RESUMO
Periodontopathic bacteria constantly stimulate the host, which causes an immune response, leading to host-induced periodontal tissue damage. The complex interaction and imbalance between Th17 and Treg cells may be critical in the pathogenesis of periodontitis. Furthermore, the RANKL/RANK/OPG system plays a significant role in periodontitis bone metabolism, and its relationship with the Th17/Treg cell imbalance may be a bridge between periodontal bone metabolism and the immune system. This article reviews the literature related to the Th17/Treg cell imbalance mediated by pathogenic periodontal microbes, and its mechanism involving RANKL/RANK/OPG in periodontitis bone metabolism, in an effort to provide new ideas for the study of the immunopathological mechanism of periodontitis.
Assuntos
Perda do Osso Alveolar , Periodontite , Humanos , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Linfócitos T Reguladores , Células Th17/metabolismoRESUMO
Dysfunction of pancreatic ß cell insulin secretion is related to the pathogenesis of type 2 diabetes (T2D). Rab proteins have been shown to be key players in insulin secretion by pancreatic ß cells, and phogrin is a marker for the processes of exocytosis and insulin secretion. The purposes of this study were to clarify the regulatory role of Rab35 in insulin secretion and analyse the Rab35/phogrin interaction mechanism in ß-TC-6 cells. We studied the effects of Rab35 gene overexpression and interference on insulin secretion and phogrin expression and levels in ß-TC-6 cells. The Rab35/phogrin interaction was verified by GST pulldown, co-IP and co-localisation experiments. Here, we report that Rab35 is mainly distributed in the ß-TC-6-cell plasma membrane and cytoplasm. Rab35 overexpression promotes insulin secretion and decreases phogrin expression in ß-TC-6 cells, whereas its silencing significantly inhibits insulin secretion, promotes phogrin expression (p < 0.05) and causes phogrin redistribution. Furthermore, Rab35 silencing suppresses exocytosis of insulin. Rab35 interacts with phogrin, and both proteins co-localise in the plasma membranes and cytoplasm of ß-TC-6 cells. Our study presents novel evidence that Rab35 regulates insulin secretion by inhibiting phogrin expression and causing intracellular phogrin redistribution in pancreatic ß cells.
Assuntos
Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/fisiologia , Proteínas rab de Ligação ao GTP/fisiologia , Células HEK293 , Humanos , Células Secretoras de Insulina/fisiologia , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/metabolismo , Proteínas rab de Ligação ao GTP/metabolismoRESUMO
INTRODUCTION: This study was aimed to assess irisin levels in obesity (OB) and T2DM individuals and investigate the dynamic changes of irisin, bone mineral density (BMD), bone mineral content, and body composition in 19 OB patients after laparoscopic bariatric procedures, and also to evaluate the correlation of irisin, with BMD and body composition. METHODS: Forty-five OB, 20 T2DM, and 20 healthy adults had been recruited. Levels of irisin were measured in all subjects. Metabolic characteristics were obtained from OB and T2DM patients. Nineteen patients were randomly assigned to be received Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) procedure and to be completed 6-month follow-up. Irisin, BMD, bone mineral content, and body composition were measured at each visit. RESULTS: Significantly higher circulating irisin levels were measured in the OB group compared with T2DM and control groups. FINS, C-P, HOMA-IR, FBCI, HBCI, ALT, AST, and UA levels of OB were significantly higher than those of T2DM patients. While FBG and HbA1c of the OB were significantly lower than T2DM group. There were significant differences among circulating irisin, BMD, and body composition after laparoscopic bariatric surgery. Levels of irisin were decreased after operations including both LRYGB and LSG surgery compared with preoperation. At each time point (1, 3, and 6 months) of postoperation, there was no significant difference in percentage of total weight loss between LSG and LRYGB group. The positive correlation of irisin levels with total BMD, muscle, and fat masses were found during 6-month follow-up after surgery. CONCLUSIONS: The levels of irisin were higher in OB patients. There were positive correlations of irisin levels with total BMD, muscle, and fat masses during 6-month follow-up after surgery. Irisin may be involved in the occurrence and development of obese and it is related to BMD and body composition. Both LRYGB and LSG operations could decrease the circulating levels of irisin.
