RESUMO
INTRODUCTION: Complexities of robotic distal gastrectomy (RDG) give reason to assess physician's surgical skill. Varying levels in surgical skill affect patient outcomes. We aim to investigate how a novel artificial intelligence (AI) model can be used to evaluate surgical skill in RDG by recognizing surgical instruments. METHODS: Fifty-five consecutive robotic surgical videos of RDG for gastric cancer were analyzed. We used Deeplab, a multi-stage temporal convolutional network, and it trained on 1234 manually annotated images. The model was then tested on 149 annotated images for accuracy. Deep learning metrics such as Intersection over Union (IoU) and accuracy were assessed, and the comparison between experienced and non-experienced surgeons based on usage of instruments during infrapyloric lymph node dissection was performed. RESULTS: We annotated 540 Cadiere forceps, 898 fenestrated bipolars, 359 suction tubes, 307 Maryland bipolars, 688 harmonic scalpels, 400 staplers, and 59 large clips. The average IoU and accuracy were 0.82 ± 0.12% and 87.2 ± 11.9% respectively. Moreover, the percentage of each instrument's usage to overall infrapyloric lymphadenectomy duration predicted by AI were compared. The use of stapler and large clip were significantly shorter in the experienced group compared to the non-experienced group. CONCLUSIONS: This study is the first to report that surgical skill can be successfully and accurately determined by an AI model for RDG. Our AI gives us a way to recognize and automatically generate instance segmentation of the surgical instruments present in this procedure. Use of this technology allows unbiased, more accessible RDG surgical skill.
OBJECTIF: Les desmosomes sont les jonctions interkératinocytaires les plus proéminentes. Le fonctionnement appropriée des épithéliums stratifiés comme épiderme dépend de leur expression. La composition moléculaire et les propriétés physicochimiques des desmosomes évoluent au cours de la différenciation épidermique. La desquamation de cornéocytes la surface du stratum corneum depend de la dégradation ordonnée des desmosomes par les enzymes endogènes. Ce processus peut être régulé par les molécules glycosylées. Notre travail consistait en détection et caractérisation de l'un des acteurs potentiellement impliqués, portant des chaînes carbohydrate. METHODES: Les approches d'analyse biochimique s'appuyant sur un anticorps monoclonal original (immunotransfert monoet bidimensionnel, immunoprécipitationimmunodétection croisées, digestions enzymatiques, tests de déglycosylation et d'inhibition de synthèse) nous ont permis la caractérisation partielle d'un protéoglycanne sécrété dans les espaces interkératinocytaires. Cette molécule s'intègre aux desmosomes en quantités proportionnelles au stade de différenciation des kératinocytes, comme le démontrent les marquages ultrastructuraux à l'or colloïdal sur des cryocoupes et tissus enrobés en résines acryliques. RESULTATS: Cet antigène, que nous avons appelé desmosealine, est clairement distinct des éléments constitutifs de desmosomes décrits jusqu'alors. Contrairement aux protéoglycannes épidermiques connus, il porte exclusivement les chaînes glycosaminoglycannes de type chondroïtine/dermatane sulfate. La desmosealine est présente dans les parties extracellulaires de desmosomes, dans la portion supérieure de l'épiderme vivant et le début du stratum corneum. CONCLUSION: L'intégration massive d'un protéoglycanne dans des parties intercellulaires de desmosomes revêt vraisemblablement une importance fonctionnelle. De par son profile biochimique, sa distribution dans l'épiderme et son affinité pour les desmosomes, le desmosealine peut s'avérer être un élément clé dans la régulation de la cohésion interkératinocytaire et la formation de la barrière de perméabilité épidermique.
