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1.
Sci Rep ; 14(1): 11114, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750118

RESUMO

Oral bacteria are known to be associated with perioperative complications during hospitalization. However, no presented reports have clarified the relationship of oral bacterial number with medical costs for inpatients. The Diagnosis Procedure Combination (DPC) database system used in Japan provides clinical information regarding acute hospital patients. The present study was conducted to determine the association of oral bacterial numbers in individual patients treated at a single institution with length of hospital stay and medical costs using DPC data. A total of 2369 patients referred by the medical department to the dental department at Hiroshima University Hospital were divided into the low (n = 2060) and high (n = 309) oral bacterial number groups. Length of hospital stay and medical costs were compared between the groups, as well as the associations of number of oral bacteria with Charlson comorbidity index (CCI)-related diseases in regard to mortality and disease severity. There was no significant difference in hospital stay length between the low (24.3 ± 24.2 days) and high (22.8 ± 20.1 days) oral bacterial number groups. On the other hand, the daily hospital medical cost in the high group was significantly greater (US$1456.2 ± 1505.7 vs. US$1185.7 ± 1128.6, P < 0.001). Additionally, there was no significant difference in CCI score between the groups, whereas the daily hospital medical costs for patients in the high group treated for cardiovascular disease or malignant tumors were greater than in the low number group (P < 0.05). Multivariate regression analysis was also performed, which showed that oral bacterial number, age, gender, BMI, cardiovascular disease, diabetes, malignant tumor, and hospital stay length were independently associated with daily hospitalization costs. Monitoring and oral care treatment to lower the number of oral bacteria in patients affected by cardiovascular disease or cancer may contribute to reduce hospitalization costs.


Assuntos
Hospitalização , Tempo de Internação , Humanos , Feminino , Masculino , Japão/epidemiologia , Idoso , Tempo de Internação/economia , Pessoa de Meia-Idade , Hospitalização/economia , Boca/microbiologia , Bases de Dados Factuais , Idoso de 80 Anos ou mais , Custos Hospitalares , Carga Bacteriana , Bactérias/isolamento & purificação , Bactérias/classificação , Custos de Cuidados de Saúde , Adulto
2.
Oral Dis ; 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225462

RESUMO

OBJECTIVE: The objective of this study was to clarify the association between preoperative periodontitis and postoperative systemic inflammation in patients with gastric cancer. SUBJECTS AND METHODS: This retrospective cohort study analyzed data from 140 gastric cancer patients who underwent surgery at Hiroshima University Hospital between May 2019 and May 2022. Periodontal inflamed surface area (PISA) scores were determined to assess periodontitis severity using modified Nesse's methods. Propensity score matching was used to compare patients with high and low PISA scores (> or < the median PISA score of 92.4, respectively). Propensity scores were calculated using a logistic regression model, based on 17 clinical parameters: age, sex, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia, cardiovascular disease, stroke, clinical stage, surgical procedure, surgical approach, neoadjuvant chemotherapy, surgery duration, blood loss during surgery, remaining teeth, and denture use. RESULTS: Thirty-seven patients were propensity-score-matched. Participants with high PISA scores had a higher incidence of surgical site infection (10.5%) than those with low PISA scores (5.3%). Moreover, participants with high PISA scores had significantly higher C-reactive protein levels on postoperative days 1 than those with low PISA scores. CONCLUSION: Preoperative periodontitis may determine the level of postoperative systemic inflammation in patients with gastric cancer.

