Omics Analysis of Ferroptosis and Establishment of Prognostic Model for multiple myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To explore the role of ferroptosis-related genes in multiple myeloma(MM) through TCGA database and FerrDb, and build a prognostic model of ferroptosis-related genes for MM patients.@*METHODS@#Using the TCGA database containing clinical information and gene expression profile data of 764 patients with MM and the FerrDb database including ferroptosis-related genes, the differentially expressed ferroptosis-related genes were screened by wilcox.test function. The prognostic model of ferroptosis-related genes was established by Lasso regression, and the Kaplan-Meier survival curve was drawn. Then COX regression analysis was used to screen independent prognostic factors. Finally, the differential genes between high-risk and low-risk patients were screened, and enrichment analysis was used to explore the mechanism of the relationship between ferroptosis and prognosis in MM.@*RESULTS@#36 differential genes related to ferroptosis were screened out from bone marrow samples of 764 MM patients and 4 normal people, including 12 up-regulated genes and 24 down-regulated genes. Six prognosis-related genes (GCLM, GLS2, SLC7A11, AIFM2, ACO1, G6PD) were screened out by Lasso regression and the prognostic model with ferroptosis-related genes of MM was established. Kaplan-Meier survival curve analysis showed that the survival rate between high risk group and low risk group was significantly different(P<0.01). Univariate COX regression analysis showed that age, sex, ISS stage and risk score were significantly correlated with overall survival of MM patients(P<0.05), while multivariate COX regression analysis showed that age, ISS stage and risk score were independent prognostic indicators for MM patients (P<0.05). GO and KEGG enrichment analysis showed that the ferroptosis-related genes was mainly related to neutrophil degranulation and migration, cytokine activity and regulation, cell component, antigen processing and presentation, complement and coagulation cascades, haematopoietic cell lineage and so on, which may affect the prognosis of patients.@*CONCLUSION@#Ferroptosis-related genes change significantly during the pathogenesis of MM. The prognostic model of ferroptosis-related genes can be used to predict the survival of MM patients, but the mechanism of the potential function of ferroptosis-related genes needs to be confirmed by further clinical studies.

Avaliação dos efeitos modulatórios da hematopoese no envelhecimento: Papel das células tronco mesenquimais medulares / Evaluation of the modulatory effects of hematopoiesis during aging: Role of bone marrow mesenchymal stem cells

O envelhecimento é um processo fisiológico que traz consigo uma série de alterações no organismo que se estendem até o nível molecular. Diante disto, este é um processo complexo que afeta diversos tecidos, sendo um deles o hematopoético, local onde, através de interações da Célula Tronco Hematopoética (CTH) com o ambiente ao seu redor, incluindo a Célula Tronco Mesenquimal (CTM), ocorre a hematopoese. Embora já sejam descritas na literatura algumas alterações na medula óssea consequentes do envelhecimento, os mecanismos por trás de tais mudanças permanecem elusivas, principalmente no âmbito das interações celulares ocorrentes na medula óssea. Portanto, este trabalho buscou investigar como o envelhecimento afeta a regulação hematopoética no contexto de sua relação com as CTM medulares. Para esta pesquisa, foram utilizados camundongos machos isogênicos da linhagem C57BL/6, dividindoos em grupos conforme sua idade: jovens (3 ­ 5 meses) e idosos (18 ­ 19 meses). Foi realizada a caracterização do modelo através de aspectos físicos como consumo proteico, variação de peso, entre outros, seguido de avaliação bioquímica e hematológica. Adicionalmente, foram coletadas células medulares e, posteriormente, realizado o isolamento das CTMs. Para estudar a relação destas células com a hematopoese, foram realizados ensaios in vitro utilizando a linhagem celular leucêmica C1498 (TIB-49™, ATCC®) mantidas em contato com o sobrenadante das CTMs isoladas. Quanto aos parâmetros bioquímicos, os animais idosos apresentaram menores níveis de albumina, aspartato alanina transferase (ALT) e de triglicerídeos quando comparados aos animais jovens. Contrariamente, os animais idosos apresentaram um maior nível de colesterol. Na avaliação hematológica, foi constatado pelo hemograma que os animais idosos apresentaram valores comparáveis aos animais jovens, todavia, o mielograma mostrou menor celularidade geral, seguido de menor número de células da linhagem eritroide e maior número de precursores granulocíticos. Através da imunofenotipagem, foi revelado um maior número de CTHs e de precursores grânulosmonocíticos na medula de animais idosos quando comparado aos jovens, e uma menor frequência de progenitores linfoides. Na imunofenotipagem de sangue periférico de animais idosos houve uma redução no número de linfócitos B e de eritrócitos, e aumento na população de células natural killers. Na imunofenotipagem de CTMs, o marcador CD73 apresentou menor expressão nos animais idosos. Avaliando o secretoma destas células estromais, foram encontrados no sobrenadante de CTMs de animais idosos aumentos significativos nas concentrações de CXCL12 e SCF e redução de IL-11. No âmbito molecular, as CTMs de animais idosos apresentaram aumento na expressão de Akt1, Nos e Ppar-γ, e redução na expressão de Csf3 e Cdh2. Adicionalmente, quando comparado a ação das CTMs de animais idosos em relação as CTMs de animais jovens, observou-se que CTMs de animais idosos foram capazes de aumentar a expressão de Sox2, Pou5f1 e Nanog e diminuir a expressão de Cdkn1a de células da linhagem C1498. O sobrenadante de CTMs de animais idosos também resultou na maior proliferação e migração de células da linhagem C1498. Portanto, levando em consideração a importância das CTMs sobre a regulação do sistema hematopoético, pode-se concluir que, no envelhecimento, as CTMs criam um ambiente propício para a proliferação celular no qual a manutenção da pluripotência é estimulada, o que pode acarretar em uma desregulação do sítio hematopoético quando habitado por células malignas

