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1.
Meat Sci ; 183: 108655, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34403850

RESUMO

During the thermal processing, proteins of Hengshan goat meat undergo structural modifications such as degradation, oxidation and denaturation, ultimately affect the palatability and acceptability. The results of several objective metrics demonstrated that thermal processing exhibited significant impacts on the tenderness of goat meat. The 551, 84, 72, and 121 proteins were identified in the control and thermal processed groups (boiled, steamed, and roasted), respectively. Compared with the control group, the 101, 98, and 109 differentially-expressed proteins were explored in the treatment groups. Furthermore, the functions of metabolic and skeletal muscle proteome were investigated and discussed. Sensory evaluation and proteomics analysis showed that steaming and boiling treatment had no significant effect on the tenderness of goat meat, while roasting significantly reduced the tenderness, indicating that the available thermal processing methods to ensure the tenderness of goat meat were steaming and boiling treatments. Thus, the established proteomics database of goat meat provided the valuable reference for rational selection of thermal processing methods.


Assuntos
Culinária/métodos , Proteínas Musculares/análise , Proteoma/análise , Carne Vermelha/análise , Adulto , Animais , Feminino , Cabras , Humanos , Masculino , Músculo Esquelético/química , Resistência ao Cisalhamento , Paladar
2.
Bioact Mater ; 9: 168-182, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34820564

RESUMO

Myocardial infarction (MI), as one of the leading causes of global death, urgently needs effective therapies. Recently, hydrogen sulfide (H2S) has been regarded as a promising therapeutic agent for MI, while its spatiotemporally controlled delivery remains a major issue limiting clinical translation. To address this limitation, we designed and synthesized a novel H2S donor (HSD-R) that can produce H2S and emit fluorescence in response to reactive oxygen species (ROS) highly expressed at diseased sites. HSD-R can specifically target mitochondria and provide red fluorescence to visualize and quantify H2S release in vitro and in vivo. Therapeutically, HSD-R significantly promoted the reconstruction of cardiac structure and function in a rat MI model. Mechanistically, myocardial protection is achieved by reducing cardiomyocyte apoptosis, attenuating local inflammation, and promoting angiogenesis. Furthermore, inhibition of typical pro-apoptotic genes (Bid, Apaf-1, and p53) played an important role in the anti-apoptotic effect of HSD-R to achieve cardioprotection, which were identified as new therapeutic targets of H2S against myocardial ischemia injury. This ROS-responsive, self-immolative, and fluorescent H2S donor can serve as a new theranostic agent for MI and other ischemic diseases.

3.
J Colloid Interface Sci ; 607(Pt 1): 229-241, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34500422

RESUMO

Distant metastases and chemotherapy repellency are the key causes of colorectal cancer (CRC)-related mortality. Regorafenib, an oral multi-kinase inhibitor approved for treating advanced CRC with distant metastases and/or chemo-resistance, however only improves median overall survival by 1.4 months. Such limited therapeutic effect is likely due to the low bioavailability of orally administered hydrophobic regorafenib. A regorafenib nanodrug is fabricated by one-step self-assembly with a clinically often-used fluorescent agent (indocyanine green) for overcoming regorafenib's limitations, towards improving regorafenib's therapeutic efficacy in advanced CRC. This nanodrug (nanoRF) was characterized, and its antitumor effects were assessed in three preclinical CRC models. NanoRF converts regorafenib's delivery approach from oral to intravenous with a significantly high encapsulation efficacy of regorafenib (96%) and a long-time colloidal stability. Nanodrug (nanoRF) markedly prolongs regorafenib's blood circulation by halving clearance rate, and enhances regorafenib's tumor accumulation. Across three preclinical CRC models (xenografted tumor, chemodrug-resistant xenografted tumor, and liver metastasis), nanoRF drastically enhances regorafenib's tumor inhibiting efficacy by 0.5-4 folds and effectively extends survival by 0.5-5 folds. This regorafenib nanodrug is a simple, safe, and efficient therapeutic nanodrug for treating advanced CRC with a ready-to-be-clinically-translated potential.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/farmacologia , Piridinas
4.
Food Chem ; 369: 130948, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34474291

