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Objective:To investigate the application of endothelial glycocalyx degradation products in assessing the severity of pulmonary edema in patients with acute respiratory distress syndrome (ARDS).Methods:A prospective study was conducted to select patients diagnosed with ARDS at Wuxi People's Hospital from July 1, 2018 to December 31, 2019. The extravascular lung water index (EVLWI) was recorded within 2 h after admission by continuous cardiac output with pulse indicator. The indexes of glycocalyx degradation products syndecan-1 (SDC-1), heparan sulfate (HS), hyaluronic acid (HA) and the concentrations of inflammatory factors [blood tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-10] were measured by enzyme-linked immunosorbent assay. Pearson correlation method was adopted to analyze the correlation of glycocalyx degradation products with EVLWI and inflammatory factors in ARDS patients. The patients were divided into the mild pulmonary edema group and severe pulmonary edema group according to EVLWI at the cut-off value of 10 mL/kg, and the differences of glycocalyx degradation products and inflammatory factors between the two groups were compared. Receiver operating characteristic (ROC) curve of the subjects were plotted to analyze the value of glycocalyx degradation products in determining the severity of pulmonary edema.Results:A total of 85 ARDS patients were enrolled. Pearson correlation analysis showed that SDC-1, HS, and HA were all positively correlated with IL-6, TNF-α, EVLWI (all P<0.05), but did not correlate with IL-10 (all P>0.05). Comparison of indicators between the mild pulmonary edema group (39 cases) and the severe pulmonary edema group (46 cases) showed that: IL-6[(33.63±3.43) ng/L vs. (39.99±4.64) ng/L], TNF-α[(43.38±6.05) ng/L vs. (50.79±7.35) ng/L], SDC-1[(494.13±47.23) ng/L vs. (563.50±56.36) ng/L], HS[(114.02±18.39) ng/mL vs. (138.93±17.02) ng/mL], and HA[(441.44±62.52) ng/mL vs. (546.23±85.24) ng/mL] were statistically different between the two groups(all P<0.05). Whereas, IL-10 [(24.37±10.11) ng/L vs. (28.75±11.98) ng/L] was not statistically different between the two groups ( P>0.05). ROC curve analysis showed that the combined prediction of SDC-1, HA and HS indicators was superior to the single indicator. The area under the ROC curve combining the three indicators was 0.928 (95% CI: 0.872-1.000), with a sensitivity and specificity of 87.5% and 86.7%, respectively. Conclusions:There is a positive correlation between glycocalyx degradation products SDC-1, HS, HA and EVLWI in ARDS patients. The application of these three glycocalyx degradation products can be used as a reliable indicators for judging the severity of pulmonary edema in ARDS patients.
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The heparin polysaccharide nanoparticles block the interaction between heparan sulfate/S protein and inhibit the infection of both wild-type SARS-CoV-2 pseudovirus and the mutated strains through pulmonary delivery.Image 1.
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RESUMEN Objetivo: Analizar la asociación entre el polimorfismo rs2291166 del gen TJP1 con los niveles de glucosaminoglucanos (GAGS) excretados en orina como marcador de las primeras etapas de la nefropatía. Material y métodos: Se analizaron 600 muestras de orina de sujetos recién diagnosticados con diabetes tipo 2, de las cuales se incluyeron 203. La detección de GAGS en orina directa se realizó mediante prueba de turbidez de albúmina ácida y precipitación con cetilpiridinio (CPC). Resultados: El 26,64% de los pacientes diabéticos se encuentran en estadios tempranos de nefropatía, lo que corresponde a pacientes con prueba GAG positiva, siendo los que tienen mayor excreción de GAGS, heterocigotos para el polimorfismo. Conclusión:Sugerimos que el polimorfismo de TJP1 rs2291166 influye en la mucopolisacariduria en pacientes diabéticos tipo 2 de la población mexicana; que podría usarse como un marcador genético/ bioquímico válido para las primeras etapas de la nefropatía diabética.
