p < 0.05). IL-1 and IL-10 levels dramatically increased in the LPS group (P < 0.05), whereas EE could decrease and increase IL-1ß and IL-10 values in the LPS + EE group (P < 0.05), respectively. TNF-α levels were traced but had not detectable values in the hippocampus. Thus, we can conclude that EE has healing effects on LPS induced neuro-inflammation and can improve learning and memory deficit; however, further studies are needed to support the findings of our study.

Diphtheria toxoid nanoparticles improve learning and memory impairment in animal model of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder involving memory. The present study aimed at evaluating the effects of encapsulated diphtheria toxoid (DT) on behavioral learning impairment, and XBP1 mRNA splicing in AD. METHODS: A DT-loaded nanoparticle (NP) carrier was prepared using the ionic gelation method. Sixty-three rats were divided into nine groups: (1) healthy, (2-4) sham, and (5-9) AD models: (5) AD was induced by intracerebroventricular injection of amyloid beta (Aß) 1-42. (6) The rats received a subcutaneous diphtheria vaccine only 28 days before Aß injection. (7) The rats received an intranasal diphtheria vaccine, in group 8, induced by administering empty chitosan NPs. 9) it was induced by administering chitosan NPs carrying DT. Morris water maze (MWM) test was used to examine the animals' learning and memory. Also, X-box binding protein 1 (XBP-1) mRNA gene splicing was studied in the hippocampus by reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: For the first time, chitosan NPs were prepared with an average diameter size of 40 nm and the effectiveness of approximately 70% during DT encapsulation. In comparison with the healthy group, the AD models exhibited significant impairment of learning and memory (P < 0.05), while DT-administrated animals showed significant improvements in learning and memory impairment (P < 0.05). XBP-1 mRNA gene splicing was only detected in an untreated AD group, while encapsulated DT completely inhibited splicing. CONCLUSION: The therapeutic effects of DT chitosan NPs against learning and memory impairment were observed in this study, and XBP1 mRNA splicing was reported in the animal models.

The impact of menopause on sexual function in women and their spouses.

BACKGROUND: The purpose of this study is to evaluate the impact of menopause on sexual function in women and their spouses. METHODS: This is a cross-sectional study that was conducted from January 2018 to May 2019 in Rasht (North of Iran). The participants included 215 menopausal women and their spouses. Data were collected using the demographic questionnaire, the Female Sexual Function Index (FSFI) questionnaire, and the International Index of Erectile Function (IIEF) questionnaire. RESULTS: On the basis of the FSFI and IIEF scores, 36.28% (78/215) women reported female sexual dysfunction (FSD) and 17.2% (37/215) men reported erectile dysfunction (ED) with 8.37% (N = 18) being mild, 5.58% (N = 12) mild to moderate, and 3.25% (N = 7) moderate ED. After adjusting differences in the female age distribution, the total score and scores of the IIEF subscales were also not significantly lower in the spouses of women with FSD than women without FSD. CONCLUSION: Although, significant correlations between male erectile function and menopausal female sexual function have not identified; but, low scores of the subscales of FSFI in female participants mostly impaired sexual satisfaction and overall satisfaction in their spouses.

Effects of Paraoxon Exposure on Expression of Apoptosis-Related Genes, Neuronal Survival, and Astrocyte Activation in Rat Prefrontal Cortex.

Paraoxon is the bioactive metabolite of organophosphate (OP) pesticide, parathion. This study aimed to evaluate the expression of apoptosis-related genes and histopathological changes in rat prefrontal cortex following exposure to three different doses of paraoxon. Paraoxon (0.3, 0.7, or 1 mg/kg) or corn oil (vehicle) were intraperitoneally injected to adult male Wistar rats. After 14 or 28 days, mRNA and protein levels of Bax, Bcl-2, and caspase-3 were measured in prefrontal cortex using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting, respectively. In addition, neuronal injury and astrocyte activation were assessed using cresyl violet staining and glial fibrillary acidic protein (GFAP) immune-positive cells, respectively. Treatment with 0.7 and 1 mg/kg of paraoxon increased mRNA and protein levels of Bax and caspase-3 at 14 and 28 days post-exposure, while mRNA and protein levels of Bcl-2 decreased only in 1 mg/kg group after 14 days. Furthermore, a significant decrease in the number of neurons and a significant increase in the number of GFAP-positive cells were observed in rats receiving 0.7 and 1 mg/kg of paraoxon at both time points. Collectively, our results showed that apoptosis is a major mechanism for neuronal damage after exposure to paraoxon. Also, paraoxon-induced neuronal loss was correlated with activation of astrocytes. Since paraoxon-induced neuronal damage is closely related to convulsion, clinical management of convulsion could protect neuronal brain damage.

Urtica Dioica and Lamium Album Decrease Glycogen Synthase Kinase-3 beta and Increase K-Ras in Diabetic Rats.

