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BACKGROUND AND OBJECTIVE: Posterior reversible encephalopathy syndrome (PRES) in systemic lupus erythematosus (SLE) is a challenging clinical dilemma. A retrospective single-center study was performed to investigate the clinical features, risk factors, outcomes, and clinical determinants of the prognosis of PRES in SLE. METHODS: A retrospective study was performed from January 2015 to December 2020. 19 episodes of lupus PRES and 19 episodes of non-lupus PRES were identified. 38 cases of patients presenting with neuropsychiatric lupus (NPSLE) hospitalized during the same period were selected as controls. Survival status was acquired via outpatient and telephone follow-up in December 2022. RESULTS: The clinical neurological presentation of PRES in lupus patients was similar to that of the non-SLE-related PRES and NPSLE populations. Nephritis-induced hypertension is the predominant trigger of PRES in SLE. Disease flare and renal failure-triggered PRES were identified in half of the patients with SLE. The mortality rate of lupus-related PRES during the 2year follow-up was 15.8%, the same as that of NPSLE. For patients with lupus-related PRES, multivariate analysis indicated that high diastolic blood pressure (ORâ¯=1.762, 95% CI: 1.031â¯~ 3.012, pâ¯= 0.038), renal involvement (ORâ¯= 3.456, 95% CI: 0.894â¯~ 14.012, pâ¯= 0.049), and positive proteinuria (ORâ¯= 1.231, 95% CI: 1.003â¯~ 1.511, pâ¯= 0.047) were independent risk factors compared to NPSLE. A strong connection between the absolute counts of T and/or B cells and prognosis in lupus patients with neurological manifestations was found (pâ¯< 0.05). The lower the counts of T and/or B cells, the worse the prognosis. CONCLUSION: Lupus patients with renal involvement and disease activity are more likely to develop PRES. The mortality rate of lupus-related PRES is similar to that of NPSLE. Focusing on immune balance might reduce mortality.
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Lúpus Eritematoso Sistêmico , Síndrome da Leucoencefalopatia Posterior , Humanos , Estudos Retrospectivos , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Síndrome da Leucoencefalopatia Posterior/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Fatores de Risco , PrognósticoRESUMO
BACKGROUND: The ovarian reserve has been reported to be diminished in patients with rheumatoid arthritis. However, these results are still controversial. Anti-Müllerian hormone (AMH) is considered a reliable biomarker for the ovarian reserve. We thus performed a meta-analysis to evaluate the AMH levels and the effect of DMARDs on the ovarian reserve in rheumatoid arthritis patients. METHODS: PubMed, EMBASE, the Cochrane Library, and 2 Chinese databases (CNKI and Wanfang database), up to September 2021, were searched for relevant studies. The Newcastle-Ottawa scale (NOS) was used to assess the quality of the included studies. Pooled standard mean difference (SMD) with 95% confidence intervals (CIs) were determined with the random-effects model. The heterogeneity was described by I2 statistic and p value from the Cochrane Q test. RESULTS: Eight eligible studies (679 patients and 1,460 controls) were included in the meta-analysis. Compared with healthy control, the AMH levels in RA patients were significantly lower with the pooled SMD of -0.40 (95% CI: -0.66 to -0.14). However, in comparison of AMH with and without DMARD treatment, there was no significant difference with the pooled SMD of -0.1 (95% CI: -0.39 to 0.19). CONCLUSION: The results indicated that there was an increased risk of ovarian failure in RA patients and which is not related to DMARD treatment.
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Antirreumáticos , Artrite Reumatoide , Reserva Ovariana , Hormônio Antimülleriano/farmacologia , Hormônio Antimülleriano/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Biomarcadores , HumanosRESUMO
OBJECTIVE: This study aimed to evaluate the magnetic resonance imaging (MRI) changes of the symphysis pubis in patients with axial spondyloarthritis (ax-SpA) and to assess its association with clinical factors. METHODS: A retrospective analysis of 172 patients with ax-SpA was performed to assess the presence of active inflammatory and structural changes of the symphysis pubis on MRI scans, and their association with clinical factors and the SPARCC (Spondyloarthritis Research Consortium of Canada) scoring of the sacroiliac joint were evaluated. RESULTS: The proportions of active inflammation and structural changes of the symphysis pubis were 69/172 (40.1%) and 54/172 (31.4%), respectively. When comparing the active inflammation and no-active inflammation symphysis pubis groups, the former had higher level C-reactive protein, higher erythrocyte sedimentation rate, and younger median age of patients. Moreover, no significant correlation was noted between the active inflammation of the symphysis pubis and SPARCC score of the sacroiliac joint. When comparing the normal and abnormal symphysis pubis groups, the latter had longer symptom duration. CONCLUSIONS: The MRI changes of the symphysis pubis were seen in 55.2% of the patients with ax-SpA and were associated with C-reactive protein, erythrocyte sedimentation rate, and symptom duration.
