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37 pages, 2305 KiB  
Review
Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases
by Che-Yu Hsu, Hieu-Huy Nguyen-Tran, Yu-An Chen, Kuan-Ting Lee, Tzong-Yuan Juang, Ming-Fu Chiang, Shin-Yi Liu and Nan-Shan Chang
Int. J. Mol. Sci. 2025, 26(11), 5132; https://doi.org/10.3390/ijms26115132 - 27 May 2025
Viewed by 1339
Abstract
Hyaluronan (HA) is essentially secreted by every cell and plays a critical role in maintaining normal cell physiology. While the structure and function of HA have been extensively investigated, questions regarding the sizes and conformation of HA under physiological and inflamed conditions, in [...] Read more.
Hyaluronan (HA) is essentially secreted by every cell and plays a critical role in maintaining normal cell physiology. While the structure and function of HA have been extensively investigated, questions regarding the sizes and conformation of HA under physiological and inflamed conditions, in relevance to its functions, remain elusive. In this article, we update our knowledge of the HA functional properties, including binding proteins and their signaling networks, as well as matrix formation, which can potentially induce phase separation and affect the mobility and behavior of small molecules, proteins, and cells. We detail the striking differences regarding the biological outcomes of signaling pathways for HA and membrane receptors versus HA and GPI-linked hyaluronidase Hyal-2. We describe: (1) the native, large-sized HA is not proapoptotic but signals with an overexpressed HYAL-2/WWOX/SMAD4 complex to induce apoptosis, which is likely to occur in an inflamed microenvironment; (2) HA-binding proteins are connected via signal pathway networks. The competitive binding of HA and TGF-β to the membrane HYAL-2 and the downstream HYAL-2/WWOX/SMAD4 signaling is addressed; (3) the phase-separated proteins or small molecules in the HA matrices may contribute to the aberrant interactions, leading to inflammation and disease progression; (4) the role of HA and complement C1q in Alzheimer’s disease via connection with a risk factor for Alzheimer’s disease WWOX is also discussed; (5) a hidden function is the inducible HA conformational changes that confer cancer suppression and, probably, retardation of neurodegeneration. Full article
(This article belongs to the Special Issue Neurodegeneration: From Genetics to Molecules—2nd Edition)
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25 pages, 12425 KiB  
Article
DBI as a Novel Immunotherapeutic Candidate in Colorectal Cancer: Dissecting Genetic Risk and the Immune Landscape via GWAS, eQTL, and pQTL
by Ting Tian, Huan Han, Jingtao Huang, Jun’e Ma and Ruoxi Ran
Biomedicines 2025, 13(5), 1115; https://doi.org/10.3390/biomedicines13051115 - 4 May 2025
Viewed by 693
Abstract
Background: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Identifying drug targets associated with CRC is crucial for developing targeted therapies. Methods: MR (IVW, Wald ratio, weighted median, and MR-Egger) and SMR analyses were used to screen candidate genes associated [...] Read more.
Background: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Identifying drug targets associated with CRC is crucial for developing targeted therapies. Methods: MR (IVW, Wald ratio, weighted median, and MR-Egger) and SMR analyses were used to screen candidate genes associated with CRC risk. Further validation was performed using The Cancer Genome Atlas (TCGA) to assess gene expression patterns and prognostic significance. Additionally, immune infiltration analysis was conducted to characterize the tumor immune microenvironment. Drug prediction was performed to explore potential therapeutic interventions. Results: Eight genes were identified associated with CRC. IGFBP3, CD72, SERPINH1, CHRDL2, LRP11, and SPARCL1 were linked to an increased risk of CRC, whereas DBI and HYAL1 were associated with a decreased risk of CRC. Notably, DBI exhibited a potentially favorable immune profile, negatively correlated with Tregs and MDSCs while positively associated with activated CD8+ and CD4+ T cells. Conclusions: Eight genes were identified as associated with CRC, among which DBI exhibited a potential protective role, correlating with improved patient survival, enhanced immune activation, and increased responsiveness to immunotherapy. The remaining proteins demonstrated diverse and complex functions within the tumor immune microenvironment, providing novel insights for the development of precision diagnostics and immunotherapeutic strategies. Full article
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15 pages, 4348 KiB  
Article
Lithospermum erythrorhizon and Forsythia suspensa Prevent Collagen Degradation and Maintain Skin Hydration by Regulating MMPs and HAS2/HYAL1 Signaling
by Xiangji Jin, Qiwen Zheng, Trang Thi Minh Nguyen, Se-Jig Park, Gyeong-Seon Yi, Su-Jin Yang and Tae-Hoo Yi
Molecules 2025, 30(5), 1083; https://doi.org/10.3390/molecules30051083 - 27 Feb 2025
Viewed by 916
Abstract
The growing demand for aesthetic enhancement has driven the development of anti-aging cosmetics, with natural compound-based formulations emerging as a new trend to enhance efficacy. This study aims to develop a 30% ethanol extract of a 1:1 mixture of Lithospermum erythrorhizon and Forsythia [...] Read more.
