NR5A2/LRH-1 regulates the PTGS2-PGE2-PTGER1 pathway contributing to pancreatic islet survival and function.

LRH-1/NR5A2 is implicated in islet morphogenesis postnatally, and its activation using the agonist BL001 protects islets against apoptosis, reverting hyperglycemia in mouse models of Type 1 Diabetes Mellitus. Islet transcriptome profiling revealed that the expression of PTGS2/COX2 is increased by BL001. Herein, we sought to define the role of LRH-1 in postnatal islet morphogenesis and chart the BL001 mode of action conferring beta cell protection. LRH-1 ablation within developing beta cells impeded beta cell proliferation, correlating with mouse growth retardation, weight loss, and hypoglycemia leading to lethality. LRH-1 deletion in adult beta cells abolished the BL001 antidiabetic action, correlating with beta cell destruction and blunted Ptgs2 induction. Islet PTGS2 inactivation led to reduced PGE2 levels and loss of BL001 protection against cytokines as evidenced by increased cytochrome c release and cleaved-PARP. The PTGER1 antagonist-ONO-8130-negated BL001-mediated islet survival. Our results define the LRH-1/PTGS2/PGE2/PTGER1 signaling axis as a key pathway mediating BL001 survival properties.

Volviéndonos mejores: necesidad de acción inmediata ante el reto de la obesidad. Una postura de profesionales de la salud.

La creciente epidemia de obesidad ha sido uno de los retos más importantes de salud pública en México durante los últimos años. Con apoyo de la Federación Mundial de Obesidad, en 2021 formamos un grupo de profesionales para identificar y resumir las acciones prioritarias en las que puede enfocarse nuestro país para hacer frente a esta epidemia. Al proceso de desarrollo y discusión de este grupo se sumaron más de 1 000 profesionales de la salud para retomar recomendaciones de documentos y guías de alto nivel previamente publicados. En conmemoración del Día Mundial de la Obesidad, en este 2022 se presenta esta postura como insumo para el desarrollo de acciones en el ámbito profesional y de los diferentes sectores, en la que se incluyen 10 recomendaciones de acción, desde la perspectiva poblacional hasta la atención individualizada, y se enfatiza en la importancia de la participación social, de las intervenciones integrales con visión centrada en la persona y de la sostenibilidad planetaria, además de mejorar la educación y las campañas de difusión, propiciar un ambiente promotor de entornos activos y blindar de conflictos de interés los esfuerzos de prevención y control. La postura hace un llamado para abordar la obesidad de manera seria, con base en la evidencia científica, oportuna e integral, con enfoque de curso de vida, de forma ética y sensible, y sin perpetuar las barreras del estigma de peso en la sociedad.

Volviéndonos mejores: necesidad de acción inmediata ante el reto de la obesidad. Una postura de profesionales de la salud / Becoming better: the need for immediate action to address obesity. A position statement from health professionals

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Abstract: In recent decades, the growing obesity epidemic in Mexico has become one of the most important public health challenges faced by the country. With support from the World Obesity Federation, we formed a working group in 2021 to identify and summarize priority actions that Mexico can take to face this epidemic. More than 1 000 health professionals joined the development and discussion process. Recommendations from previously published, high-level documents and guidelines were taken into account. In commemoration of World Obesity Day 2022, this statement is presented as input for health care professionals to develop actions to address obesity. The statement includes 10 recommendations that include population-level and individual-level actions. It emphasizes the importance of social participation, comprehensive interventions with a person- centered perspective, planetary sustainability, on improving education and communication campaigns, as well as fostering a built environment that promotes active living, and shielding prevention and control efforts from conflicts of interest. The statement calls for obesity to be treated seriously, based on scientific evidence, in a timely and comprehensive manner, employing a life-course and ethical approach that does not perpetuate weight stigma in society.

Postpartum hemorrhage with pelvic arterial embolization, study of 33 cases.

