bluuebunny/crossref_metadata_2025_split huggingface dataset:
Active form of vitamin D directly protects the blood–brain barrier in multiple sclerosis
Authors: Takahashi Shiori , Maeda Toshihiko , Sano Yasuteru , Nishihara Hideaki , Takeshita Yukio , Shimizu Fumitaka , Kanda Takashi 
Published: August 2017

AbstractObjectivesThe active form of vitamin D, 1α,25‐dihydroxyvitamin D3 (1α,25‐[OH]2D3), is reported to have protective effects for multiple sclerosis (MS), but the precise mechanisms of this effect on MS remain unclear. We hypothesized that 1α,25‐(OH)2D3 has protective effects on the blood–brain barrier (BBB) in MS.MethodsThe expression of vitamin D receptor in a human brain microvascular endothelial cell line (HBMEC) was examined. The effects of 1α,25‐(OH)2D3 on HBMEC after stimulation with tumor necrosis factor‐α were observed. In addition, we assessed the effects of sera from MS patients, including those in the acute and stable phase of relapse–remitting MS or secondary progressive MS, on the BBB property in the presence or absence of 1α,25‐(OH)2D3.ResultsHBMEC were found to express the vitamin D receptor at both the mRNA and protein level. Pretreatment of HBMEC with 1α,25‐(OH)2D3 attenuated the decrease of zonula occludens‐1 and claudin‐5, and the increase of intercellular adhesion molecule‐1 (ICAM‐1) induced by tumor necrosis factor‐α. In addition, nuclear factor kappa B activation mediated by tumor necrosis factor‐α was decreased after incubation with the activated vitamin D. Furthermore, incubation with 1α,25‐(OH)2D3 attenuated the increase of vascular cell adhesion molecule‐1 and anti‐phospho‐nuclear factor kappa B in HBMEC after exposure to sera from patients with relapse‐remitting MS and secondary progressive MS, and restored the decrease of zonula occludens‐1 and claudin‐5 in HBMEC after incubation with sera from the acute phase of relapse–remitting MS patients.ConclusionsTreatment with 1α,25‐(OH)2D3 prevents BBB disruption caused by both relapse–remitting MS and secondary progressive MS sera through upregulation of tight junction proteins and downregulation of cell adhesion molecules in HBMEC, suggesting that 1α,25‐(OH)2D3 might have the direct protective effects on the fragile BBB in MS patients.
Ethyl pyruvate does not require microglia for mediating neuroprotection after excitotoxic injury
Authors: Pieroh Philipp , Wagner Daniel‐Christoph , Ghadban Chalid , Birkenmeier Gerd , Dehghani Faramarz 
Published: August 2017

SummaryAimsEthyl pyruvate (EP) mediates protective effects after neuronal injury. Besides a direct conservation of damaged neurons, the modulation of indigenous glial cells has been suggested as one important mechanism for EP‐related neuroprotection. However, the specific contribution of glial cells is still unknown.MethodsOrganotypic hippocampal slice cultures (OHSC) were excitotoxically lesioned by 50 μmol/L N‐methyl‐D‐aspartate (NMDA, for 4 hours) or left untreated. In an additional OHSC subset, microglia was depleted using the bisphosphonate clodronate (100 μg/mL) before lesion. After removal of NMDA, EP containing culture medium (0.84 μmol/L, 8.4 μmol/L, 42 μmol/L, 84 μmol/L, 168 μmol/L) was added and incubated for 72 hours. OHSC were stained with propidium iodide to visualize degenerating neurons and isolectin IB4‐FITC to identify microglia. Effects of EP at concentrations of 0.84, 8.4, and 84 μmol/L (0‐48 hours) were analyzed in the astrocytic scratch wound assay.ResultsEP significantly reduced neurodegeneration following induced excitotoxicity except for 168 μmol/L. For 84 μmol/L, a reduction in the microglia cells was observed. Microglia depletion did not affect neuronal survival after EP treatment. EP decelerated astrocytic wound closure at 48 hours after injury.ConclusionEP‐mediated neuroprotection seems to be mediated by astrocytes and/or neurons.
A novel technique for enterotomy closure in stapled laparoscopic intracorporeal anastomosis
Authors: di Saverio S. , Birindelli A. , Segalini E. , Todero S. , Botusan R. A. , Novello M. , Kwan S. , Biondi A. 
Published: August 2017