The growing demand for aesthetic enhancement has driven the development of anti-aging cosmetics, with natural compound-based formulations emerging as a new trend to enhance efficacy. This study aims to develop a 30% ethanol extract of a 1:1 mixture of Lithospermum erythrorhizon and Forsythia suspensa (LF) as a potential material for combating UVB-induced skin aging. The bioactive components of LF extract were identified via HPLC. Antioxidant efficacy (DPPH, ABTS, and SOD) and the inhibitory effects on ROS production in cells were evaluated using flow cytometry. MMPs’ expressions were analyzed via RT-PCR, while TGF-β/Smad, ERK/AP-1, and HAS2/HYAL1 pathways were examined via ELISA and Western blot. Research findings indicate that LF effectively scavenges reactive oxygen species and enhances the activation of TGF-β signaling, promoting the synthesis of PIP (Procollagen Type I C-Peptide). Collagen degradation was mitigated through the inhibition of the AP-1 pathway, which regulates the expression of MMPs, and by suppressing the expression of TIMP. Additionally, modulation of the HAS2/HYAL1 signaling axis ensures a balanced regulation of hyaluronic acid (HA) synthesis and degradation, thereby contributing to the maintenance of collagen integrity and skin hydration. In conclusion, LF has exhibited significant protective effects against demonstrated anti-aging properties, highlighting its potential as a novel therapeutic agent in cosmetic formulations targeting aging. Full article
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17 pages, 2027 KiB  
Review
Genetic Deficiencies of Hyaluronan Degradation
by Stephen P. Fink and Barbara Triggs-Raine
Cells 2024, 13(14), 1203; https://doi.org/10.3390/cells13141203 - 16 Jul 2024
Cited by 6 | Viewed by 2358
Abstract
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, [...] Read more.
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. Full article
(This article belongs to the Special Issue Role of Hyaluronan in Human Health and Disease)
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14 pages, 2555 KiB  
Article
Hyaluron-Based Bionanocomposites of Silver Nanoparticles with Graphene Oxide as Effective Growth Inhibitors of Wound-Derived Bacteria
by Anna Lenart-Boroń, Klaudia Stankiewicz, Kinga Dworak, Klaudia Bulanda, Natalia Czernecka, Anna Ratajewicz, Karen Khachatryan and Gohar Khachatryan
Int. J. Mol. Sci. 2024, 25(13), 6854; https://doi.org/10.3390/ijms25136854 - 22 Jun 2024
Viewed by 1485
Abstract
Keeping wounds clean in small animals is a big challenge, which is why they often become infected, creating a risk of transmission to animal owners. Therefore, it is crucial to search for new biocompatible materials that have the potential to be used in [...] Read more.
