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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]

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]

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]

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]

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: 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

The pharmacokinetics (PK) of intravenous (i.v.) nivolumab is well characterized. A subcutaneous (s.c.) nivolumab formulation with and without recombinant human hyaluronidase PH20 enzyme is being evaluated in CheckMate 8KX (NCT03656718). A model‐based analysis was conducted to characterize the PK of nivolumab s.c. and predict systemic exposures after i.v. and s.c. administration to guide dosing regimen selection for nivolumab s.c. A prior i.v. model was modified to incorporate an s.c. extravascular compartment and estimate the absorption rate constant and bioavailability of nivolumab s.c. Serum concentration–time data from 82 patients treated with nivolumab s.c. 720, 960, or 1,200 mg were pooled with existing i.v. data from multiple studies for model development. Prediction‐corrected visual predictive check (pcVPC) plots assessed the model's performance. Stochastic simulations were conducted to predict exposures for i.v. and s.c. administration. The data were described by a two‐compartment model with time‐varying clearance, zero‐order infusion into the central compartment after i.v. dosing, and first‐order absorption from the extravascular compartment after s.c. dosing. The pcVPC suggested that the model adequately described the observed nivolumab s.c. data. Predicted nivolumab exposures at 1,200 mg s.c. every 4 weeks (q4w) were higher than those at the approved dose of 3 mg/kg i.v. q2w and lower than those at the highest tested safe dose of 10 mg/kg i.v. q2w. Nivolumab PK is well‐characterized using the combined s.c./i.v. population PK model. The model‐based analysis facilitated a comprehensive benefit–risk assessment of nivolumab s.c. and informed selection of 1,200 mg s.c. q4w for phase III evaluation. [ABSTRACT FROM AUTHOR]

The cultivation of Crocus sativus L. to obtain the saffron spice generates a large amount of biowaste, constituted mainly by the flower's tepals. The aim of this work was to evaluate the antioxidant and dermo-protective effect of a complex methanolic extract of C. sativus tepals. The extract's major phenolic content was analyzed using ultra-high performance liquid chromatography with electrospray ionization, coupled with quadrupole-time-of-flight-mass spectrometry (UHPLC-ESI-QTOF-MS). Then, the antioxidant in vitro activity of the extract was studied and related to their chemical composition. Likewise, the effect on intracellular ROS levels in HepG2 and Hs27 cell culture was determined in normal culture and under hydrogen-peroxide-induced oxidative stress. Finally, tyrosinase, hyaluronidase, collagenase, elastase, and xanthine oxidase assays were carried out to determine the dermo-protective capacity of the extract. The high polyphenol content, including flavonoids and anthocyanins, explains the antioxidant effect of the extract both in vitro and in culture assays. The extract has a significant and remarkable protective capacity against oxidative stress induced in culture of the two studied cell lines. It is also remarkable in its ability to inhibit hyaluronidase, tyrosinase, and xanthine oxidase. Results pointed out this biowaste extract as a promising ingredient in the composition of cosmetics. [ABSTRACT FROM AUTHOR]

Extravasation of 99mTc‐labeled radiopharmaceuticals is generally considered to require no specific intervention. In the presented case, the use of hyaluronidase could have minimized the adverse effects resulting from such an extravasation. Currently, no guidelines exist regarding the use of hyaluronidase after extravasation of [99mTc]Tc‐HDP. Considering the low risk of administering hyaluronidase, it should be considered to limit the risk of injury after extravasation of [99mTc]Tc‐HDP. [ABSTRACT FROM AUTHOR]

This article discusses the use of hyaluronidase, an enzyme that can dissolve HA fillers, in addressing complications or dissatisfaction arising from HA filler injections. It highlights various situations where hyaluronidase may be injected post-filler procedure, such as incorrect injection, excessive filler, asymmetry, migration, lumps, discomfort, patient dissatisfaction, inflammation, granulomas, Tyndall effect, and vascular complications. The article provides information on the dosage, time to effect, duration of activity, approach for vascular complications, dilution and injection technique, injection into filler masses, and potential allergic reactions associated with hyaluronidase use. It emphasizes the importance of understanding these considerations for effective and safe use of hyaluronidase. [Extracted from the article]

