RESUMO
This study aimed to explore the role of the two-component system Bae SR in the mechanism of drug resistance in carbapenem-resistant A. baumannii (CRAB) using molecular docking and real-time polymerase chain reaction (PCR). The two-component system Bae SR of Acinetobacter baumannii was subjected to molecular docking with imipenem, meropenem, and levofloxacin. Antibacterial assays and fluorescence quantitative PCR were used to explore protein-ligand interactions and molecular biological resistance mechanisms related to CRAB. The analysis of the two-component system in A. baumannii revealed that imipenem exhibited the highest docking energy in Bae S at - 5.81 kcal/mol, while the docking energy for meropenem was - 4.92 kcal/mol. For Bae R, imipenem had a maximum docking energy of - 4.28 kcal/mol, compared with - 4.60 kcal/mol for meropenem. The highest binding energies for Bae S-levofloxacin and Bae R-levofloxacin were - 3.60 and - 3.65 kcal/mol, respectively. All imipenem-resistant strains had minimum inhibitory concentration (MIC) values of 16 µg/mL, whereas levofloxacin-resistant strains had MIC values of 8 µg/mL. The time-sterilization curve showed a significant decrease in bacterial colony numbers at 2 h under the action of 8 µg/mL imipenem, indicating antibacterial effects. In contrast, levofloxacin did not exhibit any antibacterial activity. Fluorescence quantitative PCR results revealed significantly increased relative expression levels of bae S and bae R genes in the CRAB group, which were 2 and 1.5 times higher than those in the CSAB group, respectively, with statistically significant differences. Molecular docking in this study found that the combination of Bae SR and carbapenem antibiotics (imipenem, meropenem) exhibited stronger affinity and stability compared with levofloxacin. Moreover, the overexpression of the two-component system genes in carbapenem-resistant A. baumannii enhanced its resistance to carbapenem, providing theoretical and practical insights into carbapenem resistance in respiratory tract infections caused by A. baumannii.
Assuntos
Acinetobacter baumannii , Carbapenêmicos , Carbapenêmicos/farmacologia , Meropeném/farmacologia , Simulação de Acoplamento Molecular , Reação em Cadeia da Polimerase em Tempo Real , Levofloxacino/farmacologia , Antibacterianos/farmacologia , Imipenem/farmacologia , Resistência a Medicamentos , Testes de Sensibilidade Microbiana , beta-Lactamases/genéticaRESUMO
Delayed wound healing remains a challenge, and macrophages play an important role in the inflammatory process of wound healing. Morphological changes in macrophages can affect their phenotype, but little is known about the underlying mechanism. Aligned electrospun nanofibers have natural advantages in modulating cell morphology. Therefore, the current study constructed aligned electrospun nanofibers that could transform macrophages into elongated shapes. Our results demonstrated that aligned nanofibers without exogenous cytokines could downregulate the proinflammatory M1 phenotype and upregulate the prohealing M2 phenotype in an inflammatory environment. Importantly, our study revealed that aligned electrospun nanofibers could inhibit macrophage M1 polarization via the JAK-STAT and NF-κB pathways. Furthermore, the conditioned medium from macrophages cultured on aligned nanofibers could encourage fibroblast migration, proliferation and collagen secretion. In vivo, aligned nanofibers alleviated the inflammatory microenvironment, promoted angiogenesis and accelerated wound healing in mouse skin defects by modulating macrophage phenotypes. Collectively, aligned electrospun nanofibers can influence macrophage polarization via the JAK-STAT and NF-κB pathways and attenuate the local inflammatory response in skin wounds. This study provides a potential strategy to modulate macrophage polarization and promote wound healing by controlling the topology of biomaterials and offers a new perspective for the application of nanotechnology in wound healing.
Assuntos
Nanofibras , Animais , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Poliésteres , CicatrizaçãoRESUMO
BACKGROUND: Emergent endotracheal intubation (ETI) is a serious complication after Oesophagectomy. It is still unclear that perioperative risk factors and prognosis of these patients with ETI. METHODS: Between January 2015 and December 2018, 21 patients who received ETI after esophagectomy were enrolled (ETI group) at the department of thoracic surgery, Fujian Union hospital, China. Each study subject matched one patient who underwent the same surgery in the current era were included (control group). Patient characteristics and perioperative factors were collected. RESULTS: Patients with ETI were older than those without ETI (p = 0.022). The patients with history of smoking in ETI group were significantly more than those in control group (p = 0.013). The stay-time of postanesthesia care unit (PACU) in ETI group was significantly longer than that in control group (p = 0.001). The incidence of anastomotic leak or electrolyte disorder in ETI group was also higher than that in control group (p = 0.014; p = 0.002). Logistic regression analysis indicated history of smoke (HR 6.43, 95%CI 1.39-29.76, p = 0.017) and longer stay time of PACU (HR 1.04, 95%CI 1.01-1.83, p = 0.020) both were independently associated with higher risks of ETI. The 3-year overall survival (OS) rates were 47.6% in patients with ETI and 85.7% in patients without ETI (HR 4.72, 95%CI 1.31-17.00, p = 0.018). COX regression analysis indicated ETI was an independent risk factor affecting the OS. CONCLUSION: The study indicated that history of smoking and longer stay-time in PACU both were independently associated with higher risks of ETI; and ETI was an independent risk factor affecting the OS of patients after esophagectomy. TRIAL REGISTRATION: This trial was retrospectively registered with the registration number of ChiCTR2000038549.
