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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.
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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/fisiologíaRESUMEN
Humic substances as major components of waste activated sludge are refractory to degrade and have inhibition in traditional anaerobic digestion (AD). This study for the first time investigated the feasibility and mechanism of microbial electrolysis cell assisted anaerobic digestion (MEC-AD) to break the recalcitrance and inhibition of humic substances. The cumulative methane production of AD decreased from 134.7 to 117.6 mL/g-VS with the addition of humic acids and fulvic acids at 25.2-102.1 mg/g-VS. However, 0.6 V MEC-AD maintained stable methane production (155.5-158.2 mL/g-VS) under the effect of humic substances. 0.6 V MEC-AD formed electrical stimulation on microbial cells, provided anodic oxidation and cathodic reduction transformation pathways for humic substances (acting as carbon sources and electron shuttles), and aggregated functional microorganisms on electrodes, facilitating the degradation of humic substances and generation of methane. This study provides a theoretical basis for improving the energy recovery and system stability of sludge treatment.
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Electrólisis , Sustancias Húmicas , Metano , Aguas del Alcantarillado , Aguas del Alcantarillado/microbiología , Metano/metabolismo , Anaerobiosis , Electrodos , Benzopiranos , Reactores BiológicosRESUMEN
RATIONALE: Aneurysmal bone cyst (ABC) is a rare primary or secondary tumor that usually occurs in young women aged between 10 and 20 years, mostly in the long tubular bone and spine. However, there are no definite standards for its clinical treatment. To our knowledge, this is the first report of a young female patient with distal radius ABC who was successfully treated with tumor resection and autogenous fibular head transplantation. PATIENT CONCERNS: A 28-year-old married Chinese young woman presented to our hospital with swelling and pain in her right wrist for 2 years and aggravation of wrist movement restriction for 1 week. DIAGNOSES: Pathological biopsy confirmed ABC. INTERVENTIONS: We performed a pathological examination of the tumor on the right wrist and preliminarily confirmed the diagnosis of ABC. The right wrist joint was reconstructed by total surgical resection of the ABC tumor in the right wrist joint and autogenous fibular head transplantation. OUTCOMES: During follow-up within 7 years, good right wrist function was confirmed. The tumor did not recur, the swelling of the right wrist disappeared, the joint pain and limitation of movement significantly improved, and the function of the right wrist was not impaired in daily activities. Radiography showed that the fracture had healed. LESSONS: Our results suggest that autofibular head transplantation is an effective treatment for reconstruction of wrist function in adult patients with ABC of the distal radius.
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Quistes Óseos Aneurismáticos , Neoplasias Óseas , Humanos , Adulto , Femenino , Niño , Adolescente , Adulto Joven , Radio (Anatomía)/cirugía , Radio (Anatomía)/patología , Peroné/trasplante , Quistes Óseos Aneurismáticos/diagnóstico por imagen , Quistes Óseos Aneurismáticos/cirugía , Trasplante Óseo/métodos , Neoplasias Óseas/cirugía , Neoplasias Óseas/patología , Recurrencia Local de Neoplasia/patología , Articulación de la Muñeca/cirugía , Resultado del TratamientoRESUMEN
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 â ¡ 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.
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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/metabolismoRESUMEN
Gate-all-around (GAA) structures are important for future logic devices and 3D-DRAM. Inner-spacer cavity etching and channel release both require selective etching of Si0.7Ge0.3. Increasing the number of channel-stacking layers is an effective way to improve device current-driving capability and storage density. Previous work investigated ICP selective etching of a three-cycle Si0.7Ge0.3/Si multilayer structure and the related etching effects. This study focuses on the dry etching of a 15-cycle Si0.7Ge0.3/Si multilayer structure and the associated etching effects, using simulation and experimentation. The simulation predicts the random effect of lateral etching depth and the asymmetric effect of silicon nanosheet damage on the edge, both of which are verified by experiments. Furthermore, the study experimentally investigates the influence and mechanism of pressure, power, and other parameters on the etching results. Research on these etching effects and mechanisms will provide important points of reference for the dry selective etching of Si0.7Ge0.3 in GAA structures.
