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Umbilical cord as a mesenchymal stem cell source for treating joint pathologies

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World Journal of orthopedics 2011年第6期2卷 43-50页

作者： María Carmen Arufe Alexandre De la Fuente Isaac Fuentes Francisco javier De Toro Francisco javier Blanco Department of Medicine Area of Anatomy and Human EmbryologyCampus Oza s/nFac.of Health ScienceUniversity of A Coruna15006 A CorunaSpain osteoarticular and Aging Research Lab Cellular Therapy UnitINIBIC-CH Universitario A Coruna15006 A CorunaSpain Rheumatology Division INIBIC-CH Universitario A Coruna15006 A CorunaSpain Cathedra Bioiberica Universidad de A Coruna15006 A CorunaSpain CIBER-BBN-Instituto de Salud carlos III 15006 A CorunaSpain Centro de Investigacion Biomedica Hospital Universitario A CorunaC/Xubias 8415006 A CorunaSpain

Articular cartilage disorders and injuries often result in life-long chronic pain and compromised quality of ***,the regeneration of articular cartilage is a continuing challenge for biomedical *** of the most promising therapeutic approaches is cellbased tissue engineering,which provides a healthy population of cells to the injured site but requires differentiated chondrocytes from an uninjured *** use of healthy chondrocytes has been found to have limitations.A promising alternative cell population is mesenchymal stem cells(MSCs),known to possess excellent proliferation potential and proven capability for differentiation into ***“immunosuppressive”property of human MSCs makes them an important candidate for allogeneic cell *** use of allogeneic MSCs to repair large defects may prove to be an alternative to current autologous and allogeneic tissue-grafting *** allogeneic cell-based approach would enable MSCs to be isolated from any donor,expanded and cryopreserved in allogeneic MSC banks,providing a readily available source of progenitors for cell replacement *** possibilities have spawned the current exponential growth in stem cell research in pharmaceutical and biotechnology *** objective in this review is to summarize the knowledge about MSCs from umbilical cord stroma and focus mainly on their applications for joint pathologies.

关键词： Human Mesenchymal stem cell Umbilical cord Cartilage degeneration

Clival Salivary Heterotopia (Salivary Choristoma): A Rare Radiopathogical Lesión

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open Journal of Pathology 2022年第4期12卷 115-119页

作者： javier ortiz Juan carlos Paniagua Luis Chinchilla Enrique Montero Elisa Muñoz María Dolores Ludeña Dpto. de Biología Celular y Patología (Universidad de Salamanca) Servicio de Anatomía Patológica (Hospital Universitario de Salamanca) Salamanca Spain Servicio de Radiodiagnóstico (Hospital Universitario de Salamanca) Salamanca Spain

objective: To describe the radiological and pathological presentation of a salivary heterotopia in clivus. The lesion was detected incidentally in a 57-year-old woman. Material and Methods: Radiologic imaging (CT scan and MRI) and histological picture obtained from a clival lesion. Results: Radiologically the lesion presented as a well-limited lytic lesion with a diameter of 1.5 cm and accompanied by a cerebrospinal fluid secondary fistula. Histological examination revealed non-pathological salivary gland tissue. Conclusion: The differential diagnosis of this rare entity mandates a histological examination of the lesion.

关键词： Salivary Heterotopia Clivus

Paediatric non-alcoholic fatty liver disease: a more complex disease than in the adulthood?

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Hepatobiliary Surgery and Nutrition 2019年第3期8卷 270-273页

作者： María Teresa Arias-Loste Paula Iruzubieta javier Crespo Department of Gastroenterology and Hepatology University Hospital Marqués de ValdecillaSantanderSpain Investigation Institute Marques de valdecilla InfectionImmunity and Digestive Diseases GroupIDIVALSantanderSpain

While the association between obesity,type 2 diabetes(T2D)and the presence of steatosis has been established since the beginning of the last century(1),it was not until 1980 that the first references were made about a form of histologic liver lesion designated as non-alcoholic steatohepatitis(NASH).NASH is characterised by the presence of a variable degree of steatosis accompanied by lobular inflammatory infiltrate and hepatocellular damage with or without ***,the broader term of non-alcoholic fatty liver disease(NAFLD)was accepted,which more accurately encompass the entire spectrum of lesions that appear in these patients(2).Ever since then,NAFLD has become progressively the primary cause of chronic liver disease in developed countries(3).