Assuntos
Proteoglicanas de Sulfatos de Condroitina , Condroitina , Desmossomos , Humanos , Condroitina/metabolismo , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Desmossomos/metabolismoRESUMO
Chondroitin, a class of glycosaminoglycan polysaccharides, is found as proteoglycans in the extracellular matrix, plays a crucial role in tissue morphogenesis during development and axonal regeneration. Ingestion of chondroitin prolongs the lifespan of C. elegans. However, the roles of endogenous chondroitin in regulating lifespan and healthspan mostly remain to be investigated. Here, we demonstrate that a gain-of-function mutation in MIG-22, the chondroitin polymerizing factor (ChPF), results in elevated chondroitin levels and a significant extension of both the lifespan and healthspan in C. elegans. Importantly, the remarkable longevity observed in mig-22(gf) mutants is dependent on SQV-5/chondroitin synthase (ChSy), highlighting the pivotal role of chondroitin in controlling both lifespan and healthspan. Additionally, the mig-22(gf) mutation effectively suppresses the reduced healthspan associated with the loss of MIG-17/ADAMTS metalloprotease, a crucial for factor in basement membrane (BM) remodeling. Our findings suggest that chondroitin functions in the control of healthspan downstream of MIG-17, while regulating lifespan through a pathway independent of MIG-17.
Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Condroitina/metabolismo , Longevidade/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Glicosaminoglicanos/metabolismo , Metaloendopeptidases/metabolismo , Desintegrinas/metabolismoRESUMO
Solution nuclear magnetic resonance (NMR) analysis of polysaccharides can provide valuable information not only on their primary structures but also on their conformation, dynamics, and interactions under physiological conditions. One of the main problems is that non-anomeric 1H signals typically overlap, and this often hinders detailed NMR analysis. Isotope enrichment, such as with 13C and 15N, will add a new dimension to the NMR spectra of polysaccharides, and spectral analysis can be performed with enhanced sensitivity using isolated peaks. For this purpose, here we have prepared uniformly 13C- and/or 15N-labeled chondroitin polysaccharides -4)-ß-D-glucuronopyranosyl-(1-3)-2-acetamido-2-deoxy-ß-D-galactopyranosyl-(1- with molecular weights in the range from 310 to 460 k by bacterial fermentation. The enrichment ratios for 13C and 15N were 98.9 and 99.8%, respectively, based on the mass spectrometric analysis of the constituent chondroitin disaccharides. 1H and 13C NMR signals were assigned mainly based on HSQC and 13C-detection experiments including INADEQUATE, HETCOR, and HETCOR-TOCSY. The carbonyl carbon signal of the N-acetyl-ß-D-galactosamine residue was unambiguously distinguished from the C6 carbon of the ß-D-glucuronic acid residue by the observation of 13C peak splitting due to 1JCN coupling in 13C- and 15N-labeled chondroitin. The T2* and T1 were measured and indicate that both rigid and mobile sites are present in the long sequence of chondroitin. The conformation, dynamics, and interactions of chondroitin and its derivatives will be further analyzed based on the results obtained in this study.
Assuntos
Isótopos de Carbono , Espectroscopia de Ressonância Magnética , Peso Molecular , Isótopos de Nitrogênio , Espectroscopia de Ressonância Magnética/métodos , Condroitina/químicaRESUMO
Colon cancer is a common cancer with high mortality globally. The role of chondroitin polymerizing factor (CHPF) has been elucidated in various cancers. However, its role and mechanism remain unknown in colon cancer. CHPF expression was examined by GEPIA database, reverse transcription-quantitative polymerase chain reaction and western blot. The relationship between CHPF expression and the clinicopathologic characteristics as well as miR-214-3p level was determined in colon cancer patients. The role and mechanism of CHPF in the growth, ferroptosis, and glycolysis of colon cancer cells were evaluated by cell counting kit-8, biochemical detections, luciferase, and western blot experiments. Additionally, the role of CHPF was explored in xenografted mice. CHPF expression was increased and was related to advanced TNM stage, poor differentiation and shorter overall survival in patients with colon cancer. Knockdown of CHPF inhibited colon cancer cell growth, and downregulated the expression of proteins involving in ferroptosis and glycolysis both in vitro and in vivo. Besides, CHPF silencing increased the levels of ferrous iron and ROS, but decreased glucose uptake, lactate product, and ATP level in vitro. Mechanically, miR-214-3p directly targeted CHPF and negatively regulated its expression. Upregulation of miR-214-3p reduced cell viability, glucose uptake, lactate product, and ATP level, but increased the levels of ferrous iron and ROS, which were reversed by the overexpression of CHPF. Upregulation of CHPF predicted poor prognosis, and miR-214-3p/CHPF axis inhibited growth, downregulated the levels of glycolysis-related indexes, and promoted ferroptosis in colon cancer cells.