Assuntos
Esofagectomia , Intubação Intratraqueal , Humanos , Esofagectomia/efeitos adversos , Prognóstico , Fatores de Risco , Intubação Intratraqueal/efeitos adversos , China/epidemiologiaRESUMO
WHAT IS KNOWN AND OBJECTIVE: The 5-hydroxytryptamine type 3B receptor (HTR3B) is involved in postoperative vomiting. We aimed to investigate whether genomic variations of rs1176744 and rs1672717 in HTR3B are associated with postoperative vomiting (POV) in the Chinese Han female population after surgery. METHODS: Five hundred and sixty-eight female patients classified as ASA I-II undergoing breast surgery under standard general anaesthesia were enrolled in the study. Episodes of POV in the first 24 h after surgery were recorded. Targeted single nucleotide polymorphisms (SNPs) in the HTR3B gene were identified by genotyping using the SNPscanTM technique. Univariate and multivariate analyses were conducted to investigate the association between SNPs and POV. RESULTS: We eventually analysed 407 subjects undergoing breast surgery under general anaesthesia. Of these, 104(25.6%) patients suffered POV within 24 h after surgery. In the multivariate logistic regression analysis, we found that age≥50 years (p = 0.012) and longer duration of surgery (p = 0.019) were independent risk factors for POV. Simultaneously, in the dominant model of rs1672717, compared with the AA genotype, GG+GA carriers suffered more POV (OR=1.669, p = 0.038). However, the use of atropine reduced the incidence of POV in our study (p = 0.019). WHAT IS NEW AND CONCLUSION: Our investigation demonstrated that polymorphism of rs1672717 (HTR3B) may be a genetic risk factor for developing POV. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT03705026.
Assuntos
Povo Asiático , Neoplasias da Mama/cirurgia , Náusea e Vômito Pós-Operatórios/genética , Receptores 5-HT3 de Serotonina/genética , Adulto , Fatores Etários , China , Comorbidade , Feminino , Genótipo , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Náusea e Vômito Pós-Operatórios/etnologia , Fatores de Risco , Fatores SocioeconômicosRESUMO
OBJECTIVES: This study aimed to investigate the therapeutic effect of different doses of teriparatide (TPTD) on bisphosphonate-related osteonecrosis of the jaw (BRONJ). MATERIALS AND METHODS: To establish the BRONJ model, 20 mice were randomly divided into two groups: a group that received tail vein administration of zoledronic acid with dexamethasone (ZA-125 µg/kg, DEX 5 mg/kg) and a group that received saline weekly. The mice subsequently underwent bilateral maxillary first molar extraction. After 8 weeks of modelling administration, the maxilla samples were examined by micro-computed tomography and histological staining (haematoxylin and eosin, Masson's trichrome and tartrate-resistant acid phosphatase) and the cytokine level was measured (enzyme-linked immunosorbent assay and Western blot). To determine the role of TPTD in BRONJ, the same protocol as previously described was applied in 100 mice (80 received ZA + DEX, and 20 received saline). After 8 weeks of modelling administration, 80 ZA + DEX mice were randomly divided into four groups: three groups with subcutaneous administration of TPTD (i.e. T1-3, T2-10 and T3-30 µg kg-1 day-1 ) and one group with saline daily for the next 8 weeks. The other 20 saline mice continued to receive saline daily. RESULTS: In Part 1, the level of receptor activator of nuclear factor-kappa Β ligand and the numbers of osteoclasts differed between the model and control groups. In Part 2, we found that TPTD had a positive effect on BRONJ in a mouse model based on clinical and histomorphological observations. Among the three treatment groups, the T1 and T2 groups significantly differed from the model group, whereas the T3 group showed no statistical differences. CONCLUSION: Subcutaneous administration of TPTD has a beneficial effect on BRONJ in mice. Nevertheless, further studies are needed to determine whether the therapeutic effect on BRONJ is dose-dependent.
Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Maxila/patologia , Teriparatida/administração & dosagem , Animais , Maxila/efeitos dos fármacos , Camundongos , Distribuição Aleatória , Microtomografia por Raio-XRESUMO
BACKGROUND: The prognosis of hospitalized patients after emergent endotracheal intubation (ETI) remains poor. Our aim was to evaluate the 30-d hospitalization mortality of subjects undergoing ETI during daytime or off-hours and to analyze the possible risk factors affecting mortality. METHODS: A single-center retrospective study was performed at a university teaching facility from January 2015 to December 2018. All adult inpatients who received ETI in the general ward were included. Information on patient demographics, vital signs, ICU (Intensive care unit) admission, intubation time (daytime or off-hours), the department in which ETI was performed (surgical ward or medical ward), intubation reasons, and 30-d hospitalization mortality after ETI were obtained from a database. RESULTS: Over a four-year period, 558 subjects were analyzed. There were more male than female in both groups (115 [70.1%] vs 275 [69.8%]; P = 0.939). A total of 394 (70.6%) patients received ETI during off-hours. The patients who received ETI during the daytime were older than those who received ETI during off-hours (64.95 ± 17.54 vs 61.55 ± 17.49; P = 0.037). The BMI of patients who received ETI during the daytime was also higher than that of patients who received ETI during off-hours (23.08 ± 3.38 vs 21.97 ± 3.25; P < 0.001). The 30-d mortality after ETI was 66.8% (373), which included 68.0% (268) during off-hours and 64.0% (105) during the daytime (P = 0.361). Multivariate Cox regression analysis found that the significant factors for the risk of death within 30 days included ICU admission (HR 0.312, 0.176-0.554) and the department in which ETI was performed (HR 0.401, 0.247-0.653). CONCLUSIONS: The 30-d hospitalization mortality after ETI was 66.8%, and off-hours presentation was not significantly associated with mortality. ICU admission and ETI performed in the surgical ward were significant factors for decreasing the risk of death within 30 days. TRIAL REGISTRATION: This trial was retrospectively registered with the registration number of ChiCTR2000038549 .
Assuntos
Plantão Médico , Serviços Médicos de Emergência , Mortalidade Hospitalar , Intubação Intratraqueal/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Accumulating clinical and preclinical evidence indicates that chronic pain is often comorbid with persistent low mood and anxiety. However, the mechanisms underlying pain-induced anxiety, such as its causality, temporal progression, and relevant neural networks are poorly understood, impeding the development of efficacious therapeutic approaches. RESULTS: Here, we have identified the sequential emergence of anxiety phenotypes in mice subjected to dental pulp injury (DPI), a prototypical model of orofacial pain that correlates with human toothache. Compared with sham controls, mice subjected to DPI by mechanically exposing the pulp to the oral environment exhibited significant signs of anxiogenic effects, specifically, altered behaviors on the elevated plus maze (EPM), novelty-suppressed feeding (NSF) tests at 1 but not 3 days after the surgery. Notably, at 7 and 14 days, the DPI mice again avoided the open arm, center area, and novelty environment in the EPM, open field, and NSF tests, respectively. In particular, DPI-induced social phobia and increased repetitive grooming did not occur until 14 days after surgery, suggesting that DPI-induced social anxiety requires a long time. Moreover, oral administration of an anti-inflammatory drug, ibuprofen, or an analgesic agent, ProTx-II, which is a selective inhibitor of NaV1.7 sodium channels, both significantly alleviated DPI-induced avoidance in mice. Finally, to investigate the underlying central mechanisms, we pharmacologically blocked a popular form of synaptic plasticity with a GluA2-derived peptide, long-term depression, as that treatment significantly prevented the development of anxiety phenotype upon DPI. CONCLUSIONS: Together, these results suggest a temporally progressive causal relationship between orofacial pain and anxiety, calling for more in-depth mechanistic studies on concomitant pain and anxiety disorders.
