[Analysis of global liver cancer statistics].

Liver cancer is a significant contributor to the world's cancer burden. In order to comprehend the variations in its regional, age, gender, and histological subtype distributions as well as its temporal trend, this paper analyzes the worldwide statistical data of liver cancer, including the incidence, mortality, and survival. The findings indicated that the stages of liver cancer control and prevention are heterogeneous among countries and regions. The successful experience of liver cancer control and prevention in some countries should be promoted and disseminated. According to the various national conditions, comprehensive intervention measures, including reducing aflatoxin exposure, promoting vaccination, improving the treatment of chronic hepatitis infection, and implementing early diagnosis and treatment of liver cancer, should be developed.

[Establishment of acute graft-versus-host disease model after non-myeloablative haploidentical peripheral blood stem cell transplantation in aged mice].

Objective: To establish an acute graft-versus-host disease (aGVHD) model in aged mice after non-myeloablative haploidentical peripheral blood stem cell transplantation (haplo-PSCT). Methods: C57BL/6 (H-2b) male mice aged 6-8 weeks were used as donor mice, and CB6F1 (H-2b×d) female mice aged 14-16 months were used as recipient mice. The donor mice were injected subcutaneously with rehuman granulocyte-colony stimulating factor (rhG-CSF) 5 days before transplantation for hematopoietic stem cell mobilization.The recipient mice were divided into control group (CG), spleen cell low-dose group (SL), spleen cell medium-dose group (SM) and spleen cell high-dose group (SH) according to random number table method, with 16 rats in each group, all of which received total linear accelerator X-ray irradiation (TBI) with a total dose of 6 Gy. Peripheral blood mononuclear cells (PBMC) and spleen cells of different doses (0.5×107/each, 1.0×107/each and 2.0×107/each in SL group, SM group and SH group, respectively) were transfused through the tail vein within 4 hours after TBI, and only the same amount of normal saline was transfused in CG group. After transplantation, the survival and weight changes of mice in each group were observed for 30 days, and the changes of blood routine were monitored regularly. Mice peripheral blood was collected 21 days after transplantation to detect the chimerism rate of the donor. Hematoxylin-eosin staining was performed on the skin, liver and colon of mice 21 days after transplantation to analyze the histopathological changes of aGVHD target organs. Results: All the mice in each group were successfully transplanted. After TBI, the weight and activity of mice in all groups decreased, and the phenomenon of bone marrow suppression appeared. During the observation period, all mice in CG group and SL group survived, 3 mice in SM group died with survival time of (26.0±5.8) days, and 6 mice in SH group died with survival time of (20.9±7.3) days. The body weight of mice in SH group was lower than that in CG group, SL group and SM group 21days after transplantation [(25.0±0.7), (25.5±0.4), (25.0±1.4) vs (20.8±0.8) g, all P<0.05]. Compared with CG group, SL group and SM group, the levels of leukocyte, erythrocyte, hemoglobin and platelet in SH group decreased 21 days after transplantation (all P<0.05). There was no significant difference in donor chimerism rate among SL group, SM group and SH group [(95.8%±0.8%), (95.5%±1.4%) and (95.1%±1.3%), respectively, all P>0.05]. Compared with CG group, SL group and SM group, the tissue structure of aGVHD target organs in SH group was severely damaged, with a large number of inflammatory cells infiltratedand higher histopathological scores than SL group and SM group (all P<0.05). Conclusion: For aging CB6F1 mice, after 6 Gy TBI pretreatment with linear accelerator X-ray, PBMC (1×107/each) and spleen cells (2.0×107/each) were injected to successfully induce aGVHD model after non-myelablative haplo-PSCT.

miR-146a aggravates cognitive impairment and Alzheimer disease-like pathology by triggering oxidative stress through MAPK signalingmi / R-146a empeora el deterioro cognitivo y la patología tipo Alzheimer al promover el estrés oxidativo a través de la vía de señalización MAPK

