Hyaluronidase Research Articles

Objective: To investigate the potential therapeutic benefits of autoimmune antibody detection in individuals suffering from chronic hepatitis B. Methods: For the observation group, 102 patients with chronic hepatitis B who were admitted between March 2022 and March 2025 were chosen. Additionally, the control group consisted of 102 healthy people who were examined throughout the same time period. The two groups' autoimmune antibodies were identified, and patients in the observation group with positive and negative autoimmune antibodies were compared in terms of their liver function, liver fibrosis markers, and cytokine levels. Results: The total positive rate of autoimmune antibodies in the observation group was 26.47%, whereas it was 3.92% in the control group (P<0.05). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were noticeably greater in the observation group's patients with positive autoimmune antibodies than in those with negative antibodies. However, the albumin (ALB) and total protein (TP) levels were much lower than those of patients with negative antibodies. A statistically significant difference was observed (P<0.05). Type III procollagen (PCIII), hyaluronidase (HA), and the levels of laminin (LN) were statistically significant (P<0.05) higher in individuals with positive autoimmune antibodies than in those with negative antibodies. Patients with positive autoimmune antibodies had considerably higher levels of interleukin-4 (IL-4), interleukin-10 (IL-10), and interleukin-6 (IL-6) than patients with negative antibodies. Patients with negative antibodies had significantly higher levels of interferon-γ (IFN-γ) (P < 0.05). Conclusion: Autoimmune antibodies are present in patients with chronic hepatitis B, which influence liver fibrosis indicators and related cytokines. The identification of autoimmune antibodies in chronic hepatitis B patients can serve as a guide for evaluating the illness and determining prognosis.

Cumulus removal (CR), the removal of the small protective granulosa cells that surround an oocyte, is a crucial step in assisted reproductive technologies (ART). Traditional CR methods rely on vortexing or manual pipetting, which can result in inconsistencies and variability. Here, we present an open-surface platform featuring pillars that actively separates differently sized particles and removes cumulus cells from oocytes through vibration-induced flow (VIF). The platform removed 99% of small particles from the loading chamber by generating a local flow through the pillar array and separating smaller particles from larger particles. The platform was then used to remove cumulus cells from oocytes. CR under different actuation powers, time exposures, and hyaluronidase (HA) concentrations was optimized. The CR of up to 23 oocytes was accomplished simultaneously without any oocyte loss. Finally, mouse cumulus-oocyte complexes (COCs) were inseminated and CR was performed using both manual pipetting (control) and VIF. No statistical difference was observed in the fertilization and blastocyst rates, which were 90.7%, and 50.0% using manual pipetting, respectively, and 93.1% and 43.1% using VIF respectively. This platform automates CR process and reduces the technical manual labor involved in ART, paving the way for standardization and consistency within ART protocols.

IntroductionHyaluronic acid (HA) fillers are generally safe; however, the most significant complication is vascular occlusion. Several therapeutic protocols have been proposed for managing ischemia. De Lorenzi introduced the HDPH protocol, which uses a minimum of 500 IU of hyaluronidase (HYAL) per ischemic area.Materials and methodsThis case series study evaluates the efficacy of a novel protocol, “THIS and FAT,” for managing ischemia resulting from filler-induced vascular occlusion (FIVO). The protocol builds on elements from previous approaches while introducing combination therapies specifically tailored to address ischemia. The therapeutic regimen includes T: botulinum toxin type A (BTX-A), H: high-dose HYAL, I: injectable platelet-rich fibrin (iPRF), S: serum platelet-rich fibrin (sPRF), a: aspirin and antibiotics, n: nanofat, d: debridement and dermabrasion, and F: fat membrane application.ResultsA total of 25 eligible patients, including 20 women and 5 men with a mean age of 32.36 ± 6.71 years, were included. The THIS and FAT protocol involved the injection of BTX-A and HYAL, with mean doses of 50.68 ± 60.79 Units and 5970.0 ± 2791.65 IU, respectively. Additionally, iPRF and sPRF were applied to the ischemic wound surface. Debridement was performed for ischemia classified as stage three or higher. Notably, 92% of patients treated with the THIS and FAT protocol showed complete improvement without scar formation.Conclusion“THIS and FAT” Protocol for managing ischemia following FIVO shows promising outcomes. Additionally, wound management with fat membrane, iPRF injections, sPRF dressing, and nanofat application resulted in favorable outcomes in this case series.

