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1.
Sci Rep ; 14(1): 15252, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956126

RESUMO

This study aims to investigate the factors effective in predicting the persistence of reflux after the first subureteric transurethral injection (STING) of dextranomer/hyaluronic acid copolymer in pediatric patients with vesicoureteral reflux. The data of patients without a previous history of surgery to treat vesicoureteral reflux and who underwent STING for the first time between September 2011 and November 2020 were investigated retrospectively. After considering exclusion criteria, of 199 patients, 127 patients and 180 renal units were suitable for inclusion. A renal unit-based evaluation was made. Age < 61 months (univariate: p = 0.001, multivariate: p = 0.015, HR: 2.352 (1.181-4.686), OR (95% CI)), moderate reflux level (grade 3) (univariate: p < 0.001, multivariate: p = 0.019, HR: 2.703 (1.177-6.209), OR (95% CI)), DRF (differential renal function) < 45 (univariate: p = 0.020, multivariate: p = 0.047, HR: 1.992 (1.009-3.935), OR (95% CI)), and UDR (ureteral diameter ratio) > 0.15 (univariate: p < 0.001, multivariate: p = 0.005, HR: 2.786 (1.368-5.672), OR (95% CI)) were found predictors of reflux persistence after STING surgery both univariate and multivariate analysis. High reflux level (grade 4-5) was statistically significant in univariate analysis (p < 0.001) but not statistically significant in multivariate analysis (p = 0.215). In our study, UDR and DRF were found to be factors affecting reflux persistence. UDR and DRF should be considered in order to predict reflux resolution in patients who will undergo STING.


Assuntos
Dextranos , Ácido Hialurônico , Refluxo Vesicoureteral , Humanos , Refluxo Vesicoureteral/terapia , Ácido Hialurônico/administração & dosagem , Dextranos/administração & dosagem , Feminino , Masculino , Pré-Escolar , Estudos Retrospectivos , Lactente , Criança , Injeções , Resultado do Tratamento
2.
Sci Adv ; 10(27): eado9120, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38959311

RESUMO

A bioinspired hydrogel composed of hyaluronic acid-graft-dopamine (HADA) and a designer peptide HGF-(RADA)4-DGDRGDS (HRR) was presented to enhance tissue integration following spinal cord injury (SCI). The HADA/HRR hydrogel manipulated the infiltration of PDGFRß+ cells in a parallel pattern, transforming dense scars into an aligned fibrous substrate that guided axonal regrowth. Further incorporation of NT3 and curcumin promoted axonal regrowth and survival of interneurons at lesion borders, which served as relays for establishing heterogeneous axon connections in a target-specific manner. Notable improvements in motor, sensory, and bladder functions resulted in rats with complete spinal cord transection. The HADA/HRR + NT3/Cur hydrogel promoted V2a neuron accumulation in ventral spinal cord, facilitating the recovery of locomotor function. Meanwhile, the establishment of heterogeneous neural connections across the hemisected lesion of canines was documented in a target-specific manner via neuronal relays, significantly improving motor functions. Therefore, biomaterials can inspire beneficial biological activities for SCI repair.


Assuntos
Matriz Extracelular , Hidrogéis , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Animais , Hidrogéis/química , Ratos , Matriz Extracelular/metabolismo , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Cães , Axônios/metabolismo , Axônios/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Ácido Hialurônico/química , Ácido Hialurônico/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Dopamina/metabolismo , Feminino , Modelos Animais de Doenças , Ratos Sprague-Dawley , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Medula Espinal/metabolismo
3.
Biofabrication ; 16(4)2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38955197

