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1.
Int J Oral Implantol (Berl) ; 17(1): 89-100, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501401

RESUMO

PURPOSE: To establish consensus-driven guidelines that could support the clinical decision-making process for implant-supported rehabilitation of the posterior atrophic maxilla and ultimately improve long-term treatment outcomes and patient satisfaction. MATERIALS AND METHODS: A total of 33 participants were enrolled (18 active members of the Italian Academy of Osseointegration and 15 international experts). Based on the available evidence, the development group discussed and proposed an initial list of 20 statements, which were later evalu-ated by all participants. After the forms were completed, the responses were sent for blinded ana-lysis. In most cases, when a consensus was not reached, the statements were rephrased and sent to the participants for another round of evaluation. Three rounds were planned. RESULTS: After the first round of voting, participants came close to reaching a consensus on six statements, but no consensus was achieved for the other fourteen. Following this, nineteen statements were rephrased and sent to participants again for the second round of voting, after which a consensus was reached for six statements and almost reached for three statements, but no consensus was achieved for the other ten. All 13 statements upon which no consensus was reached were rephrased and included in the third round. After this round, a consensus was achieved for an additional nine statements and almost achieved for three statements, but no consensus was reached for the remaining statement. CONCLUSION: This Delphi consensus highlights the importance of accurate preoperative planning, taking into consideration the maxillomandibular relationship to meet the functional and aesthetic requirements of the final restoration. Emphasis is placed on the role played by the sinus bony walls and floor in providing essential elements for bone formation, and on evaluation of bucco-palatal sinus width for choosing between lateral and transcrestal sinus floor elevation. Tilted and trans-sinus implants are considered viable options, whereas caution is advised when placing pterygoid implants. Zygomatic implants are seen as a potential option in specific cases, such as for completely edentulous elderly or oncological patients, for whom conventional alternatives are unsuitable.


Assuntos
Implantes Dentários , Levantamento do Assoalho do Seio Maxilar , Humanos , Idoso , Maxila/cirurgia , Levantamento do Assoalho do Seio Maxilar/métodos , Consenso , Técnica Delfos , Estética Dentária , Atrofia/patologia
2.
Am J Transplant ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38514014

RESUMO

Highly inflamed and neovascularized corneal graft beds are known as high-risk (HR) environments for transplant survival. One of the primary factors leading to this rejection is reduction in the suppressive function of regulatory T cells (Treg). Our results show that myeloid-derived suppressor cells (MDSC) counteract interleukin-6-mediated Treg dysfunction by expressing interleukin-10. Additionally, MDSC maintain forkhead box P3 stability and their ability to suppress IFN-γ+ Th1 cells. Administering MDSC to HR corneal transplant recipients demonstrates prolonged graft survival via promotion of Treg while concurrently suppressing IFN-γ+ Th1 cells. Moreover, MDSC-mediated donor-specific immune tolerance leads to long-term corneal graft survival as evidenced by the higher survival rate or delayed survival of a second-party C57BL/7 (B6) graft compared to those of third-party C3H grafts observed in contralateral low-risk or HR corneal transplantation of BALB/c recipient mice, respectively. Our study provides compelling preliminary evidence demonstrating the effectiveness of MDSC in preventing Treg dysfunction, significantly improving graft survival in HR corneal transplantation, and showing promising potential for immune tolerance induction.

3.
Int J Periodontics Restorative Dent ; 44(2): 139-141, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38507398

RESUMO

Over the last 100 years, the dental profession has undergone incredible progress to address problems created by oral disease. Our ability to restore function and esthetics efficiently and predictably via modern restorative materials, regenerative treatments, dental implant therapy, and digitally driven workflows is truly remarkable. For those members of our profession privileged to work in fully developed economies, the prevailing perception is that the war against caries, periodontitis, and edentulism has been largely won. There has surely never been a more exciting time to be in dentistry. Thus, it may sound paradoxical or even alarmist to state that dentistry is falling behind in its mission to serve the needs of our patients­but it is.^ieng