OBJECTIVES: The aim of the present work is evaluating the special effects of Urtica Dioica and Lamium Album on the serum level of K-Ras and GSK-3 beta in diabetic rats. METHODS: In the present experimental study, 32 male Wistar rats randomly divided into 4 groups (Group I: normal control rats; receiving daily PBS, Group 2: diabetic control rats; receiving single dose of streptozotocin (60 mg/kg) and daily PBS, Group 3: Diabetic rats treated with 100 mg/kg of hydroalcoholic extract of the U. dioica, Group 4: Diabetic rats treated with 100 mg/kg of hydroalcoholic extract of L. Album. Diabetes-induced by an intraperitoneal injection of streptozotocin (60 mg/ kg). On the 14 th day of treatment, the weight, fasting blood sugar (FBS) and on 28 th day blood glucose, K-Ras and GSK3 beta was measured. RESULTS: In diabetic group blood GSK-3 beta increase in comparison to control group (P < 0.05), also blood K-Ras decrease in the diabetic group (P < 0.05). Both extracts reduced GSK-3 beta level, however, this reduction was only statistically significant by U. dioica (P < 0.05). Compared to diabetic group, blood K-Ras level increased by both extract (P < 0.05). Also diabetes induction increase blood glucose levels and both extracts decrease its level significantly (P < 0.05). there is no significant differences among both extract effects on blood glucose, and K-Ras. CONCLUSION: For the first time shown that both extracts by regulating GSK-3 beta and K-Ras improve blood glucose level. More studies are needed to determine all the effects of these herbs.

Effects of standardized extracts of Lamium album and Urtica dioica on rat tracheal smooth muscle contraction.

OBJECTIVE: Diseases of the respiratory system are one of the main causes of death and include situation such as chronic obstructive pulmonary disease, pneumonia or asthma. Medicinal plants have beneficial effects on multiple diseases include respiratory disorders like asthma and bronchitis. The aim of this study was to evaluate the effects of U. dioica and L. Album on tracheal smooth muscle contraction. MATERIAL AND METHODS: Hydroalcoholic extracts of L. Album and U. Dioica aerial parts were prepared by maceration method and standardized based on their total phenol content. The effect of the extracts on the KCl-induced contraction of rat trachea was examined in an organ bath chamber. Data was analyzed with spss software 22. RESULTS: The extract of L. Album (5 mg/ml), similar to theophylline (20 mM), significantly reduced the KCl-induced tracheal contraction. On the other hand, U. Dioica (1 mg/ml and 5 mg/ml) augmented the KCl-induced contraction. CONCLUSION: The relaxant effect of L. Album on the trachea makes it as a candidate for the managing patients with asthma and obstructive pulmonary diseases. But because of U. Dioica potential constrictive effect on the trachea it is suggested that patients avoid consuming it.

Efficacy of Trigonella foenum-graecum Seed Extract in Reducing Metabolic and Inflammatory Alterations Associated With Menopause.

BACKGROUND: Several experimental and clinical studies support beneficial effects of Trigonella foenum-graecum (fenugreek) in the management of metabolic diseases and inflammatory disorders. OBJECTIVES: The purpose of this study was to examine the effect of T. foenum-graecum seed extract in reducing the metabolic and inflammatory alternations associated with menopause. MATERIALS AND METHODS: In this experimental study, 49 rats were divided into seven groups: (I) sham-control, (II) ovariectomized-control, (III and IV) ovariectomized treated with 50 and 150 mg/kg of T. foenum-graecum seed ethanolic extract, (V and VI) ovariectomized treated with 50 and 150 mg/kg of T. foenum-graecum hexanic extract, (VII) ovariectomized-positive control treated with 10 µg/kg of estradiol. The extracts were injected intraperitoneally one day after ovariectomy and the treatments were lasted for 42 days. RESULTS: Fasting blood glucose and body weight gain increased significantly in the ovariectomized-control group compared with that in the sham animals (P < 0.05). Administration of estradiol and T. foenum-graecum (50 and 150 mg/dL of hexanic extract and 150 mg/kg of ethanolic extract) significantly diminished the increase in glucose and body weight (P < 0.05). The serum level of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the ovariectomized control group was significantly higher than those in the sham animals (P < 0.05). Both hexanic and ethanolic extracts as well as estradiol were able to decrease level of these cytokines in the serum of ovariectomized rats (P < 0.05). CONCLUSIONS: The results of the present study show that administration of T. foenum-graecum corrects metabolic and inflammatory alterations associated with ovariectomy and has a potential for the management of menopause.

Comparison of in vitro and in situ methods for studying lipolysis.

Lipolysis is a highly regulated process and is controlled by nervous system, hormones, and paracrine/autocrine factors. Dysregulation of lipolysis is associated with some pathophysiological conditions including diabetes, metabolic syndrome, and obesity. Nowadays, special attention isthereforepaid to study lipolysis using different experimental models. This review summarizes the current experimental methods for studying lipolysis. Culture of preadipocyte cell lines, use of differentiated stroma-vascular cells, primary culture of adipocyte, organ culture of adipose tissue, and microdialysis technique are the most widely used techniques to study lipolysis. The advantages and limitations of using these methods are discussed.