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Frontiers of Medicine ; (4): 240-262, 2023.
Article in English | WPRIM | ID: wpr-982569


Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.

Humans , Brain Neoplasms/pathology , Neoplasm Recurrence, Local/metabolism , Glioma/pathology , Neural Stem Cells/pathology , Oligodendrocyte Precursor Cells/pathology , Tumor Microenvironment
Chinese Journal of Contemporary Pediatrics ; (12): 410-415, 2021.
Article in Chinese | WPRIM | ID: wpr-879868


OBJECTIVE@#To study the effect of human oligodendrocyte precursor cell (hOPC) transplantation in the treatment of white matter injury (WMI).@*METHODS@#Neonatal rats were randomly divided into a sham-operation group, a model group, and a transplantation group (@*RESULTS@#The place navigation test using the Morris water maze showed that the model group had a significantly longer escape latency than the sham-operation group, and compared with the model group, the transplantation group had a significant reduction in escape latency (@*CONCLUSIONS@#Intrathecal hOPC transplantation may alleviate neurological injury and promote remyelination in a rat model of WMI.

Animals , Humans , Rats , Animals, Newborn , Myelin Sheath , Oligodendrocyte Precursor Cells , Oligodendroglia , White Matter
Chinese Acupuncture & Moxibustion ; (12): 519-525, 2020.
Article in Chinese | WPRIM | ID: wpr-826702


OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Jiaji" (EX-B 2) points on the proliferation and differentiation of oligodendrocyte precursor cells in rats with acute incomplete spinal cord injury, and to explore the mechanism of EA on improving motor function of spinal cord injury.@*METHODS@#A total of 72 male SPF SD rats were randomly divided into a sham operation group, a model group, an EA group and a medication group, 18 rats in each group. Each group was further divided into 1-day subgroup, 7-day subgroup and 14-day subgroup, 6 rats in each subgroup. The T acute incomplete spinal cord injury model was established by modified Allen's method in the model group, EA group and medication group. The rats in each group received intraperitoneal injection of 5-bromodeoxyuridine (BrdU, 50 mg/kg), once a day, and each subgroup received continuous injection for 1, 7, 14 times for cell proliferation labeling. The rats in the EA group were treated with EA at "Jiaji" (EX-B 2) points 3-4 mm next the spinous process of the upper and lower segments of the injured spinal cord (T, T) with a frequency of 2 Hz/100 Hz and intensity of 1-2 mA. The muscle twitch at the treatment site was taken as the degree. The treatment was given 20 min each time, once a day. In the medication group, monosialogangliosides (GM1) was injected intraperitoneally (10 mg/kg), once a day. The subgroups of EA group and medication group were treated for 1, 7, 14 times. The score of Basso Beattie Bresnahan (BBB) was used to evaluate the motor function of hind limbs. The co-expression of BrdU/NG2 positive cells was detected by immunofluorescence, and the expression of Olig2 and Sox10 was detected by Western blot.@*RESULTS@#Compared with the sham operation group, the BBB score was decreased 1 day, 7 days and 14 days after operation in the model group (<0.05), the expression of Olig2 and Sox10 was increased (<0.05), and the co-expression of BrdU/NG2 positive cells was increased 7 days and 14 days after operation (<0.05). Seven days and 14 days after operation, the BBB score in the EA group and medication group was higher than that in the model group (<0.05), and the co-expression of BrdU/NG2 in the medication group was higher than that in the model group (<0.05). Fourteen days after operation, the co-expression of BrdU/NG2 in the EA group was higher than that in the model group (<0.05); 1 day, 7 days and 14 days after operation, the expression of Olig2 and Sox10 in the EA group and medication group was higher than that in the model group (<0.05). Compared with the medication group, the co-expression of BrdU/NG2 positive cells in the EA group 14 days after operation was decreased (<0.05); 1 day, 7 days and 14 days after operation, the expression of Olig2 and Sox10 in the EA group was decreased (<0.05).@*CONCLUSION@#EA at "Jiaji" (EX-B 2) points could promote the expression of Olig2 and Sox10 after spinal cord injury, which has similar effects with GM1. It could promote the proliferation and differentiation of oligodendrocyte precursor cells into oligodendrocytes, so as to promote the recovery of motor function of rats.