OBJECTIVE: To describe our cases of postpartum hemorrhage (PPH) with pelvic arterial embolization (PAE). MATERIAL AND METHODS: All patients with PPH who underwent PAE in our center in the interval 2011-1016 were retrospectively studied, evaluating the technical procedure, clinical results, and subsequent fertility. RESULTS: There were 33 cases of PPH with PAE. The majority occurred in primiparous women (N = 22, 66.6%) who delivered vaginally (N = 20, 61%). In addition, most PPH with PAE cases had an early onset (N = 26, 79%) and were caused by uterine atony (N = 14, 42.4%). Success of PAE occurred in 27 (81.8%) cases and a satisfactory clinical follow-up was the rule, with 21 (64%) women recovering their normal menstruation, and six (18.2%) becoming pregnant in the following years. CONCLUSIONS: PAE is a safe and efficacious technique with minor complications. Moreover, it allows conservation of the uterus with preservation of fertility.

Tratamiento a largo plazo con análogos de GnRh en pacientes con endometriosis severa / Long-term treatment with GnRh analogs in patients with severe endometriosis

La endometriosis constituye aproximadamente un 15% de los diagnósticos de dolor pélvico crónico en nuestro medio. La complejidad del diagnóstico, que en muchas ocasiones requiere abordaje multidisciplinar, y la dificultad en su manejo, hacen de esta patología un auténtico reto para el ginecólogo. En casos leves, el manejo se realiza con analgésicos convencionales, preferiblemente antiinflamatorios no esteroideos, acompañados o no de contraceptivos orales combinados. En casos más graves se puede suprimir la función ovárica mediante análogos de hormona liberadora de gonadotropina que han demostrado efectividad no solo en la reducción del dolor, sino también en la disminución de tamaño de los implantes endometriósicos. La Food and Drug Administration no recomienda la terapia con análogos durante periodos superiores a 6 meses (prorrogables a 6 meses más llegando a un total de 12 meses) debido fundamentalmente al riesgo osteoporótico. Debido a este efecto secundario producido por la supresión de la función ovárica, se ha desarrollado una terapia denominada add back que se trata de administrar a las pacientes estrógenos y/o progesterona externos con el fin de paliar en cierta medida los efectos secundarios derivados del uso de análogos de hormona liberadora de gonadotropina. En este caso se expone la historia de una paciente con endometriosis severa que ha seguido tratamiento con análogos de la hormona liberadora de gonadotropina durante más de 10 años, junto con terapia hormonal con tibolona durante el mismo tiempo. Se estudia el efecto beneficioso sobre la patología de base, la aparición de efectos secundarios y la evolución de la endometriosis a lo largo de estos 10 años (AU)

Endometriosis is diagnosed in approximately 15% of every cases of chronic pelvic pain. Complexity of diagnosis that in many cases requires several disciplines and treatments make this pathology a challenge for the Gynecologist. In minor cases management is made with conventional analgesics as AINES combined or not with oral anticonceptives. In severe cases, ovaric suppression makes an option. This therapy has demonstrated effectiveness not only in reduction of pain scale but also decreases size of endometriosis implants. Food and Drug Administration does not recommend this therapy for periods larger than 6 months (with an option of 12 months) due to risk of osteoporosis. Due to this risk, add back therapy (Hormonal therapy with estrogens with/or progesterone) has been developed. In this case, it is presented the history of a patient with severe endometriosis that has been treated with analogues of gonadotropin-releasing hormone combined with tibolone during 10 years. It is studied the benefit over main patology, secondary effects and evolution of the endometriosis (AU)

The effect of PEGylated hollow gold nanoparticles on stem cell migration: potential application in tissue regeneration.

Mesenchymal stem cells (MSCs) not only can be differentiated into different cell types but also have tropism towards injured or inflamed tissues serving as repair cells. Here we have demonstrated that MSCs containing gold nanoparticles (GNPs) whose surface has been functionalized with PEG show accelerated cell migration, successful scaffold colonization and regeneration. We report the impact of GNPs on the migration (by the wound healing assay), and proliferation (by flow cytometry analysis and by the detection of metabolic mitochondrial activity) on the behaviour of different cell lines including MSCs, HeLa cells, and human dermal fibroblasts. We conclude that GNPs are easily internalized by MSCs causing an increase in their migration rate, mediated by actin and tubulin with a 4-fold increased expression level of those proteins. We also demonstrate that MSCs containing GNPs are able to successfully colonize fibrin and PCL-based scaffolds and that an enhanced osteoblastic differentiation is reached when using the nanoparticle-laden cells compared to untreated cells used as a control. These results highlight the potential use of MSCs as therapeutic nanoparticle-carriers in regenerative medicine.