ABSTRACT Objective: To analyze the association between the polymorphism rs2291166 of TJP1 gene, with the urine-excreted levels of GAGS as a marker of early stages of nephropathy. Methods: A 600 urine samples from newly diagnosed subjects with type 2 diabetes were analyzed, of which 203 were included. The GAGS detection in direct urine (corresponding to the first urine of the morning), was performed by albumin turbidity test and precipitation with cetylpyridinium (CPC). Results: The present study shows that 26.64% of diabetic patients are in early stages of nephropathy, corresponding to patients with a positive GAG test, being those with the highest GAGS excretion, heterozygous for the polymorphism. Conclusion: We suggest that the TJP1 polymorphism rs2291166 influences mucopolysacchariduria in type 2 diabetic patients of the Mexican population, which could be used as a valid genetic/biochemical marker for the early stages of diabetic nephropathy.
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Abstract Sanfilippo B is a lysosomal disorder characterized by the pathological accumulation of heparan sulfate. It is caused by mutations in the NAGLU gene that codes for the alpha-N-acetylglucosaminidase enzyme. The objective of this study was to determine the reference values and frequency of Sanfilippo B in Colombia through an enzyme analysis of leukocytes extracts. We aim to inform the community and the health system so that they can work in a preventive way, providing an early diagnosis of patients and thus providing an appropriate management of the symptoms. We carried out an endpoint assay that indirectly quantifies NAGLU activity through the cleavage of 4-methylumbelliferone from the 4-methylumbelliferyl-2-acetamido-2-deoxy-α-D-glucopyranoside substrate. The activity of 463 healthy volunteers (Range: 0.6 - 4 nmol/mg/h, Median: 1.69 +/- 0.73) as well as 462 patients referred for clinical suspicion, was calculated. From the last group, 7 cases turned out to be positive (Range: 0 - 0.24 nmol/mg/h, Median: 0.13 +/- 0.09). The cut-off point according to ROC analysis between affected patients and controls was 0.42 nmol/mg/h. To our knowledge, this study is the first in Colombia where an estimated frequency of Sanfilippo type B is calculated by providing enzyme activity ranges and a cut-off point.
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BACKGROUND Trypanosoma cruzi, the etiologic agent of Chagas disease, is capable of triggering different signaling pathways that modulate its internalisation in mammalian cells. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase protein, has been demonstrated as a mechanism of T. cruzi invasion in cardiomyocytes. Since the involved cell surface receptors are not yet known, we evaluated whether heparan sulfate proteoglycans (HSPG), a molecule involved in T. cruzi recognition and in the regulation of multiple signaling pathways, are able to trigger the FAK signaling pathway during T. cruzi invasion. METHODS To investigate the role of HSPG in the regulation of the FAK signaling pathway during trypomastigote entry, we performed heparan sulfate (HS) depletion from the cardiomyocyte surface by treatment with heparinase I or p-nitrophenyl-β-D-xylopyranoside (p-n-xyloside), which abolishes glycosaminoglycan (GAG) attachment to the proteoglycan core protein. Wild-type (CHO-k1) and GAG-deficient Chinese hamster ovary cells (CHO-745) were also used as an approach to evaluate the participation of the HSPG-FAK signaling pathway. FAK activation (FAK Tyr397) and spatial distribution were analysed by immunoblotting and indirect immunofluorescence, respectively. FINDINGS HS depletion from the cardiomyocyte surface inhibited FAK activation by T. cruzi. Cardiomyocyte treatment with heparinase I or p-n-xyloside resulted in 34% and 28% FAK phosphorylation level decreases, respectively. The experiments with the CHO cells corroborated the role of HSPG as a FAK activation mediator. T. cruzi infection did not stimulate FAK phosphorylation in CHO-745 cells, leading to a 36% reduction in parasite invasion. FAK inhibition due to the PF573228 treatment also impaired T. cruzi entry in CHO-k1 cells. MAIN CONCLUSION Jointly, our data demonstrate that HSPG is a key molecule in the FAK signaling pathway activation, regulating T. cruzi entry.
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Abstract Sanfilippo syndrome or mucopolysaccharidosis III (MPS III), includes a group of four autosomal recessive lysosomal storage disorders caused by deficient activity of enzymes involved in the catabolism of heparan sulfate. The four types of MPS III are recognized in accordance with the deficient enzyme, resulting in the accumulation of heparan sulfate with particularly deleterious effects in the central nervous system. The incidence of MPS III remains to be established in Latin American countries. We describe the journey of a patient with MPS IIIB whom, even in the presence of speech delay and deterioration, behavioral problems and motor incoordination, showed unaltered urinary glycosaminoglycans (GAGs) levels. An investigation for MPS was undertaken and enzyme analysis indicated a deficiency of alpha-N-acetylglucosaminidase, leading to the diagnosis of MPS IIIB. With the correct diagnosis, the patient's symptoms could be properly managed, and the parents received appropriate genetic counseling. The present case report reinforces the need of investigating MPS III in patients with language delay and/or regression, neurological impairment and behavioral alterations, even when urinary GAGs are within normal range. A definitive diagnosis ends the diagnostic journey and enables the medical team and family to provide a better care for the child.
