Objectives: This study aimed to evaluate the prolonged therapeutic effects of a 35 kDa molecular weight hyaluronan fragment (HA35) in alleviating pain associated with myofascial pain syndrome (MPS). Hyaluronan interac...Objectives: This study aimed to evaluate the prolonged therapeutic effects of a 35 kDa molecular weight hyaluronan fragment (HA35) in alleviating pain associated with myofascial pain syndrome (MPS). Hyaluronan interacts with various receptors in the human body, including CD44, LYVE-1, RHAMM, and TLR2, and is well-known for its analgesic effects when used in intra-articular or ultrasound-guided nerve trunk injections. Studies have shown that hyaluronidase cleaves high molecular weight HA to generate HA35, a low molecular weight fragment with enhanced tissue permeability, capable of binding to HA receptors on cell surfaces to produce broad-spectrum analgesic effects. Methods: Ten patients diagnosed with MPS were treated and assessed in this study. HA35 was administered through injection at a dosage of 100 mg daily for 15 days. Patients evaluated their MPS, overall pain levels, and treatment satisfaction using the Numerical Pain Rating Scale (NPRS), the Global Pain Scale (GPS), and the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4). Follow-up evaluations were performed three months post-treatment to assess the duration of therapeutic effects. Results: Significant improvements were observed in NPRS, GPS, and TSQM scores both during and after the treatment period (P Conclusions: HA35 provides effective and sustained relief from pain associated with MPS, demonstrating a prolonged therapeutic benefit.展开更多
The prebiotic effects of hyaluronan(HA)are widely recognized,contributing to improved gut health and immune modulation.Despite its extensive use as dietary supplement,the specific interactions between HA oligosacchari...The prebiotic effects of hyaluronan(HA)are widely recognized,contributing to improved gut health and immune modulation.Despite its extensive use as dietary supplement,the specific interactions between HA oligosaccharides(o-HAs)and the gut microbiome remain largely unexplored.To investigate its role and metabolic fate in gut homeostasis,200 mg/day of o-HAs(average molecule weight 1 kDa)were added to an automated computer-controlled SIMulator of the Gastrointestinal tract(SIMGI).The results revealed a significant reshaping of the intestinal flora composition by o-HAs,notably reducing the Firmicutes/Bacteroides ratio.Fermentation of o-HAs by gut microbiota significantly increased the abundance of Bifidobacterium,Prevotellaceae_Prevotella,Dialister,Eubacterium,and Sutterella,but decreased that of Catenibacterium,Oscillospira,Klebsiella,and Citrobacter(P<0.05).This corresponded with significant enhancements in the content of short-chain fatty acids(SCFAs)such as acetic acid,propionic acid and n-butyric acid,highlighting the significant impact of o-HAs at the genus level.Furthermore,analysis of microbial function predicted the downregulation of pathological events in nine human diseases,particularly infectious ones(parasitic and bacterial).Potential inhibitions were observed in metabolic pathways associated with pentose and glucuronate interconversions as well as cationic antimicrobial peptide resistance.These findings underscore the in vitro prebiotic effects of o-HAs and their potential relevance in managing diverticular diseases or preventing metabolic disorders through the regulation of gut microbiota.展开更多
Hyaluronan(HA),a natural high molecular weight polysaccharide,has extensive applications in cosmetology and medical treatment.Hyaluronan-degrading enzymes(Hyals)act as molecular scissors that cleave HA by breaking the...Hyaluronan(HA),a natural high molecular weight polysaccharide,has extensive applications in cosmetology and medical treatment.Hyaluronan-degrading enzymes(Hyals)act as molecular scissors that cleave HA by breaking the glucosidic linkage.Hyals are present in diverse organisms,including vertebrates,invertebrates and microorganisms,and play momentous roles in biological processes.In recent years,microbial Hyals(mHyals)have gained considerable attention for their exceptional performance in the production and processing of HA.Moreover,the applications of mHyals have been greatly extended to various biomedical fields.To explore the potential applications of mHyals,a thorough comprehension is imperative.In this context,this review systematically summarizes the sources,structures,mechanisms and enzymatic properties of mHyals and discusses their biological functions in host invasion,disease development,and regulation of intestinal flora.Furthermore,versatile applications inspired by their biological functions in medicine development,molecular biology,and industrial biotechnology are comprehensively reviewed.Finally,prospects are presented to emphasize the importance of exploration,expression and characterization of mHyals and the necessity of excavating their potential in biotechnological fields.展开更多
Hyaluronan binding protein 1 (HABP1) is a negatively charged multifunctional mammalian protein with a unique structural fold. Despite the fact that HABP1 possesses mitochondrial localization signal, it has also been l...Hyaluronan binding protein 1 (HABP1) is a negatively charged multifunctional mammalian protein with a unique structural fold. Despite the fact that HABP1 possesses mitochondrial localization signal, it has also been localized to other cellular compartments. Using indirect immunofluorescence, we examined the sub-cellular localization of HABP1 and its dynamics during mitosis. We wanted to determine whether it distributes in any distinctive manner after mitotic nuclear envelope disassembly or is dispersed randomly throughout the cell. Our results reveal the golgi localization of HABP1 and demonstrate its complete dispersion throughout the cell during mitosis. This distinctive distribution pattern of HABP1 during mitosis resembles its ligand hyaluronan, suggesting that in concert with each other the two molecules play critical roles in this dynamic process.展开更多