Fruits are very important dietary components and a source of biologically active compounds used in nutritional pharmacology. Particularly due to the presence of polyphenolic compounds, fruits play an important role in the prevention of diseases of civilization. Therefore, it is important to study the phytochemicals and biological activity of fruits, especially those with a long-standing use in ethnomedicine. In this study, we determined the chemical profile and biological activity of a methanolic extract of the Eleutherococcus divaricatus fruits. Amongst nine polyphenols studied, only chlorogenic acid, protocatechuic acid, and eleutheroside E have been detected. The extract showed a weak anti-hyaluronidase activity from bovine testicular in a range of 9.06–37.70% and quite high for human serum hyaluronidase from children diagnosed with acute leukemia in a range of 76–86%. A weak anti-tyrosinase activity was obtained in a range of 2.94–12.46%. Moreover, the extract showed antioxidant properties against DPPH radical, ABTS radical, and O2•−. In addition, the antioxidant activity of the extract was evaluated by FRAP assay and Fe2+ ion chelation assay. These preliminary studies partially justify the traditional use of the plant in inflammatory- and immune-related diseases, in which hyaluronidase and free radicals can participate. A difference in human serum hyaluronidase inhibition may result from the inter-patient variability. Regardless of that, the results mean that polyphenolic compounds may stimulate activity of hyaluronidase, as well as to protect cells from the oxidative damages. However, further studies in ex vivo and in vivo models are needed, including blood isolated from a larger number of patients. [ABSTRACT FROM AUTHOR]

Hyaluronidases (HAases) are enzymes that degrade hyaluronic acid (HA) in the animal kingdom. The HAases-HA system is crucial for HA homeostasis and plays a significant role in biological processes and extracellular matrix (ECM)-related pathophysiological conditions. This study aims to explore the role of inhibiting the HAases-HA system in acute kidney injury (AKI). We selected the potent inhibitor "sHA2.75" to inhibit HAase activity through mixed inhibitory mechanisms. The ischemia-reperfusion mouse model was established using male BALB/c mice (7–9 weeks old), and animals were subjected to subcapsular injection with 50 mg/kg sHA2.75 twice a week to evaluate the effects of sHA2.75 on AKI on day 1, 5 and 14 after ischemia-reperfusion or sham procedure. Blood and tissue samples were collected for immunohistochemistry, biochemical, and quantitative analyses. sHA2.75 significantly reduced blood urea nitrogen (BUN) and serum creatinine levels in AKI mouse models. Expression of kidney injury-related genes such as Kidney injury molecule-1 (KIM-1), Neutrophil Gelatinase-Associated Lipocalin (NGAL), endothelial nitric oxide synthase (eNOS), type I collagen (Col1), type III collagen (Col3), alpha-smooth muscle actin (α-SMA) showed significant downregulation in mouse kidney tissues after sHA2.75 treatment. Moreover, sHA2.75 treatment led to decreased plasma levels of Interleukin-6 (IL-6) proteins and reduced mRNA levels in renal tissues of AKI mice. Inhibitor sHA2.75 administration in the AKI mouse model downregulated kidney injury-related biomarkers and immune-specific genes, thereby alleviating AKI in vivo. These findings suggest the potential use of HAase inhibitors for treating ischemic reperfusion-induced kidney injury. [ABSTRACT FROM AUTHOR]

The anaerobic, rod-shaped, spore-forming bacterium Clostridium perfringens is known for its production of biochemically active substances. Most of them are proteins that have a pathogenic effect on a wide range of animal tissues and cause a specific syndrome or even a disease in humans or animals. Production of toxins is used to classify isolates of C. perfringens into 7 different toxin types (A-G). Other virulence factors (i.g. beta2-toxin, BEC toxin, sialidases, hyaluronidase etc.) only indirectly or partially participate in the development of the disease, and the function of some substances has not been fully elucidated. The article summarizes basic data on the non-typing virulence factors of C. perfringens. [ABSTRACT FROM AUTHOR]