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Objective To determine the effect of microRNA-146a (miR-146a) on the life cycle of hepatitis B virus (HBV) and investigate the underlying mechanisms.Methods The miRNA expression profiles were compared by miRNA array between HepG2 and HepG2.2.15 cells.Then miR-146a was chosen as objective,and its expression level was further confirmed by RT-PCR.After miR-146a mimic and inhibitor were transfected into HepG2.2.15 cells respectively,the quantification of HBV replication was determined by RT-PCR,and the levels of HBsAg and HBeAg in the supernatant were measured by ELISA,and the expression of HS3ST3B1 at mRNA and protein levels were tested by RT-PCR and Western blotting.Dualluciferase reporter assay was used to detect the interaction between miR-146a and potential target HS3ST3B1.Results The expression levels of totally 72 miRNAs were changed in HepG2.2.15 cells,with 27 upregulated and 45 down-regulated.RT-PCR showed the expression level of miR-146a was significantly higher in HepG2.2.15 cells than HepG2 cells (1.55-± 0.13 vs 1.00 ± 0.01,P ＜ 0.05).Transfection of miR-146a mimic into HepG2.2.15 cells resulted in significantly increased HBV replication and levels of HBsAg and HBeAg (P ＜ 0.05),while the transfection of its inhibited caused opposite results (P ＜ 0.05).Bioinformatic analysis showed that HS3ST3B1 was a potential target of miR-146a.The reporter luciferase reporter system indicated that the reported fluorescence intensity of HS3ST3B1 wild type vector was significantly lower than that of the control group (P ＜ 0.05),but showed no significant difference between HS3ST3B1 mutant vector and control group (P ＞0.05).The mRNA level of HS3ST3B1 was not significantly changed in HepG2.2.15 cells transfected with miR-146a mimic (P ＞ 0.05),but its protein level was significantly decreased (P ＜ 0.05).Conclusions miR-146a affects the life cycle of HBV,which may be through suppressing the translation of HBV inhibitory factor HS3ST3B1 3'UTR.
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Objective: To discuss the role of heparan sulfate (HS) in bone formation and bone remodeling and summarize the research progress in the osteogenic mechanism of HS.
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OBJECTIVE: To prepare heparan sulfate-vitamin E succinate (HDV) amphipathic copolymers and explore the pharmaceutical properties of doxorubicin (DOX)-loaded HDV copolymer micelles (DOX/HDV). METHODS: HDV copolymers were prepared by amide reaction and its structure was confirmed by H-NMR. DOX/HDV micelles were prepared by ultrasonic method. The particle size, morphology, Zeta potential, drug loading, entrapment efficiency, and in vitro drug release and cytotoxicity were evaluated. RESULTS: HDV amphipathic copolymers were synthesized successfully. The particle size, PDI value and Zeta potential of drug-loaded micelles were (105.0±7.3) nm, (0.239±0.484) and (-21.4±2.6) mV, respectively. The encapsulation and drug loading rate were (76.22±0.76)% and (9.53±0.58)%, respectively. The results of drug release test in vitro showed that DOX was released slowly from the micelles. Cytotoxicity experiments indicated that blank micelles had no apparent toxicity against both tumor cells and normal cells. However, DOX/HDV micelles could inhibit the tumor cells growth obviously. CONCLUSION: HDV copolymers can effectively load DOX with properties of drug sustained release and enhanced cytotoxicity against tumor cells in vitro, which indicates that HDV may be a potential candidate for cancer therapy.