RESUMO

Plasma cells (PCs) in bone marrow (BM) play an important role in both protective and pathogenic humoral immune responses, e.g. in various malignant and non-malignant diseases such as multiple myeloma, primary and secondary immunodeficiencies and autoimmune diseases. Dedicated microenvironmental niches in the BM provide PCs with biomechanical and soluble factors that support their long-term survival. There is a high need for appropriate and robust model systems to better understand PCs biology, to develop new therapeutic strategies for PCs-related diseases and perform targeted preclinical studies with high predictive value. Most preclinical data have been derived fromin vivostudies in mice, asin vitrostudies of human PCs are limited due to restricted survival and functionality in conventional 2D cultures that do not reflect the unique niche architecture of the BM. We have developed a microphysiological, dynamic 3D BM culture system (BM-MPS) based on human primary tissue (femoral biopsies), mechanically supported by a hydrogel scaffold casing. While a bioinert agarose casing did not support PCs survival, a photo-crosslinked collagen-hyaluronic acid (Col-HA) hydrogel preserved the native BM niche architecture and allowed PCs survivalin vitrofor up to 2 weeks. Further, the Col-HA hydrogel was permissive to lymphocyte migration into the microphysiological system´s circulation. Long-term PCs survival was related to the stable presence in the culture of soluble factors, as APRIL, BAFF, and IL-6. Increasing immunoglobulins concentrations in the medium confirm their functionality over culture time. To the best of our knowledge, this study is the first report of successful long-term maintenance of primary-derived non-malignant PCsin vitro. Our innovative model system is suitable for in-depthin vitrostudies of human PCs regulation and exploration of targeted therapeutic approaches such as CAR-T cell therapy or biologics.


Assuntos
Hidrogéis , Plasmócitos , Humanos , Plasmócitos/citologia , Plasmócitos/metabolismo , Hidrogéis/química , Sobrevivência Celular/efeitos dos fármacos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Células da Medula Óssea/citologia , Colágeno/química , Medula Óssea/metabolismo , Células Cultivadas , Técnicas de Cultura de Células em Três Dimensões , Modelos Biológicos , Alicerces Teciduais/química , Sefarose/química
4.
J Nanobiotechnology ; 22(1): 383, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951875

RESUMO

The characteristic features of the rheumatoid arthritis (RA) microenvironment are synovial inflammation and hyperplasia. Therefore, there is a growing interest in developing a suitable therapeutic strategy for RA that targets the synovial macrophages and fibroblast-like synoviocytes (FLSs). In this study, we used graphene oxide quantum dots (GOQDs) for loading anti-arthritic sinomenine hydrochloride (SIN). By combining with hyaluronic acid (HA)-inserted hybrid membrane (RFM), we successfully constructed a new nanodrug system named HA@RFM@GP@SIN NPs for target therapy of inflammatory articular lesions. Mechanistic studies showed that this nanomedicine system was effective against RA by facilitating the transition of M1 to M2 macrophages and inhibiting the abnormal proliferation of FLSs in vitro. In vivo therapeutic potential investigation demonstrated its effects on macrophage polarization and synovial hyperplasia, ultimately preventing cartilage destruction and bone erosion in the preclinical models of adjuvant-induced arthritis and collagen-induced arthritis in rats. Metabolomics indicated that the anti-arthritic effects of HA@RFM@GP@SIN NPs were mainly associated with the regulation of steroid hormone biosynthesis, ovarian steroidogenesis, tryptophan metabolism, and tyrosine metabolism. More notably, transcriptomic analyses revealed that HA@RFM@GP@SIN NPs suppressed the cell cycle pathway while inducing the cell apoptosis pathway. Furthermore, protein validation revealed that HA@RFM@GP@SIN NPs disrupted the excessive growth of RAFLS by interfering with the PI3K/Akt/SGK/FoxO signaling cascade, resulting in a decline in cyclin B1 expression and the arrest of the G2 phase. Additionally, considering the favorable biocompatibility and biosafety, these multifunctional nanoparticles offer a promising therapeutic approach for patients with RA.


Assuntos
Artrite Reumatoide , Proliferação de Células , Grafite , Macrófagos , Morfinanos , Pontos Quânticos , Sinoviócitos , Morfinanos/farmacologia , Morfinanos/química , Animais , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/metabolismo , Grafite/química , Grafite/farmacologia , Proliferação de Células/efeitos dos fármacos , Ratos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Masculino , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Ratos Sprague-Dawley , Camundongos , Humanos , Células RAW 264.7 , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia
6.
Nat Commun ; 15(1): 5689, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38971796

RESUMO

Leukemia is a kind of hematological malignancy originating from bone marrow, which provides essential signals for initiation, progression, and recurrence of leukemia. However, how to specifically deliver drugs to the bone marrow remains elusive. Here, we develop biomimetic vesicles by infusing hematopoietic stem and progenitor cell (HSPC) membrane with liposomes (HSPC liposomes), which migrate to the bone marrow of leukemic mice via hyaluronic acid-CD44 axis. Moreover, the biomimetic vesicles exhibit superior binding affinity to leukemia cells through intercellular cell adhesion molecule-1 (ICAM-1)/integrin ß2 (ITGB2) interaction. Further experiments validate that the vesicles carrying chemotherapy drug cytarabine (Ara-C@HSPC-Lipo) markedly inhibit proliferation, induce apoptosis and differentiation of leukemia cells, and decrease number of leukemia stem cells. Mechanically, RNA-seq reveals that Ara-C@HSPC-Lipo treatment induces apoptosis and differentiation and inhibits the oncogenic pathways. Finally, we verify that HSPC liposomes are safe in mice. This study provides a method for targeting bone marrow and treating leukemia.