3.
Am J Med ; 137(3): 273-279.e2, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37984772

RESUMO

BACKGROUND: We determined the effects and an accurate marker of periodontal treatment on serum interleukin (IL)-6 and high-sensitivity C-reactive protein (HsCRP) levels in systemically healthy individuals with periodontal disease. METHODS: This multicenter study included systemically healthy individuals with periodontal disease who received initial periodontal treatment and had no periodontal treatment history. Periodontal parameters, including periodontal inflamed surface area, masticatory efficiency, and periodontal disease classification; serum IL-6 and HsCRP levels; and serum immunoglobulin (Ig)G titers against periodontal pathogens were evaluated at baseline and after treatment. Subjects were classified as low or high responders (group) based on periodontal inflamed surface area changes. RESULTS: There were 153 participants. Only periodontal inflamed surface area changes were markedly different between low and high responders. Periodontal treatment (time point) decreased both serum IL-6 and HsCRP levels. The interaction between group and time point was remarkable only for serum IL-6 levels. Changes in serum immunoglobulin (Ig)G titers against periodontal pathogens were not associated with IL-6 changes in high responders. We analyzed the indirect effect of serum anti-Porphyromonas gingivalis type 2 IgG titer changes using mediation analysis and found no significance. However, the direct effect of group (low or high responder) on IL-6 changes was considerable. CONCLUSIONS: Periodontal treatment effectively decreased serum IL-6 levels, independent of periodontal pathogen infection, in systemically healthy individuals with periodontal disease.


Assuntos
Proteína C-Reativa , Doenças Periodontais , Humanos , Proteína C-Reativa/análise , Interleucina-6 , Inflamação , Doenças Periodontais/terapia , Imunoglobulinas
4.
J Pediatr Hematol Oncol ; 46(2): e176-e179, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38132703

RESUMO

Noonan syndrome-related myeloproliferative disorder (NS/MPD) and juvenile myelomonocytic leukemia (JMML) are rare MPDs that occur in young children. We herein report a case of NS/MPD with neonatal onset. The patient had a characteristic appearance and high monocyte count in the peripheral blood and bone marrow. Genetic testing showed the E139D mutation in PTPN11 ; however, the patient did not meet all the diagnostic criteria for JMML, and we thus diagnosed him with NS/MPD. Eight other cases of NS/MPD with neonatal onset are also summarized. The initial presentation varied, and the prognosis was considered poor compared with previous reports of NS/MPD.


Assuntos
Leucemia Mielomonocítica Juvenil , Transtornos Mieloproliferativos , Síndrome de Noonan , Humanos , Recém-Nascido , Masculino , Leucemia Mielomonocítica Juvenil/complicações , Leucemia Mielomonocítica Juvenil/diagnóstico , Leucemia Mielomonocítica Juvenil/genética , Mutação , Transtornos Mieloproliferativos/complicações , Transtornos Mieloproliferativos/genética , Síndrome de Noonan/complicações , Síndrome de Noonan/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética
5.
J Pers Med ; 13(11)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38003918

RESUMO

Oral mucositis significantly affects the quality of life in hematologic cancer patients undergoing hematopoietic stem cell transplantation. Despite global evidence supporting the efficacy of low-level laser therapy (LLLT) for mucositis prevention, its clinical adoption in Japan is limited. This study aimed to fill this gap by evaluating the safety and efficacy of LLLT in a Japanese patient population. In a single-group, non-blinded, exploratory trial, we compared 21 LLLT-treated patients against a historical control of 96 patients. The primary endpoint was the incidence of Grade ≥ 2 mucositis, based on NCI-CTCAE ver. 4.0. The LLLT group showed a significantly lower incidence of Grade ≥ 2 mucositis (23.8%) compared to the control group (64.6%) (p = 0.0006). Furthermore, Grade ≥ 2 mucositis correlated with increased oral dryness and longer hospital stays. Our study confirms the efficacy of LLLT in reducing the onset of severe oral mucositis among Japanese hematologic cancer patients, advocating for its clinical introduction as a preventive measure in Japan.