Assuntos
Neoplasias do Colo , Ferroptose , MicroRNAs , Humanos , Animais , Camundongos , Ferroptose/genética , Espécies Reativas de Oxigênio , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Ferro , Ácido Láctico , Glucose , Condroitina , Trifosfato de Adenosina , MicroRNAs/genética , Proliferação de Células , Linhagem Celular TumoralRESUMO
The formulation of microparticles composed of a mixture of carriers represents an innovative approach for lung drug delivery of dry powder. The carriers used can significantly influence the properties of the microparticles, such as size, shape, surface area, hygroscopicity, or aggregation, thus improving the aerosolization of the drugs after inhalation. The properties mentioned above are crucial for effective pulmonary therapy. The combination of carriers of a carbohydrate nature and gelling agents is advantageous for controlled drug release. The experimental work aimed to prepare by spray drying and subsequently evaluate ten batches of microparticles composed of sugar-based carriers (mannitol, maltodextrin, dextran) and gelling polymers (chitosan, chondroitin sulfate) and to select a suitable combination for follow-up experimental work aimed at drug incorporation into the microparticle matrix. The most suitable parameters were exhibited by batches whose aerodynamic diameter was close to 5 µm, particles prepared from a combination of mannitol and dextran, chitosan and chondroitin, or maltodextrin and chondroitin. These batches also showed the highest fine particle fraction value (> 43%). From a processability point of view, the batch with maltodextrin and chondroitin is preferable due to the lower viscosity of the dispersion and the more regular shape of the final microparticles.
Assuntos
Quitosana , Dextranos , Sistemas de Liberação de Medicamentos , Condroitina , ManitolRESUMO
The formulation of microparticles composed of a mixture of carriers represents an innovative approach for lung drug delivery of dry powder. The carriers used can significantly influence the properties of the microparticles, such as size, shape, surface area, hygroscopicity, or aggregation, thus improving the aerosolization of the drugs after inhalation. The properties mentioned above are crucial for effective pulmonary therapy. The combination of carriers of a carbohydrate nature and gelling agents is advantageous for controlled drug release. The experimental work aimed to prepare by spray drying and subsequently evaluate ten batches of microparticles composed of sugar-based carriers (mannitol, maltodextrin, dextran) and gelling polymers (chitosan, chondroitin sulfate) and to select a suitable combination for follow-up experimental work aimed at drug incorporation into the microparticle matrix. The most suitable parameters were exhibited by batches whose aerodynamic diameter was close to 5 µm, particles prepared from a combination of mannitol and dextran, chitosan and chondroitin, or maltodextrin and chondroitin. These batches also showed the highest fine particle fraction value (> 43%). From a processability point of view, the batch with maltodextrin and chondroitin is preferable due to the lower viscosity of the dispersion and the more regular shape of the final microparticles.
Assuntos
Quitosana , Dextranos , Sistemas de Liberação de Medicamentos , Condroitina , ManitolRESUMO
Reprogramming metabolic flux is a promising approach for constructing efficient microbial cell factories (MCFs) to produce chemicals. However, how to boost the transmission efficiency of metabolic flux is still challenging in complex metabolic pathways. In this study, metabolic flux is systematically reprogrammed by regulating flux size, flux direction, and flux rate to build an efficient MCF for chondroitin production. The ammoniation pool for UDP-GalNAc synthesis and the carbonization pool for UDP-GlcA synthesis are first enlarged to increase flux size for providing enough precursors for chondroitin biosynthesis. Then, the ammoniation pool and the carbonization pool are rematched using molecular valves to shift flux direction from cell growth to chondroitin biosynthesis. Next, the adaptability of polymerization pool with the ammoniation and carbonization pools is fine-tuned by dynamic and static valve-based adapters to accelerate flux rate for polymerizing UDP-GalNAc and UDP-GlcA to produce chondroitin. Finally, the engineered strain E. coli F51 is able to produce 9.2 g L-1 chondroitin in a 5-L bioreactor. This strategy shown here provides a systematical approach for regulating metabolic flux in complex metabolic pathways for efficient biosynthesis of chemicals.