BackgroundThe mainstay of treatment for adverse events to hyaluronic acid filler is the use of hyaluronidase (HYAL); however, the dose and dilution are not standardized.ObjectivesThe objective of this study was to examine differential dilutions and concentrations of HYAL, and to compare the effectiveness of ovine and human HYAL.MethodsFillers were selected for study based on a variety of rheologic factors. A 0.2-mL dose of product was selected for use based on previous studies. Degradation was assessed by comparing both ovine and recombinant HYAL over a range of concentrations and dilutions.ResultsIn the 2:1 dilution group, Restylane Lidocaine (Galderma, Lausanne, Switzerland) was degraded by 100 U of ovine HYAL after 50 minutes. No other filler was completely degraded; Restylane Lyft (Galderma) was partially degraded after 1 hour of treatment with 100 U of HYAL. In both the 3:1 and 4:1 dilution groups, Restylane Shaype (Galderma) and Restylane Lyft fillers were most susceptible to degradation, dissolving within 30 minutes with 100 U of recombinant HYAL and within 40 minutes with 100 U of ovine HYAL. Juvéderm and RHA4 fillers were the most resistant, requiring 300 U of HYAL for degradation within 1 hour. Beyond a 3:1 dilution ratio, no further improvement was observed.ConclusionsThis study demonstrates that 300 U of hyaluronidase is sufficient to degrade 0.2 mL of the most resistant hyaluronic acid fillers within 1 hour. Importantly, a minimum dilution of 3:1 should be used to provide adequate fluid for dissolving filler. Ovine HYAL appears to be just as effective as recombinant HYAL in terms of dissolving product.

ABSTRACTBackgroundHyaluronic acid (HA) fillers are popular for their minimally invasive nature and immediate aesthetic outcomes, but vascular compromise remains a significant complication. This study investigates optimized therapeutic strategies to prevent tissue necrosis following HA filler injections.AimsTo evaluate the efficacy of two treatment regimens for managing impending nasal skin necrosis due to HA filler injections, focusing on preventing tissue necrosis and reducing complications such as pigmentation changes, scarring, and telangiectasia.Patients and MethodsA retrospective analysis was conducted on 41 female patients (mean age: 36.2 years) treated at a single referral center between 2018 and 2023. Patients presented within 72 h after developing ischemic symptoms following HA injections for nasal augmentation. Two treatment regimens, both integrating hyperbaric oxygen therapy (HBOT), epidermal growth factor (EGF) gel, and corticosteroids, were evaluated: one using nitroglycerin (NTG) and the other using isosorbide dinitrate (ISDN).ResultsAll patients achieved complete wound healing, with no significant differences in scar formation or hypotension between the treatment groups (p > 0.05). Hyaluronidase (HSE) was administered externally at referring clinics prior to hospital admission in 31.7% of patients (without subsequent standardized HSE protocol), significantly reducing telangiectasia incidence (p < 0.05) but not affecting scarring or pigmentation (p > 0.05). Early hospital presentation (< 48 h) was associated with lower pigmentation changes (p < 0.05) but did not significantly affect scarring. Residual complications included scar formation in 9 of 41 patients (21.9%, 95% CI 12.0–36.7), telangiectasia in 16 of 41 (39.0%, 95% CI 25.7–54.3), and pigmentation changes in 22 of 41 (53.7%, 95% CI 38.7–67.9).ConclusionsCombined therapies effectively manage HA‐induced vascular compromise, with early intervention critical for reducing ischemic complications and improving patient outcomes.

