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Hyaluronan (HA) levels are dynamically regulated homeostatically through biosynthesis and degradation. HA homeostasis is often perturbed under disease conditions. HA degradation products are thought to contribute to disease pathology. The hyaluronidase CEMIP requires the presence of living cells for its HA depolymerizing activity. CEMIP is overexpressed in a variety of pathological conditions, and the inhibition of its hyaluronidase activity therefore has therapeutic potential. To identify novel inhibitors of the CEMIP hyaluronidase activity, we established here a cell-compatible, medium-throughput assay for CEMIP-dependent HA depolymerization. The assay employs ultrafiltration plates to separate low- from high-molecular-weight HA, followed by quantification of HA fragments using an HA ELISA-like assay. Using this assay, we tested a range of compounds that have been reported to inhibit other hyaluronidases. Thereby, we identified several sulfated hydrocarbon polymers that inhibit CEMIP more potently than other hyaluronidases. One of these is heparin, a sulfated glycosaminoglycan produced by mast cells that constitutes the first described physiological CEMIP inhibitor. The most potent inhibitor (IC50 of 1.8 nM) is dextran sulfate, a synthetic sulfated polysaccharide. Heparin and dextran sulfate are used in numerous established and experimental biomedical applications. Their ability to inhibit CEMIP needs to be taken into account in these contexts. [ABSTRACT FROM AUTHOR]

Skin aging is characterized by progressive loss of functionality and regenerative potential of the skin, resulting in the appearance of wrinkles, irregular pigmentation, a decrease of elasticity, dryness, and rough texture. Damage to the skin caused by oxidative stress could substantially be slowed down by the use of phytochemicals that function as natural antioxidants. Although phytochemicals have immense potential as anti-aging medicines, their effectiveness as therapeutic agents is restricted by their poor solubility, biodistribution, stability, and hydrophilicity. Given their improved stability, solubility, efficacy, and occlusive properties, nanoformulations have emerged as promising drug delivery platforms for phytochemicals to achieve anti-aging effects. The efficacy of these nanoformulated phytochemicals in suppressing enzymes that accelerate skin aging, such as collagenase, tyrosinase and hyaluronidase, as well as enhancing superoxide dismutase, catalase, and collagen levels to improve skin appearance during aging has been demonstrated. [ABSTRACT FROM AUTHOR]

The evolving oncology treatment paradigm has created an unmet need for administration options that improve patient experiences and health care efficiencies. CheckMate 67T (NCT04810078) was a phase III, open-label, multicenter, noninferiority trial in which patients with advanced/metastatic clear cell renal cell carcinoma were randomized to subcutaneous nivolumab (1200 mg every 4 weeks; coformulated with recombinant human hyaluronidase PH20 20 000 units) or intravenous nivolumab (3 mg/kg every 2 weeks). The primary objective was to assess the noninferiority of subcutaneous versus intravenous nivolumab by coprimary endpoints determined from a population pharmacokinetics analysis [time-averaged serum concentration over the first 28 days (C avgd28), and minimum steady-state serum concentration (C minss); noninferiority threshold: lower boundary of 90% confidence interval (CI) of the geometric mean ratios (GMR) ≥0.8]. Objective response rate (ORR) was a key secondary endpoint powered for noninferiority [noninferiority threshold: lower boundary of 95% CI of relative risk of ORR (subcutaneous versus intravenous nivolumab) ≥0.60]. Overall, 495 patients were randomized. Relative exposure in the subcutaneous versus intravenous arm reported by the GMR of C avgd28 and C minss was 2.098 (90% CI 2.001-2.200) and 1.774 (90% CI 1.633-1.927), respectively. After 8 months of minimum follow-up, ORR was 24.2% with subcutaneous nivolumab (95% CI 19.0%-30.0%) versus 18.2% with intravenous nivolumab [95% CI 13.6%-23.6%; relative risk: 1.33 (95% CI 0.94-1.87)]. Coprimary endpoints and ORR met noninferiority thresholds. Additional efficacy and safety measures were similar. Subcutaneous nivolumab was noninferior to intravenous nivolumab based on pharmacokinetics and ORR. No new safety signals were observed. • There is an unmet need in oncology for administration options that improve patient experiences and health care efficiencies. • This phase III noninferiority trial compared subcutaneous nivolumab with intravenous nivolumab in renal cell carcinoma. • Subcutaneous nivolumab was noninferior to intravenous nivolumab based on pharmacokinetics and ORR. • The safety profile was consistent between arms and no new safety concerns were reported with subcutaneous nivolumab. • Our findings support subcutaneous nivolumab as an option to reduce treatment burden and improve health care efficiency. [ABSTRACT FROM AUTHOR]

Hyaluronidase has been emerging as a potential target for cancer treatment. Herein, the anticancer effects against A549 NSCLC cells and hyaluronidase inhibitory activity of the ethanol extract of Xenostegia tridentata (L.) D.F. Austin & Staples and its subfractions were investigated. In correlation with their hyaluronidase inhibition, the hexane subfraction exhibited the most potent cytotoxicity, and the ethyl acetate subfraction could significantly inhibit the cancer cell migration. The hexane and ethyl acetate fractions were then further isolated to identify the active compounds responsible for the anticancer and hyaluronidase inhibitory activities. Among the 10 isolated compounds, lutein (5), a previously reported anti-lung cancer agent, showed the strongest inhibition on hyaluronidase enzyme activity. Its anticancer activities were validated. Notably, in addition to demonstrating the potential of X. tridentata extract for NSCLC treatment, this study discloses that hyaluronidase is a potential target for the anticancer activities of lutein. The cellular mechanisms underlying the hyaluronidase inhibitory activity of X. tridentata extract need to be further explored to fully understand how this inhibition contributes to its anti-cancer effects. [ABSTRACT FROM AUTHOR]

Hops (Humulus lupulus L.) are widely recognized for their use in brewing, but they also possess significant pharmacological properties due to their rich bioactive compounds, with many varieties exhibiting diverse characteristics. This study investigates the chemical composition and biological activities of extracts from six hop varieties, focusing on quantifying xanthohumol and lupulone using High-Performance Liquid Chromatography (HPLC) and Total Phenolic Content (TPC) analysis. The hop varieties demonstrated significant variability in bioactive compound concentrations, with Aurora showing the highest xanthohumol (0.665 mg/g) and Zwiegniowski the highest lupulone (9.228 mg/g). TPC analysis revealed Aurora also had the highest phenolic content (22.47 mg GAE/g). Antioxidant activities were evaluated using DPPH, ABTS, CUPRAC, and FRAP assays, with Aurora and Oregon Fuggle displaying the most potent capacities. Aurora, in particular, showed the highest activity across multiple assays, including significant acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase inhibition, with IC50 values of 24.39 mg/mL, 20.38 mg/mL, and 9.37 mg/mL, respectively. The chelating activity was also assessed, with Apolon demonstrating the strongest metal ion binding capacity (IC50 = 1.04 mg/mL). Additionally, Aurora exhibited the most effective hyaluronidase inhibition (IC50 = 10.27 mg/mL), highlighting its potential for anti-inflammatory applications. The results underscore the influence of genetic and environmental factors on the bioactive compound profiles of hop varieties and their biological activity offering promising avenues for pharmaceutical and nutraceutical applications. However, further studies are needed to fully understand the potential interactions between hop cones components. [ABSTRACT FROM AUTHOR]

Background: Voice disorders, resulting from structural or functional changes in the larynx, affect about 30% of the population. Larynx structural or functional changes that affect the speaker's functional requirements can be the cause of these disorders. In this study we aim assess voice after hyaluronidase injection in MAPLs of the vocal fold by voice handicap index. Methods: This prospective cohort research involved 24 cases diagnosed as benign vocal fold lesions who underwent vocal fold injection of the hyaluronidase (HAase) enzyme in the phoniatric unit, ENT department, faculty of medicine, Zagazig University, from June 2022 until December 2023.Results: There was significant distinction among voice handicap index scores at different periods. There wasn't a statistically significant distinction among the two studied maneuvers with regarding the voice handicap index at baseline. There was a statistically significant distinction among the two maneuvers studied with regarding the voice handicap index at 1 month. There wasn't a statistically significant distinction among the two studied maneuvers with regarding the voice handicap index at 3 months. Conclusion: In minimally associated pathological lesions (MAPLs) (Reinke's edema, polyps, & asymmetrical nodules), HAase enzyme injection is effective in improving voice, according to the results of the vocal handicap index. [ABSTRACT FROM AUTHOR]