Les injections d'acide hyaluronique sont de plus en plus banalisées par le grand public comme la communauté médicale, mais ne sont pas dénuées de risques pour autant. La survenue d'une cécité, bien qu'exceptionnelle, est dramatique pour le patient comme pour le praticien, l'un des traitements proposés dans la littérature consiste à injecter une hyaluronidase au plus près du site d'ischémie, en rétrobulbaire. Le but de notre étude est d'évaluer l'efficacité et l'intérêt que peuvent présenter les injections de hyaluronidase rétrobulbaires. Une revue de littérature a été réalisée à partir de la base de données PubMed, seuls les articles traitant des injections de hyaluronidase rétrobulbaires ont été retenus pour traiter une cécité après injection d'acide hyaluronique. Douze rapports de cas ou séries ont été retenus, incluant un total de 16 patients. Parmi ces 16 patients, 3 ont retrouvé leur vision. La hyaluronidase était injectée entre 20 minutes et 7 jours après la survenue de la complication, les doses injectées variées de 3 × 150 UI à 3 × 1500 UI. La littérature retrouve seulement 3 cas de patients traités avec succès sur 16 injections rapportées. La durée avant l'injection rétrobulbaire, ainsi que la dose ou l'expérience du praticien injecteur, pourraient faire varier le taux de succès de ce traitement. D'autres traitements, comme les injections intravasculaires de hyaluronidases, restent à explorer. Hyaluronic acid injections are becoming increasingly common among both the general public and the medical community, but they are not without risks. The occurrence of blindness, although rare, is a tragic event for both the patient and the practitioner. One of the treatments proposed in the literature is to inject hyaluronidase as close as possible to the site of ischemia, retrobulbarly. The aim of our study is to evaluate the effectiveness and potential benefits of retrobulbar hyaluronidase injections. A literature review was conducted using the PubMed database. Only articles addressing retrobulbar hyaluronidase injections for the treatment of blindness following hyaluronic acid injections were included. We identified 12 case reports or series, comprising a total of 16 patients. Among these 16 patients, 3 regained their vision. Hyaluronidase was injected between 20 minutes and 7 days after the onset of the complication, with injected doses ranging from 3 × 150 IU to 3 × 1500 IU. Literature reveals only 3 cases of successful treatment out of the 16 reported injections. The time interval before retrobulbar injection, as well as the dose and the experience of the injecting practitioner, may influence the success rate of this treatment. Other treatments, such as intravascular hyaluronidase injections, remain to be explored. [ABSTRACT FROM AUTHOR]

Medical rhinoplasty by hyaluronic acid injection (HA) has become nowadays a common practice. The number of patients requesting surgical rhinoplasty and having already undergone one or more injections of HA is increasing. However, the literature lacks publications regarding the management of these patients. The aim of this study is to discuss the management of patients who have been treated with previous nasal HA injections and who seek surgical rhinoplasty, and elaborate a treatment protocol and algorithm to standardize surgical plans. We are reporting case studies based on our clinical experience. We also reviewed the literature to suggest perioperative management for rhinoplasty with previous HA injections. Hyaluronidase injection preoperatively allows to carry out an accurate preoperative analysis of the nasal deformities to treat, in order to make an adapted treatment plan. Postoperative course is similar to other rhinoplasty cases without the use of this enzyme. Hyaluronidase should be used in all patients with nasal injections of HA (unless contraindications), who are willing to undergo a surgical rhinoplasty. The operation can be undertaken at one-week interval as soon as the edema subsides and no further treatments are necessary. [ABSTRACT FROM AUTHOR]

