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| 1 | Stem cell therapy for faecal incontinence: Current state and future perspectives显示文摘Faecal continence is a complex function involving different organs and systems. Faecal incontinence is a common disorder with different pathogeneses, disabling consequences and high repercussions for quality of life. Current management modalities are not ideal, and the development of new treatments is needed. Since 2008, stem cell therapies have been validated, 36 publications have appeared(29 in preclinical models and seven in clinical settings), and six registered clinical trials are currently ongoing. Some publications have combined stem cells with bioengineering technologies. The aim of this review is to identify and summarise the existing published knowledge of stem cell utilization as a treatment for faecal incontinence. A narrative or descriptive review is presented. Preclinical studies have demonstrated that cellular therapy, mainly in the form of local injections of muscle-derived(muscle derived stem cells or myoblasts derived from them) or mesenchymal(bone-marrow-or adipose-derived) stem cells, is safe. Cellular therapy has also been shown to stimulate the repair of both acute and subacute anal sphincter injuries, and some encouraging functional results have been obtained. Stem cells combined with normal cells on bioengineered scaffolds have achieved the successful creation and implantation of intrinsically-innervated anal sphincter constructs. The clinical evidence, based on adipose-derived stem cells and myoblasts, is extremely limited yet has yielded some promising results, and appears to be safe. Further investigation in both animal models and clinical settings is necessary to drawing conclusions. Nevertheless, if the preliminary results are confirmed, stem cell therapy for faecal incontinence may well become a clinical reality in the near future. | Jacobo Trébol Ana Carabias-Orgaz Mariano García-Arranz Damián García-Olmo | 2018 | World Journal of Stem Cells2018，10，7： | 4 |
| 2 | Human immunodeficiency virus type-1 induces a regulatory B cell-like phenotype in vitro显示文摘Individuals infected with human immunodeficiency virus type-1(HIV-1)usually show a general dysregulation and hyper-activation of the immune system.A direct influence of HIV-1 particles on B-cell phenotypes and functions has been previously described.However,the consequences of B-cell dysregulation are still poorly understood.We evaluated the phenotypic changes in primary B cells after direct contact with HIV-1 particles in comparison with different types of stimuli.The functionality of treated B cells was challenged in co-culture experiments with autologous CD4+and CD8+T cells.We demonstrated that HIV-1 induces a phenotypic change in B cells towards a regulatory B-cell phenotype,showing a higher level of IL-10,TGF-β1,EBI3 or IL-12(p35)mRNA expression and acquiring an immunosuppressive profile.The acquisition of a Breg phenotype was confirmed by co-culture experiments where HIVtreated B cells reduced the proliferation and the TNFαproduction of CD4+or CD8+T cells.This suppressive ability of HIV-treated B cells was dependent on cell-to-cell contact between these B cells and effector cells.To our knowledge,these data provide the first evidence that HIV-1 can directly induce a regulatory B cell-like immunosuppressive phenotype,which could have the ability to impair specific immune responses.This dysregulation could constitute one of the mechanisms underlying unsuccessful efforts to develop an efficient vaccine against HIV-1. | Jacobo Lopez-Abente Adrián Prieto-Sanchez Maria-Ángeles Muñoz-Fernandez Rafael Correa-Rocha Marjorie Pion | 2018 | Cellular & Molecular Immunology2018，15，10： | 2 |
| 3 | Rat model of anal sphincter injury and two approaches for stem cell administration显示文摘AIM To establish a rat model of anal sphincter injury and test different systems to provide stem cells to injured area.METHODS Adipose-derived stem cells(ASCs) were isolated from BDIX rats and were transfected with green fluorescent protein(GFP) for cell tracking. Biosutures(sutures covered with ASCs) were prepared with 1.5 × 10~6 GFPASCs, and solutions of 10~6 GFP-ASCs in normal saline were prepared for injection. Anorectal normal anatomy was studied on Wistar and BDIX female rats. Then, we designed an anal sphincter injury model consisting of a 1-cm extra-mucosal miotomy beginning at the anal verge in the anterior middle