Introduction: For upper limb procedures using the supraclavicular approach to brachial plexus block, various adjuncts to Local Anaesthetics (LA) have been employed to improve the quality and duration of anaesthesia and postoperative analgesia without leading to any adverse side-effects or prolonging the period of motor block. Hyaluronidase is an enzyme used with other drugs to accelerate their dispersion and distribution. It catalyses the hydrolysis of a component of the extracellular matrix, hyaluronan, thereby lowering its viscosity and improving tissue permeability. Aim: To evaluate the sensory and motor blockade resulting from the addition of hyaluronidase as an adjuvant to LA in Peripheral Nerve Stimulator (PNS)-guided Supraclavicular Brachial Plexus Block (SBPB). Materials and Methods: This prospective, comparative, double-blinded, randomised controlled study was conducted in a Department of Anaesthesiology S.B.K Shah Medical Institute and Research Centre, Vadodara, Gujarat, India at a tertiary care hospital on 72 patients undergoing elective upper limb surgeries under PNS-guided SBPB over 18 months from November 2022 to August 2024. Group B (n=36) received inj. bupivacaine (0.5%) 13 mL, inj. lignocaine with adrenaline (2%) (1:200,000) 13 mL, and inj. normal saline (0.9%) 4 mL, for a total of 30 mL, and Group H (n=36) received inj. bupivacaine (0.5%) 10 mL, inj. lignocaine with adrenaline (2%) (1:200,000) 10 mL, inj. hyaluronidase (900 IU) 6 mL, and inj. normal saline (0.9%) 4 mL, for a total of 30 mL. Sensory and motor blockade and rescue analgesia were recorded at 0, 1, 3, 5, 7, and 10 hours. Categorical variables were analysed using the Chi-square test. To analyse continuous variables, the student's t-test was used. The p-value of less than 0.05 was deemed statistically significant. Results: The onset time of sensory and motor block was earlier with Group H (2.36±0.25 minutes and 4.2±0.29 minutes) than with Group B (4.54±0.25 minutes and 6.51±0.29 minutes), respectively (p<0.05). The sensory and motor block lasted longer in Group B (278.8±7 minutes and 266.8±6.78 minutes) than in Group H (263.2±7 minutes and 246.3±6.78 minutes) respectively, p<0.05. The duration of analgesia was longer with Group B (240.8±7.84 minutes) compared to Group H (220±7.84 minutes) p<0.05. No major adverse effects were observed. Conclusion: Addition of hyaluronidase to a lower volume of LA results in rapid onset of the block with minimal side-effects. [ABSTRACT FROM AUTHOR]

Background Hyaluronidase is an ubiquitous enzyme, present, among others, in hymenoptera venom and in medical formulations. The latter include use as an emergency treatment or to correct undesired outcomes of medical and aesthetic procedures using hyaluronic acid fillers. Objectives By performing detailed allergy work-ups including skin-prick tests (SPTs) we investigated whether patients with a history of allergic reaction to hymenoptera venom are also sensitized to medical grade hyaluronidase. Methods Ninety patients with a history of type-1 reaction to hymenoptera venom with and without a history of previous specific venom immunotherapy were included in the study. All underwent SPTs for medical hyaluronidase. All patients also underwent serological analysis for Api m2, the only commercially available IgE test for a hymenoptera hyaluronidase. Results Of the 90 patients with previous type-1 reactions to hymenoptera venom hyaluronidase included in the study, 60 had undergone previous venom immunotherapy; 30 did not. The majority (73 of 90) were allergic to wasps, followed by honeybees (14 of 90) and three were allergic to both. Neither patients having undergone previous immunotherapy nor those allergic to bees showed positive SPTs to medical hyaluronidase. Of those with a wasp allergy and naïve to immunotherapy, over 20% (5 of 23) showed positive SPTs to medical hyaluronidase. Healthy controls (0 of 30) without previous allergic reactions to hymenoptera did not show positive SPTs to medical hyaluronidase. Conclusions Sensitization to hyaluronidase is most common in wasp-allergic patients who have not had previous specific immunotherapy. As allergic reactions to medical hyaluronidase are reported to be scarce, this group is probably at the highest risk to develop anaphylaxis to medical hyaluronidase. While all patients with untreated anaphylaxis to hymenoptera venom should consult an allergy specialist, it is particularly important that those with untreated wasp allergies seek specialist advice before treatment with medical hyaluronidase is initiated. [ABSTRACT FROM AUTHOR]

Summary: To improve the utilisation of abomasum and explore the material basis of its antioxidant and hyaluronidase inhibitory activities, a homogeneous protein RDA4‐1 was isolated from the abomasum of cultured red deer by two‐step chromatography process for the first time in this study. It has a molecular weight of 15 kDa and comprises 43.56% essential amino acids. RDA4‐1 scavenged 50.97% of DPPH• and 88.37% of ABTS+· at 1.5 mg mL−1, and inhibited hyaluronidase by 79.23% at 1 mg mL−1. The CD and fluorescence spectroscopy was used to initiate explore the hyaluronidase inhibition reaction process. With an increase in the concentration of RDA4‐1 in the inhibition reaction, the wavelength of the negative peak of CD shifted from 208 to 218 nm, and the absorption of the positive peak of CD increased from 0.5 to 8.3 mdeg. Furthermore, fluorescence absorption at a wavelength of 340 nm rose from 248 to 762 au. These findings suggest that the interaction of RDA4‐1 with hyaluronidase induces alterations in the secondary structure of the protein complex, and RDA4‐1 binds reversibly to the enzyme in a non‐covalent manner. The results of this study indicate that RDA4‐1 could serve as a potential hyaluronidase inhibitor in the development of nutraceuticals. [ABSTRACT FROM AUTHOR]

The Loxosceles genus represents one of the main arachnid genera of medical importance in Brazil. Despite the gravity of Loxosceles- related accidents, just a handful of species are deemed medically important and only a few have undergone comprehensive venom characterization. Loxosceles amazonica is a notable example of a potentially dangerous yet understudied Loxosceles species. While there have been limited reports of accidents involving L. amazonica to date, accidents related to Loxosceles are increasing in the North and Northeast regions of Brazil, where L. amazonica has been reported. In this work, we provide a complementary biochemical and immunological characterization of L. amazonica venom, considering its most relevant enzymatic activities and its immunorecognition and neutralization by current therapeutic antivenoms. Additionally, a cDNA library enriched with phospholipase D (PLD) sequences from L. amazonica venom glands was built and subsequently sequenced. The results showed that L. amazonica venom is well immunorecognised by all the tested antibodies. Its venom also displayed proteolytic, hyaluronidase, and sphingomyelinase activities. These activities were at least partially inhibited by available antivenoms. With cDNA sequencing of PLDs, seven new putative isoforms were identified in the venom of L. amazonica. These results contribute to a better knowledge of the venom content and activities of a synanthropic, yet understudied, Loxosceles species. In vivo assays are essential to confirm the medical relevance of L. amazonica, as well as to assess its true toxic potential and elucidate its related pathophysiology. [Display omitted] • Loxosceles amazonica is a synanthropic spider found in northern Brazil, extending to the North of Minas Gerais. • L. amazonica venom (Lam V) is immunorecognized by therapeutic antivenoms and by anti-phospholipase-D antibodies. • LamV shows sphingomyelinase-D, gelatinase, and hyaluronidase activities in vitro, inhibited by therapeutic antivenoms. • New isoforms of phospholipases D are described in Lam V. [ABSTRACT FROM AUTHOR]