Keeping wounds clean in small animals is a big challenge, which is why they often become infected, creating a risk of transmission to animal owners. Therefore, it is crucial to search for new biocompatible materials that have the potential to be used in smart wound dressings with both wound healing and bacteriostatic properties to prevent infection. In our previous work, we obtained innovative hyaluronate matrix-based bionanocomposites containing nanosilver and nanosilver/graphene oxide (Hyal/Ag and Hyal/Ag/GO). This study aimed to thoroughly examine the bacteriostatic properties of foils containing the previously developed bionanocomposites. The bacteriostatic activity was assessed in vitro on 88 Gram-positive (n = 51) and Gram-negative (n = 37) bacteria isolated from wounds of small animals and whose antimicrobial resistance patterns and resistance mechanisms were examined in an earlier study. Here, 69.32% of bacterial growth was inhibited by Hyal/Ag and 81.82% by Hyal/Ag/GO. The bionanocomposites appeared more effective against Gram-negative bacteria (growth inhibition of 75.68% and 89.19% by Hyal/Ag and Hyal/Ag/Go, respectively). The effectiveness of Hyal/Ag/GO against Gram-positive bacteria was also high (inhibition of 80.39% of strains), while Hyal/Ag inhibited the growth of 64.71% of Gram-positive bacteria. The effectiveness of Hyal/Ag and Hyal/Ag/Go varied depending on bacterial genus and species. Proteus (Gram-negative) and Enterococcus (Gram-positive) appeared to be the least susceptible to the bionanocomposites. Hyal/Ag most effectively inhibited the growth of non-pathogenic Gram-positive Sporosarcina luteola and Gram-negative Acinetobacter. Hyal/Ag/GO was most effective against Gram-positive Streptococcus and Gram-negative Moraxella osloensis. The Hyal/Ag/GO bionanocomposites proved to be very promising new antibacterial, biocompatible materials that could be used in the production of bioactive wound dressings. Full article
(This article belongs to the Section Materials Science)
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26 pages, 13349 KiB  
Article
Anomaly Detection and Artificial Intelligence Identified the Pathogenic Role of Apoptosis and RELB Proto-Oncogene, NF-kB Subunit in Diffuse Large B-Cell Lymphoma
by Joaquim Carreras and Rifat Hamoudi
BioMedInformatics 2024, 4(2), 1480-1505; https://doi.org/10.3390/biomedinformatics4020081 - 7 Jun 2024
Cited by 5 | Viewed by 2556
Abstract
Background: Diffuse large B-cell lymphoma (DLBCL) is one of the most frequent lymphomas. DLBCL is phenotypically, genetically, and clinically heterogeneous. Aim: We aim to identify new prognostic markers. Methods: We performed anomaly detection analysis, other artificial intelligence techniques, and conventional statistics using gene [...] Read more.
Background: Diffuse large B-cell lymphoma (DLBCL) is one of the most frequent lymphomas. DLBCL is phenotypically, genetically, and clinically heterogeneous. Aim: We aim to identify new prognostic markers. Methods: We performed anomaly detection analysis, other artificial intelligence techniques, and conventional statistics using gene expression data of 414 patients from the Lymphoma/Leukemia Molecular Profiling Project (GSE10846), and immunohistochemistry in 10 reactive tonsils and 30 DLBCL cases. Results: First, an unsupervised anomaly detection analysis pinpointed outliers (anomalies) in the series, and 12 genes were identified: DPM2, TRAPPC1, HYAL2, TRIM35, NUDT18, TMEM219, CHCHD10, IGFBP7, LAMTOR2, ZNF688, UBL7, and RELB, which belonged to the apoptosis, MAPK, MTOR, and NF-kB pathways. Second, these 12 genes were used to predict overall survival using machine learning, artificial neural networks, and conventional statistics. In a multivariate Cox regression analysis, high expressions of HYAL2 and UBL7 were correlated with poor overall survival, whereas TRAPPC1, IGFBP7, and RELB were correlated with good overall survival (p < 0.01). As a single marker and only in RCHOP-like treated cases, the prognostic value of RELB was confirmed using GSEA analysis and Kaplan–Meier with log-rank test and validated in the TCGA and GSE57611 datasets. Anomaly detection analysis was successfully tested in the GSE31312 and GSE117556 datasets. Using immunohistochemistry, RELB was positive in B-lymphocytes and macrophage/dendritic-like cells, and correlation with HLA DP-DR, SIRPA, CD85A (LILRB3), PD-L1, MARCO, and TOX was explored. Conclusions: Anomaly detection and other bioinformatic techniques successfully predicted the prognosis of DLBCL, and high RELB was associated with a favorable prognosis. Full article
(This article belongs to the Special Issue Feature Papers in Applied Biomedical Data Science)
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21 pages, 3536 KiB  
Review
Zfra Overrides WWOX in Suppressing the Progression of Neurodegeneration
by Yu-An Chen, Tsung-Yun Liu, Kuan-Yu Wen, Che-Yu Hsu, Chun-I Sze and Nan-Shan Chang
Int. J. Mol. Sci. 2024, 25(6), 3507; https://doi.org/10.3390/ijms25063507 - 20 Mar 2024
Cited by 1 | Viewed by 2466
Abstract
We reported that a 31-amino-acid Zfra protein (zinc finger-like protein that regulates apoptosis) blocks neurodegeneration and cancer growth. Zfra binds WW domain-containing oxidoreductase (WWOX) to both N- and C-termini, which leads to accelerated WWOX degradation. WWOX limits the progression of neurodegeneration [...] Read more.