6.
Support Care Cancer ; 31(9): 552, 2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37658917

RESUMO

PURPOSE: Chemotherapy-induced taste alteration is a side effect that can result in malnutrition and reduced quality of life in cancer patients. However, the underlying causes of this phenomenon remain unclear, and evidence-based treatments have not been established. This study focused on patients' subjective symptoms of taste alterations aimed to explore how the sensitivity to basic tastes changes due to anticancer agents and how alterations in one taste perception are associated with changes in other tastes during chemotherapy. METHODS: A cross-sectional questionnaire-based interview survey was conducted on 215 patients undergoing chemotherapy. The subjective sensitivity to each basic taste was assessed using a visual analog scale, and the incidence of taste alterations due to different chemotherapy regimens was calculated. Multivariate logistic regression analysis was performed to determine whether there were associations between changes in one taste sensitivity and changes in other taste sensitivities. RESULTS: Approximately half (49.5%) of the patients experienced chemotherapy-induced taste alterations. An analysis of subjective changes in basic tastes revealed that the salt and umami taste systems were more sensitive to chemotherapy than other taste systems. Patients with altered sensitivity to sweet taste were significantly more likely to report altered sensitivity to salt, bitter, and sour tastes. Moreover, umami-salt and bitter-sour taste sensitivities were significantly related to each other. CONCLUSION: This study suggests that changes in subjective sensitivities to one basic taste during chemotherapy may be accompanied by changes in other tastes in specific combinations. Considering taste associations in dietary guidance may help improve the nutritional status of cancer patients experiencing taste alterations due to chemotherapy.


Assuntos
Antineoplásicos , Disgeusia , Neoplasias , Percepção Gustatória , Inquéritos e Questionários , Disgeusia/induzido quimicamente , Estudos Transversais , Neoplasias/tratamento farmacológico , Antineoplásicos/efeitos adversos , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
7.
BMC Oral Health ; 23(1): 647, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37674208

RESUMO

PURPOSE: Several studies have found associations between periodontitis and various types of cancer. Since the site of head and neck cancer (HNC) has contiguity or proximity to the oral cavity, it may be particularly influenced by oral inflammation. This study aimed to determine whether HNC patients have poor oral health as compared to those with other types of cancer. METHODS: This study retrospectively examined oral environmental factors including periodontal inflamed surface area (PISA), a new periodontal inflammatory parameter. A total of 1030 cancer patients were divided into the HNC (n = 142) and other cancer (n = 888) groups. Furthermore, the HNC group was divided into high (n = 71) and low (n = 71) PISA subgroups, and independent risk factors affecting a high PISA value were investigated. RESULTS: Multivariate logistic regression analysis showed that number of missing teeth (odds ratio 1.72, 95% CI 1.15-2.56, P < 0.01), PISA (odds ratio 1.06, 95% CI 1.03-1.06, P < 0.05), and oral bacterial count (odds ratio 1.02, 95% CI 1.01-1.03, P < 0.01) were independent factors related to HNC. In addition, multivariate logistic regression analysis indicated that current smoker (odds ratio 7.51, 95% CI 1.63-34.71, P < 0.01) and presence of untreated dental caries (odds ratio 3.33, 95% CI 1.23-9.00, P < 0.05) were independent risk factors affecting high PISA values in HNC patients. CONCLUSION: HNC patients have higher levels of gingival inflammation and poor oral health as compared to patients with other types of cancer, indicating that prompt oral assessment and an effective oral hygiene management plan are needed at the time of HNC diagnosis.


Assuntos
Cárie Dentária , Neoplasias de Cabeça e Pescoço , Humanos , Saúde Bucal , Cárie Dentária/complicações , Cárie Dentária/epidemiologia , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/complicações , Inflamação
8.
Physiol Behav ; 267: 114224, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37148986

