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1.
Bioact Mater ; 42: 299-315, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39290337

RESUMEN

Age-related osteoporosis is a metabolic skeletal disorder caused by estrogen deficiency in postmenopausal women. Prolonged use of anti-osteoporotic drugs such as bisphosphonates and FDA-approved anti-resorptive selective estrogen receptor modulators (SERMs) has been associated with various clinical drawbacks. We recently discovered a low-molecular-weight biocompatible and osteoanabolic phytoprotein, called HKUOT-S2 protein (32 kDa), from Dioscorea opposita Thunb that can accelerate bone defect healing. Here, we demonstrated that the HKUOT-S2 protein treatment can enhance osteoblasts-induced ossification and suppress osteoporosis development by upregulating skeletal estrogen receptors (ERs) ERα, ERß, and GPR30 expressions in vivo. Also, HKUOT-S2 protein estrogenic activities promoted hMSCs-osteoblasts differentiation and functions by increasing osteogenic markers, ALP, and RUNX2 expressions, ALP activity, and osteoblast biomineralization in vitro. Fulvestrant treatment impaired the HKUOT-S2 protein-induced ERs expressions, osteoblasts differentiation, and functions. Finally, we demonstrated that the HKUOT-S2 protein could bind to ERs to exert osteogenic and osteoanabolic properties. Our results showed that the biocompatible HKUOT-S2 protein can exert estrogenic and osteoanabolic properties by positively modulating skeletal estrogen receptor signaling to promote ossification and suppress osteoporosis. Currently, there is no or limited data if any, on osteoanabolic SERMs. The HKUOT-S2 protein can be applied as a new osteoanabolic SERM for osteoporosis treatment.

2.
Nat Commun ; 15(1): 7091, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39154080

RESUMEN

The integration of extrinsic signaling with cell-intrinsic transcription factors can direct progenitor cells to differentiate into distinct cell fates. In the developing Drosophila eye, differentiation of photoreceptors R1-R7 requires EGFR signaling mediated by the transcription factor Pointed, and our single-cell RNA-Seq analysis shows that the same photoreceptors require the eye-specific transcription factor Glass. We find that ectopic expression of Glass and activation of EGFR signaling synergistically induce neuronal gene expression in the wing disc in a Pointed-dependent manner. Targeted DamID reveals that Glass and Pointed share many binding sites in the genome of developing photoreceptors. Comparison with transcriptomic data shows that Pointed and Glass induce photoreceptor differentiation through intermediate transcription factors, including the redundant homologs Scratch and Scrape, as well as directly activating neuronal effector genes. Our data reveal synergistic activation of a multi-layered transcriptional network as the mechanism by which EGFR signaling induces neuronal identity in Glass-expressing cells.


Asunto(s)
Proteínas de Unión al ADN , Proteínas de Drosophila , Drosophila melanogaster , Receptores ErbB , Regulación del Desarrollo de la Expresión Génica , Neuronas , Transducción de Señal , Factores de Transcripción , Animales , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Receptores ErbB/metabolismo , Receptores ErbB/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Neuronas/metabolismo , Neuronas/citología , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Diferenciación Celular , Células Fotorreceptoras de Invertebrados/metabolismo , Células Fotorreceptoras de Invertebrados/citología , Proteínas del Ojo/metabolismo , Proteínas del Ojo/genética , Discos Imaginales/metabolismo , Discos Imaginales/citología , Proteínas del Tejido Nervioso , Proteínas Proto-Oncogénicas , Receptores de Péptidos de Invertebrados
3.
BMC Genomics ; 25(1): 616, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38890587

RESUMEN

The Drosophila eye has been an important model to understand principles of differentiation, proliferation, apoptosis and tissue morphogenesis. However, a single cell RNA sequence resource that captures gene expression dynamics from the initiation of differentiation to the specification of different cell types in the larval eye disc is lacking. Here, we report transcriptomic data from 13,000 cells that cover six developmental stages of the larval eye. Our data show cell clusters that correspond to all major cell types present in the eye disc ranging from the initiation of the morphogenetic furrow to the differentiation of each photoreceptor cell type as well as early cone cells. We identify dozens of cell type-specific genes whose function in different aspects of eye development have not been reported. These single cell data will greatly aid research groups studying different aspects of early eye development and will facilitate a deeper understanding of the larval eye as a model system.