Assuntos
Apoptose , Medula Óssea , Citarabina , Sistemas de Liberação de Medicamentos , Células-Tronco Hematopoéticas , Leucemia , Lipossomos , Animais , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Camundongos , Citarabina/farmacologia , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Medula Óssea/metabolismo , Apoptose/efeitos dos fármacos , Leucemia/tratamento farmacológico , Leucemia/patologia , Humanos , Diferenciação Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Antígenos CD18/metabolismo , Proliferação de Células/efeitos dos fármacos , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/química , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo
7.
Oral Health Prev Dent ; 22: 257-270, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38994786

RESUMO

PURPOSE: To compare the regenerative clinical and radiographic effects of cross-linked hyaluronic acid (xHyA) with enamel matrix proteins (EMD) at six months after regenerative treatment of periodontal intrabony defects. MATERIALS AND METHODS: Sixty patients presenting one intrabony defect each were randomly assigned into control (EMD) and test (xHyA) groups. Clinical attachment level (CAL) gain was the primary outcome, while pocket probing depth (PPD), gingival recession (REC), bleeding on probing (BOP), full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), and radiographic parameters such as defect depth (BC-BD), and defect width (DW) were considered secondary outcome variables. Parameters were recorded at baseline and after 6 months. RESULTS: At the 6-month follow-up, 54 patients were available for statistical analysis. In the control and test groups, the mean CAL gain was statistically significant in the intragroup comparison (p < 0.001). 48.1% of test sites showed a CAL gain ≤ 2 mm compared with 33.3% of control sites. The mean PPD reduction was statistically significant in the intragroup comparison in both groups (p < 0.001). The mean REC increase was similar in the two groups: 1.04 ± 1.29 mm vs 1.11 ± 1.22 mm (test vs control). The mean BC-BD, DW, FMPS, FMBS, and BOP changed statistically significantly only in the intragroup comparison, not in the intergroup comparison. CONCLUSION: Both treatments, EMD and xHyA, produced similar statistically significant clinical and radiographical improvements after six months when compared with baseline.


Assuntos
Proteínas do Esmalte Dentário , Ácido Hialurônico , Humanos , Ácido Hialurônico/uso terapêutico , Proteínas do Esmalte Dentário/uso terapêutico , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Perda do Osso Alveolar/diagnóstico por imagem , Índice Periodontal , Regeneração Tecidual Guiada Periodontal/métodos
8.
Pediatr Surg Int ; 40(1): 184, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995440

RESUMO

PURPOSE: This study evaluated the outcome of pediatric patients with primary vesicoureteral reflux (VUR) and compared of the treatments between continued antibiotic prophylaxis (CAP) and endoscopic injection. METHODS: The clinical data of children diagnosed with primary vesicoureteral reflux from March 2015 to June 2020 who were treated with antibiotics or endoscopic injection were reviewed. Antibiotic was the first-chosen treatment after the diagnosis of VUR in children. Endoscopic treatment consisted of injection of dextran hyaluronic acid copolymer (DX/HA) into the ureteral opening under direct cystoscopy guidance. RESULTS: Fifty-two children (35 males, 17 females) were included in this study, and for a total 90 ureters (14 unilateral, 38 bilateral) were diagnosed with vesicoureteral reflux by Voiding cystourethrography (VCUG). Twenty-two children were treated with antibiotics (8 unilateral, 14 bilateral), for a total of 36 ureters; thirty children were treated by endoscopic injection (6 unilateral, 24 bilateral), for a total of 54 ureters. The injection surgery took 36 ± 17 min including duration of general anesthesia and circumcision and the hospital stay was 2.3 ± 1.3 days. All male patients underwent circumcision simultaneously. There were no drug and allergic reactions in the antibiotic group, and no postoperative complications occurred in the injection group. With 23 months (13-63 months) of mean follow-up, the resolution rate, defined as radiological disappearance of VUR, was 36.1% (13/36) in the antibiotic group and 57.4% (31/54) in the injection group (P = 0.048).Two cases of bilateral reflux in the injection group required a second injection before resolution could be achieved. Thus, the overall success rate of injection was 64.8% (35/54). 9 cases (9/18, 50%) in the antibiotic group had renal scars on DMSA scans, while this was seen in 20 cases (20/23, 86.9%) in the injection group. There was a statistically significant difference between the two groups (P = 0.010).The positive rates of ultrasound between the antibiotic group and the injection group were 45.5% (10/22) and 80.0% (24/30), respectively. There was a statistically significant difference between the two groups in positive rates of ultrasound (P = 0.010). CONCLUSIONS: Endoscopic injection is easy to operate with short surgical time and hospital stay, so it is a safe and feasible treatment. For the treatment of primary vesicoureteral reflux in children, the radiological resolution rate of endoscopic injection is better than antibiotic therapy. In this study, the presence of kidney scars on DMSA and the dilated of the collecting system on ultrasound are the indications for endoscopic injection.


