RESUMO
Osteomyelitis (OM) is a progressive, inflammatory infection of bone caused predominately by Staphylococcus aureus. Herein, we engineered an antibiotic-eluting collagen-hydroxyapatite scaffold capable of eliminating infection and facilitating bone healing. An iterative freeze-drying and chemical crosslinking approach was leveraged to modify antibiotic release kinetics, resulting in a layered dual-release system whereby an initial rapid release of antibiotic to clear infection was followed by a sustained controlled release to prevent reoccurrence of infection. We observed that the presence of microbial collagenase accelerated antibiotic release from the crosslinked layer of the scaffold, indicating that the material is responsive to microbial activity. As exemplar drugs, vancomycin and gentamicin-eluting scaffolds were demonstrated to be bactericidal, and supported osteogenesis in vitro. In a pilot murine model of OM, vancomycin-eluting scaffolds were observed to reduce S. aureus infection within the tibia. Finally, in a rabbit model of chronic OM, gentamicin-eluting scaffolds both facilitated radial bone defect healing and eliminated S. aureus infection. These results show that antibiotic-eluting collagen-hydroxyapatite scaffolds are a one-stage therapy for OM, which when implanted into infected bone defects simultaneously eradicate infection and facilitate bone tissue healing.
Assuntos
Antibacterianos , Gentamicinas , Osteomielite , Infecções Estafilocócicas , Staphylococcus aureus , Alicerces Teciduais , Animais , Alicerces Teciduais/química , Antibacterianos/farmacologia , Antibacterianos/química , Infecções Estafilocócicas/tratamento farmacológico , Osteomielite/tratamento farmacológico , Coelhos , Staphylococcus aureus/efeitos dos fármacos , Gentamicinas/farmacologia , Gentamicinas/administração & dosagem , Gentamicinas/química , Gentamicinas/uso terapêutico , Camundongos , Vancomicina/farmacologia , Vancomicina/química , Vancomicina/administração & dosagem , Durapatita/química , Cinética , Cicatrização/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Colágeno/química , FemininoRESUMO
Fourier transform infrared spectroscopy (FTIRS) can provide rich information on the composition and content of samples, enabling the detection of subtle changes in tissue composition and structure. This study represents the first application of FTIRS to investigate cartilage under microgravity. Simulated microgravity cartilage model was firstly established by tail-suspension (TS) for 7, 14 and 21 days, which would be compared to control samples. A self-developed hollow optical fiber attenuated total reflection (HOF-ATR) probe coupled with a FTIR spectrometer was used for the spectral acquisition of cartilage samples in situ, and one-way analysis of variance (ANOVA) was employed to analyze the changes in the contents of cartilage matrix at different stages. The results indicate that cartilage degenerates in microgravity, the collagen content gradually decreases with the TS time, and the structure of collagen fibers changes. The trends of proteoglycan content and collagen integrity show an initial decrease followed by an increase, ultimately significantly decreasing. The findings provide the basis for the cartilage degeneration in microgravity with TS time, which must be of real significance for space science and health detection.
Assuntos
Cartilagem Articular , Colágeno , Simulação de Ausência de Peso , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Cartilagem Articular/patologia , Cartilagem Articular/química , Cartilagem Articular/metabolismo , Colágeno/análise , Colágeno/metabolismo , Colágeno/química , Animais , Proteoglicanas/análise , MasculinoRESUMO
A critical shortage of donor corneas exists worldwide. Hydrogel patches with a biological architecture and functions that simulate those of native corneas have garnered considerable attention. This study introduces a stromal structure replicating corneal patch (SRCP) composed of a decellularized cornea-templated nanotubular skeleton, recombinant human collagen, and methacrylated gelatin, exhibiting a similar ultrastructure and transmittance (above 80 %) to natural cornea. The SRCP is superior to the conventional recombinant human collagen patch in terms of biomechanical properties and resistance to enzymatic degradation. Additionally, SRCP promotes corneal epithelial and stromal cell migration while preventing the trans-differentiation of stromal cells into myofibroblasts. When applied to an ocular surface (37 °C), SRCP releases methacrylated gelatin, which robustly binds SRCP to the corneal stroma after activation by 405 nm light. Compared to gelatin-based photocurable hydrogel, the SRCP better supports the restoration of normal corneal curvature and withstands deformation under an elevated intraocular pressure (100 mmHg). In an in vivo deep anterior-corneal defect model, SRCP facilitated epithelial healing and vision recovery within 2 weeks, maintained graft structural stability, and inhibited stromal scarring at 4 weeks post-operation. The ideal performance of the SRCP makes it a promising humanized corneal equivalent for sutureless clinical applications.