We reported that a 31-amino-acid Zfra protein (zinc finger-like protein that regulates apoptosis) blocks neurodegeneration and cancer growth. Zfra binds WW domain-containing oxidoreductase (WWOX) to both N- and C-termini, which leads to accelerated WWOX degradation. WWOX limits the progression of neurodegeneration such as Alzheimer’s disease (AD) by binding tau and tau-hyperphosphorylating enzymes. Similarly, Zfra binds many protein targets and accelerates their degradation independently of ubiquitination. Furthermore, Zfra4-10 peptide strongly prevents the progression of AD-like symptoms in triple-transgenic (3xTg) mice during aging. Zfra4-10 peptide restores memory loss in 9-month-old 3xTg mice by blocking the aggregation of a protein cascade, including TPC6AΔ, TIAF1, and SH3GLB2, by causing aggregation of tau and amyloid β. Zfra4-10 also suppresses inflammatory NF-κB activation. Zfra-activated Hyal-2+ CD3- CD19- Z cells in the spleen, via Hyal-2/WWOX/Smad4 signaling, are potent in cancer suppression. In this perspective review, we provide mechanistic insights regarding how Zfra overrides WWOX to induce cancer suppression and retard AD progression via Z cells. Full article
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15 pages, 1221 KiB  
Article
Programmed Death-Ligand (PD-L1), Epidermal Growth Factor (EGF), Relaxin, and Matrix Metalloproteinase-3 (MMP3): Potential Biomarkers of Malignancy in Canine Mammary Neoplasia
by Makchit Galadima, Mariana Teles, Josep Pastor, Javier Hernández-Losa, Joan Enric Rodríguez-Gil and Maria Montserrat Rivera del Alamo
Int. J. Mol. Sci. 2024, 25(2), 1170; https://doi.org/10.3390/ijms25021170 - 18 Jan 2024
Cited by 2 | Viewed by 1771
Abstract
Gene expression has been suggested as a putative tool for prognosis and diagnosis in canine mammary neoplasia (CMNs). In the present study, 58 formalin-fixed paraffin-embedded (FFPE) paraffined canine mammary neoplasias from 27 different bitches were included. Thirty-seven tumours were classified as benign, whereas [...] Read more.
Gene expression has been suggested as a putative tool for prognosis and diagnosis in canine mammary neoplasia (CMNs). In the present study, 58 formalin-fixed paraffin-embedded (FFPE) paraffined canine mammary neoplasias from 27 different bitches were included. Thirty-seven tumours were classified as benign, whereas thirty-one were classified as different types of canine carcinoma. In addition, mammary samples from three healthy bitches were also included. The gene expression for vascular endothelial growth factor-α (VEGFα), CD20, progesterone receptor (PGR), hyaluronidase-1 (HYAL-1), programmed death-ligand 1 (PD-L1), epidermal growth factor (EGF), relaxin (RLN2), and matrix metalloproteinase-3 (MMP3) was assessed through RT-qPCR. All the assessed genes yielded a higher expression in neoplastic mammary tissue than in healthy tissue. All the evaluated genes were overexpressed in neoplastic mammary tissue, suggesting a role in the process of tumorigenesis. Moreover, PD-L1, EGF, relaxin, and MMP3 were significantly overexpressed in malignant CMNs compared to benign CMNs, suggesting they may be useful as malignancy biomarkers. Full article
(This article belongs to the Special Issue A Molecular Perspective on Reproductive Health)
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19 pages, 3189 KiB  
Review
A Review of Ixodid Ticks (Acari: Ixodidae) Associated with Lacerta spp. (Reptilia: Lacertidae) from the Caucasus and Adjacent Territory
by Maria V. Orlova, Igor V. Doronin, Marina A. Doronina and Nikolay V. Anisimov
Diversity 2023, 15(9), 1026; https://doi.org/10.3390/d15091026 - 21 Sep 2023
Cited by 4 | Viewed by 2822
Abstract
Based on a literature review, as well as on our own data, 14 ixodid tick species belonging to 5 genera were registered for the lizard hosts of the genus Lacerta (L. agilis, L. media, and L. strigata) in the [...] Read more.