Coffee silverskin (CS), the main by-product of coffee roasting production, contains various valuable bioactive compounds in its chemical compositions. Hydrothermal water extraction (HDTE) is one of the promising techniques for valorizing the organic fraction of CS into functional bioactive ingredients, which can be further exploited in various applications. This study aimed to evaluate the hyaluronidase and α-glucosidase inhibition activities of the CS extracts obtained under optimized water extraction conditions. Process optimization was performed using central composite design response surface methodology (CCD-RSM) with a broader range of extraction temperatures (25, 137.5, and 250 °C), reaction times (5, 38.5, and 72 min), and solid-to-liquid ratios (1:10, 1:80, and 1:150). The highest yield of 39.62% was obtained at 137.5 °C, with a reaction time of 72 min and an S/L ratio of 1:80. The total caffeoylquinic acid contents (T-CQA) were quantified based on the sum of three major isomers, including 3-CQA, 4-CQA, and 5-CQA. The results revealed that the highest T-CQA (2.76 ± 0.20 mg/g CS) was significantly obtained (p < 0.05) by subcritical water extraction (SWE) at 143.2 °C with an S/L ratio of 1:10 and an extraction time of 10.41 min. At such conditions, the total phenolic content (TPC), antioxidant properties (AP), and caffeine were 96.13 mg gallic acid equivalence per gram (GAE/g) CS, 20.85 ± 0.17 mg Trolox equivalence per gram (TE/g) CS, and 10.84 ± 1.25 mg/g CS, respectively. The 50% inhibition capacity (IC50) of hyaluronidase and α-glucosidase inhibition of the CS extracted were 5.00 mg/mL and 9.00 mg/mL, respectively. Our results supported the potential direct or indirect applications of CS, such as hydrothermal CS extract (HDT-CSE), in functional food or drinks. Repurposing CS residue to manufacture new products can efficiently reduce the amount of organic waste in landfills, thus conserving resources and energy and contributing to a lower overall carbon footprint in coffee production. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions VYC‐25L is a robust, structural hyaluronic acid (HA) filler designed for facial volumizing, lifting, and contouring. It was first approved in 2019.A group of doctors with various specialties, who have used VYC‐25L extensively since it first became available in their countries (3–5 years), share clinical experience and guidance on optimal use.VYC‐25L has a unique rheological and physicochemical profile that provides elevated lift capacity and enhanced projection, significant moldability immediately after injection, high levels of tissue integration, reversibility with hyaluronidase, and a long duration of clinical effects—typically lasting at least 24 months. The properties of VYC‐25L have created new possibilities for nonsurgical facial medical aesthetics. However, as with any novel product, it is important that injectors recognize how best to use it for the benefit of patients. When first utilizing VYC‐25L, it is advisable to start with the chin and jawline to gain familiarity with the gel characteristics before moving into other facial areas, and to consider splitting treatment over two or more sessions. Attention must also be given to injection volume, with less product typically required with VYC‐25L compared to other fillers with similar indications. Key principles of good practice should be followed, including appropriate patient selection and pretreatment education, suitable choice of injection device and plane, aseptic technique, slow and careful administration method, and sufficient posttreatment follow‐up.By adhering to these principles, VYC‐25L can produce natural‐looking and highly durable outcomes without substantial safety concerns. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objective Method Results Conclusion Dermal filler‐induced alopecia is a rare yet significant complication of aesthetic procedures primarily associated with vascular occlusion and subsequent tissue ischemia. Hyaluronic acid (HA) fillers, though widely used for facial rejuvenation, can lead to adverse outcomes such as skin necrosis and hair loss, particularly in high‐risk areas like the temples and glabella.This case report aims to highlight the clinical presentation, diagnostic approach, and multidisciplinary management of filler‐induced alopecia, contributing to the existing literature with a comprehensive review of previously reported cases.A 21‐year‐old female presented with localized skin necrosis and alopecia four days after receiving 7 mL of HA filler injections in the temples, tear trough, and eyebrow glabella regions. Trichoscopy revealed follicular dropout and white dots, consistent with ischemic hair loss. Treatment included hyaluronidase injections (1500 units), intralesional corticosteroids, topical minoxidil, and CO2 laser therapy. Over 1 year of follow‐up, the patient achieved complete hair regrowth and resolution of facial scarring.Only 16 cases of filler‐induced alopecia have been documented, predominantly involving HA fillers. This case underscores the importance of early recognition and intervention with hyaluronidase to mitigate ischemic damage. The multidisciplinary management approach employed here demonstrates the potential for full cosmetic recovery.Filler‐induced alopecia, though rare, necessitates heightened awareness among dermatologists and aesthetic practitioners. Adhering to recommended injection techniques and dosages, alongside the judicious use of ultrasound guidance, can minimize risks and improve patient safety. [ABSTRACT FROM AUTHOR]

Desmoplasia is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC) that contributes significantly to treatment resistance. Approaches to enhance drug delivery into fibrotic PDAC tumors continue to be an important unmet need. In this study, we have engineered a tumor-colonizing E. coli-based agent that expresses both collagenase and hyaluronidase as a strategy to reduce desmoplasia and enhance the intratumoral perfusion of anticancer agents. Overall, we observed that the tandem expression of both these enzymes by tumor-colonizing E. coli resulted in the reduced presence of intratumoral collagen and hyaluronan, which likely contributed to the enhanced chemotherapeutic efficacy observed when used in combination. These results highlight the importance of combination treatments involving the depletion of desmoplastic components in PDAC before or during treatment. [ABSTRACT FROM AUTHOR]

Sensitization to cross-reactive allergens complicates identifying the culprit insect in Hymenoptera venom allergy via diagnostic tests. This study evaluates sensitization to hyaluronidases (Api m 2 from honey bee (Apis mellifera) venom, HBV; Pol d 2 from European paper wasp (Polistes dominula) venom, PDV; and Ves v 2.0101 and Ves v 2.0201 from yellow jacket (Vespula vulgaris) venom, YJV) and their cross-reactivity in allergic patients from Italy, Spain, and Germany using ImmunoCAPs, ELISA, and basophil activation tests. Sensitization rates were 45% for Api m 2 in HBV-allergic subjects, 25% for Pol d 2 in PDV-allergic individuals, and 20% and 10% for Ves v 2.0201 and Ves v 2.0101 in YJV-allergic patients, respectively. Patients primarily sensitized to Api m 2 showed minimal cross-reactivity to vespid hyaluronidases, whereas those primarily sensitized to Pol d 2 or Ves v 2.0201 exhibited IgE reactivity to Api m 2. Neither Pol d 2 nor Ves v 2.0201 triggered basophil activation. Cross-reactivity of Api m 2, Pol d 2, and Ves v 2.0201 depends on the primary sensitizing venom. Sensitization to Pol d 2 and Ves v 2.0201 remains below 25%, yet these patients may exhibit cross-reactivity to Api m 2. Conversely, HBV-allergic patients sensitized to Api m 2 show minimal reactivity to Pol d 2 or Ves v 2.0201. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Natural compounds are widely incorporated into cosmetic products for many purposes. Diterpenes often function as fragrances, enhancing the sensory experience of these formulations. However, current trends in cosmetic science aim to develop multifunctional products, where compounds traditionally used for texture or fragrance also possess biological activities that contribute to the product's efficacy. In this context, this study focuses on synthesizing derivatives of phytol—a compound already presents in cosmetic formulations—to enhance its anti-aging properties. The derivatives were synthesized through esterification with substituted benzoic and cinnamic acids, known for their antioxidant and enzyme inhibition properties. Reaction yields ranged from 91.0% to 5.2%, depending on the substituents in acid derivatives. The structures of the synthesized compounds were confirmed through NMR and MS techniques. Both the natural and newly synthesized derivatives were evaluated for their cosmeceutical potential using antioxidant assays and inhibition assays for tyrosinase, elastase, collagenase, and hyaluronidase. This work presents the first report of the synthesis and cosmetic evaluation of several of these derivatives. Comparing with phytol (1), which presented an IC50 of 77.47 µM, four of the derivatives presented improved tyrosinase inhibitory activity, with phytyl 4-methoxybenzoate being the most active (IC50 = 27.9 µM), followed by phytyl benzoate with an IC50 of 34.73 µM. Substitutions at other positions on the aromatic ring were less effective. Molecular docking studies confirmed that the modifications potentiated a stronger interaction between the synthesized compounds and tyrosinase. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by sustained fibrotic lesions. Orally administered drugs usually fail to efficiently penetrate the interstitial tissue and reach the lesions, resulting in low treatment efficiency. Luteolin (Lut) is a natural flavonoid, active metabolites of which possess antioxidant, anti‐inflammatory, anti‐fibrotic, and anti‐apoptotic properties. In this study, a nano‐formulation is developed by loading Lut into hyaluronidase nanoparticles (Lut@HAase). These Lut@HAase nanoparticles (NPs) exhibit small size and good stability, suitable for noninvasive inhalation and accumulation in the lungs, and hyaluronidase at the site of lesions can degrade hyaluronic acid in the interstitial tissue, enabling efficient penetration of Lut. Lut's therapeutic effect, when administered via NPs, is studied both in vitro (using MRC5 cells) and in vivo (using IPF mice models), and its anti‐fibrotic properties are found to inhibit inflammation and eliminate reactive oxygen species. Conclusively, this study demonstrates that Lut@HAase can improve lung function and enhance survival rates while reducing lung damage with few abnormalities during IPF treatment. [ABSTRACT FROM AUTHOR]