Assuntos
Cirurgia Bariátrica , Composição Corporal , Densidade Óssea , Calcificação Fisiológica , Fibronectinas/sangue , Laparoscopia , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Adulto , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Obesidade Mórbida/sangue , Obesidade Mórbida/complicaçõesRESUMO
OBJECTIVE: To investigate the relationship between baseline snoring sound energy (SSE) and disease severity, changes in SSE after adenotonsillectomy, and the predictors of surgical success in children with obstructive sleep apnoea (OSA). DESIGN: Prospective cohort study. SETTING: Tertiary referral medical centre. PARTICIPANTS: Thirty-two children with OSA whose apnoea-hypopnoea index ≥5 or apnoea-hypopnoea index ≥1.5 with OSA comorbidities were recruited. Patients with complicated OSA were excluded. All participants underwent snoring sound analysis, polysomnography, and adenotonsillectomy. MAIN OUTCOME MEASURES: Snoring sound energy and apnoea-hypopnoea index were assessed at baseline and 6 months after adenotonsillectomy. Surgical success was defined as a postoperative apnoea-hypopnoea index <1.5. RESULTS: The median age, body mass index, and apnoea-hypopnoea index was 9 years, 19.0 kg/m2 , and 13.2 events/h, respectively. Multivariate logistic regression showed that a baseline tonsil size of IV (odds ratio 15.7 [95% CI: 1.5-166.3]) and SSE of 801-1000 Hz > 21.9 dB (odds ratio 32.3 [95% CI: 2.6-396.6]) were significantly related to severe OSA. Following adenotonsillectomy, apnoea-hypopnoea index decreased significantly (P < 0.001). SSE of 41-200 Hz, 201-400 Hz and 801-1000 Hz also decreased significantly (P = 0.04, 0.01 and 0.006, respectively). Baseline SSE of 801-1000 Hz < 8.5 dB significantly predicted surgical success (odds ratio 11.0 [95% CI: 1.4-85.2]). CONCLUSIONS: Our findings suggest the potential utility of SSE of 801-1000 Hz to screen for severe OSA, predict surgical success and assess therapeutic outcomes. Specific baseline SSE may represent a potential biomarker for childhood OSA.
Assuntos
Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/cirurgia , Ronco/fisiopatologia , Ronco/cirurgia , Adenoidectomia , Criança , Feminino , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos , Índice de Gravidade de Doença , TonsilectomiaRESUMO
Importance: Pregnancy may contribute to the development or exacerbation of obstructive sleep apnea (OSA) and increase the risk of gestational complications. Continuous positive airway pressure (CPAP) is the first-line and criterion standard treatment for OSA and is regarded as the most feasible choice during pregnancy. However, the association between CPAP therapy in pregnant women with OSA and reduced gestational complications remains inconclusive. Objective: To investigate the association between CPAP therapy in pregnant women with OSA and the reduction of adverse hypertensive outcomes during gestation. Data Sources: Keyword searches of PubMed, Embase, and the Cochrane Database of Systematic Reviews and Clinical Trials were conducted from inception to November 5, 2023. Study Selection: Original studies reporting the treatment effect of CPAP use on lowering hypertension and preeclampsia risks in pregnant women with OSA were selected. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed in the reporting of reviews. Data were independently extracted by 2 authors. Random-effects model meta-analyses were performed and risk ratios (RRs) reported. Subgroup analysis, meta-regression based on age and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and publication bias assessment were also conducted. Main Outcome and Measures: The primary outcome was the RR of gestational hypertension and preeclampsia between pregnant women with OSA receiving CPAP treatment and those who did not receive CPAP treatment. Results: Six original studies in 809 participants (mean age, 31.4 years; mean BMI, 34.0) were identified and systematically reviewed for meta-analysis. The pooled results showed significant differences between the intervention (CPAP use) and the control (non-CPAP use) groups in reducing the risk of gestational hypertension (RR, 0.65; 95% CI, 0.47-0.89; P = .008) and preeclampsia (RR, 0.70; 95% CI, 0.50-0.98; P = .04). Meta-regression revealed that patients' age (coefficient, -0.0190; P = .83) and BMI (coefficient, -0.0042; P = .87) were not correlated with reduction of risk of hypertension and preeclampsia. Conclusions and Relevance: These findings suggest that implementing CPAP treatment in pregnant women with OSA may reduce the risk of gestational hypertension and preeclampsia.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono , Humanos , Gravidez , Feminino , Pressão Positiva Contínua nas Vias Aéreas/métodos , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/complicações , Adulto , Pré-Eclâmpsia , Hipertensão Induzida pela Gravidez/epidemiologia , Resultado da Gravidez/epidemiologiaRESUMO
This study aimed to report the clinical characteristics and COMP gene mutation of a family with pseudoachondroplasia (PSACH), a relatively rare spinal and epiphyseal dysplasia that is inherited as an autosomal dominant trait. Clinical information on a 5-year-2-month-old PSACH child and his parents was collected and analyzed. Diagnosis was confirmed by PCR amplification and direct sequencing of all the 19 exons and their flanking sequences of COMP gene, and the mutation was further ascertained by cloning analysis of exon 10. The child presented with short and stubby fingers, bow leg, short limb dwarfism and metaphysic broadening in long bone as well as lumbar lordosis. A mutation c.1048_1116del (p.Asn350_Asp372del) in exon 10, inherited from his father who did not demonstrate any phenotypic feature of PSACH, was detected in the child. PSACH was diagnosed definitively by means of COMP mutation analysis, on the basis of the child's clinical and imaging features. The non-penetrance phenomenon of COMP mutation was described for the first time in PSACH.