4.
Artigo em Inglês | MEDLINE | ID: mdl-38265357
5.
J Clin Periodontol ; 51(2): 177-195, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37963451

RESUMO

BACKGROUND: The aim of this systematic review was two-fold: (i) to evaluate the long-term (≥5 years) stability of the gingival margin position, keratinized tissue width (KTW) and gingival thickness (GT) in sites that underwent root coverage (RC) or gingival augmentation (GA); and (ii) to assess the influence of different local variables on the long-term stability of dental and gingival tissues. MATERIALS AND METHODS: Randomized controlled trials (RCTs) and non-RCTs reporting short-term (i.e., 6-12 months after baseline surgical intervention) and long-term (≥5 years) follow-up data after surgical treatment of adult patients presenting single or multiple mucogingival deformities, defined as sites presenting gingival recession defects (GRDs) and/or (KTW) deficiency (i.e., <2 mm), were considered eligible for inclusion. MEDLINE-PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases were searched for articles published up to 15 May 2023. Mixed-effects multiple linear regression was used to assess the association between KTW, type of surgical procedure and time (i.e., independent variables) on the stability of the gingival margin in sites that received RC or GA therapy. RESULTS: Of the 2569 potentially eligible records, 41 (reporting 40 studies) met the eligibility criteria. Graphical estimates including data from all RC procedures found an upward trend in recession depth (RD) increase over time. Conversely, it was observed that in 63.63% of RC studies and in 59.32% of RC treatment arms KTW increased over time, particularly in sites treated with subepithelial connective tissue grafts (SCTGs). Conversely, sites that underwent GA procedures generally exhibited an overall reduction of KTW over time. However, sites treated with free gingival grafts (FGGs) showed a decrease in RD after 10 years of follow-up. Three main findings derived from the pooled estimates were identified: (i) Gingival margin stability was associated with the amount of KTW present during short-term assessment (i.e. the greater the KTW at 6-12 months after treatment, the more stable the gingival margin). (ii) The use of autogenous soft-tissue grafts was associated with lower RD increase over time. (iii) Treatment approaches that contribute to the three-dimensional enhancement of the gingival phenotype, as clearly demonstrated by FGG, were associated with gingival margin stability. CONCLUSIONS: The extent of apical migration of the gingival margin appears to be directly related to the amount of KTW and GT upon tissue maturation. Interventions involving the use of autogenous grafts, either SCTG or FGG, are associated with greater short-term KTW gain and lower RD increase over time.


Assuntos
Retração Gengival , Retalhos Cirúrgicos , Adulto , Humanos , Retalhos Cirúrgicos/cirurgia , Raiz Dentária/cirurgia , Gengiva/cirurgia , Retração Gengival/cirurgia , Regeneração Tecidual Guiada Periodontal/métodos , Tecido Conjuntivo/transplante , Resultado do Tratamento
6.
Artigo em Inglês | MEDLINE | ID: mdl-37819852

RESUMO

Ultrathin ceramic veneers are a viable therapeutic option to manage esthetic challenges in the anterior zone. Proper conditioning of the intaglio surface of porcelain veneers is essential to achieve an adequate bonding. In clinical practice, this is typically done with chemical etching using an acid-containing agent, such as hydrofluoric acid. While it is well established that the etching effect is dependent on etching time and the acid concentration, little is known about the impact of etching time and the veneer fabrication method. The purpose of this pilot study was to evaluate, using scanning electron microscopy (SEM), the effect that different etching-time protocols have on the intaglio surface characteristics of ultrathin ceramic veneers fabricated with either the platinum foil technique or the refractory die technique. Several replicas of an ultrathin feldspathic ceramic veneer for a maxillary central incisor were fabricated. Individual specimens were processed according to different intaglio surface-etching protocols: no etching, etching for 90 seconds, etching for 120 seconds, and etching for 150 seconds (9.6% hydrofluoric acid used for all etching groups). It was observed that the 120-second etching protocol resulted in a favorable microroughness surface pattern in the platinum foil group. This pattern was comparable to that obtained by etching for 90 seconds with hydrofluoric acid the intaglio surface of veneers fabricated with the refractory die technique. Increasing the etching time to 150 seconds did not result in a more favorable roughness pattern.