Aging is a physiological process in which occurs a series of alterations in an organism that extend to a molecular level. It is a complex process that affects various tissues, one of them being the bone marrow, wherethrough the interactions of the hematopoietic stem cell (CTH) with its surrounding environment, including with the mesenchymal stem cell (CTM), hematopoiesis takes place. Although some aging-associated alterations in the bone marrow can be found described in the literature, the mechanisms behind said changes remain elusive, especially when regarding the cellular interactions present inside the bone marrow. Therefore, this research aimed to investigate how aging affects the regulation of hematopoiesis in the context of its interactions with bone marrow-derived CTMs. For this investigation, male isogenic C57BL/6 mice were used as animal models. These were separated in two groups according to their age: young (3 ­ 5 months) and aged (18 ­ 19 months). The animal models were characterized by their physical properties such as protein intake and weight variation, followed by biochemical and hematological evaluation. Bone marrow cells were obtained and identified through immunophenotyping, thus isolating different cell populations, including the CTMs. To study the relationship between these cells and hematopoiesis, in vitro assays were conducted utilizing the leukemic cell lineage C1498 (TIB-49™, ATCC®) maintained in contact with the supernatant of isolated CTMs. By their biochemical profile, aged mice showed lower levels of albumin, alanine-aspartate transferase (ALT) and triglycerides compared to the young group. In contrast, aged mice had a higher cholesterol level. Hematological evaluation by total blood count showed similar results between the two groups, however, the myelogram revealed that the aged animals had lower cellularity, with less frequent cells from the erythroid lineage, with an increase in granulocytic precursors. Through immunophenotyping, it was also revealed that aged mice have higher numbers of hematopoietic stem cells, while also being noted a reduced population of lymphoid progenitors. An increase in the granulomonocytic progenitors was also found. Immunophenotyping peripheral blood cells of aged mice revealed reduced numbers of B lymphocytes and erythrocytes, and an increased natural killer cell population. Additionally, the cell surface marker CD73 was found to be less expressed in aged mice CTMs. The secretome of these stromal cells obtained from aged mice showed higher levels of CXCL12 and SCF, and lower levels of IL-11when compared to the young counterparts. At a molecular level, CTMs obtained from aged mice expressed more Akt1, Nos and Ppar-γ, while the expression of Csf3 and Cdh2 was reduced. Additionally, when comparing the effects of aged mice CTMs with young mice CTMs, it was observed that the first expressed were capable of increasing the expression of Sox2, Pou5f1 and Nanog, while decreasing Cdkn1a expression in the C1498 cell lineage. The supernatant obtained from aged mice also favored the proliferation and cell migration of the C1498 cell line. Thus, considering the importance that CTMs have over the hematopoietic system, we can conclude that, in aging, CTMs create a special environment which favors cell proliferation and maintenance of pluripotency, which can result in a dysregulation of the hematopoietic tissue when malignant cells are present

Laserterapia transcutânea para efeitos adversos hematopoiéticos de quimioterápicos antineoplásicos: Ensaio clínico randomizado / Terapia con láser transcutáneo para los efectos adversos hematopoyéticos de la quimioterapia antineoplásica: Ensayo clínico aleatorizado / Transcutaneous laser therapy for hematopoietic adverse effects of antineoplastic chemotherapeutics: Randomized clinical trial

Objetivo. Avaliar a eficácia dos protocolos de aplicação transcutânea do Intravenous Laser Irradiation of Blood 30' e 60', sobre os efeitos adversos no tecido hematopoiético por agentes quimioterápicos antineoplásicos endovenosos em adultos. Método. Ensaio clínico, randomizado e unicego, realizado em serviço ambulatorial de quimioterapia de hospital público do estado de São Paulo realizado de abril de 2018 a março de 2019. A amostra constituiu de 55 pacientes com tumores sólidos, a partir do segundo ciclo de tratamento com fármacos endovenosos citotóxicos para o tecido hematopoiético. O comprimento de onda utilizado foi de 660 nm, por via transcutânea, sob artéria radial. Resultado. Comparado ao tipo de hemocomponente, obtivemos, respectivamente aos protocolos do Intravenous Laser Irradiation of Blood 30' e 60': hemoglobina (85%; 86%), plaquetas (100%; 100%) e neutrófilos (95%; 92%). Conclusão. Considerou-se ambos os protocolos eficazes e, portanto, sugere-se implantá-los em unidades de quimioterapia(AU)