关键词： liver NAFLD damage

Postoperative radiotherapy in resected non-small cell lung cancer:The never-ending story

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World Journal of Clinical oncology 2021年第10期12卷 833-844页

作者： javier Serrano Patricia Calvo Crespo Begoña Taboada Ana Alvarez Gonzalez Rafael Garcia García Antonio Gomez Caamaño Juan carlos Trujillo Reyes Xabier Mielgo-Rubio Felipe Couñago Department of Radiation Therapy Clinica Universidad de NavarraMadrid 28027Spain Department of Radiation oncology Hospital Clínico Universitario Santiago de CompostelaSantiago de Compostela 15706Spain Department of Radiation oncology HGU Gregorio MarañónMadrid 28007Spain Department of Radiation oncology Hospital Ruber InternacionalMadrid 28034Spain Department of Radiation oncology Hospital Clínico Universitario Santiago de CompostelaA Coruña 15706Spain Department of Thoracic Surgery Hospital de La Santa Creu I Sant PauBarcelona 08026Spain Department of Medical oncology Hospital Universitario Fundación AlcorcónMadrid 28922Spain Department of Radiation oncology Hospital Universitario Quirónsalud MadridHospital La LuzUniversidad Europea de MadridMadrid 28223Spain

This manuscript collects in a joint and orderly manner the existing evidence at the present time about postoperative treatment with radiotherapy in non-small cell lung *** also systematically reviews the current evidence,the international recommendations in the most relevant guidelines,the most controversial aspects in clinical and pathological staging,the specific technical aspects of radiotherapy treatment,and also collects all the potential risk factors that have been postulated as significant in the prognosis of these patients,evaluating the possibility of segmenting a particularly sensitive subpopulation with a high risk of relapse on which an adjuvant treatment with radiotherapy could have an impact on their clinical ***,currently active trials that aspire to provide more evidence on this topic are reviewed.

关键词： Non-small lung cancer Radiotherapy Postoperative Lung cancer

Clinical significance of occult hepatitis B virus infection

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World Journal of Gastroenterology 2011年第12期17卷 1549-1552页

作者： Miriam Romero Antonio Madejón Conrado Fernández-Rodríguez javier García-Samaniego Hepatology Unit Hospital Carlos ⅢCIBERehd28029 MadridSpain Service of Gastroenterology Hospital Universitario Fundación AlcorcónAv Budapest-128922 AlcorcónMadridSpain

occult hepatitis B virus(HBv) infection(oBI) is defined as the presence of HBv DNA in the liver(with or without detectable HBv DNA in serum) for individuals testing HBv surface antigen *** recently,the clinical effect of oBI was unclear on the progression of liver disease;on the development of hepatocellular carcinoma;and on the risk for reactivation or transmission of HBv *** studies suggest a high prevalence of oBI among patients with cryptogenic chronic liver disease,but its role in the progression to cirrhosis remains *** oBI has been well documented in human immunodeficiency virus(HIv) -positive patients,especially among those coinfected with hepatitis C virus,further studies are needed to determine its current clinical impact in HIv setting.

关键词： occult hepatitis B virus infection Liver dis-ease Cryptogenic cirrosis Hepatitis B virus coinfection Human immunodeficiency virus

Pharmacological inhibition of cannabinoid receptor 1 stimulates gastric release of nesfatin-1 via the mToR pathway

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World Journal of Gastroenterology 2017年第35期23卷 6403-6411页

作者： Cintia Folgueira Silvia Barja-Fernandez Laura Prado omar Al-Massadi Cecilia Castelao veronica Pena-Leon Patricia Gonzalez-Saenz javier Baltar Ivan Baamonde Rosaura Leis carlos Dieguez Uberto Pagotto Felipe F Casanueva Sulay A Tovar Ruben Nogueiras Luisa M Seoane Grupo Fisiopatología Endocrina Instituto de Investigación Sanitaria de Santiago de Compostela CIBER Fisiopatología obesidad y Nutrición Instituto de Salud Carlos III Department of Physiology Research Centre of Molecular Medicine and Chronic Diseases Department of Pediatric Universidad de Santiago de Compostela Servicio de Cirugía General Complexo Hospitalario Universitario de Santiago Endocrinology Unit and Center for Applied Biomedical Research Department of Medical and Surgical SciencesHospital S.Orsola-MalpighiAlma Mater University of Bologna Laboratorio de Endocrinología Molecular y Celular.Universidad de Santiago de Compostela Instituto de Investigación Sanitaria de Santiago de CompostelaComplexo Hospitalario Universitario de Santiago