Assuntos
Colagem Dentária , Porcelana Dentária , Humanos , Ácido Fluorídrico , Microscopia Eletrônica de Varredura , Platina , Projetos Piloto , Condicionamento Ácido do Dente/métodos , Propriedades de Superfície , Cerâmica , Teste de Materiais , Cimentos de Resina
7.
Am J Pathol ; 194(1): 150-164, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37827217

RESUMO

Corneal endothelial cells (CEnCs) regulate corneal hydration and maintain tissue transparency through their barrier and pump function. However, these cells exhibit limited regenerative capacity following injury. Currently, corneal transplantation is the only established therapy for restoring endothelial function, and there are no pharmacologic interventions available for restoring endothelial function. This study investigated the efficacy of the neuropeptide α-melanocyte-stimulating hormone (α-MSH) in promoting endothelial regeneration during the critical window between ocular injury and the onset of endothelial decompensation using an established murine model of injury using transcorneal freezing. Local administration of α-MSH following injury prevented corneal edema and opacity, reduced leukocyte infiltration, and limited CEnC apoptosis while promoting their proliferation. These results suggest that α-MSH has a proregenerative and cytoprotective function on CEnCs and shows promise as a therapy for the prevention and management of corneal endothelial dysfunction.


Assuntos
Córnea , Edema da Córnea , alfa-MSH , Feminino , Gravidez , Animais , Camundongos , Camundongos Endogâmicos BALB C , Humanos , Linhagem Celular , Córnea/citologia , Células Endoteliais , Edema da Córnea/tratamento farmacológico , Edema da Córnea/patologia , Preservação de Tecido , alfa-MSH/uso terapêutico , Citoproteção , Infiltração de Neutrófilos , Monócitos/metabolismo , Macrófagos/metabolismo , Cicatrização/efeitos dos fármacos
8.
Artigo em Inglês | MEDLINE | ID: mdl-37819850

RESUMO

The aim of this PRISMA-compliant systematic review was to analyze the evidence pertaining to disease resolution after treatment of peri-implant diseases (PROSPERO: CRD42022306999) with the following PICO question: what is the rate of disease resolution following non-surgical and surgical therapy for peri-implant diseases in adult human subjects? A literature search to identify studies that fulfilled a pre-established eligibility criteria was conducted. Data on primary therapeutic outcomes, including treatment success, rate of disease resolution and/or recurrence, as well as a variety of secondary outcomes was extracted and categorized. Fifty-five articles were included. Few studies investigated the efficacy of different non-surgical and surgical therapies to treat peri-implant diseases using a set of pre-defined criteria and with follow-up periods of at least one year. The definition of treatment success and outcomes of disease resolution differed considerably among the included studies. Treatment of peri-implant mucositis was most commonly reported to be successful in arresting disease progression for ≤60% of the cases, whereas most studies on peri-implantitis treatment reported disease resolution occurring in <50% of the fixtures. In conclusion, disease resolution is generally unpredictable and infrequently achieved after the treatment of peri-implant diseases. A great variety of definitions have been used to define treatment success. Notably, percentages of treatment success and disease resolution were generally underreported. The use of standardized parameters to evaluate disease resolution should be considered an integral component in future clinical studies.