RESUMO

As preservative are extensively applied to prevent the quality degradation of Hengshan goat meat sausages, safety assessment based on lipid and elucidation of dynamic change mechanism is urgently needed. The effect of preservatives on lipidome profiles of sausages was investigated using UHPLC-Q-Orbitrap. Totally, 9 subclasses of 70 characteristic lipids (Cer, DG, LPC, PC, PE, PI, PS, SM, TG) were quantified accurately (LOD with 0.68-2.96 µg kg-1, LOQ with 2.25-9.79 µg kg-1, RSD < 3%). The decrease of TG concentration was the most significant, from 1072.43 mg kg-1 in preservative-free samples to 838.53, 786.41 and 681.35 mg kg-1 in natamycin, potassium sorbate and sodium diacetate treated samples, respectively. With regard to preservation and nutrition, natamycin was a potential preservative than two other preservatives. Significant lipid variables were primarily associated with glycerophospholipid and sphingolipid metabolism. Integration of both techniques provided a guide for meat industries to control spoilage with innovative strategies.


Assuntos
Cabras , Lipidômica , Animais , Cromatografia Líquida de Alta Pressão , Lipídeos , Carne/análise
5.
Food Chem ; : 131633, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34848089

RESUMO

Assessments of human exposure to sodium perchlorate via dairy sources are limited. The current study applied untargeted metabolomics (LOD, 1.08-35.60 µg L-1; LOQ, 2.54-90.58 µg L-1; RSD < 6.2%) and proteomics methods by UHPLC-Q-Orbitrap HRMS to investigate the metabolic pathways and nutritional quality of goat milk contaminated with sodium perchlorate. Specifically, 11 metabolites including lactose (from 2.01 to 0.58 mg L-1), adenosine 5'-monophosphate (from 1.23 to 0.45 mg L-1), hypoxanthine (from 0.63 to 0.08 mg L-1), etc. and 3 crucial enzymes include α-lactalbumin, xanthine dehydrogenase and creatine kinase related to the quality traits of goat milk after sodium perchlorate treatment. Overall, except for spermidine, other related metabolites significantly decreased with the increase of sodium perchlorate concentration 0-160 µg L-1 and storage time (4-12 h). Collectively, we provide previously uncharacterized goat milk nutritional quality degradation mechanism induced by sodium perchlorate and a reference to ensure its safe use in human health.

6.
Neoplasma ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34734530

RESUMO

Emerin (EMD) plays diverse roles in cellular polarity organization, nuclear stability, and cell motility, however, the biological role of EMD relevant to the migration and invasion of hepatocellular carcinoma (HCC) cells has not yet been illustrated. In the present study, we initially found that the upregulation of EMD in HCC tissues, and EMD expression was negatively correlated with the spontaneous metastatic potential of HCC cell lines. Loss of EMD in HCC cells facilitated cell migration and invasion in vitro and metastasis in vivo. Meanwhile, we demonstrated that EMD knockdown induced EMT but enhanced p21 expression in HCC cells. Notably, silencing of EMD in HCC cells increased the cytoplasmic localization of p21 protein, whereas p21 knockdown partially abrogated the migratory and invasive ability, EMT, and the actin cytoskeleton rearrangement induced by EMD knockdown in HCC cells. Our results indicated a significant role of EMD knockdown in the HCC cell motility and metastasis through upregulating the cytoplasmic p21, unveiling a novel mechanism of cell motility regulation induced by EMD.

