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In this study, we examined the mechanisms of cadmium exposure-induced endoplasmic reticulum (ER) stress response and apoptosis in spermatocytes. Responses to cadmium toxicity were investigated using spermatocytes overexpressing p50ATF6, ATF4, and spliced XBP1s, belonging to the 3 unfolded protein response pathways. The ER stress and apoptosis response to cadmium were most strongly stimulated through the activating transcription factor 6 (ATF6) pathway; in contrast, siRNA-induced inhibition of protein expression could reduce apoptosis under stressful conditions. An in vivo experiment using mice confirmed that upregulation of p50ATF6 in the testis increased apoptosis in response to cadmium exposure. Further, when confirming the correlation between ER stress and MAPK in cadmium toxicity, p38 MAPK phosphorylation was strongly regulated by p50ATF6; p-p38 also mediated the activity of p50ATF6. Overall, these findings suggest that modulating the activity of p38 MAPK and p50ATF6 in cadmium exposure-induced toxicity can be considered a potential strategy to treat infertility. [ABSTRACT FROM AUTHOR]

In Alzheimer's disease, reactive oxygen species (ROS) are generated by the deposition of amyloid-beta oligomers (AβOs), which represent one of the important causes of neuronal cell death. Additionally, AβOs are known to induce autophagy via ROS induction. Previous studies have shown that autophagy upregulation aggravates neuronal cell death. In this study, the effects of peroxiredoxin 2 (Prx2), a member of the peroxidase family of antioxidant enzymes, on regulating AβO-mediated autophagy were investigated. Prx2 decreased AβO-mediated oxidative stress and autophagy in N2a-APPswe cells. Further, we examined the relationship between the neuronal protective effect of Prx2 and a decrease in autophagy. Similar to the effects of N-acetyl cysteine, Prx2 decreased AβO-induced ROS and inhibited p62 protein expression levels by downregulating the activation of NRF2 and its translocation to the nucleus. In addition, treatment with 3-methyladenine, an autophagy inhibitor, ameliorates neuronal cell death. Overall, these results demonstrate that the Prx2-induced decrease in autophagy was associated with the inhibition of ROS via the ROS–NRF2–p62 pathway in N2a-APPswe cells. Therefore, our results revealed that Prx2 is a potential therapeutic target in anti-Alzheimer therapy. [ABSTRACT FROM AUTHOR]

The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer's disease (AD). We generated hBOs from human induced pluripotent stem cells, investigated their characteristics according to neuronal markers and electrophysiological features, and then evaluated the protective effect of hNTSCs against amyloid-β peptide (Aβ1–42) neurotoxic activity in vitro in hBOs and in vivo in a mouse model of AD. Treatment of hBOs with Aβ1–42 induced neuronal cell death concomitant with decreased expression of neuronal markers, which was suppressed by hNTSCs cocultured under Aβ1–42 exposure. Cytokine array showed a significantly decreased level of osteopontin (OPN) in hBOs with hNTSC coculture compared with hBOs only in the presence of Aβ1–42. Silencing OPN via siRNA suppressed Aβ-induced neuronal cell death in cell culture. Notably, compared with PBS, hNTSC transplantation significantly enhanced performance on the Morris water maze, with reduced levels of OPN after transplantation in a mouse model of AD. These findings reveal that hBO models are useful to evaluate the therapeutic effect and mechanism of stem cells for application in treating AD. [ABSTRACT FROM AUTHOR]

Objectives: Although glutamate is an essential factor in the neuronal system, excess glutamate can produce excitotoxicity. We previously reported that Peroxiredoxin 5 (Prx5) protects neuronal cells from glutamate toxicity via its antioxidant effects. However, it is unclear whether cytosolic or mitochondrial Prx5 provides greater neuroprotection. Here, we investigated differences in the neuroprotective effects of cytosolic and mitochondrial Prx5. Methods: We analyzed patterns of cytosolic and mitochondrial H2O2 generation in glutamate toxicity using HyPer protein. And then, we confirmed the change of intracellular ROS level and apoptosis with respective methods. The mitochondrial dynamics was assessed with confocal microscope imaging and western blotting. Results: We found that the level of mitochondrial H2O2 greatly increased compared to cytosolic H2O2 and it affected cytosolic H2O2 generation after glutamate treatment. In addition, we confirmed that mitochondrial Prx5 provides more effective neuroprotection than cytosolic Prx5. Discussion: Overall, our study reveals the mechanisms of cytosolic and mitochondrial ROS in glutamate toxicity. Our findings suggest that mitochondrial ROS and Prx5 are attractive therapeutic targets and that controlling these factors be useful for the prevention of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