Assuntos
Antibacterianos , Antibioticoprofilaxia , Cistoscopia , Dextranos , Ácido Hialurônico , Refluxo Vesicoureteral , Humanos , Refluxo Vesicoureteral/terapia , Refluxo Vesicoureteral/tratamento farmacológico , Masculino , Feminino , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Ácido Hialurônico/administração & dosagem , Dextranos/administração & dosagem , Pré-Escolar , Estudos Retrospectivos , Cistoscopia/métodos , Antibioticoprofilaxia/métodos , Lactente , Criança , Resultado do Tratamento , Injeções/métodos
9.
Mikrochim Acta ; 191(8): 447, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963544

RESUMO

An intelligent nanodrug delivery system (Cu/ZIF-8@GOx-DOX@HA, hereafter CZGDH) consisting of Cu-doped zeolite imidazolate framework-8 (Cu/ZIF-8, hereafter CZ), glucose oxidase (GOx), doxorubicin (DOX), and hyaluronic acid (HA) was established for targeted drug delivery and synergistic therapy of tumors. The CZGDH specifically entered tumor cells through the targeting effect of HA and exhibited acidity-triggered biodegradation for subsequent release of GOx, DOX, and Cu2+ in the tumor microenvironment (TME). The GOx oxidized the glucose (Glu) in tumor cells to produce H2O2 and gluconic acid for starvation therapy (ST). The DOX entered the intratumoral cell nucleus for chemotherapy (CT). The released Cu2+ consumed the overexpressed glutathione (GSH) in tumor cells to produce Cu+. The generated Cu+ and H2O2 triggered the Fenton-like reaction to generate toxic hydroxyl radicals (·OH), which disrupted the redox balance of tumor cells and effectively killed tumor cells for chemodynamic therapy (CDT). Therefore, synergistic multimodal tumor treatment via TME-activated cascade reaction was achieved. The nanodrug delivery system has a high drug loading rate (48.3 wt%), and the three-mode synergistic therapy has a strong killing effect on tumor cells (67.45%).


Assuntos
Cobre , Doxorrubicina , Glucose Oxidase , Ácido Hialurônico , Estruturas Metalorgânicas , Microambiente Tumoral , Zeolitas , Cobre/química , Doxorrubicina/farmacologia , Doxorrubicina/química , Microambiente Tumoral/efeitos dos fármacos , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Humanos , Zeolitas/química , Animais , Estruturas Metalorgânicas/química , Ácido Hialurônico/química , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Linhagem Celular Tumoral , Camundongos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Neoplasias/tratamento farmacológico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Imidazóis
10.
Hepatol Commun ; 8(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38967589