Hyaluronidase is an enzyme that breaks down primarily hyaluronic acid, thereby disrupting the structural integrity of the extracellular matrix (ECM) found in connective tissues, which is considered a virulence factor. The aim of this research was to study the effect of a plant-active compound (vasicine) that was separated from a plant sample as an inhibitor agent for the hyaluronidase enzyme that was isolated from Staphylococcus aureus, which is considered a virulence factor. 120 samples were randomly isolated from infected burns. The isolates showing highly hydrolyzed zones were identified. Cell growth as well as hyaluronidase activity are measured spectrophotometrically by the turbidity reduction assay. The results showed that 100 out of 120 clinical samples grew bacteria when cultured on blood agar medium. Also, it was found that of the 100 isolates, 56 (56%) belonged to S. aureus and had an inhibitory zone of hyaluronidase of 5–26 mm, and the inhibitory zone was increasing over time. [ABSTRACT FROM AUTHOR]

Background: Nonsurgical cosmetic procedures, particularly the use of hyaluronic acid (HA)‐based soft tissue fillers, are becoming increasingly popular. This trend has catalyzed the development of a plethora of HA‐based products differing in product characteristics, thereby catering to an ever‐widening spectrum of aesthetic applications. However, complications rise concomitant with the increasing number of procedures. Among the strategies to manage such adverse events is the enzymatic breakdown with hyaluronidase. Objective: To analyze the response of different HA‐based soft tissue filler materials to hyaluronidase injections. Methods: A total of 11 different HA‐based soft tissue fillers were evaluated using noninvasive ultrasound imaging to assess their behavior in response to hyaluronidase injections. The HA‐based soft tissue fillers were categorized according to their product characteristics into a structuring, volumizing, and lip volumizing group. Standardized injections of 0.2 cc were performed in chicken breast to simulate human tissue. Ultrasound measurements of width, height, and calculated volume were performed immediately after filler injection, 1 h and 24 h following hyaluronidase injection. Results: Regardless of the soft tissue filler analyzed, the most significant volume reduction occurred within the first h after applying hyaluronidase, with a 64.1% decrease from the initial volume. After 24 h, the total volume reduction reached 81.7%. No statistically significant differences were found when comparing the three groups at each follow‐up time period, except for the height measurement after 1 h. While width was statistically significant in all groups between the investigated follow‐up groups, the volume reduction was only statistically significant in the groups with the highest and second highest G' values (i.e., Group 1—structuring, Group 2—volumizing). Conclusion: The effectiveness of hyaluronidase in dissolving HA‐based fillers is initially independent of product characteristics of HA‐based fillers such as G‐prime, with increased efficacy in fillers with higher G‐prime values, as evidenced by significant volume reductions in such groups. [ABSTRACT FROM AUTHOR]

Hyaluronan (HA) is a glycosaminoglycan that forms a gel-like barrier in the subcutaneous (SC) space, limiting bulk fluid flow and the dispersion of SC-administered therapeutics. Recombinant human hyaluronidase PH20 (rHuPH20) facilitates the rapid delivery of co-administered therapeutics by depolymerizing HA in the SC space. Administration of rHuPH20 can induce the formation of anti-rHuPH20 antibodies, or anti-drug antibodies (ADAs), with the potential to bind endogenous PH20 hyaluronidase in the adult testes and epididymis. Using a variety of relevant animal models and multiple dose regimens of rHuPH20 across the full spectrum of animal development, we demonstrated that rHuPH20 administration resulted in the formation of ADAs. Although these ADAs can bind both the recombinant rHuPH20 enzyme and recombinant versions of animal model-specific hyaluronidases, they had no impact on fertility parameters (as measured by sperm concentration and motility, litter size, and litter viability) or fetal development. We present the result of our nonclinical studies in order of the developmental lifecycle, beginning with adults. Toxicology studies that extend beyond the standard package are also presented. These studies demonstrate the favorable safety profile of rHuPH20 and ADAs in nonclinical models. Additionally, we identified substantial safety margins for clinically relevant doses of rHuPH20. [Display omitted] • rHuPH20 facilitates subcutaneous administration of therapeutics. • Impact of rHuPH20 and anti-drug antibodies observed in multiple nonclinical models. • rHuPH20 anti-drug antibodies did not negatively alter fertility or development. • Substantial safety margins were identified when compared to human-equivalent doses. • Studies support favorable safety profile of rHuPH20. [ABSTRACT FROM AUTHOR]

Background: The safety, tolerability, and immunogenicity of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% (dual-vial unit of human immunoglobulin 10% and recombinant human hyaluronidase [rHuPH20]) were assessed in children with primary immunodeficiency diseases (PIDs). Methods: This phase 4, post-authorization, prospective, interventional, multicenter study (NCT03116347) conducted in the European Economic Area, enrolled patients aged 2 to < 18 years with a documented PID diagnosis who had received immunoglobulin therapy for ≥ 3 months before enrollment. New fSCIG 10% starters underwent fSCIG 10% dose ramp-up for ≤ 6 weeks (epoch 1) before receiving fSCIG 10% for ≤ 3 years (epoch 2); patients pretreated with fSCIG 10% entered epoch 2 directly. The primary outcome was the number and rate (per infusion) of all noninfectious treatment-related serious and severe adverse events (AEs). Results: In total, 42 patients were enrolled and dosed (median [range] age: 11.5 [3–17] years; 81% male; 23 new starters; 19 pretreated). Overall, 49 related noninfectious, treatment-emergent AEs (TEAEs) were reported in 15 patients; most were mild in severity (87.8%). No treatment-related serious TEAEs were reported. Two TEAEs (infusion site pain and emotional distress) were reported as severe and treatment-related in a single new fSCIG 10% starter. The rate of local TEAEs was lower in pretreated patients (0.1 event/patient-year) versus new starters (1.3 events/patient-year). No patients tested positive for binding anti-rHuPH20 antibodies (titer of ≥ 1:160). Conclusions: No safety signals were identified, and the incidence of local AEs declined over the duration of fSCIG 10% treatment. This study supports fSCIG 10% long-term safety in children with PIDs. Trial registration number (ClinicalTrials.gov): NCT03116347. [ABSTRACT FROM AUTHOR]

Background: Complications of temporary and permanent fillers have been extensively studied. However, there is a lack of comparative data regarding poly‐L‐lactic acid (PLLA), calcium hydroxyapatite (CaHA), and polycaprolactone (PCL) known as collagen biostimulators. Aims: This study addressed the complications of collagen biostimulators concerning their diagnosis, type of product, treatment, and monitoring. Patients/Methods: An electronic questionnaire was sent to Brazilian dermatologic ultrasound experts to identify complications related to biostimulators. The type of biostimulator, location of application, number of vials injected, application plan, time between injection treatment and complication, injector profile, treatment, and prognosis were assessed. Results: Fifty‐five cases were identified, of which 49.1% were caused by PLLA‐Elleva®, 23.6% by CaHA (alone or combined with hyaluronic acid), 20.0% by PLLA‐Sculptra®, and 7.3% by PCL. The most affected area was the face (72.7%), with nodules being the most common clinical form (89.1%), generally occurring late (60.0%) (>1 month). Only one case was injected at an incorrect depth (musculoaponeurotic system—SMAS). Despite several treatments, including saline (45.5%), hyaluronidase (25.5%), diluted corticosteroids (23.6%), and energy‐based devices (10.9%), only five cases showed complete resolution. Hyaluronidase was beneficial in complications related to fillers when there was an association of calcium hydroxyapatite with hyaluronic acid (p < 0.01). Conclusions: Complications from collagen biostimulators were more common on the face, typically manifesting about 1 month after treatment. These issues seemed to be related more to the properties of the products rather than inadequate technique. Furthermore, hyaluronidase demonstrated efficacy only in cases where there was an association with HA. [ABSTRACT FROM AUTHOR]