Objective: To evaluate the effectiveness of the protocols for transcutaneous application of the Intravenous Laser Irradiation of Blood 30' and 60', on the adverse effects on hematopoietic tissue by intravenous antineoplastic chemotherapeutic agents in adults. Method. Clinical, randomized and single-blind trial, carried out in an outpatient chemotherapy service of a public hospital in the state of São Paulo, carried out from April 2018 to March 2019. The sample consisted of 55 patients with solid tumors, from the second cycle of treatment with cytotoxic intravenous drugs for hematopoietic tissue. The wavelength used was 660 nm, transcutaneously, under the radial artery. Result. Compared to the type of blood component, we obtained, respectively from the Intravenous Laser Irradiation of Blood 30' and 60' protocols: hemoglobin (85%; 86%), platelets (100%; 100%) and neutrophils (95%; 92%). Conclusion. Both protocols were considered effective and, therefore, it is suggested to implant them in chemotherapy units.(AU)

Objetivo. Evaluar la efectividad de los protocolos de aplicación transcutánea de Irradiación Láser Intravenosa de Sangre 30' y 60', sobre los efectos adversos sobre el tejido hematopoyético por agentes quimioterápicos antineoplásicos intravenosos en adultos. Método. Ensayo clínico, aleatorizado y simple ciego, realizado en un servicio de quimioterapia ambulatoria de un hospital público del estado de São Paulo, realizado de abril de 2018 a marzo de 2019. La muestra estuvo compuesta por 55 pacientes con tumores sólidos, del segundo ciclo. del tratamiento con fármacos intravenosos citotóxicos para el tejido hematopoyético. La longitud de onda utilizada fue de 660 nm, por vía transcutánea, bajo la arteria radial. Resultado. En comparación con el tipo de componente sanguíneo, obtuvimos, respectivamente, de los protocolos de Irradiación Intravenosa con Láser de Sangre 30' y 60': hemoglobina (85%; 86%), plaquetas (100%; 100%) y neutrófilos (95%; 92%). %). Conclusión. Ambos os protocolos se consideraron efectivos, por lo que se sugiere implantarlos en las unidades de quimioterapia(AU)

Caracterización epidemiológica de las neoplasias del tejido hematopoyético y linfoide atendidos en el Instituto Oncológico Nacional-SOLCA Guayaquil / Epidemiological characterization of Hematopoietic and Lymphoid Neoplasms treated at the National Oncological Institute-SOLCA Guayaquil

Introducción: Dentro de las cinco primeras neoplasias en el mundo están las Leucemias, la misma que ha venido incrementándose en las últimas décadas. El objetivo del presente estudio fue determi-nar las características epidemiológicas de las Neoplasias del tejido Hematopoyético y linfoide en pacientes atendidos en el Instituto Oncológico Nacional-SOLCA Guayaquil durante los años 2015 al 2019. Metodología: Se efectuó un estudio de diseño observacional, descriptivo poblacional; donde el universo y la muestra fueron 891 casos nuevos de neoplasias del Tejido Hematopoyético y Linfoide, recolectándose los datos en una matriz, que fueron tomados del programa informático del registro de tumores. Resultados: se diagnosticaron Leucemias Linfoideas (69.58%) y Leucemias Mieloides (30.30%); más en hombres (53.33%) que mujeres (44.67%); siendo los casos en menores de 19 años en Gua-yaquil del 57.33% y en Otras ciudades con el 64.36%; en Guayaquil el grupo de edad de 5 ­ 9 años fue más frecuente con 20.57% seguido de los menores de 5 años con 19.02%; mientras que en Otras ciudades fueran los menores de 5 años con 20.72% seguido del grupo etario de 5 ­ 9 años con 18.33%; entre otros grupos. Su mayor frecuencia en Guayaquil fueron en parroquias Tarqui, Ximena y en Otras ciudades en Región Costa (81.47%). Conclusión: Dentro de las neoplasias del Tejido Hematopoyético y Linfoide la más común fue las Leucemias Linfoideas en la población menor de 19 años con énfasis en los niños menores de 5 años mostrando una presencia importante en los años de estudio en Guayaquil y en la región Costa del Ecuador.

Introduction: Leukemias are among the first five neoplasms in the world, the same one that has been increasing in recent decades. The aim of this study was to determine the epidemiological char-acteristics of Hematopoietic and Lymphoid Neoplasms in patients treated at the National Oncological Institute-SOLCA Guayaquil during the years 2015 to 2019. Methodology: An observational, descriptive population study was carried out; Where the universe and the sample were 891 new cases of Hematopoietic and Lymphoid neoplasms, the data was col-lected in a matrix, taken from the tumor registry computer program. Results: Lymphoid Leukemias were diagnosed in 69.58% and Myeloid Leukemias with 30.30%; more in men (53.33%) than women (44.67%); being the cases in minors of 19 years in Guayaquil 57.33% and in Other cities it had 64.36%; in Guayaquil the age group of 5 - 9 years was more frequent with 20.57% followed by those under 5 years with 19.02%; while in Other cities under 5 years old with 20.72% followed by the age group of 5 - 9 years old with 18.33%; among other groups. Its highest frequency in Guayaquil was in Tarqui and Ximena parishes and in other cities it was in the Coastal Region with 81.47%. Conclusion: Among the Hematopoietic and Lymphoid neoplasms the most common was Lym-phoid Leukemias in the population under 19 years of age, with emphasis on children under 5 years of age, showing an important presence in the years of study in Guayaquil and in the Ecuadorian Coastal region.