In recent years, the effectiveness of traditional treatment in non-small cell lung cancer (NSCLC) has become increasingly poor, and a new therapeutic strategy should be explored to solve the current problem of poor efficacy. Phototherapy based on stimuli-responsive nanocarriers combined with chemotherapy has drawn considerable attention as a kind of and significant potential tumour treatment method. By loading the drug osimertinib (AZD) and the targeting agent hyaluronic acid (HA) onto red-emitting carbon dots, a biocompatible multifunctional nanocrystalline drug carrier system (RCDs-HA@AZD) with dual stimulation of pH and hyaluronidase has been developed for chemotherapy/photothermal combination therapy of NSCLC. RCDs-HA@AZD has the ability to target NSCLC tumours with the loading of HA. Simultaneously, the tumour killing ability can be enhanced through a reasonable synergistic effect of the photothermal effect of RCDs and the anti-tumour function of AZD. This work provides inspiration for a combined anti-NSCLC therapeutic strategy as well as offers promising prospects in both fundamental and clinical investigations. [ABSTRACT FROM AUTHOR]

Aim: The present study aimed to compare the effectiveness of intralesional placentrex versus hyaluronidase + dexamethasone injection in the symptomatic management of stage II OSMF. Materials and Methods: This was a non-randomized prospective study conducted over a period of 14 months at a tertiary referral center. Patients with clinical stage II OSMF were randomly grouped into A(n = 18) and B(n = 17). These patients were treated with weekly intralesional injection of placentrex and hyaluronidase + dexamethasone respectively, over a period of six weeks. Variables such as mouth opening, burning sensation and colour of mucosa were evaluated at baseline(T0), second week(T1), fourth week(T3), sixth week(T4) of follow up. A p-value < 0.05 was considered statistically significant. Results: A total of 15 patients completed the study in each group with regular follow up. The mean improvement in mouth opening was 4.3 ± 0.57 mms in group A(p-value < 0.001) and 7.2 ± 0.76 mms in group B(p-value < 0.001) which were significant at the end of six weeks. Mean change in burning sensation at the end of six weeks in group A was 1.2 ± 0.73(p-value < 0.001), and 3.6 ± 0.63(p-value < 0.001) in group B. Mean change in colour of mucosa at the end of six weeks was 1.4 in group A(p-value > 0.05) and 2 in group B(p-value > 0.05). On comparison between both groups, patients in group B exhibited better mouth opening and reduction of burning sensation than patients in group A(p-value < 0.001). Conclusion: Both intralesional placentrex and hyaluronidase + dexamethasone injection are effective in alleviating the symptoms of stage II OSMF. However, hyaluronidase + dexamethasone injection showed slightly better improvement in mouth opening and burning sensation after six weeks. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis (OSMF) is a chronic debilitating and a well-recognized potentially malignant condition of the oral cavity, sometimes involving oropharynx associated with trismus and burning sensation. Apart from medical management and counselling, local injection of hyaluronidase mixed with triamcinolone acetonide has been used at our centre for the last 20 years with satisfactory clinical results and without any significant side effects. The problem with the treatment was that the doses and duration of treatment has not been standardized. Therefore, in this study, authors aim to evaluate and compare the efficacy of Triamcinolone alone versus Triamcinolone acetonide plus Hyaluronidase at weekly interval and improvement in Clinical and Histopathological staging of disease after 6 weeks of treatment. This study was conducted in Department of Otorhinolaryngology & Head Neck Surgery, with a total sample of 80 participants divided into two Groups, group A received Inj. Triamcinolone acetonide and group B received Inj. Triamcinolone Acetonide and Hyaluronidase 1500 IU at weekly interval. Pre-treatment and post-treatment clinical and histopathological profile of the patients were recorded and analyzed using SPSS 16 software. According to pre-treatment status, the proportion of clinical grades I, II and III were found in proportion 12.5%, 18.8% and 15.0% respectively. No significant difference was found in proportion of various grades between the groups (p = 0.388). At post treatment, the grading was reduced with changed proportion of grades I, II and III cases as 33.8%, 41.3% and 7.5% respectively. There was no significant difference in proportion of various grades between the groups (p = 0.681). Further, the intragroup comparison showed significant improvement Pre to post in group A (p = 0.002), Group B (p < 0.001) and overall, as well (p < 0.001). The inj. Triamcinolone acetonide and Inj. Hyaluronidase showed a better improvement on post treatment histopathological grading although the difference between the two groups was not significant statistically. [ABSTRACT FROM AUTHOR]