Introduction: Information about analyte stability is of crucial importance. The aims of this study were to determine the short- and long-term stability of synovial fluid calprotectin at various temperature conditions (4-8 °C for 7 days, - 20 °C and - 80 °C for 6 weeks). Materials and methods: Eleven samples from patients were included in this study. The samples were promptly transported at room temperature (RT) to the laboratory immediately after arthrocentesis. Upon arrival, the samples were transferred into plastic tubes without additives and pretreated with hyaluronidase solution. After centrifugation at 1500xg for 10 minutes at RT, the baseline calprotectin concentrations were determined. Seven aliquots were stored in LoBind tubes (Eppendorf) at 4-8 °C and the calprotectin was measured every day. Six additional aliquots were stored at temperatures - 20 °C and - 80 °C and the concentration of calprotectin was measured weekly. Analysis was done using Buhlmann fCAL turbo reagent on analyzer Siemens Atellica Solution (Siemens Healthcare, Erlangen, Germany). Data were analyzed by Microsoft Excel and MedCalc statistical software. The percentage difference (PD%) was calculated. The maximum permissible difference (MPD) was 9.1% for PD%. Results: The PD% with the corresponding 95% confidence intervals were inside the predefined MPD. The instability equations and correlation coefficient for storage temperatures were PD% = 0.1644 x time (day), r = 0.06, P = 0.614 for 4-8°C, PD% = 0.5190 x time (week), r = - 0.22, P = 0.080 for - 20°C, and PD% = 0.1316 x time (week), r = 0.08, P = 0.545 for - 80°C. Conclusions: The calprotectin in the synovial fluid is stable when stored long-term for 6 weeks at - 20 °C or at - 80 °C or short-term (7 days) at 4-8 °C. [ABSTRACT FROM AUTHOR]

Background: Vascular adverse events (VAEs) occurring during injections of soft‐tissue fillers are still considered a challenging issue for both patients and practitioners. Hyaluronidase can dissolve hyaluronic acid (HA)‐based soft‐tissue fillers during a VAE. For VAEs induced by non‐HA fillers, the absence of an "antidote" is regarded as exceptionally challenging. Methods: This multicenter study describes a case series of three VAEs induced by non‐HA fillers, for which ultrasound‐guided hyaluronidase injections were incorporated into the treatment approach. Results: Two cases of calcium hydroxylapatite and one case of poly‐L‐lactic acid‐induced VAEs are described, all of which were resolved without necrosis or scarring using a treatment approach with ultrasound‐guided hyaluronidase injections. Conclusions: Unlike the mechanical hypothesis, which assumes filler particles travel antegrade to block arterioles in a large skin area, we hypothesize vasoconstriction as the pivot in VAEs. Filler injection‐induced spasms could lead to long‐lasting vasoconstriction of the perforator arteries stemming from the central facial arteries. Our results underscore that perforasome vasoconstriction might be the leading cause of the ischemia and subsequent necrosis in VAEs and that relaxation of these perforasomes, rather than dissolving the filler material, resolves the clinical symptoms associated with VAEs. [ABSTRACT FROM AUTHOR]

The tamarillo, or Solanum betaceum, recognized for its comprehensive nutritional profile, has long been valued for its diverse ethnobotanical uses. This study delves into the potential therapeutic applications of S. betaceum by analyzing its polyphenolic content (TPC), total flavonoid content (TFC), anti-skin aging activities against key enzymes like elastase, tyrosinase, and hyaluronidase, and its cytotoxic effects on oral carcinoma cells. Extracts from the seeds, pulp, and peel of red and yellow fruits were prepared using methanol, ethanol, and acetone. The highest TPC was found in the methanol extract from red fruit seeds (9.89 mg GAE/g), and the highest TFC was found in the methanol extract of yellow fruit peel (3.02 mg QUE/g). Some of these extracts significantly inhibited skin aging-associated enzymes with the red fruit seed extract (100 μg/mL) showing up to 50.4% inhibition of tyrosinase. Additionally, the red fruit seed extract obtained using methanol demonstrated potential anticancer effects against Ca9-22 oral carcinoma cells by inhibiting cell survival, migration, and proliferation as well as inducing apoptosis. These results underscore the potential of S. betaceum fruit extracts, especially from red fruit seeds, as promising agents for anti-skin aging and anticancer applications, meriting further exploration for therapeutic uses. [ABSTRACT FROM AUTHOR]

Human hyaluronidase 1 (HYAL1) and PH20 play vital roles in degrading hyaluronic acids through the substrate-assisted double displacement mechanism. While HYAL1, a lysosomal enzyme, functions optimally under acidic conditions, PH20, a sperm surface hyaluronidase, displays a broader pH range, from acidic to neutral. Our objective was to extend HYAL1's pH range towards neutral pH by introducing repulsive charge-charge interactions involving the catalytic Glu131, increasing its pKa as the proton donor. Substituting individual acidic residues in the β3-loop (S77D), β3′-β3″ hairpin (T86D and P87E), and at Ala132 (A132D and A132E) enabled HYAL1 to demonstrate enzyme activity at pH 7, with the mutants S77D, P87E, and A132E showing the highest activity in the substrate gel assay. However, double and triple substitutions, including S77D/T86D/A132E as found in the PH20 configuration, did not result in enhanced activity compared to single substitutions. Conversely, PH20 mutants with non-acidic substitutions, such as D94S in the β3-loop and D103T in the β3′-β3″ hairpin, significantly reduced activity within the pH range of 4 to 7. However, the PH20 mutant E149A, reciprocally substituted compared to A132E in HYAL1, exhibited activity similar to PH20 wild-type (WT) at pH 7. In a turbidimetric assay, HYAL1 mutants with single acidic substitutions exhibited activity similar to that of PH20 WT at pH 7. These results suggest that substituting acidic residues near Glu131 results in HYAL1 activity at neutral pH through electrostatic repulsion. This study highlights the significance of charge-charge interactions in both HYAL1 and PH20 in regulating the pH-dependent activity of hyaluronidases. [ABSTRACT FROM AUTHOR]

Keloids are fibroproliferative disorders caused due to injury to skin. The recurrence rate has been found to be as high as 100% even after surgical excision. The high recurrence rate has led to the need for various adjuvant therapies as a single approach alone has not been found to be efficient in preventing recurrence. This attributes to the need for a multimodal approach. Steroids are found to be useful in preventing recurrence. To evaluate the efficacy of the combination of hyaluronidase with corticosteroid injection compared to corticosteroid injection alone in the prevention of recurrence of keloid after surgical excision. This randomized controlled study was conducted in the Department of Otorhinolaryngology among 50 patients with ear keloids who underwent surgical excision. Patients were divided into two groups. One group was given Triamcinolone injection alone and the other was given Triamcinolone with Hyaluronidase on postoperative weeks 1, 2, and 3. Patients were followed up for 6 months and recurrence was noted and compared. Statistical analysis was done and the results were considered significant with a p-value of less than 0.05. Of the total 50 patients, there were a total of eight male and 39 female patients. In a single therapy group, recurrence was noted in one patient after 3 months and in three more patients after 6 months. In the group with combination therapy, there was no recurrence after 3 months but three patients had recurrence after 6 months. Triamcinolone and hyaluronidase injection protected from recurrence for about 3 to 5 months after which patients had recurrence. Further studies are recommended with prolonged duration of hyaluronidase injection. [ABSTRACT FROM AUTHOR]

Background: Hyaluronic acids (HAs) can have very different actions not only depending on injector and host factors but also depending on their molecular weight. Whereas short chain HA has immunological activity long chain HA influences fibroblasts and may stimulate them to produce collagen. Although this is generally thought to be a positive feature it may be disadvantageous in certain localizations. Patients and Methods: We have encountered 23 patients who developed fibrous tissue next to the nasolabial folds accentuating them and becoming very obvious while smiling. Hyaluronidase injection did not reduce this mass. Results: Intralesional triamcinolone acetonide injection led to rapid improvement. Discussion: Fibrotic tissue reaction not responding to hyaluronidase may be the result of HA injection and can effectively be treated with intralesional steroid injection [ABSTRACT FROM AUTHOR]

