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1.
Proc Natl Acad Sci U S A ; 117(45): 28102-28113, 2020 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-33106410

RESUMEN

Better understanding myelination of peripheral nerves would benefit patients affected by peripheral neuropathies, including Charcot-Marie-Tooth disease. Little is known about the role the Golgi compartment plays in Schwann cell (SC) functions. Here, we studied the role of Golgi in myelination of peripheral nerves in mice through SC-specific genetic inactivation of phosphatidylinositol 4-kinase beta (PI4KB), a Golgi-associated lipid kinase. Sciatic nerves of such mice showed thinner myelin of large diameter axons and gross aberrations in myelin organization affecting the nodes of Ranvier, the Schmidt-Lanterman incisures, and Cajal bands. Nonmyelinating SCs showed a striking inability to engulf small diameter nerve fibers. SCs of mutant mice showed a distorted Golgi morphology and disappearance of OSBP at the cis-Golgi compartment, together with a complete loss of GOLPH3 from the entire Golgi. Accordingly, the cholesterol and sphingomyelin contents of sciatic nerves were greatly reduced and so was the number of caveolae observed in SCs. Although the conduction velocity of sciatic nerves of mutant mice showed an 80% decrease, the mice displayed only subtle impairment in their motor functions. Our analysis revealed that Golgi functions supported by PI4KB are critically important for proper myelination through control of lipid metabolism, protein glycosylation, and organization of microvilli in the nodes of Ranvier of peripheral nerves.


Asunto(s)
Aparato de Golgi/metabolismo , Antígenos de Histocompatibilidad Menor , Vaina de Mielina/metabolismo , Nervios Periféricos/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol) , Células de Schwann/metabolismo , Animales , Colesterol/metabolismo , Ratones , Ratones Noqueados , Antígenos de Histocompatibilidad Menor/genética , Antígenos de Histocompatibilidad Menor/metabolismo , Fosfatidilinositoles/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo
2.
Proc Natl Acad Sci U S A ; 113(16): 4314-9, 2016 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-27044099

RESUMEN

Lenz-Majewski syndrome (LMS) is a rare disease characterized by complex craniofacial, dental, cutaneous, and limb abnormalities combined with intellectual disability. Mutations in thePTDSS1gene coding one of the phosphatidylserine (PS) synthase enzymes, PSS1, were described as causative in LMS patients. Such mutations render PSS1 insensitive to feedback inhibition by PS levels. Here we show that expression of mutant PSS1 enzymes decreased phosphatidylinositol 4-phosphate (PI4P) levels both in the Golgi and the plasma membrane (PM) by activating the Sac1 phosphatase and altered PI4P cycling at the PM. Conversely, inhibitors of PI4KA, the enzyme that makes PI4P in the PM, blocked PS synthesis and reduced PS levels by 50% in normal cells. However, mutant PSS1 enzymes alleviated the PI4P dependence of PS synthesis. Oxysterol-binding protein-related protein 8, which was recently identified as a PI4P-PS exchanger between the ER and PM, showed PI4P-dependent membrane association that was significantly decreased by expression of PSS1 mutant enzymes. Our studies reveal that PS synthesis is tightly coupled to PI4P-dependent PS transport from the ER. Consequently, PSS1 mutations not only affect cellular PS levels and distribution but also lead to a more complex imbalance in lipid homeostasis by disturbing PI4P metabolism.


Asunto(s)
Anomalías Múltiples/enzimología , Enfermedades del Desarrollo Óseo/enzimología , Membrana Celular/enzimología , Retículo Endoplásmico/enzimología , Aparato de Golgi/enzimología , Discapacidad Intelectual/enzimología , Mutación , Transferasas de Grupos Nitrogenados/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Anomalías Múltiples/genética , Enfermedades del Desarrollo Óseo/genética , Membrana Celular/genética , Retículo Endoplásmico/genética , Aparato de Golgi/genética , Células HEK293 , Humanos , Discapacidad Intelectual/genética , Antígenos de Histocompatibilidad Menor , Transferasas de Grupos Nitrogenados/genética , Fosfatos de Fosfatidilinositol/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo
3.
Materials (Basel) ; 14(8)2021 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-33924487

RESUMEN

Osseointegration of titanium implant is important for the success of both dental and medical implants. Previous studies have attempted to improve osseointegration by considering the use of plasma jet technology, where information with animal models and parameters related to osseointegration is still lacking. Therefore, this study investigated the effects of non-thermal atmospheric pressure plasma jet (NTAPPJ) treatment on titanium implants in terms of osseointegration in mongrel dogs. A total of 41 implants; 21 NTAPPJ treated and 20 control, were placed in the maxilla and mandible of six mongrel dogs for either 4 or 8 weeks. The bone volume (BV) and bone-to-implant contact (BIC) ratio were determined by region of interest (ROI). Statistical analysis was performed with the Wilcoxon rank-sum test. The NTAPPJ group at 4 weeks showed higher numbers in both BV and BIC (p < 0.05) compared to the control group. However, at 8 weeks there were less significant differences between the control or experimental group as the control group had caught up with the experimental group. Hence, NTAPPJ may be an effective treatment for the initial healing period which is critical to ensure reliable long-term predictability. The BV and BIC have been clinically proven to accelerate in the initial stages with the use of NTAPPJ to aid in the healing and initial stability of implants.

4.
Health Soc Care Community ; 26(3): e378-e385, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29285823

RESUMEN

This study aimed to evaluate the effects of a community-based oral hygiene service on general and periodontal health indicators of patients with hypertension and type 2 diabetes mellitus visiting a community health centre in Korea. The study used a one-group pretest-posttest and interrupted time-series design. A total of 151 participants (45% male), with a mean age of 63 ± 8.4 years, were included in the study; these included patients with hypertension (62%), diabetes (12%) and both hypertension and diabetes (26%). Two dental hygienists dedicated 2 days per week to this project, providing oral hygiene services to 10-13 participants per day. Four oral hygiene service sessions were provided per patient. The objective oral hygiene status and subjective self-reported periodontal status were compared before and after the service. The changes in blood pressure and glycosylated haemoglobin levels were also assessed. A lower frequency of subjective swelling was reported at the fourth session (37.9%) compared to the first (55.6%) session. Further, significantly fewer cases of calculus and bleeding were observed (p < .05), and significantly more patients reported having no gum problems at the fourth session (43.1% vs. 27.2%; p < .05) than at the first session. Finally, the participants maintained stable blood pressures at each of the four sessions, and their glycosylated haemoglobin levels were significantly lower at the fourth session. In conclusion, the findings of this study suggest that community oral hygiene services provided by dental hygienists can promote objective oral hygiene and subjective periodontal status in the local community, and may help in the control of hypertension and diabetes.


Asunto(s)
Centros Comunitarios de Salud/organización & administración , Diabetes Mellitus Tipo 2/epidemiología , Hipertensión/epidemiología , Higiene Bucal/métodos , Enfermedades Periodontales/prevención & control , Adulto , Anciano , Presión Sanguínea , Diabetes Mellitus Tipo 2/sangre , Femenino , Hemoglobina Glucada , Humanos , Masculino , Persona de Mediana Edad , República de Corea/epidemiología
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