Based on a literature review, as well as on our own data, 14 ixodid tick species belonging to 5 genera were registered for the lizard hosts of the genus Lacerta (L. agilis, L. media, and L. strigata) in the Caucasus and the adjacent territories: Haemaphysalis sulcata, Haem. punctata, Haem. parva, Haem. caucasica, Haem. concinna, Haem. inermis, Ixodes ricinus, I. redikorzevi, Dermacentor marginatus, D. reticulatus, Hyalomma marginatum, Rhipicephalus bursa, Rh. rossicum, and Rh. turanicum. Tick species Haem. caucasica were recorded from Armenia for the first time. Our findings of Haem. punctata represent the first record of this species for Chechnya, Ingushetia (Russia), Armenia, and Azerbaijan. Most of the parasite species are associated with L. agilis (13) and L. strigata (12); L. media is a host of 6 tick species. Data on the infestation of Lacerta spp. by four tick species from our material (I. ricinus, Haem. punctata, Haem. caucasica, and Hyal. marginatum) are presented in the article. In addition, our article contains information on the range of infections associated with the above tick species. Castor bean tick I. ricinus (236 specimens), the most represented species in our collection, parasitizes all available terrestrial vertebrates including humans and can be vector of many various pathogens, so our study provides significant epidemiological information. Full article
(This article belongs to the Special Issue Herpetofauna of Eurasia)
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14 pages, 2169 KiB  
Article
Investigation of Crosslinking Parameters and Characterization of Hyaluronic Acid Dermal Fillers: From Design to Product Performances
by Stefano Pluda, Cecilia Salvagnini, Anna Fontana, Anna Marchetti, Alba Di Lucia, Devis Galesso and Cristian Guarise
Gels 2023, 9(9), 733; https://doi.org/10.3390/gels9090733 - 9 Sep 2023
Cited by 12 | Viewed by 6920
Abstract
Despite process similarities, distinctive manufacturing technologies offer hyaluronic acid dermal fillers with different in vitro physicochemical and rheological properties due to peculiar crosslinked hydrogel networks. A better understanding of dermal filler properties could provide specific clinical indications and expectations with more accurate performance [...] Read more.
Despite process similarities, distinctive manufacturing technologies offer hyaluronic acid dermal fillers with different in vitro physicochemical and rheological properties due to peculiar crosslinked hydrogel networks. A better understanding of dermal filler properties could provide specific clinical indications and expectations with more accurate performance correlations. In this study, with an emphasis on the degree of modification, hyaluronic acid concentration and molecular weight, these process parameters were able to modulate dermal filler properties, especially rheology. Moreover, an extensive characterization of commercial hyaluronic acid injectables of the Hyal System line was described to present product properties and help to elucidate related clinical effects. Standardized methodologies were applied to correlate in vitro parameters with feasible clinical indications. In view of an optimized dermal filler design, the results of the extrudability measurements allowed the quantification of the effect of hydrogel composition, rheological properties and needle size on injectability. Composition, dynamic viscosity and needle size showed an impactful influence on hydrogel extrudability. Finally, the positive influence of 200 KDa hyaluronic acid in comparison to fragments of ether-crosslinked hyaluronic acid on fibroblast recognition were shown with a migration assay. Full article
(This article belongs to the Special Issue State-of-the-Art Gel Research in Italy)
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12 pages, 1244 KiB  
Article
Thermosensitive Intravitreal In Situ Implant of Cefuroxime Based on Poloxamer 407 and Hyaluronic Acid
by Elena O. Bakhrushina, Anastasia I. Dubova, Maria S. Nikonenko, Viktoriya V. Grikh, Marina M. Shumkova, Tatyana V. Korochkina, Ivan I. Krasnyuk and Ivan I. Krasnyuk
Gels 2023, 9(9), 693; https://doi.org/10.3390/gels9090693 - 28 Aug 2023
Cited by 4 | Viewed by 2122
Abstract
The main method of treatment and prevention of endophthalmitis is a combination of intravitreal and topical administration of antibiotics, such as cefuroxime moxifloxacin or vancomycin. However, this method is ineffective due to the rapid elimination of the drug. This problem can be solved [...] Read more.
