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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 | Antimicrobial susceptibility testing before first-line treatment for Helicobacter pylori infection in patients with dual or triple antibiotic resistance显示文摘AIM To evaluate the efficacy of antimicrobial susceptibilityguided therapy before first-line treatment for infection in patients with dual or triple antibiotic resistance.METHODS A total of 1034 patients infected by Helicobacter pylori(H. pylori) during 2013-2014 were tested for antimicrobial susceptibility. 157 of 1034(15%) patients showed resistance to two(127/1034; 12%) and to three(30/1034; 3%) antibiotics. Sixty-eight patients with dual H. pylori-resistance(clarithromycin, metronidazole or levofloxacin) were treated for 10 d with triple therapies: OAL(omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and levofloxacin 500 mg b.i.d.) 43cases, OAM(omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg b.i.d.) 12 cases and OAC(omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.) 13 cases based on the antimicrobial susceptibility testing. Twelve patients showed triple H. pylori-resistance(clarithromycin, metronidazole and levofloxacin) and received for 10 d triple therapy with OAR(omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and rifabutin 150 mg b.i.d.). Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire. RESULTS Intention-to-treat eradication rates were: OAL(97.6%), OAM(91.6%), OAC(92.3%) and OAR(58.3%). Cure rate was significantly higher in na?ve patients treated with OAR-10 compared to patients who had two or three previous treatment failures(83% vs 33%). Adverse events rates for OAL, OAM, OAC and OAR were 22%, 25%, 23% and 17%, respectively, all of them mild-moderate. CONCLUSION Antimicrobial susceptibility-guided triple therapies during 10 d for first-line treatment leads to an eradication rate superior to 90% in patients with dual antibiotic H. pylori resistance. | Angel Cosme Milagrosa Montes Begona Ibarra Esther Tamayo Horacio Alonso Usua Mendarte Jacobo Lizasoan Marta Herreros-Villanueva Luis Bujanda | 2017 | World Journal of Gastroenterology2017，23，18： | 4 |
| 3 | Long-term follow-up of patients undergoing adipose-derived adult stem cell administration to treat complex perianal fistulas显示文摘 | Hector Guadalajara Dolores Herreros Paloma De-La-Quintana Jacobo Trebol Mariano Garcia-Arranz Damian Garcia-Olmo | 2012 | International Journal of Colorectal Disease2012，，5： | 3 |
| 4 | Heart rate variability to assess ventilatory thresholds in professional basketball players显示文摘Purpose: The aim of this study was to determine if heart rate variability(HRV) during incremental test could be used to estimate ventilatory threshold(VT) in professional basketball players, with sufficient precision to be used in their training. Furthermore, the second aim was to analyse the association between HRV and 3 methods of VT determination by gas analysis.Methods: Twenty-four professional basketball players(age: 23.4 ± 4.9 years; height: 195.4 ± 9.8 cm; body mass: 92.2 ± 11.9 kg) performed an incremental running test to exhaustion. First ventilatory threshold(VT1) was determined by ventilatory equivalent(VE) and HRV and second ventilatory threshold(VT2) was determined by 3 methods of gases analysis(V-slope, VE and gas exchange ratio(R), and HRV). Pearson's coefficient(r) was used to detect differences between data and the strength of each relationship. The mean of absolute differences and Bland–Altman analysis were used to evaluate whether there was agreement.Results: The results showed no significant differences in HR and oxygen consumption(VO2) at VT1 between the 2 methods. Furthermore, no significant differences among the methods of gases analysis and HRV were observed in speed, HR, and VO2 at VT2. Moreover, VTs estimated using HRV and gas methods were significantly correlated. Correlation in HR values was higher between R and HRV(r = 0.96) and VE and HRV(r = 0.96) than V-slope and HRV(r = 0.90).Conclusion: These findings provide a practical, inexpensive approach for evaluating specific training loads when determining VT2 in basketball players. Therefore, HRV is an alternative method to determine VT2 without the application of expensive technology that limits its use to laboratories. | Domingo Jesús Ramos-Campo Jacobo A. Rubio-Arias Vicente Avila-Gandia Cristian Marin-Pagan Antonio Luque Pedro E. Alcaraz | 2017 | Journal of Sport and Health Science2017，6，4： | 3 |