Assuntos
Ansiedade/patologia , Polpa Dentária/lesões , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Comportamento Animal , Polpa Dentária/efeitos dos fármacos , Polpa Dentária/fisiopatologia , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Humanos , Ibuprofeno/administração & dosagem , Ibuprofeno/farmacologia , Ibuprofeno/uso terapêutico , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Modelos Neurológicos , Nociceptividade/efeitos dos fármacos , Medição da Dor , Fenótipo , Comportamento Social , Venenos de Aranha/administração & dosagem , Venenos de Aranha/farmacologia , Venenos de Aranha/uso terapêutico , Fatores de TempoRESUMO
BACKGROUND: We aimed to compare the effects of bisphosphonate on the remodeling of irregular bones (the jaw and ilium) in mice after trauma. METHODS: To verify the feasibility of modeling osteonecrosis, 20 mice were injected intraperitoneally with zoledronate and dexamethasone (ZOL&DEX group), dexamethasone (DEX group), or phosphate-buffered saline (PBS) [control (CTR) group]. Mice then underwent extraction of the right maxillary first molar and creation of an artificial bony cavity in the ilium. Bone sections were stained with H&E for morphological studies. To further compare differences between the maxilla and the ilium caused by similar traumas, 80 mice were injected intraperitoneally with ZOL&DEX or PBS. Pathological progression at the injury sites was assessed at 1 day and at 1, 3, and 8 weeks after trauma using micro-computed tomography (CT), H&E and immunohistochemistry analyses, high-performance liquid chromatography-mass spectrometry, and enzyme-linked immunosorbent assay. RESULTS: Only the ZOL&DEX model group effectively developed osteonecrosis. Bony sequestra, osseous sclerosis, unhealed mucosa, and radiopaque alveolar bone were found in the maxilla. In the ilium, there was a lower frequency of osteonecrotic disease and osseous sclerosis, and less suppression of bone remodeling than in the maxilla following long-term bisphosphonate administration. Zoledronate levels were higher in the maxilla. ZOL&DEX treatment suppressed the levels of RANKL and IL-17, but induced an upregulation of osteoprotegerin and FAM20C in both bones. CONCLUSION: Accumulation of bisphosphonate may increase the incidence of osteonecrosis. The RANKL/OPG pathway and IL-17 and FAM20C cytokines play key roles in the progression of pathologically abnormal bone remodeling.
Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Dexametasona/farmacologia , Difosfonatos/farmacologia , Imidazóis/farmacologia , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Proteínas da Matriz Extracelular/metabolismo , Feminino , Ílio/efeitos dos fármacos , Ílio/patologia , Imuno-Histoquímica , Interleucina-17/metabolismo , Arcada Osseodentária/efeitos dos fármacos , Arcada Osseodentária/patologia , Maxila/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Ligante RANK/metabolismo , Ácido ZoledrônicoRESUMO
To investigate the effects of long intergenic noncoding RNA-erythroid prosurvival (lincRNA-EPS) on periodontal inflammation mediated by inflammasomes and to explore its mechanism. Experimental periodontitis was induced in KO (lincRNA-EPS-/- ) and WT (lincRNA-EPS+/+ ) mice to compare the periodontal bone loss and inflammation by using micro-computed tomography, immunofluorescence staining and haematoxylin and eosin staining. The expression and activation of cysteinyl aspartate-specific proteinase-11 (caspase-11) and NOD-like receptor protein 3 (NLRP3) inflammasomes, as well as nuclear factor-kappa B (NF-κB) activation in mouse gingival fibroblasts (MGFs), were measured by real-time quantitative polymerase chain reaction, Western blotting, enzyme-linked immunosorbent and lactate dehydrogenase assays. MGFs were transfected with overexpression plasmids to assess the biological functions of lincRNA-EPS. RNA pull-down and immunoprecipitation experiments were performed to identify the interacting protein of lincRNA-EPS. LincRNA-EPS-expressing lentivirus was locally administered to inflamed periodontal tissues to evaluate its salvage function in periodontitis. The absence of lincRNA-EPS increased bone loss and expression of myeloperoxidase, interleukin-1α (IL-1α) and IL-1ß in the inflammatory periodontium. LincRNA-EPS KO MGFs exhibited increased expression and activation of caspase-11/NLRP3 inflammasome components than WT MGFs under lipopolysaccharide (LPS) stimulation. The expression and activation of these molecules were inhibited in lincRNA-EPS overexpressed MGFs. Mechanistically, lincRNA-EPS directly bound to transactive response DNA-binding protein 43 (TDP43) in the nucleus of MGFs, and TDP43 knockdown exerted a similar inhibitory effect on NF-κB activation and the inflammasomes as lincRNA-EPS overexpression. Locally injecting lincRNA-EPS-expressing lentivirus weakened the periodontal damage. LincRNA-EPS inhibits the LPS-induced production and activation of caspase-11 and NLRP3 inflammasomes by suppressing the activation of the NF-κB signalling pathway via interacting with TDP43, thereby alleviating periodontitis.