Animals , Humans , Male , Rats , Acupuncture Points , Cell Differentiation , Cell Proliferation , Electroacupuncture , Oligodendrocyte Precursor Cells , Cell Biology , Oligodendrocyte Transcription Factor 2 , Metabolism , Random Allocation , Rats, Sprague-Dawley , SOXE Transcription Factors , Metabolism , Spinal Cord , Spinal Cord Injuries , Therapeutics
Neuroscience Bulletin ; (6): 434-446, 2019.
Article in English | WPRIM | ID: wpr-775427


The obstacle to successful remyelination in demyelinating diseases, such as multiple sclerosis, mainly lies in the inability of oligodendrocyte precursor cells (OPCs) to differentiate, since OPCs and oligodendrocyte-lineage cells that are unable to fully differentiate are found in the areas of demyelination. Thus, promoting the differentiation of OPCs is vital for the treatment of demyelinating diseases. Shikimic acid (SA) is mainly derived from star anise, and is reported to have anti-influenza, anti-oxidation, and anti-tumor effects. In the present study, we found that SA significantly promoted the differentiation of cultured rat OPCs without affecting their proliferation and apoptosis. In mice, SA exerted therapeutic effects on experimental autoimmune encephalomyelitis (EAE), such as alleviating clinical EAE scores, inhibiting inflammation, and reducing demyelination in the CNS. SA also promoted the differentiation of OPCs as well as their remyelination after lysolecithin-induced demyelination. Furthermore, we showed that the promotion effect of SA on OPC differentiation was associated with the up-regulation of phosphorylated mTOR. Taken together, our results demonstrated that SA could act as a potential drug candidate for the treatment of demyelinating diseases.

Animals , Female , Rats , Apoptosis , Cell Differentiation , Cell Proliferation , Cells, Cultured , Demyelinating Diseases , Encephalitis , Encephalomyelitis, Autoimmune, Experimental , Mice, Inbred C57BL , Myelin Basic Protein , Metabolism , Neuroprotective Agents , Oligodendrocyte Precursor Cells , Metabolism , Remyelination , Shikimic Acid , TOR Serine-Threonine Kinases , Metabolism
Neuroscience Bulletin ; (6): 247-260, 2018.
Article in English | WPRIM | ID: wpr-777042


The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is essential for myelination and remyelination in the CNS. The failure of OPCs to achieve terminal differentiation in demyelinating lesions often results in unsuccessful remyelination in a variety of human demyelinating diseases. However, the molecular mechanisms controlling OPC differentiation under pathological conditions remain largely unknown. Myt1L (myelin transcription factor 1-like), mainly expressed in neurons, has been associated with intellectual disability, schizophrenia, and depression. In the present study, we found that Myt1L was expressed in oligodendrocyte lineage cells during myelination and remyelination. The expression level of Myt1L in neuron/glia antigen 2-positive (NG2) OPCs was significantly higher than that in mature CC1 oligodendrocytes. In primary cultured OPCs, overexpression of Myt1L promoted, while knockdown inhibited OPC differentiation. Moreover, Myt1L was potently involved in promoting remyelination after lysolecithin-induced demyelination in vivo. ChIP assays showed that Myt1L bound to the promoter of Olig1 and transcriptionally regulated Olig1 expression. Taken together, our findings demonstrate that Myt1L is an essential regulator of OPC differentiation, thereby supporting Myt1L as a potential therapeutic target for demyelinating diseases.

Animals , Mice , Cell Differentiation , Physiology , Demyelinating Diseases , Lysophosphatidylcholines , Toxicity , Mice, Inbred C57BL , Nerve Tissue Proteins , Metabolism , Oligodendrocyte Precursor Cells , Cell Biology , Metabolism , Oligodendroglia , Cell Biology , Metabolism , Remyelination , Physiology , Transcription Factors , Metabolism
Chinese Journal of Contemporary Pediatrics ; (12): 326-331, 2018.
Article in Chinese | WPRIM | ID: wpr-689632


White matter damage, characterized by demyelination due to the damage of oligodendrocyte precursor cells (OPCs), is the most common type of brain damage in preterm infants. Survivors are often subject to long-term neurodevelopmental sequelae because of the lack of effective treatment. In recent years, it has been found that cell transplantation has the potential for the treatment of white matter damage. OPCs are frequently used cells in cell transplantation therapy. With abilities of migration and myelinization, OPCs are the best seed cells for the treatment of white matter damage. Several studies have found that OPCs may not only replace impaired cells to reconstruct the structure and function of white matter, but also inhibit neuronal apoptosis, promote the proliferation of endogenous neural stem cells, and enhance the repairment of the blood-brain barrier. However, the clinical application of OPC transplantation therapy faces many challenges, such as the effectiveness, risk of tumorigenesis and immune rejection. With reference to these studies, this article reviewed the development of myelination, the obtainment of OPCs, the therapeutic mechanism as well as application research, and analyzed the current challenges of OPC transplantation, in order to provide a new direction for clinical treatment of white matter damage in preterm infants.