Assuntos
Condroitina , Escherichia coli , Condroitina/química , Condroitina/metabolismo , Escherichia coli/metabolismo , Difosfato de Uridina/metabolismoRESUMO
Chondroitin polymerizing factor (CHPF) is an important glycosyltransferases that participates in the biosynthesis of chondroitin sulfate (CS). Our previous study showed that silencing CHPF expression inhibited glioma cell proliferation in vitro, but the molecular mechanisms by which CHPF contributes to development of glioma have not been characterized. In this study, we found that CHPF was up-regulated in glioma tissues and was positively correlated with malignant clinical pathological characteristics of patients with glioma. Silencing CHPF expression inhibited proliferation, colony formation, migration, and cell cycle of glioma cells. Moreover, silencing CHPF suppressed glioma malignance in vivo. Immunoprecipitation, co-immunoprecipitation, GST pulldown, and liquid chromatography-mass spectrometry (LC-MS/MS) assays were used to verify the interaction between CHPF and Mitotic arrest deficient 1-like 1 (MAD1L1). In addition, Chromatin Immunoprecipitation (ChIP)-PCR analysis showed that HNF4A bound to the CHPF promoter region, which indicated that the transcription factor hepatocyte nuclear factor 4A (HNF4A) could regulate the expression of CHPF in glioma cells.
Assuntos
Condroitina , Glioma , Humanos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Glioma/patologia , Fatores Nucleares de Hepatócito/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Ciclo Celular/metabolismo , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismoRESUMO
The causal effects of chondroitin, glucosamine, and vitamin/mineral supplement intake on kidney function remain unknown, despite being commonly used. We conducted a two-sample summary-level Mendelian randomization (MR) analysis to test for causal associations between regular dietary supplement intake and kidney function. Genetic instruments for chondroitin, glucosamine, and vitamin/mineral supplement intake were obtained from a genome-wide association study of European ancestry. Summary statistics for the log-transformed estimated glomerular filtration rate (log-eGFR) were provided by the CKDGen consortium. The multiplicative random-effects inverse-variance weighted method showed that genetically predicted chondroitin and glucosamine intake was causally associated with a lower eGFR (chondroitin, eGFR change beta = -0.113%, standard error (SE) = 0.03%, p-value = 2 × 10-4; glucosamine, eGFR change beta = -0.240%, SE = 0.035%, p-value = 6 × 10-12). However, a genetically predicted vitamin/mineral supplement intake was associated with a higher eGFR (eGFR change beta = 1.426%, SE = 0.136%, p-value = 1 × 10-25). Validation analyses and pleiotropy-robust MR results for chondroitin and vitamin/mineral supplement intake supported the main results. Our MR study suggests a potential causal effect of chondroitin and glucosamine intake on kidney function. Therefore, clinicians should carefully monitor their long-term effects.
Assuntos
Glucosamina , Vitaminas , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Condroitina , Polimorfismo de Nucleotídeo Único , Rim , MineraisRESUMO
Breast cancer remains the leading cause of cancer-associated mortality in women. Research investigating novel therapeutic approaches is thus crucial, including phytotherapeutics. Pterostilbene (PTS) is a phytochemical agent with promising efficacy against breast cancer. Poor solubility, low bioavailability and chemical instability are major drawbacks compromising PTS functionality. Herein, novel PTS-loaded solid lipid nanoparticles (PTS-SLNs) were fabricated using the ultrasonication technique. Dual-functionalization with lactoferrin (Lf) and chondroitin-sulfate (CS; CS/Lf/PTS-SLNs) was adopted as active-targeting approach. CS/Lf/PTS-SLNs demonstrated nanoparticle-size (223.42 ± 18.71 nm), low PDI (0.33 ± 0.017), acceptable zeta potential (-11.85 ± 0.07 mV) and controlled release (72.93 ± 2.93% after 24 h). In vitro studies on triple-negative MDA-MB-231 revealed prominent cytotoxicity of CS/Lf/PTS-SLNs (2.63-fold IC50 reduction), higher anti-migratory effect and cellular uptake relative to PTS-solution. The in vivo anti-tumor efficacy in an orthotopic cancer model verified the superiority of CS/Lf/PTS-SLNs; achieving 2.4-fold decrease in tumor growth compared to PTS-solution. On the molecular level, CS/Lf/PTS-SLNs enhanced suppression of VEGF, down-regulated cyclin D1 and upregulated caspase-3 and BAX, compared to PTS-solution. Also, immunohistochemical assay confirmed the higher anti-tumorigenic effect of CS/Lf/PTS-SLNs (5.87-fold decrease in Bcl-2 expression) compared to PTS-solution. Our findings highlight CS/Lf/PTS-SLNs as a promising nanoplatform for phytotherapeutic targeted-breast cancer therapy.