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Proteína C-Reativa/metabolismo , Sínfise Pubiana/diagnóstico por imagem , Espondilartrite/sangue , Espondilartrite/diagnóstico por imagem , Adolescente , Adulto , Idoso , Sedimentação Sanguínea , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Sínfise Pubiana/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Espondilartrite/patologia , Adulto JovemRESUMO
Introduction: The microgravity environment astronauts experience during spaceflight can lead to an increased risk of oral diseases and possible changes in oral microecology. In this study, we aimed to assess changes in the microbial community of supragingival plaques to explore the effects of spaceflight microgravity environment on oral microecology. Methods: Sixteen healthy male volunteers were recruited, and supragingival plaque samples were collected under -6° head-down bed rest (HDBR) at five-time points: day 1 before HDBR; days 5, 10, and 15 of HDBR; and day 6 of recovery. Bacterial genomic DNA was sequenced using gene sequencing technology with 16S ribosomal ribonucleic acid V3-V4 hypervariable region amplification and the obtained data were analyzed bioinformatically. Results: Alpha diversity analysis showed a significant increase in species richness in supragingival plaque samples on day 15 of HDBR compared with that at pre-HDBR. Beta diversity analysis revealed that the community composition differed among the groups. Species distribution showed that, compared with those at pre-HDBR, the relative abundances of Corynebacterium and Aggregatibacter increased significantly during HDBR, while those of Veillonella, Streptococcus, and Lautropia decreased significantly. Moreover, compared with those at pre-HDBR, the relative abundance of Leptotrichia increased significantly on day 6 of recovery, whereas the relative abundances of Porphyromonas and Streptococcus decreased significantly. Network analysis showed that the interaction relationship between the dominant genera became simpler during HDBR, and the positive and negative correlations between them showed dynamic changes. Phylogenetic investigation of communities by reconstruction of unobserved states analysis showed that the amino acid metabolism function of plaque microorganisms was more enriched during HDBR. Discussion: In summary, in a 15-day simulated microgravity environment, the diversity, species distribution, interaction relationship, and metabolic function of the supragingival plaque microbial community changed, which suggests that microgravity may affect the oral microecosystem by changing the balance of supragingival plaque microbial communities and further leading to the occurrence and development of oral diseases.
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Lupus nephritis (LN), a leading cause of death in Systemic Lupus Erythematosus (SLE) patients, presents significant diagnostic and prognostic challenges. Although renal pathology offers critical insights regarding the diagnosis, classification, and therapy for LN, its clinical utility is constrained by the invasive nature and limited reproducibility of renal biopsies. Moreover, the continuous monitoring of renal pathological changes through repeated biopsies is impractical. Consequently, there is a growing interest in exploring urine as a non-invasive, easily accessible, and dynamic "liquid biopsy" alternative to guide clinical management. This paper examines novel urinary biomarkers from a renal pathology perspective, encompassing cellular components, cytokines, adhesion molecules, auto-antibodies, soluble leukocyte markers, light chain fragments, proteins, small-molecule peptides, metabolomics, urinary exosomes, and ribonucleic acids. We also discuss the application of combined models comprising multiple biomarkers in assessing lupus activity. These innovative biomarkers and models offer insights into LN disease activity, acute and chronic renal indices, fibrosis, thrombotic microangiopathy, podocyte injury, and other pathological changes, potentially improving the diagnosis, management, and prognosis of LN. These urinary biomarkers or combined models may serve as viable alternatives to traditional renal pathology, potentially revolutionizing the method for future LN diagnosis and observation.
