Degradation Of Hyaluronic Acid Research Articles

Photoelectrocatalytic degradation of hyaluronic acid and regulation effects of its degradation products on gut microbiota in vitro

Photoelectrocatalytic degradation of hyaluronic acid and regulation effects of its degradation products on gut microbiota in vitro

In vitro study of the gel cohesivity and persistence to hyaluronidase degradation of a novel stabilized composition of 26 mg/mL of high molecular weight HA

Aim: Hyaluronic acid (HA) is extensively used in injectable skin quality products due to its documented role in skin rejuvenation. The rapid in vivo degradation of HA by the enzyme hyaluronidase necessitates the development of advanced formulations to ensure the efficacy and longevity of the treatments. In this context, a novel 2.6% high molecular weight HA (H-HA)/3.2% sorbitol composition has been introduced, featuring stabilization through hydrogen bonds rather than traditional crosslinking. Methods: The stabilized composition was evaluated through two in vitro enzymatic degradation tests. In the first test, the efficiency on the gel degradation was followed by rheology and compared with two crosslinked HA products available on the market. In the second test, the effect on the gel structure of a less diluted hyaluronidase dose was followed by rheological and cohesivity measurements. Results: In vitro study demonstrates that, before its complete degradation into a liquid-like state, the stabilized composition exhibits high elasticity and cohesivity during the enzymatic degradation process, surpassing traditional crosslinked HA products. Conclusion: The stabilization provided by the sorbitol in the stabilized composition effectively enhances product properties and protects them during gel degradation. These attributes indicate significant potential for improved clinical outcomes in skin quality treatments.

Effects of Hyaluronic Acid (HA) and Platelet-Rich Plasma (PRP) on Mandibular Mobility in Temporomandibular Joint Disorders: A Controlled Clinical Trial.

Hyaluronic acid (HA) is a glycosaminoglycan composed of D-glucuronic acid and N-acetylglucosamine with an up-to-several-million-Daltons chain-length responsible for the lubricating properties of the temporomandibular joint (TMJ) synovial fluid. Arthritis results in the predominance of HA degradation over synthesis leading to temporomandibular disorders (TMDs). TMD injection treatments are divided into HA supplementation and platelet-rich plasma (PRP) inflammation suppression. We questioned whether either approach lubricated the TMJ better and answered it in a two-arm equal-allocation trial with a non-concurrent active treatment control (two groups of 39 patients each). HA statistically significantly improved (p < 0.01) and PRP did not statistically significantly change (0.06 ≤ p ≤ 0.53) articular mobility compared to baselines in 128 TMJs. Statistically significant inter-group discrepancies were observed for abduction (MD = -4.05 mm; SE = 1.08; p = 0.00; d = -0.85) and protrusion (MD = -0.97 mm; SE = 0.43; p = 0.03; d = -0.51) but not for rightward (MD = -0.21; SE = 0.43; p = 0.63; d = -0.11) and leftward (MD = -0.30; SE = 0.42; p = 0.47; d = -0.16) movements. HA supplementation proved superior to PRP autografting in ad hoc TMJ lubrication and hence is more appropriate in hypomobile TMD cases of symptomatic treatment.

Development of Dual-Targeted Mixed Micelles Loaded with Celastrol and Evaluation on Triple-Negative Breast Cancer Therapy.