Humans , Infant, Newborn , Cell Separation , Demyelinating Diseases , Therapeutics , Infant, Premature , Oligodendrocyte Precursor Cells , Transplantation , White Matter , Pathology
Tempus (Brasília) ; 11(2): 41-52, abr.-jun. 2017.
Article in Portuguese | LILACS | ID: biblio-881367


Objetivos: O objetivo do presente trabalho foi analisar a vulnerabilidade ao HIV de jovens estudantes universitários. Métodos: Trata-se de pesquisa descritiva tipo levantamento realizada com estudantes universitários de ambos os sexos (n=243), com idade entre 15 a 24 anos (19,23±1,54). Aplicamos o questionário: "Eu preciso fazer o teste do HIV/AIDS?", adicionando questões sobre idade, sexo e relação sexual mais frequente. Resultados: Na amostra, 73,20% eram do sexo feminino (n=177). A relação sexual mais frequente foi heterossexual (66,70%), seguida pelo homossexual (7,70%) e bissexual (1,20%). Cerca de 23,60% não iniciaram a vida sexual. Encontramos 93,80% da amostra com média ou muita vulnerabilidade ao HIV, sendo 39,10% muito vulnerável, sem diferença significativa (p=0,800) entre sexos. Foi encontrada relação (p=0,000) entre o aumento da idade e maior vulnerabilidade, sendo que 57,9% dos homossexuais e 100% dos bissexuais são muito vulneráveis. Conclusão: A totalidade da população de jovens universitários estudada é vulnerável ao HIV. Embora a amostra tenha acesso ao conhecimento, não o utiliza na prática, sugerindo uma percepção de invulnerabilidade deste grupo.

Objective: The aim of the present study was to analyze the vulnerability to HIV of young undergraduate students. Methods: This was a descriptive survey carried out with undergraduate students of both sexes (n =243), aged between 15 and 24 years (19.23 ± 1.54). We applied the questionnaire: "Do I need to be tested for HIV/AIDS?", adding questions about age, sex and more frequent sexual intercourse. Results: In the sample, 73.2% were female (n=177). The most frequent sexual intercourse was heterosexual (66.7%), followed by homosexual (7.7%) and bisexual (1.2%). About 23.6% did not initiate sex life. We found 93.8% of the sample with medium or highly vulnerable to HIV, being 39.1% with high vulnerability, with no significant difference (p=0.8) between sexes. There was a relationship (p=0) between increasing age and greater vulnerability, with 57.9% of homosexuals and 100% of bisexuals with high vulnerability. Conclusion: Although the sample has access to knowledge, it does not use it in practice, suggesting a perception of invulnerability of this group.

Objetivos: El objetivo del presente trabajo fue analizar la vulnerabilidad al VIH de los estudiantes universitarios jóvenes. Métodos: Se trata de una encuesta descriptiva realizada con estudiantes de ambos sexos (n=243), con edades comprendidas entre 15 y 24 años (19,23 ± 1,54). Hemos aplicado el cuestionario: "¿Tengo que hacerme la prueba del VIH/SIDA?", Añadiendo preguntas sobre la edad, el sexo y las relaciones sexuales más frecuentes. Resultados: En la muestra, el 73,20% eran mujeres (n = 177). Las relaciones sexuales más frecuentes fueron heterosexuales (66,70%), seguidas de homosexuales (7,70%) y bisexuales (1,20%). Alrededor del 23,60% no inició la vida sexual. Encontramos 93,80% de la muestra con una alta o media vulnerabilidad al VIH, siendo 39,10% con alta vulnerabilidad, sin diferencias significativas (p=0,800) entre los sexos. Hubo una relación (p=0,000) entre el aumento de la edad y mayor vulnerabilidad, con el 57,90% de los homosexuales y el 100% de los bisexuales con alta vulnerabilidad. Conclusión: Aunque la muestra tiene acceso al conocimiento, no lo utiliza en la práctica, sugiriendo una percepción de invulnerabilidad de este grupo.