AbstractAimThe proximal edge of the enterotomy in a side‐to‐side anastomosis has been shown to be the site at highest risk of leakage. Several methods have been described to overcome this vulnerability. The technical challenge of intra‐corporeal anastomosis (ICA) is to re‐create angles between tissues and instruments, similar to those in an open anastomosis. The axis between the suture line and the needle driver is paramount and this angle should be < 45°.MethodThe crotch stitch of the enterotomy is difficult because of the narrow space between the loops and the depth of the anastomosis. The usual technique is suturing right‐handed, ‘out–in and in–out’, colonic edge first to small bowel. The risk of suture misplacement (e.g. ‘out–in/out–in’ or ‘out–out’) is similar to open procedures but laparoscopically the second bite is challenging, due to the straight needle‐driver. This may lead to asymmetrical closure of the corner resulting in a slightly larger angle on the bowel side and a potential postoperative leak/fistula. Rotating the small bowel loop to counterbalance this issue, risks tearing of the staple line. The rationale is that starting with a back‐handed stitch and taking the small bowel edge first would allow the necessary acute angled bite to be achieved. Subsequently, mounting the needle right‐handed for taking the colonic edge also allows achievement of an acute angled bite.ResultsOur novel technique, named the ‘back‐handed, left‐to‐right stitch’ technique, is intended to achieve symmetrical approximation of the ileal and colonic edges during laparoscopy, with an optimal closure of the deepest extremity of the enterotomy. Such a stitch, used in a series of 10 patients, may be useful to avoid leaving an opening within this angle and/or to avoid potential technical pitfalls when closing the deepest apex of the enterotomy.ConclusionThis ‘back‐handed, left‐to‐right’ stitch described here allows a properly angled closure of the proximal edge of the enterotomy and a safe approximation of the corner of the enterotomy in a side‐to‐side ICA.
Immune roles of dendritic cells in stem cell transplantation
Authors: Zhang Cheng , Liao Wenwei , Liu Furong , Zhu Xiaofeng , He Xiaoshun , Hu Anbin 
Published: August 2017

AbstractDendritic cells (DCs) are professional antigen‐presenting cells and initial stimulators for immune response. DCs can shape their functions based on their immune states, which are crucial for the balance of immunity and tolerance to preserve homeostasis. In the immune response involved in stem cell transplantation, DCs also play important roles in inducing immune tolerance and antitumor immunity. After the rapid development of stem cell transplantation technology in recent years, the risks of graft rejection, tumor recurrence, and tumorigenicity are still present after stem cell transplantation. It is important to understand the mechanisms of DC‐mediated immune tolerance and stimulation during stem cell transplantation. In this review, we will summarize and analyze the regulatory mechanisms of DCs in stem cell transplantation and their application in clinical settings. It may help to promote the innovation in basic theories and therapeutic approaches of stem cell transplantation.
Ralstonia solanacearum decreases volumetric growth of trees and yield of kraft cellulose of Eucalyptus spp.
Authors: Ferreira M. A. , Mafia R. G. , Alfenas A. C. 
Published: August 2017

SummaryRalstonia solanacearum is currently one of the most important plant pathogenic bacteria worldwide, with a wide geographical distribution and host diversity. The pathogen infects more than 200 plant species belonging to approximately 50 plant families, including Eucalyptus spp. Although, high losses have been reported in nurseries, little is known on the negative impact of the disease in the field. In this study, we evaluated the incidence of R. solanacearum and its effect on volumetric growth and cellulose yield of discoloured wood chips obtained from infected trees of one clone of Eucalyptus urophylla and two hybrid clones of Eucalyptus urophylla × E. grandis. The average incidence of bacterial wilt ranged between 60.6% and 72.4%. Volumetric growth of infected trees disease decreased 78.6% and 81.7% at 18 and 30 months, respectively. The pulp screen yield of three clones decreased between 3.2 and 6.4%, with an average 4.3%. The results of this work provide useful information on the losses of volumetric growth and pulp yield of eucalypt caused by R. solanacearum.
Early intervention for bipolar disorder in adolescents: A psychosocial perspective
Authors: McAulay Claire , Mond Jonathan , Touyz Stephen 
Published: August 2017