Assuntos
Periodontite , RNA Longo não Codificante , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , NF-kappa B/metabolismo , Proteínas NLR , Caspases , Lipopolissacarídeos/farmacologia , Microtomografia por Raio-X , Inflamação/metabolismo , Fibroblastos/metabolismo , Periodontite/genética , Interleucina-1beta/metabolismoRESUMO
PURPOSE: The use of postoperative radiotherapy (PORT) in patients with oral squamous cell carcinoma (OCSCC) lacks clear boundaries due to the non-negligible toxicity accompanying its remarkable cancer-killing effect. This study aims at validating the ability of deep learning models to develop individualized PORT recommendations for patients with OCSCC and quantifying the impact of patient characteristics on treatment selection. METHODS: Participants were categorized into two groups based on alignment between model-recommended and actual treatment regimens, with their overall survival compared. Inverse probability treatment weighting was used to reduce bias, and a mixed-effects multivariate linear regression illustrated how baseline characteristics influenced PORT selection. RESULTS: 4990 patients with OCSCC met the inclusion criteria. Deep Survival regression with Mixture Effects (DSME) demonstrated the best performance among all the models and National Comprehensive Cancer Network guidelines. The efficacy of PORT is enhanced as the lymph node ratio (LNR) increases. Similar enhancements in efficacy are observed in patients with advanced age, large tumors, multiple positive lymph nodes, tongue involvement, and stage IVA. Early-stage (stage 0-II) OCSCC may safely omit PORT. CONCLUSIONS: This is the first study to incorporate LNR as a tumor character to make personalized recommendations for patients. DSME can effectively identify potential beneficiaries of PORT and provide quantifiable survival benefits.
RESUMO
The primary pathology of periodontitis involves the gradual deterioration of periodontal tissues resulting from the inflammatory reaction triggered by bacterial infection. In this study, a novel drug for periodontal pocket injection, known as the Shed-Cu-HA hydrogel, was developed by incorporating copper ions (Cu2+) and Shed-derived exosomes (Shed-exo) inside the hyaluronic acid (HA) hydrogel. Suitable concentrations of Cu2+ and Shed-exo released from Shed-Cu-HA enhanced cell viability and cell proliferation of human periodontal ligament stem cells. Additionally, the Shed-Cu-HA demonstrated remarkable antibacterial effects against the key periodontal pathogen (Aa) owing to the synergistic effect of Cu2+ and HA. Furthermore, the material effectively suppressed macrophage inflammatory response via the IL-6/JAK2/STAT3 pathway. Moreover, the Shed-Cu-HA, combining the inflammation-regulating properties of HA with the synergistic osteogenic activity of Shed-exo and Cu2+, effectively upregulated the expression of genes and proteins associated with osteogenic differentiation. The experimental findings from a mouse periodontitis model demonstrated that the administration of Shed-Cu-HA effectively reduced the extent of inflammatory cell infiltration and bacterial infections in gingival tissues and facilitated the regeneration of periodontal bone tissues and collagen after 2 and 4 weeks of injection. Consequently, it holds significant prospects for future applications in periodontitis treatment.
Assuntos
Antibacterianos , Regeneração Óssea , Cobre , Exossomos , Ácido Hialurônico , Hidrogéis , Osteogênese , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Animais , Osteogênese/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Humanos , Camundongos , Cobre/química , Cobre/farmacologia , Regeneração Óssea/efeitos dos fármacos , Exossomos/metabolismo , Exossomos/química , Ligamento Periodontal/efeitos dos fármacos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Periodontite/tratamento farmacológico , Periodontite/patologia , Periodontite/microbiologia , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacosRESUMO
Periodontitis is a chronic inflammatory disease that can result in the irreversible loss of tooth-supporting tissues and elevate the likelihood and intensity of systemic diseases. The presence of reactive oxygen species (ROS) and associated related oxidative stress is intricately linked to the progression and severity of periodontal inflammation. Targeted removal of local ROS may serve to attenuate inflammation, improve the unfavorable periodontal microenvironment and potentially reverse ensuing pathological cascades. These ROS scavenging nanoparticles, which possess additional characteristics such as anti-inflammation and osteogenic differentiation, are highly sought after for the treatment of periodontitis. In this study, negative charged human serum albumin-crosslinked manganese-doped self-assembling Prussian blue nanoparticles (HSA-MDSPB NPs) were fabricated. These nanoparticles demonstrate the ability to scavenge multiple ROS including superoxide anion, free hydroxyl radicals, singlet oxygen and hydrogen peroxide. Additionally, HSA-MDSPB NPs exhibit the capacity to alleviate inflammation in gingiva and alveolar bone both in vitro and in vivo. Furthermore, HSA-MDSPB NPs have been shown to play a role in promoting the polarization of macrophages from the M1 to M2 phenotype, resulting in reduced production of pro-inflammatory cytokines. More attractively, HSA-MDSPB NPs have been demonstrated to enhance cellular osteogenic differentiation. These properties of HSA-MDSPB NPs contribute to decreased inflammation, extracellular matrix degradation and bone loss in periodontal tissue. In conclusion, the multifunctional nature of HSA-MDSPB NPs provides a promising therapeutic approach for the treatment of periodontitis.