This study aimed to compare the results of injection triamcinolone and hyaluronidase combination with injection Platelet Rich Plasma (PRP) in management of Oral Submucous Fibrosis (OSMF). Present study was carried out in randomly divided two groups of 30 patients each of OSMF who all are presented with chief complain of reduced mouth opening. Group A patients were given 1 ml of injection triamcinolone and hyaluronidase combination. Group B patients received 1 ml of injection Platelet Rich Plasma. Both injections were given intralesionally once a week for 6 weeks. Results of ANOVA shows significant better results in improving mouth opening in group B patients receiving injection Platelet Rich Plasma as a treatment. In Group A, patients shows improvement in Maximum interincisal distance (MIID) of mean 6.51 ± 1.02 mm as compared to the patients in group B shows improvement in MIID of mean 9.53 ± 1.06 mm (p value < 0.05). Treatment of OSMF with injection Platelet Rich Plasma is a novel method and found to be more efficient than treatment with injection triamcinolone and hyaluronidase combination. [ABSTRACT FROM AUTHOR]

Subcutaneous (SC) infusion of large volumes at rapid flow rates has historically been limited by the glycosaminoglycan hyaluronan (HA), which forms a barrier to bulk fluid flow in the SC space. Recombinant human hyaluronidase PH20 (rHuPH20) depolymerizes HA, temporarily eliminating this barrier to rapid SC delivery of large volume co-administered therapeutics. Using a miniature pig model, in-line pressure and applied force to the delivery hardware were measured when subcutaneously infusing a representative macromolecule (human polyclonal immunoglobulin [Ig]), at varying concentrations and viscosities (20–200 mg/mL), co-formulated with and without rHuPH20 (2000 U/mL and 5000 U/mL). Maximal flow rate (Qmax) was calculated as the flow rate producing a statistically significant difference in mean applied force between injections administered with or without rHuPH20. There was a significant reduction in mean applied force required for SC delivery of 100 mg/mL Ig solution with 5000 U/mL rHuPH20 versus Ig solution alone. Similar significant reductions in mean applied force were observed for most Ig solution concentrations, ranging from 25–200 mg/mL when administered with or without 2000 U/mL rHuPH20. Qmax was inversely proportional to Ig solution viscosity and Qmax for solutions co-formulated with 5000 U/mL rHuPH20 was approximately double that of 2000 U/mL rHuPH20 solutions. Mathematical simulation of a hypothetical 800 mg Ig dose co-formulated with rHuPH20 showed that delivery times <30 s could be achieved across a broad range of concentrations. Addition of rHuPH20 can help overcome volume and time constraints associated with SC administration across a range of concentrations in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Background: Facial overfilled syndrome is an adverse event following minimally invasive soft tissue filler injections. It presents in most cases as excess midfacial volume and/or as unnatural smile which is difficult to detect due to the absence of standardized evaluation methods. Objective: To showcase how to identify, evaluate, and treat facial overfilled syndrome by utilizing facial ultrasound and simultaneous hyaluronidase injections. Methods: Twenty‐eight consecutive patients (26 females, 2 males) were enrolled in this study in which facial ultrasound was performed to evaluate the location previously implanted filler material. The position of the oral commissure was objectively measured in relation to bony landmarks, and the severity of lateral canthal lines was assessed by independent and blinded raters. Results: The material was identified in 35.7% inside the subdermal fatty layer, in 28.6% inside the deep supra‐periosteal fatty layer, in 10.7% inside the fibrous layer deep to the subdermal fatty layer, whereas in 25.0%, the product was not possible to locate clearly inside one specific layer. On average, 81.6 I.U. [range: 75–150] of hyaluronidase were injected. Lateral canthal line severity was before the treatment 2.28 (1.4) and was after the hyaluronidase treatment 2.02 (1.3) with p = 0.578. The position of the oral commissure increased by 0.60 cm in vertical and by 0.30 cm in horizontal directions (both p < 0.001). Conclusion: Facial overfilled syndrome following aesthetic soft tissue filler injections can present as excess midfacial volume but also as unnatural smile. Targeted hyaluronidase injections into the culprit pockets inside the midfacial soft tissues have shown to re‐establish a natural smile, to reduce excess midfacial volume, and to decrease lateral canthal line severity. [ABSTRACT FROM AUTHOR]