Hyaluronic acid (HA) is a key component of the extracellular matrix involved in regulating inflammation, fibrosis, and tissue repair. Its biological properties depend on molecular weight: high-molecular-weight HA (HMW-HA) exhibits anti-inflammatory effects, whereas low-molecular-weight fragments (LMW-HA) induce inflammation and fibrosis by activating CD44, TLR, and RHAMM receptors. An imbalance between these forms may contribute to chronic inflammatory and fibrotic processes. HA metabolism is regulated by synthases (HAS) and hyaluronidases (HYAL). During chronic inflammation, HYAL-2 degrades HMW-HA into LMW-HA, which accumulates and sustains the inflammatory response. Native hyaluronidase preparations have limited efficacy due to rapid inactivation. Conjugation of the enzyme with azoximer enhances its resistance to inhibitors and proteases while prolonging its action. Bovhyaluronidase azoximer (Longidaza) breaks down pro-inflammatory LMW-HA into safe ultra-low-molecular-weight fragments, suppressing inflammation and fibrosis. The drug is active in the acidic environment of inflamed tissues without damaging healthy tissue. Its anti-fibrotic and anti-adhesive properties have been confirmed experimentally and clinically. Clinical studies demonstrate the drug’s efficacy in various fields: preventing postoperative adhesions, treating fibrotic changes in pulmonology, and correcting scars in dermatology. Thus, modulation of HA metabolism using conjugated hyaluronidase represents a promising approach for managing chronic inflammatory and fibrotic conditions.

OBJECTIVE: Hyaluronidases (HYAse) break down hyaluronic acid, which is found in high levels in the cumulus-oocyte complex during oocyte preparation for IVF. Using HYAse, we aimed to investigate whether a growth factor, midkine (MK), has a role in the proliferation and viability of cumulus cells (CCs) during the denudation process. STUDY DESIGN: A prospective, randomized study was done with 90 females aged 21-40 undergoing ICSI from September 2017 to September 2018. CCs were cultured via a mechanical application from male factor cases at the IVF clinic of a private hospital. HYAses in concentrations of 0.1 IU/mL (The lowest concentration), 1 IU/mL, and 10 IU/mL (The highest concentration) were applied to CCs. Every 48 hours of 24 hours, cell proliferation and apoptosis indices (Flow cytometry) with MK levels (ELISA) and the ultrastructure of cumulus cells (TEM) at the 48th were evaluated. A one-way ANOVA test was used, and P&lt;0.05 was considered statistically significant. RESULTS: All concentrations decreased the cumulus cell numbers for 48 hours. The highest decrease in cell number was detected at the highest concentration at the 48th h. In concordance with this result, the highest increase in apoptotic and dead cell rates with the lowest viable cell rate was detected at the highest concentration at the 48th h. The highest concentration led to the highest decrease in MK levels at the 48th h. CONCLUSIONS: HYAse inhibits the proliferation of CCs by inhibiting MK in a time and concentration-dependent manner.

Innovative separation of melittin from bee venom using micro-free-flow electrophoresis: An experimental and theoretical study.

Failed back surgery syndrome is a common problem faced by chronic pain management specialists. Steroid-only epidural injections have modest efficacy because of excessive scarring. Epidural hyaluronidase (HA), functions as a depolymerizing agent, successfully breaking down adhesions and collagen bundles, whereas dexmedetomidine (DEX) helps to reduce inflammation. The current study is a randomized, double blind, clinical trial. The study cohort included population with persistent (> 6 months) back and/or radicular lower limb pain after laminectomy. Group I (HA group) received bupivacaine 0.5% (5 mg), triamcinolone 40 mg, sterile saline (2 ml), and HA (1500 IU) instilled in 1 mL of distilled water. Group II (DEX group) received bupivacaine 0.5% (5 mg), triamcinolone 40 mg (1 ml), DEX (0.5 mcg/kg), and sterile saline (2 ml). Both groups showed significant reductions in VAS scores at all follow-ups compared to the pre-injection values. At 6 months, the DEX group experienced a significantly greater reduction in pain scores than the HA group (P = 0.003). In terms of the MODI, both groups showed significant reductions in disability scores at all follow-ups relative to the pre-injection values. The DEX group showed greater improvement in MODI values than the HA group. No significant complications were reported. Both DEX and HA yielded significant improvements in pain and disability scores compared with pre-injection levels. The DEX group showed a more substantial and long-term reduction in both pain scores and disability index than the HA group.