Assuntos
Acondroplasia/genética , Proteína de Matriz Oligomérica de Cartilagem/genética , Mutação , Pré-Escolar , Clonagem Molecular , Humanos , MasculinoRESUMO
Continuous positive airway pressure is the first-line and gold-standard treatment for obstructive sleep apnea (OSA). Pharmacotherapy is not commonly used in treating OSA until recently. Combined noradrenergic and antimuscarinic agents have been clinically applied for OSA patients with variable results. This meta-analysis study aimed to investigate the efficacy of the combined regimen on OSA. A systematic literature search was performed up to November 2022 for the effects of the combined regimen on OSA. Eight randomized controlled trials were identified and systematically reviewed for meta-analysis. There were significant mean differences between OSA patients taking a combined regimen and placebo in apnea-hypopnea index (AHI) [mean difference (MD) -9.03 events/h, 95%CI (-16.22, -1.83 events/h; P = 0.01] and lowest oxygen saturation [MD 5.61%, 95% CI % (3.43, 7.80); P < 0.01]. Meta-regression showed that a higher proportion of male participants was associated with a greater reduction of AHI (p = 0.04). This study showed a positive but modest effect of pharmacotherapy in the reduction of OSA severity. The combination drugs are most applicable to male OSA patients based on their efficacy and pharmacological susceptibility. Pharmacotherapy may be applied as an alternative, adjunctive or synergistic treatment under careful consideration of its side effects.
Assuntos
Apneia Obstrutiva do Sono , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Apneia Obstrutiva do Sono/terapia , Pressão Positiva Contínua nas Vias Aéreas , Norepinefrina/uso terapêuticoRESUMO
Bisphenol A (BPA) and parabens (PBs) are chemicals that are extensively used in personal care products (PCPs). In early childhood development, hearing is critical to speech and language development, communication, and learning. In vitro and in vivo, BPA/PBs exhibited neurotoxicity through elevated levels of oxidative stress. BPA also has the potential to be an ototoxicant. Therefore, this study aimed to determine the association of exposure to BPA/PBs with sensorineural hearing loss in children. A cross-sectional study based on hearing tests was conducted. This study enrolled 320 children aged 6-12 years from elementary school. Urinary BPA and PB concentrations were analyzed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Logistic regression models were employed to determine the association of BPA/PB exposure with sensorineural hearing loss. Children with sensorineural hearing loss had higher BPA concentrations than normal-hearing children (0.22 ng/ml vs. 0.10 ng/ml, p = 0.05). After adjustment for covariates, the risk of hearing loss at middle frequencies reached 1.83-fold (95% CI: 1.12-2.99) when BPA concentrations increased by 1 log10. The risk of slight hearing loss reached 2.24-fold (95% CI: 1.05-4.78) when children had a tenfold increase in ethyl paraben (EP) concentration. This study clarifies the role of exposure to BPA/PBs in hearing loss in children. Future research needs to be expanded to include cohort designs and nationwide studies to identify causality.