Assuntos
Neoplasias da Mama , Nanopartículas , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Lactoferrina/química , Condroitina/uso terapêutico , Lipídeos/química , Nanopartículas/química , Portadores de Fármacos/uso terapêutico , Tamanho da PartículaRESUMO
Chondroitin anchored crystalline nano-capsules bearing Imatinib (IMT), and simvastatin (SMV) was developed using Poly (L-lactic acid) (PLLA) by two-step method, i.e., firstly, by synthesizing chondroitin (CSA) anchored simvastatin (SMV) using cystamine as a spacer (SMV-SS-CSA) for disulfide triggered glutathione (GSH) sensitive release and secondly, by developing phenyl boronic ester grafted Pluronic F68 (PEPF) for H2O2 responsive release. By combining these conjugates, we have prepared crystalline nano-capsules (CNs) for preferential targeting of CD44 receptors. The developed CNs were spherical when characterized through SEM, TEM, and AFM for surface morphology, while changes in particle size and crystalline structure were confirmed through Quasi-Elastic light scattering (QELS) and Wide Angle X-ray Scattering (WAXS). The enhanced cellular uptake was noted in chondroitin-modified nano-capsules IMT/SMV-SS-CSA@CNs compared to unmodified nano-capsules IMT+SMV@CNs. IMT/SMV-SS-CSA@CNs displayed significantly higher G2/M phase arrest (76.9%) than unmodified nano-capsules. The prototype formulation (IMT/SMV-SS-CSA@CNs) showed an overall improved pharmacokinetic profile in terms of both half-life and AUC0-α. When tested in the 4T1 subcutaneously injected tumor-bearing Balb/c mice model, the tumor growth inhibition rate of IMT/SMV-SS-CSA@CNs was significantly higher (91%) than the IMT+SMV combination. Overall, the findings suggest that the proposed dual responsive chondroitin-modified drug delivery could have a step forward in achieving spatial and temporal targeting at the tumor site.
Assuntos
Peróxido de Hidrogênio , Neoplasias , Animais , Camundongos , Mesilato de Imatinib/farmacologia , Sinvastatina , Condroitina , OxirreduçãoRESUMO
Introduction: Glucosamine and chondroitin are supplements that are often, but not always, used in combination for arthritis and joint pain. Multiple studies have suggested that glucosamine and chondroitin may be associated with reduced risk of several diseases, as well as all-cause, cancer- and respiratory disease-specific mortality. Methods: Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) were used to further evaluate the association between glucosamine and chondroitin with mortality. Participants include 38,021 adults, ages 20+ years and older, who completed the detailed NHANES between 1999 and 2014. Participants were followed for death through linkage with the National Death Index through the end of 2015, over which time 4905 deaths occurred. Adjusted hazard ratios (HRs) for overall and cause-specific mortality were estimated using Cox regression models. Results: Despite glucosamine and chondroitin use appearing to be inversely associated with mortality in the minimally adjusted models, no association was observed in multivariable models (glucosamine: HR = 1.02; 95% confidence interval [CI]: 0.86-1.21, chondroitin: HR = 1.04, 95% CI: 0.87-1.25). No association with cancer mortality or other mortality rate was observed after multivariable adjustment. There was a suggestive, nonsignificant inverse association for cardiovascular-specific mortality (glucosamine HR = 0.72; 95% CI: 0.46-1.15, chondroitin: HR = 0.76; 95% CI: 0.47-1.21). Conclusion: The lack of significant relationship between glucosamine and chondroitin use and all-cause or cause-specific mortality after adjusting extensively for multiple covariates in this nationally representative adult population was in contrast to prior literature. Given the limited power to explore the cause-specific mortality, future well-powered studies will be needed to better understand the potential association with cardiovascular-specific mortality.