7.
Mol Med ; 27(1): 141, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732133

RESUMO

BACKGROUND: We aimed to investigate the functions and underlying mechanism of lncRNA SNHG1 in bone differentiation and angiogenesis in the development of osteoporosis. METHODS: The differential gene or proteins expressions were measured by qPCR or western blot assays, respectively. The targeted relationships among molecular were confirmed through luciferase reporter, RIP and ChIP assays, respectively. Alkaline phosphatase (ALP), alizarin red S (ARS) and TRAP staining were performed to measure the osteoblast/osteoclast differentiation of BMSCs. The viability, migration and angiogenesis in BM-EPCs were validated by CCK-8, clone formation, transwell and tube formation assays, respectively. Western blot and immunofluorescence detected the cytosolic/nuclear localization of ß-catenin. Ovariectomized (OVX) mice were established to confirm the findings in vitro. RESULTS: SNHG1 was enhanced and miR-181c-5p was decreased in serum and femoral tissue from OVX mice. SNHG1 directly inhibited miR-181c-5p to activate Wnt3a/ß-catenin signaling by upregulating SFRP1. In addition, knockdown of SNHG1 promoted the osteogenic differentiation of BMSCs by increasing miR-181c-5p. In contrast, SNHG1 overexpression advanced the osteoclast differentiation of BMSCs and inhibited the angiogenesis of BM-EPCs, whereas these effects were all reversed by miR-181c-5p overexpression. In vivo experiments indicated that SNHG1 silencing alleviated osteoporosis through stimulating osteoblastogenesis and inhibiting osteoclastogenesis by modulating miR-181c-5p. Importantly, SNHG1 could be induced by SP1 in BMSCs. CONCLUSIONS: Collectively, SP1-induced SNHG1 modulated SFRP1/Wnt/ß-catenin signaling pathway via sponging miR-181c-5p, thereby inhibiting osteoblast differentiation and angiogenesis while promoting osteoclast formation. Further, SNHG1 silence might provide a potential treatment for osteoporosis.

8.
Biol Open ; 10(11)2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34731235

RESUMO

Adult stem cells are critical for the maintenance of tissue homeostasis. However, how the proliferation and differentiation of intestinal stem cells (ISCs) are regulated remains not fully understood. Here, we find a mutant, stum 9-3, affecting the proliferation and differentiation of Drosophila adult ISCs in a forward genetic screen for factors regulating the proliferation and differentiation ISCs. stum 9-3 acts through the conserved Notch signaling pathway, upstream of the S2 cleavage of the Notch receptor. Interestingly, the phenotype of stum 9-3 mutant is not caused by disruption of stumble (stum), where the p-element is inserted. Detailed mapping, rescue experiments and mutant characterization show that stum 9-3 is a new allele of O-fucosyltransferase 1 (O-fut1). Our results indicate that unexpected mutants with interesting phenotype could be recovered in forward genetic screens using known p-element insertion stocks.

9.
Pain Res Manag ; 2021: 3624614, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760032

RESUMO

Objective: Current findings suggest that percutaneous vertebroplasty (PVP) is a suitable therapeutic approach for osteoporotic vertebral compression fractures (OVCFs). However, a significant minority of patients still experience residual back pain after PVP. The present retrospective study was designed to determine the risk factors for residual back pain after PVP and provides a nomogram for predicting the residual back pain after PVP. Methods: We retrospectively reviewed the medical records of patients with single-segment OVCFs who underwent bilateral percutaneous vertebroplasty. Patients were divided into group N and group R according to the postoperative VAS score. Group R is described as the VAS score of residual back pain ≥ 4. Pre- and postoperative factors that may affect back pain relief were evaluated between two groups. Univariate and multivariate logistic regression analysis were performed to identify risk factors affecting residual back pain after PVP. We provided a nomogram for predicting the residual back pain and used the receiver operating characteristic curve (ROC), concordance index (C-index), calibration curve, and decision curve analyses (DCA) to evaluate the prognostic performance. Results: Among 268 patients treated with PVP, 37 (13.81%) patients were classified postoperative residual back pain. The results of the multivariate logistical regression analysis showed that the presence of an intravertebral vacuum cleft (IVC) (OR 3.790, P=0.026), posterior fascia oedema (OR 3.965, P=0.022), severe paraspinal muscle degeneration (OR 5.804, P=0.01; OR 13.767, P < 0.001), and blocky cement distribution (OR 2.225, P=0.041) were independent risk factors for residual back pain after PVP. The AUC value was 0.780, suggesting that the predictive ability was excellent. The prediction nomogram presented good discrimination, with a C-index of 0.774 (0.696∼0.852) and was validated to be 0.752 through bootstrapping validation. The calibration curve of the nomogram demonstrated a good consistency between the probabilities predicted by the nomogram and the actual probabilities. The nomogram showed net benefits in the range from 0.06 to 0.66 in DCA. Conclusions: The presence of IVC, posterior fascia oedema, blocky cement distribution, and severe paraspinal muscle degeneration were significant risk factors for residual back pain after PVP for OVCFs. Patients with OVCFs after PVP who have these risk factors should be carefully monitored for the possible development of residual back pain. We provide a nomogram for predicting the residual back pain after PVP.