AIM To determine whether Nucb2/nesfatin1 production is regulated by the cannabinoid system through the intracellular m ToR pathway in the *** Sprague Dawley rats were treated with vehicle, rimonabant, rapamycin or rapamycin+rimonabant. Gastric tissue obtained from the animals was used for biochemical assays: Nucb2 m RNA measurement by real time PCR, gastric Nucb2/nesfatin protein content by western blot, and gastric explants to obtain gastric secretomes. Nucb2/nesfatin levels were measured in gastric secretomes and plasma using enzyme-linked immunosorbent assay. RESULTS The inhibition of cannabinoid receptor 1(CB1) by the peripheral injection of an inverse agonist, namely rimonabant, decreases food intake and increases the gastric secretion and circulating levels of Nucb2/nesfatin-1. In addition, rimonabant treatment activates m ToR pathway in the stomach as showed by the increase in pm ToR/m ToR expression in gastric tissue obtained from rimonabant treated animals. These effects were confirmed by the use of a CB1 antagonist, AM281. When the intracellular pathway m ToR/S6 k was inactivated by chronic treatment with rapamycin, rimonabant treatment was no longer able to stimulate the gastric secretion of Nucb2/*** The peripheral cannabinoid system regulates food intake through a mechanism that implies gastric production and release of Nucb2/Nesfatin-1, which is mediated by the m ToR/S6 k pathway.

关键词： NUCB2/nesfatin-1 Stomach Food intake Cannabinoid receptor 1 mToR

The Study of Carbamoyl Phosphate Synthetase 1 Deficiency Sheds Light on the Mechanism for Switching on/off the Urea Cycle

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Journal of Genetics and Genomics 2015年第5期42卷 249-260页

作者： Carmen Díez-Fernández José Gallego Johannes H?berle javier Cervera vicente Rubio Institute for Biomedicine of valencia of the Spanish Research Council Medical School of the Catholic University of valencia University Children's Hospital Zurich and Children's Research Center Centre for Biomedical Networking Research on Rare Diseases of the carlos Ⅲ Health Institute

Carbamoyl phosphate synthetase i （CPS1） deficiency （CPS1D） is an inborn error of the urea cycle having autosomal （2q34） recessive inheritance that can cause hyperammonemia and neonatal death or mental retardation. We analyzed the effects on CPS1 activity, kinetic parameters and enzyme stability of missense mutations reported in patients with CPS1 deficiency that map in the 20-kDa C-terminal domain of the enzyme. This domain turns on or off the enzyme depending on whether the essential allosteric activator of CPS 1, N-acetyl- L-glutamate （NAG）, is bound or is not bound to it. To carry out the present studies, we exploited a novel system that allows the expression in vitro and the purification of human CPS1, thus permitting site-directed mutagenesis. These studies have clarified disease causation by individual mutations, identifying functionally important residues, and revealing that a number of mutations decrease the affinity of the enzyme for NAG. Patients with NAG affinity-decreasing mutations might benefit from NAG site saturation therapy with N-carbamyl-L- glutamate （a registered drug, the analog of NAG）. our results, together with additional present and prior site-directed mutagenesis data for other residues mapping in this domain, suggest an NAG-triggered conformational change in the 134-~4 loop of the C-terminal domain of this enzyme. This change might be an early event in the NAG activation process. Molecular dynamics simulations that were restrained according to the observed effects of the mutations are consistent with this hypothesis, providing further backing for this structurally plausible signaling mechanism by which NAG could trigger urea cycle activation via CPS1.

关键词： Urea cycle diseases Inborn errors Hyperammonemia Site-directed mutagenesis Restrained molecular dynamics Allosteric regulation Carbamoyl phosphate synthetase 1 Enzyme

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过早逝去的生命枪支暴力阴影下的美国年轻人

南风窗 2012年第17期 53-57页

作者： carlos javier ortiz 钟智

造成12人死亡59人受伤的丹佛影院枪击案刚过两周,8月5日,美国威斯康星州奥克利克锡克教寺庙又发生枪击事件,造成7人死亡,4人受伤,半月全美两度宣布下半旗致哀。枪支泛滥造成的暴力犯罪就像一场无声的战争在美国本土进行,虽从未宣战,却... 详细信息