Comparative in-vitro degradation of hyaluronic acids exposed to different hyaluronidase enzymes.

Metagenomics and metabolomics to investigate the effect of Amygdalus mongolica oil on intestinal microbiota and serum metabolites in rats.

Oral submucous fibrosis (OSMF) is a potentially cancerous disorder that affects the oral mucosa and causes a range of symptoms. Therefore it is of interest to assessing the function of oral alpha lipoic acid as a therapy for OSMF is intriguing. Hence, fifty patients with OSMF symptoms were evaluated both before and after treatment. They were split into two groups: group A, which served as the control, received 1 ml steroid injection of thioacetamide and 1500 IU of hyaluronidase (HYAL) weekly along with the oral antioxidant α-lipoic acid for three months. Group B, which served as the case study, also received 3 months of steroid injection of thioacetamide and HYAL. Patients in group B were recalled for a clinical examination using a vernier caliper, and visual analog scale (VAS) and fibrous bands (FB) were assessed at the 1st, 3rd and 6th month. We found that controls had a comparable distribution pattern across visits when compared to the case. Treatment with alpha lipoic acid in conjunction with intralesional injection of thioacetamide and HYAL significantly reduced the severity of symptoms, especially burning sensation and mouth opening, in the case group over time, as previously determined.

Vascularized lymph node transfer (VLNT) is an advanced surgical approach for secondary lymphedema (SLE) treatment, but tissue fibrosis around the lymph node flap (VLNF) inhibiting lymphangiogenesis is the biggest challenge undermining its therapeutic efficacy. This study explored the effects of periodic hyaluronidase (HLD) injection in reducing fibrosis and promoting lymphangiogenesis in 52 Sprague–Dawley rats with a VLNF over 13 weeks. The results demonstrated that HLD administration significantly enhanced swelling reduction, lymphatic drainage efficiency, and lymphatic vessel regeneration, with up to a 26% decrease in tissue fibrosis around the VLNF. These findings suggest that combining VLNT with periodic injections of HLD could substantially improve SLE treatment outcomes in clinical settings. It offers a promising direction for future therapeutic strategies and drug development aimed at increasing the efficacy of surgical treatment for SLE patients.

Introduction. The lymphatic system plays a key role in spreading pathogens, including those causing intraabdominal infections. An urgent task of pharmacology is to create methods for the targeted delivery of antibiotics to lymphatic vessels and intestinal tissues. One approach is to use agents acting as endolymphatic conductors to achieve a high drug concentration in the lymphatic system. Aim. To evaluate the effect of various drugs on the concentration of cefotaxime, a third-generation antibiotic, in blood and intestinal tissues, as well as on lymphatic drainage in experiments on mice. Materials and methods. We investigated the effect of hyaluronidase (HLRD), bovgialuronidase azoximer (BovGLRD+Az), terrilitin (TRL), papaya milky juice (PMJ ), sodium heparin (HepS ), aprotinin (APRT), azoximer bromide (AzBrom), furosemide (FRSD) and sodium deoxyribonucleate (DRN) on the removal time of lymphotropic dye from mouse mesentery and the cefotaxime concentration in blood plasma and intestinal tissues by high-performance liquid chromatography. Results. HLRD reduced the time of dye removal from the mesentery by 26.2%, BovGLRD+Az – by 33.5%, TRL – by 36%, PMS – by 23.1%, HepS – by 30.1%, APRT – by 34.6%. The differences in lymphostimulating activity between these drugs were not statistically significant. AzBrom and FRSD increased the dye removal time by 8.3% and 6%, respectively; the DRN had no effect. HLRD, BovGLRD, TRL, PMJ, HepS and APRT increased the CF concentration in blood and intestinal tissues 1.5 and 24 hours after injection, in contrast to the single injection of antibiotic. AzBrom increased the CF concentration only after 1.5 hours. FRSD increased the antibiotic concentration in intestinal tissues but not in blood plasma. The DRN did not affect the studied indicators. Conclusion. Lymphostimulating drugs HLRD, BovGLRD, TRL, PMJ, HepS and APRT effectively direct the antibiotic to the lymphatic system and can be used for lymphotropic therapy.

