RESUMEN
The cGAS-STING pathway mediates cytoplasmic DNA-triggered innate immunity. STING activation is initiated by cyclic-GMP-AMP (cGAMP)-induced translocation from the endoplasmic reticulum and sulfated glycosaminoglycans-induced polymerization at the Golgi. Here, we examine the mechanisms underlying STING transport and activation beyond the Golgi. A genome-wide CRISPR-Cas9 screen identified Armadillo-like helical domain-containing protein 3 (ARMH3) as critical for STING activation. Upon cGAMP-triggered translocation, ARMH3 interacted with STING at the Golgi and recruited phosphatidylinositol 4-kinase beta (PI4KB) to synthesize PI4P, which directed STING Golgi-to-endosome trafficking via PI4P-binding proteins AP-1 and GGA2. Disrupting PI4P-dependent lipid transport through RNAi of other PI4P-binding proteins impaired STING activation. Consistently, disturbed lipid composition inhibited STING activation, whereas aberrantly elevated cellular PI4P led to cGAS-independent STING activation. Armh3fl/fllLyzCre/Cre mice were susceptible to DNA virus challenge in vivo. Thus, ARMH3 bridges STING and PIK4B to generate PI4P for STING transportation and activation, an interaction conserved in all eukaryotes.
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Factores de Restricción Antivirales , Proteínas del Dominio Armadillo , Proteínas de la Membrana , Animales , Ratones , 1-Fosfatidilinositol 4-Quinasa/metabolismo , Proteínas Portadoras , Endosomas/metabolismo , Inmunidad Innata , Lípidos , Proteínas de la Membrana/metabolismo , Nucleotidiltransferasas/metabolismo , Proteínas del Dominio Armadillo/metabolismoRESUMEN
Activation of the cyclic guanosine monophosphate (GMP)-AMP (cGAMP) sensor STING requires its translocation from the endoplasmic reticulum to the Golgi apparatus and subsequent polymerization. Using a genome-wide CRISPR-Cas9 screen to define factors critical for STING activation in cells, we identified proteins critical for biosynthesis of sulfated glycosaminoglycans (sGAGs) in the Golgi apparatus. Binding of sGAGs promoted STING polymerization through luminal, positively charged, polar residues. These residues are evolutionarily conserved, and selective mutation of specific residues inhibited STING activation. Purified or chemically synthesized sGAGs induced STING polymerization and activation of the kinase TBK1. The chain length and O-linked sulfation of sGAGs directly affected the level of STING polymerization and, therefore, its activation. Reducing the expression of Slc35b2 to inhibit GAG sulfation in mice impaired responses to vaccinia virus infection. Thus, sGAGs in the Golgi apparatus are necessary and sufficient to drive STING polymerization, providing a mechanistic understanding of the requirement for endoplasmic reticulum (ER)-to-Golgi apparatus translocation for STING activation.
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Glicosaminoglicanos/metabolismo , Aparato de Golgi/metabolismo , Proteínas de la Membrana/metabolismo , Nucleótidos Cíclicos/metabolismo , Animales , Células COS , Línea Celular , Línea Celular Tumoral , Chlorocebus aethiops , Cricetinae , Citosol/metabolismo , Retículo Endoplásmico/metabolismo , Células HeLa , Humanos , Ratones , Polimerizacion , Transducción de Señal/fisiología , Transportadores de Sulfato/metabolismo , Vaccinia/metabolismo , Virus Vaccinia/patogenicidadRESUMEN
Viral infection triggers host innate immune responses that result in the production of various cytokines including type I interferons (IFN), activation of inflammasomes, and programmed cell death of the infected cells. Tight control of inflammatory cytokine production is crucial for the triggering of an effective immune response that can resolve the infection without causing host pathology. In examining the inflammatory response of Asc-/- and Casp1-/- macrophages, we found that deficiency in these molecules resulted in increased IFN production upon DNA virus infection, but not RNA virus challenge. Investigation of the underlying mechanism revealed that upon canonical and non-canonical inflammasome activation, caspase-1 interacted with cyclic GMP-AMP (cGAMP) synthase (cGAS), cleaving it and dampening cGAS-STING-mediated IFN production. Deficiency in inflammasome signaling enhanced host resistance to DNA virus in vitro and in vivo, and this regulatory role extended to other inflammatory caspases. Thus, inflammasome activation dampens cGAS-dependent signaling, suggesting cross-regulation between intracellular DNA-sensing pathways.