Eleutherococcus divaricatus (Siebold and Zucc.) S. Y. Hu. has been used in Traditional Chinese Medicine (TCM) due to its anticancer, immunostimulant, and anti-inflammatory activities. However, its mechanism of action and chemical composition are still insufficiently understood and require more advanced research, especially for cases in which anti-inflammatory properties are beneficial. The aim of this study was to evaluate the impact of E. divaricatus root extracts and fractions on proinflammatory serum hyaluronidase and tyrosinase in children diagnosed with acute lymphoblastic leukemia. Antioxidant and anti-melanoma activities were also examined and correlated with metabolomic data. For the first time, we discovered that the ethyl acetate fraction significantly inhibits hyaluronidase activity, with mean group values of 55.82% and 63.8% for aescin used as a control. However, interestingly, the fraction showed no activity against human tyrosinase, and in A375 melanoma cells treated with a doxorubicin fraction, doxorubicin activity decreased. This fraction exhibited the most potent antioxidant activity, which can be attributed to high contents of polyphenols, especially caffeic acid (24 mg/g). The findings suggest an important role of the ethyl acetate fraction in hyaluronidase inhibition, which may additionally indicate its anti-inflammatory property. The results suggest that this fraction can be used in inflammatory-related diseases, although with precautions in cases of patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Ananteris is a scorpion genus that inhabits dry and seasonal areas of South and Central America. It is located in a distinctive morpho-group of Buthids, the 'Ananteris group', which also includes species distributed in the Old World. Because of the lack of information on venom composition, the study of Ananteris species could have biological and medical relevance. We conducted a venomics analysis of Ananteris platnicki, a tiny scorpion that inhabits Panama and Costa Rica, which shows the presence of putative toxins targeting ion channels, as well as proteins with similarity to hyaluronidases, proteinases, phospholipases A2, members of the CAP-domain family, and hemocyanins, among others. Venom proteolytic and hyaluronidase activities were corroborated. The determination of the primary sequences carried out by mass spectrometry evidences that several peptides are similar to the toxins present in venoms from Old World scorpion genera such as Mesobuthus, Lychas, and Isometrus, but others present in Tityus and Centruroides toxins. Even when this venom displays the characteristic protein families found in all Buthids, with a predominance of putative Na+-channel toxins and proteinases, some identified partial sequences are not common in venoms of the New World species, suggesting its differentiation into a distinctive group separated from other Buthids. [ABSTRACT FROM AUTHOR]

Introduction: Epidermoid cysts (E.C.s), also known as sebaceous cysts, are benign asymptomatic subepidermal nodules filled with keratin material. These cysts originate from the follicular infundibulum, which when obstructed by keratin, results in cyst formation. Conventionally, E.C.s have been managed surgically with a high success rate and minimal complications. In this report, we present the successful resolution of an E.C. using a minimally invasive technique involving the intralesional injection of recombinant hydrolytic enzymes like hyaluronidase, collagenase, and lipase. Case Presentation: A 44-year-old woman with no significant medical history presented to the clinic with a mass on her right cheek that had been evolving for over 10 years. Skin and soft tissue ultrasound confirmed the presence of an E.C. of 9.3× 6.6 × 9.3 mm. Owing to the size and location of the cyst, a decision was made to infiltrate the lesion with recombinant enzymes. Remarkably, significant clinical improvement was observed on Day 21, and complete dissolution of the E.C. occurred 40 days after the initial intervention. Importantly, no recurrences were observed during the 4-year follow-up period. Conclusion: Intralesional administration of hydrolytic enzymes represents an innovative technique in the management of E.C.s. However, further controlled studies are required to determine the efficacy and safety of this procedure. [ABSTRACT FROM AUTHOR]

Hyaluronan (HA) is a large polysaccharide that is broadly distributed and highly abundant in the soft connective tissues and embryos of vertebrates. The constitutive turnover of HA is very high, estimated at 5 g per day in an average (70 kg) adult human, but HA turnover must also be tightly regulated in some processes. Six genes encoding homologues to bee venom hyaluronidase (HYAL1, HYAL2, HYAL3, HYAL4, HYAL6P/HYALP1, SPAM1/PH20), as well as genes encoding two unrelated G8-domain-containing proteins demonstrated to be involved in HA degradation (CEMIP/KIAA1199, CEMIP2/TMEM2), have been identified in humans. Of these, only deficiencies in HYAL1, HYAL2, HYAL3 and CEMIP have been identified as the cause or putative cause of human genetic disorders. The phenotypes of these disorders have been vital in determining the biological roles of these enzymes but there is much that is still not understood. Deficiencies in these HA-degrading proteins have been created in mice and/or other model organisms where phenotypes could be analyzed and probed to expand our understanding of HA degradation and function. This review will describe what has been found in human and animal models of hyaluronidase deficiency and discuss how this has advanced our understanding of HA's role in health and disease. [ABSTRACT FROM AUTHOR]

Introduction: Blood pressure (BP) regulation is a complex process involving several factors, among which water-sodium balance holds a prominent place. Arginin-vasopressin (AVP), a key player in water metabolism, has been evoked in hypertension development since the 1980s, but, to date, the matter is still controversial. Hyaluronic acid metabolism has been reported to be involved in renal water management, and AVP appears to increase hyaluronidase activity resulting in decreased high-molecular-weight hyaluronan content in the renal interstitium, facilitating water reabsorption in collecting ducts. Hence, our aim was to evaluate urinary hyaluronidase activity in response to an oral water load in hypertensive patients (HT, n=21) compared to normotensive subjects with (NT+, n=36) and without (NT-, n=29) a family history of hypertension, and to study its association with BP and AVP system activation, expressed by serum copeptin levels and urine Aquaporin 2 (AQP2)/creatinine ratio. Methods: Eighty-six Caucasian men were studied. Water load test consisted in oral administration of 15-20 ml of water/kg body weight over 40-45 min. BP, heart rate, serum copeptin, urine hyaluronidase activity and AQP2 were monitored for 4 hours. Results: In response to water drinking, BP raised in all groups with a peak at 20-40 min. Baseline levels of serum copeptin, urinary hyaluronidase activity and AQP2/creatinine ratio were similar among groups and all decreased after water load, reaching their nadir at 120 min and then gradually recovering to baseline values. Significantly, a blunted reduction in serum copeptin, urinary hyaluronidase activity and AQP2/creatinine ratio was observed in NT+ compared to NT-subjects. A strong positive correlation was also found between urinary hyaluronidase activity and AQP2/creatinine ratio, and, although limited to the NT- group, both parameters were positively associated with systolic BP. Discussion: Our results demonstrate for the first time the existence in men of a close association between urinary hyaluronidase activity and vasopressinergic system and suggest that NT+ subjects have a reduced ability to respond to water loading possibly contributing to the blood volume expansion involved in early-stage hypertension. Considering these data, AVP could play a central role in BP regulation by affecting water metabolism through both hyaluronidase activity and AQP2 channel expression. [ABSTRACT FROM AUTHOR]

In our study, using chromatographic techniques, we isolated three bioactive compounds, which were structurally elucidated as (E)-2-(3-(3,4-dimethoxyphenyl)acrylamido)-N-methylbenzamide (1), 4-Hydroxyquinoline-2-carboxylic acid (2), and (E)-2-Cyano-3-(4-hydroxyphenyl)acrylic acid (3), using spectroscopic methods. The anti-melanogenic, anti-inflammatory, antioxidant, and anti-aging properties were evaluated in vitro by measuring the activity of pharmacological targets including tyrosinase, melanin, NF-κB, hyaluronidase, elastase, collagenase, and Nrf2. Our results show that compound 1 is the most active with IC50 values of 14.19 μM (tyrosinase inhibition), 22.24 μM (melanin inhibition), 9.82–12.72 μM (NF-κB inhibition), 79.71 μM (hyaluronidase inhibition), 80.13 μM (elastase inhibition), 76.59 μM (collagenase inhibition), and 116–385 nM (Nrf2 activation) in the THP-1, HEK001, WS1, and HMCB cells. These findings underscore the promising profiles of the aqueous extract of R. urticifolius at safe cytotoxic concentrations. Additionally, we report, for the first time, the isolation and characterisation of these nitrogenous compounds in the R. urticifolius species. Finally, compound 1, isolated from R. urticifolius, is a promising candidate for the development of more effective and safer compounds for diseases related to skin pigmentation, protection against inflammation, and oxidative stress. [ABSTRACT FROM AUTHOR]

We have found that the ketogenic (Keto) diet is able to, unexpectedly, promote the metastatic potential of cancer cells in complementary mouse models. Notably, the Keto diet-induced tumor metastasis is dependent on BTB domain and CNC homolog 1 (BACH1) and its up-regulation of pro-metastatic targets, including cell migration-inducing hyaluronidase 1, in response to the Keto diet. By contrast, upon genetic knockout or pharmacological inhibition of endogenous BACH1, the Keto diet-mediated activation of those targets is largely diminished, and the effects on tumor metastasis are completely abolished. Mechanistically, upon administration of the Keto diet, the levels of activating transcription factor 4 (ATF4) are markedly induced. Through direct interaction with BACH1, ATF4 is recruited to those pro-metastatic target promoters and enhances BACH1-mediated transcriptional activation. Together, these data implicate a distinct transcription regulatory program of BACH1 for tumor metastasis induced by the Keto diet. Our study also raises a potential health risk of the Keto diet in human patients with cancer. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the hyaluronidase and gelatinase inhibitory activities and toxicity potentials of Persea americana Mill. extract and its synthesized hybrid nanoflowers. In the first part of the study, characterization of the nanoflower structures was carried out and then, enzyme inhibitory activities of the methanol extract and hybrid nanoflowers were investigated. It was determined that the enzyme inhibitory activity of both nanoflowers was higher than the methanol extract. Zinc nanoflower was more effective in hyaluronidase enzyme inhibition, while copper nanoflower showed higher inhibitory activity on gelatinase enzyme. In the second part of the study, toxicological profiles of these compounds were investigated. Toxicological evaluations demonstrated that zinc nanoflower may be a safer therapeutic alternative than the copper nanoflower, especially at high concentrations. All these data appear to contribute to the development of effective new generation preparations including nanoflowers for skin problems using Persea americana leaves extract and its nanostructures. [ABSTRACT FROM AUTHOR]