Despite extensive advances in cancer research, glioblastoma (GBM) still remains a very locally invasive and thus challenging tumor to treat, with a poor median survival. Tumor cells remodel their microenvironment and utilize extracellular matrix to promote invasion and therapeutic resistance. We aim here to determine how GBM cells exploit hyaluronan (HA) to maintain proliferation using ligand-receptor dependent and ligand-receptor independent signaling. We use tissue engineering approaches to recreate the three-dimensional tumor microenvironment in vitro, then analyze shifts in metabolism, hyaluronan secretion, HA molecular weight distribution, as well as hyaluronan synthetic enzymes (HAS) and hyaluronidases (HYAL) activity in an array of patient derived xenograft GBM cells. We reveal that endogenous HA plays a role in mitochondrial respiration and cell proliferation in a tumor subtype dependent manner. We propose a tumor specific combination treatment of HYAL and HAS inhibitors to disrupt the HA stabilizing role in GBM cells. Taken together, these data shed light on the dual metabolic and ligand - dependent signaling roles of hyaluronan in glioblastoma.

BackgroundSynovial fluid (SF) is often used for diagnostic and research purposes as it reflects the local inflammatory environment. Owing to its complex composition, especially the presence of hyaluronic acid, SF is usually viscous and non-homogeneous. The presence of high-molar-mass hyaluronan in this fluid gives it the required viscosity for its function as a lubricant. Viscosity is the greatest major hydraulic attribute of the SF in articular cartilage.MethodsEmpirical modeling of previously published results was performed. In this study, we explored the flow of a non-Newtonian fluid that could be used to model the SF flow. Analyzing the flow in a simple geometry can help explain the model’s efficacy and assess the SF models. By employing some viscosity data reported elsewhere, we summarized the dynamic viscosity values of normal human SF of the knee joints in terms of time after injecting hyaluronidase (HYAL) at 25°C. The suggested quadratic behavior was obtained through extrapolation. For accurate diagnosis or prediction, the comparison between three specific parameters (ai, t0, and ln η0) was made for normal and pathological cases under the same experimental conditions for treatment by addition of HYAL and for investigation of the rheological properties. A new model on the variation of viscosity on the SF of knee joints with time after injection of HYAL with respect to normal and postmortem samples at different velocity gradients was proposed using data previously reported elsewhere.ResultsThe rheological behavior of SF changes progressively over time from non-Newtonian to a Newtonian profile, where the viscosity has a limiting constant value (η0) independent of the gradient velocity at a unique characteristic time (t0 ≈ 8.5 h). The proposed three-parameter model with physical meaning offers insights into future pathological cases. The outcomes of this work are expected to offer new perspectives for diagnosis, criteria, and prediction of pathological case types through comparisons with new parameter values treated under the same experimental conditions as HYAL injection. This study also highlights the importance of HYAL treatment for better intra-assay precision.