Assuntos
Substância Própria , Hidrogéis , Humanos , Animais , Hidrogéis/química , Gelatina/química , Cicatrização/efeitos dos fármacos , Colágeno/química , Coelhos , Procedimentos Cirúrgicos sem Sutura/métodos , CórneaRESUMO
Introduction: The critical early stages of infection and innate immune responses to porcine epidemic diarrhea virus (PEDV) at the intestinal epithelium remain underexplored due to the limitations of traditional cell culture and animal models. This study aims to establish a porcine enteroid culture model to investigate potential differences in susceptibility to infection across segments of the porcine small intestine (duodenum, jejunum, and ileum). Methods: Intestinal crypt cells from nursery pigs were cultured in Matrigel to differentiate into porcine enteroid monolayer cultures (PEMCs). Following characterization, PEMCs were enzymatically dissociated and subcultured on transwell inserts (PETCs) for apical surface exposure and infection studies. Characterization of region-specific PEMCs and PETCs included assessment of morphology, proliferation, viability, and cellular phenotyping via immunohistochemistry/immunocytochemistry and gene expression analysis. Subsequently, PETCs were inoculated with 105 TCID50 (50% tissue culture infectious dose)/mL of a high pathogenic PEDV non-S INDEL strain and incubated for 24 h. Infection outcomes were assessed by cytopathic effect, PEDV N protein expression (immunofluorescence assay, IFA), and PEDV N-gene detection (quantitative reverse transcription polymerase chain reaction, RT-qPCR). Results: No significant morphological and phenotypical differences were observed among PEMCs and PETCs across intestinal regions, resembling the porcine intestinal epithelium. Although PETCs established from different segments of the small intestine were susceptible to PEDV infection, jejunum-derived PETCs exhibited higher PEDV replication, confirmed by IFA and RT-qPCR. Discussion: This segment-specific enteroid culture model provides a reliable platform for virological studies, offering a controlled environment that overcomes the limitations of in vivo and traditional cell culture methods. Standardizing culture conditions and characterizing the model are essential for advancing enteroid-based infection models.
Assuntos
Infecções por Coronavirus , Intestino Delgado , Vírus da Diarreia Epidêmica Suína , Animais , Vírus da Diarreia Epidêmica Suína/fisiologia , Suínos , Intestino Delgado/imunologia , Intestino Delgado/virologia , Infecções por Coronavirus/virologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/imunologia , Laminina , Combinação de Medicamentos , Doenças dos Suínos/virologia , Doenças dos Suínos/imunologia , Suscetibilidade a Doenças , Colágeno/metabolismo , Organoides/virologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/virologia , Proteoglicanas , Células CultivadasRESUMO
Achilles tendinopathy is often attributed to overuse, but its pathophysiology remains poorly understood. Disruption to the molecular structure of collagen is fundamental for the onset and progression of tendinopathy but has mostly been investigated in vitro. Here, we interrogated the in vivo molecular structure changes of collagen in rat Achilles tendons following treadmill running. Unexpectedly, the tendons' collagen molecules were not mechanically unfolded by running but denatured through proteolysis during physiological post-run remodeling. We further revealed that running induces inflammatory gene expressions in Achilles tendons and that long-term running causes prolonged, elevated collagen degradation, leading to the accumulation of denatured collagen and tendinopathy development. For applications, we demonstrated magnetic resonance imaging of collagenase-induced Achilles tendon injury in vivo using a denatured collagen targeting contrast agent. Our findings may help close the knowledge gaps in the mechanobiology and pathogenesis of Achilles tendinopathy and initiate new strategies for its imaging-based diagnosis.