RESUMO

OBJECTIVES: The causes of hypogeusia include zinc deficiency, systemic illness, and consumption of drugs. Notably, patients with oral cavity diseases such as oral candidiasis and salivary gland hypofunction may present with risk factors that remain unreported. Hence, this study aimed to investigate the relationship between age, sex, smoking status, serum zinc concentration, oral candidiasis, saliva volume, and taste function in patients with hypogeusia. SUBJECTS AND METHODS: Overall, 335 participants who complained of taste abnormalities underwent a taste test. Based on the recognition threshold value, the participants were classified as normal individuals (recognition threshold of 1 and 2) and patients with hypogeusia (recognition threshold of ≥3). The clinical characteristics, including resting saliva volume (RSV) and stimulated saliva volume (SSV), were compared, and a multivariate logistic regression analysis focusing on RSV was performed. RESULTS: Patients with hypogeusia had a lower RSV than normal individuals for all tastes, but not for SSV. Based on the results of regression analysis, RSV was identified as an independent predictor of hypogeusia for salty and bitter tastes. Moreover, the proportion of patients with decreased RSV increased as the number of taste qualities exceeding the reference recognition threshold increased. Furthermore, a decrease in RSV was associated with an increase in the recognition threshold for salty and bitter tastes. CONCLUSIONS: Based on the results of the present study, moisturizing the oral cavity may be useful against hypogeusia.


Assuntos
Ageusia , Candidíase Bucal , Humanos , Ageusia/etiologia , Saliva , Estudos Retrospectivos , Candidíase Bucal/complicações , Paladar , Fatores de Risco , Zinco , Limiar Gustativo
9.
Pediatr Nephrol ; 38(8): 2873-2876, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36451038

RESUMO

BACKGROUND: Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by thrombocytopenia and eczema and is caused by a mutation in the WAS gene. WAS has heterogeneous clinical manifestations, and its clinically milder form is called X-linked thrombocytopenia (XLT). Patients with WAS/XLT sometimes have kidney complications, the most common of which is immunoglobulin (Ig)A nephropathy associated with aberrant glycosylation of IgA. CASE DIAGNOSIS/TREATMENT: The patient was a 6-year-old girl who was diagnosed with female XLT at the age of 4 years; she presented with microscopic hematuria and proteinuria at a school urinalysis. Her father had thrombocytopenia and IgA nephropathy while in his 20 s. The patient and her father had the same WAS gene mutations. A kidney biopsy was performed, and no abnormal findings were observed by light microscopy. Immunofluorescence analysis revealed a granular pattern of IgG staining along the capillary wall. Electron microscopy revealed small electron-dense deposits in subepithelial lesions. Consequently, we diagnosed her with membranous nephropathy (MN). Tissue PLA2R and THSD7A were negative, and she was judged unlikely to have secondary MN on the basis of blood test findings and IgG staining. We started the administration of angiotensin-converting enzyme inhibitors, and her proteinuria gradually decreased. CONCLUSION: To our knowledge, this is the first report of MN in a female WAS/XLT patient. WAS protein expression defects affect all immune system cells; however, the mechanisms underlying the occurrence of autoimmunity are not completely understood. In WAS/XLT patients, MN may develop as a result of increased autoantibody production, similar to other types of immunodeficiency.


Assuntos
Glomerulonefrite por IGA , Glomerulonefrite Membranosa , Trombocitopenia , Síndrome de Wiskott-Aldrich , Humanos , Feminino , Pré-Escolar , Criança , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/genética , Síndrome de Wiskott-Aldrich/complicações , Síndrome de Wiskott-Aldrich/genética , Glomerulonefrite por IGA/complicações , Proteinúria/genética , Proteinúria/complicações , Imunoglobulina G
10.
Breast Cancer ; 30(1): 151-155, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36271187