Considering that the precise delivery of Celastrol (Cst) into mitochondria to induce mitochondrial dysfunction may be a potential approach to improve the therapeutic outcomes of Cst on TNBC, a novel tumor mitochondria dual-targeted mixed-micelle nano-system was fabricated via self-synthesized triphenylphosphonium-modified cholesterol (TPP-Chol) and hyaluronic acid (HA)-modified cholesterol (HA-Chol). The Cst-loaded mixed micelles (Cst@HA/TPP-M) exhibited the characteristics of a small particle size, negative surface potential, high drug loading of up to 22.8%, and sustained drug release behavior. Compared to Cst-loaded micelles assembled only by TPP-Chol (Cst@TPP-M), Cst@HA/TPP-M decreased the hemolysis rate and upgraded the in vivo stability and safety. In addition, a series of cell experiments using the triple-negative breast cancer cell line MDA-MB-231 as a cell model proved that Cst@HA/TPP-M effectively increased the cellular uptake of the drug through CD44-receptors-mediated endocytosis, and the uptake amount was three times that of the free Cst group. The confocal results demonstrated successful endo-lysosomal escape and effective mitochondrial transport triggered by the charge converse of Cst@HA/TPP-M after HA degradation in endo-lysosomes. Compared to the free Cst group, Cst@HA/TPP-M significantly elevated the ROS levels, reduced the mitochondrial membrane potential, and promoted tumor cell apoptosis, showing a better induction effect on mitochondrial dysfunction. In vivo imaging and antitumor experiments based on MDA-MB-231-tumor-bearing nude mice showed that Cst@HA/TPP-M facilitated drug enrichment at the tumor site, attenuated drug systemic distribution, and polished up the antitumor efficacy of Cst compared with free Cst. In general, as a target drug delivery system, mixed micelles co-constructed by TPP-Chol and HA-Chol might provide a promising strategy to ameliorate the therapeutic outcomes of Cst on TNBC.

Identification and Characterization of a Highly Active Hyaluronan Lyase from Enterobacter asburiae.

Hyaluronic acid (HA) is a well-known functional marine polysaccharide. The utilization and derivative development of HA are of great interest. Hyaluronan lyase has wide application prospects in the production of HA oligosaccharides and lower molecular weight HA. In this study, a strain of Enterobacter asburiae CGJ001 with high hyaluronan lyase activity was screened from industrial wastewater. This strain exhibited an impressive enzyme activity of 40,576 U/mL after being incubated for 14 h. Whole genome sequencing analysis revealed that E. asburiae CGJ001 contained a cluster of genes involved in HA degradation, transport, and metabolism. A newly identified enzyme responsible for glycosaminoglycan degradation was designated as HylEP0006. A strain of E. coli BL21(DE3)/pET-22b(+)-hylEP0006 was successfully constructed. HylEP0006 exhibited optimal degradation at 40 °C and pH 7.0, showing a high activity of 950,168.3 U/mg. HylEP0006 showed specific activity against HA. The minimum degradation fragment of HylEP0006 was hyaluronan tetrasaccharides, and HylEP0006 could efficiently degrade HA into unsaturated disaccharides (HA2), with HA2 as the final product. These characteristics indicate that HylEP0006 has a potential application prospect for the extraction and utilization of hyaluronic acid.

KIAA1199/CEMIP knockdown attenuates cardiac remodeling post myocardial infarction by activating TSP4 pathway in mice

BackgroundExcessive activation of cardiac fibroblasts (CFs) significantly contributes to adverse cardiac remodeling post-myocardial infarction (MI). CEMIP, initially recognized as an enzyme involved in hyaluronic acid (HA) degradation, has also been implicated in the activation of pulmonary fibroblasts. Nevertheless, the role and mechanism of CEMIP in adverse cardiac remodeling following MI remain largely unexplored. Materials and methodsRNA sequencing (RNA-seq) was performed on cardiac tissue harvested from the infarct/peri-infarct region of mice 28 days post-MI. RNA-seq was conducted on primary cardiac fibroblasts (CFs) transfected with adenovirus overexpressing CEMIP. Adeno-associated virus serotype 9 (AAV9) was engineered for in vivo CEMIP knockdown to elucidate its impact on cardiac remodeling. Immunoprecipitation coupled with mass spectrometry (IP-MS) and co-immunoprecipitation (co-IP) were employed to elucidate the mechanism by which CEMIP affected cardiac remodeling. Key findingsRNA-seq of fibrotic heart tissue at day 28 post-MI revealed a significant upregulation of CEMIP. In vitro, CEMIP facilitated the activation of cardiac fibroblasts. In vivo, knockdown of CEMIP markedly reduced cardiac fibrosis and improved cardiac function post-MI. IP-MS and co-immunoprecipitation (co-IP) confirmed that CEMIP interacted with TSP4 through the G8 domain. Further experiments confirmed that CEMIP promoted TSP4 degradation in lysosomes in an ACTN4-dependent manner, thereby activating the FAK signaling pathway. SignificanceOur findings suggest that CEMIP significantly contributes to cardiac remodeling post-MI, which might be a novel approach for treating cardiac fibrosis following MI.