Assuntos
Tendão do Calcâneo , Colágeno , Imageamento por Ressonância Magnética , Tendinopatia , Tendão do Calcâneo/metabolismo , Tendão do Calcâneo/diagnóstico por imagem , Tendão do Calcâneo/patologia , Animais , Tendinopatia/diagnóstico por imagem , Tendinopatia/metabolismo , Tendinopatia/patologia , Tendinopatia/etiologia , Imageamento por Ressonância Magnética/métodos , Colágeno/metabolismo , Colágeno/química , Ratos , Fenômenos Biomecânicos , Masculino , Corrida , Desnaturação Proteica , Modelos Animais de Doenças , Ratos Sprague-DawleyRESUMO
BACKGROUND: N6-Methyladenosine (m6A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m6A methylation in photoaging remains unknown. OBJECTIVES: This study aims to investigate the biological role and underlying mechanism of m6A methylation in photoaging. METHODS: m6A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m6A level and specific m6A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m6A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay. RESULTS: m6A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m6A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m6A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-bRII and upregulation of MMP1 in UVR-irradiated human dermal fibroblasts (HDFs). Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m6A modification and KIAA1429 might suppress collagen synthesis through an m6A-MFAP4-mediated process. CONCLUSIONS: The increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging.
Assuntos
Colágeno , Envelhecimento da Pele , Envelhecimento da Pele/efeitos da radiação , Envelhecimento da Pele/genética , Colágeno/metabolismo , Animais , Adenosina/análogos & derivados , Adenosina/metabolismo , Camundongos , Humanos , Raios Ultravioleta , Metilação , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiaçãoRESUMO
Fibrosis is an abnormal tissue healing process characterized by the excessive accumulation of ECM components, such as COL I and COL III, in response to tissue injury or chronic inflammation. Recent advances in epitranscriptomics have underscored the importance of m6A modification in fibrosis. m6A, the most prevalent modification in eukaryotic RNA, is catalyzed by methyltransferases (e.g., METTL3), removed by demethylases (e.g., FTO), and recognized by reader proteins (e.g., YTHDF1/2). These modifications are crucial in regulating collagen metabolism and associated diseases. Understanding the role of m6A modification in fibrosis and other collagen-related conditions holds promise for developing targeted therapies. This review highlights the latest progress in this area.
Assuntos
Adenosina , Fibrose , Metiltransferases , Humanos , Adenosina/análogos & derivados , Adenosina/genética , Adenosina/metabolismo , Fibrose/genética , Metiltransferases/genética , Epigênese Genética/genética , Doenças do Colágeno/genética , Animais , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Colágeno/genética , Colágeno/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , RNA/genéticaRESUMO
Myopia is a common ocular condition characterized by biomechanical weakening revealed by increasing creep rate, cyclic softening scleral thinning, change of collagen fibril crimping, and excessive elongation of the posterior sclera resulting in blurred vision. Animal studies support scleral crosslinking as a potential treatment for myopia control by strengthening the weakened sclera and slowing scleral expansion. While multiple studies investigated aspects of the biomechanical weakening and strengthening effects in myopia and after scleral crosslinking, a comprehensive analysis of the underlying mechanical changes including the effect of vehicle injections is still missing. The purpose of this study was to provide a comprehensive analysis of biomechanical changes by scleral inflation testing in experimental myopia, after retrobulbar vehicle injections and scleral crosslinking using genipin in tree shrews. Our results suggest that biomechanical weakening in myopia involves an increased creep rate and higher strain levels at which collagen fibers uncrimp. Both weakening effects were reduced after scleral crosslinking using genipin at doses that were effective in slowing myopia progression. Vehicle injections increased mechanical hysteresis and had a small but significant effect on slowing myopia progression. Also, our results support scleral crosslinking as a potential treatment modality that can prevent or counteract scleral weakening effects in myopia. Furthermore, vehicle solutions may cause independent biomechanical effects, which should be considered when developing and evaluating scleral crosslinking procedures.