造成12人死亡59人受伤的丹佛影院枪击案刚过两周,8月5日,美国威斯康星州奥克利克锡克教寺庙又发生枪击事件,造成7人死亡,4人受伤,半月全美两度宣布下半旗致哀。枪支泛滥造成的暴力犯罪就像一场无声的战争在美国本土进行,虽从未宣战,却真实而残酷地夺去越来越多人的生命。据2011年1月9日美国《外交政策》披露,美国每年3万多人死于枪支暴力,20万人因枪支暴力受伤。人们因而人心惶惶,更多人选择购买枪支以确保人身安全。目前,美国有2.8亿支枪,32%的家庭拥有枪支。然而,一直在全球范围宣扬自由民主、致力反恐的美国政府却始终未提出任何枪支管制的新举措。

关键词：枪支暴力美国美利坚合众国北美洲芝加哥生命年轻人

Phase Ⅱ trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/CDKN2A

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5518-5527页

作者： javier Martin-Broto Jeronimo Martinez-Garcia David SMoura Andres Redondo Antonio Gutierrez Antonio Lopez-Pousa javier Martinez-Trufero Isabel Sevilla Roberto Diaz-Beveridge Maria Pilar Solis-Hernandez Amancio Carnero Marco Perez David Marcilla Jesus Garcia-Foncillas Pablo Romero javier Fernandez-Jara Daniel Lopez-Lopez Ivan Arribas Nadia Hindi Health Research Institute-Fundación Jiménez Díaz University Hospital Universidad Autónoma de Madrid(IIS-FJDUAM)28040MadridSpain Medical oncology Department Fundación Jimenez Diaz University Hospital28040MadridSpain General de villalba University Hospital 28400MadridSpain Medical oncology Department University Hospital Virgen de la Arrixaca30120MurciaSpain Department of Medical oncology Hospital Universitario La Paz-IdiPAZP.Castellana26128046MadridSpain Hematology Department University Hospital Son Espases07120MallorcaSpain Medical oncology Department Sant Pau Hospital08025BarcelonaSpain Medical oncology Department University Hospital Miguel Servet50009ZaragozaSpain Investigación Clínica y Traslacional en Cáncer/Instituto de Investigaciones Biomédicas de Malaga(IBIMA)/Hospitales Universitarios Regional y virgen de la victoria de Malaga MalagaSpain Medical oncology Department Hospital Universitari i Politècnic La Fe46026ValenciaSpain Medical oncology Department Central University Hospital of Asturias33011OviedoSpain Instituto de Biomedicina de Sevilla(IBiS HUVRCSICUS)41013SevillaSpain Pathology Department Virgen del Rocio University Hospital41013SevillaSpain Radiology Department Fundación Jimenez Diaz University Hospital28040MadridSpain Computational Medicine Platform Fundación progreso y salud(FPS)Hospital Virgen del Rocío41013SevilleSpain Bioinformatics in Rare Diseases(BiER).Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER) FPSHospital Virgen del RocioSevillaSpain Universitat de valència-ERI-CES 46010ValenciaSpain

Cyclin-dependent kinases 4 and 6(CDK4/6)inhibitors demonstrated activity in terms of progression-free survival(PFS)in advanced dedifferentiated liposarcoma(DD-LPS),a sarcoma with CDK4 ***4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK *** investigators of this study found that CDK4 overexpression,while not of CDKN2A,was the most consistent predictive factor for palbociclib efficacy in *** adult-type soft-tissue sarcoma,excluding DD-LPS,or bone sarcoma patients,progressing after at least one systemic line,whose tumors overexpressed CDK4,but not CDKN2A at baseline biopsy,were accrued in this single-arm phase II trial(EudraCT number:2016-004039-19).With the main endpoint of a 6-month PFS rate,40%was considered promising in this *** was administered orally at 125 mg/day for 21 days in 28-day cycles.A total of 214 patients with 236 CDK4/CDKN2A determinations were assessed for prescreening,archival material(141),and screening,baseline biopsy(95).There were 28(29%)with favorable mRNA profiles from 95 screened patients at *** 23 enrolled patients,21 evaluable,the 6-month PFS rate was 29%(95%CI 9–48),and there were 6 patients out of 21 with a PFS longer than 6 *** median PFS and overall survival were 4.2(95%CI 3.6–4.8)and 12(95%CI 8.7–15.4)months,*** research showed a significant correlation between CDK4 mRNA and protein *** was active in a variety of sarcoma subtypes,selected by CDK4/CDKN2A,and deserves further investigation in the sarcoma context.

关键词： CDKN2A sarcoma CDK4