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Caspasa 1/inmunología , Infecciones por Virus ADN/inmunología , Inflamasomas/inmunología , Nucleotidiltransferasas/inmunología , Animales , Caspasa 1/metabolismo , Infecciones por Virus ADN/metabolismo , Modelos Animales de Enfermedad , Inflamasomas/metabolismo , Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Nucleotidiltransferasas/metabolismoRESUMEN
BACKGROUND Osteoarthritis (OA) is a chronic degenerative disease characterized by synovitis and has been implicated in sphingolipid metabolism disorder. However, the role of sphingolipid metabolism pathway (SMP)-related genes in the occurrence of OA and synovial immune dysregulation remains unclear. MATERIAL AND METHODS In this study, we obtained synovium-related databases from GEO (n=40 for both healthy controls and OA) and analyzed the expression levels of SMP-related genes. Using 2 algorithms, we identified hub genes and developed a diagnostic model incorporating these hub genes to predict the occurrence of OA. Subsequently, the hub genes were further validated in peripheral blood samples from OA patients. Additionally, CIBERSORT and MCP-counter analyses were employed to explore the correlation between hub genes and immune dysregulation in OA synovium. WGCNA was used to determine enriched modules in different clusters. RESULTS Overall, the expression levels of SMP genes were upregulated in OA synovium. We identified 6 hub genes of SMP and constructed an excellent diagnostic model (AUC=0.976). The expression of re-confirmed hub genes showed associations with immune-related cell infiltration and levels of inflammatory cytokines. Furthermore, we observed heterogeneity in the expression patterns of hub genes across different clusters of OA. Notably, older patients displayed increased susceptibility to elevated levels of pain-related inflammatory cytokines and infiltration of immune cells. CONCLUSIONS The SMP-related hub genes have the potential to serve as diagnostic markers for OA patients. Moreover, the 4 hub genes of SMP demonstrate wide participation in immune dysregulation in OA synovium. The activation of different pathways is observed among different populations of patients with OA.
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Osteoartritis , Esfingolípidos , Membrana Sinovial , Humanos , Membrana Sinovial/metabolismo , Osteoartritis/genética , Osteoartritis/diagnóstico , Osteoartritis/metabolismo , Osteoartritis/inmunología , Esfingolípidos/metabolismo , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Masculino , Femenino , Transcriptoma/genética , Bases de Datos Genéticas , Persona de Mediana Edad , Estudios de Casos y ControlesRESUMEN
BACKGROUND: Osteoarthritis (OA) is one of degenerative-related arthritis, which can be aggravated by low-grade synovitis. It is known that arachidonic acid (AA) dysmetabolism brings OA synovitis. However, the impact of synovial AA metabolism pathway (AMP) related genes on OA remains uncovered. METHODS: Here, we conducted a comprehensive analysis to explore the impact of AA metabolism genes in OA synovium. We obtained transcriptome expression profiles from three raw datasets related to OA synovium (GSE12021, GSE29746, GSE55235) and identified the hub genes of AA metabolism pathways (AMP) in OA synovium. An OA occurrence diagnostic model was constructed and validated based on the identified hub genes. Then, we explored the correlation between hub gene expression and the immune-related module using CIBERSORT and MCP-counter analysis. The unsupervised consensus clustering analysis and weighted correlation network analysis (WGCNA) were utilized to identify robust clusters of identified genes in each cohort. Moreover, the interaction between the hub genes of AMP and immune cells was elucidated through single-cell RNA (scRNA) analysis by scRNA sequencing data from GSE152815. RESULTS: We found that the expression of AMP-related genes was up-regulated in OA synovium, and seven hub genes (LTC4S, PTGS2, PTGS1, MAPKAPK2, CBR1, PTGDS, and CYP2U1) were identified. The diagnostic model that combined the identified hub genes showed great clinical validity in diagnosing OA (AUC = 0.979). Moreover, significant associations were noticed between the hub genes' expression, immune cell infiltration, and inflammatory cytokine levels. The 30 OA patients were randomized and clustered into three groups using WGCNA analysis based on the hub genes, and diverse immune status was found in different clusters. Of interest, older patients were more likely to be classified into a cluster with higher levels of inflammatory cytokines IL-6 and less infiltration of immune cells. Based on the scRNA-sequencing data, we found that the hub genes had relatively higher expression in macrophages and B cells than other immune cells. Moreover, inflammation-related pathways were significantly enriched in macrophages. CONCLUSION: These results suggest that AMP-related genes are closely involved in alterations of OA synovial inflammation. The transcriptional level of hub genes could serve as a potential diagnostic marker for OA.