Assuntos
Modelos Animais de Doenças , Iridoides , Miopia , Esclera , Tupaiidae , Animais , Esclera/efeitos dos fármacos , Esclera/metabolismo , Iridoides/farmacologia , Iridoides/administração & dosagem , Miopia/tratamento farmacológico , Miopia/fisiopatologia , Fenômenos Biomecânicos/efeitos dos fármacos , Reagentes de Ligações Cruzadas , Colágeno/metabolismoRESUMO
The peripheral nervous system consists of ganglia, nerve trunks, plexuses, and nerve endings, that transmit afferent and efferent information. Regeneration after a peripheral nerve damage is sluggish and imperfect. Peripheral nerve injury frequently causes partial or complete loss of motor and sensory function, physical impairment, and neuropathic pain, all of which have a negative impact on patients' quality of life. Because the mechanism of peripheral nerve injury and healing is still unclear, the therapeutic efficacy is limited. As peripheral nerve injury research has processed, an increasing number of studies have revealed that biological scaffolds work in tandem with progenitor cells to repair peripheral nerve injury. Here, we fabricated collagen chitosan nerve conduit bioscaffolds together with collagen and then filled neuroepithelial stem cells (NESCs). Scanning electron microscopy showed that the NESCs grew well on the scaffold surface. Compared to the control group, the NESCs group contained more cells with bigger diameters and myelinated structures around the axons. Our findings indicated that a combination of chitosan-collagen bioscaffold and neural stem cell transplantation can facilitate the functional restoration of peripheral nerve tissue, with promising future applications and research implications.
Assuntos
Quitosana , Colágeno , Regeneração Nervosa , Traumatismos dos Nervos Periféricos , Alicerces Teciduais , Quitosana/química , Regeneração Nervosa/fisiologia , Colágeno/química , Animais , Alicerces Teciduais/química , Traumatismos dos Nervos Periféricos/terapia , Ratos , Células Neuroepiteliais/citologia , Células-Tronco Neurais/citologia , Nervos Periféricos/fisiologia , Nervo Isquiático/fisiologiaRESUMO
Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) is the leading cause of childhood chronic kidney failure and a significant cause of chronic kidney disease in adults. Genetic and environmental factors are known to influence CAKUT development, but the currently known disease mechanism remains incomplete. Our goal is to identify affected pathways and networks in CAKUT, and thereby aid in getting a better understanding of its pathophysiology. With this goal, the miRNome, peptidome, and proteome of over 30 amniotic fluid samples of patients with non-severe CAKUT was compared to patients with severe CAKUT. These omics data sets were made findable, accessible, interoperable, and reusable (FAIR) to facilitate their integration with external data resources. Furthermore, we analysed and integrated the omics data sets using three different bioinformatics strategies: integrative analysis with mixOmics, joint dimensionality reduction and pathway analysis. The three bioinformatics analyses provided complementary features, but all pointed towards an important role for collagen in CAKUT development and the PI3K-AKT signalling pathway. Additionally, several key genes (CSF1, IGF2, ITGB1, and RAC1) and microRNAs were identified. We published the three analysis strategies as containerized workflows. These workflows can be applied to other FAIR data sets and help gaining knowledge on other rare diseases.
Assuntos
Colágeno , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Colágeno/metabolismo , Colágeno/genética , Biologia Computacional/métodos , MicroRNAs/genética , MicroRNAs/metabolismo , Refluxo Vesicoureteral/genética , Refluxo Vesicoureteral/metabolismo , Feminino , Proteoma/metabolismo , Líquido Amniótico/metabolismo , Sistema Urinário/metabolismo , Multiômica , Anormalidades UrogenitaisRESUMO
BACKGROUND: A new indication for use of silver collagen oxidized regenerated cellulose (ORC) dressing in conjunction with negative pressure wound therapy (NPWT) and reticulated open cell foam (ROCF) dressings has recently become available. OBJECTIVE: An in-person meeting with 7 health care providers (HCPs) was held to identify clinical care settings and appropriate use of silver collagen ORC dressings in conjunction with NPWT and ROCF dressings. METHODS: Consensus statements were developed using a modified Delphi technique. An additional 25 HCPs completed an anonymous survey on the consensus statements. Consensus was defined as ≥80% agreement among survey respondents. RESULTS: Use of silver collagen ORC dressings with NPWT and ROCF dressings was recommended in inpatient and outpatient health care settings. Use in traumatic wounds, surgical wounds, diabetic ulcers, venous leg ulcers, and pressure injuries/ulcers was supported. Use was not recommended in the presence of exposed unprotected organs or exposed unprotected vessels, when the potential for inadequate wound hemostasis exists, acutely ischemic wounds, third-degree burns, or surgically closed incisions, or with patient hypersensitivity to product components. CONCLUSIONS: Limited evidence exists on use of NPWT in conjunction with silver collagen ORC dressings. A panel developed 12 consensus statements detailing the recommended and contraindicated uses of NPWT in conjunction with silver collagen ORC dressings.