The main method of treatment and prevention of endophthalmitis is a combination of intravitreal and topical administration of antibiotics, such as cefuroxime moxifloxacin or vancomycin. However, this method is ineffective due to the rapid elimination of the drug. This problem can be solved with the help of intravitreal in situ injection systems, which are injected with a syringe into the vitreous body and provide prolonged action of the drug at the focus of inflammation. Under the influence of temperature, the liquid drug undergoes a phase transition and turns into a gel after injection. This ensures its prolonged action. The study aimed to develop an intravitreal in situ cefuroxime delivery system for the treatment of endophthalmitis based on a thermosensitive biodegradable composition of poloxamer 407 and hyaluronic acid. A combination of poloxamer Kolliphor® P407, Kolliphor® P188, and PrincipHYAL® hyaluronic acids of different molecular weights was used as a delivery system. The potency of cefuroxime solid dispersion with polyvinylpyrrolidone-10000, polyethylene glycol-400, and polyethylene glycol-1500 in a 1:2 ratio was studied for prolonged action compared to cefuroxime substance. The experimental formulations were studied for the parameters of gelation temperature in a long-term test (4 months), pH, and release of cefuroxime using dialysis bags. To study the distribution parameter in the vitreous body, an in vitro model (1/13) was developed, which was a hollow agar sphere filled with 1% (w/v) polyacrylate gel. For the superior formulations, a HET-CAM test (chorioallantoic membrane test) was performed to determine the absence of irritant effects. According to the study results, a formulation containing a solid dispersion of cefuroxime:PEG-400 (1:2), the matrix of which contained 18% (w/v) Kolliphor® P407 poloxamer, 3% (w/v) Kolliphor® P188 poloxamer, and 0.5% (w/v) hyaluronic acid (1400–1800), was selected. This sample had an average gelation temperature of 34.6 °C, pH 6.7 ± 0.5, and a pronounced prolonged effect. Only 7.6% was released in 3 h of the experiment, whereas about 38% of cefuroxime was released in 72 h. No irritant effect on the chorioallantoic membrane was observed for any formulations studied. Full article
(This article belongs to the Special Issue Research on Hydrogels for Controlled Drug Delivery)
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20 pages, 4962 KiB  
Article
Effects of Water–Ethanol Extracts from Four Sphagnum Species on Gene Expression of Selected Enzymes in Normal Human Dermal Fibroblasts and Their Antioxidant Properties
by Maria Zych, Katarzyna Urbisz, Magdalena Kimsa-Dudek, Maria Kamionka, Sławomir Dudek, Barbara Klaudia Raczak, Stanisław Wacławek, Damian Chmura, Ilona Kaczmarczyk-Żebrowska and Adam Stebel
Pharmaceuticals 2023, 16(8), 1076; https://doi.org/10.3390/ph16081076 - 28 Jul 2023
Cited by 6 | Viewed by 2822
Abstract
Mosses (Bryophyta), particularly species of the genus Sphagnum, which have been used for centuries for the treatment of skin diseases and damage, are still not explored enough in terms of their use in cosmetics. The purpose of this study was to determine [...] Read more.