Hyaluronan is a kind of polysaccharide with high molecule weight, hs structure is relatively complicated and tertiary structure exists among the HA molecules when reaching to o certain solution concentration . FT- IR ...Hyaluronan is a kind of polysaccharide with high molecule weight, hs structure is relatively complicated and tertiary structure exists among the HA molecules when reaching to o certain solution concentration . FT- IR spectrum has been acquired to shou the groups and their ascription in HA. The results of FT-IR spectrum in this essay accords well with that issued by ASTM. As to the newly appearing absorption peaks, sensible explanation has been given, In ADDITION , Ramon spectrum has been employed as a proof for the result of the FT-IR spectnun. Based on the preliminary acknowledge of the functional groups in HA, circular dichroism of the material has also been explored.展开更多
Hyaluronan(HA)is a naturally occurring polysaccharide in the organism.As one of the main components of the extracellular matrix,it plays an important role in regulating various cellular processes,including proliferati...Hyaluronan(HA)is a naturally occurring polysaccharide in the organism.As one of the main components of the extracellular matrix,it plays an important role in regulating various cellular processes,including proliferation,differentiation,inflammation,and immunity,through interaction with HA receptors.HA is widely found in the human body,particularly in the skin and joints,thus playing a crucial role in the functioning of these tissues.The aging of the skin and the occurrence of osteoarthritis are related to the loss of HA.Supplementing HA in the appropriate areas can delay or prevent these processes.Common methods of HA supplementation include topical application to the skin or injection into the joint cavities,both of which have shown efficacy in restoring HA levels and improving tissue function.In recent years,studies have shown that oral administration of HA can also have similar effects.Oral HA first passes through the gastrointestinal tract and then enters the liver with the blood circulation.Therefore,in addition to supplementing the HA content in the body,oral HA can also exert beneficial effects on the gastrointestinal tract and the liver,such as enhancing the barrier function of the gastrointestinal tract,regulating the intestinal flora,and reducing inflammation.Supplementation of HA has numerous benefits for the skin,orthopedic disorders,gastrointestinal tract and liver.Therefore,it is important to understand the mechanisms through which HA exerts these effects.This article describes the basic properties of HA and reviews its relationship with skin,orthopedic diseases,gastrointestinal tract and liver,as well as its applications in these areas.展开更多
Hyaluronan is a rapidly turned over component of the vertebrate extracellular matrix. Its levels are determined, in part, by the hyaluronan synthases, HAS1, HAS2, and HAS3, and three hyaluronidases, HYAL1, HYAL2 and H...Hyaluronan is a rapidly turned over component of the vertebrate extracellular matrix. Its levels are determined, in part, by the hyaluronan synthases, HAS1, HAS2, and HAS3, and three hyaluronidases, HYAL1, HYAL2 and HYAL3. Hyaluronan binding proteins also regulate hyaluronan levels although their involvement is less well understood. To date, two genetic disorders of hyaluronan metabolism have been reported in humans: HYAL1 deficiency(Mucopolysaccharidosis IX) in four individuals with joint pathology as the predominant phenotypic finding and HAS2 deficiency in a single person having cardiac pathology. However, inherited disorders and induced mutations affecting hyaluronan metabolism have been characterized in other species. Overproduction of hyaluronan by HAS2 results in skin folding and thickening in shar-pei dogs and the naked mole rat, whereas a complete deficiency of HAS2 causes embryonic lethality in mice due to cardiac defects. Deficiencies of murine HAS1 and HAS3 result in a predisposition to seizures. Like humans, mice with HYAL1 deficiency exhibit joint pathology. Mice lacking HYAL2 have variably penetrant developmental defects, including skeletal and cardiac anomalies. Thus, based on mutant animal models, a partial deficiency of HAS2 or HYAL2 might be compatible with survival in humans, while complete deficiencies of HAS1, HAS3, and HYAL3 may yet be recognized.展开更多
Pasteurella multocida hyaluronan synthase (PmHAS) is a bi-functional glycosyltransferase, containing a β1,3-glucuronyltransferase and β1,4-N-acetylglucosaminetransferase domain. PmHAS catalyzes the elongation of hya...Pasteurella multocida hyaluronan synthase (PmHAS) is a bi-functional glycosyltransferase, containing a β1,3-glucuronyltransferase and β1,4-N-acetylglucosaminetransferase domain. PmHAS catalyzes the elongation of hyaluronan (HA) through the sequential addition of single monosaccharides to the non-reducing end of the hyaluronan chain. Research is focused on the relation between the length of the HA oligosaccharide and the single-step elongation kinetics from HA4 up to HA9. It was found that the turnover number kcat increased with length to maximum values of 11 and 14 s-1 for NAc- and UA-transfer, respectively. Interestingly, the specificity constant kcat/KM increased with polymer length from HA5 to HA7 to a value of 44 mM-1s-1, indicating an oligosaccharide binding site with increasing specificity towards a heptasaccharide at the UA domain. The value of kcat/KM remained moderately constant around 8 mM-1s-1 for HA4, HA6, and HA8, indicating a binding site with significantly lower binding specificity at the NAc domain than at the UA domain. These findings are further corroborated by a structural homology model of PmHAS, revealing two distinct sites for binding of oligosaccharides of different sizes, one in each transferase domain. Structural alignment studies between PmHAS and glycosyltransferases of the GT-A fold showed significant similarity in the binding of the UDP-sugars and the orientation of the acceptor substrate. These similarities in substrate orientation in the active site and in essential amino acid residues involved in substrate binding were utilized to localize the two HA oligosaccharide binding sites.展开更多