Assuntos
Celulose Oxidada , Colágeno , Consenso , Tratamento de Ferimentos com Pressão Negativa , Cicatrização , Humanos , Tratamento de Ferimentos com Pressão Negativa/métodos , Celulose Oxidada/uso terapêutico , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/terapia , Bandagens , Úlcera por Pressão/terapia , Técnica DelphiRESUMO
OBJECTIVE: To investigate the efficacy of ribose-crosslinked collagen (RCLC) matrices functionalized by crosslinked hyaluronic acid (xHya) for reconstructive treatment of class I and III (b-c) peri-implantitis lesions in a transmucosal healing mode. MATERIALS AND METHODS: Thirteen patients presenting with 15 implants were included in this prospective case series. Upon flap reflection, the implants were thoroughly decontaminated employing glycine powder air polishing and adjunctive sodium hypochlorite. For defect augmentation, xHyA was administered to the bony defect walls, exposed implant surfaces, and the RCLC matrix before defect grafting. The full-thickness flap was readapted and sutured around the implant neck for transmucosal healing. Baseline and respective values at the 12 months post-op evaluation were recorded for the clinical parameters peri-implant probing depth (PPD), buccal soft tissue dehiscence (BSTD) and bleeding on probing (BoP). Furthermore, two independent investigators analyzed radiographic changes in the defect area. The mean changes for all variables were analyzed with a paired t-test. RESULTS: The initial mean PPD was 7.2 ± 1.9 mm, and BoP was present in 63% of sites. After 12 months, PPD at the latest visit was 3.2 ± 0.66 mm, which amounted to a respective 3.9 ± 1.85 mm reduction, while the BoP frequency dropped to 10% at all sites. Radiographic bone fill was accomplished for 62.8% of the former defect area, accompanied by a mean MBL gain of 1.02 mm around the treated implants (all p < 0.001). CONCLUSIONS: Within the limits of this case series, we conclude that the proposed treatment sequence substantially improved peri-implant defects and offered a simplified but predictive technique. CLINICAL RELEVANCE: Reconstructive treatment approaches for peri-implantitis are effective but remain non-superior to open flap debridement. Further research on novel biomaterial combinations that may improve reconstructive treatment outcomes are warranted. Ribose-crosslinked collagen matrices biofunctionalized by hyaluronic acid used in this study yield improved clinical and radiographic peri-implant conditions after 12 months.
Assuntos
Colágeno , Ácido Hialurônico , Peri-Implantite , Ribose , Humanos , Estudos Prospectivos , Ácido Hialurônico/química , Masculino , Feminino , Pessoa de Meia-Idade , Ribose/química , Peri-Implantite/cirurgia , Resultado do Tratamento , Retalhos Cirúrgicos , Adulto , Reagentes de Ligações Cruzadas/química , Idoso , Procedimentos de Cirurgia Plástica/métodos , Cicatrização , Implantes DentáriosAssuntos
Colágeno , Reagentes de Ligações Cruzadas , Pressão Intraocular , Ceratocone , Ceratectomia Fotorrefrativa , Ceratocone/cirurgia , Ceratocone/fisiopatologia , Ceratocone/diagnóstico , Humanos , Ceratectomia Fotorrefrativa/métodos , Pressão Intraocular/fisiologia , Colágeno/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Crosslinking CorneanoRESUMO
PURPOSE: This study aimed to identify preoperative factors that predict visual acuity and Kmax 3 years after corneal cross-linking (CXL) in patients with keratoconus (KC), and to develop a prediction model. METHODS: We enrolled 68 patients with KC and followed up on 100 eyes that received CXL for at least 3 years. Preoperative data, including age, UDVA, CDVA, cylinder, SE, and the parameters of tomography including Kmax were collected as predictors. The primary outcomes were changes in CDVA (Delta CDVA) and Kmax (Delta Kmax) postoperatively. Univariate and multivariate linear regression were used to identify the correlation between the primary outcomes and predictors and establish prediction models. RESULTS: Both CDVA and Kmax remained stable from baseline to 3 years after CXL: from 0.25 ± 0.18 to 0.22 ± 0.20 (P = 0.308) and from 58.70 ± 9.52 D to 57.02 ± 8.83 D (P = 0.187), respectively. Multivariate analysis showed that worse preoperative CDVA (ß coefficient - 0.668, P < 0.001) and lower preoperative Kmean (ß coefficient 0.018,P < 0.001) were associated with greater improvement in CDVA after CXL. A smaller preoperative eccentricity (ß coefficient 8.896, P = 0.01) and a higher preoperative Kmean (ß coefficient - 1.264, P < 0.001) predicted a more flattening of postoperative Kmax. The prediction model for CDVA (R2 = 0.43) and Kmax (R2 = 0.37) could accurately estimate treatment outcomes. CONCLUSIONS: CXL is highly effective in halting or preventing further progression of KC. The preoperative factors CDVA and Kmean were able to predict visual acuity changes 3 years after CXL. And preoperative eccentricity and Kmean could predict Kmax changes 3 years after CXL.