AimEarly intervention in bipolar disorder (BD) has received increasing attention in recent years. The identification of risk factors has improved, but researchers continue to struggle to find an effective treatment once the illness has become established. The aetiology of BD and feasibility of early intervention present a challenge, making it difficult to decide who to target, as well as how.MethodsThis essay seeks to address the lack of guidance for managing patients with a possible emerging bipolar illness, by presenting a rough roadmap to psychological care. The psychological techniques currently showing the most potential for this challenging group are reviewed. Markers of risk and supplementary clinical targets, such as anxiety and sleep disruption, are also discussed.ResultsWhile research in this group remains in its infancy, various avenues of enquiry show promise, such as family‐based approaches, CBT that targets features beyond the core illness, psychoeducation, and interventions that consider physical health. However, clearer pathways for establishing the course and stage of the illness are required to inform the intensity and type of treatment.ConclusionIt is argued that treating early, indistinct symptoms of psychological distress, that may or may not signify prodromal BD, is valuable beyond its utility as an early intervention tool, as it has the capacity to improve help‐seeking behaviour, quality of life and the likelihood of functional recovery in those who go on to develop the illness as adults.
Clinical relevance of abnormal neuroimaging findings and long‐term risk of stroke recurrence
Authors: Nam K.‐W. , Kwon H.‐M. , Lim J.‐S. , Han M.‐K. , Lee Y.‐S. 
Published: August 2017

Background and purposePrevious studies have revealed that the predictors of short‐ and long‐term stroke recurrence are different. We designed a comprehensive stroke recurrence (CSR) model, composed of demographic, clinical and radiological findings, to predict long‐term ischaemic stroke recurrences.MethodsWe retrospectively collected the derivation cohort from consecutive patients with first‐ever ischaemic stroke within 7 days of symptom onset. Univariate and multivariable Cox regression analysis were used to evaluate the association between 2‐year recurrence and demographic, clinical and neuroradiological factors. The CSR score was calculated by adding the integer value of independent predictors that was derived from the β‐coefficient in the multivariable analysis. To qualify the model, we analyzed the receiver operating characteristics curve. We assessed internal validation with bootstrap methods and assessed external validation with another independent cohort.ResultsA total of 958 patients were enrolled, and 63 patients had recurrent strokes during the follow‐up periods. The rate of stroke recurrence was 7.0% at 2 years. In the multivariable analysis, multiple stage lesions, isolated cortical lesions on diffusion‐weighted imaging, severe white matter hyperintensities, multiple lacunar infarctions and relevant arterial stenosis were independently associated with stroke recurrence. The CSR model showed good discrimination [area under the curve (AUC), 0.81 (0.74–0.88)], which was consistent with internal [AUC, 0.75 (0.66–0.85)] and external [AUC, 0.80 (0.69–0.90)] validation.ConclusionsAbnormal neuroimaging findings, rather than cardiovascular risk factors, are predictive of long‐term ischaemic stroke recurrence. Causative mechanism of stroke and underlying hostile brain milieu seem to be associated with long‐term stroke recurrence.
Treatment with lacosamide impedes generalized seizures in a rodent model of cortical dysplasia
Authors: Nemes Ashley D. , O'Dwyer Rebecca , Najm Imad M. , Ying Zhong , Gonzalez‐Martinez Jorge , Alexopoulos Andreas V. 
Published: August 2017

SummaryObjectiveEpilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30–40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD). We sought to compare LCM to levetiracetam (LEV), a drug that is currently used for the treatment of both partial and generalized epilepsy and to test its proficiency.MethodsPregnant rats were irradiated to produce pups with malformed cortices in a model of CD, which will be referred to as the “first hit.” Adult animals, developed normally (NL) and irradiated (XRT), were surgically implanted with electroencephalography (EEG) electrodes. Baseline EEG was recorded on all rats prior to pretreatments with either LCM, LEV, or placebo (PBO). After 30 min, all rats were injected with a subconvulsive dose of pentylenetetrazole (PTZ), a γ‐aminobutyric acid receptor A (GABAA) antagonist used to provoke generalized seizures as a “second hit.”ResultsLCM and LEV were both effective against seizures induced by PTZ. XRT rats had a higher seizure incidence with longer and more severe seizures than NL rats. Seizure duration was decreased with both LCM and LEV in all animals. In XRT rats, there was a significant reduction in acute seizure incidence and severity with both LCM and LEV after PTZ injection.SignificanceOur results suggest that LCM could be used as a potential treatment option for generalized epilepsy with CD as the underlying pathology.
How to perform ovariectomy through a colpotomy
Authors: Prado T. , Schumacher J. 
Published: August 2017