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OBJECTIVE: To evaluate the protection of calcium alginate hydrogel beads for mouse preosteoblastic cell line (MC3T3-E1) during the setting reaction of calcium phosphate cement (CPC) pastes and to analyze related influencing factors. METHODS: The MC3T3-E1 cells encapsulated in alginate hydrogel beads were cultured in vitro with ß-tricalcium phosphate/calcium phosphate cement (ß-TCP/CPC) pastes and discs until 2 d. The cell viability and number of live/dead cells were tested using the CCK-8, Calcein-AM and PI, respectively. The effects of CPC paste and CPC disc, different treatment and time to renewal medium on cell viability were compared. RESULTS: There were no significant differences in optical density and number of live cells between ß-TCP/CPC pastes and discs (1 d: P=0.827; 2 d: P=0.965). There were different influences on cell viability between different treatment and time to renewal medium. CONCLUSION: The results indicated that the calcium alginate hydrogel beads had a good protection to MC3T3-E1 cells during the setting reaction of CPC pastes. CPC paste might affect the cell proliferation even when solidification. After setting reaction, it may be favorable for cell viability to renew the medium every 6 h in 1 d.
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Alginatos/farmacologia , Fosfatos de Cálcio/química , Sobrevivência Celular/efeitos dos fármacos , Osteoblastos/citologia , Células 3T3 , Animais , Substitutos Ósseos/química , Proliferação de Células/efeitos dos fármacos , Ácido Glucurônico/farmacologia , Ácidos Hexurônicos/farmacologia , Hidrogéis/farmacologia , Camundongos , Microesferas , Substâncias Protetoras/farmacologiaRESUMO
Background: The microbial community structure in saliva differs at different altitudes. However, the impact of acute high-altitude exposure on the oral microbiota is unclear. This study explored the impact of acute high-altitude exposure on the salivary microbiome to establish a foundation for the future prevention of oral diseases. Methods. Unstimulated whole saliva samples were collected from 12 male subjects at the following three time points: one day before entering high altitude (an altitude of 350 m, pre-altitude group), seven days after arrival at high altitude (an altitude of 4,500 m, altitude group) and seven days after returning to low altitude (an altitude of 350 m, post-altitude group). Thus, a total of 36 saliva samples were obtained. 16S rRNA V3-V4 region amplicon sequencing was used to analyze the diversity and structure of the salivary microbial communities, and a network analysis was employed to investigate the relationships among salivary microorganisms. The function of these microorganisms was predicted with a Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. Results: In total, there were 756 operational taxonomic units (OTUs) identified, with 541, 613, and 615 OTUs identified in the pre-altitude, altitude, and post-altitude groups, respectively. Acute high-altitude exposure decreased the diversity of the salivary microbiome. Prior to acute high-altitude exposure, the microbiome mainly consisted of Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Actinobacteria. After altitude exposure, the relative abundance of Streptococcus and Veillonella increased, and the relative abundance of Prevotella, Porphyromonas, and Alloprevotella decreased. The relationship among the salivary microorganisms was also affected by acute high-altitude exposure. The relative abundance of carbohydrate metabolism gene functions was upregulated, while the relative abundance of coenzyme and vitamin metabolism gene functions was downregulated. Conclusion: Rapid high-altitude exposure decreased the biodiversity of the salivary microbiome, changing the community structure, symbiotic relationships among species, and abundance of functional genes. This suggests that the stress of acute high-altitude exposure influenced the stability of the salivary microbiome.
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Altitude , Microbiota , Humanos , Masculino , RNA Ribossômico 16S/genética , Filogenia , Microbiota/genética , Bactérias/genética , Bacteroidetes/genéticaRESUMO
[This corrects the article DOI: 10.3389/fendo.2022.862849.].