Assuntos
Colágeno , Topografia da Córnea , Reagentes de Ligações Cruzadas , Ceratocone , Fotoquimioterapia , Fármacos Fotossensibilizantes , Riboflavina , Raios Ultravioleta , Acuidade Visual , Humanos , Ceratocone/tratamento farmacológico , Ceratocone/diagnóstico , Ceratocone/metabolismo , Reagentes de Ligações Cruzadas/uso terapêutico , Feminino , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Adulto , Colágeno/metabolismo , Riboflavina/uso terapêutico , Fotoquimioterapia/métodos , Adulto Jovem , Seguimentos , Estudos Retrospectivos , Resultado do Tratamento , Adolescente , Refração Ocular/fisiologia , Córnea/patologia , Córnea/diagnóstico por imagem , Fatores de Tempo , Substância Própria/metabolismo , Substância Própria/efeitos dos fármacos , Crosslinking CorneanoRESUMO
OBJECTIVE: Osteoarthritis (OA) is the most common joint disorder in humans and dogs. Due to its chronic progressive nature, the predominant clinical signs after a certain point are pain and immobility. The similar pathogenesis allows conclusions to be drawn from canine to human OA. Current treatments are limited and often attempt to treat OA symptoms rather than improve joint structure and function. Collagen hydrolysates as oral supplements are a promising therapeutic option to achieve this advanced therapeutic aim in both species. The effects of oral supplementation were therefore investigated in canine OA patients. METHOD: In a systematic, placebo-controlled, double-blind interventional study in 31 dogs with naturally occurring OA, the efficacy of oral supplementation of specific bioactive collagen peptides (BCP) was tested in comparison to the approved combination of the active substances omega-3 fatty acids and vitamin E. The dogs were examined on a horizontal treadmill with 4 integrated piezoelectric force plates at the beginning and end of a twelve-week test period. At both points, the owners completed a specific questionnaire containing the validated Canine Brief Pain Inventory (CBPI) and the dogs were fitted with accelerometers to record total daily activity data. RESULTS: Only the oral supplementation of BCP resulted in a significant improvement of several kinetic parameters measured using a force-plate fitted treadmill, and the quality of life assessed by CBPI, while accelerometry was unaffected by the intervention. CONCLUSION: The results of this three-month BCP supplementation study using objective measurement parameters in dogs with naturally occurring OA demonstrate an efficacy, suggesting the therapeutic use of BCP in canine OA patients and demonstrating the relevance of this collagen hydrolysate formulation for the treatment of OA in human patients as well.