Toxic Effects of Long-term Exposure to PM / 中国实验血液学杂志

OBJECTIVE@#To investigate the toxic damage and possible mechanism of chronic exposure of ambient particulate matter (PM@*METHODS@#Mice were treated with different doses (150, 300, 600 mg/kg) of chitosan after exposure to PM@*RESULTS@#Compared with the mice in control group, IL-2 secretion and CXCL12 expression were decreased in the bone marrow of PM@*CONCLUSION@#Chronic exposure of PM

Bioinformatics Analysis of the Influence of Coronavirus Infection on Hematopoietic System and Potential Intervention Drugs and Their Significance for COVID-19 / 中国实验血液学杂志

OBJECTIVE@#To analyze and predict the effect of coronavirus infection on hematopoietic system and potential intervention drugs, and explore their significance for coronavirus disease 2019 (COVID-19).@*METHODS@#The gene expression omnibus (GEO) database was used to screen the whole genome expression data related with coronavirus infection. The R language package was used for differential expression analysis and KEGG/GO enrichment analysis. The core genes were screened by PPI network analysis using STRING online analysis website. Then the self-developed apparent precision therapy prediction platform (EpiMed) was used to analyze diseases, drugs and related target genes.@*RESULTS@#A database in accordance with the criteria was found, which was derived from SARS coronavirus. A total of 3606 differential genes were screened, including 2148 expression up-regulated genes and 1458 expression down-regulated genes. GO enrichment mainly related with viral infection, hematopoietic regulation, cell chemotaxis, platelet granule content secretion, immune activation, acute inflammation, etc. KEGG enrichment mainly related with hematopoietic function, coagulation cascade reaction, acute inflammation, immune reaction, etc. Ten core genes such as PTPRC, ICAM1, TIMP1, CXCR5, IL-1B, MYC, CR2, FSTL1, SOX1 and COL3A1 were screened by protein interaction network analysis. Ten drugs with potential intervention effects, including glucocorticoid, TNF-α inhibitor, salvia miltiorrhiza, sirolimus, licorice, red peony, famciclovir, cyclosporine A, houttuynia cordata, fluvastatin, etc. were screened by EpiMed plotform.@*CONCLUSION@#SARS coronavirus infection can affect the hematopoietic system by changing the expression of a series of genes. The potential intervention drugs screened on these grounds are of useful reference significance for the basic and clinical research of COVID-19.

Síndrome de Hiper IgD: espectros clínicos, achados genéticos e condutas terapêuticas / Hyper-IgD syndrome: clinical spectrum, genetic findings, and therapeutic approaches

A deficiência de mevalonato quinase (MVK; MIM #142680; ORPHA #343) é uma doença genética, espectral, rara, associadas a mutações ao longo do gene MVK causando distúrbios na síntese do colesterol, que culminam em: inflamação sistêmica com febre, adenopatia, sintomas abdominais e outros achados clínicos. Enquanto no polo leve da doença os achados mais comuns são febres recorrentes com linfadenopatia, no polo mais grave adiciona-se o acometimento do sistema nervoso central (meningites assépticas, vasculites e atraso do desenvolvimento neuropsicomotor) e do sistema hematopoiético (síndrome de ativação macrofágica). Apesar de inúmeras terapêuticas, os bloqueadores da interleucina-1 ainda são os únicos medicamentos capazes de controlar a doença e de impedir a evolução para amiloidose. Os estudos atuais visam tentar novos tratamentos, como o transplante de células-tronco hematopoiéticas, ou mesmo a terapia gênica.

Mevalonate kinase deficiency (MVK; MIM #142680; ORPHA #343) is a rare spectral genetic disorder linked to mutations along the MVK gene leading to impaired cholesterol synthesis, clinically observed as systemic inflammation with fever, adenopathy, abdominal manifestations, and other clinical findings. While on mild forms recurrent fever with lymphadenopathy is commonly observed, severe forms add to that neurological (aseptic meningitis, vasculitis, and neuropsychomotor developmental delay) and hematopoietic involvement (macrophage activation syndrome). Despite of several therapeutic approaches, blocking interleukin-1 is the only effective method to control the disease and prevent the development of systemic amyloidosis. Ongoing studies aim to test new treatments, such as hematopoietic stem cell transplantation and gene therapy.