Introduction: Hyaluronic acid (HA) is a safe and commonly used filler for soft tissue augmentation. However, some complications can occur, particularly if the technique of application is inadequate or the quality of the material is poor. Objective: To underline the importance of clinical examination in the era of rapid technological development. Case report: A 27-year-old woman presented to our clinic due to poor aesthetic results after multiple lip augmentation using hyaluronic acid injections followed by an unsuccessful treatment in a different medical centre in which she was overdiagnosed. The patient underwent several hyaluronidase injections and an ultrasound-guided core biopsy. Hyaluronic acid was not found in any of the taken specimens. Next, surgical removal of the filler was proposed. We proposed hyaluronidase and antibiotic treatment that resulted in a satisfactory aesthetic effect. Conclusions: Additional tests can be useful in managing complications of hyaluronic acid procedures, but they should be correlated with clinical expertise. [ABSTRACT FROM AUTHOR]

Hyaluronidase increases tissue permeability and diffusion of the extracellular fluid by cleaving hyaluronan, the primary component of the extracellular matrix. Hyaluronidase pegylation (Hyal-PEG) decreases its clearance and enhances biodistribution. The pro- and anticancer activity of Hyal-PEG and a combination of Hyal-PEG with doxorubicin were studied in vitro (morphological analysis of rat glioblastoma 101.8 spheroids) and in vivo (by the survival time of rats after intracerebral transplantation of the tumor and morphological analysis). In the presence of doxorubicin and Hyal-PEG in the culture medium in vitro, spheroids lost their ability to adhere to the substrate and disintegrate into individual cells. Intracerebral transplantation of the tumor tissue with Hyal-PEG did not accelerate glioblastoma growth. The mean survival time for animals receiving transplantation of the tumor alone and in combination with Hyal-PEG was 13 and 20 days, respectively. In one rat with transplanted tumor and Hyal-PEG, this parameter increased by 53%. The survival time of rats receiving systemic therapy with doxorubicin and Hyal-PEG significantly increased (p=0.003). Antitumor effect of therapeutic doses of doxorubicin combined with Hyal-PEG was demonstrated on the model of rat glioblastoma 101.8 in vitro. Hyal-PEG inhibited adhesion of tumor cells, but did not cause their death. Transplantation of Hyal-PEG-treated tumor did not reduce animal survival time. Systemic administration of therapeutic doses of doxorubicin with Hyal-PEG increased survival time of rats with glioblastoma 101.8. [ABSTRACT FROM AUTHOR]

Sambuci folium (elderberry leaves) have been used in traditional medicine, mainly externally, to treat skin diseases and wounds. Therefore, the aim of this study was to screen the biological activity of elderberry leaves (antioxidant potential and possibility of inhibition of tyrosinase and hyaluronidase enzymes) combined with phytochemical analysis. For this purpose, a phytochemical analysis was carried out. Elderberry leaves of 12 varieties ("Sampo", "Obelisk", "Dwubarwny", "Haschberg", "Haschberg 1", "Koralowy", "Sambo", "Black Beauty", "Black Tower", "Golden hybrid", "Samyl", "Samyl 1") in two growth stages. The compounds from the selected groups, phenolic acids (chlorogenic acid) and flavonols (quercetin), were chromatographically determined in hydroalcoholic leaf extracts. All tested elderberry leaf extracts showed antioxidant effects, but the most promising potential: very high compounds content (TPC = 61.85 mg GAE/g), antioxidant (e.g., DPPH IC50 = 1.88 mg/mL; CUPRAC IC0.5 = 0.63 mg/mL) and optimal anti-inflammatory (inhibition of hyaluronidase activity 41.28%) activities were indicated for older leaves of the "Sampo" variety. Additionally, the extract obtained from "Sampo" and "Golden hybrid" variety facilitated the treatment of wounds in the scratch test. In summary, the best multidirectional pro-health effect in treating skin inflammation was specified for "Sampo" leaves II extract (leaves during the flowering period); however, wound treatment was noted as rich in chlorogenic acid younger leaf extracts of the "Golden hybrid" variety. [ABSTRACT FROM AUTHOR]

Brevibacillus sp. JNUCC 41, characterized as a plant-growth-promoting rhizobacterium (PGPR), actively participates in lipid metabolism and biocontrol based on gene analysis. This study aimed to investigate the crucial secondary metabolites in biological metabolism; fermentation, extraction, and isolation were performed, revealing that methyl indole-3-acetate showed the best hyaluronidase (HAase) inhibitory activity (IC50: 343.9 μM). Molecular docking results further revealed that the compound forms hydrogen bonds with the residues Tyr-75 and Tyr-247 of HAase (binding energy: −6.4 kcal/mol). Molecular dynamics (MD) simulations demonstrated that the compound predominantly binds to HAase via hydrogen bonding (MM-PBSA binding energy: −24.9 kcal/mol) and exhibits good stability. The residues Tyr-247 and Tyr-202, pivotal for binding in docking, were also confirmed via MD simulations. This study suggests that methyl indole-3-acetate holds potential applications in anti-inflammatory and anti-aging treatments. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate and compare the efficacy of 2% lidocaine containing adrenaline with and without hyaluronidase in inferior alveolar nerve blocks for patients requiring bilateral mandibular extractions. Patients and Methods: This was the split‐mouth study conducted on 26 patients requiring bilateral mandibular teeth extraction. All the patients were assigned randomly to one of the two groups: (i) 2% lignocaine HCl + 1:2,00,000 adrenaline + hyaluronidase (75 IU) solution will be administered on one side which is the experimental side and (ii) 2% lignocaine HCl + 1:2,00,000 adrenaline solution on the other side is control side. In the first session, the patients randomly received the inferior alveolar nerve block with or without hyaluronidase in one side of the oral cavity. One week later, the same patient received the other technique which was not received in the first session. We also evaluated the onset, duration and need of any supplementary anaesthesia in both the groups. Results: Comparison of VAS score in the control group (2.73 ± 0.724) and experimental group (3 ± 0.693) showed statistically insignificant results (p = 0.177). Whereas the onset of local anaesthesia showed a statistically significant difference between the two groups (p < 0.001) mean of control group (2.73 ± 0.47) and experimental group (1.15 ± 0.23). Comparison of duration of anaesthesia showed a statistically significant difference (p < 0.001) with the mean duration of the experimental group being higher (106 ± 7.94) than the control group (86.27 ± 3.90). Comparison for the need for supplementary anaesthesia showed no statistically significant difference between the two groups. Conclusion: We conclude that if hyaluronidase is used, better blocks with smaller volumes are produced. LAs with hyaluronidase have been shown to improve the quality and effectiveness of anaesthetic blocks and shorten the time it takes for anaesthesia to begin, accelerate the onset of akinesia and lessen the need for additional anaesthesia. It also increases the duration of anaesthesia. [ABSTRACT FROM AUTHOR]

Background: Vascular occlusion induced by hyaluronic acid injections is rare, but can lead to severe adverse events, including necrosis, blindness, and cerebral infarction. Objective: This study aims to explore methods of reducing the risk of complications such as embolism induced by hyaluronic acid injection, and to study the impact of comprehensive systematic treatment on the prognosis of patients with hyaluronic acid embolism. Methods: The clinical data of three female patients with vascular occlusion due to hyaluronic acid injection was analyzed. Their median age was 26 years, with symptoms presenting 1–6 h postinjection. Hospital stays averaged 6 days. Two patients had ptosis, diplopia, and severe pain after injection of eyebrows. The other, who had a nose enhancement, experienced facial skin color changes and intense pain. Results: Two patients received comprehensive, systematic treatment based on injectable hyaluronidase. One patient self‐discharged after receiving injectable hyaluronidase, antispasmodic, and vasodilator treatment on the night of embolism and returned to the hospital 3 days later with worsening embolism symptoms and received symptomatic treatment again. Two patients who received comprehensive, systematic treatment based on injectable hyaluronidase showed significant improvement, while the patient who did not undergo systematic treatment left scars on the face. Conclusion: Vascular occlusion caused by hyaluronic acid facial filling is a severe adverse event, and timely, comprehensive, systematic treatment can effectively improve irreversible damage caused by thrombosis, and even cure it. [ABSTRACT FROM AUTHOR]