Assuntos
Glucosamina , Neoplasias , Humanos , Adulto , Estados Unidos/epidemiologia , Glucosamina/uso terapêutico , Condroitina/uso terapêutico , Inquéritos Nutricionais , Estudos ProspectivosRESUMO
Chondroitin sulfate proteoglycans (CSPGs) are polyanionic extra/pericellular matrix macromolecules that surround almost all cell types and create microenvironmental niches to support miscellaneous cellular events. In general, the multifunctional properties of CSPGs are attributable to the structural divergence of the CS glycosaminoglycan (GAG) moieties. Because the expression profiles of the GAG chains of CSPGs change with developmental stage, aging, and disease progression, characterization of the GAG chains is essential to understand the functional roles of CSPGs. This chapter describes the basic protocols for GAG moiety-based immunochemical detection of CSPGs in biological samples in conjunction with CS disaccharide composition analysis.
Assuntos
Proteoglicanas de Sulfatos de Condroitina , Glicosaminoglicanos , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Glicosaminoglicanos/metabolismo , Dissacarídeos , Sulfatos de Condroitina/química , CondroitinaRESUMO
The anti-inflammatory properties of glucosamine and chondroitin suggest that they may have potential effects in cancer prevention. We performed this meta-analysis to assess the protective function of glucosamine and/or chondroitin intake against cancer risk. We searched the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) databases. The odds ratio (OR), corresponding to the 95% confidence interval (95% CI), was used to assess the association between chondroitin and/or glucosamine intake and cancer risk. Thirteen studies met the inclusion criteria, with 1,690,918 participants and 55,045 cancer cases. Overall, chondroitin and/or glucosamine intake was associated with a lower risk of colorectal cancer (OR = 0.91, 95% CI, 0.87-0.94) and lung cancer (OR = 0.84, 95% CI, 0.79-0.89). Subgroup analysis supported the protective effect of different SYSADOAs (chondroitin and/or glucosamine) intake. However, the protective effect was not observed in the only chondroitin intake group and in the NSAIDs group. Our meta-analysis found that the intake of glucosamine and/or chondroitin decreased the risk of colorectal and lung cancers. Moreover, NSAIDs use may have a synergistic protective effect.
Assuntos
Condroitina , Neoplasias Pulmonares , Humanos , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Condroitina/uso terapêutico , Glucosamina , Neoplasias Pulmonares/prevenção & controleRESUMO
Interaction of ß-D-glucopyranuronic acid (GlcA), N-acetyl-ß-D-glucosamine (GlcNAc), N-acetyl-ß-D-galactosamine (GalNAc) and two natural decameric glycosaminoglycans, hyaluronic acid (HA) and Chondroitin (Ch) with carboxylated carbon nanotubes, were studied using molecular dynamics simulations in a condensed phase. The force field used for carbohydrates was the GLYCAM-06j version, while functionalized carbon nanotubes (fCNT) were described using version two of the general amber force field. We found a series of significant differences in carbohydrate-fCNT adsorption strength depending on the monosaccharide molecule and protonation state of surface carboxyl groups. GlcNAc and GalNAc reveal a strong adsorption on fCNT with deprotonated carboxyl groups, and a slightly weaker adsorption on the fCNT with protonated carboxyl groups. On the contrary, GlcA weakly adsorbs on fCNT. The change in protonation state of surface carboxyl groups leads to the reversal orientation of GlcNAc and GalNAc in reference to the fCNT surface, while GlcA is not sensitive to that factor. Adsorption of decameric oligomers on the surface of fCNT weakens with the increasing number of monosaccharide units. Chondroitin adsorbs weaker than hyaluronic acid and incorporation of four Ch molecules leads to partial detachment of them from the fCNT surface. The glycan-fCNT interactions are strong enough to alter the conformation of carbohydrate backbone; the corresponding conformational changes act toward a more intensive contact of glycan with the fCNT surface. Structural and energetic features of the adsorption process suggest the CH-π interaction-driven mechanism.