RESUMO

PURPOSE: Oral hygiene is crucial in the management of oral and febrile complications during chemotherapy for cancer. This study aimed to investigate the impact of oral hygiene on the incidence of febrile neutropenia (FN) throughout the course of chemotherapy for breast cancer. METHODS: A total of 137 patients with breast cancer who underwent four cycles of adjuvant chemotherapy with docetaxel and cyclophosphamide (TC) combination therapy or docetaxel alone were assessed for oral hygiene by quantifying the number of oral bacteria they harbored. These patients received professional oral health care (POHC). Eighteen patients underwent primary prophylaxis with granulocyte colony-stimulating factors. The relationship between oral bacteria count and FN incidence was retrospectively assessed. RESULTS: The FN incidence rate was 47.4% throughout all treatment cycles (32.8%, 13.5%, 14.3%, and 14.4% in cycles 1, 2, 3, and 4, respectively). The oral bacteria count decreased with each treatment cycle (cycle 1: 9.10 × 106 colony-forming units (CFU)/mL, cycle 2: 5.89 × 106 CFU/mL, cycle 3: 4.61 × 106 CFU/mL, cycle 4: 5.85 × 106 CFU/mL, P = 0.004). Among 281 treatment cycles, FN occurred in 63 (22.4%). In the treatment cycle-based analysis, high oral bacteria count was an independent risk factor for FN. CONCLUSION: FN incidence decreased with each treatment cycle and was associated with changes in oral bacteria counts. The oral bacterial count was one of risk factors for FN development in breast cancer.


Assuntos
Neoplasias da Mama , Neutropenia Febril , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/etiologia , Docetaxel/uso terapêutico , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/epidemiologia , Neutropenia Febril/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Higiene Bucal , Estudos Retrospectivos
11.
Sci Rep ; 12(1): 2483, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35169215

RESUMO

Febrile neutropenia (FN) is an infectious complication that develops during chemotherapy. Although the oral cavity can be an important infection route, it is unknown whether the oral environment is associated with FN. The present study examined the relationship between the oral environment using periodontal inflamed surface area (PISA), a new periodontal disease parameter, and FN in hematologic cancer patients undergoing chemotherapy. In this retrospective cohort study, 157 patients were divided into FN onset during chemotherapy (n = 75) and the FN negative groups (n = 82). The associations of risk factors related to the intraoral environment were assessed. Logistic regression analysis showed that types of blood cancer (odds ratio 1.98; P < 0.01), use of a high-risk regimen (odds ratio 4.44; P < 0.05), prophylaxis treatment with human granulocyte colony-stimulating factor (G-CSF) (odds ratio 4.15; P < 0.01) and PISA (odds ratio 1.02; P < 0.01) were independent factors associated with FN onset. Finally, propensity score matching was performed between two groups; 37 matched pairs were generated. PISA was significantly higher in the FN group than the FN negative group. There was a significant relationship between PISA and FN onset (P = 0.035). The present findings indicate that periodontitis treatment before starting cancer treatment is recommended as supportive care for preventing FN onset during chemotherapy.


Assuntos
Neutropenia Febril Induzida por Quimioterapia/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Neoplasias Hematológicas/tratamento farmacológico , Boca , Periodontite/etiologia , Idoso , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Periodontite/prevenção & controle , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco
12.
Mol Clin Oncol ; 15(3): 177, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34276996

RESUMO

Almost a quarter of a century has passed since the term sarcopenia was defined. Sarcopenia is recognized as a poor prognostic factor in a variety of cancer types. In ovarian cancer, it remains controversial whether sarcopenia affects prognosis and how it should be evaluated. The present study aimed to evaluate the association between the volume of the psoas major muscle and survival in patients with epithelial ovarian cancer. Medical charts of patients with epithelial ovarian cancer who received first-line chemotherapy with paclitaxel and carboplatin at the National Defense Medical College Hospital (Tokorozawa, Japan) between April 2010 and January 2015 were retrospectively reviewed. The bilateral psoas major muscle areas at the fifth lumbar vertebra were measured using computed tomography images. The Institutional Review Board at National Defense Medical College Hospital (Tokorozawa, Japan) approved the study protocol. A total of 72 patients with epithelial ovarian cancer who received combination therapy with paclitaxel and carboplatin were identified and enrolled. The median psoas muscle index (PMI; psoas muscle major cross-sectional area divided by height squared) was 5.4 cm2/m2 (range, 3.3-10.0). Patients with higher PMI had significantly improved overall survival (OS) compared with those with lower PMI [log-rank test P=0.014; hazard ratio (HR), 2.61; 95% confidence interval (CI), 1.21-6.06]. Multivariate analysis for OS revealed that lower PMI was an independent unfavorable prognostic factor (HR, 3.87; 95% CI, 1.37-12.1; P=0.0098). The volume of psoas major muscle mass could be a potential biomarker for prognosis in patients with epithelial ovarian cancer.