RESUMO

BACKGROUND: Novel noninvasive predictors of disease severity and prognosis in primary sclerosing cholangitis (PSC) are needed. This study evaluated the ability of extracellular matrix remodeling markers to diagnose fibrosis stage and predict PSC-related fibrosis progression and clinical events. METHODS: Liver histology and serum markers of collagen formation (propeptide of type III collagen [Pro-C3], propeptide of type IV collagen, propeptide of type V collagen), collagen degradation (type III collagen matrix metalloproteinase degradation product and type IV collagen matrix metalloproteinase degradation product), and fibrosis (enhanced liver fibrosis [ELF] score and its components [metalloproteinase-1, type III procollagen, hyaluronic acid]) were assessed in samples from baseline to week 96 in patients with PSC enrolled in a study evaluating simtuzumab (NCT01672853). Diagnostic performance for advanced fibrosis (Ishak stages 3-6) and cirrhosis (Ishak stages 5-6) was evaluated by logistic regression and AUROC. Prognostic performance for PSC-related clinical events and fibrosis progression was assessed by AUROC and Wilcoxon rank-sum test. RESULTS: Among 234 patients, 51% had advanced fibrosis and 11% had cirrhosis at baseline. Baseline Pro-C3 and ELF score and its components provided moderate diagnostic ability for discrimination of advanced fibrosis (AUROC 0.73-0.78) and cirrhosis (AUROC 0.73-0.81). Baseline Pro-C3, ELF score, and type III procollagen provided a moderate prognosis for PSC-related clinical events (AUROC 0.70-0.71). Among patients without cirrhosis at baseline, median changes in Pro-C3 and ELF score to week 96 were higher in those with than without progression to cirrhosis (both p < 0.001). CONCLUSIONS: Pro-C3 correlated with fibrosis stage, and Pro-C3 and ELF score provided discrimination of advanced fibrosis and cirrhosis and predicted PSC-related events and fibrosis progression. The results support the clinical utility of Pro-C3 and ELF score for staging and as prognostic markers in PSC.


Assuntos
Anticorpos Monoclonais Humanizados , Biomarcadores , Colangite Esclerosante , Progressão da Doença , Matriz Extracelular , Cirrose Hepática , Humanos , Colangite Esclerosante/tratamento farmacológico , Colangite Esclerosante/sangue , Colangite Esclerosante/patologia , Masculino , Feminino , Biomarcadores/sangue , Prognóstico , Adulto , Cirrose Hepática/sangue , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/etiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Pessoa de Meia-Idade , Matriz Extracelular/patologia , Índice de Gravidade de Doença , Ácido Hialurônico/sangue , Fígado/patologia
11.
BMC Vet Res ; 20(1): 294, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970005

RESUMO

Since its identification in the vitreous humour of the eye and laboratory biosynthesis, hyaluronic acid (HA) has been a vital component in several pharmaceutical, nutritional, medicinal, and cosmetic uses. However, little is known about its potential toxicological impacts on aquatic inhabitants. Herein, we investigated the hematological response of Clarias gariepinus to nominal doses of HA. To achieve this objective, 72 adult fish were randomly and evenly distributed into four groups: control, low-dose (0.5 mg/l HA), medium-dose (10 mg/l HA), and high-dose (100 mg/l HA) groups for two weeks each during both the exposure and recovery periods. The findings confirmed presence of anemia, neutrophilia, leucopoenia, lymphopenia, and eosinophilia at the end of exposure to HA. In addition, poikilocytosis and a variety of cytomorphological disturbances were observed. Dose-dependent histological alterations in spleen morphology were observed in the exposed groups. After HA removal from the aquarium for 2 weeks, the groups exposed to the two highest doses still exhibited a notable decline in red blood cell count, hemoglobin concentration, mean corpuscular hemoglobin concentration, and an increase in mean corpuscular volume. Additionally, there was a significant rise in neutrophils, eosinophils, cell alterations, and nuclear abnormalities percentages, along with a decrease in monocytes, coupled with a dose-dependent decrease in lymphocytes. Furthermore, only the highest dose of HA in the recovered groups continued to cause a significant increase in white blood cells. White blood cells remained lower, and the proportion of apoptotic RBCs remained higher in the high-dose group. The persistence of most of the haematological and histological disorders even after recovery period indicates a failure of physiological compensatory mechanisms to overcome the HA-associated problems or insufficient duration of recovery. Thus, these findings encourage the inclusion of this new hazardous agent in the biomonitoring program and provide a specific pattern of hematological profile in HA-challenged fish. Further experiments are highly warranted to explore other toxicological hazards of HA using dose/time window protocols.


