Artritis reumatoidea asociada a colangitis biliar primaria bajo tratamiento con medicamentos biológicos

El abordaje terapéutico de pacientes con dos o más enfermedades autoinmunes es un verdadero desafío, especialmente cuando el tratamiento enfocado en una de ellas podría precipitar la progresión de la otra. Si bien la asociación de artritis reumatoidea (AR) con colangitis biliar primaria (CBP) no es tan frecuente, cuando coexisten, la utilización de metotrexato u otras drogas hepatotóxicas debe decidirse con cautela. Con la indicación más generalizada de las drogas biológicas modificadoras del curso de la AR (DMARb) han aparecido algunos reportes de pacientes con AR y CBP tratados con etanercept, infliximab, rituximab, tocilizumab y abatacept. Presentamos una serie de casos de 4 pacientes con AR y CBP que fueron tratados con DMARb. Nuestro reporte sería el primero en describir dos casos con golimumab para controlar la AR y el segundo en reportar un caso con adalimumab y otro con abatacept. Con rituximab, ya existen tres casos publicados. En ninguno de los pacientes de nuestra serie empeoraron los síntomas de CBP y, al contrario, en dos de ellos hubo mejoría de los parámetros bioquímicos

A Novel Micropeptide, \u3cem\u3eSlitharin\u3c/em\u3e, Exerts Cardioprotective Effects in Myocardial Infarction

Purpose: Micropeptides are an emerging class of proteins that play critical roles in cell signaling. Here, we describe the discovery of a novel micropeptide, dubbed slitharin (Slt), in conditioned media from Cardiosphere-derived cells (CDCs), a therapeutic cardiac stromal cell type. Experimental design: We performed mass spectrometry of peptide-enriched fractions from the conditioned media of CDCs and a therapeutically inert cell type (human dermal fibrobasts). We then evaluated the therapeutic capacity of the candidate peptide using an in vitro model of cardiomyocyte injury and a rat model of myocardial infarction. Results: We identified a novel 24-amino acid micropeptide (dubbed Slitharin [Slt]) with a non-canonical leucine start codon, arising from long intergenic non-coding (LINC) RNA 2099. Neonatal rat ventricular myocytes (NRVMs) exposed to Slt were protected from hypoxic injury in vitro compared to a vehicle or scrambled control. Transcriptomic analysis of cardiomyocytes exposed to Slt reveals cytoprotective capacity, putatively through regulation of stress-induced MAPK-ERK. Slt also exerted cardioprotective effects in rats with myocardial infarction as shown by reduced infarct size 48 h post-injury. Conclusions and clinical relavance: Thus, Slt is a non-coding RNA-derived micropeptide, identified in the extracellular space, with a potential cardioprotective function

Modulatory effects of ghrelin on sperm quality alterations induced by a fructose-enriched diet

The objectives of this study were: 1) to evaluate the effects of a fructose enriched diet (FED) on rat3 sperm quality, epididymal function (i.e. oxidative stress and alpha-glucosidase expression) and4 testosterone concentrations; 2) to determine if the administration of ghrelin (Ghrl), reverses the5 effects induced by FED.6 After validating the protocol as an inductor of metabolic syndrome like-symptoms, adult male rats7 were assigned to one of the following treatments for 8 weeks: FED=10% fructose enriched in water8 (v/v); FED+Ghrl=fructose enriched diet plus Ghrl (6 nmol/animal/day, s.c.) from week 6 to 8; or9 C=water without fructose (n=5-10 animals/group).10 FED significantly decreased sperm concentration and motile sperm count/ml vs C (FED:19.0±1.6x106sperm/ml and 834.6±137.0, respectively vs C: 25.8±2.8x10611 and 1300.4±202.4,respectively; p<0.05); ghrelin injection reversed this negative effect (23.5±1.6x10612 sperm/ml and13 1381.7±71.3 respectively). FED resulted in hypogonadism, but Ghrl could not normalize testosterone14 concentrations (C: 1.4±0.1 ng/ml vs FED: 0.8±0.2 ng/ml and FED+Ghrl: 0.6±0.2 ng/ml ;p<0.05).15 Ghrelin did not reverse metabolic abnormalities secondary to FED. FED did not alter epididymal16 expression of antioxidants enzymes (superoxido-dismutase, catalase and glutathione peroxidases ?17 Gpx-). Nevertheless, FED+Ghrl significantly increased the expression of Gpx3 (FED+Ghrl:18 3.47±0.48 vs FED: 0.69±0.28 and C: 1.00±0.14; p<0.05). The expression of neutral alpha19 glucosidase, which is a marker of epididymal function, did not differ between treatments.20 In conclusion, the administration of Ghrl modulated the negative effects of FED on sperm quality,21 possibly by an epididymal increase in Gpx3 expression. However, Ghrl could not neither normalize22 the metabolism of FED animals, nor reverse hypogonadism.Fil: Ramirez, Nicolás David. Universidad Nacional de Córdoba. Facultad de Medicina. Departamento de Fisiología Humana y Física Biomédica. Cátedra de Fisiología Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Luque, Eugenia Mercedes. Universidad Nacional de Córdoba. Facultad de Medicina. Departamento de Fisiología Humana y Física Biomédica. Cátedra de Fisiología Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Jones, Xaviar Michael. Universidad Nacional de Córdoba. Facultad de Medicina. Departamento de Fisiología Humana y Física Biomédica. Cátedra de Fisiología Humana; ArgentinaFil: Torres, Pedro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Moreira Espinoza, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Cantarelli, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Ponzio, Marina Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Arja, Ana. Universidad Nacional de Córdoba. Facultad de Medicina. Departamento de Fisiología Humana y Física Biomédica. Cátedra de Fisiología Humana; ArgentinaFil: Rabaglino, Maria Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Martini, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentin

Harnessing the benefits of yoga for myositis, muscle dystrophies, and other musculoskeletal disorders

The recent global increase in popularity of home-based yoga, an ancient Indian technique practiced for thousands of years, has translated into its use as a complementary therapy for a multitude of ailments. This review aims to examine the published literature regarding the effects of yoga therapy on systemic chronic diseases; in particular on the inflammatory myopathies (IMs) and other muscle disorders. Despite the fact that the evidence base for yoga in inflammatory myositis is in its infancy, collateral results in other disorders such as muscular dystrophies are promising. A beneficial effect of yoga in chronic pain has been shown alongside an improvement in motor function and muscle strength. Patients with Duchenne muscular dystrophy with respiratory involvement may find improvement in lung function. Elderly patients may experience reduction in falls secondary to an improvement in balance while practicing long-term yoga therapy. Further benefits are improving disorders of mental health such as depression and anxiety. A reported improvement in overall quality of life further suggests its efficacy in reducing morbidity in patients with chronic diseases, who often suffer co-existent psychological comorbidities

TDO2‐augmented fibroblasts secrete EVs enriched in immunomodulatory Y‐derived small RNA

Abstract Mounting evidence implicates extracellular vesicles (EVs) factors as mediators of cell therapy. Cardiosphere‐derived cells are cardiac‐derived cells with tissue reparative capacity. Activation of a downstream target of wnt/β‐catenin signalling, tryptophan 2,3 dioxygenase (TDO2) renders therapeutically inert skin fibroblasts cardioprotective. Here, we investigate the mechanism by which concentrated conditioned media from TDO2‐augmented fibroblasts (TDO2‐CCM) exert cardioprotective effects. TDO2‐CCM is cardioprotective in a mouse model of MI compared to CCM from regular fibroblasts (HDF‐CCM). Transcriptomic analysis of cardiac tissue at 24 h demonstrates broad suppression of inflammatory and cell stress markers in animals given TDO2‐CCM compared to HDF‐CCM or vehicle. Sequencing analysis of TDO2‐EV RNA demonstrated abundance of a small Y‐derived small RNA dubbed ‘NT4’. Purification of TDO2‐EVs by size‐exclusion chromatography and RNAse protection assays demonstrated that NT4 is encapsulated inside EVs. Consistently with TDO2‐CCM, macrophages exposed to NT4 showed suppression of the inflammatory and cell stress mediators, particularly p21/cdkn1a. NT4‐depleted TDO2‐CCM resulted in diminished immunomodulatory capacity. Finally, administration of NT4 alone was cardioprotective in an acute model of myocardial infarction. Taken together, these findings elucidate the mechanism by which TDO2 augmentation mediates potency in secreted EVs through enrichment of NT4 which suppresses upstream cell stress mediators including p21/cdkn1a

Loss of Karma transposon methylation underlies the mantled somaclonal variant of oil palm

Somaclonal variation arises in plants and animals when differentiated somatic cells are induced into a pluripotent state, but the resulting clones differ from each other and from their parents. In agriculture, somaclonal variation has hindered the micropropagation of elite hybrids and genetically modified crops, but the mechanism responsible remains unknown. The oil palm fruit 'mantled' abnormality is a somaclonal variant arising from tissue culture that drastically reduces yield, and has largely halted efforts to clone elite hybrids for oil production. Widely regarded as an epigenetic phenomenon, 'mantling' has defied explanation, but here we identify the MANTLED locus using epigenome-wide association studies of the African oil palm Elaeis guineensis. DNA hypomethylation of a LINE retrotransposon related to rice Karma, in the intron of the homeotic gene DEFICIENS, is common to all mantled clones and is associated with alternative splicing and premature termination. Dense methylation near the Karma splice site (termed the Good Karma epiallele) predicts normal fruit set, whereas hypomethylation (the Bad Karma epiallele) predicts homeotic transformation, parthenocarpy and marked loss of yield. Loss of Karma methylation and of small RNA in tissue culture contributes to the origin of mantled, while restoration in spontaneous revertants accounts for non-Mendelian inheritance. The ability to predict and cull mantling at the plantlet stage will facilitate the introduction of higher performing clones and optimize environmentally sensitive land resources