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1.
Sheng Li Xue Bao ; 76(4): 561-575, 2024 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-39192789

RESUMEN

As the largest organelle in eukaryotic cells, the endoplasmic reticulum (ER) plays a crucial role in regulating intracellular protein folding, translation and assembly. Multiple quality control mechanisms in the ER ensure accurate modification of proteins in the ER lumen are accurately modified, thus maintaining calcium homeostasis, oxidative stress, cellular senescence and apoptosis. These mechanisms include ER stress (ERS), ER autophagy (ER-phagy, ERPA) and ER-associated degradation (ERAD). Intervertebral disc degeneration (IDD) is an age-related degenerative disease of the spine. Although the pathogenesis of IDD has not been fully elucidated, emerging evidence suggests that the ER quality control system may be involved in its progression. Previous studies have focused on mitochondrial quality control and its related mechanisms in diseases, with limited systematic summaries on the ER quality control system. In this paper, we comprehensively reviewed the molecular mechanisms of the ER quality control system and investigated its association with IDD. In addition, we summarized the potential therapeutic strategies targeting the ER quality control system to attenuate IDD progression, offering new insights into the pathogenesis and regenerative repair strategies of IDD.


Asunto(s)
Autofagia , Estrés del Retículo Endoplásmico , Retículo Endoplásmico , Degeneración del Disco Intervertebral , Humanos , Degeneración del Disco Intervertebral/terapia , Degeneración del Disco Intervertebral/fisiopatología , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/fisiología , Autofagia/fisiología , Estrés del Retículo Endoplásmico/fisiología , Animales , Degradación Asociada con el Retículo Endoplásmico/fisiología
2.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5294-5303, 2023 Oct.
Artículo en Chino | MEDLINE | ID: mdl-38114119

RESUMEN

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-ß-galactosidase(SA-ß-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1ß(IL-1ß), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1ß and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1ß and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.


Asunto(s)
FN-kappa B , Núcleo Pulposo , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Interleucina-10 , Núcleo Pulposo/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Agrecanos/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , ARN Mensajero/metabolismo
3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 42(3): 156-9, 2008 Mar.
Artículo en Chino | MEDLINE | ID: mdl-18788577

RESUMEN

OBJECTIVE: To understand the current situations of saturnism and blood lead levels of children resided in village and circumjacent areas, and to know its relations with sex, age and other factors on children' s health as to providing some evidences for prevention and control. METHODS: An epidemiological survey was conducted for finding out the pollution sources and for a better understanding of the surrounding environment. All 221 children under 14 years old, from the lead pollution villages and surrounding establishments were enrolled, and their blood lead levels were detected by graphite atomizer absorption spectrophotometer method. Symptoms of the saturnism were investigated through a standardized questionnaire. SPSS13.0 software was administrated for data analysis. RESULTS: High blood lead level identification rate was 66.06% (146/221), and saturnism rate 32.13% (71/221). The children's blood lead levels among group 1, group 2, group 3 in this village and jade factory were (161.20 +/- 32.94), (176.60 +/- 43.62), (258.00 +/-106.08) and (238.01 +/- 55.20) microg/L respectively and the significant differences were observed through Kruskal-Wallis test (chi2 = 51.84, df= 3, P<0. 01). The blood lead levels of children from group 3 in this village and the jade factory were higher than those of other two groups. No correlation was found between children's age and blood lead level (r = 0.10, P = 0.13). There was a significant difference in blood lead levels between boys and girls (t' = 3.83, P<0.01). With the children's blood lead levels rising, the occurrence rate of main saturnism symptoms was significantly increased. This survey suggested that the pollution source was a coarse lead smelter. CONCLUSION: The blood lead level should ke overwhelmingly increased among children who live nearby the higher level of lead blood, that living nearby the lead smeltery,might result in stautnism and negative effect on children's healthy.


Asunto(s)
Contaminación Ambiental/análisis , Intoxicación por Plomo/epidemiología , Plomo/sangre , Niño , Femenino , Humanos , Residuos Industriales , Masculino , Metalurgia
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