9.
Artigo em Inglês | MEDLINE | ID: mdl-37655973

RESUMO

This study aimed at determining the correlation between gingival stippling (GS) and other phenotypical characteristics. Adult subjects in need of cone-beam computed tomography scans (CBCT) and comprehensive dental treatment in the maxillary anterior region were recruited. Facial gingival thickness [GT] and buccal bone thickness [BT] were assessed utilizing CBCT. Standardized intraoral photographs were obtained to determine keratinized tissue width (KTW), presence of GS in all facial and interproximal areas between the maxillary canines, and other variables of interest, such as gingival architecture (GA), tooth shape, and location. Statistical analyses to assess different correlations among recorded variables were conducted. A total of 100 participants and 600 maxillary anterior teeth constituted the study population and sample, respectively. Facial GS was observed in 56% of males and 44% of females, and it was more frequently associated with flat GA, triangular and square/tapered teeth, central incisors, and males. Greater mean values of GT, BT, and KTW were observed in facial areas that exhibited GS. Interdental GS was present in 73% of the sites and it was more frequently observed in males, the central incisor region, and when facial GS was present. Multilevel logistic regression revealed a statistically significant association between the presence of GS and KTW, BT measured at 3mm apical to the bone crest, and tooth type. This information can be used in the recognition of common periodontal phenotypical patterns associated with specific features of great clinical significance.

10.
Periodontol 2000 ; 93(1): 183-204, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37486029

RESUMO

Rehabilitation of the edentulous maxilla with implant-supported fixed dental prostheses can represent a significant clinical challenge due to limited bone availability and surgical access, among other factors. This review addresses several treatment options to replace missing teeth in posterior maxillary segments, namely the placement of standard implants in conjunction with maxillary sinus floor augmentation, short implants, tilted implants, and distal cantilever extensions. Pertinent technical information and a concise summary of relevant evidence on the reported outcomes of these different therapeutic approaches are presented, along with a set of clinical guidelines to facilitate decision-making processes and optimize the outcomes of therapy.


Assuntos
Implantes Dentários , Arcada Edêntula , Boca Edêntula , Levantamento do Assoalho do Seio Maxilar , Humanos , Implantação Dentária Endóssea , Maxila/cirurgia , Planejamento de Prótese Dentária , Boca Edêntula/cirurgia , Prótese Dentária Fixada por Implante , Arcada Edêntula/reabilitação , Resultado do Tratamento
11.
J Clin Periodontol ; 50(10): 1360-1370, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37424138

RESUMO

AIM: To determine the structural and gene expression features of different intra-oral soft tissue donor sites (i.e., anterior palate, posterior palate, maxillary tuberosity and retromolar pad). MATERIALS AND METHODS: Standardized mucosal tissue punch biopsies were collected from at least one donor site per subject. Histological processing was performed to determine tissue morphometry and quantify collagen composition. Site-specific gene distribution was mapped using targeted gene expression analysis and validated using real time polymerase chain reaction (qPCR). RESULTS: A total of 50 samples from 37 subjects were harvested. Epithelial thickness did not differ between sites. However, lamina propria was thicker in the maxillary tuberosity (2.55 ± 0.92 mm) and retromolar pad (1.98 ± 0.71 mm) than in the lateral palate. Type I collagen was the predominant structural protein in the lamina propria (75.06%-80.21%). Genes involving collagen maturation and extracellular matrix regulation were highly expressed in the maxillary tuberosity and retromolar pad, while lipogenesis-associated genes were markedly expressed in the lateral palate. The retromolar pad showed the most distinct gene expression profile, and the anterior and posterior palate displayed similar transcription profiles. CONCLUSIONS: Tissue samples harvested from the anterior and posterior palate differed morphologically from those from the maxillary tuberosity and retromolar pad. Each intra-oral site showed a unique gene expression profile, which might impact their biological behaviour and outcomes of soft tissue augmentation procedures.