Mechanism of Hematopoietic Reconstruction in Mice Treated with Danggui Buxue Decoction combined with Muscle-Derived Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanism of hematopoietic reconstruction in mice treated with Danggui Buxue Decoction (DBD) combined with the muscle-derived stem cell transplantation (MDSCT).@*METHODS@#Female Kunming mice were randomly divided into the 6 groups: irradiation model, the bone marrow transplantation, the MDSC transplantation, the DBD 1 (4.5 g/kg), 2 (13.5 g/kg), and 3 (22.5 g/kg) + MDSC transplantation. After a week of oral administration of normal saline or different doses of DBD, The mice were exposied to 8 Gy Cs γ ray and were followed by bone marrow or MDSC transplantation. The expression levels of Notch1, Jagged1 and Hes1 in bone marrow, thymus and spleen were measured at 3 and 8 weeks after irradiation and transplantation.@*RESULTS@#In the bone marrow, 3 weeks after above-mentioned treatment, the expression of Notch1 mRNA increased obviously and the expression of Jagged1, Hes1 mRNA decreased obviously in each intervention group, compared with the irradiation model group. 8th week after treatment, the expression of Notch1 mRNA decreased obviously in each intervention group, the Jagged1 mRNA expression decreased obviously except the bone marrow group, and Hes1 mRNA expression increased (P＜0.05) in each intervention group. 3 weeks after treatment, compared with the irradiation model group, the expression of Notch1 mRNA in the thymocytes increased only in DBD1+MDSC group, Jagged1, Hes1 mRNA was increased in the MDSC transplantation group and the DBD1、2+MDSC group. 8th week after treatment, the expression of Notch1, Jagged1 mRNA expression decreased in each intervention group, the expression of Hes1 mRNA increased obviously in the MDSC transplantation group and the DBD1、2+MDSC group (P＜0.05). In the spleen, 3 weeks after treatment, the expression of Notch1, Jagged1 mRNA in the spleen of each intervention group decreased obviously, compared with the irradiation model group. The expression of Jagged1, Hes1 mRNA in each intervention group were increased obviously 8th week after treatment (P＜0.05).@*CONCLUSION@#MDSC transplantation after pretreatment of DBD can improve the hematopoietic reconstitution in mice with lethal dose radiation damage. Notch1、Jagged1 and Hes1 play different roles in this process, but the concrete mechanism needs to be further studied.

Material didáctico para la enseñanza aprendizaje del sistema hemolinfopoyético en la carrera Bioanálisis Clínico / Teaching aid for the teaching-learning of the hemolinfopoietic system in the Clinical Bioanalysis degree

RESUMEN Fundamento: la educación superior efectúa transformaciones profundas que se convierten en un factor clave para la puesta en marcha de procesos necesarios en el enfrentamiento a los desafíos del mundo existente. Objetivo: elaborar un material didáctico para la enseñanza aprendizaje del sistema hemolinfopoyético, con énfasis en el extendido de sangre periférica en la carrera de Bioanálisis Clínico. Métodos: se realizó un estudio descriptivo transversal en el período septiembre 2017-febrero 2018, en la Facultad Tecnológica "Octavio de la Concepción y de la Pedraja" de la Universidad de Ciencias Médicas "Carlos J. Finlay", de Camagüey. Se emplearon métodos teóricos: analítico-sintético e inductivo-deductivo; empíricos: observación a clases, la encuesta en forma de entrevista a docentes y la prueba exploratoria a estudiantes; y matemático-estadísticos para el cálculo de las frecuencias absolutas y el porcentaje. El producto fue valorado por criterios de especialistas. Resultados: se evidenciaron insuficiencias en el proceso enseñanza aprendizaje por los profesores para trabajar de manera integrada los procesos cognitivos sobre extendidos de sangre periférica como una vía para analizar las células hematopoyéticas; entre los estudiantes primaron el uso incorrecto de técnicas y procederes en los análisis y en la elaboración de los informes a partir de la observación e interpretación de extendidos de sangre periférica como componente esencial de la Hematología. Conclusiones: se elaboró un material didáctico que fue valorado por criterios de especialistas en las categorías de muy adecuado y adecuado en todos los indicadores propuestos, por lo que se consideró factible de ser aplicado.

ABSTRACT Background: Higher education carries out profound transformations that become a key factor for the implementation of necessary processes in the face of world challenges. Objective: to develop a teaching aid for the teaching - learning of the hemolinfopoietic system, with emphasis on the spread of peripheral blood in the Clinical Bioanalysis degree. Methods: a descriptive cross-sectional study was carried out from September 2017-to February 2018, at the "Octavio de la Concepción y de la Pedraja" Technological Faculty of the "Carlos J. Finlay" Camagüey University of Medical Sciences. Theoretical methods were used: analytical-synthetic and inductive-deductive; Empirical ones: observation to classes, the survey in the form of teacher interviews and the exploratory test to students; and mathematical-statistics for the calculation of the absolute frequencies and the percentage. The product was valued by criteria of specialists. Results: inadequacies in the teaching-learning process were evidenced by teachers to work in a comprehensive way on the cognitive processes on peripheral blood as a way to analyze hematopoietic cells; Among the students, the incorrect use of techniques and procedures prevailed in the analysis and in the preparation of the reports based on the observation and interpretation of peripheral blood spreads as an essential component of Hematology. Conclusions: a teaching aid was developed that was assessed by criteria of specialists in the categories of very adequate and adequate in all the proposed indicators, so it was considered feasible to be applied.

