The Effect of Curcumin on Penile Fibrotic Plaque in Rats with Experimental Peyronie's Disease

Objective: No effective medical approach for the treatment of Peyronie's disease (PD) has to date been described. This study was intended to evaluate the antifibrotic, antioxidant, and antiinflammatory effects of curcumin on fibrotic tissue in the tunica albuginea (TA) in a rat model of PD. Materials and Methods: Twenty-four male Sprague Dawley rats aged 10 months were randomized into three groups (n = 8 in each). No PD model was induced in the control group. The PD+saline (PD+Ps) group received fibrin injection, followed two weeks later by saline administration by oral gavage for 14 days. The PD+Curcumin (PD+Cur) group received fibrin injection into the TA followed two weeks later by curcumin administration by oral gavage for 14 days. At the end of the experiment, fibrotic activity was evaluated using stereological and histopathological methods. Transforming growth factor-β1 (TGF-β1), one of the most fibrogenic cytokines, was evaluated using immunohistochemistry with an anti-TGF-β1 rabbit monoclonal antibody. Results: Stereological analysis revealed significantly greater Peyronie-like plaque areas in the TA in the PD+Ps group than in the control and PD+Cur groups (p<0.0001). No significant difference was observed between the control and PD+Cur groups (p=0.35). The PD+Ps group exhibited strong TGF-β1 immunoreactivity with increased expression in the collagenous connective tissues and fibroblasts around the TA. Conclusion: Curcumin reduced fibrotic tissue in the TA and may represent a novel therapeutic option in the treatment of PD

Benign paroxysmal positional vertigo after radiologic scanning: a case series

<p>Abstract</p> <p>Introduction</p> <p>Benign paroxysmal positional vertigo (BPPV) is the most common type of vertigo. It is frequently seen in elderly patients, and the course of the attack may easily mimic cerebrovascular disease. A BPPV attack after a radiologic examination has not been reported previously. We report the cases of two patients who had BPPV attacks after radiologic imaging.</p> <p>Case presentation</p> <p>The first patient with headache and tremor was admitted to the radiology department for cranial computed tomography (CT) imaging. During scanning, she was asked to lie in the supine position with no other head movements for approximately 10 minutes. After the cranial CT imaging, she stood up rapidly, and suddenly experienced a vertigo attack and nausea. The second patient was admitted to the radiology department for evaluation of his renal arteries. During the renal magnetic resonance angiography, he was in the supine position for 20 minutes and asked not to move. After the examination, he stood up rapidly with the help of the technician and suddenly experienced a vertigo attack with nausea and vomiting. The results of standard laboratory analyses and their neurologic examinations were within normal limits and Dix-Hallpike tests showed rotatory nystagmus in both cases. An Epley maneuver was performed to the patients. The results of a control Dix-Hallpike tests after 1 Epley maneuver were negative in both patients.</p> <p>Conclusion</p> <p>Radiologists and clinicians must keep in mind that after radiologic imaging in which the patient is still for some time in the supine position and then helped to stand up rapidly, a BPPV attack may occur.</p

Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling

Organoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and characterized the hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell (iPSC)-derived EpCAM-positive endodermal cells as an intermediate. eHEPOs can be produced within 2 weeks and expanded long term (>16 months) without any loss of differentiation capacity to mature hepatocytes. Starting from patient-specific iPSCs, we modeled citrullinemia type 1, a urea cycle disorder caused by mutations in the argininosuccinate synthetase (ASS1) enzyme. The disease-related ammonia accumulation phenotype in eHEPOs could be reversed by the overexpression of the wild-type ASS1 gene, which also indicated that this model is amenable to genetic manipulation. Thus, eHEPOs are excellent unlimited cell sources to generate functional hepatic organoids in a fast and efficient manner

Controversies on electromagnetic field exposure and the nervous systems of children

This paper reviewed possible health effects from exposure to low levels of electromagnetic field (EMF) in children, arising from electrical power sources and mobile phones. Overall, the information about effects on developmental processes and cognitive functions is insufficient and further research on children and adolescents is critically needed. New research approaches are required focused on the effects on the developmental processes of children exposed to electromagnetic fields, using consistent protocols. When the current data were considered in detail, it was noted that children's unique vulnerabilities make them more sensitive to EMFs emitted by electronics and wireless devices, as compared to adults. Some experimental research shows a neurological impact and exposure in humans may lead to the cognitive and behavioral impairments. Because of the proliferation of wireless devices, public awareness of these dangers now is important to safeguard children’s future healthy brain development

A Novel Function for KLF4 in Modulating the De-Differentiation of EpCAM−/CD133− nonStem Cells into EpCAM+/CD133+ Liver Cancer Stem Cells in HCC Cell Line HuH7