High concentrations of glutamate induce neurotoxicity by eliciting reactive oxygen species (ROS) generation and intracellular Ca2+ influx. The disruption of Ca2+ homeostasis in the endoplasmic reticulum (ER) evokes ER stress, ultimately resulting in neuronal dysfunction. Additionally, glutamate participates in the development of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Peroxiredoxins (Prxs) are members of a family of antioxidant enzymes that protect cells from neurotoxic factor-induced apoptosis by scavenging hydrogen peroxide (H2O2). Prx4 is located in the ER and controls the redox condition within the ER. The present study investigated the protective effects of Prx4 against glutamate-induced neurotoxicity linked to ER stress. HT22 cells in which Prx4 was either overexpressed or silenced were used to elucidate the protective role of Prx4 against glutamate toxicity. The expression of Prx4 in HT22 cells was significantly increased in response to glutamate treatment, while ROS scavengers and ER chemical chaperones reduced Prx4 levels. Moreover, Prx4 overexpression reduces glutamate-induced apoptosis of HT22 cells by inhibiting ROS formation, Ca2+ influx, and ER stress. Therefore, we conclude that Prx4 has protective effects against glutamate-induced HT22 cell damage. Collectively, these results suggest that Prx4 could contribute to the treatment of neuronal disorders. [ABSTRACT FROM AUTHOR]

Glutamate-induced neurotoxicity is related to excessive oxidative stress accumulation and results in the increase of neuronal cell death. In addition, glutamate has been reported to lead to neurodegenerative diseases, including Parkinson's and Alzheimer's diseases.It is well known that Fraxinus rhynchophylla contains a significant level of oleuropein (Ole), which exerts various pharmacological effects. However, the mechanism of neuroprotective effects of Ole is still poorly defined. In this study, we aimed to investigate whether Ole prevents glutamate-induced toxicity in HT-22 hippocampal neuronal cells. The exposure of the glutamate treatment caused neuronal cell death through an alteration of Bax/Bcl-2 expression and translocation of mitochondrial apoptosis-inducing factor (AIF) to the cytoplasm of HT-22 cells. In addition, glutamate induced an increase in dephosphorylation of dynamin-related protein 1 (Drp1), mitochondrial fragmentation, and mitochondrial dysfunction. The pretreatment of Ole decreased Bax expression, increased Bcl-2 expression, and inhibited the translocation of mitochondrial AIF to the cytoplasm. Furthermore, Ole amended a glutamate-induced mitochondrial dynamic imbalance and reduced the number of cells with fragmented mitochondria, regulating the phosphorylation of Drp1 at amino acid residue serine 637. In conclusion, our results show that Ole has a preventive effect against glutamate-induced toxicity in HT-22 hippocampal neuronal cells. Therefore, these data imply that Ole may be an efficient approach for the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Objectives:Chrysophanol, also called chrysophanic acid, is a natural anthraquinone compound found inRheum palmatum. R. palmatumhas been used in oriental medicine in ancient East Asia. Microglial cells represent not only the forefront immune defense in the central nervous system but also the most reactive sensors to various threats. However, activated microglia can exert neurotoxic effectsviaexcessive production of cytotoxic molecules and proinflammatory cytokines. Therefore, modulation of microglial cell activation is important for maintaining neuronal function. Materials and methods:Pretreatment of chrysophanol in BV-2 murein microglial cells was carried out for 1 hour, followed by stimulation with 1 μg/mL LPS. Level of proteins and RNAs were detected by western blotting and Reverse Transcriptase PCR. DsRed2-Mito-expressing cells were used for detecting mitochondrial morphology. Results:In this study, we determined the effects of chrysophanol on lipopolysaccharide (LPS)-induced microglial activation. Chrysophanol inhibited the LPS-induced production of proinflammatory mediators and cytokinesviasuppression of mitogen-activated protein kinase/nuclear factor kappa-B activation and reactive oxygen species generation. In addition, chrysophanol downregulated LPS-induced mitochondrial fission by diminishing dynamin-related protein 1 (Drp1) dephosphorylation. Taken together, chrysophanol suppressed the proinflammatory response of activated microglia via inhibition of Drp1-dependent mitochondrial fission. Conclusion:Our findings can provide the basis for the use of chrysophanol in microglial inflammatory response-mediated neurodegenerative diseases. Furthermore, our study can contribute to the production of new drugs for inflammatory response-mediated neurodegenerative diseases by purification of chrysophanol. [ABSTRACT FROM PUBLISHER]