line. The sphincter lesion was confirmed with conventional histology(hematoxylin and eosin) and immunofluorescence with 4', 6-diamidino-2-phenylindole(commonly known as DAPI), GFP and α-actin. Functional effect was assessed with basal anal manometry, prior to and after injury. After sphincter damage, 36 BDIX rats were randomized to three groups for:(1) Cell injection without repair;(2) biosuture repair; and(3) conventional suture repair and cell injection. Functional and safety studies were conducted on all the animals. Rats were sacrificed after 1, 4 or 7 d. Then, histological and immunofluorescence studies were performed on the surgical area.RESULTS With the described protocol, biosutures had been covered with at least 820000-860000 ASCs, with 100% viability. Our studies demonstrated that some ASCs remained adhered after suture passage through the muscle. Morphological assessment showed that the rat anal anatomy is comparable with human anatomy; two sphincters are present, but the external sphincter is poorly developed. Anal sphincter pressure data showed spontaneous, consistent, rhythmic anal contractions, taking the form of 'plateaus' with multiple twitches(peaks) in each pressure wave. These basal contractions were very heterogeneous; their frequency was 0.91-4.17 per min(mean 1.6980, SD 0.57698), their mean duration was 26.67 s and mean number of peaks was 12.53. Our morphological assessment revealed that with the aforementioned surgical procedure, both sphincters were completely sectioned. In manometry, the described activity disappeared and was replaced by a gentle oscillation of basal line, without a recognizable pattern. Surprisingly, these findings appeared irrespective of injury repair or not. ASCs survived in this potentially septic area for 7 d, at least. We were able to identify them in 84% of animals, mainly in the muscular section area or in the tissue between the muscular endings. ASCs formed a kind of 'conglomerate' in rats treated with injections, while in the biosuture group, they wrapped the suture. ASCs were also able to migrate to the damaged zone. No relevant adverse events or mortality could be related to the stem cells in our study. We also did not find unexpected tissue growths. CONCLUSION The proposed procedure produces a consistent sphincter lesion. Biosutures and injections are suitable for cell delivery. ASCs survive and are completely safe in this clinical setting. | Jacobo Trébol Tihomir Georgiev-Hristov Luz Vega-Clemente Ignacio García-Gómez Ana Carabias-Orgaz Mariano García-Arranz Damián García-Olmo | 2018 | World Journal of Stem Cells2018，10，1： | 2 |
| 4 | Purgin II, a resin glycoside ester-type dimer and inhibitor of multidrug efflux pumps from ipomoea purga 显示文摘 | Castaneda-Gomez J Figueroa-Gonzalez G Jacobo N | 2013 | J Nat Prod2013，76，： | 1 |
| 5 | Improved optimization formulations for launching nose of incrementally launched prestressed concrete bridges显示文摘 | ARTURO N F JACOBO M D AITOR B | 2011 | Journal of Bridge Engineering2011，16，3： | 1 |
| 6 | Contemporary Sediment-Transport Processes in Submarine Canyons显示文摘 | Pere Puig Albert Palanques Jacobo Martín | 2014 | Annual Review of Marine Science2014，，： | 1 |
| 7 | Percutaneous laser nucleolysis of the intervertebral lumbar disc显示文摘 | Jacobo N | 1997 | Clin Orthop1997，337，： | 1 |
| 8 | Neural activity associated with metaphor comprehension: spatial analysis显示文摘 | María Sotillo Luis Carretié José A. Hinojosa Manuel Tapia Francisco Mercado Sara López-Martín Jacobo Albert | 2004 | Neuroscience Letters2004，，1： | 1 |
| 9 | NF-kappa B modulators from Vnleriana officinalis显示文摘 | Jacobo Herrera N J Vartiainen N Bremner P | 2006 | Phytother Res2006，20，10： | 1 |
| 10 | Towards newformulations for journal bearing alloys 显示文摘 | BRAVO A E DURáN H A JACOBO V H | 2013 | Wear2013，302，： | 1 |
| 11 | Factors affecting the abandonment of breastingfeeding in a support program for the same in the hospital for women, Morelia michoacan in the period from September to November 2014显示文摘 | M6ndez Jacobo N Garcfa Rojas Vazquez L E Reyes Barretero DY | 2015 | Nutr Hosp2015，32，6： | 1 |
| 12 | 水光互映——西班牙马尔贝拉私宅显示文摘项目是位于阳光海岸波多黎各巴努斯郊区的一栋独户住宅,它背靠大山,临近海岸,拥有大量地中海植被。由于其特殊的地理位置,决定了房子的设计必须适宜于周边环境,且能观赏到地中海的美景,这两点要求都在设计中都得以实现。项目的设计分为三个层次:一层是最大的公共空间,包括客厅、厨房、餐厅、洗衣室和一个小服务室。二层是最私人的空间,主要包括卧室和一个小办公室。地下一层是最休闲的空间,包括水疗区、室内泳池、健身房和车库。 | Joaquín Torres Rafael Llamazares Jacobo Espaa(Negami) | 2014 | 设计家2014，，6： | 0 |
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