RESUMO
We explored gum irritation and cytotoxicity caused by nickel-chromium (Ni-Cr) alloy porcelain by interleukin-8 (IL-8), interleukin-6 (IL-6) and gingival crevicular fluid (GCF) volumes at different time points peri-crown restoration. This prospective study was conducted in 60 young adults. The total amount and concentrations of IL-8 and IL-6 per site, GCF volumes, and blood neutrophil counts were performed prior to and at 1 week, 3 months, and 6 months after Ni-Cr alloy-porcelain crown restoration. Thirty male and 30 female subjects, aged 20-35 years old were enrolled. The total amount and concentrations of IL-8 and IL-6 per site, GCF volumes increased after nickel-chromium (Ni-Cr) alloy-porcelain crown restoration, and reached its peak at the third month as the GCF volume increased by 52.20 %, the total amount and concentrations of IL-8 increased by 112.11 and 22.75 %; the total amount and concentrations of IL-6 increased by 77.66 and 17.17 % when compared to baseline. In particular, the increase of IL-8 concentration was found in female patients at 3 months after restoration; while the neutrophil count of the peripheral blood did not change significantly. The increase in the total amount and the concentrations of IL-8 and IL-6 and GCF volume may be related to the cytotoxicity induced by Ni-Cr alloy. The significant increase of IL-8 concentration in females indicates that more attention should be given to women during Ni-Cr alloy porcelain crown restoration.
Assuntos
Ligas de Cromo , Coroas , Reparação de Restauração Dentária , Líquido do Sulco Gengival/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Ligas Metalo-Cerâmicas , Adulto , Ligas de Cromo/efeitos adversos , Ligas de Cromo/química , Ligas de Cromo/farmacologia , Reparação de Restauração Dentária/métodos , Feminino , Líquido do Sulco Gengival/química , Líquido do Sulco Gengival/efeitos dos fármacos , Humanos , Interleucina-6/análise , Interleucina-8/análise , Contagem de Leucócitos , Masculino , Ligas Metalo-Cerâmicas/efeitos adversos , Ligas Metalo-Cerâmicas/química , Ligas Metalo-Cerâmicas/farmacologia , Neutrófilos/citologia , Neutrófilos/metabolismo , Fatores de Tempo , Adulto JovemRESUMO
We used forebrain-specific conditional presenilin 1 (PS1) and presenilin 2 (PS2) double knockout mice (dKO mice) that exhibit symptoms of neurodegenerative diseases, especially Alzheimer's disease, to investigate whether ibuprofen can rescue brain and periodontal tissue abnormalities by attenuating the inflammatory response. Mandibles were dissected for alveolar bone-height analysis. Maxillae were fixed and decalcified for histological observation and osteoclast detection. ELISA measurements from the hippocampus, cortex, and gingiva of the mandibular incisor teeth were used to assay inflammatory mediators. We confirmed periodontal tissue abnormalities and inflammatory responses in brain and periodontal tissues in naive nine- and 12-month-old dKO mice. The other two groups of age-matched dKO mice that received 375-ppm ibuprofen treatment for six consecutive months exhibited significantly attenuated damage in periodontal tissues and reduction in several inflammation-related factors in brain and periodontal tissues. Our findings showed that the anti-inflammatory drug ibuprofen significantly decreased inflammation through the cyclooxygenase (COX) pathway in brain and periodontal tissues in dKO mice, and then attenuated abnormalities in periodontal tissues. This suggests that ibuprofen could be an ideal drug for preventing both nervous system and periodontal tissue damage caused by inflammatory responses.
Assuntos
Ibuprofeno/uso terapêutico , Doenças Periodontais/tratamento farmacológico , Doenças Periodontais/metabolismo , Periodonto/metabolismo , Presenilina-1/deficiência , Presenilina-2/deficiência , Animais , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Camundongos , Camundongos Knockout , Presenilina-1/genética , Presenilina-2/genéticaRESUMO
The aim of this study was to investigate the feasibility and advantages of the dual delivery of bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF) from nano-composite scaffolds (PLGA/PCL/nHA) loaded with vascular stents (PLCL/Col/nHA) for large bone defect regeneration in rabbit mandibles. Thirty-six large bone defects were repaired in rabbits using engineering bone composed of allogeneic bone marrow mesenchymal stem cells (BMSCs), bFGF, BMP-2 and scaffolds composed of PLGA/PCL/nHA loaded with PLCL/Col/nHA. The experiments were divided into six groups: BMSCs/bFGF/BMP-2/scaffold, BMSCs/BMP-2/scaffold, BMSCs/bFGF/scaffold, BMSCs/scaffold, scaffold alone and no treatment. Sodium alginate hydrogel was used as the carrier for BMP-2 and bFGF and its features, including gelling, degradation and controlled release properties, was detected by the determination of gelation and degradation time coupled with a controlled release study of bovine serum albumin (BSA). AlamarBlue assay and alkaline phosphatase (ALP) activity were used to evaluate the proliferation and osteogenic differentiation of BMSCs in different groups. X-ray and histological examinations of the samples were performed after 4 and 12 weeks post-implantation to clarify new bone formation in the mandible defects. The results verified that the use of sodium alginate hydrogel as a controlled release carrier has good sustained release ability, and the combined application of bFGF and BMP-2 could significantly promote the proliferation and osteogenic differentiation of BMSCs (p < 0.05 or p < 0.01). In addition, X-ray and histological examinations of the samples exhibited that the dual release group had significantly higher bone formation than the other groups. The above results indicate that the delivery of both growth factors could enhance new bone formation and vascularization compared with delivery of BMP-2 or bFGF alone, and may supply a promising way of repairing large bone defects in bone tissue engineering.
Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Regeneração Óssea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Fator 2 de Crescimento de Fibroblastos/farmacologia , Mandíbula/patologia , Nanocompostos/química , Stents , Alicerces Teciduais/química , Alginatos/farmacologia , Fosfatase Alcalina/metabolismo , Animais , Materiais Biocompatíveis/farmacologia , Prótese Vascular , Densidade Óssea/efeitos dos fármacos , Bovinos , Proliferação de Células/efeitos dos fármacos , Ácido Glucurônico/farmacologia , Ácidos Hexurônicos/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Implantes Experimentais , Mandíbula/diagnóstico por imagem , Mandíbula/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Coelhos , Radiografia , Soroalbumina Bovina/metabolismoRESUMO
Background: This study was to explore the effect of different doses of rocuronium bromide on neuromonitoring during Da Vinci robot thyroid surgery. Methods: This was a prospective, randomized, double-blind, controlled trial that included 189 patients who underwent Da Vinci robot thyroidectomy with intraoperative neuromonitoring(IONM). Patients were randomly divided into three groups and given three different doses of rocuronium (0.3mg/kg, 0.6mg/kg, 0.9mg/kg). Outcome measurements included IONM evoked potential, postoperative Voice Handicap Index-30(VHI-30), intraoperative body movement incidence rate, Cooper score, and hemodynamic changes during anesthesia induction.Results: The difference in IONM evoked potentials at various time points between the three groups was not statistically significant (P>0.05). The difference in Cooper scores and intraoperative body movement incidence rate between 0.6 and 0.9mg/kg groups was statistically significant compared with the 0.3mg/kg group (both P<0.001). There was no statistically significant difference in VHI-30 score and hemodynamic changes during anesthesia induction among the three groups (both P>0.05). Conclusions: For patients undergoing Da Vinci robot thyroidectomy, a single dose of rocuronium at 0.6 and 0.9mg/kg during anesthesia induction can provide stable IONM evoked potential. Additionally, compared to 0.3 mg/kg, it can offer better tracheal intubation conditions and lower incidence of body movements during surgery. It is worth noting that the use of higher doses of rocuronium should be adjusted based on the duration of IONM and local practices.
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Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Glândula Tireoide/cirurgia , Rocurônio , Estudos ProspectivosRESUMO
Two major issues are currently hindering the clinical practice of titanium dental implants for the lack of biological activities: immediate/early loading risks and peri-implantitis. To solve these issues, it is urgent to develop multifunctional implants modified with effective osteogenic and antibacterial properties. Zinc oxide nanoparticles (ZnO NPs) possess superior antibacterial activity; however, they can rapidly release Zn2+, causing cytotoxicity. In this study, a potential dental implant modification was creatively developed as ZnO nanoparticle-loaded mesoporous TiO2 coatings (nZnO/MTC-Ti) via the evaporation-induced self-assembly method (EISA) and one-step spin coating. The mesoporous TiO2 coatings (MTCs) regulated the synthesis and loading of ZnO NPs inside the nanosized pores. The synergistic effects of MTC and ZnO NPs on nZnO/MTC-Ti not only controlled the long-term steady-state release of Zn2+ but also optimized the charge distribution on the surface. Therefore, the cytotoxicity of ZnO NPs was resolved without triggering excessive reactive oxygen species (ROS). The increased extracellular Zn2+ further promoted a favorable intracellular zinc ion microenvironment through the modulation of zinc transporters (ZIP1 and ZnT1). Owing to that, the adhesion, proliferation, and osteogenic activity of bone mesenchymal stem cells (BMSCs) were improved. Additionally, nZnO/MTC-Ti inhibited the proliferation of oral pathogens (Pg and Aa) by inducing bacterial ROS production. For in vivo experiments, different implants were implanted into the alveolar fossa of Sprague-Dawley rats immediately after tooth extraction. The nZnO/MTC-Ti implants were found to possess a higher capability for enhancing bone regeneration, antibiosis, and osseointegration in vivo. These findings suggested the outstanding performance of nZnO/MTC-Ti implants in accelerating osseointegration and inhibiting bacterial infection, indicating a huge potential for solving immediate/early loading risks and peri-implantitis of dental implants.