Assuntos
Peixes-Gato , Ácido Hialurônico , Baço , Animais , Ácido Hialurônico/sangue , Baço/efeitos dos fármacos , Baço/patologia , Relação Dose-Resposta a Droga
12.
Support Care Cancer ; 32(7): 439, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888632

RESUMO

PURPOSE: This study aimed to map the use of hyaluronic acid (HA) in preventing and controlling radiotoxicity in women with gynecological cancer undergoing radiotherapy. METHODS: We conducted a scoping review of eight electronic databases: CINAHL, Cochrane CENTRAL, LILACS, PubMed, Scopus, Embase, LIVIVO, and the Web of Science Core Collection. In addition, a grey literature search was performed using Google Scholar and ProQuest Dissertations & Theses Global. A manual search was also identified additional references. The search was conducted on May 18, 2023. We included primary studies, reviews, and guidelines that discussed the use of HA to prevent and manage the toxicities resulting from gynecological radiotherapy. RESULTS: Eighteen studies were included in this scoping review, published between 2009 and 2022. There was heterogeneity in the use of HA, particularly in the method of application (moisturizing gel, vaginal ovules, spacer gel, and bladder instillations). Furthermore, the radiotoxicities varied among studies, encompassing, among others, vaginal atrophy, dryness, dyspareunia, telangiectasis, adhesions, vaginal stenosis, bleeding, hematuria, and bladder issues. Most studies addressed the potential benefits of HA in managing the signs and symptoms resulting from radiotherapy. CONCLUSION: HA has been utilized in clinical practice, in various formulations, for managing signs and symptoms in patients with gynecological cancer undergoing radiotherapy. However, further studies are necessary to thoroughly investigate the most effective method of HA application and its effectiveness in managing radiotoxicity.


Assuntos
Neoplasias dos Genitais Femininos , Ácido Hialurônico , Lesões por Radiação , Humanos , Ácido Hialurônico/administração & dosagem , Feminino , Neoplasias dos Genitais Femininos/radioterapia , Lesões por Radiação/etiologia
13.
Nanoscale ; 16(24): 11610-11622, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38855987

RESUMO

Nanomedicine aims to develop smart approaches for treating cancer and other diseases to improve patient survival and quality of life. Novel nanoparticles as nanodiamonds (NDs) represent promising candidates to overcome current limitations. In this study, NDs were functionalized with a 200 kDa hyaluronic acid-phospholipid conjugate (HA/DMPE), enhancing the stability of the nanoparticles in water-based solutions and selectivity for cancer cells overexpressing specific HA cluster determinant 44 (CD44) receptors. These nanoparticles were characterized by diffuse reflectance Fourier-transform infrared spectroscopy, Raman spectroscopy, and photoluminescence spectroscopy, confirming the efficacy of the functionalization process. Scanning electron microscopy was employed to evaluate the size distribution of the dry particles, while dynamic light scattering and zeta potential measurements were utilized to evaluate ND behavior in a water-based medium. Furthermore, the ND biocompatibility and uptake mediated by CD44 receptors in three different models of human adenocarcinoma cells were assessed by performing cytofluorimetric assay and confocal microscopy. HA-functionalized nanodiamonds demonstrated the advantage of active targeting in the presence of cancer cells expressing CD44 on the surface, suggesting higher drug delivery to tumors over non-tumor tissues. Even CD44-poorly expressing cancers could be targeted by the NDs, thanks to their good passive diffusion within cancer cells.


Assuntos
Receptores de Hialuronatos , Ácido Hialurônico , Nanodiamantes , Humanos , Nanodiamantes/química , Ácido Hialurônico/química , Receptores de Hialuronatos/metabolismo , Linhagem Celular Tumoral , Fosfolipídeos/química , Imagem Óptica , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Neoplasias/metabolismo
14.
Nanoscale ; 16(24): 11762-11773, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38869001

RESUMO

Nanohydroxyapatite (nHAp) has attracted significant attention for its tumor suppression and tumor microenvironment modulation capabilities. However, a strong tendency to aggregate greatly affects its anti-tumor efficiency. To address this issue, a hydrogel platform consisting of thiolated hyaluronic acid (HA-SH) modified nanohydroxyapatite (nHAp-HA) and HA-SH was developed for sustained delivery of nHAp for melanoma therapy. The hydrophilic and negatively charged HA-SH significantly improved the size dispersion and stability of nHAp in aqueous media while conferring nHAp targeting effects. Covalent sulfhydryl self-cross-linking between HA-SH and nHAp-HA groups ensured homogeneous dispersion of nHAp in the matrix material. Meanwhile, the modification of HA-SH conferred the targeting properties of nHAp and enhanced cellular uptake through the HA/CD44 receptor. The hydrogel platform could effectively reduce the aggregation of nHAp and release nHAp in a sustained and orderly manner. Antitumor experiments showed that the modified nHAp-HA retained the tumor cytotoxicity of nHAp in vitro and inhibited the growth of highly malignant melanomas up to 78.6% while being able to induce the differentiation of macrophages to the M1 pro-inflammatory and antitumor phenotype. This study will broaden the application of nanohydroxyapatite in tumor therapy.