Assuntos
Perda Auditiva Neurossensorial , Parabenos , Humanos , Criança , Pré-Escolar , Cromatografia Líquida , Parabenos/análise , Estudos Transversais , Espectrometria de Massas em Tandem , Compostos Benzidrílicos/análise , Perda Auditiva Neurossensorial/induzido quimicamenteRESUMO
Aim: There is a bidirectional association between diabetes and periodontitis. However, the effect of diabetes on the periodontitis salivary microbiota has not been elucidated. The aim of this study was to determine the effect of the presence of diabetes on the microbiota among Chinese patients with periodontitis. Materials and Methods: Unstimulated whole saliva samples were collected from the periodontitis with diabetes group (TC), chronic periodontitis group (CP), and periodontally healthy and systemically healthy group (H) by spitting method. Bacterial genomic DNA was PCR-amplified at the V4 variable region of 16S rRNA gene. The library was constructed according to the obtained sequence results, and biological analysis and statistical analysis were carried out. Functional prediction of three groups of microbial communities was performed by the PICRUSt algorithm. Results: There was no significant difference in bacterial diversity between the TC and CP groups. Compared with the H group, the TC group and CP group presented a higher diversity of salivary flora. Firmicutes, Streptococcus, Haemophilus, Veillonella, and Haemophilus parainfluenzae dominated the H group. Corynebacterium, Leptotrichia, Dialister, Comamonas, Capnocytophaga, Catonella, Filifactor, Campylobacter, Treponema, Campylobacter concisus, Prevotella oralis, and Porphyromonas gingivalis were significantly enriched in the TC and CP groups. Among them, Treponema and P. oralis were the most abundant in the TC group. The PICRUSt results showed that many pathways related to cell motility and functional metabolism of the salivary microbial flora changed in the TC group and the CP group. Conclusions: Diabetes was not the main factor causing the altered diversity of salivary microbiota in patients with periodontitis; however, the presence of diabetes altered the abundance of some microbiota in saliva.
Assuntos
Periodontite Crônica , Diabetes Mellitus , Microbiota , China , Periodontite Crônica/microbiologia , DNA Bacteriano/genética , Humanos , Microbiota/genética , Porphyromonas gingivalis/genética , RNA Ribossômico 16S/genética , Saliva/microbiologiaRESUMO
The objective of the study was to investigate the relationship between obstructive sleep apnea (OSA) and auditory dysfunction, and to clarify the role of snoring sounds in contributing to auditory dysfunction. A comprehensive assessment of OSA and the auditory system was performed, including overnight polysomnography, detection of the intra-ear canal snoring sound energy (SSE), pure tone average (PTA), tinnitus pitch matching, the tinnitus handicap inventory (THI), and the Epworth sleepiness scale (ESS). The patients were identified as having tinnitus if their THI score was higher than zero or their tinnitus pitches were matched to specific frequencies. The median age, body mass index, and apnea-hypopnea index score were 41 years, 26.4 kg/m2, and 29.9 events/h, respectively. Among the 50 participants, 46 (92%) had a normal PTA, and only 4 (8%) patients had mild hearing loss. There was no significant difference in PTA among OSA severities (p = 0.52). Among the 50 participants, 33 patients (66%) were identified as having tinnitus. In the tinnitus group (n = 33), the ESS score (p = 0.01) and intra-ear canal SSE of 851-1500 Hz (p = 0.04) were significantly higher than those in the non-tinnitus group (n = 17). OSA patients with a higher ESS score had a higher risk of tinnitus (odds ratio 1.22 [95% CI: 1.01-1.46]). OSA-related auditory dysfunction emerged in tinnitus rather than in hearing impairment. OSA patients with daytime sleepiness had a higher risk of tinnitus. High-frequency SSE can jeopardize cochlea and is a potential mechanism contributing to tinnitus. Detection of snoring sounds through an intra-ear canal device may be more precise in assessing acoustic trauma from snoring sounds to vulnerable auditory system and thus warrants further research.