This article examines the adverse drug reactions caused by hyaluronidase and lignocaine in regional ophthalmic anesthesia. The study found that hyaluronidase had a higher incidence rate of positive test results compared to lignocaine. Patients with a history of bronchial asthma or allergic rhinitis were more likely to have a positive reaction to hyaluronidase. The study suggests that the longer residence time of hyaluronidase in the eye may contribute to the higher incidence of allergic reactions. The authors recommend conducting preoperative allergic skin tests for hyaluronidase, especially in patients with allergies, and suggest using ropivacaine as an alternative local anesthetic for patients who have a positive reaction to the combined lignocaine and hyaluronidase test dose. The article emphasizes the importance of considering potential risks and conducting appropriate tests to ensure patient safety during eye surgeries. [Extracted from the article]

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Electrochemiluminescence nanoprobes with a core–shell–shell structure have been designed and applied for hyaluronidase detection. The nanoprobes can precipitate efficiently through target-regulation wettability for collection, and enrich near to the hydrophobic electrode surface through hydrophobic interaction to enhance the performance of the biosensor. [ABSTRACT FROM AUTHOR]

Objective: Larvae of Hermitia illucens, or black soldier fly larvae (BSFL), have been recognized for their high lipid yield with a remarkable fatty acid profile. BSFL oil (SFO) offers the added value of a low environmental footprint and a sustainable product. In this study, the characteristics and cosmetic-related activities of SFO were investigated and compared with rice bran oil, olive oil and krill oil which are commonly used in cosmetics and supplements. Methods: The physicochemical characteristics were determined including acid value, saponification value, unsaponifiable matter and water content of SFO. The fatty acid composition was determined using GC-MS equipped with TR-FAME. The in vitro antioxidant properties were determined using DPPH, FRAP and lipid peroxidation inhibition assays. Antihyaluronidase (anti-HAase) activity was measured by detecting enzyme activity and molecular docking of candidate compounds toward the HAase enzyme. The safety assessment towards normal human cells was determined using the MTT assay and the UVB protection upon UVB-irradiated fibroblasts was determined using the DCF-DA assay. The whitening effect of SFO was determined using melanin content inhibition. Results: SFO contains more than 60% polyunsaturated fatty acids followed by saturated fatty acids (up to 37%). The most abundant component found in SFO was linoleic acid (C18:2 n-6 cis). Multiple anti-oxidant mechanisms of SFO were discovered. In addition, SFO and krill oil prevented hyaluronic acid (HA) degradation via strong HAase inhibition comparable with the positive control, oleanolic acid. The molecular docking confirmed the binding interactions and molecular recognition of major free fatty acids toward HAase. Furthermore, SFO exhibited no cytotoxicity on primary human skin fibroblasts, HaCaT keratinocytes and PBMCs (IC50 values > 200 μg/mL). SFO possessed significant in-situ antioxidant activity in UVB-irradiated fibroblasts and the melanin inhibition activity as effective as well-known anti-pigmenting compounds (kojic acid and arbutin, p < 0.05). Conclusion: This study provides scientific support for various aspects of SFO. SFO can be considered an alternative oil ingredient in cosmetic products with potential implications for anti-skin aging, whitening and UVB protection properties, making it a potential candidate oil in the cosmetic industry. [ABSTRACT FROM AUTHOR]