In order to contribute to the development of minimally invasive surgery techniques for autologous chondrocyte implantation, a novel self-assembling biomaterial consisting of thermoresponsive poly(N-isopropylacrylamide...In order to contribute to the development of minimally invasive surgery techniques for autologous chondrocyte implantation, a novel self-assembling biomaterial consisting of thermoresponsive poly(N-isopropylacrylamide)-grafted hyaluronan (PNIPAAm-g-HA) has been synthesized as an injectable scaffold for cartilage tissue engineering. The aim of this study was to investigate the efficacy and cytocompatibility of PNIPAAm-g-HA to normal chondrocytes by using reverse transcription-polymerase chain reaction (RT-PCR) analysis and histochemical staining in preliminary in vitro and in vitro experiments. Hematoxylin and eosin staining showed homogeneous distribution of cells in the PNIPAAm-g-HA hydrogel in 3-dimensional in vitro cultivation. Alcian blue staining also indicated that abundant extracellular matrix formation, including acidic glycosaminoglycans, occurred in tissue-engineered cartilage over time in vitro. Cartilage-related gene expression patterns, which were tested in rabbit normal chondrocytes embedded in the hydrogel, were almost maintained for 4 weeks. Transforming growth factor-β1 (TGF-β1) stimulation enhanced the expression of SRY-related HMG box-containing gene 9 (Sox9) and type X collagen genes suggesting promotion of chondrogenic differentiation. Histochemical evaluation showed neocartilage formation following subcutaneous implantation of the chondrocyte-gel mixture in nude mice. Furthermore, TGF-β1 stimulation promoted production and maturation of the extracellular matrix of the in situ tissue engineered hyaline cartilage. These data suggested that PNIPAAm-g-HA could be a promising biomaterial, i.e., a self-assembling and injectable scaffold for cartilage tissue engineering.展开更多
A novel injectable hydrogel that was synthesized by in situ crosslinking of hyaluronan and polyvinyl phosphonic acid was proposed in this study. Fourier transform infrared spectrum (FT-IR) analysis, scanning electron ...A novel injectable hydrogel that was synthesized by in situ crosslinking of hyaluronan and polyvinyl phosphonic acid was proposed in this study. Fourier transform infrared spectrum (FT-IR) analysis, scanning electron microscope (SEM), pH measurement, and biodegradation test were used to confirm its characteristics. The results permitted to prove successful crosslinking, observe the inner morphology of hydrogel and pore sizes distribution, and determine the decomposition of hydrogel components during incubation time. Result of pH measurement showed that the pH scale of hydrogel decreased when volume of PVPA increased. As a consequence, it affected the cytotoxicity value, cell proliferation, and cell growth behaviors of each hydrogel. Optical microscope observation showed that chondroblasts cell proliferated well on HA-PVPA hydrogel. Therefore, these results suggest that the new injectable hydrogel is appropriate for bone/cartilage regeneration applications.展开更多
Purpose: The purpose of this study is to determine the presence of bacteriostatic effects of hyaluronan-based bioresorbable membrane (HA/CMC) on selected major bacterial strains in digestive organs. Methods: We firstl...Purpose: The purpose of this study is to determine the presence of bacteriostatic effects of hyaluronan-based bioresorbable membrane (HA/CMC) on selected major bacterial strains in digestive organs. Methods: We firstly evaluated the growth inhibition effect of HA/CMC for E. coli and S. aureus by determining the optical density (OD)650 in the incubation medium. At second, to determine the viable counts of bacteria, total adenosine triphosphate (ATP) were measured with five groups;several concentrations of HA/CMC and control. Results: OD curve gradually elevated and reached to plateau at 4 hours in E. coli. and 6 hours in S. aureus. After reaching plateau, the growth inhibition of both strains was statistically significantly correlated to the concentrations of HA/CMC. The ATP productions had statistically significant differences at 6 hours after incubation and inhibited in dose-dependence of a well-dissolved HA/CMC. Conclusion: HA/CMC may have dose-dependently bacteriostatic effects on S. aureus and E. coli.展开更多
Objective: Prepare cross-linked HA gels with higher mechanical stability, lower degradation velocity and desirable biocompatibility,so as to extend the usage of HA.Method:1.Test molecular weight of HA (Mr_ HA ) by vis...Objective: Prepare cross-linked HA gels with higher mechanical stability, lower degradation velocity and desirable biocompatibility,so as to extend the usage of HA.Method:1.Test molecular weight of HA (Mr_ HA ) by viscosimetry;2.prepare cross-linked HA gels by DVS, GTA, DEC;3.discuss the cross-linking and degradation procedure;4.evaluate the biocompatibility of the best HA gels. Results:The mechanical stability and durability to degradation of HA-DVS gels are superior to those of other gels, and when HA:DVS = 40:1(g/g), at 35℃ and in 0.2 M NaOH solution, the HA-DVS gel shows the best mechanical stability, and its cytotoxicity reaches class I, hemolysis ratio is lower than 5%. Conclusion:Our HA-DVS gel can be used to prepare biologic scaffolds.展开更多