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Metabolismo de los Lípidos , Osteoartritis , Humanos , Ácido Araquidónico , Citocinas , Inflamación , Osteoartritis/diagnóstico , Osteoartritis/genética , Análisis de Secuencia de ARN , Familia 2 del Citocromo P450RESUMEN
BACKGROUND: Schatzker IV-C is a high-energy tibial plateau fracture often accompanied by lateral meniscus injuries. While imaging examinations are routine preoperative measurements, the correlation between CT imaging shift parameters of the lateral plateau and lateral meniscal injury in Schatzker IV-C fractures remains uncovered. METHODS: This retrospective study enrolled a total of 60 patients with Schatzker IV-C tibial plateau fractures at the First People's Hospital of Hefei. Prior to surgery, CT imaging was used to measure the numerical values of lateral plateau depression (LPD) and lateral plateau widening (LPW). The degree of lateral meniscus injury was confirmed based on intraoperative direct vision, with patients being classified into meniscus injury and non-meniscus injury groups. Dichotomous logistic regression was employed to evaluate the correlation between LPD, LPW, and lateral meniscus injury, while the optimal cut-off points for predicting lateral meniscal injury with LPD and LPW were determined using receiver operator characteristic (ROC) curves. RESULTS: The meniscus injury group exhibited a mean LPD of 15.3 ± 3.5 mm, which was significantly higher than the non-meniscus injury group's mean LPD of 8.4 ± 3.4 mm (P < 0.05). Similarly, the meniscus injury group had a larger mean LPW of 9.4 ± 1.8 mm compared to the non-meniscus injury group's mean LPW of 6.9 ± 0.9 mm (P < 0.05). The optimal cut-off points for predicting lateral meniscal injury were determined to be 8.40 mm for LPD (with a sensitivity of 95%, specificity of 85%, and AUC of 0.898) and 7.90 mm for LPW (with a sensitivity of 75%, specificity of 90%, and AUC of 0.897). CONCLUSIONS: Patients with Schatzker IV-C tibial plateau fractures are at a significantly higher risk of lateral meniscal injury when the LPD exceeds 8.40 mm and/or the LPW exceeds 7.90 mm. Our results may provide novel reference metrics for the early diagnosis of lateral meniscal injury in Schatzker IV-C tibial plateau fracture patients when the MRI examination is not available.