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Luminal surface of vascular endothelium is decorated with a variety of polysaccharide-protein complexes,which constitute the glycocalyx.It has been demonstrated that vascular endothelial glycocalyx plays an important role in modulation of selective permeability of vessels,mediation of the blood cell-endothelial cell interactions and the release of nitric oxide induced by fluid shear stress under physiological condition.In inflammation condition,sheding of glycocalyx due to inflammation mediator leads to its functional weakening in vessel protection.At the same time,heparan sulfate as a major constituent of vascular endothelial glycocalyx could be involved in regulating the evolution of inflammation.Heparan sulfate interacts with L-selectin to mediating leukocyte rolling,presents chemokines on luminal surfaces of endothelial cells to mediate leukocyte crawling and firm adhesion,participates in transcytosis of chemokines from tissue to luminal side of endothelial cells during inflammation.Various risk factors of atherosclerosis,as an inflammatory disease,are closely associated with vascular endothelial glycocalyx.This paper is aimed to review the role of vascular endothelial glycocalyx in inflammation and atherosclerosis.
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Hepatitis B virus (HBV) is the prototype of hepatotropic DNA viruses (hepadnaviruses) infecting a wide range of human and non-human hosts. Previous studies with duck hepatitis B virus (DHBV) identified duck carboxypeptidase D (dCPD) as a host specific binding partner for full-length large envelope protein, and p120 as a binding partner for several truncated versions of the large envelope protein. p120 is the P protein of duck glycine decarboxylase (dGLDC) with restricted expression in DHBV infectible tissues. Several lines of evidence suggest the importance of dCPD, and especially p120, in productive DHBV infection, although neither dCPD nor p120 cDNA could confer susceptibility to DHBV infection in any cell line. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a binding partner for the N-terminus of HBV large envelope protein. Importantly, knock down and reconstitution experiments unequivocally demonstrated that NTCP is both necessary and sufficient for in vitro infection by HBV and hepatitis delta virus (HDV), an RNA virus using HBV envelope proteins for its transmission. What remains unclear is whether NTCP is the major HBV receptor in vivo. The fact that some HBV patients are homozygous with an NTCP mutation known to abolish its receptor function suggests the existence of NTCP-independent pathways of HBV entry. Also, NTCP very likely mediates just one step of the HBV entry process, with additional co-factors for productive HBV infection still to be discovered. NTCP offers a novel therapeutic target for the control of chronic HBV infection.
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Animals , Carboxypeptidases/genetics , Gene Products, pol/genetics , Heparan Sulfate Proteoglycans/metabolism , Hepatitis B virus/physiology , Hepatocytes/metabolism , Organic Anion Transporters, Sodium-Dependent/antagonists & inhibitors , RNA Interference , Symporters/antagonists & inhibitors , Viral Envelope Proteins/metabolism , Virus InternalizationABSTRACT
OBJECITVE: To prepare a heparan sulfate dodecasaccharide and analyze its structural sequence. METHODS: HS-derived oligosaccharide was prepared by heparinase II depolymerization. Size-uniform dodecasaccharide mixture was acquired by low pressure gel permeation chromatography on Bio-Gel P-10 column. The dodecasaccharides were further separated by strong anion-ex-change high-performance liquid chromatography (SAX-HPLC) to get a charge-uniform dodecasaccharide. The dodecasaccharide was completely hydrolyzed by heparinases I, II, and III, its disaccharides composition was analyzed by HPLC, and its structural sequence was confirmed by electrospray collision-induced dissociation mass spectrometry (ES-CID-MSn). RESULTS: One size- and charge-uniform pure dodecasaccharide was separated from HS enzymatic hydrolyzed mixture, and it was composed by δUA-GlcNAc (IV-A) and AUA-GlcNS (IV-S) with the relative ratio of 5-1. Based on the ES-CID-MSn analysis, its structural sequence was δUA-GlcNAc-GlcA-GlcNS-GlcA-GlcNAc-GlcA-GlcNAc- GlcA-GlcNAc-GlcA-GlcNAc. CONCLUSION: The dodecasaccharide was prepared from HS, its detailed structure is analyzed, and it will offer a basis for the structure-activity relationship study of HS oligosaccharide.
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Heparan sulfate (HS) and heparin (HP) are highly sulfated and heterogeneous polysaccharides composed of repeating disaccharide units. HS takes part in regulation of many related biological functions through its interaction with proteins and plays an important role in them. HS is also shown to have promising perspectives as a potential antivirus agent. As a special structure type of HS,HP is also widely used as the clinical anticoagulant drug and demonstrated to be a promising candidate for anticancer and anti-inflammatory drugs. Progress of the research in the areas of anticoagulant， anticancer， anti-inflammatory and antivirus activity of HS/HP and their chemoenzymatic synthesis is summarized in this review.