Humans , Vulnerability Study , Acquired Immunodeficiency Syndrome , Oligodendrocyte Precursor Cells , Population Characteristics , Population Studies in Public Health , Public Health , Sexually Transmitted Diseases
Chinese Journal of Contemporary Pediatrics ; (12): 1003-1007, 2017.
Article in Chinese | WPRIM | ID: wpr-297166


<p><b>OBJECTIVE</b>To investigate the long-term effect of oligodendrocyte precursor cell (OPC) transplantation on a rat model of white matter injury (WMI) in the preterm infant.</p><p><b>METHODS</b>A total of 80 Sprague-Dawley rats aged 3 days were randomly divided into sham-operation group, model control group, 5-day ventricular/white matter transplantation group, 9-day ventricular/white matter transplantation group, 14-day ventricular/white matter transplantation group (n=10 each). All groups except the sham-operation group were treated with right common carotid artery ligation and hypoxia for 80 minutes to establish a rat model of WMI in the preterm infant. OPCs were prepared from the human fetal brain tissue (10-12 gestational weeks). At 5, 9, and 14 days after modeling, 3×10OPCs were injected into the right lateral ventricle or white matter in each transplantation group, and myelin sheath and neurological function were evaluated under an electron microscope at ages of 60 and 90 days.</p><p><b>RESULTS</b>Electron microscopy showed that at an age of 60 days, each transplantation group had a slight improvement in myelin sheath injury compared with the model control group; at an age of 90 days, each transplantation group had significantly thickened myelin sheath and reduced structural damage compared with the model control group, and the 14-day transplantation groups had the most significant changes. There were no significant differences in the degree of myelin sheath injury between the ventricular and white matter transplantation groups at different time points. At an age of 60 or 90 days, the transplantation groups had a significantly higher modified neurological severity score (mNSS) than the sham-operation group and a significantly lower mNSS than the model control group (P<0.05).</p><p><b>CONCLUSIONS</b>OPC transplantation may have a long-term effect in the treatment of WMI in the preterm infant, and delayed transplantation may enhance its therapeutic effect.</p>

Animals , Rats , Animals, Newborn , Disease Models, Animal , Myelin Sheath , Pathology , Oligodendrocyte Precursor Cells , Transplantation , Rats, Sprague-Dawley , White Matter , Wounds and Injuries , Pathology
Arch. med ; 16(2): 326-334, 20161200.
Article in Spanish | LILACS | ID: biblio-875095


Objetivo: caracterizar el comportamiento de la sífilis congénita y gestacional en el departamento de Caldas durante el periodo 2009-2013 según las características socio demográficas y de la atención en salud del binomio madre-hijo con sífilis. Materiales y métodos: se realizó un estudio descriptivo de 71 casos de sífilis congénita y 316 casos de sífilis gestacional, reportados a través del sistema de vigilancia epidemiológica SIVIGILA. Resultados: el comportamiento de la sífilis congénita y gestacional en este periodo, indica un descenso de los casos en los no afiliados e incremento de los mismos en el régimen contributivo y subsidiado. Las gestantes con sífilis en edades entre 16 a 35 años, afiliadas al régimen subsidiado, residentes en las cabeceras municipales y no hospitalizadas, presentaron una fuerte correspondencia con la condicional final viva.Los neonatos con sífilis hospitalizados, con una condición final de vivos presentaron una fuerte correspondencia a pertenecer al régimen subsidiado. Conclusiones: la población con mayor número de casos registrados de sífilis gestacional en el departamento de Caldas en este estudio, corresponde a las gestantes del régimen subsidiado que residen en las cabeceras municipales atendidas en el segundo y tercer nivel de servicios de salud. El régimen subsidiado en salud diagnostica la sífilis gestacional durante los controles prenatales; mientras que, el régimen contributivo diagnostica sífilis gestacional en el parto. Independiente del régimen en salud las parejas de gestantes con sífilis no acuden a los servicios de salud...(AU)

Objective: to characterize the behavior of gestational and congenital syphilis in the department of Caldas during the 2009-2013 period according to sociodemographic characteristics and health care of mothers and children with syphilis. Materials and Methods: a descriptive study of 71 cases of congenital syphilis and 316 cases of gestational syphilis reported through the surveillance system was conducted SIVIGILA.Results: the behavior of congenital syphilis and gestational during the study, indicating a decline in cases unaffiliated and increase them in the contributory scheme and subsidized. Pregnant women with syphilis diagnosed between the ages of 16-35 years affiliated with the subsidized regime, which reside in the municipalities and were not hospitalized, had a strong correspondence with the final conditional alive. Infants with syphilis who were hospitalized, with a final condition of living showed a strong correspondence to belong to the subsidized regime. Conclusions: the population with the highest number of reported cases of gestational syphilis in the department of Caldas, in the last five years, corresponding to the subsidized pregnant residing in the municipalities with secondary and tertiary health care. The subsidized health regime gestational syphilis diagnosed during prenatal care mainly; however, with a less strong relationship, the tax regime gestational syphilis diagnosed at birth. To this we add, regardless of the health system, which couples of pregnant women with syphilis do not attend health services...(AU)

Humans , Oligodendrocyte Precursor Cells