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Fracturas de la Tibia , Fracturas de la Meseta Tibial , Humanos , Meniscos Tibiales/diagnóstico por imagen , Meniscos Tibiales/cirugía , Estudios Retrospectivos , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/cirugía , Fracturas de la Tibia/complicaciones , Tomografía Computarizada por Rayos X/métodosRESUMEN
Programmed death ligand-1 (PD-L1)/PD-1 checkpoint extensively serves as a central mediator of immunosuppression. A tumor-promoting role for abundant PD-L1 in several cancers is revealed. However, the importance of PD-L1 and how the PD-L1 expression is controlled in breast cancer remains obscure. Here, the mechanisms of controlling PD-L1 at the transcription and protein acetylation levels in promoting breast cancer growth are presented. Overexpressed PD-L1 accelerates breast cancer growth in vitro and in vivo. RNA-seq uncovers that PD-L1 can induce some target genes affecting many cellular processes, especially cancer development. In clinical breast cancer tissues and cells, PD-L1 and HBXIP are both increased, and their expressions are positively correlated. Mechanistic exploration identifies that HBXIP stimulates the transcription of PD-L1 through co-activating ETS2. Specifically, HBXIP induces PD-L1 acetylation at K270 site through interacting with acetyltransferase p300, leading to the stability of PD-L1 protein. Functionally, depletion of HBXIP attenuates PD-L1-accelerated breast tumor growth. Aspirin alleviates breast cancer via targeting PD-L1 and HBXIP. Collectively, the findings display new light into the mechanisms of controlling tumor PD-L1 and broaden the utility for PD-L1 as a target in breast cancer therapy.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Antígeno B7-H1/metabolismo , Neoplasias de la Mama/patología , Animales , Western Blotting , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Proliferación Celular , Inmunoprecipitación de Cromatina , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Células MCF-7 , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Solvent-free mechanical milling is a new, environmentally friendly and cost-effective technology that is now widely used in the field of organic synthesis. The mechanochemical solvent-free synthesis of furoxans from aldoximes was achieved through dimerization of the in situ generated nitrile oxides in the presence of sodium chloride, Oxone and a base. A variety of furoxans was obtained with up to a 92% yield. The present protocol has the advantages of high reaction efficiency and mild reaction conditions.
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Oxadiazoles , Oximas , Técnicas de Química Sintética , Dimerización , SolventesRESUMEN
BACKGROUND: Diosmetin is a bioflavonoid compound naturally abundant in citrus fruits. It is found to perform a variety of activities, while its antitumor property in osteosarcoma, a malignant tumor with unmet clinical treatment, remained unknown. METHODS: Colony formation assay, cell cycle analysis and apoptosis analysis were conducted respectively to observe the effect of diosmetin on cell proliferation and apoptosis in human osteosarcoma cells. Western blot and immunoprecipitation were used to detect the expression of apoptotic molecules and activation of STAT3/c-Myc pathway in Saos-2 and U2SO cells. RESULTS: Diosmetin significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and promoted cell apoptosis in both Saos-2 and U2SO cells. Moreover, Diosmetin downregulated the expression of anti-apoptotic protein Bcl-xL while upregulated the levels of pro-apoptotic proteins including cleaved Caspase-3, cleaved-PARP and Bax. Furthermore, diosmetin dose-dependently inhibited STAT3 phosphorylation, reduced the expression of its downstream protein c-Myc and impeded the interaction between STAT3 molecules. CONCLUSIONS: These results suggest that diosmetin exerts anti-osteosarcoma effects by suppressing cell proliferation and inducing apoptosis via inhibiting the activation of STAT3/c-Myc signaling pathway, which provide the possibility for diosmetin to be a chemotherapeutic candidate for osteosarcoma.