Carnosine and Retinol Synergistically Inhibit UVB-Induced PGE2 Synthesis in Human Keratinocytes through the Up-Regulation of Hyaluronan Synthase 2.

Skin aging results from complex interactions of intrinsic and extrinsic factors, leading to structural and biochemical changes such as wrinkles and dryness. Ultraviolet (UV) irradiation leads to the degradation of hyaluronic acid (HA) in the skin, and the with fragmented HA contributes to inflammation. This study revealed that the synergistic combination of carnosine and retinol (ROL) increases HA production in normal human epidermal keratinocytes (NHEKs) by upregulating hyaluronan synthase 2 (HAS2) gene transcription. Simultaneously, the combined treatment of carnosine and ROL significantly attenuates UVB-induced prostaglandin E2 (PGE2) synthesis in NHEKs. A significant correlation exists between the increase of HA synthesis and the inhibition of PGE2 production. This study suggested that combined treatment of carnosine and ROL can improve skin aging phenotypes associated with UVB irradiation.

Clinical applications of a novel poly-L-lactic acid microsphere and hyaluronic acid suspension for facial depression filling and rejuvenation.

Poly L-lactic acid (PLLA) can stimulate fibrous tissue regeneration to exert a filling effect. However, severe inflammatory reactions and unsatisfactory effects remain a concern. Herein, we describe the mechanism of action, efficacy, and safety of PLLA microspheres in suspension (PLLA-b-PEG/HA) for facial contouring and soft tissue augmentation. PLLA-b-PEG/HA, ssynthesized by copolymerization with ethylene glycol, were suspended in hyaluronic acid (HA). Physiological verification was performed using scanning electron microscopy and X-ray computed tomography. PLLA-b-PEG/HA were subcutaneously injected into the dorsal region of 4-month-old rabbits. Ultrasound assessed volumetric capacity at 3 days and 1, 2, 4, and 12 weeks. The inflammatory response, collagen production, and HA degradation were evaluated. A retrospective case series of 10 patients who received PLLA-b-PEG/HA injections was conducted to assess long-term efficacy and safety. PLLA-b-PEG exhibited a spherical structure with a smooth surface (20-45 μm diameter). In rabbits, implant site volume increased within 4 weeks, gradually decreasing thereafter. Fibrous capsules, microvessel density, and new collagen fiber formation progressively increased at 4, 12, and 26 weeks after injection. Clinical data demonstrated significant improvements in face contouring at months 3 and 12 after injection. All patients showed improved internal contours based on the Global Aesthetic Improvement Scale. After 12 months, 90% of the patients retained good shaping and support effects with minimal adverse reactions. PLLA-b-PEG/HA demonstrated superior biocompatibility and facial regeneration potential, with outstanding dual collagen-stimulating properties. The clinical efficacy and safety of PLLA-b-PEG/HA have been validated and established as a promising therapeutic option.

Lubricating adhesive hyaluronate patch promotes cartilage regeneration and functional restoration in osteoarthritis

Osteoarthritis (OA) is a common chronic degenerative joint disease characterized by gradual deterioration and pain. Viscosupplementation, involving hyaluronic acid (HA) injection into the affected joint, is a minimally invasive option to reduce pain by improving joint lubrication and potentially avoiding the need for replacement surgery. However, the low adhesion and rapid degradation of HA often lead to inadequate therapeutic effects. In this study, we present lubricating adhesive HA-based hydrogel patches designed to effectively treat OA. The HA patches, modified with pyrogallol, have high elastic and compressive moduli, delaying degradation when exposed to external stimuli. Furthermore, they securely adhere to cartilage tissue surfaces and efficiently lubricate damaged cartilage, leading to a reduced friction and wear. In addition to these benefits, our HA patches exhibit scavenging effect of reactive oxygen species and sustainably release an encapsulated anti-inflammatory drug (dexamethasone: Dex). These features further enhance their therapeutic potential for OA treatment. In a mouse OA model, the hydrogel patches loaded with Dex promote healing of damaged cartilage and restore its motor function. Overall, our bioinspired HA hydrogel patches present a promising treatment option for managing the debilitating joint disease by offering enhanced adhesion, lubrication for cartilage protection, antioxidant effect, and sustained drug release.