The rising use of soft tissue fillers for aesthetic procedures has seen an increase in complications, including vascular occlusions and neurological symptoms that resemble stroke. This study synthesizes information on central nervous system (CNS) complications post-filler injections and evaluates the effectiveness of hyaluronidase (HYAL) treatment. A thorough search of multiple databases, including PubMed, EMBASE, Scopus, Web of Science, Google Scholar, and Cochrane, focused on publications from January 2014 to January 2024. Criteria for inclusion covered reviews and case reports that documented CNS complications related to soft tissue fillers. Advanced statistical and computational techniques, including logistic regression, machine learning, and Bayesian analysis, were utilized to dissect the factors influencing therapeutic outcomes. The analysis integrated findings from 20 reviews and systematic analyses, with 379 cases reported since 2018. Hyaluronic acid (HA) was the most commonly used filler, particularly in nasal region injections. The average age of patients was 38, with a notable increase in case reports in 2020. Initial presentation data revealed that 60.9% of patients experienced no light perception, while ptosis and ophthalmoplegia were present in 54.3 and 42.7% of cases, respectively. The statistical and machine learning analyses did not establish a significant linkage between the HYAL dosage and patient recovery; however, the injection site emerged as a critical determinant. The study concludes that HYAL treatment, while vital for managing complications, varies in effectiveness based on the injection site and the timing of administration. The non-Newtonian characteristics of HA fillers may also affect the incidence of complications. The findings advocate for tailored treatment strategies incorporating individual patient variables, emphasizing prompt and precise intervention to mitigate the adverse effects of soft tissue fillers. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The glycocalyx (GC) is a densely structured, gel-like matrix that coats the inner lining of the vascular endothelium. The GC plays a pivotal role in regulating the integrity of the vascular endothelium, primarily through mechano-sensing and -transducing shear stress, while also preserving endothelial barrier function. With advancing age, the GC deteriorates concomitantly with its essential constituent, hyaluronan (HA), which may lead to endothelial dysfunction. Therefore, we hypothesized that advanced age and reduced HA synthesis alone or together will impair GC integrity resulting in endothelial dysfunction. We have generated a tamoxifen-inducible, endothelial cell-specific, knockout mouse model of a hyaluronan producing enzyme, hyaluronan synthase 2 (HAS2), in young (4-6 mo) and old (22-23 mo, n=9-12/group). HAS2 mRNA expression in carotid endothelial cell lysates were reduced by ~47% in endothelial cell HAS2 knockout (ecHAS2KO) vs wildtype (ecHAS2WT, p=0.004) after tamoxifen treatment. The perfused boundary region (PBR), indicative of GC barrier function, was evaluated in vivo in the mesenteric microcirculation. The PBR was significantly impaired with aging (young vs old ecHAS2WT, p=0.047) and genotype (young ecHAS2WT vs KO, p=0.012) but there was no additive effect of aging and genotype (old ecHAS2WT vs KO, p=0.989). Subsequently, GC thickness was determined by measuring the depth of GC collapsed by leukocyte passage through the mesenteric segments. GC thickness was diminished by ~53% with aging (young vs old ecHAS2WT, p&lt;0.0001) and ~59% with genotype (young ecHAS2WT vs KO, p&lt;0.0001) but there was no synergistic effect of aging and genotype (old ecHAS2WT vs KO, p=0.893). Mechano-sensing and -transducing properties of the GC were assessed using ex vivo flow-induced vasodilation in isolated carotid arteries with and without the intra-luminal infusion of HA degrading enzyme, hyaluronidase (HYAL). Flow-induced vasodilation was diminished with aging (young vs old ecHAS2WT, p&lt;0.0001) but this age-related decline was dampened with HYAL (p=0.212). The vasodilatory response to flow was reduced with genotype (young ecHAS2WT vs KO, p&lt;0.0001) but this effect was weakened with HYAL (p=0.953). There was no augmentative effect of aging and genotype with and without HYAL (all p≥0.883). Acetylcholine induced endothelium-dependent dilation (EDD), a measure of endothelial function, was examined ex vivo in isolated mesenteric arteries. The maximal EDD was diminished by ~23% with aging (young vs old ecHAS2WT, p=0.04) but not genotype (young ecHAS2WT vs KO, p=0.962). There was an additive reduction in maximal EDD by ~46% with aging and genotype (old ecHAS2KO vs WT, p=0.021). Endothelium-independent dilation in response to sodium nitroprusside, an exogenous nitric oxide donor, was not different across groups with either aging, genotype, or both (ALL p&gt;0.05). In conclusion, aging and reduced HA synthesis independently impaired GC integrity. As a result, mechano-sensing and -transducing property of GC was disturbed and further diminished by HYAL activity. In addition, endothelial function was impaired with aging and further exacerbated after a reduction in HA synthesis. Funded in part by awards from National Institutes of Health Awards R01 AG060395, R01 AG077751, R01 AG076748, T32 HL007576, T32 HL139451, Veteran's Affairs Merit Review Award I01 BX004492 and Nora Eccles Treadwell Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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

Elevated fluid and glycosaminoglycan content in the Achilles tendon contribute to higher intratendinous pressures: Implications for Achilles tendinopathy