The autophagy Protein Atg5 Plays a Crucial Role in the Maintenance and Reconstitution Ability of Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) in bone marrow are pluripotent cells that can constitute the hematopoiesis system through self-renewal and differentiation into immune cells and red blood cells. To ensure a competent hematopoietic system for life, the maintenance of HSCs is tightly regulated. Although autophagy, a self-degradation pathway for cell homeostasis, is essential for hematopoiesis, the role of autophagy key protein Atg5 in HSCs has not been thoroughly investigated. In this study, we found that Atg5 deficiency in hematopoietic cells causes survival defects, resulting in severe lymphopenia and anemia in mice. In addition, the absolute numbers of HSCs and multiple-lineage progenitor cells were significantly decreased, and abnormal erythroid development resulted in reduced erythrocytes in blood of Vav_Atg5(−/−) mice. The proliferation of Lin⁻Sca-1⁺c-Kit⁺ HSCs was aberrant in bone marrow of Vav_Atg5(−/−) mice, and mature progenitors and terminally differentiated cells were also significantly altered. Furthermore, the reconstitution ability of HSCs in bone marrow chimeric mice was significantly decreased in the presence of Atg5 deficiency in HSCs. Mechanistically, impairment of autophagy-mediated clearance of damaged mitochondria was the underlying cause of the HSC functional defects. Taken together, these results define the crucial role of Atg5 in the maintenance and the reconstitution ability of HSCs.

Haematopoietic stem cell transplantation in South Africa: Current limitations and future perspectives

The growing need for haematopoietic stem cell transplantation (HSCT) is reflected in the increasing number of transplants performed globally each year. HSCT provides life-changing and potentially curative therapy for a range of pathologies including haematological malignancies; other indications include certain congenital and acquired disorders of the haematopoietic system, autoimmune conditions and hereditary diseases. The primary goals of HSCT are either to replace haematopoietic stem and progenitor cells (HSPC) following myeloablative chemotherapy or to cure the original pathology with allogeneic HSPCs. Success depends on optimal outcomes at various stages of the procedure including mobilisation of marrow stem/progenitor cells for harvesting from the patient or donor, long-term and sustainable engraftment of these cells in the recipient, and prevention of graft-versus-host disease in the case of allogeneic HSCT. Challenges in South Africa include high cost, limited infrastructure and lack of appropriately trained staff, as well as limitations in securing suitable haematopoietic stem cell donors. This review aims to provide an overview of HSCT and some of the challenges that are faced in the South African context

Transplantation of gene-modified haematopoietic stem cells: Application and clinical considerations

Autologous and allogeneic haematopoietic stem cell (HSC) transplantation has been performed in patients with various malignant and non-malignant haematological disorders for more than 50 years. Ex vivo gene modification of HSCs for autologous transplantation opens up new therapeutic avenues for genetic and infectious diseases. Major advances have been made over the last three decades with respect to gene modification of HSCs and transplantation strategies, ultimately culminating in the approval of two such therapies in Europe (Strimvelis for a rare primary immune deficiency, and LentiGlobin for beta-thalassaemia). Newer gene-modifying technologies and treatment regimens have also recently come to the fore, which hold great promise for the development of safer and more effective treatments. We provide an overview of the current state of gene-modified HSC therapies, highlighting success stories, limitations and important considerations for achieving successful translation of these therapies to the clinic

Adult Stem Cells in Hibernation: Future Perspectives of Space Travel

Space traveling is imperative for mankind in the future. Expectedly, hibernation will become an option for space traveler to overcome the endless voyage. With regard to some of the studies pointed out that during hibernation, muscle will undergo atrophy and meantime neurogenesis will reduce, these obstacles were frequently related with stem cell regeneration. Thus, investigation on whether hibernation will lead to dysfunction of stem cell becomes an important issue. By going through four main systems in this article, such as, hematopoietic system, skeletal muscle system, central nervous system and orthopedic system, we are expecting that stem cells regeneration capacity will be affected by hibernation. To date, these researches are majorly the read-out from short term or seasonal hibernating mammals. Proposing and creating a simulated long-term hibernation animal model is turning essential for the further investigation on the effect of longer period of hibernation to human stem cells.

Solitary mastocytoma presenting at birth

Mastocytosis is a rare disease which occurs in both children and adults, and it can manifest as a solitary or multiple skin lesions. Both can cause cutaneous or systemic symptoms. Because of the heterogeneity of clinical presentation of mastocytosis and its rare prevalence, it can be hard to suspect the mastocytosis at the first time. Most solitary mastocytomas are about 1–5 cm in diameter and have features of brownish-yellow, minimally elevated plaques with a smooth shiny surface. This article presents a case of solitary mastocytoma which occurred in neonate and that we treated through surgical excision. In histopathological examination, it consisted of c-kit-positive mast cells. Although pediatric cutaneous mastocytosis might regress spontaneously, clinicians should keep in mind that it could be associated with systemic mastocytosis which involves hematopoietic system.