Function and contribution of two putative Enterococcus faecalis glycosaminoglycan degrading enzymes to bacteremia and catheter-associated urinary tract infection.

Enterococcus faecalis is a common cause of healthcare-acquired bloodstream infections and catheter-associated urinary tract infections (CAUTIs) in both adults and children. Treatment of E. faecalis infection is frequently complicated by multi-drug resistance. Based on protein homology, E. faecalis encodes two putative hyaluronidases, EF3023 (HylA) and EF0818 (HylB). In other Gram-positive pathogens, hyaluronidases have been shown to contribute to tissue damage and immune evasion, but the function in E. faecalis has yet to be explored. Here, we show that both hylA and hylB contribute to E. faecalis pathogenesis. In a CAUTI model, ΔhylA exhibited defects in bladder colonization and dissemination to the bloodstream, and ΔhylB exhibited a defect in kidney colonization. Furthermore, a ΔhylAΔhylB double mutant exhibited a severe colonization defect in a model of bacteremia while the single mutants colonized to a similar level as the wild-type strain, suggesting potential functional redundancy within the bloodstream. We next examined enzymatic activity, and demonstrate that HylB is capable of digesting both hyaluronic acid (HA) and chondroitin sulfate in vitro, while HylA exhibits only a very modest activity against heparin. Importantly, HA degradation by HylB provided a modest increase in cell density during the stationary phase and also contributed to dampening of lipopolysaccharide-mediated NF-κB activation. Overall, these data demonstrate that glycosaminoglycan degradation is important for E. faecalis pathogenesis in the urinary tract and during bloodstream infection.

Fine-tuning of liposome integrity for differentiated transcytosis and enhanced antitumor efficacy

Transcytosis-inducing nanomedicines have been developed to improve tumor extravasation. However, the fate during transcytosis across multicell layers and the structural integrity of the nanomedicines before reaching tumor cells could impact antitumor therapy. Here, a BAY 87–2243 (a hypoxia-inducible factor-1 inhibitor)-loaded liposomal system (HA-P-LBAY) modified by low molecular weight protamine (LMWP) and crosslinked by hyaluronic acid (HA) was constructed. This system could accomplish differentiate cellular transport in endothelial and tumor cells by fine-tuning its structural integrity, i.e. transcytosis across the endothelial cells while preserving structural integrity, facilitating subsequent retention and drug release within tumor cells via degradation-induced aggregation. In vitro cellular uptake and transwell studies demonstrated that HA-P-LBAY were internalized by endothelial cells (bEnd.3) via an active, caveolin and heparin sulfate proteoglycan (HSPG)-mediated endocytosis, and subsequently achieved transcytosis mainly through the ER/Golgi pathway. Moreover, the fluorescence resonance energy transfer (FRET) study showed that HA-crosslinking maintained higher integrity of HA-P-LBAY after transcytosis, more efficiently than electrostatic coating of HA (HA/P-LBAY). In addition, more HA-P-LBAY was retained in tumor cells (4T1) compared to HA/P-LBAY corresponding to its enhanced in vitro cytotoxicity. This may be attributed to better integrity of HA-P-LBAY post endothelial transcytosis and more degradation of HA in tumor cells, leading to more liposome aggregation and inhibition of their transcytosis, which was inferred by both TEM images and the HAase responsiveness assay proved by FRET. In vivo, HA-P-LBAY exhibited more potency in tumor suppression than the other formulations in both low and high permeability tumor models. This highlighted that fine-tuning of structural integrity of nanocarriers played a key role no matter whether the transcytosis of nanocarriers contributed to cellular transport. Collectively, this study provides a promising strategy for antitumor therapies by fine-tuning liposome integrity to achieve active trans-endothelial transport with structural integrity and selective aggregation for prolonged tumor retention.