The complex and heterogeneous nature of hepatocellular carcinoma (HCC) hampers the identification of effective therapeutic strategies. Cancer stem cells (CSCs) represent a fraction of cells within tumors with the ability to self-renew and differentiate, and thus significantly contribute to the formation and maintenance of heterogeneous tumor mass. Increasing evidence indicates high plasticity in tumor cells, suggesting that non-CSCs could acquire stem cell properties through de-differentiation or reprogramming processes. In this paper, we reveal KLF4 as a transcription factor that can induce a CSC-like phenotype in non-CSCs through upregulating the EpCAM and E-CAD expression. Our studies indicated that KLF4 could directly bind to the promoter of EpCAM and increase the number of EpCAM+/CD133+ liver cancer stem cells (LCSCs) in the HuH7 HCC cell line. When KLF4 was overexpressed in EpCAM&minus;/CD133&minus; non-stem cells, the expressions of hepatic stem/progenitor cell genes such as CK19, EpCAM and LGR5 were significantly increased. KLF4 overexpressing non-stem cells exhibited greater cell viability upon sorafenib treatment, while the cell migration and invasion capabilities of these cells were suppressed. Importantly, we detected an increased membranous expression and colocalization of &beta;-CAT, E-CAD and EpCAM in the KLF4-overexpressing EpCAM&minus;/CD133&minus; non-stem cells, suggesting that this complex might be required for the cancer stem cell phenotype. Moreover, our in vivo xenograft studies demonstrated that with a KLF4 overexpression, EpCAM&minus;/CD133&minus; non-stem cells attained an in vivo tumor forming ability comparable to EpCAM+/CD133+ LCSCs, and the tumor specimens from KLF4-overexpressing xenografts had increased levels of both the KLF4 and EpCAM proteins. Additionally, we identified a correlation between the KLF4 and EpCAM protein expressions in human HCC tissues independent of the tumor stage and differentiation status. Collectively, our data suggest a novel function for KLF4 in modulating the de-differentiation of tumor cells and the induction of EpCAM+/CD133+ LCSCs in HuH7 HCC cells

Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling

Organoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and characterized the hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell (iPSC)-derived EpCAM-positive endodermal cells as an intermediate. eHEPOs can be produced within 2 weeks and expanded long term (>16 months) without any loss of differentiation capacity to mature hepatocytes. Starting from patient-specific iPSCs, we modeled citrullinemia type 1, a urea cycle disorder caused by mutations in the argininosuccinate synthetase (ASST) enzyme. The disease-related ammonia accumulation phenotype in eHEPOs could be reversed by the overexpression of the wild-type ASS1 gene, which also indicated that this model is amenable to genetic manipulation. Thus, eHEPOs are excellent unlimited cell sources to generate functional hepatic organoids in a fast and efficient manner

A Novel Function for KLF4 in Modulating the De-Differentiation of EpCAM(-)/CD133(-) nonStem Cells into EpCAM(+)/CD133(+) Liver Cancer Stem Cells in HCC Cell Line HuH7

The complex and heterogeneous nature of hepatocellular carcinoma (HCC) hampers the identification of effective therapeutic strategies. Cancer stem cells (CSCs) represent a fraction of cells within tumors with the ability to self-renew and differentiate, and thus significantly contribute to the formation and maintenance of heterogeneous tumor mass. Increasing evidence indicates high plasticity in tumor cells, suggesting that non-CSCs could acquire stem cell properties through de-differentiation or reprogramming processes. In this paper, we reveal KLF4 as a transcription factor that can induce a CSC-like phenotype in non-CSCs through upregulating the EpCAM and E-CAD expression. Our studies indicated that KLF4 could directly bind to the promoter of EpCAM and increase the number of EpCAM(+)/CD133(+) liver cancer stem cells (LCSCs) in the HuH7 HCC cell line. When KLF4 was overexpressed in EpCAM(-)/CD133(-) non-stem cells, the expressions of hepatic stem/progenitor cell genes such as CK19, EpCAM and LGR5 were significantly increased. KLF4 overexpressing non-stem cells exhibited greater cell viability upon sorafenib treatment, while the cell migration and invasion capabilities of these cells were suppressed. Importantly, we detected an increased membranous expression and colocalization of beta -CAT, E-CAD and EpCAM in the KLF4-overexpressing EpCAM(-)/CD133(-) non-stem cells, suggesting that this complex might be required for the cancer stem cell phenotype. Moreover, our in vivo xenograft studies demonstrated that with a KLF4 overexpression, EpCAM(-)/CD133(-) non-stem cells attained an in vivo tumor forming ability comparable to EpCAM(+)/CD133(+) LCSCs, and the tumor specimens from KLF4-overexpressing xenografts had increased levels of both the KLF4 and EpCAM proteins. Additionally, we identified a correlation between the KLF4 and EpCAM protein expressions in human HCC tissues independent of the tumor stage and differentiation status. Collectively, our data suggest a novel function for KLF4 in modulating the de-differentiation of tumor cells and the induction of EpCAM(+)/CD133(+) LCSCs in HuH7 HCC cells