Chrysophanic acid, or chrysophanol, is an anthraquinone found in Rheum palmatum, which was used in the preparation of oriental medicine in ancient China. The hippocampus plays a major role in controlling the activities of the short- and long-term memory. It is one of the major regions affected by excessive cell death in Alzheimer's disease. Therefore, neuronal cell-death modulation in the hippocampus is important for maintaining neuronal function. We investigated chrysophanol's effects on glutamate-induced hippocampal neuronal cell death. Chrysophanol reduced glutamate-induced cell death via suppression of proapoptotic factors and reactive oxygen species generation. Furthermore, it downregulated glutamate-induced mitochondrial fission by inhibiting dynamin-related protein 1 (Drp1) dephosphorylation. Thus, chrysophanol suppressed hippocampal neuronal cell death via inhibition of Drp1-dependent mitochondrial fission, and can be used as a therapeutic agent for treating neuronal cell death-mediated neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Bladder dysfunction induced by spinal cord injury (SCI) can become problematic and severely impair the quality of life. Preclinical studies of spinal cord injury have largely focused on the recovery of limb function while neglecting to investigate bladder recovery. Objective: The present study was performed to investigate and review the effect of stem cell-based cell therapy on bladder recovery in SCI. Methods: We conducted a meta-analysis of urodynamic findings of experimental trials that included studies of stem cell-based cell therapy in SCI. Relevant studies were searched using MEDLINE, EMBASE and Cochrane Library (January 1990 - December 2012). Final inclusion was determined by a urodynamic study involving detailed numerical values. Urodynamic parameters for analysis included voiding pressure, residual urine, bladder capacity and non-voiding contraction (NVC). Meta-analysis of the data, including findings from urodynamic studies, was performed using the Mantel-Haenszel method. Results: A total of eight studies were included with a sample size of 224 subjects. The studies were divided into different subgroups by different models of SCI. After a stem cell-based cell therapy, voiding pressure (-6.35, p <0.00001, I2 = 77%), NVC (-3.58, p <0.00001, I2 = 82%), residual urine (-024, p = 0.004, I2 = 95%) showed overall significant improvement. Bladder capacity showed improvement after treatment only in the transection type (-0.23, p = 0.0002, I2 = 0%). Conclusion: After stem cell-based cell therapy in SCI, partial bladder recovery including improvement of voiding pressure, NVC, and residual urine was demonstrated. Additional studies are needed to confirm the detailed mechanism and to obtain an ideal treatment strategy for bladder recovery. [ABSTRACT FROM AUTHOR]

In this study, we investigated the secretome of human oligodendrocytes (F3.Olig2 cells) generated from human neural stem cells by transduction with the gene encoding the Olig2 transcription factor. Using mRNA sequencing and protein cytokine arrays, we identified a number of biologically important secretory proteins whose expression has not been previously reported in oligodendrocytes. We found that F3.Olig2 cells secrete IL-6, PDGF-AA, GRO, GM-CSF, and M-CSF, and showed prominent expression of their corresponding receptors. Co-expression of ligands and receptors suggests that autocrine signaling loops may play important roles in both differentiation and maintenance of oligodendrocytes. We also found that F3.Olig2 cells secrete matrix metalloproteinases and matrix metalloproteinase-associated proteins associated with functional competence of oligodendrocytes. The results of our secretome analysis provide insights into the functional and molecular details of human oligodendrocytes. To the best of our knowledge, this is the first systematic analysis of the secretome of oligodendrocytes. [ABSTRACT FROM AUTHOR]