Nuevas estrategias en trasplante de precursores hematopoyético / New strategies in hematopoietic precursor transplantation

El trasplante hematopoyético es una estrategia terapéutica que permite posibilidad de curación en diversas enfermedades benignas y malignas. El autotrasplante tiene demostrada utilidad en mieloma y linfomas permitiendo recuperar la hematopoyesis luego de quimioterapias de alta intensidad. El alotrasplante permite reemplazar hematopoyesis defectuosa y/o introducir un potente efecto inmunológico llamado "efecto de injerto contra tumor". En los últimos años, se han desarrollado nuevos fármacos que permiten optimizar la recolección de progenitores autólogos y se han modificado los esquemas de trasplante, permitiendo un uso más amplio. El haplo trasplante alogénico ha favorecido que los enfermos tengan mejores posibilidades de encontrar donantes. En esta revisión, se analizan brevemente estas nuevas modalidades adoptadas en nuestro programa de trasplante hematopoyético.(AU)

Hematopoietic transplantation offers cure or control in several benign or malignant diseases. Autologous transplantation has proven to be useful in myeloma and lymphoma patients allowing hematopoiesis recovery after high-intensity chemotherapies. Allogeneic transplantation can replace defective hematopoiesis and / or introduce graft-versus-tumor effect. In recent years, new strategies have been developed to optimize autologous progenitor's collection and haploidentical modalities have allowed a wider use of allotransplants. In this brief review these new modalities adopted in our program are analyzed.(AU)

Role of SOX7 in Hematopoietic System Development and Hematological Malignancies--Review / 中国实验血液学杂志

The sex-determining region Y-box 7 (Sox7) is a important member of SOX family containing high mobi- lity group (HMG), mapped to human chromosome 8p23.1. Wnt/β-catenin signaling pathway plays an important role in cell survival, differentiation, self-renewal, proliferation and apoptosis, and is closely related with carcinogenesis. SOX7 gene is likely to be a tumor suppressor gene in MDS and other hematological malignancies. As a negative regulator of the WNT/β-catenin signaling pathway, the function loss of this gene can lead to carcinogenesis. The methylation of SOX7 gene leads to the silence of this gene, resulting in tumorigenesis. The decision of hematopoietic stem cells to self-renew or differentiate is a stochastic process, but SOX7 can promote the differentiation into all blood cell types. This review focuses on the role of SOX7 in hematopoietic system development and hematological malignancies.

Changes in serum uric acid levels after allogeneic hematologic stem cell transplantation: A retrospective cohort study

BACKGROUND: Since cell turnover in the hematopoietic system constitutes a major source of uric acid (UA) production, we investigated whether hematopoietic stem cell transplantation (HSCT) is associated with significant changes in serum UA levels in patients with hematological disorders. METHODS: Patients who underwent HSCT at our institution between 2001 and 2012 were retrospectively enrolled. Serum UA levels at 3 months before, 1 week before, and 3 months and 1 year after HSCT were examined. RESULTS: Complete clinical and laboratory information including data regarding UA levels was available for 93 patients. At baseline, the mean UA level was 4.9±2.1 mg/dL, with an overall prevalence of hyperuricemia of 15% (defined as serum UA>6.8 mg/dL). Mean UA levels tended to be higher in patients with acute myeloid leukemia (4.8±2.0 mg/dL) and non-Hodgkin lymphoma (5.1±2.3 mg/dL) and lower in patients with aplastic anemia (mean, 4.2±1.8 mg/dL). UA levels dropped during myeloablative conditioning, reaching a nadir on the day of HSCT (3.27±1.4 mg/dL). Over the 3 months following HSCT, UA levels rose sharply (5.0±2.1 mg/dL) and remained stable up to 1 year after HSCT (5.5±1.6 mg/dL). UA levels in HSCT recipients at 12 months correlated with those of their respective graft donors (Pearson r=0.406, P=0.001). CONCLUSION: HSCT is associated with significant changes in uric acid levels in patients with hematologic disorders.

Importancia del estudio de la médula ósea en el Hospital Carlos Andrade Marín en el año 2013 / Importance of the bone marrow study of the year 2013 in Carlos Andrade Marin Hospital

Objetivo: el estudio de la biopsia de la médula ósea tiene como objetivo el diagnosticar los problemas que existen con los diversos tipos de células sanguíneas, con el fin de realizar un tratamiento y obtener un pronóstico adecuados; en el tiempo este exámen ha ido ampliándose y junto con el aspirado ayudan a la evaluación de patologías como anemia, trombocitopenia, linfomas, leucemias, tumores metastáticos, síndromes mieloproliferativos entre otros. Materiales y métodos: estudio retrospectivo, descriptivo y con diseño transversal. Se analizaron 450 muestras obtenidas desde enero a diciembre del 2013 para evaluar las distintas patologías que se presentan frecuentemente en nuestro hospital, de acuerdo a edad y sexo. Resultados: de los 450 casos receptados, analizados y reportados en el 2013; 236 muestras fueron negativas; 27 fueron muestras insuficientes e inadecuadas y 187 fueron positivas para lesiones benignas, borderline y malignas. La mayor parte de lesiones fueron más en hombres y en edades comprendidas entre 40 y 69 años. Las lesiones benignas más frecuentes fue la Hipoplasia y dentro de las lesiones malignas la infiltración linfocitica de inmunofenotipo B, la misma que se corroboró con estudio de Inmunohistoquimica. Conclusión: se determina que de los estudios realizados, la patología que con mayor frecuencia afecta a los pacientes del Hospital Carlos Andrade Marín, sometidos a biopsia de médula ósea en el año 2013 es la Infiltración de estirpe linfoide con biopsy has become important for the treatment and prognosis of diseases. Inmunofenotipo B. De ahí que el estudio de biopsia de médula ósea se ha tornado importante para el tratamiento y pronóstico de las diferentes patologías hematológicas y metastásicas.