Assuntos
Tecido Conjuntivo , Palato , Humanos , Tecido Conjuntivo/transplante , Palato/anatomia & histologia , Colágeno , Mucosa , Perfilação da Expressão Gênica
12.
Artigo em Inglês | MEDLINE | ID: mdl-37471159

RESUMO

The primary aim of this study was to evaluate the efficacy of alveolar ridge preservation (ARP) therapy compared with unassisted socket healing (USH) in attenuating interproximal soft tissue atrophy. Adult subjects that underwent maxillary single-tooth extraction with or without ARP therapy were included in this study. Surface scans and cone beam computed tomography were obtained to digitally assess interproximal soft tissue height changes and measure facial bone thickness (FBT), respectively. Logistic regression models were conducted to investigate the individual effect of demographic and clinical variables. Ninety-six subjects (USH=49; ARP=47) constituted the study population. Linear soft tissue assessments revealed a significant reduction of the interproximal soft tissue over time within and between groups (P<.0001). ARP therapy significantly attenuated interproximal soft tissue height reduction compared to USH (USH mesial: -2.0±0.9mm vs. ARP mesial: -1.0±0.5mm / USH distal -1.9±0.7mm vs. ARP distal: -1.1±0.5mm; P<.0001). Thin FBT (≤1mm) upon extraction was associated with greater interproximal soft tissue atrophy compared with thick FBT (>1mm), independently of the treatment received (P<.0001). Nevertheless, ARP therapy resulted in better preservation of interproximal soft tissue height especially in thin bone phenotype by a factor of 2 for the mesial site (+1.3mm) and a factor of 1.6 (+0.9mm) for the distal site. This study demonstrated that ARP therapy largely attenuates interproximal soft tissue dimensional reduction after maxillary single-tooth extraction compared with USH.

13.
J Periodontol ; 94(11): 1315-1323, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37332251

RESUMO

BACKGROUND: This study aimed to evaluate the reliability and reproducibility of different non-invasive methods for the assessment of peri-implant mucosal thickness. METHODS: Subjects with two adjacent dental implants in the central maxillary region were included in this study. Three different methods to assess facial mucosal thickness (FMT) were compared: digital file superimposition using Digital Imaging and Communication in Medicine (DICOM) and stereolithography (STL) files of the arch of interest (DICOM-STL), DICOM files alone, and non-ionizing ultrasound (US). Inter-rater reliability agreements between different assessment methods were analyzed using inter-class correlation coefficients (ICCs). RESULTS: A total of 50 subjects with 100 bone-level implants constituted the study population. Assessment of FMT using STL and DICOM files demonstrated excellent inter-rater reliability agreement. Mean ICC values of 0.97 and 0.95 were observed in the DICOM-STL and DICOM groups, respectively. Comparison between the DICOM-STL and US revealed good agreement, with an ICC of 0.82 (95% CI: 0.74 to 0.88) and a mean difference of -0.13 ± 0.50 mm (-1.13 to 0.86). Comparison between DICOM files alone versus US showed good agreement, with an ICC of 0.81 (95% CI: 0.73 to 0.89) and a mean difference of -0.23 ± 0.46 mm (-1.12 to 0.67). Comparison between DICOM-STL and DICOM files revealed excellent agreement, with an ICC of 0.94 (95% CI: 0.91 to 0.96) and a mean difference of 0.1 ± 0.29 mm (LOA -0.47 to 0.46). CONCLUSIONS: Quantification of peri-implant mucosal thickness via analysis of DICOM-STL files, DICOM files, or US assessment are comparably reliable and reproducible methods.


Assuntos
Implantes Dentários , Maxila , Humanos , Estudos Transversais , Reprodutibilidade dos Testes , Maxila/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico
14.
J Clin Periodontol ; 50 Suppl 25: 5-21, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37143289