Stroke is a serious, adverse neurological event and the third leading cause of death and disability worldwide. Most strokes are caused by a block in cerebral blood flow, resulting in neurological deficits through the death of brain tissue. Recombinant tissue plasminogen activator (rt-PA) is currently the only immediate treatment medication for stroke. The goal of rt-PA administration is to reduce the thrombus and/or embolism via thrombolysis; however, the administration of rt-PA must occur within a very short therapeutic timeframe (3 h to 6 h) after symptom onset. Components of the pathological mechanisms involved in ischemic stroke can be used as potential biomarkers in current treatment. However, none are currently under investigation in clinical trials; thus, further studies investigating biomarkers are needed. After ischemic stroke, microglial cells can be activated and release inflammatory cytokines. These cytokines lead to severe neurotoxicity via the overactivation of microglia in prolonged and lasting insults such as stroke. Thus, the balanced regulation of microglial activation may be necessary for therapy. Stem cell therapy is a promising clinical treatment strategy for ischemic stroke. Stem cells can increase the functional recovery of damaged tissue after post-ischemic stroke through various mechanisms including the secretion of neurotrophic factors, immunomodulation, the stimulation of endogenous neurogenesis, and neovascularization. To investigate the use of stem cell therapy for neurological diseases in preclinical studies, however, it is important to develop imaging technologies that are able to evaluate disease progression and to "chase" (i.e., track or monitor) transplanted stem cells in recipients. Imaging technology development is rapidly advancing, and more sensitive techniques, such as the invasive and non-invasive multimodal techniques, are under development. Here, we summarize the potential risk factors and biomarker treatment strategies, stem cell-based therapy and emerging multimodal imaging techniques in the context of stroke. This current review provides a conceptual framework for considering the therapeutic targets and directions for the treatment of brain dysfunctions, with a particular focus on ischemic stroke. [ABSTRACT FROM AUTHOR]

A review of the article "A Modular Speed-Drooped System for High Reliability Integrated Modular Motor Drives" by Alessandro Galassini is presented.

Background: The core question of the study was whether adequately achieved HD affected the sexual dysfunction in women on hemodialysis (HD) with chronic renal failure (CRF).Methods: Thirty-seven female patients on HD, including 18 women with adequate HD and 19 women with non-adequate HD, and 36 healthy controls were included in this study. Demographic and clinical variables, including the sexual hormones estradiol and testosterone, were recorded. Sexual function was assessed according to the Female Sexual Function Index (FSFI) and results were compared between groups. Adequate HD was defined as an average urea clearance of over 1.3 (Kt/V) over three consecutive months.Results: All domains of the FSFI questionnaire, with the exception of satisfaction, were higher in the control group than in the HD group. In comparing the adequate and non-adequate HD groups, there was no difference in any of the six domains of the FSDI questionnaire. Among the clinical variables, the number of menopausal women was higher in the HD group than in the control group (P = 0.023). Estradiol and testosterone levels were higher in the control group than in the HD group (P = 0.003, 0.027, respectively). The number of menopausal women and estradiol and testosterone levels showed no differences between the adequate and non-adequate HD groups. Correlation analysis between Kt/V and FSFI showed no significant relationship, but estrogen did show a significant relationship with FSFI (correlation coefficient = 0.399, P = 0.001).Conclusions: HD adequacy alone does not have a significant impact on sexual dysfunction. Other treatments options should be considered to treat sexual dysfunction in women with CRF. [ABSTRACT FROM AUTHOR]