Transvaginal oocyte retrieval (TVOR) is a common yet painful procedure in assisted reproductive technologies (ART) like in vitro fertilization (IVF). Effective pain management during and after TVOR is essential, parti...Transvaginal oocyte retrieval (TVOR) is a common yet painful procedure in assisted reproductive technologies (ART) like in vitro fertilization (IVF). Effective pain management during and after TVOR is essential, particularly since anesthesia may influence oocyte quality and treatment outcomes. This case report aims to evaluate the analgesic efficacy of 35 kDa hyaluronan fragments (HA35) to manage TVOR-associated pain. A 40-year-old patient with infertility underwent two TVOR procedures ten months apart under nearly identical preparatory conditions, including a subcutaneous injection of recombinant human chorionic gonadotropin to stimulate oocyte maturation. During the first procedure, pain management consisted of diclofenac sodium suppositories alone, while the second procedure included additional subcutaneous and topical HA35 administration alongside diclofenac sodium. The primary outcome measured was the patient’s self-reported pain level on the Numeric Pain Rating Scale (NPRS), alongside secondary indicators of postoperative recovery and discomfort. Results demonstrated that the addition of HA35 reduced the patient’s pain score by half, shortened the duration of pain, significantly improved comfort, and prevented postoperative bleeding, allowing for immediate discharge. This case suggests that HA35 may offer an effective, low-risk approach to enhance analgesia, reduce side effects, and improve patient recovery in TVOR procedures.展开更多
Hyaluronan (HA), the consistent glycosaminoglycans in extracellular matrix, is a kind of biomaterials with wonderful biocompatibility. To develop drug release system (DDS) with HA as drug carrier is a new hotspot in t...Hyaluronan (HA), the consistent glycosaminoglycans in extracellular matrix, is a kind of biomaterials with wonderful biocompatibility. To develop drug release system (DDS) with HA as drug carrier is a new hotspot in the field of pharmaceutics. In this paper, we applied technique of ultrosound and reversed phase (Water/Oil) emulsification to develop dexamethasone (DEX)-HA-STMP cross-linking microspheres (DEX-HA MS) with STMP as cross-linker. DEX-HA MS has a wonderful shape and property of dispersion. There is a negative correlation between diameter of DEX-HA MS and the content of cross-linker, or the content of emulsifier, and a positive correlation between the diameter and CHA . When CHA≤1%,DEX/HA≤1/10 (g/g),there is a positive correlation between the factors mentioned below and drug loading (DL%)/loading efficiency (LE%),the content of STMP, the content of emulsifier,CHA and the content of DEX. DEX-HA-MS can realize function of slow release. In vitro drug release experiment shows that cumulative release (CR%) of DEX-HA MS fits in with pervasion-corrosion equation, and there is a negative correlation between the content of STMP, CHA and CR%, a positive correlation between emulsifier and CR%. When DEX/HA≤1/5 (g/g) there is a negative correlation between the content of DEX and CR%.展开更多
Progression of cancer is often associated with interactions between cancer cells and extracellular matrix(ECM) surrounding them. Increasing evidence has suggested that accumulation of hyaluronan(HA), a major component...Progression of cancer is often associated with interactions between cancer cells and extracellular matrix(ECM) surrounding them. Increasing evidence has suggested that accumulation of hyaluronan(HA), a major component of ECM, provides a favorable microenvironment for cancer progression. Pancreatic ductal adenocarcinoma(PDAC) is characterized typically by a dense desmoplastic stroma with a large amount of HA, making this molecule as an attractive target for therapy. Several studies have shown efficacy of inhibitors of HA synthesis or signaling for the treatment of PDAC. Recent studies have also demonstrated substantial improvements in the effects of chemotherapy by a targeted depletion of stromal HA in PDAC using an enzymatic agent. Thus, targeting HA has been recognized as a promising therapeutic strategy to treat this highly aggressive neoplasm. In this review article, we summarize our current understanding of the role of HA in the progression of PDAC and discuss possible therapeutic approaches targeting HA.展开更多
Sustained inflammation associated with dysregulated macrophage activation prevents tissue formation and healing of chronic wounds.Control of inflammation and immune cell functions thus represents a promising approach ...Sustained inflammation associated with dysregulated macrophage activation prevents tissue formation and healing of chronic wounds.Control of inflammation and immune cell functions thus represents a promising approach in the development of advanced therapeutic strategies.Here we describe immunomodulatory hyaluronan/collagen(HA-AC/coll)-based hydrogels containing high-sulfated hyaluronan(sHA)as immunoregulatory component for the modulation of inflammatory macrophage activities in disturbed wound healing.Solute sHA downregulates inflammatory activities of bone marrow-derived and tissue-resident macrophages in vitro.This further affects macrophage-mediated pro-inflammatory activation of skin cells as shown in skin ex-vivo cultures.In a mouse model of acute skin inflammation,intradermal injection of sHA downregulates the inflammatory processes in the skin.This is associated with the promotion of an anti-inflammatory gene signature in skin macrophages indicating a shift of their activation profile.For in vivo translation,we designed HA-AC/coll hydrogels allowing delivery of sHA into wounds over a period of at least one week.Their immunoregulatory capacity was analyzed in a translational experimental approach in skin wounds of diabetic db/db mice,an established model for disturbed wound healing.The sHA-releasing hydrogels improved defective tissue repair with reduced inflammation,augmented pro-regenerative macrophage activation,increased vascularization,and accelerated new tissue formation and wound closure.展开更多
Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’dir...Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS.展开更多
文摘Objectives: This study aimed to evaluate the prolonged therapeutic effects of a 35 kDa molecular weight hyaluronan fragment (HA35) in alleviating pain associated with myofascial pain syndrome (MPS). Hyaluronan interacts with various receptors in the human body, including CD44, LYVE-1, RHAMM, and TLR2, and is well-known for its analgesic effects when used in intra-articular or ultrasound-guided nerve trunk injections. Studies have shown that hyaluronidase cleaves high molecular weight HA to generate HA35, a low molecular weight fragment with enhanced tissue permeability, capable of binding to HA receptors on cell surfaces to produce broad-spectrum analgesic effects. Methods: Ten patients diagnosed with MPS were treated and assessed in this study. HA35 was administered through injection at a dosage of 100 mg daily for 15 days. Patients evaluated their MPS, overall pain levels, and treatment satisfaction using the Numerical Pain Rating Scale (NPRS), the Global Pain Scale (GPS), and the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4). Follow-up evaluations were performed three months post-treatment to assess the duration of therapeutic effects. Results: Significant improvements were observed in NPRS, GPS, and TSQM scores both during and after the treatment period (P Conclusions: HA35 provides effective and sustained relief from pain associated with MPS, demonstrating a prolonged therapeutic benefit.
基金financially supported by the National Natural Science Foundation of China(32000058)the Fundamental Research Funds for the Central Universities(JUSRP622003)。
文摘The prebiotic effects of hyaluronan(HA)are widely recognized,contributing to improved gut health and immune modulation.Despite its extensive use as dietary supplement,the specific interactions between HA oligosaccharides(o-HAs)and the gut microbiome remain largely unexplored.To investigate its role and metabolic fate in gut homeostasis,200 mg/day of o-HAs(average molecule weight 1 kDa)were added to an automated computer-controlled SIMulator of the Gastrointestinal tract(SIMGI).The results revealed a significant reshaping of the intestinal flora composition by o-HAs,notably reducing the Firmicutes/Bacteroides ratio.Fermentation of o-HAs by gut microbiota significantly increased the abundance of Bifidobacterium,Prevotellaceae_Prevotella,Dialister,Eubacterium,and Sutterella,but decreased that of Catenibacterium,Oscillospira,Klebsiella,and Citrobacter(P<0.05).This corresponded with significant enhancements in the content of short-chain fatty acids(SCFAs)such as acetic acid,propionic acid and n-butyric acid,highlighting the significant impact of o-HAs at the genus level.Furthermore,analysis of microbial function predicted the downregulation of pathological events in nine human diseases,particularly infectious ones(parasitic and bacterial).Potential inhibitions were observed in metabolic pathways associated with pentose and glucuronate interconversions as well as cationic antimicrobial peptide resistance.These findings underscore the in vitro prebiotic effects of o-HAs and their potential relevance in managing diverticular diseases or preventing metabolic disorders through the regulation of gut microbiota.
基金financially supported by the National Key Research and Development Program of China(No.2021YFC2100900)the National Natural Science Foundation of China(No.32171261)+1 种基金the Taishan Industry Leading Talent of Shandong Province(No.tscx202211017)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX23_2575).
文摘Hyaluronan(HA),a natural high molecular weight polysaccharide,has extensive applications in cosmetology and medical treatment.Hyaluronan-degrading enzymes(Hyals)act as molecular scissors that cleave HA by breaking the glucosidic linkage.Hyals are present in diverse organisms,including vertebrates,invertebrates and microorganisms,and play momentous roles in biological processes.In recent years,microbial Hyals(mHyals)have gained considerable attention for their exceptional performance in the production and processing of HA.Moreover,the applications of mHyals have been greatly extended to various biomedical fields.To explore the potential applications of mHyals,a thorough comprehension is imperative.In this context,this review systematically summarizes the sources,structures,mechanisms and enzymatic properties of mHyals and discusses their biological functions in host invasion,disease development,and regulation of intestinal flora.Furthermore,versatile applications inspired by their biological functions in medicine development,molecular biology,and industrial biotechnology are comprehensively reviewed.Finally,prospects are presented to emphasize the importance of exploration,expression and characterization of mHyals and the necessity of excavating their potential in biotechnological fields.