SummaryBilateral ovariectomy of mares is performed most commonly to eliminate or diminish unwanted behaviour, create a teaser mare, sterilise a mare so that it can be registered in its breed association, or produce a recipient mare for embryo transfer. A practical technique of bilateral ovariectomy that can be easily performed without the mare sedated and without a surgical facility is ovariectomy through a colpotomy. Ovariectomy through a colpotomy is less expensive than ovariectomy using other approaches because it is performed with the mare standing, can be performed quickly and the only specialised instrument required is a chain écraseur. Complications of ovariectomy performed through a colpotomy are uncommon when the mare is correctly prepared for the procedure and when proper precautions are taken during and after the procedure.
Towards the development of a RNAi‐based topical treatment for psoriasis: Proof‐of‐concept in a 3D psoriasis skin model
Authors: Desmet Eline , Van Gele Mireille , Grine Lynda , Remaut Katrien , Lambert Jo 
Published: August 2017

Abstract
RNA interference has emerged as a powerful tool for therapeutic gene silencing, as it offers the possibility to silence virtually any known pathology‐causing gene. However, in vivo delivery of RNAi molecules is hampered by their unfavourable physicochemical characteristics and susceptibility to degradation by endogenous enzymes. To overcome these limitations, we recently developed an elastic liposomal formulation, called DDC642, as topical delivery system of therapeutic RNAi molecules for skin disorders. In this study, we validated the therapeutic efficacy of DDC642‐encapsulated RNAi molecules in the treatment of psoriasis using 3 different in vitro models: a standardized keratinocyte monolayer culture, psoriasis‐induced keratinocytes and a psoriasis‐reconstructed skin model. Four genes (IL22RA1, KRT17, DEFB4 and TSLP), known to be upregulated in psoriatic lesions, and thereby key players in psoriasis pathogenesis were selected. Moreover, the possibility of using a combined siRNA therapy in the topical treatment of psoriasis was explored. Results indicate a successful gene silencing of each different target, both at mRNA and protein levels. Additionally, siRNA‐DDC642 treatment resulted in a reduced expression of specific psoriasis markers, indicating their potential in future therapeutic approach. The examined siRNA combination (ie simultaneous knockdown of KRT17, DEFB4 and TSLP) showed an enhanced reduction in TSLP expression, whereas the decrease in K17 protein expression was impaired in psoriatic keratinocytes. Although the here examined siRNA combination could still be further improved, our study proved already in vitro the clinical potential of targeting multiple genes at once, each playing a different role in a complex disease such as psoriasis.
In vitro and in vivo models to investigate the pathomechanisms and novel treatments for pemphigoid diseases
Authors: Bieber Katja , Koga Hiroshi , Nishie Wataru 
Published: August 2017

AbstractPemphigoid diseases (PD) are a subgroup of rare acute or chronic autoimmune skin disorders characterized and caused by autoantibodies directed against distinct structural components of the dermal‐epidermal junction. Binding of autoantibodies to their targets leads to the formation of blisters and erosions in patients.PDs comprise eight disorders for which the molecular target antigens have been identified. First, we review the available in vitro and ex vivo models for analysis of distinct aspects of the pathogenesis ofPDs. This includes the binding of autoantibodies to skin sections, the analysis of blister formation capability and skin complement activation as well as investigation of neutrophil and keratinocyte activation. In addition to this, several animal models ofPDhave been developed during the last decades. These animal models have greatly contributed to our current understanding of the pathogenesis ofPDs. We summarize spontaneously arisingPDin animals and the induction ofPDby transfer of (auto)antibodies, transfer of (auto)‐antigen‐specific lymphocytes and by immunization. In combined use, these models allow dissecting all aspects ofPDpathogenesis, for example loss of tolerance, autoantibody production and inflammatory skin processes that lead to blister formation. Overall, we aimed to foster translational biomedical research, to deepen our understanding ofPDpathogenesis and to develop novel treatments for patients suffering from these life‐threatening and difficult‐to‐treat autoimmune diseases.
Cytotoxic antimelanoma drugs suppress the activation of M2 macrophages
Authors: Fujimura Taku , Kakizaki Aya , Kambayashi Yumi , Sato Yota , Tanita Kayo , Lyu Chunbing , Furudate Sadanori , Aiba Setsuya 
Published: August 2017