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Heparan sulfate (HS) takes part in regulation of many related animal biological functions by its interaction with proteins and plays an important role. As a special structure type of HS, heparin (HP) is also widely used as clinical anticoagulant drug and demonstrated to be a promising candidate for anticancer and anti-inflammatory drugs. Natural HS and HP are highly heterogeneous mixtures differing in their polysaccharide chain lengths, sulfation patterns and so on, which restricts elucidation of the relationship between their structures and functions and further application of their drug potential. There has recently been a breakthrough in chemoenzymatic method developed for an alternative approach different from chemical synthesis, which shortens the synthesis and improves the product yields significantly. Application of chemoenzymatic synthesis accelerates elucidation of structure-function relationships in HS/HP and low-molecular-weight heparins (LMWH) with reversible anticoagulative activity have been obtained. Along with improvement and optimization of chemoenzymatic method and further understanding of structure-function relationship, it will gradually become possible to synthesize structure-specific HS/HP drugs with better and more stable effects and less adverse effects in the future. Recent progress of HS/HP chemoenzymatic synthesis is summarized in this review.
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Heparan sulfate (HS)takes part in regulation of many related animal biological functions by its interaction with proteins and plays an important role. As a special structure type of HS,heparin (HP)is also widely used as clinical anticoagulant drug and demonstrated to be a promising candidate for anticancer and anti-inflammatory drugs. Natural HS and HP are highly heterogeneous mixtures differing in their polysaccharide chain lengths,sulfation patterns and so on,which restricts elucidation of the relationship between their structures and functions and further application of their drug potential. There has recently been a breakthrough in chemoenzymatic method developed for an alternative approach different from chemical synthesis,which shortens the synthesis and improves the product yields significantly. Application of chemoenzymatic synthesis accelerates elucidation of structure-function relationships in HS/HP and low-molecular-weight heparins (LMWH) with reversible anticoagulative activity have been obtained. Along with improvement and optimization of chemoenzymatic method and further understanding of structure-function relationship,it will gradually become possible to synthesize structure-specific HS/HP drugs with better and more stable effects and less adverse effects in the future. Recent progress of HS/HP chemoenzymatic synthesis is summarized in this review.
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Heparan sulfate (HS) and heparin (HP) are highly sulfated and heterogeneous polysaccharides composed of repeating disaccharide units. HS takes part in regulation of many related biological functions through its interaction with proteins and plays an important role in them. HS is also shown to have promising perspectives as a potential antivirus agent. As a special structure type of HS, HP is also widely used as the clinical anticoagulant drug and demonstrated to be a promising candidate for anticancer and anti-inflammatory drugs. Progress of the research in the areas of anticoagulant, anticancer, anti-inflammatory and antivirus activity of HS/HP and their chemoenzymatic synthesis is summarized in this review.
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For decades, various systemic therapies have been explored for the treatment of advanced hepatocellular carcinoma (HCC), the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Nevertheless, no satisfactory results have been obtained so far. Glypican-3 (GPC-3) is a cell-surface heparan sulfate proteoglycans (HSPGs) that emerged as a promising diagnostic marker as well as target for therapy. Therefore; we investigated antitumor activity of antiglypican-3 (antiGPC3), a specific antibody aginst GPC-3, against HepG2, human HCC, cell line. HepG2 cells were treated with AntiGPC3 at (5, 10 and 20 μg/ml). HepG2 cell proliferation was measured by MTT and lactate dehydrogenase (LDH) assays. GPC-3, HSPG and sulfatase-2 (SULF2) levels were measured by ELISA. Moreover, apoptosis was assessed by measuring Caspase-3 activity. We found that, antiGPC3 reduced HepG2 cells survival and showed cell cytotoxicity in a dose-dependent manner. In addition, antiGPC3 was able to increase the apoptosis measured by capase-3 activity in hepG2 cells. Finally, antiGPC3 restored HSPG level without affecting SULF2 in HepG2 cells. We can conclude that, antiGPC3 possesses cytotoxic effects, which can be partially explained by restoration of HSPGs and increase of caspase-3 apoptotic pathway. GPC-3 represents a promising target of HCC therapy.