RESUMO

AIM: Lack of consistently reported outcomes limits progress in evidence-based implant dentistry and quality of care. The objective of this initiative was to develop a core outcome set (COS) and measurements for implant dentistry clinical trials (ID-COSM). MATERIALS AND METHODS: This Core Outcome Measures in Effectiveness Trials (COMET)-registered international initiative comprised six steps over 24 months: (i) systematic reviews of outcomes reported in the last 10 years; (ii) international patient focus groups; (iii) a Delphi project with a broad range of stakeholders (care providers, clinical researchers, methodologists, patients and industry representatives); (iv) expert group discussions organizing the outcomes in domains using a theoretical framework and identifying the COSs; (v) identification of valid measurement systems to capture the different domains and (vi) final consensus and formal approval involving experts and patients. The methods were modified from the best practice approach following the Outcome Measures in Rheumatoid Arthritis Clinical Trial and COMET manuals. RESULTS: The systematic reviews and patient focus groups identified 754 (665 + 89, respectively) relevant outcome measures. After elimination of redundancies and duplicates, 111 were formally assessed in the Delphi project. By applying pre-specified filters, the Delphi process identified 22 essential outcomes. These were reduced to 13 after aggregating alternative assessments of the same features. The expert committee organized them into four core outcome areas: (i) pathophysiology, (ii) implant/prosthesis lifespan, (iii) life impact and (iv) access to care. In each area, core outcomes were identified to capture both the benefits and harms of therapy. Mandatory outcome domains included assessment of surgical morbidity and complications, peri-implant tissue health status, intervention-related adverse events, complication-free survival and overall patient satisfaction and comfort. Outcomes deemed mandatory in specific circumstances comprised function (mastication, speech, aesthetics and denture retention), quality of life, effort for treatment and maintenance and cost effectiveness. Specialized COSs were identified for bone and soft-tissue augmentation procedures. The validity of measurement instruments ranged from international consensus (peri-implant tissue health status) to early identification of important outcomes (patient-reported outcomes identified by the focus groups). CONCLUSIONS: The ID-COSM initiative reached a consensus on a core set of mandatory outcomes for clinical trials in implant dentistry and/or soft tissue/bone augmentation. Adoption in future protocols and reporting on the respective domain areas by currently ongoing trials will contribute to improving evidence-informed implant dentistry and quality of care.


Assuntos
Implantes Dentários , Projetos de Pesquisa , Humanos , Resultado do Tratamento , Consenso , Qualidade de Vida , Estética Dentária , Avaliação de Resultados em Cuidados de Saúde
15.
Clin Oral Implants Res ; 34 Suppl 25: 4-21, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37232121

RESUMO

AIM: Lack of consistently reported outcomes limits progress in evidence-based implant dentistry and quality of care. The objective of this initiative was to develop a core outcome set (COS) and measurements for implant dentistry clinical trials (ID-COSM). MATERIALS AND METHODS: This Core Outcome Measures in Effectiveness Trials (COMET)-registered international initiative comprised six steps over 24 months: (i) systematic reviews of outcomes reported in the last 10 years; (ii) international patient focus groups; (iii) a Delphi project with a broad range of stakeholders (care providers, clinical researchers, methodologists, patients and industry representatives); (iv) expert group discussions organizing the outcomes in domains using a theoretical framework and identifying the COSs; (v) identification of valid measurement systems to capture the different domains and (vi) final consensus and formal approval involving experts and patients. The methods were modified from the best practice approach following the Outcome Measures in Rheumatoid Arthritis Clinical Trial and COMET manuals. RESULTS: The systematic reviews and patient focus groups identified 754 (665 + 89, respectively) relevant outcome measures. After elimination of redundancies and duplicates, 111 were formally assessed in the Delphi project. By applying pre-specified filters, the Delphi process identified 22 essential outcomes. These were reduced to 13 after aggregating alternative assessments of the same features. The expert committee organized them into four core outcome areas: (i) pathophysiology, (ii) implant/prosthesis lifespan, (iii) life impact and (iv) access to care. In each area, core outcomes were identified to capture both the benefits and harms of therapy. Mandatory outcome domains included assessment of surgical morbidity and complications, peri-implant tissue health status, intervention-related adverse events, complication-free survival and overall patient satisfaction and comfort. Outcomes deemed mandatory in specific circumstances comprised function (mastication, speech, aesthetics and denture retention), quality of life, effort for treatment and maintenance and cost effectiveness. Specialized COSs were identified for bone and soft-tissue augmentation procedures. The validity of measurement instruments ranged from international consensus (peri-implant tissue health status) to early identification of important outcomes (patient-reported outcomes identified by the focus groups). CONCLUSIONS: The ID-COSM initiative reached a consensus on a core set of mandatory outcomes for clinical trials in implant dentistry and/or soft tissue/bone augmentation. Adoption in future protocols and reporting on the respective domain areas by currently ongoing trials will contribute to improving evidence-informed implant dentistry and quality of care.