Xanthone Derivatives and Their Potential Usage in the Treatment of Telangiectasia and Rosacea

Xanthone derivatives, a class of natural compounds abundantly found in plants such as mangosteen (Garcinia mangostana) and certain herbs, have garnered substantial interest due to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. Recent investigations have unveiled their potential as modulators of enzymatic activity, prompting exploration into their effects on hyaluronidase-mediated hyaluronic acid (HA) degradation, and their effects in topical treatment of telangiectasia and rosacea. Telangiectasia and rosacea are common dermatological conditions characterized by chronic skin inflammation, vascular abnormalities, and visible blood vessels, resulting in significant cosmetic concerns and impaired quality of life for affected individuals. This review aims to provide a comprehensive overview of the current understanding regarding the interplay between the mechanisms of action by which xanthone derivatives exert their therapeutic effects, including the inhibition of pro-inflammatory cytokines, modulation of oxidative stress pathways, and regulation of vascular endothelial growth factors. Furthermore, we will discuss the implications of harnessing xanthone derivatives as therapeutic agents for mitigating vascular dysfunction and its associated pathologies, thereby offering insights into future research directions and therapeutic strategies in the field of vascular biology.

WNT5B drives osteosarcoma stemness, chemoresistance and metastasis.

Treatment for osteosarcoma, a paediatric bone cancer with no therapeutic advances in over three decades, is limited by a lack of targeted therapies. Osteosarcoma frequently metastasises to the lungs, and only 20% of patients survive 5 years after the diagnosis of metastatic disease. We found that WNT5B is the most abundant WNT expressed in osteosarcoma tumours and its expression correlates with metastasis, histologic subtype and reduced survival. Using tumor-spheroids to model cancer stem-like cells, we performed qPCR, immunoblotting, and immunofluorescence to monitor changes in gene and protein expression. Additionally, we measured sphere size, migration and forming efficiency to monitor phenotypic changes. Therefore, we characterised WNT5B's relevance to cancer stem-like cells, metastasis, and chemoresistance and evaluated its potential as a therapeutic target. In osteosarcoma cell lines and patient-derived spheres, WNT5B is enriched in stem cells and induces the expression of the stemness gene SOX2. WNT5B promotes sphere size, sphere-forming efficiency, and cell proliferation, migration, and chemoresistance to methotrexate (but not cisplatin or doxorubicin) in spheres formed from conventional cell lines and patient-derived xenografts. In vivo, WNT5B increased osteosarcoma lung and liver metastasis and inhibited the glycosaminoglycan hyaluronic acid via upregulation of hyaluronidase 1 (HYAL1), leading to changes in the tumour microenvironment. Further, we identified that WNT5B mRNA and protein correlate with the receptor ROR1 in primary tumours. Targeting WNT5B through inhibition of WNT/ROR1 signalling with an antibody to ROR1 reduced stemness properties, including chemoresistance, sphere size and SOX2 expression. Together, these data define WNT5B's role in driving osteosarcoma cancer stem cell expansion and methotrexate resistance and provide evidence that the WNT5B pathway is a promising candidate for treating osteosarcoma patients. WNT5B expression is high in osteosarcoma stem cells leading to increased stem cell proliferation and migration through SOX2. WNT5B expression in stem cells increases rates of osteosarcoma metastasis to the lungs and liver in vivo. The hyaluronic acid degradation enzyme HYAL1 is regulated by WNT5B in osteosarcoma contributing to metastasis. Inhibition of WNT5B with a ROR1 antibody decreases osteosarcoma stemness.

Hyaluronidase inhibits TGF-β-mediated rat periodontal ligament fibroblast expression of collagen and myofibroblast markers: An in vitro exploration of periodontal tissue remodeling

ObjectiveTo determine the effect of hyaluronic acid (HA) degradation by hyaluronidase (HYAL) in inhibiting collagen fiber production by rat periodontal ligament cells (rPDLCs). DesignPrimary rPDLCs were isolated from the euthanized rats and used for in vitro experiments. The appropriate HYAL concentration was determined through CCK-8 testing for cytotoxicity detection and Alizarin red staining for mineralization detection. RT-qPCR and western blot assays were conducted to assess the effect of HYAL, with or without TGF-β, on generation of collagen fiber constituents and expression of actin alpha 2, smooth muscle (ACTA2) of rPDLCs. ResultsNeither cell proliferation nor mineralization were significantly affected by treatment with 4 U/mL HYAL. HYAL (4 U/mL) alone downregulated type I collagen fiber (Col1a1 and Col1a2) and Acta2 mRNA expression; however, ACTA2 and COL1 protein levels were only downregulated by HYAL treatment after TGF-β induction. ConclusionsTreatment of rPDLCs with HYAL can inhibit TGF-β-induced collagen matrix formation and myofibroblast transformation.