文摘Hyaluronan binding protein 1 (HABP1) is a negatively charged multifunctional mammalian protein with a unique structural fold. Despite the fact that HABP1 possesses mitochondrial localization signal, it has also been localized to other cellular compartments. Using indirect immunofluorescence, we examined the sub-cellular localization of HABP1 and its dynamics during mitosis. We wanted to determine whether it distributes in any distinctive manner after mitotic nuclear envelope disassembly or is dispersed randomly throughout the cell. Our results reveal the golgi localization of HABP1 and demonstrate its complete dispersion throughout the cell during mitosis. This distinctive distribution pattern of HABP1 during mitosis resembles its ligand hyaluronan, suggesting that in concert with each other the two molecules play critical roles in this dynamic process.
文摘Hyaluronan is a kind of polysaccharide with high molecule weight, hs structure is relatively complicated and tertiary structure exists among the HA molecules when reaching to o certain solution concentration . FT- IR spectrum has been acquired to shou the groups and their ascription in HA. The results of FT-IR spectrum in this essay accords well with that issued by ASTM. As to the newly appearing absorption peaks, sensible explanation has been given, In ADDITION , Ramon spectrum has been employed as a proof for the result of the FT-IR spectnun. Based on the preliminary acknowledge of the functional groups in HA, circular dichroism of the material has also been explored.
基金supported by the Key Technologies Research and Development Program[2021YFC2103100]the Key Technology and Development Program of Shandong Province[2022SFGC0103]+2 种基金funded by Shandong Excellent Young Scientists(Overseas)Fund Program[2023HWYQ-002]Taishan Scholars Program[TSQN202312003]the Qilu Young Scholar Fund of Shandong University.
文摘Hyaluronan(HA)is a naturally occurring polysaccharide in the organism.As one of the main components of the extracellular matrix,it plays an important role in regulating various cellular processes,including proliferation,differentiation,inflammation,and immunity,through interaction with HA receptors.HA is widely found in the human body,particularly in the skin and joints,thus playing a crucial role in the functioning of these tissues.The aging of the skin and the occurrence of osteoarthritis are related to the loss of HA.Supplementing HA in the appropriate areas can delay or prevent these processes.Common methods of HA supplementation include topical application to the skin or injection into the joint cavities,both of which have shown efficacy in restoring HA levels and improving tissue function.In recent years,studies have shown that oral administration of HA can also have similar effects.Oral HA first passes through the gastrointestinal tract and then enters the liver with the blood circulation.Therefore,in addition to supplementing the HA content in the body,oral HA can also exert beneficial effects on the gastrointestinal tract and the liver,such as enhancing the barrier function of the gastrointestinal tract,regulating the intestinal flora,and reducing inflammation.Supplementation of HA has numerous benefits for the skin,orthopedic disorders,gastrointestinal tract and liver.Therefore,it is important to understand the mechanisms through which HA exerts these effects.This article describes the basic properties of HA and reviews its relationship with skin,orthopedic diseases,gastrointestinal tract and liver,as well as its applications in these areas.
基金Supported by Canadian Institutes of Health Research(to Triggs-Raine B)
文摘Hyaluronan is a rapidly turned over component of the vertebrate extracellular matrix. Its levels are determined, in part, by the hyaluronan synthases, HAS1, HAS2, and HAS3, and three hyaluronidases, HYAL1, HYAL2 and HYAL3. Hyaluronan binding proteins also regulate hyaluronan levels although their involvement is less well understood. To date, two genetic disorders of hyaluronan metabolism have been reported in humans: HYAL1 deficiency(Mucopolysaccharidosis IX) in four individuals with joint pathology as the predominant phenotypic finding and HAS2 deficiency in a single person having cardiac pathology. However, inherited disorders and induced mutations affecting hyaluronan metabolism have been characterized in other species. Overproduction of hyaluronan by HAS2 results in skin folding and thickening in shar-pei dogs and the naked mole rat, whereas a complete deficiency of HAS2 causes embryonic lethality in mice due to cardiac defects. Deficiencies of murine HAS1 and HAS3 result in a predisposition to seizures. Like humans, mice with HYAL1 deficiency exhibit joint pathology. Mice lacking HYAL2 have variably penetrant developmental defects, including skeletal and cardiac anomalies. Thus, based on mutant animal models, a partial deficiency of HAS2 or HYAL2 might be compatible with survival in humans, while complete deficiencies of HAS1, HAS3, and HYAL3 may yet be recognized.