Asunto(s)
Ojo , Larva , Análisis de la Célula Individual , Animales , Larva/genética , Larva/crecimiento & desarrollo , Larva/metabolismo , Ojo/metabolismo , Ojo/crecimiento & desarrollo , Perfilación de la Expresión Génica , Transcriptoma , Regulación del Desarrollo de la Expresión Génica , Drosophila/genética , Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Análisis de Secuencia de ARN
4.
Acta Biomater ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38876454

RESUMEN

Biodegradable Zn alloys show great potential for vascular stents due to their moderate degradation rates and acceptable biocompatibility. However, the poor mechanical properties limit their applications. In this study, low alloyed Zn-2Cu-xLi (x = 0.004, 0.01, 0.07 wt %) alloys with favorable mechanical properties were developed. The microstructure consists of fine equiaxed η-Zn grains, micron, submicron-sized and coherent nano ε-CuZn4 phases. The introduced Li exists as a solute in the η-Zn matrix and ε-CuZn4 phase, and results in the increase of ε-CuZn4 volume fraction, the refinement of grains and more uniform distribution of grain sizes. As Li content increases, the strength of alloys is dramatically improved by grain boundary strengthening, precipitate strengthening of ε-CuZn4 and solid solution strengthening of Li. Zn-2Cu-0.07Li alloy has the optimal mechanical properties with a tensile yield strength of 321.8 MPa, ultimate tensile strength of 362.3 MPa and fracture elongation of 28.0 %, exceeding the benchmark of stents. It also has favorable mechanical property stability, weak tension compression yield asymmetry and strain rate sensitivity. It exhibits uniform degradation and a little improved degradation rate of 89.5 µm∙year-1, due to the improved electrochemical activity by increased ε-CuZn4 volume fraction, and generates Li2CO3 and LiOH. It shows favorable cytocompatibility without adverse influence on endothelial cell viability by trace Li+. The fabricated microtubes show favorable mechanical properties, and stents exhibit an average radial strength of 118 kPa. The present study indicates that Zn-2Cu-0.07Li alloy is a potential and promising candidate for vascular stent applications. STATEMENT OF SIGNIFICANCE: Zn alloys are promising candidates for biodegradable vascular stents. However, improving their mechanical properties is challenging. Combining the advantages of Cu and trace Li, Zn-2Cu-xLi (x < 0.1 wt %) alloys were developed for stents. As Li increases, the strength of alloys is dramatically improved by refined grains, increased volume fraction of ε-CuZn4 and solid solution of Li. Zn-2Cu-0.07Li alloy exhibits a TYS exceeding 320 MPa, UTS exceeding 360 MPa and fracture EL of nearly 30 %. It shows favorable mechanical stability, degradation behaviors and cytocompatibility. The alloy was fabricated into microtubes and stents for mechanical property tests to verify application feasibility for the first time. This indicates that Zn-2Cu-0.07Li alloy has great potential for vascular stent applications.

5.
Bioact Mater ; 40: 19-33, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38882001

RESUMEN

Infection and poor tissue repair are the key causes of percutaneous implantation failure. However, there is a lack of effective strategies to cope with due to its high requirements of sterilization, soft tissue healing, and osseointegration. In this work, l-arginine (L-Arg) was loaded onto a sulfonated polyetheretherketone (PEEK) surface to solve this issue. Under the infection condition, nitric oxide (NO) and reactive oxygen species (ROS) are produced through catalyzing L-Arg by inducible nitric oxide synthase (iNOS) and thus play a role in bacteria sterilization. Under the tissue repair condition, L-Arg is catalyzed to ornithine by Arginase-1 (Arg-1), which promotes the proliferation and collagen secretion of L929 and rBMSCs. Notably, L-Arg loading samples could polarize macrophages to M1 and M2 in infection and tissue repair conditions, respectively. The results in vivo show that the L-Arg loading samples could enhance infected soft tissue sealing and bone regeneration. In summary, L-Arg loading sulfonated PEEK could polarize macrophage through metabolic reprogramming, providing multi-functions of antibacterial abilities, soft tissue repair, and bone regeneration, which gives a new idea to design percutaneous implantation materials.