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Objectives: This study aimed to analyze the differences of etiologies and clinical features between patients with autoimmune-associated hemophagocytic syndrome (AAHS) and those with other underlying diseases of hemophagocytic syndrome (HPS). Patients and methods: The retrospective study was performed with 130 HPS patients (70 males, 60 females; mean age: 50.4±18.1 years; range, 13 to 85 years) between January 1st, 2011, and April 1st, 2022. The patients fulfilled at least five of the eight criteria proposed by the Histiocytosis Society in 2004. The underlying diseases related to HPS were divided into four categories: autoimmune, infection, malignancy and idiopathic diseases. And the clinical manifestations, laboratory examinations, treatments, and prognosis were analyzed respectively. Results: Nineteen (14.6%) patients had AAHS, 45 (34.6%) had infection-associated HPS, 57 (43.8%) had malignancy-associated HPS, and nine (6.9%) had idiopathic HPS. The most common symptoms of HPS were unremitting fever in 123 (94.6%) of 130 patients and splenomegaly in 92 (70.8%). All patients manifested a decline of at least two lineages of hematopoietic cells. The absolute values of T cells and B cells of AAHS were significantly higher than that of malignancy-associated HPS. The levels of soluble CD25 (interleukin-2 receptor) of AAHS were the lowest among all-cause HPS (p<0.05). The all-cause mortality rate of hospitalized patients with HPS was 46.2%. The patients with AAHS had a better prognosis compared to other etiologies (odds ratio [OR]=0.091, 95% confidence interval [CI]: 0.011-0.775, p=0.028). Epstein-Barr virus infection (OR=4.761, 95% CI: 1.619-14.004, p=0.005) and pulmonary involvement (OR=4.555 95% CI: 1.524-13.609, p=0.007) were independent predictors of poor outcome in HPS. Thrombocytopenia (OR=0.978, 95% CI: 0.968-0.999, p=0.040) had a boundary effect on prognosis. Conclusion: Patients with HPS secondary to autoimmune disease have better outcomes compared to patients complicated with Epstein-Barr virus infection or pulmonary involvement.
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BACKGROUND: People with dermatomyositis (DM) or polymyositis (PM) often die from cancer, pulmonary, cardiac complications, or infections. In such cases, DM or PM might not be designated as the underlying cause of death (UCD) for mortality tabulation. In this study, we investigated DM/PM mortality trends in the USA from 1981 to 2020 with respect to UCD and multiple causes of death (MCD) data. METHODS: We used the MCD data to identify all deaths with DM or PM mentioned anywhere on the death certificate and as the UCD in the USA from 1981-1982 to 2019-2020. We calculated age-adjusted mortality rates (AAMRs) and annual percentage changes (APCs) based on joinpoint regression analysis. RESULTS: We identified 12,249 (3985 with DM and 7097 with PM) and 23,608 (8264 with DM and 15,344 with PM) people who died between 1981 and 2020 according to the UCD and MCD data, respectively. For DM, the APC was - 6.7% (from 1981-1982 to 1985-1986), - 0.1% (from 1985-1986 to 2003-2004), and - 1.9% (from 2003-2004 to 2019-2020) according UCD and was - 1.2% (from 1981-1982 to 2003-2004), - 2.5% (from 2003-2004 to 2015-2016), and 2.8% (from 2015-2016 to 2019-2020) according MCD. For PM, the APC was 1.9% (from 1981-1982 to 1989-1990), - 2.3% (from 1989-1990 to 2005-2006), and - 5.2% (from 2005-2006 to 2019-2020) according UCD and was 1.3% (from 1981-1982 to 1991-1992) and - 4.1% (from 1991-1992 to 2019-2020) according MCD. CONCLUSION: We identified two times as many DM/PM deaths using the MCD as those identified using the UCD. Similar downward DM/PM mortality trends were noted according to UCD and MCD. However, the year of significant decline in PM mortality was about 10 years earlier according to MCD than those according to UCD.