文摘Pasteurella multocida hyaluronan synthase (PmHAS) is a bi-functional glycosyltransferase, containing a β1,3-glucuronyltransferase and β1,4-N-acetylglucosaminetransferase domain. PmHAS catalyzes the elongation of hyaluronan (HA) through the sequential addition of single monosaccharides to the non-reducing end of the hyaluronan chain. Research is focused on the relation between the length of the HA oligosaccharide and the single-step elongation kinetics from HA4 up to HA9. It was found that the turnover number kcat increased with length to maximum values of 11 and 14 s-1 for NAc- and UA-transfer, respectively. Interestingly, the specificity constant kcat/KM increased with polymer length from HA5 to HA7 to a value of 44 mM-1s-1, indicating an oligosaccharide binding site with increasing specificity towards a heptasaccharide at the UA domain. The value of kcat/KM remained moderately constant around 8 mM-1s-1 for HA4, HA6, and HA8, indicating a binding site with significantly lower binding specificity at the NAc domain than at the UA domain. These findings are further corroborated by a structural homology model of PmHAS, revealing two distinct sites for binding of oligosaccharides of different sizes, one in each transferase domain. Structural alignment studies between PmHAS and glycosyltransferases of the GT-A fold showed significant similarity in the binding of the UDP-sugars and the orientation of the acceptor substrate. These similarities in substrate orientation in the active site and in essential amino acid residues involved in substrate binding were utilized to localize the two HA oligosaccharide binding sites.
文摘In order to contribute to the development of minimally invasive surgery techniques for autologous chondrocyte implantation, a novel self-assembling biomaterial consisting of thermoresponsive poly(N-isopropylacrylamide)-grafted hyaluronan (PNIPAAm-g-HA) has been synthesized as an injectable scaffold for cartilage tissue engineering. The aim of this study was to investigate the efficacy and cytocompatibility of PNIPAAm-g-HA to normal chondrocytes by using reverse transcription-polymerase chain reaction (RT-PCR) analysis and histochemical staining in preliminary in vitro and in vitro experiments. Hematoxylin and eosin staining showed homogeneous distribution of cells in the PNIPAAm-g-HA hydrogel in 3-dimensional in vitro cultivation. Alcian blue staining also indicated that abundant extracellular matrix formation, including acidic glycosaminoglycans, occurred in tissue-engineered cartilage over time in vitro. Cartilage-related gene expression patterns, which were tested in rabbit normal chondrocytes embedded in the hydrogel, were almost maintained for 4 weeks. Transforming growth factor-β1 (TGF-β1) stimulation enhanced the expression of SRY-related HMG box-containing gene 9 (Sox9) and type X collagen genes suggesting promotion of chondrogenic differentiation. Histochemical evaluation showed neocartilage formation following subcutaneous implantation of the chondrocyte-gel mixture in nude mice. Furthermore, TGF-β1 stimulation promoted production and maturation of the extracellular matrix of the in situ tissue engineered hyaline cartilage. These data suggested that PNIPAAm-g-HA could be a promising biomaterial, i.e., a self-assembling and injectable scaffold for cartilage tissue engineering.
文摘A novel injectable hydrogel that was synthesized by in situ crosslinking of hyaluronan and polyvinyl phosphonic acid was proposed in this study. Fourier transform infrared spectrum (FT-IR) analysis, scanning electron microscope (SEM), pH measurement, and biodegradation test were used to confirm its characteristics. The results permitted to prove successful crosslinking, observe the inner morphology of hydrogel and pore sizes distribution, and determine the decomposition of hydrogel components during incubation time. Result of pH measurement showed that the pH scale of hydrogel decreased when volume of PVPA increased. As a consequence, it affected the cytotoxicity value, cell proliferation, and cell growth behaviors of each hydrogel. Optical microscope observation showed that chondroblasts cell proliferated well on HA-PVPA hydrogel. Therefore, these results suggest that the new injectable hydrogel is appropriate for bone/cartilage regeneration applications.
文摘Purpose: The purpose of this study is to determine the presence of bacteriostatic effects of hyaluronan-based bioresorbable membrane (HA/CMC) on selected major bacterial strains in digestive organs. Methods: We firstly evaluated the growth inhibition effect of HA/CMC for E. coli and S. aureus by determining the optical density (OD)650 in the incubation medium. At second, to determine the viable counts of bacteria, total adenosine triphosphate (ATP) were measured with five groups;several concentrations of HA/CMC and control. Results: OD curve gradually elevated and reached to plateau at 4 hours in E. coli. and 6 hours in S. aureus. After reaching plateau, the growth inhibition of both strains was statistically significantly correlated to the concentrations of HA/CMC. The ATP productions had statistically significant differences at 6 hours after incubation and inhibited in dose-dependence of a well-dissolved HA/CMC. Conclusion: HA/CMC may have dose-dependently bacteriostatic effects on S. aureus and E. coli.
基金The Second Hospital of Tianjin Medical University,300211 Tianjin,China
文摘Objective: Prepare cross-linked HA gels with higher mechanical stability, lower degradation velocity and desirable biocompatibility,so as to extend the usage of HA.Method:1.Test molecular weight of HA (Mr_ HA ) by viscosimetry;2.prepare cross-linked HA gels by DVS, GTA, DEC;3.discuss the cross-linking and degradation procedure;4.evaluate the biocompatibility of the best HA gels. Results:The mechanical stability and durability to degradation of HA-DVS gels are superior to those of other gels, and when HA:DVS = 40:1(g/g), at 35℃ and in 0.2 M NaOH solution, the HA-DVS gel shows the best mechanical stability, and its cytotoxicity reaches class I, hemolysis ratio is lower than 5%. Conclusion:Our HA-DVS gel can be used to prepare biologic scaffolds.