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Flavonoides , Osteosarcoma , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Flavonoides/farmacología , Humanos , Osteosarcoma/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-myc , Factor de Transcripción STAT3RESUMEN
Mitochondrial antiviral-signaling protein (MAVS) transmits signals from RIG-I-like receptors after RNA virus infections. However, the mechanism by which MAVS activates downstream components, such as TBK1 and IKKα/ß, is unclear, although previous work suggests the involvement of NEMO or TBK1-binding proteins TANK, NAP1, and SINTBAD. Here, we report that MAVS-mediated innate immune activation is dependent on TRAFs, partially on NEMO, but not on TBK1-binding proteins. MAVS recruited TBK1/IKKε by TRAFs that were pre-associated with TBK1/IKKε via direct interaction between the coiled-coil domain of TRAFs and the SDD domain of TBK1/IKKε. TRAF2-/-3-/-5-/-6-/- cells completely lost RNA virus responses. TRAFs' E3 ligase activity was required for NEMO activation by synthesizing ubiquitin chains that bound to NEMO for NF-κB and TBK1/IKKε activation. NEMO-activated IKKα/ß were important for TBK1/IKKε activation through IKKα/ß-mediated TBK1/IKKε phosphorylation. Moreover, individual TRAFs differently mediated TBK1/IKKε activation and thus fine-tuned antiviral immunity under physiological conditions.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Quinasa I-kappa B/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Células HEK293 , Humanos , Inmunidad Innata/inmunología , Fosforilación , Proteínas Serina-Treonina Quinasas/genética , Virus Sendai , UbiquitinaciónRESUMEN
Cytosolic dsDNA activates the cyclic GMP-AMP synthase (cGAS)-stimulator of IFN genes (STING) pathway to produce cytokines, including type I IFNs. The roles of many critical proteins, including NEMO, IKKß, and TBK1, in this pathway are unclear because of the lack of an appropriate system to study. In this article, we report that lower FBS concentrations in culture medium conferred high sensitivities to dsDNA in otherwise unresponsive cells, whereas higher FBS levels abrogated this sensitivity. Based on this finding, we demonstrated genetically that NEMO was critically involved in the cGAS-STING pathway. Cytosolic DNA activated TRIM32 and TRIM56 to synthesize ubiquitin chains that bound NEMO and subsequently activated IKKß. Activated IKKß, but not IKKα, was required for TBK1 and NF-κB activation. In contrast, TBK1 was reciprocally required for NF-κB activation, probably by directly phosphorylating IKKß. Thus, our findings identified a unique innate immune activation cascade in which TBK1-IKKß formed a positive feedback loop to assure robust cytokine production during cGAS-STING activation.
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Quinasa I-kappa B/inmunología , Factor 3 Regulador del Interferón/inmunología , Péptidos y Proteínas de Señalización Intracelular/inmunología , Proteínas de la Membrana/inmunología , FN-kappa B/inmunología , Nucleotidiltransferasas/inmunología , Transducción de Señal/inmunología , Animales , Células HeLa , Humanos , Quinasa I-kappa B/genética , Factor 3 Regulador del Interferón/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Células MCF-7 , Proteínas de la Membrana/genética , Ratones , FN-kappa B/genética , Nucleotidiltransferasas/genética , Transducción de Señal/genéticaRESUMEN
Mammalian hepatitis B X-interacting protein (HBXIP) is an 18-kDa protein that regulates a large number of transcription factors such as TF-IID, E2F1, SP1, STAT3, c-Myc, and LXR by serving as an oncogenic transcription coactivator and plays an important role in the development of breast cancer. We previously showed that HBXIP as an oncoprotein could enhance the promoter activity of MDM2 through coactivating p53, promoting the MDM2 transcription in breast cancer. In this study we investigated the molecular mechanisms underlying the modulation of MDM2/p53 interaction by HBXIP in human breast cancer MCF-7 cells in vitro and in vivo. We showed that HBXIP could up-regulate MDM2 through inducing DNA methylation of miR-18b, thus suppressing the miR-18b expression, leading to the attenuation of p53 in breast cancer cells. In addition, HBXIP could promote the phosphorylation of MDM2 by increasing the level of pAKT and bind to pMDM2, subsequently enhancing the interaction between MDM2 and p53 for the down-regulation of p53 in breast cancer cells. In MCF-7 breast cancer xenograft nude mice, we also observed that overexpression of HBXIP promoted breast cancer growth through the miR-18b/MDM2 and pAKT/MDM2 pathways. In conclusion, oncoprotein HBXIP suppresses miR-18b to elevate MDM2 and activates pAKT to phosphorylate MDM2 for enhancing the interaction between MDM2 and p53, leading to p53 degradation in promotion of breast cancer growth. Our findings shed light on a novel mechanism of p53 down-regulation during the development of breast cancer.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias de la Mama/metabolismo , Proteínas Oncogénicas/metabolismo , Transducción de Señal/fisiología , Proteína p53 Supresora de Tumor/metabolismo , Animales , Línea Celular Tumoral , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones Endogámicos BALB C , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteína p53 Supresora de Tumor/genética , Regulación hacia ArribaRESUMEN