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Dermatomiosite , Polimiosite , Humanos , Causas de Morte , Dermatomiosite/mortalidade , Polimiosite/mortalidade , Estados Unidos/epidemiologiaRESUMO
Microgravity influences are prevalent during orbital flight and can adversely affect astronaut physiology. Notably, it may affect the physicochemical properties of saliva and the salivary microbial community. Therefore, this study simulates microgravity in space using a ground-based -6° head-down bed rest (HDBR) test to observe the effects of microgravity on oral salivary secretion function and the salivary microbiome. Sixteen healthy young male volunteers were recruited for the 15-day -6° HDBR test. Non-stimulated whole saliva was collected on day 1 (pre-HDBR), on days 5, 10, and 15 of HDBR, and day 6 of recovery. Salivary pH and salivary flow rate were measured, and the V3-V4 region of the 16S rRNA gene was sequenced and analyzed in 80 saliva samples. The results showed that there were no significant differences in salivary pH, salivary flow rate, and alpha diversity between any two time points. However, beta diversity analysis revealed significant differences between pre-HDBR and the other four time points. After HDBR, the relative abundances of Actinomyces, Parvimonas, Peptostreptococcus, Porphyromonas, Oribacterium, and Capnocytophaga increased significantly, whereas the relative abundances of Neisseria and Haemophilus decreased significantly. However, the relative abundances of Oribacterium and Capnocytophaga did not recover to the pre-HDBR level on day 6 of recovery. Network analysis revealed that the number of relationships between genera decreased, and the positive and negative correlations between genera changed in a complex manner after HDBR and did not reach their original levels on day 6 of recovery. PICRUSt analysis demonstrated that some gene functions of the salivary microbiome also changed after HDBR and remained significantly different from those before HDBR on day 6 of recovery. Collectively, 15 days of -6° HDBR had minimal effect on salivary secretion function but resulted in significant changes in the salivary microbiome, mainly manifested as an increase in oral disease-related bacteria and a decrease in oral health-related commensal bacteria. Further research is required to confirm these oral microbial changes and explore the underlying pathological mechanisms to determine the long-term effects on astronauts embarking on long-duration voyages to outer space.
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Background: The prevalence of rheumatoid arthritis (RA) has significant gender and age difference. The peak age of RA is consistent with the age of menopause, which is accompanied by a sharp increase in serum follicle-stimulating hormone (FSH) level. This study aims to identify the FSH levels in female RA patients and the relationship with diseases activity. Methods: In total, 79 female RA patients and 50 age-matched controls were included in our study. Serum sex hormones levels were measured using chemiluminescence. RA patients were grouped by FSH quartile. Disease activity and inflammatory marks were analyzed among groups. Results: Lower sex hormones and higher gonadotropin were found in RA patients. Serum FSH level was significantly higher in RA patients than in the age-match controls (57.58 ± 15.94 vs. 43.11 ± 19.46, p=0.025). Even after adjusting for age (OR: 1.071; 95%CI: 1.006-1.139; p = 0.031), luteinizing hormone (LH), estradiol (E), and testosterone (T) OR: 1.066; 95%CI: 1.003-1.133; p = 0.039), the OR were still more than one. RA patients in the higher quartiles had higher ESR, DAS28-ESR and DAS28-CRP (p<0.05) than the lowest quartile. Besides, menopause age was significantly related with onset age in post-menopause RA patients (r = 0.432, p =0.008). Conclusion: High FSH appears to be a risk factor for RA and is positively associated with their disease activity. Early menopause might be an essential factor of RA.
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Artrite Reumatoide , Hormônio Foliculoestimulante , Artrite Reumatoide/epidemiologia , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônios Esteroides Gonadais/sangue , Humanos , Hormônio Luteinizante/sangue , Testosterona/sangueRESUMO
The potential risk associated with ACP nanoparticles (ACP NPs) cultured with immune cells and their indirect effects on osteogenesis have not been studied deeply. This project aims to evaluate the safety of ACP NPs in macrophages, the responses of macrophages (macrophage polarization, the cytokine secretion pattern of macrophages and intracellular homeostasis) to ACP NPs and the effect of ACP NPs/macrophage-modulated environments on the osteogenic ability of BMSCs. The cell proliferation rate and apoptosis were detected by CCK-8 and Annexin V Apoptosis Detection kits. ROS and autophagy expression were evaluated by ROS test kits and Western blot (WB). Macrophage polarization and cytokine expression were determined by SEM, cytoskeletal staining, RT-PCR and ELISA. TMT™ quantitative protein analysis was used to evaluate protein expression. BMSC osteogenic differentiation was detected by ALP staining, Alizarin Red solution staining and RT-PCR. ACP NPs were safe to macrophages but promoted autophagy and induced ROS production at high concentrations. ACP NPs changed morphology of macrophages and induced polarization into M1 type, thus promoting the expression of inflammatory cytokines. ACP NPs/macrophage-modulated environments weakened the osteogenic ability of BMSCs. ACP NPs polarize macrophages into the M1 phenotype and change the cytokine secretion pattern. ACP NPs/macrophage-modulated environments weaken the osteogenic ability of BMSCs. ACP NPs may cause aseptic inflammation and attenuate osteogenesis.