RESUMO
BACKGROUND: Many patients with obstructive sleep apnea (OSA) are mouth-breathers. Mouth-breathing not only narrows the upper airway, consequently worsening the severity of OSA, but also it affects compliance with nasal continuous positive airway pressure (CPAP) treatment. This study aimed to investigate changes in OSA by the use of mouth tape in mouth-breathers with mild OSA. METHOD: Mouth-breathers with mild OSA who met inclusion criteria and tolerated the sealing of the mouth were enrolled in the study. We used 3M silicone hypoallergenic tape was used to seal the mouths of the participants during sleep. The home sleep test (HST) used in this study was ApneaLink®. Subjects received both a baseline HST and an outcome HST to be used 1 week later while their mouths were taped. The changes between the baseline and the outcome HSTs were compared, and the factors that influenced the differences in the sleep-test parameters after the shift of the breathing route were analyzed. A "responder" was defined as a patient who experienced a reduction from the baseline snoring index of at least 50% under mouth-taping in the HST; otherwise, patients were considered as having a poor response. RESULTS: A total of 20 patients with mild OSA were included. Following the taping of the mouth, a good response was found in 13 patients (65%). The median apnea/hypopnea index (AHI) decreased significantly, from 8.3 to 4.7 event/h (by 47%, p = 0.0002), especially in supine AHI (9.4 vs. 5.5 event/h, p = 0.0001). The median snoring index (SI) was also improved (by 47%, 303.8 vs. 121.1 event/h, p = 0.0002). Despite no significant difference in the mean saturation, improvements in the oxygen desaturation index (8.7 vs. 5.8, p = 0.0003) and the lowest saturation (82.5% vs. 87%, p = 0.049) were noted. The change in AHI was associated with baseline AHI (r = -0.52, p = 0.02), oxygen desaturation index (ODI) (r = -0.54, p = 0.01), and SI (r = -0.47, p = 0.04). The change in SI was strongly associated with baseline SI (r = -0.77, p = 0.001). CONCLUSIONS: Mouth-taping during sleep improved snoring and the severity of sleep apnea in mouth-breathers with mild OSA, with AHI and SI being reduced by about half. The higher the level of baseline AHI and SI, the greater the improvement was shown after mouth-taping. Mouth-taping could be an alternative treatment in patients with mild OSA before turning to CPAP therapy or surgical intervention.
RESUMO
Nuclear factor E2-related factor 2(Nrf2) is a transcription factor that mainly regulates oxidative stress in the body. It initiates the expression of several downstream antioxidants, anti-inflammatory proteins and detoxification enzymes through the Kelch-like ECH-associating protein 1 (Keap1) -nuclear factor E2-related factor 2(Nrf2) -antioxidant response element (ARE) signaling pathway. Its anti-apoptosis, anti-oxidative stress and anti-inflammatory effects have gradually become the focus of periodontal disease research in recent years. In this paper, the structure and function of Nrf2 pathway and its mechanism of action in the treatment of periodontitis in recent years were analyzed and summarized, so as to further clarify the relationship between Nrf2 pathway and oxidative stress in the occurrence and development of periodontitis, and to provide ideas for the development of new treatment drugs targeting Nrf2 pathway.
Assuntos
Fator 2 Relacionado a NF-E2 , Doenças Periodontais , Humanos , Peroxidação de Lipídeos , Proteína 1 Associada a ECH Semelhante a Kelch , Anti-InflamatóriosRESUMO
miRNAs pose a good prospect in the diagnosis and treatment of type 2 diabetes (T2D). This study is aimed at investigating whether miR-720 targets Rab35 to regulate insulin secretion in MIN6 cells and its molecular mechanism and the clinical value of miR-720 as a specific biomarker of T2D. Fifty-five samples of new diagnosis T2D patients and normal control were collected. Levels of miR-720, fasting blood glucose, insulin, and other indicators of glucose and lipid metabolism were determined. We increased and decreased the miR-720 expression using miR-720 mimic and inhibitor to identify the effect of miR-720 on insulin secretion in MIN6 cells, respectively. Then, we used miR-720 mimic, miR-720 inhibitor, and dual luciferase reporter gene assays to prove miR-720 which regulates insulin secretion by targeting Rab35 in MIN6 cells. In addition, we overexpressed and silenced the Rab35 gene to detect the expression of PI3K, Akt, and mTOR in MIN6 cells by RT-PCR and western blot. In this study, circulating miR-720 was significantly higher in the T2D group than the control group, and miR-270 was positive correlated with FBG, while negatively correlated with FINS. The overexpression of miR-720 inhibited insulin secretion, and miR-720 downregulation promoted insulin secretion. miR-720 regulated insulin secretion by targeting Rab35 in MIN6 cells. Compared with the control group, the expression of PI3K, Akt, and mTOR was significantly decreased by the overexpression of the Rab35 gene, while the silencing Rab35 gene could induce the expression of PI3K, Akt, and mTOR. Furthermore, miR-720 mimic could activate the PI3K pathway. We conclude that miR-720 may be a potential biomarker for the diagnosis of T2D. Increase of miR-720 reduced the Rab35 expression then activate the PI3K/Akt/mTOR signal pathway, thus inhibiting insulin secretion.