Assuntos
Condroitina , Nanotubos de Carbono , Glicosaminoglicanos , Ácido Hialurônico , Simulação de Dinâmica Molecular , Nanotubos de Carbono/química , Monossacarídeos , Ácidos CarboxílicosRESUMO
Salmon nasal cartilage proteoglycan (PG) was orally administered to mice. The PG digest was recovered from the small intestine, and its sugar chain size and unsaturated disaccharide content were examined. The elution position of the PG digest following Sepharose CL-4B chromatography was consistent with that of actinase-digested PG prior to administration. The PG digest was incubated with chondroitinase ABC, which resulted in the elution pattern of the unsaturated disaccharides being identical to that of the degraded product of actinase-digested PG. The core protein of PG was digested in the mouse small intestine, but chondroitin sulfate, which is the sugar chain of PG, was not degraded at all. Then, the effects of chondroitin 4- and 6-sulfates on human colon cancer cells were examined. These chondroitin sulfates were found to suppress the expression of interleukin-6 induced by TNF-α. Overall, the chondroitin sulfate chain may act on the intestinal epithelium and suppress inflammation of the intestinal tract.
Assuntos
Sulfatos de Condroitina , Fator de Necrose Tumoral alfa , Camundongos , Humanos , Animais , Sulfatos de Condroitina/metabolismo , Interleucina-6 , Proteoglicanas/metabolismo , Condroitina , Dissacarídeos , Proteoglicanas de Sulfatos de Condroitina/metabolismoRESUMO
AIMS: Though glucosamine and chondroitin have become common practices for treating knee osteoarthritis, the clinical value of these two drugs in combination are still questionable. To evaluate the efficacy and safety of the combination of glucosamine (GS) and chondroitin (CS) in knee osteoarthritis (KOA) treatment. METHODS: We searched electronic databases, including PubMed, Embase, Web of Science, SCOPUS, The Cochrane Central Register of Controlled Trials (CENTRAL), OVID, Chinese Clinical Trial Registry (ChiCTR), CBM, CNKI, WanFang and VIP from their inception to August 20, 2020, for literature concerning the combination of glucosamine and chondroitin in knee osteoarthritis treatment. The Cochrane Collaboration's tool for assessing risk of bias and Jadad scale were used to evaluate the risk of bias and quality of literature. The meta-analysis was performed using Review Manager 5.3 software. RESULTS: Eight randomized controlled trials (RCTs) were included, including 7 studies in English and 1 study in Chinese. While the number of included papers was quite limited, the number of participants was decent, and quality appraisal result is acceptable. The total number of patients was 3793, with 1067 patients receiving a combination of glucosamine and chondroitin and 2726 patients receiving other treatments. The meta-analysis results revealed the following: (1) Regarding the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, compared with the placebo group, the combination group showed a statistically significant advantage [MD = - 12.04 (- 22.33 ~ - 1.75); P = 0.02], while the other groups showed no significance. (2) Regarding the VAS score, none of the comparisons showed significance. (3) In the secondary outcomes, except the comparison of JSN between the combination and placebo groups (MD = - 0.09 (- 0.18 ~ - 0.00); P = 0.04) and the comparison of the WOMAC stiffness score between the combination and CS groups [MD = - 4.70 (- 8.57 ~ - 0.83); P = 0.02], none of the comparisons showed a significant difference. (4)Safety analysis results show that none of the comparisons have significant differences. CONCLUSION: Our study confirmed that the combination of glucosamine and chondroitin is effective and superior to other treatments in knee osteoarthritis to a certain extent. It is worthwhile to popularize and apply the combination in KOA treatment considering the point of effect, tolerability and economic costs. Additionally, regarding the limited number of studies and uneven trial quality, more high-quality trials are required to investigate the accurate clinical advantages of the combination. PROSPERO REGISTRATION ID: CRD42020202093.