Introduction: Mir-146a-5p has been widely recognized as a critical regulatory element in the immune response. However, recent studies have shown that miR-146a-5p may also be involved in the development of Alzheimer disease (AD). Regrettably, the related mechanisms are poorly understood. Here, we investigated the effects of miR-146a in mice models and SH-SY5Y cells treated with amyloid β (Aβ)1–42. Methods: To create a model of AD, SH-SY5Y cells were treated with Aβ1–42 and mice received intracerebroventricular injections of Aβ1–42. Then, the transcriptional levels of miR-146a were estimated by real-time PCR. We transiently transfected the miR-146a-5p mimic/inhibitor into cells and mice to study the role of miR-146a. The role of signaling pathways including p38 and reactive oxygen species (ROS) was studied by using specific inhibitors. Aβ and amyloid-beta precursor protein (APP)levels were measured by immunoblotting. Furthermore, Aβ expression was analyzed by immunofluorescence and histochemical examinations. Results: Aβ1–42-stimulated SH-SY5Y cells displayed increased transcriptional levels of miR-146a and APP. Moreover, the p38 MAPK signaling pathway and ROS production were activated upon stimulation with a miR-146a-5p mimic. However, treatment with a miR-146a-5p inhibitor decreased the levels of APP, ROS, and p-p38 MAPK. A similar phenomenon was also observed in the animals treated with Aβ1–42, in which miR-146a upregulation increased the expression of Aβ, p-p38, and ROS, while the inhibition of miR-146a had the opposite effect. This suggests that miR-146a increases Aβ deposition and ROS accumulation via the p-p38 signaling pathway. Conclusions: Our research demonstrates that miR-146a-5pa increases Aβ deposition by triggering oxidative stress through activation of MAPK signaling.(AU)

Introducción: miR-146a-5p es un elemento regulador clave en la respuesta inmune. Sin embargo, estudios recientes sugieren que miR-146a-5p también está involucrado en el desarrollo de la enfermedad de Alzheimer (EA), aunque aún no se conoce con exactitud el mecanismo por el que esto sucede. Analizamos los efectos de miR-146a en un modelo animal y en células SH-SY5Y expuestas a β-amiloide (Aβ)1-42. Métodos: Tratamos células SH-SY5Y con Aβ1-42 e inyectamos Aβ1-42 en los ventrículos cerebrales de ratones para generar un modelo celular y otro animal de EA. Estimamos los niveles transcripcionales de miR-146a mediante PCR en tiempo real. Al mismo tiempo, transfectamos temporalmente las células y los ratones con imitador/inhibidor de miR-146a-5p para evaluar el papel de miR-146a. Estudiamos el papel de algunas vías de señalización, como la de p38, y los niveles de especies reactivas de oxígeno (ERO) con inhibidores específicos. Los niveles de Aβ y de proteína precursora amiloidea (APP) se determinaron con inmunoblot. También se analizó la expresión de Aβ mediante inmunofluorescencia y análisis histoquímico. Resultados: Las células SH-SY5Y expuestas a Aβ1-42 mostraron altos niveles transcripcionales de miR-146a y APP. La vía de señalización p-38 MAPK y la producción de EROs se activaron al utilizar un imitador de miR-146a-5p. Sin embargo, el bloqueo de miR-146a-5p con un inhibidor redujo los niveles de APP, EROs y p-p38 MAPK. Se observó un fenómeno similar en los ratones tratados con Aβ1-42: la sobrerregulación de miR-146a aumentó la expresión de Aβ, p-p38 y EROs, mientras que la inhibición de miR-146a tuvo el efecto contrario. Esto sugiere que miR-146a está involucrado en el aumento de acumulación de Aβ y de producción de EROs por medio de la vía de señalización p-p38. Conclusiones: Nuestro estudio muestra que miR146a-5p aumenta la acumulación de Aβ al promover el estrés oxidativo a través de la activación de la vía de señalización MAPK.(AU)

Voluntary exercise prior to traumatic brain injury alters miRNA expression in the injured mouse cerebral cortex

MicroRNAs (miRNAs) may be important mediators of the profound molecular and cellular changes that occur after traumatic brain injury (TBI). However, the changes and possible roles of miRNAs induced by voluntary exercise prior to TBI are still not known. In this report, the microarray method was used to demonstrate alterations in miRNA expression levels in the cerebral cortex of TBI mice that were pretrained on a running wheel (RW). Voluntary RW exercise prior to TBI: i) significantly decreased the mortality rate and improved the recovery of the righting reflex in TBI mice, and ii) differentially changed the levels of several miRNAs, upregulating some and downregulating others. Furthermore, we revealed global upregulation of miR-21, miR-92a, and miR-874 and downregulation of miR-138, let-7c, and miR-124 expression among the sham-non-runner, TBI-non-runner, and TBI-runner groups. Quantitative reverse transcription polymerase chain reaction data (RT-qPCR) indicated good consistency with the microarray results. Our microarray-based analysis of miRNA expression in mice cerebral cortex after TBI revealed that some miRNAs such as miR-21, miR-92a, miR-874, miR-138, let-7c, and miR-124 could be involved in the prevention and protection afforded by voluntary exercise in a TBI model.