Garcinol: A novel and potent inhibitor of hyaluronidase enzyme

Extracellular matrix (ECM) contains hyaluronic acid (HA) as its integral part that is involved in numerous functional activities within the body. Degradation of HA by hyaluronidase enzyme involved in many pathophysiological conditions such as asthma, arthritis, COPD and in venom spreading during envenomation. Inhibitor of hyaluronidase enzyme has a wide range of application along with the hyaluronan-hyaluronidase system. In this present study, we have evaluated the inhibitory effect of garcinol against hyaluronidase from Hippasa partita spider venom (HPHyal), bovine testicular hyaluronidase (BTH) and human serum hyaluronidase. Garcinia indica fruit rind has been used to isolate the active component garcinol. Garcinol has been used in treatment of diverse ailments. Garcinol has exhibited anti-oxidant, anti-inflammatory, HAT inhibition and miRNA deregulator in development and progression of cancers. Experimental data have shown that garcinol completely inhibited all the three tested hyaluronidase enzymes. The inhibition was found to be non-competitive pattern with reversible type. In the docking study, garcinol with hyaluronidase enzyme has been stabilized by hydrogen bonding and hydrophobic interactions. Thus, garcinol could be a potent novel inhibitor of hyaluronidase enzyme which can be further used for pharmacotherapeutic applications.

Abstract 4273: Genetically engineered mesenchymal stromal cells degrade hyaluronic acid to disrupt the ECM and enhance cancer therapy outcomes

Abstract The extracellular matrix (ECM) is a vital component of cancer pathophysiology. However, little is known about how to modulate the ECM for therapeutic benefit effectively. Hyaluronic acid (HA) is a polysaccharide component of the ECM with increased deposition during tissue injury or inflammation. HA in the tumor microenvironment (TME) has been linked to aggressive cancer progression. We have found enhanced ECM remodeling behavior linked to pre-metastatic niche formation and metastatic progression. To remodel this ECM-enriched microenvironment, we developed HA-targeting genetically engineered mesenchymal stromal cells (GEMesys) expressing hyaluronidase (Hyal), the enzyme responsible for HA degradation. We examined the impact of Hyal-GEMesys in osteosarcoma (F42010), rhabdomyosarcoma (M-3-9M), and pancreatic cancer (Panc02) syngeneic murine models. Hyal-GEMesys delivered to tumor-bearing mice homed to primary tumor sites and successfully degraded HA in the TME. The degradation of HA also resulted in a significant remodeling of collagen. T cells in Hyal-GEMesy treated tumors display an activated CD4+CD44+ phenotype with a reduction of LAG3+PD1+ exhaustion markers. Additionally, Hyal-GEMesy treatment results in a significant decrease in hypoxic regions within tumors and reorganization of the tumor vasculature to a more normalized phenotype, marked by diminished CD31 expression. Hyal-GEMesy treatment reduces tumor volumes in osteosarcoma, rhabdomyosarcoma, and pancreatic cancer models and enhances chemotherapeutic efficacy. These findings suggest that reorganizing the tumor ECM with Hyal-GEMesys holds the potential to dismantle the protective stroma of the tumor, which often shields malignant cells from therapeutic reach, and combining anti-cancer and anti-stroma agents can enhance anti-tumor efficacy and patient outcomes. Citation Format: Alice T. Browne, Miranda Clements, Wei Ju, Rosandra Kaplan. Genetically engineered mesenchymal stromal cells degrade hyaluronic acid to disrupt the ECM and enhance cancer therapy outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4273.