Assuntos
Condroitina , Osteoartrite do Joelho , Humanos , Condroitina/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Glucosamina/uso terapêutico , Resultado do TratamentoRESUMO
Tecnologia: Combinação de glicosamina e condroitina. Indicação: Tratamento de osteoartrite em adultos. Pergunta: O tratamento com a combinação de glicosamina e condroitina é mais eficaz e seguro que os demais tratamentos para osteoartrite disponíveis no SUS? Métodos: Uma revisão rápida de evidências, uma revisão de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2. Resultados: Foi selecionada uma revisão sistemática, que atendiam aos critérios de inclusão. Conclusão: A combinação de glicosamina com condroitina, comparados ao placebo, mostrou ser mais eficaz para tratamento da dor e função e alcançou o segundo lugar nas alternativas terapêuticas para tratamento da dor e função
Technology: Combination of glucosamine and chondroitin. Indication: Treatment of osteoarthritis in adults. Question: Is the treatment with the combination of glucosamine and chondroitin more effective and safer than the other treatments for osteoarthritis available in the Brazilian Public Health System? Methods: A rapid review of evidence, a overview of systematic reviews, with bibliographic search done in PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed using AMSTAR-2. Results: A systematic review was selected, which met the inclusion criteria. Conclusion: The combination of glucosamine and chondroitin, compared to placebo, proved to be more effective for the treatment of pain and function and reached second place in therapeutic alternatives for the treatment of pain and function
Assuntos
Humanos , Masculino , Feminino , Osteoartrite/tratamento farmacológico , Condroitina/uso terapêutico , Glucosamina/uso terapêutico , Eficácia , Combinação de Medicamentos , Pesquisa Comparativa da Efetividade , Revisão SistemáticaRESUMO
With osteoarthritis being the most common degenerative disease in pet animals, a very broad panel of natural health products is available on the market for its management. The aim of this systematic review and meta-analysis, registered on PROSPERO (CRD42021279368), was to test for the evidence of clinical analgesia efficacy of fortified foods and nutraceuticals administered in dogs and cats affected by osteoarthritis. In four electronic bibliographic databases, 1578 publications were retrieved plus 20 additional publications from internal sources. Fifty-seven articles were included, comprising 72 trials divided into nine different categories of natural health compound. The efficacy assessment, associated to the level of quality of each trial, presented an evident clinical analgesic efficacy for omega-3-enriched diets, omega-3 supplements and cannabidiol (to a lesser degree). Our analyses showed a weak efficacy of collagen and a very marked non-effect of chondroitin-glucosamine nutraceuticals, which leads us to recommend that the latter products should no longer be recommended for pain management in canine and feline osteoarthritis.
Assuntos
Produtos Biológicos , Canabidiol , Doenças do Gato , Doenças do Cão , Osteoartrite , Animais , Produtos Biológicos/uso terapêutico , Canabidiol/uso terapêutico , Gatos , Condroitina/uso terapêutico , Colágeno/uso terapêutico , Suplementos Nutricionais , Doenças do Cão/tratamento farmacológico , Cães , Glucosamina/uso terapêutico , Osteoartrite/tratamento farmacológico , Osteoartrite/veterináriaRESUMO
Some bacteria produce non-sulfated chondroitin (CH). Accurate, rapid, and high throughput methods to quantify CH in fermented cultures helps to improve microbial breeding and fermentation conditions efficiently. In this study, highly sensitive methods to quantify bacterial CH were developed based on ELISA techniques. An assay using an anti-K4 antiserum successfully determined the concentration of fructosylated CH in the range from 9 to 800 ng/mL. The method also enabled the determination of CH concentration exceeding 9 µg/mL. To improve the assay sensitivity for CH, hyaluronan (HA) binding protein (HABP) was applied instead of a capture antibody. HABP was bound to CH, but not to chemically desulfated chondroitin sulfate or fructosylated CH. The quantification limit of CH was 18 µg/mL in the HA assay using HABP. Replacing the HA-coated microplate with a CH-coated microplate increased the sensitivity >1000 times (assay range = 14 to 1000 ng/mL). Pretreatment with hyaluronidase enabled us to accurately quantify CH in samples mixed with HA.