文摘Transvaginal oocyte retrieval (TVOR) is a common yet painful procedure in assisted reproductive technologies (ART) like in vitro fertilization (IVF). Effective pain management during and after TVOR is essential, particularly since anesthesia may influence oocyte quality and treatment outcomes. This case report aims to evaluate the analgesic efficacy of 35 kDa hyaluronan fragments (HA35) to manage TVOR-associated pain. A 40-year-old patient with infertility underwent two TVOR procedures ten months apart under nearly identical preparatory conditions, including a subcutaneous injection of recombinant human chorionic gonadotropin to stimulate oocyte maturation. During the first procedure, pain management consisted of diclofenac sodium suppositories alone, while the second procedure included additional subcutaneous and topical HA35 administration alongside diclofenac sodium. The primary outcome measured was the patient’s self-reported pain level on the Numeric Pain Rating Scale (NPRS), alongside secondary indicators of postoperative recovery and discomfort. Results demonstrated that the addition of HA35 reduced the patient’s pain score by half, shortened the duration of pain, significantly improved comfort, and prevented postoperative bleeding, allowing for immediate discharge. This case suggests that HA35 may offer an effective, low-risk approach to enhance analgesia, reduce side effects, and improve patient recovery in TVOR procedures.
文摘Hyaluronan (HA), the consistent glycosaminoglycans in extracellular matrix, is a kind of biomaterials with wonderful biocompatibility. To develop drug release system (DDS) with HA as drug carrier is a new hotspot in the field of pharmaceutics. In this paper, we applied technique of ultrosound and reversed phase (Water/Oil) emulsification to develop dexamethasone (DEX)-HA-STMP cross-linking microspheres (DEX-HA MS) with STMP as cross-linker. DEX-HA MS has a wonderful shape and property of dispersion. There is a negative correlation between diameter of DEX-HA MS and the content of cross-linker, or the content of emulsifier, and a positive correlation between the diameter and CHA . When CHA≤1%,DEX/HA≤1/10 (g/g),there is a positive correlation between the factors mentioned below and drug loading (DL%)/loading efficiency (LE%),the content of STMP, the content of emulsifier,CHA and the content of DEX. DEX-HA-MS can realize function of slow release. In vitro drug release experiment shows that cumulative release (CR%) of DEX-HA MS fits in with pervasion-corrosion equation, and there is a negative correlation between the content of STMP, CHA and CR%, a positive correlation between emulsifier and CR%. When DEX/HA≤1/5 (g/g) there is a negative correlation between the content of DEX and CR%.
基金supported in part by a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technologies of Japan (26462076)
文摘Progression of cancer is often associated with interactions between cancer cells and extracellular matrix(ECM) surrounding them. Increasing evidence has suggested that accumulation of hyaluronan(HA), a major component of ECM, provides a favorable microenvironment for cancer progression. Pancreatic ductal adenocarcinoma(PDAC) is characterized typically by a dense desmoplastic stroma with a large amount of HA, making this molecule as an attractive target for therapy. Several studies have shown efficacy of inhibitors of HA synthesis or signaling for the treatment of PDAC. Recent studies have also demonstrated substantial improvements in the effects of chemotherapy by a targeted depletion of stromal HA in PDAC using an enzymatic agent. Thus, targeting HA has been recognized as a promising therapeutic strategy to treat this highly aggressive neoplasm. In this review article, we summarize our current understanding of the role of HA in the progression of PDAC and discuss possible therapeutic approaches targeting HA.
基金This work was funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)project number 59307082-TRR67 subprojects A3,B3,Z3project FR2671/4-1 to SFproject 420160411 to SR.
文摘Sustained inflammation associated with dysregulated macrophage activation prevents tissue formation and healing of chronic wounds.Control of inflammation and immune cell functions thus represents a promising approach in the development of advanced therapeutic strategies.Here we describe immunomodulatory hyaluronan/collagen(HA-AC/coll)-based hydrogels containing high-sulfated hyaluronan(sHA)as immunoregulatory component for the modulation of inflammatory macrophage activities in disturbed wound healing.Solute sHA downregulates inflammatory activities of bone marrow-derived and tissue-resident macrophages in vitro.This further affects macrophage-mediated pro-inflammatory activation of skin cells as shown in skin ex-vivo cultures.In a mouse model of acute skin inflammation,intradermal injection of sHA downregulates the inflammatory processes in the skin.This is associated with the promotion of an anti-inflammatory gene signature in skin macrophages indicating a shift of their activation profile.For in vivo translation,we designed HA-AC/coll hydrogels allowing delivery of sHA into wounds over a period of at least one week.Their immunoregulatory capacity was analyzed in a translational experimental approach in skin wounds of diabetic db/db mice,an established model for disturbed wound healing.The sHA-releasing hydrogels improved defective tissue repair with reduced inflammation,augmented pro-regenerative macrophage activation,increased vascularization,and accelerated new tissue formation and wound closure.
基金This work was supported by grants from the NIH(DK46635,HL18645 and DK53004)the JDRF(The Center for Translational Research at BRI)PLB is supported by NIH K-08 grant DK080178-01 and an NIH LRP grant.The authors would like to thank Nathan Standifer and Michael Kinsella for their helpful comments and Tuan Nguyen for tissue processing.
文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS.