AbstractTogether with regulatory T cells (Tregs), tumor‐associated macrophages (TAMs) play roles in maintaining the tumor microenvironment. Although cytotoxic antimelanoma drugs such as dacarbazine (DTIC), nimustine hydrochloride (ACNU) and vincristine (VCR) have been used for the treatment of malignant melanoma as adjuvant therapy in Japan, the detailed mechanisms of their immunomodulatory effects are not fully understood. As the majority of TAMs are alternatively activated M2 macrophages that favour tumor development, the aim of this study was to elucidate the immunomodulatory effects of these reagents on human monocyte‐derived M2 macrophages. First, mRNA expressions and protein production of immune checkpoint molecules, PD‐L1 and chemokines by CD163+ CD206+ M2 macrophages derived from peripheral blood mononuclear cells were investigated to determine the immunomodulatory effects of DTIC, ACNU, and VCR. DTIC and VCR significantly decreased PD‐L1 mRNA expression, which was confirmed by flow cytometry. Moreover, the mRNA expression and production of CCL22 were significantly decreased by DTIC, which suggested that DTIC might suppress the recruitment of Tregs in the tumor site. Furthermore, the decreased expression of PD‐L1 and production of CCL22 were validated in vivo, using the B16F10 mouse melanoma model, leading to abrogation of the suppressive function of T‐cell proliferation. The present report suggests one of the possible antimelanoma mechanisms of DAV combination chemotherapy for melanoma patients.
Regression of diffuse B‐cell lymphoma of the leg with intralesional gentian violet
Authors: Rao Shikha , Morris Robert , Rice Zakiya P. , Arbiser Jack L. 
Published: August 2017

AbstractIn this case report, a patient of primary cutaneous diffuse B‐cell lymphoma, leg type was treated with intralesional gentian violet as she was judged to be too medically fragile for conventional chemotherapy due to advanced age and multiple serious comorbidities. Gentian violet (crystal violet/hexamethyl pararosaniline) is a triphenylmethane dye. It has been shown to have an inhibitory effect on NADPH oxidase, an enzyme family which is found in abundance in reactive oxygen‐driven tumors such as melanoma and lymphoma. We hypothesize that intralesional gentian violet treatment caused signalling changes in the lymphoma which allowed for immune clearance of the lymphoma. Complete resolution of the patient's lesion was noted on a follow‐up visit.
High expression of B lymphocyte stimulator in lesional keratinocytes of patients with cutaneous lupus erythematosus
Authors: Wenzel Joerg , Landmann Aysche , Vorwerk Gero , Kuhn Annegret 
Published: August 2017

AbstractBelimumab, an anti‐B lymphocyte stimulator (BLyS) monoclonal antibody, is approved for systemic lupus erythematosus; however, it is unclear if it can be used to treat specific skin lesions in this disease. In this analysis, we investigated the expression of BLyS and its receptors in skin lesions of different subtypes of cutaneous lupus erythematosus (CLE) using immunohistochemistry and gene expression analyses. Compared to healthy controls, the expression of BLyS was significantly higher in skin lesions of all included CLE subtypes. Similar results were seen for the BLyS receptors BAFF‐R and BCMA. Moreover, CLE‐typical pro‐inflammatory mediators (immunostimulatory DNAs) significantly enhanced the BLyS expression of keratinocytes in vitro. This study suggests a potential role for BLyS as therapeutic target in the treatment of CLE skin lesions.
Overexpression of p53 explains isotretinoin's teratogenicity
Authors: Melnik Bodo C. 
Published: August 2017

AbstractThe precise molecular basis of retinoid embryopathy is yet unknown. This hypothesis predicts that isotretinoin (13‐cis retinoic acid), the prodrug of all‐trans retinoic acid (ATRA), exaggerates neural crest cell (NCC) apoptosis via upregulation of the pro‐apoptotic transcription factor p53, the guardian of the genome. Increased p53 signalling is associated with Treacher Collins‐, CHARGE‐ and fetal alcohol syndrome, which exhibit dysmorphic craniofacial features resembling retinoid embryopathy. In addition, developmental studies of NCC homeostasis in the zebrafish support the pivotal role of p53. Translational evidence implies that isotretinoin‐stimulated overactivation of p53 during embryogenesis represents the molecular basis of isotretinoin′s teratogenicity.