Assuntos
Implantes Dentários , Peri-Implantite , Óxido de Zinco , Ratos , Animais , Óxido de Zinco/farmacologia , Titânio/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Ratos Sprague-Dawley , Osteogênese , Zinco/farmacologia , Antibacterianos/farmacologia , Propriedades de Superfície , Materiais Revestidos Biocompatíveis/farmacologiaRESUMO
In this study, vascular stents were fabricated from poly (lactide-É-caprolactone)/collagen/nano-hydroxyapatite (PLCL/Col/nHA) by electrospinning, and the surface morphology and breaking strength were observed or measured through scanning electron microscopy and tensile tests. The anti-clotting properties of stents were evaluated for anticoagulation surfaces modified by the electrostatic layer-by-layer self-assembly technique. In addition, nano-composite scaffolds of poly (lactic-co-glycolic acid)/polycaprolactone/nano-hydroxyapatite (PLGA/PCL/nHA) loaded with the vascular stents were prepared by thermoforming-particle leaching and their basic performance and osteogenesis were tested in vitro and in vivo. The results show that the PLCL/Col/nHA stents and PLGA/PCL/nHA nano-composite scaffolds had good surface structures, mechanical properties, biocompatibility and could guide bone regeneration. These may provide a new way to build vascularized-tissue engineered bone to repair large bone defects in bone tissue engineering.
Assuntos
Nanocompostos/química , Stents , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis , Prótese Vascular , Células da Medula Óssea/citologia , Regeneração Óssea , Células Cultivadas , Células-Tronco Mesenquimais/citologia , Microscopia Eletrônica de Varredura , Nanocompostos/ultraestrutura , Coelhos , Engenharia TecidualRESUMO
PURPOSE: To evaluate the teaching effect of making custom trays via CAD in dental postgraduates. METHODS: Twenty-seven dental postgraduates from first to third grade at the School and Hospital of Stomatology, Tongji University, Shanghai were given an informed consent to explain and request participation in the study. First, a lecture about the theory and process of fabricating custom tray via traditional hand-made method and CAD technique was given, then the students fabricated custom trays via the two methods and completed an online survey. The working time, margin extension and students' preference were analyzed with SPSS 22.0 software package. RESULTS: The working time was shorter, the margin extension was superior, and students' preference was higher via CAD than traditional method, the difference was significant(Pï¼0.05). CONCLUSIONS: CAD is more conducive to enhance students' understanding of custom tray manufacturing process and relevant theoretical knowledge. It is recommended to integrate digital technology into dental curriculum.
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Desenho Assistido por Computador , Técnica de Moldagem Odontológica , China , Humanos , EstudantesRESUMO
INTRODUCTION: For adults with small radial arteries, ultrasound-guided radial artery cannulation remains challenging and the relevant data is currently lacking. The study aimed to test the hypothesis that modified long-axis in-plane ultrasound guidance (M-LAIP) would improve success rates of radial artery cannulation in this population. PATIENTS AND METHODS: This was a prospective, randomised, and controlled clinical study that enrolled 201 adult patients with diameters of the radial artery less than 2.2 mm. Patients were randomised to M-LAIP, short-axis out-of-plane (SAOP), or conventional palpation (C-P) group according to different approaches of radial artery cannulation (M-LAIP, SAOP, and C-P). Outcome measurements included the success rate, cannulation time, and cannulation-related adverse events. RESULTS: The cannulation success rate was significantly higher in the M-LAIP group than in the SAOP or C-P groups (first success rate: 80.3% vs. 53.8% or 33.8%; P < 0.001; total success rate: 93.9% vs. 78.5% or 50.8%; P < 0.001). Total cannulation time in the M-LAIP group was shorter than that in the SAOP group (P = 0.002) or the C-P group (P < 0.001). The rates of posterior wall puncture and haematoma in the M-LAIP group were lower than that in the SAOP group or C-P group (P < 0.008). CONCLUSION: The use of the M-LAIP approach significantly improved the success rate of radial artery cannulation, shortened procedure time, and lowered the rates of posterior wall puncture and haematoma in adults with radial artery diameters less than 2.2 mm, compared with that achieved by the SAOP or C-P approach.