Injectable dermal fillers continue to increase in popularity in aesthetic medicine. Although rare, vision loss secondary to filler injections is a devastating complication associated with a poor visual prognosis. The mechanism for vision loss is thought to be related to retrograde embolization of the dermal filler from peripheral vessels in the face into the ophthalmic arterial system. Early recognition and prompt management are essential if vision is to be salvaged. The use of retrobulbar hyaluronidase is still contentious, however when administered by a specialist, this treatment gives the best chance at visual recovery and should be considered for all cases. [ABSTRACT FROM AUTHOR]

Changes in the quantitative content and specific activity of hyaluronidase enzyme after ultrasonic treatment of solutions of bovhyaluronidase azoximer were studied. Solutions of the finished dosage form of bovhyaluronidase azoximer (Longidase® lyophilizate for preparation of solution for injection, 3000 IE) and bovhyaluronidase azoximer drug substance (Longidase® substance-lyophilizate) were studied. The aim of the study was to determine the effect of ultrasound (US) on the stability of bovhyaluronidase azoximer determined from the measured quantitative content and enzymatic activity of the substance in solution. US at a radiation intensity of 61.4 W/L during treatment in an ultrasonic bath did not significantly affect the quantitative content of the bovhyaluronidase azoximer drug substance in solution, while the decrease in the enzymatic activity of the active substance in Longidase solution after 20 and 30 min of ultrasonic treatment was statistically significant. At the same time, the enzymatic activity of the active substance determined by a biochemical method differed significantly (residual activity from 99.70% to 59.27%) depending on the design features of the nebulizers and the nebulization time after nebulization of the bovhyaluronidase azoximer solution in mesh nebulizers from various manufacturers. Nebulization times of min were least associated with the risk of significant loss of stability of bovhyaluronidase azoximer. [ABSTRACT FROM AUTHOR]

Electroporation (EP) stands out as a promising non-viral plasmid delivery strategy, although achieving optimal transfection efficiency in vivo remains a challenge. A noteworthy advancement in the field of in vivo EP is the application of hyaluronidase, an enzyme with the capacity to degrade hyaluronic acid in the extracellular matrix, which thereby enhances DNA transfer efficiency by 2- to 3-fold. This paper focuses on elucidating the mechanism of hyaluronidase's impact on transfection efficiency. We demonstrate that hyaluronidase promotes a more uniform distribution of plasmid DNA (pDNA) within skeletal muscle. Additionally, our study investigates the effect of the timing of hyaluronidase pretreatment on EP efficiency by including time intervals of 0, 5, and 30 min between hyaluronidase treatment and the application of pulses. Serum levels of the pDNA-encoded transgene reveal a minimal influence of the hyaluronidase pretreatment time on the final serum protein levels following delivery in both mice and rabbit models. Leveraging bioimpedance measurements, we capture morphological changes in muscle induced by hyaluronidase treatment, which result in a varied pDNA distribution. Subsequently, these findings are employed to optimize EP electrical parameters following hyaluronidase treatment in animal models. This paper offers novel insights into the potential of hyaluronidase in enhancing the effectiveness of in vivo EP, as well as guides optimized electroporation strategies following hyaluronidase use. [ABSTRACT FROM AUTHOR]

Predicting the subcutaneous (SC) pharmacokinetics (PK) of antibodies in humans is challenging, with clinical data currently being the only reliable data source for modeling SC absorption and bioavailability. Recombinant human hyaluronidase PH20 (rHuPH20) is an enzyme that facilitates SC delivery of high‐dose, high‐volume therapeutics. Numerous monoclonal antibodies have been co‐administered SC with rHuPH20 in a clinical setting, establishing an extensive PK database. The goal of this work is to demonstrate how aggregated clinical data can be leveraged in a universal modeling framework for characterizing SC antibody PK, resulting in parameterization that can be used in predictive simulations of new antibodies. Data for 10 individual antibodies co‐administered SC with rHuPH20 were obtained from publicly available sources. PK modeling of each antibody was conducted using the same model structure, but uniquely parameterized. The model structure consisted of a two‐compartment model to capture linear kinetics, plus a target‐binding mechanism to accommodate nonlinear kinetics driven by antibody‐target complex formation and elimination. The clinical PK profiles for all antibodies were accurately described using the universal modeling framework. The SC PK parameters of absorption and bioavailability were consistent across the range of antibody and target properties evaluated. SC administration with rHuPH20 yielded a 30% increase in absorption rate on average and similar or better bioavailability. These parameter values can serve as initial conditions for model‐based PK predictions for new antibodies co‐administered SC with rHuPH20 to enable evaluation of optimal SC dose and schedule regimens prior to and during clinical development. [ABSTRACT FROM AUTHOR]

The scorpion of Androctinus crassicauda is one of the Buthida family members whose neurotoxic venom is deadly to humans. Enzymes are abundant components of animal venom that play roles in local and systemic symptoms following envenoming. The venom of this scorpions contains various pathological enzymes, among which studies have reported the toxic effects of venom's hyaluronidase and phospholipase A2 enzymes. This study aimed to measure the activity of venom enzymes of hyaluronidase and phospholipase A2 from scorpion of A. crassicauda and its fractions. For this purpose, the venom from scorpion of A. crassicauda were collected and lyophilized. The whole venom was fractionated on a gel filtration (Sephadex G-50) column. Then protein concentration, hyaluronidase and phospholipase A2 activity of the crude venom and its fractions were determined. Gel filtration on Sephadex G-50 and SDS-PAGE electrophoresis of A. crassicauda crude venom revealed four protein picks and 15 protein bands with the majority of molecular masses between 10.0 and 15.0 kDa, respectively. The supernatant obtained from crude venom clarification showed protein content 71.80%, high hyaluronidase (92.40%) and low PLA2 (302±2.1 mg/U) enzyme activity. Fraction 1 showed highest hyaluronidase and phospholipase A2 activities. We found that pH 5 is the optimum pH for hyaluronidase activity and phospholipase A2 activity increases with increasing incubation time. In conclusion, venom of A. crassicauda displayed the hyaluronidase and phospholipase A2 enzymes activity, which were separated by gel filtration chromatography in fraction I. Such information is important both for predicting the biological activity of venom components and useful for developing effective antivenoms based on these venom components. [ABSTRACT FROM AUTHOR]

The carnivorous pitcher plants of the genus Nepenthes have long been known for their ethnobotanical applications. In this study, we prepared various extracts from the pitcher, stem, and leaf of Nepenthes miranda using 100% ethanol and assessed their inhibitory effects on key enzymes related to skin aging, including elastase, tyrosinase, and hyaluronidase. The cytotoxicity of the stem extract of N. miranda on H838 human lung carcinoma cells were also characterized by effects on cell survival, migration, proliferation, apoptosis induction, and DNA damage. The cytotoxic efficacy of the extract was enhanced when combined with the chemotherapeutic agent 5-fluorouracil (5-FU), indicating a synergistic effect. Flow cytometry analysis suggested that the stem extract might suppress H838 cell proliferation by inducing G2 cell cycle arrest, thereby inhibiting carcinoma cell proliferation. Gas chromatography–mass spectrometry (GC–MS) enabled the tentative identification of the 15 most abundant compounds in the stem extract of N. miranda. Notably, the extract showed a potent inhibition of the human RPA32 protein (huRPA32), critical for DNA replication, suggesting a novel mechanism for its anticancer action. Molecular docking studies further substantiated the interaction between the extract and huRPA32, highlighting bioactive compounds, especially the two most abundant constituents, stigmast-5-en-3-ol and plumbagin, as potential inhibitors of huRPA32's DNA-binding activity, offering promising avenues for cancer therapy. Overall, our findings position the stem extract of N. miranda as a promising source of natural compounds for anticancer therapeutics and anti-skin-aging treatments, warranting further investigation into its molecular mechanisms and potential clinical applications. [ABSTRACT FROM AUTHOR]