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Fosfatos de Cálcio/farmacologia , Macrófagos/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas/administração & dosagem , Osteogênese/efeitos dos fármacos , Animais , Macrófagos/imunologia , Macrófagos/metabolismo , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteogênese/fisiologia , Células RAW 264.7RESUMO
Dental pulp stem cells (DPSCs) are ideal seed cells for the regeneration of dental tissues. However, DPSC senescence restricts its clinical applications. Metformin (Met), a common prescription drug for type 2 diabetes, is thought to influence the aging process. This study is aimed at determining the effects of metformin on DPSC senescence. Young and aging DPSCs were isolated from freshly extracted human teeth. Flow cytometry confirmed that DPSCs expressed characteristic surface antigen markers of mesenchymal stem cells (MSCs). Cell Counting Kit-8 (CCK-8) assay showed that a concentration of 100 µM metformin produced the highest increase in the proliferation of DPSCs. Metformin inhibited senescence in DPSCs as evidenced by senescence-associated ß-galactosidase (SA-ß-gal) staining and the expression levels of senescence-associated proteins. Additionally, metformin significantly suppressed microRNA-34a-3p (miR-34a-3p) expression, elevated calcium-binding protein 39 (CAB39) expression, and activated the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. Dual-luciferase reporter assay confirmed that CAB39 is a direct target for miR-34a-3p. Furthermore, transfection of miR-34a-3p mimics promoted the senescence of DPSCs, while metformin treatment or Lenti-CAB39 transfection inhibited cellular senescence. In conclusion, these results indicated that metformin could alleviate the senescence of DPSCs by downregulating miR-34a-3p and upregulating CAB39 through the AMPK/mTOR signaling pathway. This study elucidates on the inhibitory effect of metformin on DPSC senescence and its potential as a therapeutic target for senescence treatment.
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This study was conducted to compare the in vitro proliferation and osteogenic differentiation potential of mesenchymal stem cells (MSCs) derived from mandibular (M-MSCs) or femur (F-MSCs) tissues of rats. M-MSC and F-MSC cultures were isolated and established from the same rat. Cultures were observed for morphological changes by microscope and growth characteristics by CCK-8 and cloning assays. Cell adhesion ability on a culture plate and titanium sheet was detected by staining with toluidine blue and Hoechst 33258, respectively. The levels of Ca, P, and ALP (serially) during osteogenic differentiation were evaluated. Cultures were analyzed for mineralization potential with alizarin red and ALP staining methods and for differentiation markers with RT-PCR (ALP, Runx2, and OCN). M-MSCs and F-MSCs were successfully isolated from the same rat with uncontaminated culture, which showed significant differences in morphology. The proliferation rate of M-MSCs was higher than F-MSCs in primary culture, but significantly lower after passage. More colonies are formed from F-MSCs than from M-MSCs. M-MSCs showed a significantly higher mineralization and osteogenic differentiation potential, which might be of significance for use in bone/dental tissue engineering. In vitro, cell passage will decrease the proliferation ability of M-MSCs. The higher mineralization and osteogenic differentiation potential of M-MSCs could make them an approachable stem cell source for further application in stem cell-based clinical therapies.