10.
Biomed Pharmacother ; 145: 112462, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34844105

RESUMO

A previous study indicated that microRNA-378b (miR-378b) plays a critical role in controlling hepatic insulin resistance by targeting insulin receptor (IR) and p110α in alcoholic liver disease (ALD). Methyl ferulic acid (MFA), a bioactive ingredient in Securidaca inappendiculata Hassk rhizomes, exhibits multiple pharmacological activities. It has been reported that MFA ameliorates insulin resistance in ALD, whereas the underlying molecular mechanism remains unclear. The objective of study was to evaluate the influence of MFA on insulin sensitivity in ethanol-induced L-02 cells as well as alcohol-fed mice and illuminate the function of miR-378b-mediated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway in system. MFA was found to remarkably down-regulate miR-378b level and increase IR and p110α expressions. Furthermore, the effect of MFA on modulating miR-378b/PI3K-AKT pathway to enhance insulin sensitivity was corroborated by overexpressing and inhibiting miR-378b. Taken together, MFA exhibited a positive effect against ALD by attenuating the inhibition of miR-378b on IR/p110α and partly activating the insulin signaling to alleviate alcohol-induced hepatic insulin resistance.

11.
BMC Pediatr ; 21(1): 526, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837997

RESUMO

BACKGROUND: Kawasaki disease (KD) is an acute febrile vasculitis that often occurs in children under 5 years. Ptosis and muscle weakness associated with KD are rarely documented. CASE PRESENTATION: We present a case of KD with eyelid ptosis and muscle weakness in a 3-year-old boy. At admission, grade IV and grade III muscle strength were recorded for upper and lower limbs, respectively. Diminished patellar tendon reflex was noted. Laboratory evaluation showed hypokalemia with the serum potassium concentration of 2.62 mmol/L. Intravenous immunoglobulin (IVIG) and aspirin were initiated immediately accompanied with methylprednisolone for adjunctive therapy. Potassium supplement was administered at the same time, which resulted in the correction of hypokalemia on the 2nd day of admission but no improvement in ptosis and muscle weakness. Neostigmine testing, lumber puncture, electromyography, and cerebral and full spine MRI were performed, which, however, did not find evidence for neural and muscle diseases. On the 5th day, the fever was resolved. On the 6th day, eyelid ptosis disappeared. And on the 14th day, the muscle strength and muscle tension returned to normal, patellar tendon reflex could be drawn out normally, and the boy regained full ambulatory ability. CONCLUSIONS: KD might affect the neural and muscular systems, and KD complicated with eyelid ptosis and muscle weakness is responsive to the standard anti-inflammatory treatment plus adjunctive corticosteroid therapy.

13.
Int J Gen Med ; 14: 8211-8216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815694

RESUMO

Background: Aspirin remains a key component of the standard therapy for Kawasaki disease (KD) in children. Although it is well known that aspirin can cause hypersensitivity such as aspirin-induced urticaria (AIU), AIU in children with KD has not been described. Methods: A retrospective case-control study was conducted to investigate AIU clinical features, biochemical parameters, treatment and outcomes in children with KD. Furthermore, biomarkers for predicting AIU were explored using the receiver operating characteristic (ROC) curve analysis. Results: We identified 46 AIU cases with 22 boys and 24 girls during April 2015-May 2019. Eighty-nine age-matched KD patients without AIU were randomly chosen as controls. The proportions of children with allergy history and aspirin doses administered in the 2 groups were found not to be significantly different. AIU group had substantially higher baseline C-reactive protein and NT-proBNP levels, and increased neutrophil percent. AIU appeared 6.0 (4.0, 8.0) days after aspirin treatment. Aspirin withdrawal and anti-allergic treatment were applied for AIU, and AIU disappeared in 1-3 days. Baseline NT-proBNP predicted AIU with an AUC of 0.70 (95% CI [0.60 to 0.79]) for sensitivity and specificity of 72.1% and 62.5%, respectively, for a cut-off value of 612.9 mg/L. The length of hospital stay for AIU patients was significantly greater compared with controls. Conclusion: AIU in KD children is not related to gender or aspirin dose, and those with AIU have more severe inflammation at admission. Aspirin should be withdrawn for AIU management. Baseline NT-proBNP may serve as a valuable biomarker to predict AIU.

