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1.
EMBO J ; 43(8): 1388-1419, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38514807

RESUMO

Neocortex expansion during evolution is linked to higher numbers of neurons, which are thought to result from increased proliferative capacity and neurogenic potential of basal progenitor cells during development. Here, we show that EREG, encoding the growth factor EPIREGULIN, is expressed in the human developing neocortex and in gorilla cerebral organoids, but not in the mouse neocortex. Addition of EPIREGULIN to the mouse neocortex increases proliferation of basal progenitor cells, whereas EREG ablation in human cortical organoids reduces proliferation in the subventricular zone. Treatment of cortical organoids with EPIREGULIN promotes a further increase in proliferation of gorilla but not of human basal progenitor cells. EPIREGULIN competes with the epidermal growth factor (EGF) to promote proliferation, and inhibition of the EGF receptor abrogates the EPIREGULIN-mediated increase in basal progenitor cells. Finally, we identify putative cis-regulatory elements that may contribute to the observed inter-species differences in EREG expression. Our findings suggest that species-specific regulation of EPIREGULIN expression may contribute to the increased neocortex size of primates by providing a tunable pro-proliferative signal to basal progenitor cells in the subventricular zone.


Assuntos
Epirregulina , Neocórtex , Animais , Humanos , Camundongos , Proliferação de Células , Epirregulina/genética , Epirregulina/metabolismo , Gorilla gorilla/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neocórtex/citologia , Neocórtex/metabolismo , Primatas/fisiologia
2.
Science ; 377(6611): eabl6422, 2022 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-36074851

RESUMO

Neanderthal brains were similar in size to those of modern humans. We sought to investigate potential differences in neurogenesis during neocortex development. Modern human transketolase-like 1 (TKTL1) differs from Neanderthal TKTL1 by a lysine-to-arginine amino acid substitution. Using overexpression in developing mouse and ferret neocortex, knockout in fetal human neocortical tissue, and genome-edited cerebral organoids, we found that the modern human variant, hTKTL1, but not the Neanderthal variant, increases the abundance of basal radial glia (bRG) but not that of intermediate progenitors (bIPs). bRG generate more neocortical neurons than bIPs. The hTKTL1 effect requires the pentose phosphate pathway and fatty acid synthesis. Inhibition of these metabolic pathways reduces bRG abundance in fetal human neocortical tissue. Our data suggest that neocortical neurogenesis in modern humans differs from that in Neanderthals.


Assuntos
Homem de Neandertal , Neocórtex , Neurogênese , Transcetolase , Animais , Células Ependimogliais/citologia , Furões , Humanos , Camundongos , Homem de Neandertal/embriologia , Homem de Neandertal/genética , Neocórtex/embriologia , Neurogênese/genética , Neurogênese/fisiologia , Transcetolase/genética , Transcetolase/metabolismo
3.
Exp Ther Med ; 23(3): 215, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35126718

RESUMO

In recent years, platelet-rich plasma (PRP) therapy has been a subject of controversy in orthopedics field. Our objective was to assess the efficiency of PRP therapy for patients who have suffered grade 2 meniscal lesions and grade 2 anterior cruciate ligament (ACL) lesions, graded by magnetic resonance imaging (MRI). A retrospective observational study was conducted, which included 72 young recreational athletes who had been diagnosed with grade 2 meniscal injury, graded using MRI, that benefited from PRP therapy as an enhancement of the primary treatment, after cast immobilization. The Lysholm score, the pain intensity and the resuming of the physical activity before the PRP treatment and one month after were analyzed. Our study revealed that patients had an improved subjective perception of pain after PRP therapy and an improvement of the Lysholm score. Concurrently, 83.3% of patients could return to sports and daily physical activity. It can be concluded that PRP therapy is a safe, easy to manage treatment, efficient for pain relief and in resuming of sports activities for young recreational athletes who have sustained partial meniscal or ACL tears. In terms of pain relief, it appears that the PRP therapy could be more efficient for young patients with ACL injuries.

4.
Children (Basel) ; 8(11)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34828779

RESUMO

BACKGROUND AND OBJECTIVES: Osteogenesis imperfecta is a rare pathology involving the bones and the connective tissues, generating alterations that lead to frequent fractures during childhood. When fractures occur at birth, they are associated with an impairment of walking and the quality of life. Although surgical techniques have significantly improved in recent years, functional outcomes and the quality of life for pediatric patients that benefited from surgical management with telescopic rods have been less evaluated. This study aimed to measure functional results and determine the factors that influence the quality of life for the pediatric population diagnosed with Osteogenesis imperfecta and surgically treated using the telescopic rod approach after suffering a fracture or severe deformity. MATERIALS AND METHODS: We conducted a cohort study that consisted of 15 patients diagnosed with Osteogenesis imperfecta (average age of 11.6 years). All individuals possessed at least one intramedullary telescopic rod as a result of the surgical treatment. RESULTS: We observed that the pain, both acute and chronic, impairs the quality of life and interferes with daily living activities, for instance, self-care tasks. CONCLUSIONS: Osteogenesis imperfecta is associated with a severely damaged level of walking. All of the aspects of the pediatric patient's daily life activity seem to be affected. Furthermore, these patients, especially those residing in rural areas, have a poor quality of life.

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