Background: The efficacy of medical treatment among obese men with lower urinary tract symptoms (LUTS) has been less clear, especially regarding the improvement of QoL. We aimed to investigate the difference in efficacy and consequent satisfaction of life quality after medical treatment of male LUTS according to obesity.Methods: An 8-week prospective study was performed for a total of 140 patients >50 years old with International Prostate Symptom Scores (IPSS) > 12 points and prostate volume > 20 mL. Obesity was determined by either body mass index (BMI) or waist circumference (WC). Patients were divided into 2 groups according to BMI or WC. Patients received tamsulosin at a dose of 0.4 mg daily for 8 weeks. The changes from baseline in the IPSS, maximal urinary flow rate (Qmax), post-void residual volume, questionnaire of quality of life (QoL), and King's Health Questionnaire (KHQ) were analyzed.Results: Of the 150 enrolled patients, 96 completed the study. Seventy-five patients (78.1%) had BMI ≥ 23 kg/m2, and 24 (25.0%) had WC > 90 cm. Overall, the IPSS, IPSS QoL, and total KHQ showed significant improvement. Obese (BMI ≥ 23 kg/m2) and non-obese (BMI < 23 kg/m2) both showed improvement of the IPSS and IPSS QoL scores, but only the obese (BMI ≥ 23 kg/m2) group showed improvement of the total KHQ score (P < 0.001 vs. P = 0.55). Only the obese (WC > 90 cm) group showed improvement of the IPSS and total KHQ scores (P < 0.001).Conclusions: Our preliminary study showed the different efficacy of an alpha-blocker for improvement of LUTS and life quality according to obesity. Obese patients, defined by BMI or WC, showed the tendency toward a more favorable improvement of LUTS and life quality.Trial Registration: Current Controlled Trials 2010-058. Registered 2 September 2010 in Soonchunhyang University Hospital. [ABSTRACT FROM AUTHOR]

To date, stem cell therapy for the bladder has been conducted mainly on an experimental basis in the areas of bladder dysfunction. The therapeutic efficacy of stem cells was originally thought to be derived from their ability to differentiate into various cell types. Studies about stem cell therapy for bladder dysfunction have been limited to an experimental basis and have been less focused than bladder regeneration. Bladder dysfunction was listed in MESH as "urinary bladder neck obstruction", "urinary bladder, overactive", and "urinary bladder, neurogenic". Using those keywords, several articles were searched and studied. The bladder dysfunction model includes bladder outlet obstruction, cryoinjured, diabetes, ischemia, and spinal cord injury. Adipose derived stem cells (ADSCs), bone marrow stem cells (BMSCs), and skeletal muscle derived stem cells (SkMSCs) are used for transplantation to treat bladder dysfunction. The main mechanisms of stem cells to reconstitute or restore bladder dysfunction are migration, differentiation, and paracrine effects. The aim of this study is to review the stem cell therapy for bladder dysfunction and to provide the status of stem cell therapy for bladder dysfunction. [ABSTRACT FROM AUTHOR]

Globally, colorectal cancer (CRC) is common cause of cancer-related deaths. The high mortality rate of patients with colon cancer is due to cancer cell invasion and metastasis. Initiation of the epithelial-to-mesenchymal transition (EMT) is essential for the tumorigenesis. Peroxiredoinxs (PRX1-6) have been reported to be overexpressed in various tumor tissues, and involved to be responsible for tumor progression. However, the exact role of PRX5 in colon cancer remains to be investigated enhancing proliferation and promoting EMT properties. In this study, we constructed stably overexpressing PRX5 and suppressed PRX5 expression in CRC cells. Our results revealed that PRX5 overexpression significantly enhanced CRC cell proliferation, migration, and invasion. On the other hand, PRX5 suppression markedly inhibited these EMT properties. PRX5 was also demonstrated to regulate the expression of two hallmark EMT proteins, E-cadherin and Vimentin, and the EMT-inducing transcription factors, Snail and Slug. Moreover, in the xenograft mouse model, showed that PRX5 overexpression enhances tumor growth of CRC cells. Thus, our findings first provide evidence in CRC that PRX5 promotes EMT properties by inducing the expression of EMT-inducing transcription factors. Therefore, PRX5 can be used as a predictive biomarker and serves as a putative therapeutic target for the development of clinical treatments for human CRC. [ABSTRACT FROM AUTHOR]