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Células da Medula Óssea/citologia , Diferenciação Celular , Fêmur/citologia , Mandíbula/citologia , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Células da Medula Óssea/metabolismo , Células da Medula Óssea/fisiologia , Cálcio/metabolismo , Proliferação de Células , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/fisiologia , Especificidade de Órgãos , Osteoblastos/metabolismo , Osteoblastos/fisiologia , Osteocalcina/genética , Osteocalcina/metabolismo , Fósforo/metabolismo , Cultura Primária de Células/métodos , Ratos , Ratos Sprague-Dawley , Engenharia Tecidual/métodosRESUMO
As a bone implant material, porous tantalum (Ta) has better corrosion resistance and more suitable elastic modulus than titanium. Surface nanomodification can accelerate the integration of Ta implants with bone tissue, which has broad application prospects in the field of dental implantology. Due to mechanical stress and load wear, nanoscale Ta fragments are inevitably exfoliated from the implant surface and brought into direct contact with osteoblasts surrounding the implant. These wear fragments may affect the biological characteristics of osteoblasts and thus the stability of implants. To date, the interaction of nanoscale Ta fragments with osteoblasts has not been clearly investigated. In the current study, we used the mouse osteoblast cell line MC3T3-E1 to explore the effects of Ta nanoparticles (Ta-NPs) on the cytotoxicity, oxidative stress and autophagy of osteoblasts. We found that a low concentration (12.5 µg/mL) of Ta-NPs can promote the proliferation of osteoblasts, while the Ta-NPs began to induce a decrease in cell viability at concentrations ≥25 µg/mL. Increased cell mortality, reactive oxygen species (ROS) production and decreased mitochondrial membrane potential (MMP) occurred in a dose-dependent manner after Ta-NP treatment. Moreover, with Ta-NP stimulation, the ratio of LC3-II/LC3-I increased, and the level of p62 protein was reduced. However, the degradation of p62 was not continuously increased when the concentration of Ta-NPs was ≥25 µg/mL. These results indicate that Ta-NPs induced osteoblast damage via oxidative stress. Autophagy activation may be a key factor in the cellular response to Ta-NP toxicity and could have an important impact on determining the survival or death of osteoblasts.
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Nanopartículas , Tantálio , Animais , Autofagia , Sobrevivência Celular , Camundongos , Osteoblastos , Estresse Oxidativo , Espécies Reativas de Oxigênio , Tantálio/toxicidadeRESUMO
The relationship between mechanical force and alveolar bone remodeling is an important issue in orthodontics because tooth movement is dependent on the response of bone tissue to the mechanical force induced by the appliances used. Mechanical cyclical stretch plays an essential role in the cell osteogenic differentiation involved in bone remodeling. However, the underlying mechanisms are unclear, particularly the molecular pathways regulated by mechanical stimulation. In the present study, we reported a dynamic change of p21 level in response to mechanical cyclical stretch, and shRNA-p21 in bone marrow mesenchymal stem cells (BMSCs) induced osteogenic differentiation. The mechanism was mediated through TWIST/E2A/p21 axis. These results supported the mechanical stimulation-induced osteogenic differentiation is negatively regulated by p21.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células da Medula Óssea/metabolismo , Diferenciação Celular , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Mecanotransdução Celular , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Proteína 1 Relacionada a Twist/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/genética , Regulação da Expressão Gênica , Masculino , Ratos Sprague-Dawley , Estresse Mecânico , Proteína 1 Relacionada a Twist/genéticaRESUMO
Background and Objective: Patients with psoriasis have a significantly elevated risk of periodontitis compared with the nonpsoriasis controls. However, the data regarding the difference in the periodontal health status of the psoriasis patients and the nonpsoriasis controls are limited and inconsistent; hence, a specialized meta-analysis that quantitatively compared the periodontal status between the psoriasis and nonpsoriasis subjects by evaluating the related clinical periodontal indexes was needed. The aim of this meta-analysis was to quantitatively evaluate whether the periodontal status of psoriasis patients is worse than that of nonpsoriasis subjects. Methods: We searched PubMed and EMBASE for all eligible studies that compared the periodontal status between psoriasis patients and nonpsoriasis subjects. The studies were screened based on pre-established inclusion criteria. After extracting the available periodontal indexes from the included studies, the weighted mean difference (WMD) with 95% confidence intervals (CIs) was calculated by pooling the mean and standard deviations (SD) of each index. Results: In total, 8 studies, including 812 psoriasis patients and 772 nonpsoriasis subjects, were included in our meta-analysis, and the publication dates ranged from 2013 to 2019; eight periodontal indexes were analyzed. The WMD (95% CIs) for each index were: bleeding on probing (%), 9.188 (4.046-14.330, P < 0.001); probing depth (mm), 0.524 (0.183-0.865, P = 0.003); clinical attachment loss (mm), 0.408 (0.051-0.765, P = 0.025); plaque index, 0.186 (-0.170 to 0.543, P = 0.306); gingival index, 0.458 (-0.413 to 1.328, P = 0.303), remaining teeth, -1.709 (-2.106 to -1.312, P < 0.001); missing teeth, 1.130 (0.275-1.985, P = 0.010); the level of alveolar bone loss (mm), 0.400 (0.102-0.698, P = 0.008). Conclusion: In summary, our meta-analysis revealed that psoriasis patients suffer from worse periodontal health than do nonpsoriasis subjects, mainly characterized by worse gingival inflammation, more alveolar bone loss, fewer remaining teeth and more missing teeth. Considering the limitations of this meta-analysis, more high-quality and well-designed studies are needed to validate our conclusions in the future.