6.
Adv Mater ; 36(31): e2404485, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38760003

RESUMEN

Achieving bacterial killing and osteogenic formation on an implant surface rarely occurs. In this study, a novel surface design-a palladium hydride (PdHx) film that enables these two distinct features to coexist is introduced. The PdHx lattice captures protons in the extracellular microenvironment of bacteria, disrupting their normal metabolic activities, such as ATP synthesis, nutrient co-transport, and oxidative stress. This disruption leads to significant bacterial death, as evidenced by RNA sequence analysis. Additionally, the unique enzymatic activity and hydrogen-loading properties of PdHx activate the human antioxidant system, resulting in the rapid clearance of reactive oxygen species. This process reshapes the osteogenic immune microenvironment, promoting accelerated osteogenesis. These findings reveal that the downregulation of the NOD-like receptor signaling pathway is critical for activating immune cells toward M2 phenotype polarization. This novel surface design provides new strategies for modifying implant coatings to simultaneously prevent bacterial infection, reduce inflammation, and enhance tissue regeneration, making it a noteworthy contribution to the field of advanced materials.


Asunto(s)
Antioxidantes , Osteogénesis , Paladio , Propiedades de Superficie , Paladio/química , Osteogénesis/efectos de los fármacos , Humanos , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/metabolismo , Protones , Antibacterianos/farmacología , Antibacterianos/química , Especies Reactivas de Oxígeno/metabolismo , Hidrógeno/química , Hidrógeno/metabolismo , Animales , Estrés Oxidativo/efectos de los fármacos
7.
ACS Nano ; 18(23): 15114-15129, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38798240

RESUMEN

Implant-related secondary infections are a challenging clinical problem. Sonodynamic therapy (SDT) strategies are promising for secondary biofilm infections by nonsurgical therapy. However, the inefficiency of SDT in existing acoustic sensitization systems limits its application. Therefore, we take inspiration from popular metamaterials and propose the design idea of a metainterface heterostructure to improve SDT efficiency. The metainterfacial heterostructure is defined as a periodic arrangement of heterointerface monoclonal cells that amplify the intrinsic properties of the heterointerface. Herein, we develop a TiO2/Ti2O3/vertical graphene metainterface heterostructure film on titanium implants. This metainterface heterostructure exhibits extraordinary sonodynamic and acoustic-to-thermal conversion effects under low-intensity ultrasound. The modulation mechanisms of the metainterface for electron accumulation and separation are revealed. The synergistic sonodynamic/mild sonothermal therapy disrupts biofilm infections (antibacterial rates: 99.99% for Staphylococcus aureus, 99.54% for Escherichia coli), and the osseointegration ability of implants is significantly improved in in vivo tests. Such a metainterface heterostructure film lays the foundation for the metainterface of manipulating electron transport to enhance the catalytic performance and holding promise for addressing secondary biofilm infections.


Asunto(s)
Antibacterianos , Biopelículas , Escherichia coli , Staphylococcus aureus , Titanio , Terapia por Ultrasonido , Biopelículas/efectos de los fármacos , Titanio/química , Titanio/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Escherichia coli/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Grafito/química , Grafito/farmacología , Ratones , Animales , Pruebas de Sensibilidad Microbiana
8.
Mater Horiz ; 11(11): 2759, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38716898

RESUMEN

Correction for 'A differential-targeting core-shell microneedle patch with coordinated and prolonged release of mangiferin and MSC-derived exosomes for scarless skin regeneration' by Shang Lyu et al., Mater. Horiz., 2024, https://doi.org/10.1039/D3MH01910A.

9.
Nat Commun ; 15(1): 3769, 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38704393

RESUMEN

Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with bone deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow upon estrogen deficiency or obesity. Mechanistically, adipocyte ESRRA interferes with E2/ESR1 signaling resulting in transcriptional repression of secreted phosphoprotein 1 (Spp1); yet positively modulates leptin expression by binding to its promoter. ESRRA abrogation results in enhanced SPP1 and decreased leptin secretion from both visceral adipocytes and BMAds, concertedly dictating bone marrow stromal stem cell fate commitment and restoring type H vessel formation, constituting a feed-forward loop for bone formation. Pharmacological inhibition of ESRRA protects obese mice against bone loss and high marrow adiposity. Thus, our findings highlight a therapeutic approach via targeting adipocyte ESRRA to preserve bone formation especially in detrimental adipocyte-rich bone milieu.