Assuntos
Durapatita , Ácido Hialurônico , Hidrogéis , Melanoma , Durapatita/química , Durapatita/farmacologia , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Camundongos , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/metabolismo , Linhagem Celular Tumoral , Humanos , Receptores de Hialuronatos/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Nanopartículas/química , Células RAW 264.7
15.
Sci Rep ; 14(1): 13957, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886515

RESUMO

Heteropolysaccharides are among the most widely distributed compounds in nature, acting as both tissue building blocks and as a source of nutrients. Their physicochemical and biological properties have been studied thoroughly; however, the microstructural properties of heteropolysaccharides are still poorly understood. This study aims to investigate the micro-structural peculiarities of agarose, gum arabic, hyaluronic and alginic acids by means of confocal laser scanning microscopy (CLSM) and cryogenic scanning electron microscopy (cryo-SEM). Herein, attention is paid to layered complexity of the microstructure differentiating surface, under surface, inner, and substrate interface layers. The scale and pattern of the polysaccharide's microstructure depend on the concentration, changing from lamellae to cell-like porous structures. This work provides the insight into micro- and nanoscale mechanisms of self-healing and substrate-induced reorganisation. Thus, investigation of the self-healing mechanism revealed that this diffusion-based process starts from the fibres, turning into lamellae, following by cell-like structures with smaller dimensions. Investigation of the substrate-induced reorganisation ability showed that nano-to-micro (scale) porous substrate causes reorganisation in the interface layer of the studied heteropolysaccharides. This work contributes to understanding the structural peculiarities of heteropolysaccharides by looking at them through a supramolecular, micro-level prism.


Assuntos
Polissacarídeos , Polissacarídeos/química , Microscopia Confocal , Soluções , Alginatos/química , Microscopia Eletrônica de Varredura , Goma Arábica/química , Sefarose/química , Ácido Hialurônico/química , Microscopia Crioeletrônica
17.
J Eur Acad Dermatol Venereol ; 38 Suppl 4: 45-52, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38881437

RESUMO

Anti-aging trends in Australia have changed considerably since the country emerged from the lockdowns associated with the SARS-Cov2 pandemic. People now rely on social media influencers for skin care advice and skin care products, including professional skin care treatments that can be purchased on Internet platforms. The quest for the perfect 'zoom face' led to a 300% rise in cosmetic procedures across Australia in the year to April 2021. People now want to use less products on their skin, while looking healthy and natural (termed 'skin minimalism'). The popularity of retinoid derivatives for preventing wrinkles has been superseded by non-irritating actives like hyaluronic acid (HA) and niacinamide that provide skin barrier protection, skin hydration, plumping and anti-inflammatory effects. Botulinum toxin injections remain the most popular non-surgical cosmetic procedure, followed by HA fillers, and biostimulators that promote the synthesis of collagen and give longer lasting but more gradual results than HA fillers. Laser resurfacing is widely used for epidermal resurfacing and skin tightening, as well as non-ablative lasers, intense pulsed light and radiofrequency or ultrasound skin tightening devices. Superficial chemical peels are still popular because they are relatively gentle, inexpensive, and require no downtime, whereas medium-to-deep chemical peels have largely been superseded by laser technology. However, the most efficient approach to prevent skin aging is adopting a healthy lifestyle and taking action against all factors of the skin aging exposome.


Assuntos
Técnicas Cosméticas , Envelhecimento da Pele , Humanos , Austrália , Técnicas Cosméticas/tendências , COVID-19/prevenção & controle , COVID-19/epidemiologia , Ácido Hialurônico/uso terapêutico , Preenchedores Dérmicos/uso terapêutico
18.
J Eur Acad Dermatol Venereol ; 38 Suppl 4: 15-22, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38881445

RESUMO

Skin aging has long been considered a purely cosmetic problem. However, as life expectancy increases, skin aging is taking on a functional dimension that goes beyond cosmetics and appearance. Preventive or therapeutic strategies are needed to target cellular senescence, a key process underlying the alterations in skin function and appearance that occur with aging, as well as to address the age-related skin changes associated with 'dermatoporosis' and chronic skin insufficiency/fragility syndrome. Thus, given the need for effective anti-aging products that improve both the appearance and function of the skin, it is essential to distinguish active ingredients that have been proven to be effective, among the large number of available over-the-counter cosmeceuticals. This brief review focuses on a core group of topical actives, describing their clinical effects on senescence and aging, and their molecular mechanisms of action. These actives include hyaluronic acid, which has hydrating and viscoelastic properties and has been shown to reduce skin atrophy; retinaldehyde, which activates retinoid receptors and increases cutaneous elasticity; vitamins C and E, which provide stable oxidative protection; and niacinamide, which reduces inflammation and mitigates the effects of senescence.