| 5 | Phylogeography of SARS-CoV-2 pandemic in Spain:a story of multiple introductions,micro-geographic stratification,founder effects,and super-spreaders显示文摘Spain has been one of the main global pandemic epicenters for coronavirus disease 2019(COVID-19).Here,we analyzed>41000 genomes(including>26000 high-quality(HQ)genomes)downloaded from the GISAID repository,including 1245(922 HQ)sampled in Spain.The aim of this study was to investigate genome variation of novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and reconstruct phylogeographic and transmission patterns in Spain.Phylogeographic analysis suggested at least 34 independent introductions of SARS-CoV-2 to Spain at the beginning of the outbreak.Six lineages spread very successfully in the country,probably favored by super-spreaders,namely,A2 a4(7.8%),A2 a5(38.4%),A2 a10(2.8%),B3 a(30.1%),and B9(8.7%),which accounted for 87.9% of all genomes in the Spanish database.One distinct feature of the Spanish SARS-Cov-2 genomes was the higher frequency of B lineages(39.3%,mainly B3 a+B9)than found in any other European country.While B3 a,B9,(and an important sub-lineage of A2 a5,namely,A2 a5 c)most likely originated in Spain,the other three haplogroups were imported from other European locations.The B3 a strain may have originated in the Basque Country from a B3 ancestor of uncertain geographic origin,whereas B9 likely emerged in Madrid.The time of the most recent common ancestor(TMRCA)of SARS-CoV-2 suggested that the first coronavirus entered the country around 11 February 2020,as estimated from the TMRCA of B3 a,the first lineage detected in the country.Moreover,earlier claims that the D614 G mutation is associated to higher transmissibility is not consistent with the very high prevalence of COVID-19 in Spain when compared to other countries with lower disease incidence but much higher frequency of this mutation(56.4% in Spain vs.82.4% in rest of Europe).Instead,the data support a major role of genetic drift in modeling the micro-geographic stratification of virus strains across the country as well as the role of SARS-CoV-2 super-spreaders. | Alberto Gomez-Carballa Xabier Bello Jacobo Pardo-Seco Maria Luisa Perez del Molino Federico Martinon-Torres Antonio Salas | 2020 | Zoological Research2020，41，6： | 3 |
| 6 | 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 |
| 7 | 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 |
| 8 | Solid-phase microextraction method for the determination of volatile compounds associated to oxidation of fish muscle显示文摘 | Jacobo Iglesias Isabel Medina | 2008 | Journal of Chromatography A2008，，1： | 2 |
| 9 | Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress显示文摘 | Andrzej Slominski Jacobo Wortsman Thomas Luger | 2000 | Physiol Rev2000，80，： | 1 |
| 10 | Solid-phase mieroextraction method for the determination of volatile compounds associated to oxidation of fish nmscle显示文摘 | Jacobo Iglesias Isabel Medina | 2008 | Journal of Chromatography A2008，1192，1： | 1 |
| 11 | Influence of the iron content on the formation process of substituted Co–Nd strontium hexaferrite prepared by the citrate precursor method显示文摘 | S.E. Jacobo C. Herme P.G. Bercoff | 2009 | Journal of Alloys and Compounds2009，，2： | 1 |
| 12 | Large-scale simulation of elastic wave propagation in heterogeneous media on parallel computers显示文摘 | Hesheng Bao Jacobo Bielak Omar Ghattas Loukas F. Kallivokas David R. O’Hallaron Jonathan R. Shewchuk Jifeng Xu | 1998 | Computer Methods in Applied Mechanics and Engineering1998，，1： | 1 |
| 13 | Composite of polyaniline containing iron oxide 显示文摘 | Aphesteguy J C Jacobo S E | 2004 | Physica B: Condensed matter2004，354，14： | 1 |
| 14 | Molecular Pathology of Soft Tissue and Bone Tumors:A Review显示文摘 | Andrzej S Jacobo W Andrew C | 1999 | Arch Pathol Lab Med1999，123，： | 1 |
| 15 | The influence of Nd–Co substitution on the magnetic properties of non-stoichiometric strontium hexaferrite nanoparticles显示文摘 | P.G. Bercoff C. Herme S.E. Jacobo | 2009 | Journal of Magnetism and Magnetic Materials2009，，14： | 1 |
| 16 | Ionic imprinted polymer for nickel recognition by using the bi-functionalized 5-vinyl-8-hydroxyquinoline as a monomer:Application as a new solid phase extraction support显示文摘 | JACOBO O R | 2009 | Microchemical Journal2009，93，2： | 1 |
| 17 | Potential interation of troglitazone and cyclosprine显示文摘 | kalan B friedman G Jacobos M | 1998 | Transplantation1998，2765，10： | 1 |
| 18 | 显示文摘 | Terzzodi M C Duhalde S Jacobo S | 2004 | J Alloys Compds2004，369，： | 1 |
| 19 | CD4^+ and CD8^+ T cells producing Th1 and Th17 cytokines are involved in the pathogene- sis of autoimmune orchitis 显示文摘 | Jacobo P Perez CV Theas MS | 2011 | Reproduction2011，141，2： | 1 |
| 20 | Treatment of enterocutaneous fistula in Crohn’s Disease with adipose-derived stem cells: a comparison of protocols with and without cell expansion显示文摘 | Damian Garcia-Olmo Dolores Herreros Maria Pascual Isabel Pascual Paloma De-La-Quintana Jacobo Trebol Mariano Garcia-Arranz | 2009 | International Journal of Colorectal Disease2009，，1： | 1 |
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