Assuntos
Secreção de Insulina/genética , MicroRNAs/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Adulto , Idoso , Animais , Estudos de Casos e Controles , Linhagem Celular , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Masculino , Camundongos , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Adulto Jovem , Proteínas rab de Ligação ao GTP/genéticaRESUMO
Herein, a label-free electrochemical aptasensor for alpha-fetoprotein (AFP) analysis was established. The AFP aptamer (AFP-Apt), as the recognition molecule, was immobilized on the surface of a screen-printed carbon electrode, which was modified by gold-platinum metallic nanoparticles and reduced graphene oxide-chitosan-ferrocene nanohybrids (Au-Pt NPs/RGO-CS-Fc), to build the AFP electrochemical aptasensor. The construction process of the aptasensor was characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and electrochemical impedance spectroscopy. With the addition of AFP, the formation of the AFP-aptamer conjugation blocked the electron transfer reaction, reducing the differential pulse voltammetric responses of the current of Fc in the RGO-CS-Fc nanohybrids. By optimizing the experimental parameters, AFP could be detected with the dynamic concentration range of 0.001 to 10.0 µg mL-1 and with a detection limit of 0.3013 ng mL-1. In addition, the approach was manifested to have good selectivity, reproducibility, and stability. The fabricated aptasensor had a good recovery rate of 102.36% to 118.09% in real human serum samples. This work demonstrates that the electrochemical aptasensor is a useful tool for analyzing AFP inexpensively, rapidly, and accurately.
Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , Nanocompostos , Técnicas Eletroquímicas , Ouro , Grafite , Humanos , Platina , Reprodutibilidade dos Testes , alfa-FetoproteínasRESUMO
To explore the ectopic osteogenesis effect of sequential sustained release application of recombinant human bone morphogenic protein-2 (rhBMP-2) and basic fibroblast growth factor (bFGF). Antigen-extracted xenogeneic cancellous bone coupled with growth factor-loaded chitosan nanocapsules were implanted in rats in intramuscular site in accordance with the following experimental pattern: group A: simultaneous burst release of rhBMP-2 and bFGF; group B: simultaneous sustained release of rhBMP-2 and bFGF; group C: preferential burst release of rhBMP-2, then sustained release of bFGF; group D: preferential burst release of bFGF, then sustained release of rhBMP-2; group E: sustained release of rhBMP-2 alone; group F: sustained release of bFGF alone, blank control group G: antigen-extracted xenogeneic cancellous bone graft only; negative control group H: not filled with anything. Specimens were obtained after executing the animals at 2 and 4 weeks for general observation and weighing, calcium content detection, micro-CT scanning and bone parameter measurement analysis, H&E staining, ALP staining and CD34 staining. The materials weight of A-2, B-2, C-2, A-4, B-4, C-4, D-4 and E-4 were significantly higher than that of preoperative materials ( P < 0.05). The concentration of calcium of group B-4 was the highest (414.7 ± 12.03 mg/dl). Micro-CT scanning and bone parameter measurement analysis showed that the values of bone mineral density and trabecular thickness of group A, B, D, E at 4 weeks were both higher than the ones at 2 weeks ( P < 0.05), and both the bone mineral density (367.52 ± 11.64 mg/cc) and the trabecular thickness (126.17 ± 11.36 µm) of group B-4 were the highest. H&E staining showed that a large region of calcified cartilage and haemopoietic tissues were newly formed, especially in group B-4. ALP staining and CD34 staining showed the most positive expression region in group B-4. Therefore, we conclude that simultaneous sustained release of rhBMP-2 and bFGF is the ideal way to release drug, and has better inducement of antigen-extracted xenogeneic cancellous bone graft.