14.
Peptides ; 147: 170682, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34742787

RESUMO

INTRODUCTION: Renal ischemia/reperfusion injury (IRI) is the most common cause of acute kidney injury (AKI), and patients with AKI have a high rate of mortality. Apelin is a therapeutic candidate for treatment of IRI and Elabela (ELA) is a recently discovered hormone that also activates the apelin receptor (APJ). We examined the use of ELA as a preventive treatment for IRI using in vitro and in vivo models. METHODS: Male mice were subjected to renal IRI, with or without administration of a stabilized form of ELA (Fc-ELA-21) for 4 days. Renal tubular lesions were measured using H&E staining, reactive oxygen species (ROS) were measured using a dihydroethidium stain assay, and renal cell apoptosis was measured using the TUNEL assay and flow cytometry. Immortalized human proximal tubular epithelial (HK-2) cells were pretreated with or without LY294002 and/or ELA-32, maintained at normoxic or hypoxic conditions, and then returned to normal culture conditions to mimic IRI. Cell apoptosis was determined using the TUNEL assay and cell proliferation was determined using the MTT assay. The levels of Akt, p-Akt, ERK1/2, p- ERK1/2, Bcl-2, Bax, caspase-3 and cleaved caspase-3 were measured using western blotting. RESULTS: Fc-ELA-21 administration reduced renal tissue damage, ROS production, and apoptosis in mice that had renal IRI. ELA-32 reduced HK-2 cell apoptosis and restored the proliferation of cells subjected to IRI. Akt phosphorylation had a role in the anti-apoptotic effect of ELA. CONCLUSION: This study of in vitro and in vivo models of IRI indicated that the preventive and anti-apoptotic effects of ELA were mediated via the PI3K/Akt signaling pathway.

16.
Nat Commun ; 12(1): 5777, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599195

RESUMO

Electrorefining process has been widely used to separate and purify metals, but it is limited by deposition potential of the metal itself. Here we report in-situ anodic precipitation (IAP), a modified electrorefining process, to purify aluminium from contaminants that are more reactive. During IAP, the target metals that are more cathodic than aluminium are oxidized at the anode and forced to precipitate out in a low oxidation state. This strategy is fundamentally based on different solubilities of target metal chlorides in the NaAlCl4 molten salt rather than deposition potential of metals. The results suggest that IAP is able to efficiently and simply separate components of aluminum alloys with fast kinetics and high recovery yields, and it is also a valuable synthetic approach for metal chlorides in low oxidation states.

17.
Front Mol Neurosci ; 14: 688050, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630032

RESUMO

Recurrent chest blast exposure can lead to brain inflammation, oxidative stress, and mental disorders in soldiers. However, the mechanism that underlies brain injury caused indirectly by chest blasts remains unclear. It is urgent to find additional reliable biomarkers to reveal the intimate details of the pathogenesis of this phenomenon. We used the term tandem mass tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to screen for differentially expressed proteins in rat brain at different time points after a chest blast. Data are available via ProteomeXchange with the identifier PXD025204. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), the Database for Annotation, Visualization and Integrated Discovery (DAVID), and Cytoscape analyses were used to analyze the proteomic profiles of blast-exposed rats. In addition, we performed Western blotting to verify protein levels. We identified 6,931 proteins, of which 255 were differentially expressed and 43, 84, 52, 97, and 49 were identified in brain tissues at 12, 24, 48, and 72 h and 1 week after chest blast exposure, respectively. In this study, the GO, KEGG, Clusters of Orthologous Groups of proteins, and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analyses indicated that brain damage caused by chest blast exposure involved many important biological processes and signaling pathways, such as inflammation, cell adhesion, phagocytosis, neuronal and synaptic damage, oxidative stress, and apoptosis. Furthermore, Western blotting confirmed that these differentially expressed proteins and affected signaling pathways were associated with brain damage caused by chest blast exposure. This study identifies potential protein biomarkers of brain damage caused indirectly by chest blast and new targets for the treatment of this condition.