Assuntos
Colágeno , Suplementos Nutricionais , Marcha , Osteoartrite , Qualidade de Vida , Animais , Cães , Osteoartrite/veterinária , Osteoartrite/tratamento farmacológico , Osteoartrite/dietoterapia , Administração Oral , Masculino , Marcha/efeitos dos fármacos , Feminino , Modelos Animais de Doenças , Método Duplo-Cego , Peptídeos/uso terapêutico , Peptídeos/farmacologia , Peptídeos/administração & dosagem , Doenças do Cão/tratamento farmacológico , Doenças do Cão/dietoterapiaRESUMO
BACKGROUND: The endoplasmic reticulum (ER) stress is a crucial toxic signaling event triggered by chronic exposure to Ultraviolet B radiation (UVB), which significantly exacerbate photodamage responses in the irradiated skin. Therefore, the identification of agents capable of inhibiting ER stress could serve as a promising therapeutic strategy for addressing the unmet clinical needs in the treatment of UVB-induced photodamage. METHODS: A UVB-irradiated mouse model was used and topical administration of Panax ginseng extract was carried out for a duration of 9 weeks. Vitamin E was used as a positive control. After 9 weeks of administration, the skin appearance, epidermal hyperplasia, infiltration of inflammatory cells, apoptosis, and collagen content were measured. The keratinocytes were irradiated with 6 mJ/cm2 UVB to establish an in vitro model. The levels of ER stress and apoptosis were investigated both in vivo and in vitro using qRT-PCR, immunoblotting, and immunofluorescence. RESULTS: Among the 14 extracts derived from 13 distinct plant species that were screened, Panax ginseng, Prunus mume, and Camellia japonica showed inhibitory effect on UVB-induced ER stress. Notably, Panax ginseng effectively inhibits collagen degradation and apoptosis in both irradiated keratinocytes and Balb/C mice skin. Furthermore, the silencing of VMP1 significantly impeded the cellular protective effect of Panax ginseng extract on UVB-irradiated keratinocytes, indicating that Panax ginseng exerts its protective effects through targeted promotion of VMP1. CONCLUSION: Our data suggest that Panax ginseng extract possess a therapeutical effect on UVB radiation-induced photodamage by promoting VMP1-mediated inhibition of ER stress.
Assuntos
Apoptose , Estresse do Retículo Endoplasmático , Queratinócitos , Panax , Extratos Vegetais , Pele , Raios Ultravioleta , Animais , Feminino , Humanos , Camundongos , Apoptose/efeitos dos fármacos , Colágeno/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos da radiação , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos BALB C , Panax/química , Extratos Vegetais/farmacologia , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversosRESUMO
The following amendments are made to the published article: Int J Oral Implantol (Berl) 2024;17(1):105-117; First published 19 March 2024.
Assuntos
Derme Acelular , Colágeno , Alicerces Teciduais , Humanos , Masculino , Feminino , Implantes Dentários para Um Único Dente , Aloenxertos , Adulto , Pessoa de Meia-Idade , Carga Imediata em Implante Dentário/métodosRESUMO
OBJECTIVE: While most xenograft wound matrices are flat sheets not designed for deep or tunnelling wounds, three-dimensional acellular collagen matrices (3D-ACM) can fill deep wound beds and enable full wound wall apposition. This case series examines the use of 3D-ACM in treating diabetic foot ulcers (DFUs) that are deep, tunnelling, undermining, or irregularly shaped. We report outcomes of cases where 3D-ACM was applied to deep or tunnelling DFUs present for at least four weeks. METHOD: In this retrospective case series, 3D-ACM was applied, healing was monitored and measurements were collected. Additional 3D-ACM was applied as needed. RESULTS: In total, 11 patients with 13 wounds were treated. Improved wound appearance and reduced size were observed at most follow-ups. Mean initial wound depth was 1.6cm, and several wounds showed significant depth reductions shortly after therapy initiation. In total, 62% of wounds (8/13) reached 50% closure by four weeks. Additionally, 54% (7/13) were fully closed by 12 weeks. The remaining 46% (6/13) took between 12-22.3 weeks to heal. Overall mean therapy time was 13.1 weeks (range: 2.0-22.3 weeks). Deeper wounds generally took longer to close. CONCLUSION: The findings of this case series showed that 3D-ACM could offer a protective microenvironment for wound management for deep or tunnelling DFUs. While some took >12 weeks to close, this may be attributable to large initial depths and volumes, rather than a failure to respond to the treatment modality. Other wounds that require a conforming 3D matrix, enabling full wound wall apposition, may benefit from 3D-ACM. Further investigations would be beneficial to understand the capabilities of this treatment modality.