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PURPOSE: Titanium implant is a widely used method for dental prosthesis restoration. Nevertheless, in patients with systemic diseases, including osteoporosis, diabetes, and cancer, the success rate of the implant is greatly reduced. This study investigates a new implant material loaded with insulin-like growth factor 1 (IGF1), which could potentially improve the implant success rate, accelerate the occurrence of osseointegration, and provide a new strategy for implant treatment in osteoporotic patients. MATERIALS AND METHODS: Biofunctionalized polyelectrolyte multilayers (PEMs) with polyethylenimine as the excitation layer and gelatin/chitosan loaded with IGF1 were prepared on the surface of titanium implant by layer-by-layer self-assembly technique. The physical and chemical properties of the biofunctionalized PEMs, the biological characteristics of bone marrow mesenchymal stem cells (BMMSCs), and bone implant contact correlation test indexes were detected and analyzed in vitro and in vivo using osteoporosis rat model. RESULTS: PEMs coatings loaded with IGF1 (TNS-PEM-IGF1-100) implant promoted the early stage of BMMSCs adhesion. Under the action of body fluids, the active coating showed sustained release of growth factors, which in turn promoted the proliferation and differentiation of BMMSCs and the extracellular matrix. At 8 weeks from implant surgery, the new bone around the implants was examined using micro-CT and acid fuchsin/methylene blue staining. The new bone formation increased with time in each group, while the TNS-PEM-IGF1-100 group showed the highest thickness and continuity. CONCLUSION: TNS-PEM-IGF1-100 new implants can promote osseointegration in osteoporotic conditions both in vivo and in vitro and provide a new strategy for implant repair in osteoporotic patients.
Assuntos
Fator de Crescimento Insulin-Like I/farmacologia , Osseointegração/efeitos dos fármacos , Osteoporose/fisiopatologia , Polieletrólitos/química , Próteses e Implantes , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Interface Osso-Implante , Quitosana/química , Materiais Revestidos Biocompatíveis/química , Materiais Dentários/química , Modelos Animais de Doenças , Feminino , Células-Tronco Mesenquimais/fisiologia , Ratos Sprague-Dawley , Titânio/químicaRESUMO
As an injectable scaffold material for bone tissue engineering, calcium phosphate cement (CPC) has good biocompatibility, self-setting, and osteoconduction properties. Alginate-microencapsulated seed cells can pick up the degradation speed and bioactivity of CPC. The aim of this study was to explore the osteogenic ability of a composite of microencapsulated rabbit bone marrow mesenchymal stem cells (rBMMSCs) with ß-tricalcium phosphate/calcium phosphate cement (ß-TCP/CPC) in vivo. Cavity defects were created in both femoral condylar regions of New Zealand White rabbits. ß-TCP/CPC (control group) and alginate microencapsulated rBMMSCs/ß-TCP/CPC composite (composite group) were implanted separately into the bone defects of both femurs. Bone substitute degradation and new bone formation were evaluated by CBCT, and the defects were examined histologically 8, 16, and 24 weeks after implantation. In addition, fluorescent carbocyanine CM-Dil was used to track the rBMMSCs in vivo after implantation. The results showed that far more new bone and bone marrow grew into the bone defects in the composite group. Few CM-Dil labeled positive cells were observed postoperatively. However more native cells were detected in the graft areas of the composite group than those of the control group. The study indicates that a composite of microencapsulated seed cells/ß-TCP/CPC might be considered as a promising injectable material for the generation of new bone tissue.