Assuntos
Implantes Dentários , Projetos de Pesquisa , Humanos , Resultado do Tratamento , Consenso , Qualidade de Vida , Avaliação de Resultados em Cuidados de Saúde , Técnica Delfos
16.
Am J Transplant ; 23(9): 1345-1358, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37245642

RESUMO

Corneal transplantation is the most common form of solid tissue grafting, with an approximately 80% to 90% success rate. However, success rates may decline when donor tissues are derived from patients with a history of diabetes mellitus (DM). To evaluate the underlying immunopathologic processes that cause graft rejection, we used streptozotocin-induced type 1 DM (DM1) and transgenic Lepob/ob type 2 DM (DM2) diabetic murine models as donors and nondiabetic BALB/c as recipients. DM resulted in an increased frequency of corneal antigen-presenting cells (APCs) with an acquired immunostimulatory phenotype. Following transplantation, recipients that received either type of diabetic graft showed increased APC migration and T helper type 1 alloreactive cells, impaired functional regulatory T cells, and graft survival. Insulin treatment in streptozotocin-induced diabetic mice led to an increased tolerogenic profile of graft APC, lower T helper type 1 sensitization, and a higher frequency of functional regulatory T cells with high suppressive capacity, reflected in increased graft survival. We conclude that both DM1 and DM2 in donors can impact corneal APC functional phenotype, rendering the tissue more immunogenic and thereby increasing the risk of graft failure.


Assuntos
Transplante de Córnea , Diabetes Mellitus Experimental , Animais , Camundongos , Diabetes Mellitus Experimental/cirurgia , Diabetes Mellitus Experimental/patologia , Estreptozocina , Córnea , Células Apresentadoras de Antígenos
17.
Front Microbiol ; 14: 1092166, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37007481

RESUMO

Heme is best known for its role as a versatile prosthetic group in prokaryotic and eukaryotic proteins with diverse biological functions including gas and electron transport, as well as a wide array of redox chemistry. However, free heme and related tetrapyrroles also have important roles in the cell. In several bacterial strains, heme biosynthetic precursors and degradation products have been proposed to function as signaling molecules, ion chelators, antioxidants and photoprotectants. While the uptake and degradation of heme by bacterial pathogens is well studied, less is understood about the physiological role of these processes and their products in non-pathogenic bacteria. Streptomyces are slow growing soil bacteria known for their extraordinary capacity to produce complex secondary metabolites, particularly many clinically used antibiotics. Here we report the unambiguous identification of three tetrapyrrole metabolites from heme metabolism, coproporphyrin III, biliverdin and bilirubin, in culture extracts of the rufomycin antibiotic producing Streptomyces atratus DSM41673. We propose that biliverdin and bilirubin may combat oxidative stress induced by nitric oxide production during rufomycin biosynthesis, and indicate the genes involved in their production. This is, to our knowledge, the first report of the production of all three of these tetrapyrroles by a Streptomycete.

18.
ACS Catal ; 13(7): 4742-4751, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37066047

RESUMO

Methionine sulfoxide reductase A (MsrA) enzymes have recently found applications as nonoxidative biocatalysts in the enantioselective kinetic resolution of racemic sulfoxides. This work describes the identification of selective and robust MsrA biocatalysts able to catalyze the enantioselective reduction of a variety of aromatic and aliphatic chiral sulfoxides at 8-64 mM concentration with high yields and excellent ees (up to 99%). Moreover, with the aim to expand the substrate scope of MsrA biocatalysts, a library of mutant enzymes has been designed via rational mutagenesis utilizing in silico docking, molecular dynamics, and structural nuclear magnetic resonance (NMR) studies. The mutant enzyme MsrA33 was found to catalyze the kinetic resolution of bulky sulfoxide substrates bearing non-methyl substituents on the sulfur atom with ees up to 99%, overcoming a significant limitation of the currently available MsrA biocatalysts.