Asunto(s)
Adipocitos , Médula Ósea , Leptina , Osteogénesis , Receptores de Estrógenos , Animales , Osteogénesis/genética , Adipocitos/metabolismo , Adipocitos/citología , Ratones , Leptina/metabolismo , Leptina/genética , Médula Ósea/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/genética , Células Madre Mesenquimatosas/metabolismo , Obesidad/metabolismo , Obesidad/patología , Obesidad/genética , Receptor Relacionado con Estrógeno ERRalfa , Receptor alfa de Estrógeno/metabolismo , Receptor alfa de Estrógeno/genética , Femenino , Masculino , Ratones Endogámicos C57BL , Transducción de Señal , Células de la Médula Ósea/metabolismo , Ratones Noqueados
10.
Mater Horiz ; 11(11): 2667-2684, 2024 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-38669042

RESUMEN

Microneedles for skin regeneration are conventionally restricted by uncontrollable multi-drug release, limited types of drugs, and poor wound adhesion. Here, a novel core-shell microneedle patch is developed for scarless skin repair, where the shell is composed of hydrophilic gelatin methacryloyl (GelMA) loaded with mangiferin, an anti-inflammatory small molecule, and the core is composed of hydrophobic poly (lactide-co-propylene glycol-co-lactide) dimethacrylates (PGLADMA) loaded with bioactive macromolecule and human mesenchymal stromal cell (hMSC)-derived exosomes. This material choice provides several benefits: the GelMA shell provides a swelling interface for tissue interlocking and rapid release of mangiferin at an early wound healing stage for anti-inflammation, whereas the PGLADMA core offers long-term encapsulation and release of exosomes (30% release in 3 weeks), promoting sustained angiogenesis and anti-inflammation. Our results demonstrate that the core-shell microneedle possesses anti-inflammatory properties and can induce angiogenesis both in vitro in terms of macrophage polarization and tube formation of human umbilical vein endothelial cells (HUVECs), and in vivo in terms of anti-inflammation, re-epithelization, and vessel formation. Importantly, we also observe reduced scar formation in vivo. Altogether, the degradation dynamics of our hydrophilic/hydrophobic materials enable the design of a core-shell microneedle for differential and prolonged release, promoting scarless skin regeneration, with potential for other therapies of long-term exosome release.


Asunto(s)
Exosomas , Células Endoteliales de la Vena Umbilical Humana , Células Madre Mesenquimatosas , Agujas , Cicatrización de Heridas , Xantonas , Exosomas/metabolismo , Humanos , Xantonas/administración & dosificación , Xantonas/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Animales , Regeneración/efectos de los fármacos , Regeneración/fisiología , Piel/metabolismo , Piel/efectos de los fármacos , Gelatina/química , Preparaciones de Acción Retardada , Ratones , Masculino
11.
Nat Commun ; 15(1): 1030, 2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38310104

RESUMEN

Secretin, though originally discovered as a gut-derived hormone, is recently found to be abundantly expressed in the ventromedial hypothalamus, from which the central neural system controls satiety, energy metabolism, and bone homeostasis. However, the functional significance of secretin in the ventromedial hypothalamus remains unclear. Here we show that the loss of ventromedial hypothalamus-derived secretin leads to osteopenia in male and female mice, which is primarily induced by diminished cAMP response element-binding protein phosphorylation and upregulation in peripheral sympathetic activity. Moreover, the ventromedial hypothalamus-secretin inhibition also contributes to hyperphagia, dysregulated lipogenesis, and impaired thermogenesis, resulting in obesity in male and female mice. Conversely, overexpression of secretin in the ventromedial hypothalamus promotes bone mass accrual in mice of both sexes. Collectively, our findings identify an unappreciated secretin signaling in the central neural system for the regulation of energy and bone metabolism, which may serve as a new target for the clinical management of obesity and osteoporosis.


Asunto(s)
Hipotálamo , Secretina , Ratones , Masculino , Femenino , Animales , Secretina/metabolismo , Hipotálamo/metabolismo , Obesidad/genética , Obesidad/metabolismo , Homeostasis/fisiología , Metabolismo Energético
13.
BMC Genomics ; 25(1): 103, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38262913