Mosses (Bryophyta), particularly species of the genus Sphagnum, which have been used for centuries for the treatment of skin diseases and damage, are still not explored enough in terms of their use in cosmetics. The purpose of this study was to determine the antioxidant properties of water–ethanol extracts from four selected species of the genus Sphagnum (S. girgenshonii Russow, S. magellanicum Brid., S. palustre L., and S. squarrosum Crome) and their impact on the expression of genes encoding key enzymes for the functioning of the skin. In this study, the effects of Sphagnum extracts on the expression of genes encoding tyrosinase, collagenase, elastase, hyaluronidase and hyaluronic acid synthase in human dermal fibroblasts were determined for the first time in vitro. The extracts inhibited tyrosinase gene expression and showed antioxidant activity. The experiment showed an increase in the expression of some genes encoding collagenase (MMP1) or hyaluronidase (HYAL2, HYAL3 and HYAL4) and a decrease in the hyaluronan synthase (HAS1, HAS2 and HAS3) genes expression by the tested extracts. The obtained results suggest that using extracts from the tested Sphagnum species in anti-aging cosmetics does not seem beneficial. Further studies are needed to clarify their impact on the skin. Full article
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15 pages, 2306 KiB  
Article
Targeting BET Proteins Decreases Hyaluronidase-1 in Pancreatic Cancer
by Krishan Kumar, Deepak Kanojia, David J. Bentrem, Rosa F. Hwang, Jonathan P. Butchar, Susheela Tridandapani and Hidayatullah G. Munshi
Cells 2023, 12(11), 1490; https://doi.org/10.3390/cells12111490 - 27 May 2023
Cited by 7 | Viewed by 2788
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of dense stroma that is enriched in hyaluronan (HA), with increased HA levels associated with more aggressive disease. Increased levels of the HA-degrading enzymes hyaluronidases (HYALs) are also associated with tumor progression. In [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of dense stroma that is enriched in hyaluronan (HA), with increased HA levels associated with more aggressive disease. Increased levels of the HA-degrading enzymes hyaluronidases (HYALs) are also associated with tumor progression. In this study, we evaluate the regulation of HYALs in PDAC. Methods: Using siRNA and small molecule inhibitors, we evaluated the regulation of HYALs using quantitative real-time PCR (qRT-PCR), Western blot analysis, and ELISA. The binding of BRD2 protein on the HYAL1 promoter was evaluated by chromatin immunoprecipitation (ChIP) assay. Proliferation was evaluated by WST-1 assay. Mice with xenograft tumors were treated with BET inhibitors. The expression of HYALs in tumors was analyzed by immunohistochemistry and by qRT-PCR. Results: We show that HYAL1, HYAL2, and HYAL3 are expressed in PDAC tumors and in PDAC and pancreatic stellate cell lines. We demonstrate that inhibitors targeting bromodomain and extra-terminal domain (BET) proteins, which are readers of histone acetylation marks, primarily decrease HYAL1 expression. We show that the BET family protein BRD2 regulates HYAL1 expression by binding to its promoter region and that HYAL1 downregulation decreases proliferation and enhances apoptosis of PDAC and stellate cell lines. Notably, BET inhibitors decrease the levels of HYAL1 expression in vivo without affecting the levels of HYAL2 or HYAL3. Conclusions: Our results demonstrate the pro-tumorigenic role of HYAL1 and identify the role of BRD2 in the regulation of HYAL1 in PDAC. Overall, these data enhance our understanding of the role and regulation of HYAL1 and provide the rationale for targeting HYAL1 in PDAC. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Cell Death in Gastrointestinal Disease)
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24 pages, 5999 KiB  
Article
Hydrangea serrata Hot Water Extract and Its Major Ingredient Hydrangenol Improve Skin Moisturization and Wrinkle Conditions via AP-1 and Akt/PI3K Pathway Upregulation
by Ji Hye Yoon, Sang Hee Park, Si Eun Yoon, Seong Yoon Hong, Jun Bae Lee, Jongsung Lee and Jae Youl Cho
Nutrients 2023, 15(11), 2436; https://doi.org/10.3390/nu15112436 - 24 May 2023
Cited by 6 | Viewed by 3521
Abstract
Hydrangea serrata is a plant grown in Korea and Japan with a particular natural compound, hydrangenol. H. serrata has been researched for its anti-fungal properties, and ability to attenuate allergies and promote muscle growth. Its ability to reduce skin dryness is poorly understood. For [...] Read more.