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Heparan sulphate (HS) and the related polysaccharide, heparin, exhibit conformational and charge arrangement properties, which provide a degree of redundancy allowing several seemingly distinct sequences to exhibit the same activity. This can also be mimicked by other sulphated polysaccharides, both in overall effect and in the details of interactions and structural consequences of interactions with proteins. Together, these provide a source of active compounds suitable for further development as potential drugs. These polysaccharides also possess considerable size, which bestows upon them an additional useful property: the capability of disrupting processes comprising many individual interactions, such as those characterising the attachment of microbial pathogens to host cells. The range of involvement of HS in microbial attachment is reviewed and examples, which include viral, bacterial and parasitic infections and which, in many cases, are now being investigated as potential targets for intervention, are identified.
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Humans , Bacteria/drug effects , Bacterial Adhesion/drug effects , Heparitin Sulfate/chemistry , Heparitin Sulfate/pharmacology , Polysaccharides/chemistry , Heparin/chemistry , Heparin/pharmacology , Surface PropertiesABSTRACT
Glycosaminoglycans are important structural components in the skin and exist as various proteoglycan forms, except hyaluronic acid. Heparan sulfate (HS), one of the glycosaminoglycans, is composed of repeated disaccharide units, which are glucuronic acids linked to an N-acetyl-glucosamine or its sulfated forms. To investigate acute ultraviolet (UV)-induced changes of HS and HS proteoglycans (HSPGs), changes in levels of HS and several HSPGs in male human buttock skin were examined by immunohistochemistry and real-time quantitative polymerase chain reaction (qPCR) after 2 minimal erythema doses (MED) of UV irradiation (each n = 4-7). HS staining revealed that 2 MED of UV irradiation increased its expression, and staining for perlecan, syndecan-1, syndecan-4, CD44v3, and CD44 showed that UV irradiation increased their protein levels. However, analysis by real-time qPCR showed that UV irradiation did not change mRNA levels of CD44 and agrin, and decreased perlecan and syndecan-4 mRNA levels, while increased syndecan-1 mRNA level. As HS-synthesizing or -degrading enzymes, exostosin-1 and heparanase mRNA levels were increased, but exostosin-2 was decreased by UV irradiation. UV-induced matrix metalloproteinase-1 expression was confirmed for proper experimental conditions. Acute UV irradiation increases HS and HSPG levels in human skin, but their increase may not be mediated through their transcriptional regulation.
Subject(s)
Adult , Humans , Male , Young Adult , Agrin/genetics , Hyaluronan Receptors/genetics , Base Sequence , DNA Primers/genetics , Gene Expression/radiation effects , Glucuronidase/genetics , Heparan Sulfate Proteoglycans/genetics , Heparitin Sulfate/metabolism , Matrix Metalloproteinase 1/genetics , N-Acetylglucosaminyltransferases/genetics , RNA, Messenger/genetics , Skin/metabolism , Skin Aging/genetics , Syndecan-1/genetics , Syndecan-4/genetics , Ultraviolet Rays/adverse effectsABSTRACT
OBJECTIVE: To analyze the amount of glycosaminoglycans in the uterine cervix during each phase of the rat estrous cycle. DESIGN: Based on vaginal smears, forty female, regularly cycling rats were divided into four groups (n = 10 for each group): GI - proestrous, GII - estrous, GIII - metaestrous and GIV - diestrous. Animals were sacrificed at each phase of the cycle, and the cervix was immediately removed and submitted to biochemical extraction and determination of sulfated glycosaminoglycans and hyaluronic acid. The results were analyzed by ANOVA followed by the Bonferroni post-hoc test. RESULTS: The uterine cervix had the highest amount of total sulfated glycosaminoglycans and dermatan sulfate during the estrous phase (8.90 ± 0.55 mg/g of cetonic extract, p<0.001; and 8.86 ± 0.57 mg/g of cetonic extract, p<0.001). In addition, there was more heparan sulfate at the cervix during the proestrous phase (0.185 ± 0.03 mg/g of cetonic extract) than during any other phase (p<0.001). There were no significant changes in the concentration of hyaluronic acid in the uterine cervix during the estrous cycle. CONCLUSION: Our data suggest that the amount of total sulfated glycosaminoglycans may be influenced by hormonal fluctuations related to the estrous cycle, with dermatan sulfate and heparan sulfate being the glycosaminoglycans most sensitive to hormonal change.