Degradation and fermentation of hyaluronic acid by Bacteroides spp. from the human gut microbiota

Bacteroides spp. are prominent members of the human gut microbiota that play critical roles in the metabolism of complex carbohydrates from the daily diet. Hyaluronic acid (HA) is a multifunctional polysaccharide which has been extensively used in the food and biomedical industry. However, how HA is degraded and fermented by Bacteroides spp. has not been fully characterized. Here, we comprehensively investigated the detailed degradation profiles and fermentation characteristics of four different HAs with discrete molecular weight (Mw) by fourteen distinctive Bacteroides spp. from the human gut microbiota. Our results indicated that high-Mw HAs were more degradable and fermentable than low-Mw HAs. Interestingly, B. salyersiae showed the best degrading capability for both high-Mw and low-Mw HAs, making it a keystone species for HA degradation among Bacteroides spp.. Specifically, HA degradation by B. salyersiae produced significant amounts of unsaturated tetrasaccharide (udp4). Co-culture experiments indicated that the produced udp4 could be further fermented and utilized by non-proficient HA-degraders, suggesting a possible cross-feeding interaction in the utilization of HA within the Bacteroides spp.. Altogether, our study provides novel insights into the metabolism of HA by the human gut microbiota, which has considerable implications for the development of new HA-based nutraceuticals and medicines.

An oncolytic vaccinia virus encoding hyaluronidase reshapes the extracellular matrix to enhance cancer chemotherapy and immunotherapy

BackgroundThe redundant extracellular matrix (ECM) within tumor microenvironment (TME) such as hyaluronic acid (HA) often impairs intratumoral dissemination of antitumor drugs. Oncolytic viruses (OVs) are being studied extensively for cancer...

Gold nanoclusters encapsulated microneedle patches with antibacterial and self‐monitoring capacities for wound management

AbstractThe management of infected wounds is always of great significance and urgency in clinical and biomedical fields. Recent efforts in this area are focusing on the development of functional wound patches with effective antibacterial, drug delivery, and sensor properties. Here, we present novel hyaluronic acid (HA) microneedle patches with these features by encapsulating aminobenzeneboronic acid‐modified gold nanoclusters (A‐GNCs) for infected wound management. The A‐GNCs loaded microneedle patches were derived from negative‐mold replication and showed high mechanical strength to penetrate the skin. The release of the A‐GNCs was realized by the degradation of HA, and the self‐monitor of the released actives was based on the dynamic bright orange fluorescence emitted from A‐GNCs under ultraviolet radiation. As the A‐GNCs could destroy bacteria membranes, the microneedle patches were with excellent in vitro antibiosis ability. Based on these features, we have demonstrated the bacteria inhibition, residual drug self‐monitoring, and wound healing promotion abilities of the microneedle patches in Escherichia coli‐ or Staphylococcus aureus‐infected wound management. These results indicated the great potential of such A‐GNCs loaded microneedle patches for clinical applications.

Evaluation of Antioxidants’ Ability to Enhance Hyaluronic Acid-Based Topical Moisturizers

Introduction: Hyaluronic acid (HA) is a unique molecule with multiple biological activities. In skin, HA plays an essential role as a humectant, capable of binding up to 1000 times its mass with water, leading to both skin moisturization and extracellular matrix rigidity. HA concentration and synthesis decreases significantly in aging skin, due to exogenous and endogenous factors, including photoaging and HA metabolism, respectively. A key driver for HA degradation and decrease in concentration is mediated via the induction of reactive oxygen species (ROS) and other free radicals. In this study, we evaluate antioxidant ingredients essential in the development of next-generation multi-weight HA-based topical formulations aimed at leveraging hyaluronic acid’s ability to maximize anti-aging properties. Methods: Two antioxidants, glycine saponin and glycyrrhetinic acid, were evaluated for stimulation of endogenous HA production and inhibition of endogenous hyaluronidase activity in an in vitro and cell-free assay. Results: The antioxidant glycine saponin induced endogenous HA synthesis in keratinocytes, while the antioxidant glycyrrhetinic acid demonstrated an approximately 54% reduction of hyaluronidase activity for the HA-degrading enzyme HYAL1. Conclusion: This study demonstrates the ability of two antioxidants (glycine saponin and glycyrrhetinic acid, essential in the development of the next generation of multi-weight HA plus antioxidant complex-based topical skin formulations) to limit the signs of aging skin, addressing limitations of many currently available topical HA-based formulations.