OBJECTIVE: To investigate the risk factors for recurrent wheezing in infants and young children suffering from dust mite allergy after their first wheezing. METHODS: A total of 1 236 infants and young children who experienced a first wheezing episode and were hospitalized between August 2014 and February 2015 were enrolled, among whom 387 were allergic to dust mites. These infants and young children were followed up to 1 year after discharge. A total of 67 infants and young children who experienced 3 or more recurrent wheezing episodes within 1 year were enrolled as the recurrent wheezing group, while 84 infants and young children who did not experience recurrent wheezing during follow-up were enrolled as the control group. Univariate analysis and multivariate logistic stepwise regression analysis were performed to investigate the risk factors for recurrent wheezing in these patients. RESULTS: The univariate analysis showed that the age on admission, wheezing time before admission, Mycoplasma pneumoniae infection rate, and influenza virus infection rate were associated with recurrent wheezing. The multivariate logistic stepwise regression analysis showed that the older age on admission (OR=2.21, P=0.04) and Mycoplasma pneumoniae infection (OR=3.54, P=0.001) were independent risk factors for recurrent wheezing. CONCLUSIONS: Infants and young children who are allergic to dust mites, especially young children, have a significantly increased risk of recurrent wheezing if they are complicated by Mycoplasma pneumoniae infection during the first wheezing episode.
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Hipersensibilidad/complicaciones , Pyroglyphidae/inmunología , Ruidos Respiratorios/etiología , Animales , Preescolar , Femenino , Humanos , Lactante , Modelos Logísticos , Masculino , Recurrencia , Factores de RiesgoRESUMEN
Because both refined "waste oil" and the third category "waste oil" known as frying old oil experience a longer history at temperature higher than 200 °C compared to the vegetable oil. In this study, the relative change rates of content of conjugated fatty acid glycerides, content of tans-fatty acid glycerides and unsaturation were investigated after being at high temperature for several hours by using FTIR-ATR in order to find out specific targets for "waste oil". The results show that (1) Starting from 160 °C, the contents of conjugated fatty acids glycerides and trans-fatty acid glycerids in the vegetable oils increase but unsaturation decreases with heating temperature and heating time increasing. (2) When heating temperature reaches 200 °C or more, the heating time up to four hours or longer, the three indicators(conjugated fatty glycerids, trans-fatty acid glycerids and unsaturation) of six kinds of vegetable oils have substantial changes. (3) The content of linoleic acid in the vegetable oil has some contributions to the change amplitude of contents of conjugated fatty acid glycerides, and the content of oleic acid in the vegetable oil has some contributions to the change amplitude of content of trans-fatty acid glycerides. (4) In addition, during the warranty period change amplitudes of three indicators are relative small compared with the case of after being at high temperature for several hours. Unsaturation decrease and content of conjugated fatty acid glycerides increase with storage-time increasing. However, unlike the case of after being at high temperature for several hours, the content of trans-fatty acid glycerids decreases with storage-time increasing. Experimental results show that three index value and its variation can be used as specific indicators for refined "waste oil" and "waste oil".
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Ácidos Grasos/análisis , Aceites de Plantas/análisis , CalorRESUMEN
In the present study, by measuring the A3 005 (representing unsaturation), A985 (representing conjugated fatty acids), A960 + A985 (representing trans-fatty acid ) of southern common vegetable oils (peanut oil, corn oil, canola oil, soybean oil, sunflower oil, tea seed oil and olive oil), "waste oil" and overdue vegetable oils, the pass-setting-range of these three index values for the vegetable oils was obtained. On this basis, a method for rapid screening unqualified vegetable oil (expired, adding low-cost oil, adding "waste oil") was established. The method effectively improved the monitoring efficiency of vegetable oil. With this method of screening a number of suspected substandard oils were proved unqualified by determination of fatty acid composition and 11, 12, 13, 17 fatty acid content. Through the combination of several detection methods, the causes for disqualification of vegetable oils can be further inferred.