19.
FASEB J ; 37(4): e22855, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36906286

RESUMO

Chronic uveitis comprises heterogeneous clinical entities characterized by sustained and recurrent intraocular inflammation that is believed to be driven by autoimmune responses. The management of chronic uveitis is challenging with the limited availability of efficacious treatments, and the underlying mechanisms mediating disease chronicity remain poorly understood as the majority of experimental data are derived from the acute phase of the disease (the first 2-3 weeks post-induction). Herein, we investigated the key cellular mechanisms underlying chronic intraocular inflammation using our recently established murine model of chronic autoimmune uveitis. We demonstrate unique long-lived CD44hi IL-7R+ IL-15R+ CD4+ memory T cells in both retina and secondary lymphoid organs after 3 months postinduction of autoimmune uveitis. These memory T cells functionally exhibit antigen-specific proliferation and activation in response to retinal peptide stimulation in vitro. Critically, these effector-memory T cells are capable of effectively trafficking to the retina and accumulating in the local tissues secreting both IL-17 and IFN-γ upon adoptively transferred, leading to retinal structural and functional damage. Thus, our data reveal the critical uveitogenic functions of memory CD4+ T cells in sustaining chronic intraocular inflammation, suggesting that memory T cells can be a novel and promising therapeutic target for treating chronic uveitis in future translational studies.


Assuntos
Doenças Autoimunes , Doenças Retinianas , Uveíte , Camundongos , Humanos , Animais , Modelos Animais de Doenças , Linfócitos T CD4-Positivos , Inflamação
20.
J Periodontol ; 94(8): 944-955, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36797817

RESUMO

BACKGROUND: The purpose of this study was to determine the association between periodontal supracrestal soft tissue dimensions (PSSTDs) and other phenotypic features in non-molar maxillary teeth. MATERIALS AND METHODS: Adult subjects in need of comprehensive dental treatment were recruited. Periodontal phenotypic variables (i.e., facial and palatal gingival thickness [GT], alveolar bone thickness [BT], and PSSTDs, namely distance from the gingival margin to the bone crest defined as periodontal supracrestal tissue height [PSTH] and distance from the cementoenamel junction to the bone crest [CEJ-BC]) were recorded using cone-beam computed tomography scans. Standardized intraoral photographs were obtained to assess facial keratinized tissue width (KTW) and other anatomical parameters (i.e., tooth type, gingival architecture, and interproximal papilla height). RESULTS: The study sample was constituted of 87 participants that contributed with a total of 522 maxillary anterior teeth. Differences in mean values of PSSTDs, KTW, GT, and BT were observed between tooth types and sex. Males exhibited a thicker GT and BT, and taller PSTH and KTW compared to females. Shorter CEJ-BC was associated with shorter PSTH, wider KTW, and thicker GT and BT. Shorter PSTH was associated with thicker facial BT. Notably, BT and GT were positively correlated at both facial and palatal sites, meaning that the thicker the gingival phenotype, the thicker the bone morphotype. Facial BT and facial GT were positively correlated with KTW. A flat gingival architecture was associated with the thick periodontal phenotype. Square teeth had shorter CEJ-BC, wider KTW, and thicker GT. CONCLUSIONS: Periodontal phenotypic features vary across and within subjects, between facial and palatal sites at different apico-coronal levels, and as a function of sex and tooth type. The shorter the PSSTDs, the wider the KTW and the thicker the GT and BT. PSSTDs, particularly PSTH, should be considered an integral component of the periodontal phenotype.


Assuntos
Gengiva , Maxila , Masculino , Feminino , Animais , Estudos Transversais , Maxila/diagnóstico por imagem , Gengiva/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/métodos , Fenótipo
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