Assuntos
Senescência Celular , Envelhecimento da Pele , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/fisiologia , Humanos , Senescência Celular/efeitos dos fármacos , Ácido Hialurônico/farmacologia , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Vitamina E/farmacologia , Cosmecêuticos/farmacologia , Pele/patologia , Pele/efeitos dos fármacos
19.
Int J Mol Sci ; 25(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38892078

RESUMO

The aim of this work was to develop and characterize a thin films composed of hyaluronic acid/ellagic acid for potential medical application. Its principal novelty, distinct from the prior literature in terms of hyaluronic acid films supplemented with phenolic acids, resides in the predominant incorporation of ellagic acid-a distinguished compound-as the primary constituent of the films. Herein, ellagic acid was dissolved in two different solvents, i.e., acetic acid (AcOH) or sodium hydroxide (NaOH), and the surface properties of the resultant films were assessed using atomic force microscopy and contact angle measurements. Additionally, various physicochemical parameters were evaluated including moisture content, antioxidant activity, and release of ellagic acid in phosphate buffered saline. Furthermore, the evaluation of films' biocompatibility was conducted using human epidermal keratinocytes, dermal fibroblasts, and human amelanotic melanoma cells (A375 and G361), and the antimicrobial activity was elucidated accordingly against Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 15442. Our results showed that the films exhibited prominent antibacterial properties particularly against Staphylococcus aureus, with the 80HA/20EA/AcOH film indicating the strong biocidal activity against this strain leading to a significant reduction in viable cells. Comparatively, the 50HA/50EA/AcOH film also displayed biocidal activity against Staphylococcus aureus. This experimental approach could be a promising technique for future applications in regenerative dermatology or novel strategies in terms of bioengineering.


Assuntos
Materiais Biocompatíveis , Ácido Elágico , Ácido Hialurônico , Staphylococcus aureus , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Humanos , Staphylococcus aureus/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Ácido Elágico/farmacologia , Ácido Elágico/química , Pseudomonas aeruginosa/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antioxidantes/farmacologia , Antioxidantes/química , Fibroblastos/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Linhagem Celular Tumoral , Propriedades de Superfície
20.
Int J Mol Sci ; 25(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38892229

RESUMO

Synthetic deer antler peptides (TSKYR, TSK, and YR) stimulate the proliferation of human chondrocytes and osteoblasts and increase the chondrocyte content of collagen and glycosamino-glycan in vitro. This study investigated the peptide mixture's pain relief and chondroprotective effect in a rat model of collagenase-induced osteoarthritis. Thirty-six adult male Sprague-Dawley rats were divided into three groups: control (saline), positive control (hyaluronic acid), and ex-perimental (peptides). Intra-articular collagenase injections were administered on days 1 and 4 to induce osteoarthritis in the left knees of the rats. Two injections of saline, hyaluronic acid, or the peptides were injected into the same knees of each corresponding group at the beginning of week one and two, respectively. Joint swelling, arthritic pain, and histopathological changes were evaluated. Injection of the peptides significantly reduced arthritic pain compared to the control group, as evidenced by the closer-to-normal weight-bearing and paw withdrawal threshold test results. Histological analyses showed reduced cartilage matrix loss and improved total cartilage degeneration score in the experimental versus the control group. Our findings suggest that intra-articular injection of synthetic deer antler peptides is a promising treatment for osteoarthritis.


Assuntos
Chifres de Veado , Cervos , Modelos Animais de Doenças , Osteoartrite do Joelho , Peptídeos , Ratos Sprague-Dawley , Animais , Injeções Intra-Articulares , Chifres de Veado/química , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/induzido quimicamente , Masculino , Ratos , Peptídeos/administração & dosagem , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Ácido Hialurônico/administração & dosagem , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Cartilagem Articular/metabolismo , Colagenases
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