Objective: the study of bone marrow biopsy aims to diagnose the problems that exist with the different types of blood cells, with the aim of treatment and obtain an acertive prognosis, with time this test has become popular and together with the aspirate helps with the evaluation of diseases such as anemia, trombocitopenia, leucemias, lymphomas among others, myeloproliferative syndromes, and metastatic tumors. Materials and methods: a retrospective descriptive study with cross-sectional design was used to analyze 450 samples obtained from january to december of 2013 in order to evaluate the different pathologies that arise frequently in our hospital, profiled by age and sex. Results: of the 450 analyzed cases and reported in the 2013; 236 samples were negative; 27 were insufficient and inadequate samples, 187 were positive for benign lesions, borderline or malignant. Most of the lesions were in men aged between 40 and 69 years; Hypoplasia was amongst the most benign lesions and among the malignant lesions was the Immune B Lymphocytic Infiltration, which was corroborated with inmunohistochemical staining. Conclusion: this study determines that the disease which most often affects patients of the Hospital Carlos Andrade Marín undergoing bone marrow biopsy in the year 2013 was lineage with Immune B lymphoid infiltration. Hence the study of bone marrow biopsy has become important for the treatment and prognosis of diseases.

Rapamycin decreases irradiation-induced hematopoietic system damage / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the protection function of rapamycin in hematopoietic system damage induced by irradiation.</p><p><b>METHODS</b>Six to eight week old C57BL/6J male mice were used for experiment. Mice received 4 mg/kg rapamycin by i.p.injection every other day for 5 times. The day after the last injection, mice were exposed to a dose (5 Gy) of total body irradiation (TBI). Peripheral blood was measured by a complete blood count at 0.5, 1, 2, 3, 5, 7, 40, 70 days after TBI. The hematoxylin-eosin staining was used to observe the pathologic changes in sternum obtained from mice at day 5 after TBI. CFU-S of spleen was measured by immerging in Tellyesniczky solution for 24 h at day 5 after TBI.</p><p><b>RESULTS</b>Before TBI, WBC and LYM decreased in rapamycin-treated mice compared with control (P<0.01); RBC and HGB increased (P<0.05); there was no difference in PLT; HE staining of bone marrow from rapamcin-treated and control mice before irradiation showed no difference in marrow cellularity. After TBI, WBC and LYM decreased significantly, with no difference at 0.5 d to 7 d between rapamycin-treated and control. The counts of WBC and LYM in rapamycin-treated mice restored to normal at 40 d and 70 d. RBC and HGB decreased at irradiation group at 3 d to 7 d, but rapamycin stimulated them to a higher level, both of them tended to normal at 40 d and 70 d. HE staining of bone marrow after 5 day of 5 Gy irradiation, nucleated cells in control decreased significantly, but restored in rapamycin-treated mice. CFU-S results showed the colony number in rapamycin-treated mice was much higher than control mice after 5 Gy irradiation, with 40.00±12.86 and 13.20±2.31 (P=0.035), respectively.</p><p><b>CONCLUSION</b>Administration of rapamycin to mice before irradiation protected the mice from hematopoietic damage induced by irradiation by maintaining the bone marrow nucleated cells, slowing down decrease and promoting the restoration of peripheral blood cells and protecting hematopoitic stem/progenitor cells in spleen.</p>

Evaluation and management of lead exposure

Lead, which is widely used in industry, is a common element found in low concentrations in the Earth's crust. Implementations to reduce environmental lead concentrations have resulted in a considerable reduction of lead levels in the environment (air) and a sustained reduction in the blood lead levels of the average citizen. However, people are still being exposed to lead through a variety of routes in everyday commodities. Lead causes health problems such as toxicity of the liver, kidneys, hematopoietic system, and nervous system. Having a carcinogenic risk as well, the IARC classifies inorganic lead compounds as probably carcinogenic to humans (Group 2A). Occupational lead poisonings have decreased due to the efforts to reduce the lead concentrations in the working environment. In contrast, health hazards associated with long-term environmental exposure to low concentrations of lead have been reported steadily. In particular, chronic exposure to low concentrations of lead has been reported to induce cognitive behavioral disturbances in children. It is almost impossible to remove lead completely from the human body, and it is not easy to treat health hazards due to lead exposure. Therefore, reduction and prevention of lead exposure are very important. We reviewed the toxicity and health hazards, monitoring and evaluation, and management of lead exposure.