18.
Front Neurol ; 12: 683532, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630273

RESUMO

Background: The successful application of subthalamic nucleus (STN) deep brain stimulation (DBS) surgery relies mostly on optimal lead placement, whereas the major challenge is how to precisely localize STN. Microstimulation, which can induce differentiating inhibitory responses between STN and substantia nigra pars reticulata (SNr) near the ventral border of STN, has indicated a great potential of breaking through this barrier. Objective: This study aims to investigate the feasibility of localizing the boundary between STN and SNr (SSB) using microstimulation and promote better lead placement. Methods: We recorded neurophysiological data from 41 patients undergoing STN-DBS surgery with microstimulation in our hospital. Trajectories with typical STN signal were included. Microstimulation was applied near the bottom of STN to determine SSB, which was validated by the imaging reconstruction of DBS leads. Results: In most trajectories with microstimulation (84.4%), neuronal firing in STN could not be inhibited by microstimulation, whereas in SNr long inhibition was observed following microstimulation. The success rate of localizing SSB was significantly higher in trajectories with microstimulation than those without. Moreover, results from imaging reconstruction and intraoperative neurological assessments demonstrated better lead location and higher therapeutic effectiveness in trajectories with microstimulation and accurately identified SSB. Conclusion: Microstimulation on microelectrode recording is an effective approach to localize the SSB. Our data provide clinical evidence that microstimulation can be routinely employed to achieve better lead placement.

19.
Comput Intell Neurosci ; 2021: 9590502, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616447

RESUMO

Personalized courses recommendation technology is one of the hotspots in online education field. A good recommendation algorithm can stimulate learners' enthusiasm and give full play to different learners' learning personality. At present, the popular collaborative filtering algorithm ignores the semantic relationship between recommendation items, resulting in unsatisfactory recommendation results. In this paper, an algorithm combining knowledge graph and collaborative filtering is proposed. Firstly, the knowledge graph representation learning method is used to embed the semantic information of the items into a low-dimensional semantic space; then, the semantic similarity between the recommended items is calculated, and then, this item semantic information is fused into the collaborative filtering recommendation algorithm. This algorithm increases the performance of recommendation at the semantic level. The results show that the proposed algorithm can effectively recommend courses for learners and has higher values on precision, recall, and F1 than the traditional recommendation algorithm.


Assuntos
Educação à Distância , Reconhecimento Automatizado de Padrão
20.
J Biomater Sci Polym Ed ; : 1-14, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34704529

RESUMO

Osteoarthritis (OA) is a degenerative joint disease, which can lead to joint pain, stiffness, deformity and dysfunction, that seriously affects the quality of life in patients. At present, the treatments of OA mainly include early pharmacological treatment and late joint replacement. However, current pharmacological treatment has limited efficacy and undesired side effects.Chitosan oligosaccharide (COS) is a kind of nontoxic and biodegradable oligo-saccharide, which is composed of 2-20 glucosamine or N-acetylglucosamine linked by ß-1,4 glycosidic bond. Studies have shown that COS has significant biological properties like antimicrobial, anti-inflammatory, antioxidant, and anti-tumor, as well as immunoregulation ability. However, the effects of COS on OA have not been clarified. In this study, we explored the protective effects of COS with different degrees of deacetylation on chondrocytes stimulated by interleukin 1ß (IL-1ß) in vitro.The results showed that IL-1ß inhibited cell proliferation and promoted cell apoptosis. Besides that, IL-1ß increased the expression of the major chondro-degrading genes MMP13 and ADAMTS-5, while decreased the expression of COL2A and ACAN. COS with different degrees of deacetylation (HDACOS, MDACOS, LDACOS) had different effects on IL-1ß induced inflammation. LDACOS had the most obvious anti-inflammatory effects to inhibit the expression of MMP13 and ADAMTS-5 while promoted the expression of COL2A and ACAN. In addition, we found that the expression of autophagy-related gene Beclin-1 was up-regulated, and the ratio of LC3-II/LC3-I was increased in the LDACOS group. Furthermore, transmission electron microscopy (TEM) analysis showed that the number of intracellular autophagosomes increased significantly with the treatment of LDACOS. Based on our research, we suggested that LDACOS could inhibit chondrocytes inflammation and promote cell autophagy, and might be a protective drug for the treatment of OA.

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