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ETHNOPHARMACOLOGICAL RELEVANCE: Lower back pain (LBP) is a common and frequent clinical condition, and intervertebral disc degeneration (IDD) is recognized as the leading cause of LBP, typically manifested by increased nucleus pulposus cell (NPC) senescence and death. In recent years, the treatment of IDD with stem cell injections has had great potential compared to surgical treatment. Combining the two may achieve better results, as BuShenHuoXueFang (BSHXF) is an herbal formula that improves the survival rate of transplanted stem cells and enhances their efficacy. AIM OF THE STUDY: We aimed to qualitatively and quantitatively analyze BSHXF-medicated serum and investigate the molecular mechanism of BSHXF-mediated serum in promoting the differentiation of adipose mesenchymal stem cells (ADSCs) into NPCs and delaying the senescence of NPCs by regulating the TGF-ß1/Smad pathway. MATERIALS AND METHODS: In this study, an ultrahigh-performance liquid chromatography-quadrupole-time-of-flight mass spectrometer (UPLC-Q-TOF-MS) was used to establish a method for the analysis of rat serum samples to track the active components in vivo; the oxidative damage model of NPCs was induced by T-BHP, and a Transwell chamber was used to construct a coculture system of ADSCs and NPCs. Flow cytometry was used to determine the cell cycle; SA-ß-Gal staining was used to assess cell senescence; ELISA was used to detect IL-1ß, IL-6 inflammatory factors, CXCL-1, CXCL-3, CXCL-10 chemokines, and TGF-ß1 in the supernatants of ADSCs and NPCs. WB was used to detect COL2A1, COL1A1, and Aggrecan in ADSCs to assess the manifestation of NP differentiation in ADSCs, and the WB method was used to detect COL2A1, COL1A1, Aggrecan, p16, p21, p53, and p-p53 protein expression in NPCs to reflect the cellular senescence status and to detect TGF-ß1, Smad2, Smad3, p- Smad2, and p- Smad3 protein expression in NPCs to reflect the pathway condition. RESULTS: We finally identified 70 blood components and their metabolites, including 38 prototypes, from the BSHXF-medicated serum. Compared with that in the nonmedicated serum group, the TGF-ß1/Smad pathway was activated in the medicated serum group, ADSCs moved toward NPC characteristics, the number of NPCs in the S/G2M phase increased, the number of senescent NPCs decreased, IL-1ß and IL-6 inflammatory factors in the Transwell decreased, CXCL-1, CXCL-3, and CXCL-10 chemokines decreased, and the expression of p16, p21, p53 and p-p53 proteins in NPCs was inhibited. CONCLUSION: By regulating the TGF-ß1/Smad pathway, BSHXF-medicated serum promoted ADSCs to NPCs, effectively alleviated the cycle blockage of NPCs after oxidative damage, encouraged the growth and proliferation of NPCs, delayed the aging of NPCs, improved the deteriorating microenvironment around NPCs, and repaired oxidatively damaged NPCs. The combination of BSHXF or its compounds with ADSCs has great potential for the treatment of IDD in the future.
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Degeneración del Disco Intervertebral , Factor de Crecimiento Transformador beta1 , Ratas , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Proteína p53 Supresora de Tumor , Agrecanos/metabolismo , Interleucina-6/metabolismo , Degeneración del Disco Intervertebral/terapia , Degeneración del Disco Intervertebral/metabolismoRESUMEN
The non-lichenized ascomycete Bulgaria inquinans (Fries), growing in the Changbai Mountain of China, has been used as medicinal diet for many years. In a previous study, we have reported that a heteropolysaccharide BIWS-4b from the fruit bodies of B. inquinans (Fries) exhibited markedly antimalarial and immunostimulating activities. In this paper, the structural features and antioxidant activity of BIWS-4b were investigated. The results showed that BIWS-4b contains an α-(1â2), (1â6)-mannan core to which the glucogalactan chains are attached. The glucogalactan chains were composed of (1â6)-, (1â5)- and (1â5,6)-linked ß-Galf, (1â4)-linked and non-reducing terminal ß-Glcp units, and might be attached to the mannan core at the O-2 positions of α-Manp units. The antioxidant assays showed that BIWS-4b exhibited good activities, including free radicals scavenging effects, ferrous ion-chelating ability and reducing power. Thus, BIWS-4b could be used as a natural antioxidant agent for food and pharmaceutical industries.
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Antioxidantes/química , Ascomicetos/química , Cuerpos Fructíferos de los Hongos/química , Polisacáridos/química , Antioxidantes/aislamiento & purificación , Secuencia de Carbohidratos , China , Datos de Secuencia Molecular , Polisacáridos/aislamiento & purificaciónRESUMEN
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.