Assuntos
Colágeno , Pé Diabético , Cicatrização , Humanos , Pé Diabético/terapia , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Colágeno/uso terapêutico , Derme Acelular , Idoso de 80 Anos ou mais , Resultado do Tratamento , AdultoRESUMO
This study aims to investigate the effects of the skin tissue derived peptides on proliferation, apoptosis, migration and collagen expressions in keloid fibroblasts. From January 2015 to January 2017, patients with hypertrophic scar who underwent surgical excision in department of plastic surgery of Nanjing maternal and child health hospital were included in this retrospective study. Four peptides were selected from the differential peptides between human hypertrophic scar and normal skin tissue. They were named as peptide deregulated in hypertrophic scar 2-5 (PDHPS2-5). Bioinformatics and functional analysis were performed. A low dose of 10 µmol/L of four peptides were respectively added to the culture medium of human primary keloid fibroblasts for 24 h. Cell counting kit-8 (CCK-8) were used to detect the changes in cell viability. Cell apoptosis was detected by flow cytometry. Cell migration ability was checked by Transwell chamber. The protein expressions of collagen COL1A2 (Collagen type I alpha 2) and the myofibroblast marker gene ACTA2 (Actin alpha 2) were analyzed by Western blot. The results showed that bioinformatics prediction analysis revealed that peptide PDHPS4 has the longest half-life and the highest thermal stability. Compared with the control group, low dose of four peptides had no significant effect on the survival rate and apoptosis of keloid fibroblasts tested by CCK-8 assay and flowcytometry. Transwell analysis showed that one peptides (PDHPS5) can significantly inhibit the cell migration ability (The optical density value in Control is 0.81±0.11, in PDHPS5 is 0.27±0.03, t=8.61, P=0.001). Western blot analysis showed that four peptides (PDHPS2, PDHPS3, PDHPS4, PDHPS5) can significantly inhibit the protein expressions of COL1A2 (The relative protein band intensity in Control is 1.02±0.02, in PDHPS2 is 0.21±0.04, in PDHPS3 is 0.26±0.03, in PDHPS4 is 0.53±0.04, in PDHPS5 is 0.73±0.04, t=31.38, 38.54, 18.88, 11.07 respectively, all P value are less than 0.01). Three peptides (PDHPS2, PDHPS3, PDHPS5) can significantly inhibit the protein expressions of ACTA2 (The relative protein band intensity in Control is 1.02±0.02, in PDHPS2 is 0.64±0.05, in PDHPS3 is 0.77±0.06, in PDHPS5 is 0.47±0.07, t=12.08, 6.38, 14.06 respectively, all P value are less than 0.01). In conclusion, the differentially expressed peptides in human hypertrophic scar tissue can affect the function of keloid fibroblasts and collagen expressions to varying degrees. Among them, two peptides (PDHPS2,PDHPS3) significantly inhibit the protein expressions of COL1A2 and ACTA2. The peptide PDHPS5 has high stability, significantly suppresses cell migration, and reduces the protein expressions of COL1A2 and ACTA2, which may provide a new strategy for scar prevention and treatment.
Assuntos
Apoptose , Fibroblastos , Queloide , Peptídeos , Pele , Humanos , Fibroblastos/metabolismo , Queloide/metabolismo , Peptídeos/farmacologia , Pele/metabolismo , Movimento Celular , Células Cultivadas , Cicatriz Hipertrófica/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Estudos Retrospectivos , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Proliferação de Células , Actinas/metabolismoRESUMO
Chronic kidney disease poses a significant threat to public health. Renal replacement therapy is the primary treatment option for end-stage kidney disease. However, there is a promising and relatively new method in regenerative medicine for creating a functional organ known as whole kidney decellularization. This method uses the intrinsic vasculature to perfuse the decellularizing agent into the tissue, effectively penetrating and removing cellular material. The regenerated bioscaffolds could serve as a source of organ donation. This study is focused on evaluating the effectiveness of various SDS exposures in decellularizing human fetal kidneys. The study included human fetal kidneys harvested from fetuses terminated before 14 weeks of gestational age. Kidneys were divided into six treatment groups based on SDS concentration and duration of perfusion. Decellularization, scanning electron microscopy, histopathological staining, immunofluorescent staining, and immunohistochemistry staining were performed to evaluate the adequacy of the process. The statistical analysis revealed that the SDS 0.1% treatment group had the highest collagen deposition after 24 h, significantly greater than the SDS 0.5% treatment group at 24 and 48 h. No significant differences were observed among the other treatment groups. The study concludes that the SDS 0.1% treatment group for 24 h was the most effective in terms of ECM content preservation and effective cell removal. This treatment showed better results than the other treatment groups and can be considered for future whole kidney decellularization studies.