Hydrangea serrata is a plant grown in Korea and Japan with a particular natural compound, hydrangenol. H. serrata has been researched for its anti-fungal properties, and ability to attenuate allergies and promote muscle growth. Its ability to reduce skin dryness is poorly understood. For that reason, we investigated whether H. serrata hot water extracts (Hs-WE) can moisturize keratinocytes. In clinical studies (Approval Code: GIRB-21929-NY and approval Date: 5 October 2021), skin wrinkles and skin moisturizing levels were improved in subjects applying 0.5% Hs-WE compared to the placebo group. We confirmed the components of Hs-WE from the LC/MS-MS analysis. Hs-WE and hydrangenol did not show cytotoxicity in HaCaT cells at all concentrations. Cell growth was also promoted by Hs-WE (5–20 µg/mL) and hydrangenol (15–60 µM) in a wound healing assay. Skin moisturizing factors were upregulated by the presence of Hs-WE or hydrangenol, and the hyaluronidases (HYAL) were inhibited at the mRNA level. Meanwhile, COL1A1 was increased by the presence of Hs-WE or hydrangenol. MAPK, AP-1, and Akt/PI3k signaling proteins, which are associated with cell proliferation and moisturizing factors, were increased by the administration of Hs-WE and hydrangenol. Has-1, 2, and 3 levels were enhanced via JNK when using the inhibitors of MAPK proteins and Hs-WE and hydrangenol, respectively. Taken together, Hs-WE could be used as cosmeceutical materials for improving skin conditions. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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34 pages, 22996 KiB  
Article
Effects of Therapeutic Platelet-Rich Plasma on Overactive Bladder via Modulating Hyaluronan Synthesis in Ovariectomized Rat
by Jian-He Lu, Kuang-Shun Chueh, Tai-Jui Juan, Jing-Wen Mao, Rong-Jyh Lin, Yi-Chen Lee, Mei-Chen Shen, Ting-Wei Sun, Hung-Yu Lin and Yung-Shun Juan
Int. J. Mol. Sci. 2023, 24(9), 8242; https://doi.org/10.3390/ijms24098242 - 4 May 2023
Cited by 6 | Viewed by 3013
Abstract
Postmenopausal women who have ovary hormone deficiency (OHD) may experience urological dysfunctions, such as overactive bladder (OAB) symptoms. This study used a female Sprague Dawley rat model that underwent bilateral ovariectomy (OVX) to simulate post-menopause in humans. The rats were treated with platelet-rich [...] Read more.
Postmenopausal women who have ovary hormone deficiency (OHD) may experience urological dysfunctions, such as overactive bladder (OAB) symptoms. This study used a female Sprague Dawley rat model that underwent bilateral ovariectomy (OVX) to simulate post-menopause in humans. The rats were treated with platelet-rich plasma (PRP) or platelet-poor plasma (PPP) after 12 months of OVX to investigate the therapeutic effects of PRP on OHD-induced OAB. The OVX-treated rats exhibited a decrease in the expression of urothelial barrier-associated proteins, altered hyaluronic acid (hyaluronan; HA) production, and exacerbated bladder pathological damage and interstitial fibrosis through NFƘB/COX-2 signaling pathways, which may contribute to OAB. In contrast, PRP instillation for four weeks regulated the inflammatory fibrotic biosynthesis, promoted cell proliferation and matrix synthesis of stroma, enhanced mucosal regeneration, and improved urothelial mucosa to alleviate OHD-induced bladder hyperactivity. PRP could release growth factors to promote angiogenic potential for bladder repair through laminin/integrin-α6 and VEGF/VEGF receptor signaling pathways in the pathogenesis of OHD-induced OAB. Furthermore, PRP enhanced the expression of HA receptors and hyaluronan synthases (HAS), reduced hyaluronidases (HYALs), modulated the fibroblast-myofibroblast transition, and increased angiogenesis and matrix synthesis via the PI3K/AKT/m-TOR pathway, resulting in bladder remodeling and regeneration. Full article
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