RESUMEN

The Ets domain transcription factors direct diverse biological processes throughout all metazoans and are implicated in development as well as in tumor initiation, progression and metastasis. The Drosophila Ets transcription factor Pointed (Pnt) is the downstream effector of the Epidermal growth factor receptor (Egfr) pathway and is required for cell cycle progression, specification, and differentiation of most cell types in the larval eye disc. Despite its critical role in development, very few targets of Pnt have been reported previously. Here, we employed an integrated approach by combining genome-wide single cell and bulk data to identify putative cell type-specific Pnt targets. First, we used chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) to determine the genome-wide occupancy of Pnt in late larval eye discs. We identified enriched regions that mapped to an average of 6,941 genes, the vast majority of which are novel putative Pnt targets. Next, we integrated ChIP-seq data with two other larval eye single cell genomics datasets (scRNA-seq and snATAC-seq) to reveal 157 putative cell type-specific Pnt targets that may help mediate unique cell type responses upon Egfr-induced differentiation. Finally, our integrated data also predicts cell type-specific functional enhancers that were not reported previously. Together, our study provides a greatly expanded list of putative cell type-specific Pnt targets in the eye and is a resource for future studies that will allow mechanistic insights into complex developmental processes regulated by Egfr signaling.


Asunto(s)
Drosophila , Genómica , Animales , Diferenciación Celular , Receptores ErbB , Larva , Proteínas Proto-Oncogénicas c-ets
14.
ACS Biomater Sci Eng ; 9(12): 6849-6859, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-37942941

RESUMEN

The development of magnesium-derived biomaterials is one of the most promising research in bone tissue engineering, and related strategies have been extensively used for tendon, skull, cartilage, and bone regeneration. Also, alendronate, a well-recognized drug for osteoporosis treatment, has recently attracted a great deal of attention for bone repair. However, rapid corrosion in vivo of Mg2+ and low systemic bioavailability of alendronate are the main limitations hampering their full exploitation. In this work, by means of physical and chemical cross-linking conjugating magnesium-metal-organic frameworks (Mg-MOFs) and bone-targeting alendronate to biocompatible gelatin scaffolds, a facile method is developed for the preparation of organic/inorganic nanocomposite gel scaffolds. The results affirmed that the nanocomposite gel scaffolds possessed excellent biocompatibility, continuous slow release of Mg2+ and alendronate, strong bone affinity, and bone regeneration. It is noteworthy that the continuous slow release of Mg2+ and alendronate could induce the macrophage switch to the M2 phenotype and promote osteogenic differentiation in the early stage, resulting in improved bone regeneration during implanting the scaffolds into the distal femoral. In summary, Mg-MOFs-loaded alendronate-modified gelatin gel scaffolds have been developed, exhibiting great potential for bone regenerative.


Asunto(s)
Difosfonatos , Osteogénesis , Difosfonatos/farmacología , Alendronato/farmacología , Magnesio/farmacología , Gelatina/farmacología , Nanogeles , Andamios del Tejido , Regeneración Ósea
15.
Nat Commun ; 14(1): 7205, 2023 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-37938573

RESUMEN

The Drosophila eye is a powerful model system to study the dynamics of cell differentiation, cell state transitions, cell maturation, and pattern formation. However, a high-resolution single cell genomics resource that accurately profiles all major cell types of the larval eye disc and their spatiotemporal relationships is lacking. Here, we report transcriptomic and chromatin accessibility data for all known cell types in the developing eye. Photoreceptors appear as strands of cells that represent their dynamic developmental timelines. As photoreceptor subtypes mature, they appear to assume a common transcriptomic profile that is dominated by genes involved in axon function. We identify cell type maturation genes, enhancers, and potential regulators, as well as genes with distinct R3 or R4 photoreceptor specific expression. Finally, we observe that the chromatin accessibility between cones and photoreceptors is distinct. These single cell genomics atlases will greatly enhance the power of the Drosophila eye as a model system.


Asunto(s)
Ascomicetos , Drosophila , Animales , Drosophila/genética , Diferenciación Celular/genética , Cromatina , Genómica , Larva/genética
16.
Contact Dermatitis ; 89(6): 442-452, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37700557