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Ácidos Grasos/análisis , Aceites de Plantas/análisis , Aceite de Maíz , Ácidos Grasos Monoinsaturados , Aceite de Oliva , Aceite de Cacahuete , Aceite de Brassica napus , Aceite de Soja , Aceite de Girasol , Aceite de Árbol de TéRESUMEN
Osteoarthritis (OA) is a prevalent joint disease that can be exacerbated by lipid metabolism disorders. The intra-articular fat pad (IFP) has emerged as an active participant in the pathological changes of knee OA (KOA). However, the proteomic and lipidomic differences between IFP tissues from KOA and control individuals remain unclear. Samples of IFP were collected from individuals with and without OA (n = 6, n = 6). Subsequently, these samples underwent liquid chromatography/mass spectrometry-based label-free quantitative proteomic and lipidomic analysis to identify differentially expressed proteins (DEPs) and lipid metabolites (DELMs). The DEPs were further subjected to enrichment analysis, and hub DEPs were identified using multiple algorithms. Additionally, an OA diagnostic model was constructed based on the identified hub DEPs or DELMs. Furthermore, CIBERSORT was utilized to investigate the correlation between hub protein expression and immune-related modules in IFP of OA. Our results revealed the presence of 315 DEPs and eight DELMs in IFP of OA patients compared to the control group. Enrichment analysis of DEPs highlighted potential alterations in pathways related to coagulation, complement, fatty acid metabolism, and adipogenesis. The diagnostic model incorporating four hub DEPs (AUC = 0.861) or eight DELMs (AUC = 0.917) exhibited excellent clinical validity for diagnosing OA. Furthermore, the hub DEPs were found to be associated with immune dysfunction in IFP of OA. This study presents a distinct proteomic and lipidomic landscape of IFP between individuals with OA and those without. These findings provide valuable insights into the molecular changes associated with potential mechanisms underlying OA.
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Tejido Adiposo , Lipidómica , Osteoartritis de la Rodilla , Proteómica , Humanos , Osteoartritis de la Rodilla/metabolismo , Osteoartritis de la Rodilla/patología , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Proteómica/métodos , Lipidómica/métodos , Masculino , Femenino , Persona de Mediana Edad , Metabolismo de los Lípidos , Anciano , Relevancia ClínicaRESUMEN
Objective: To investigate early effectiveness of arthroscopic superior fulcrum reconstruction in the treatment of irreparable massive rotator cuff tear (IMRCT). Methods: A retrospective analysis was conducted on the clinical data of 24 patients with IMRCT who met the inclusion criteria between January 2020 and April 2022. Among them, there were 11 males and 13 females with an average age of 56.2 years (range, 42-68 years). There were 12 cases of falling injuries, 3 cases of traction injuries, and the other 9 cases had no obvious causes. The disease duration ranged from 1 to 25 months (median, 6 months). The rotator cuff tears were classified as Hamada grade 2 in 18 cases and grade 3 in 6 cases, and Goutallier grade 1 in 3 cases, grade 2 in 20 cases, and grade 3 in 1 case. All patients were treated with arthroscopic superior fulcrum reconstruction. Visual analogue scale (VAS) score, Constant-Murley score, the University of California at Los Angeles (UCLA) score, and the American Shoulder and Elbow Surgeons (ASES) score were recorded before operation and at 1, 3, 6, and 12 months after operation. Results: The operations were all successfully completed. The incisions healed by first intention and no related complications occurred. All patients were followed up 12-33 months (mean, 24.6 months). The VAS, Constant-Murley, UCLA, and ASES scores at different time points after operation were superior to those before operation ( P<0.05). All of the above indicators further improved with time. Except for no significant difference in VAS and Constant-Murley scores between 6 and 12 months ( P>0.05), the differences between the other time points were significant ( P<0.05). At 12 months after operation, according to UCLA scoring standard, shoulder joint function was rated as excellent in 4 cases, good in 19 cases, and poor in 1 case, with an excellent and good rate of 96.0%. MRI showed that there was no graft re-tear and the transplanted tendon and bone tunnel healed. Conclusion: The arthroscopic superior fulcrum reconstruction for IMRCT can effectively relieve the pain, improve the shoulder range of motion, and restore good shoulder function.