Assuntos
Proteína Morfogenética Óssea 2/química , Osso Esponjoso/transplante , Quitosana/química , Fator 2 de Crescimento de Fibroblastos/química , Nanocápsulas/química , Osteogênese/efeitos dos fármacos , Fator de Crescimento Transformador beta/química , Animais , Materiais Biocompatíveis/química , Proteína Morfogenética Óssea 2/farmacologia , Cálcio/análise , Preparações de Ação Retardada , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Masculino , Ratos , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia , Suínos , Fator de Crescimento Transformador beta/farmacologiaRESUMO
OBJECTIVE: To analyze the correlation of serum levels of visfatin, leptin, resistin, and adiponectin (APN) with glycolipid metabolism and inflammatory factors in obese patients with periodontal disease. METHODS: 116 obese adults (OB), of whom 78 participants were diagnosed with different degrees of chronic periodontitis (CP), and 50 healthy adults were recruited into the study. Fasting peripheral venous blood was extracted to determine serum levels of adipocytokines (e.g., visfatin, leptin, resistin, and APN), glucolipid metabolism (e.g., fasting blood glucose (FBG), fasting insulin (FINS), C-peptide (C-P), cortisol (Cor), homeostasis model of assessment for insulin resistance index (HOMA-IR), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and non-high-density lipoprotein cholesterol (non-HDL)), and micro-inflammation-related indexes like C-reactive protein (CRP), interleukin (IL)-1ß, IL-6, IL-10, and tumor necrosis factor (TNF)-α. Correlation between levels of adipocytokines and levels of glucolipid metabolism and inflammatory factors was further analyzed. RESULTS: Assays for plasma levels of adipocytokines showed that both the OB group and the OB with CP group had significantly higher serum levels of visfatin, leptin, and resistin than the normal control group and significantly lower serum levels of ANP than the normal control group (P<0.05). Detection of serum glucolipid metabolism levels showed that FBG, FINS, C-P, Cor, HOMA-IR, TG, TC, LDL-C, HDL-C, Non-HDL-C of OB group, and OB with CP patients were significantly higher than those of normal patients (P<0.05). Assay for plasma levels of inflammatory factors showed that both the OB group and the OB with CP group had significantly higher serum levels of CRP, IL-1ß, IL-6, and TNF-α than the normal control group and significantly lower serum levels of IL-10 than the normal control group. Spearman's correlation analysis revealed that serum levels of visfatin, leptin, resistin, and APN were significantly correlated with concentrations of FBG, FINS, C-P, Cor, TG, TC, LDL-C, HDL-C, Non-HDL-C, CRP, IL-1ß, IL-6, IL-10, and TNF-α. CONCLUSIONS: There were high expression levels of inflammatory factors and glucolipid metabolism disorder in obese patients with periodontal disease and excessively expressed adipocytokines may be important factors of persistent and worsened obesity and of periodontitis.
RESUMO
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a hereditary metabolic disease arising from biallelic mutations of SLC25A13. This study aimed to explore the characteristics of fasting blood glucose (FBG), fasting insulin (FINS) and C-peptide (C-P) levels in NICCD infants, analyze their SLC25A13 genetic mutations and further discuss the correlation between SLC25A13 genetic mutations and biochemical changes. Seventy-two cases of infants with cholestasis disease were gathered. Among them, 36 cases with NICCD diagnosis were case group. Meanwhile, 36 cases with unknown etiology but excluded NICCD were control group. FBG, FINS, C-P, ALT, AST, GGT, ALP, TG, HDL-C, LDL-C and Non-HDL-C were collected from all subjects, and DNA was extracted from venous blood for SLC25A13 mutations detection. The incidence of hypoglycemia was 3% in NICCD group. There were no significant statistical difference of FBG, FINS and C-P between NICCD and INC groups ( P > 0.05). ALT, LDL-C and Non-HDL-C levels in NICCD group were lower than the INC group, while SLC25A13 mutations were associated with the level of GGT ( P < 0.05). Ten different SLC25A13 genetic mutations were detected, among which, 851del4, IVS16ins3kb, IVS6+5 G > A and 1638ins23 mutations made up 82% of all mutations. The incidence of hypoglycemia may be higher in small gestational age infants with NICCD. Low LDL-C may be one of the characteristics of dyslipidemia in NICCD infants. There was a correlation between SLC25A13 gene mutations distribution and the GGT level, but the meaning of this finding remains to be further in-depth study. Impact statement This study aims to compare FBG, FINS, C-P, other biochemical and clinical manifestations between NICCD and non-NICCD infants, and discuss differential diagnosis of NICCD and INC beyond the genetic analysis. And investigate the correlation between SLC25A13 genetic mutations and biochemical changes. This work presented that incidence of hypoglycemia may be higher in small gestational age infants with NICCD. Low LDL-C may be one of the characteristics of dyslipidemia in NICCD infants. There was a correlation between SLC25A13 gene mutations distribution and the GGT level.