RESUMEN

BACKGROUND: Allergic contact dermatitis (ACD) is an inflammatory disease with a complex pathophysiology in which epidermal-resident memory CD8+ T (TRM ) cells play a key role. The mechanisms involved in the activation of CD8+ TRM cells during allergic flare-up responses are not understood. METHODS: The expression of CD100 and its ligand Plexin B2 on CD8+ TRM cells and keratinocytes before and after allergen exposure was determined by flow cytometry and RT-qPCR. The role of CD100 in the inflammatory response during the challenge phase of ACD was determined in a model of ACD in CD100 knockout and wild-type mice. RESULTS: We show that CD8+ TRM cells express CD100 during homeostatic conditions and up-regulate it following re-exposure of allergen-experienced skin to the experimental contact allergen 1-fluoro-2,4-dinitrobenzene (DNFB). Furthermore, Plexin B2 is up-regulated on keratinocytes following exposure to some contact allergens. We show that loss of CD100 results in a reduced inflammatory response to DNFB with impaired production of IFNγ, IL-17A, CXCL1, CXCL2, CXCL5, and IL-1ß and decreased recruitment of neutrophils to the epidermis. CONCLUSION: Our study demonstrates that CD100 is expressed on CD8+ TRM cells and is required for full activation of CD8+ TRM cells and the flare-up response of ACD.


Asunto(s)
Dermatitis Alérgica por Contacto , Animales , Ratones , Alérgenos , Dermatitis Alérgica por Contacto/metabolismo , Dinitrofluorobenceno/metabolismo , Queratinocitos/metabolismo , Piel
17.
Contact Dermatitis ; 89(5): 323-334, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37619972

RESUMEN

BACKGROUND: The junctional adhesion molecule-like protein (JAML) plays important roles in wound healing and activation of epidermal γδ T cells in mice. Whether JAML plays a role in contact hypersensitivity (CHS), the animal model of allergic contact dermatitis (ACD), is not known. METHODS: To examine the role of JAML in CHS, we used various mouse models of CHS in JAML knockout (KO) and wild-type (WT) mice. Furthermore, the expression of the JAML ligand coxsackievirus and adenovirus receptor (CXADR) on keratinocytes was accessed in vitro and in vivo. RESULTS: JAML KO mice had a diminished inflammatory response during both the sensitization and elicitation phase of CHS and had reduced numbers of CD8+ and CD4+ T cells in the epidermis. Furthermore, interferon γ (IFNγ), interleukin 1ß (IL-1ß) and CXCL10 production were significantly reduced in JAML KO mice during the elicitation phase. We found that CD8+ T cells express JAML and that JAML is essential for rapid flare-up responses to contact allergens. Finally, we show that keratinocytes up-regulate the JAML ligand CXADR following exposure to contact allergens. CONCLUSION: Our study is the first to show a central role of JAML in CHS and reveals a potential new target for the treatment of ACD in humans.


Asunto(s)
Linfocitos T CD8-positivos , Dermatitis Alérgica por Contacto , Humanos , Ratones , Animales , Moléculas de Adhesión de Unión , Ligandos , Epidermis , Ratones Noqueados , Ratones Endogámicos C57BL
18.
J Biomed Mater Res A ; 111(12): 1888-1902, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37555381

RESUMEN

Biomaterials for nucleus pulposus (NP) replacement and regeneration have great potential to restore normal biomechanics in degenerated intervertebral discs following nucleotomy. Mechanical characterizations are essential for assessing the efficacy of biomaterial implants for clinical applications. While traditional compression tests are crucial to quantify various modulus values, relaxation behaviors and fatigue resistance, rheological measurements should also be conducted to investigate the viscoelastic properties, injectability, and overall stability upon deformation. To recapitulate the physiological in vivo environment, the use of spinal models is necessary to evaluate the risk of implant extrusion and the restoration of biomechanics under different loading conditions. When designing devices for NP replacement, injectable materials are ideal to fully fill the nucleus cavity and prevent implant migration. In addition to achieving biocompatibility and desirable mechanical characteristics, biomaterial implants should be optimized to avoid implant extrusion or re-herniation post-operatively. This review discusses the most commonly used testing protocols for assessing mechanical properties of biomaterial implants and serves as reference material for enabling researchers to characterize NP implants through a unified approach whereby newly developed biomaterials may be compared and contrasted to existing devices.


Asunto(s)
Degeneración del Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Materiales Biocompatibles , Disco Intervertebral/cirugía , Disco Intervertebral/fisiología , Prótesis e Implantes , Regeneración , Degeneración del Disco Intervertebral/cirugía
19.
Biomater Sci ; 11(15): 5347-5348, 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37403749

RESUMEN

Correction for 'Construction of perfluorohexane/IR780@liposome coating on Ti for rapid bacteria killing under permeable near infrared light' by Xiuhua Wang et al., Biomater. Sci., 2018, 6, 2460-2471, https://doi.org/10.1039/C8BM00602D.

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