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Lesiones del Manguito de los Rotadores , Articulación del Hombro , Masculino , Femenino , Humanos , Persona de Mediana Edad , Lesiones del Manguito de los Rotadores/cirugía , Manguito de los Rotadores/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Artroscopía , Articulación del Hombro/cirugía , Rango del Movimiento ArticularRESUMEN
Circular RNA (circRNA) THBS1 has been shown to exist as an oncogene in non-small-cell lung cancer, but its role in cervical cancer is still unclear. Our experiment aimed to uncover the functions and specific mechanism of circRNA THBS1 in cervical cancer cells. Levels of circRNA THBS1 and miR-543 in cervical cancer tissues and cell lines were assessed by RT-qPCR. starBase and dual luciferase reporter gene assay were applied for investigating the correlation between miR-543 and circRNA THBS1/HMGB2. Cell proliferation and apoptosis were evaluated by MTT and flow cytometry, respectively. Furthermore, the levels of HMGB2, E-cadherin, and N-cadherin in HeLa cells were determined by RT-qPCR and western blot analysis. Our data revealed that circRNA THBS1 was significantly upregulated and miR-543 was low expressed in cervical cancer tissues and cell lines. circRNA THBS1 interacted with miR-543 and negatively regulated miR-543 expression in HeLa cells. Silencing of circRNA THBS1 remarkably suppressed HeLa cells' viability, accelerated cells' apoptosis, and inhibited the EMT of HeLa cells, while these changes were reversed by miR-543 inhibitor. Moreover, miR-543 affected HeLa cells by targeting HMGB2. In conclusion, circRNA THBS1 silencing inhibited the malignant biological behaviors of cervical cancer cells via the regulation of miR-543/HMGB2 axis.
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Rotator cuff tears are still among the serious challenges encountered by sports medicine surgeons. With the development of arthroscopic technology, the treatment options for irreparable massive rotator cuff tears (IMRCTs) have gradually increased, but postoperatively, these options are prone to graft retears, reoperations, infections, revision surgical procedures, and so on. On the basis of studies on the balance of the force couples of the rotator cuff, more scholars believe that when addressing IMRCTs, attention should be paid to the reconstruction of the force couples of the rotator cuff; hence, we developed the superior fulcrum reconstruction technique. This article describes an alternative approach to IMRCT repair with superior fulcrum reconstruction using autologous ipsilateral peroneus longus tendon.
RESUMEN
Due to the large specific surface area and rich pore structure, chitosan nanofiber membrane has many advantages over conventional gel-like or film-like products. However, the poor stability in acidic solutions and relatively weak antibacterial activity against Gram-negative bacteria severely restrict its use in many industries. Here, we present a chitosan-urushiol composite nanofiber membrane prepared by electrospinning. Chemical and morphology characterization revealed that the formation of chitosan-urushiol composite involved the Schiff base reaction between catechol and amine groups and the self-polymerization of urushiol. The unique crosslinked structure and multiple antibacterial mechanisms endowed the chitosan-urushiol membrane with outstanding acid resistance and antibacterial performance. After immersion in HCl solution at pH 1, the membrane maintained its intact appearance and satisfactory mechanical strength. In addition to its good antibacterial performance against Gram-positive Staphylococcus aureus (S. aureus), the chitosan-urushiol membrane exhibited synergistic antibacterial activity against Gram-negative Escherichia coli (E. coli) that far exceeded that of neat chitosan membrane and urushiol. Moreover, cytotoxicity and hemolysis assays revealed that the composite membrane had good biocompatibility similar to that of neat chitosan. In short, this work provides a convenient, safe, and environmentally friendly method to simultaneously enhance the acid resistance and broad-spectrum antibacterial activity of chitosan nanofiber membranes.