Assuntos
Glicemia/análise , Citrulinemia/sangue , Citrulinemia/diagnóstico , Insulina/sangue , Proteínas de Transporte da Membrana Mitocondrial/genética , Peptídeo C/análise , Colestase/sangue , Colestase/diagnóstico , Colestase/genética , Citrulinemia/genética , Diagnóstico Diferencial , Feminino , Humanos , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Incidência , Lactente , Recém-Nascido , Doenças do Recém-Nascido/sangue , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/genética , Masculino , MutaçãoRESUMO
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) primarily manifests in neonates or infants with hepatomegaly, liver dysfunction, and hypoglycemia. This study investigated the functions of islet beta cells and their correlations with liver dysfunction in NICCD patients.We retrospectively analyzed clinical data on liver function and islet beta cell functions for 36 patients diagnosed with NICCD and 50 subjects as the control group. The NICCD group had significantly higher total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate amino transferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) and alpha-fetoprotein (AFP) levels and albumin/globulin ratio (A/G) (Pâ<â.05), and lower ALB and GLB levels than the control group (Pâ<â.05). The differences in fasting blood glucose (FBG), fasting insulin, C-peptide (C-P), the homeostasis model of assessment for the insulin resistance index (HOMA-IR), fasting beta cell function (FBCI), and the HOMA beta cell function index (HBCI) between the NICCD and control groups were not significant (Pâ>â.05). A linear correlation was found between FBG and fasting insulin (Pâ<â.001) and between FBG and C-P in the NICCD patients (Pâ=â.001). Fasting insulin (Pâ=â.023), HOMA-IR (Pâ=â.023), FBCI (Pâ=â.049), and HBCI (Pâ=â.048) were positively correlated with increases in the ALT level. There was no difference in islet beta cell functions between the NICCD and control groups. The liver dysfunction may be correlated with islet beta cell functions in NICCD patients.
Assuntos
Citrulinemia/fisiopatologia , Células Secretoras de Insulina/fisiologia , Fígado/fisiopatologia , Peptídeo C/sangue , Citrulinemia/genética , Feminino , Humanos , Lactente , Insulina/sangue , Masculino , Proteínas de Transporte da Membrana Mitocondrial/genética , Estudos RetrospectivosRESUMO
The effects of a large-piece of xenogeneic bone that was separated from healthy pigs as a scaffold for the repair of a mandibular defect was investigated, and the applicability of antigen-extracted xenogeneic cancellous bone (AXCB) soaked with recombinant human bone morphogenetic protein-2 (rhBMP-2) in bone defect repair was assessed. Mandibular defects were created in 48 New Zealand rabbits, and the animals were randomly divided into four groups, in which the mandibular defects were grafted with AXCB, AXCB soaked with rhBMP-2, and autograft bone, or left blank. An equal number of animals from each group were classified into three time points (4, 8, and 12 weeks) after surgery for gross pathological observation, hematoxylin and eosin (H and E) staining, radiographic examination, and bone density measurement. H and E staining revealed that the area percentage of bone regeneration in the group of the AXCB/rhBMP-2 graft was 27.72 ± 4.68, 53.90 ± 21.92, and 77.35 ± 9.83 at 4 weeks, 8 weeks, and 12 weeks, respectively. These results were better than those of the autogenous bone graft, suggesting that the group of the AXCB/rhBMP-2 graft achieved a good osteogenic effect. With regard to the AXCB graft without rhBMP-2, the area percentage of bone regeneration was only 14.03 ± 5.02, 28.49 ± 11.35, and 53.90 ± 21.92. Therefore, the osteogenic effect of the AXCB/rhBMP-2 graft was demonstrated to have the best effect. In the group of the AXCB/rhBMP-2 graft, the area percentage of bone regeneration increased, and the implanted materials were gradually degraded and replaced by autogenous bone regeneration over time. We conclude that the AXCB graft soaked with rhBMP-2 showed good osteogenic effect in the repair of bone defects and good biocompatibility. AXCB serves as a good carrier of rhBMP-2, which promotes bone formation.