13.
Leuk Res ; 105: 106570, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33838549

RESUMO

Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome, which spontaneously resolves within several weeks or months after birth, may represent a special form of leukemia developing in the fetal liver (FL). To explore the role of hepatoblasts, one of the major constituents of the FL hematopoietic microenvironment, in the pathogenesis of TAM, we investigated the influence of a human hepatoblastoma cell line, HUH-6, on the in vitro growth and differentiation of TAM blasts. In a coculture system with membrane filters, which hinders cell-to-cell contact between TAM blasts and HUH-6 cells, the growth and megakaryocytic differentiation of TAM blast progenitors were increased in the presence of HUH-6 cells. The culture supernatant of HUH-6 cells contained hematopoietic growth factors, including stem cell factor (SCF) and thrombopoietin (TPO). The neutralizing antibody against SCF abrogated the growth-stimulating activity of the culture supernatant of HUH-6 cells, demonstrating that, among the growth factors produced by HUH-6 cells, SCF may be the major growth stimulator and that TPO may be involved in megakaryocytic differentiation, rather than growth, of TAM blasts. This suggests that hepatoblasts function in the regulation of the growth and differentiation of TAM blasts in the FL through the production of hematopoietic growth factors, including SCF and TPO, and are involved in the leukemogenesis of TAM.


Assuntos
Síndrome de Down/patologia , Hepatoblastoma , Hepatócitos , Reação Leucemoide/patologia , Células Progenitoras de Megacariócitos , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Técnicas de Cocultura , Hepatoblastoma/metabolismo , Hepatoblastoma/patologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Leucemia Megacarioblástica Aguda/patologia , Células Progenitoras de Megacariócitos/metabolismo , Células Progenitoras de Megacariócitos/patologia , Mielopoese/fisiologia , Células-Tronco/metabolismo , Células-Tronco/patologia
14.
Oral Dis ; 27(6): 1542-1550, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33067895

RESUMO

OBJECTIVE: Whether oral health care during the perioperative period can lead to a better outcome after heart valve surgery has not been adequately elucidated. We examined the effects of perioperative oral care on postoperative inflammation response in patients who underwent heart valve surgery. MATERIALS AND METHODS: In this retrospective cohort study, 223 patients scheduled for single valve heart surgery were divided into the oral care, who underwent professional teeth cleaning or scaling within 3 days prior to surgery, and also following surgery at least twice a week (n = 111), and non-oral care (n = 112) groups. After propensity score matching, records of both groups (80:80) were examined after surgery to evaluate inflammation markers (white blood cell count [WBC], neutrophil/white blood cell ratio [NWR], C-reactive protein [CRP] level, body temperature [BT]). RESULTS: WBC, NWR, CRP level, and BT were increased in both groups the day following surgery. Thereafter, CRP level, WBC, NWR, and BT on various days after surgery in the oral care group showed greater decreases as compared to the non-oral care group. CONCLUSIONS: Perioperative oral health care can decrease postoperative inflammation in patients undergoing heart valve surgery and may be important to ensure a better outcome in those patients.


Assuntos
Proteína C-Reativa , Procedimentos Cirúrgicos Cardíacos , Proteína C-Reativa/análise , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Valvas Cardíacas/química , Valvas Cardíacas/cirurgia , Humanos , Inflamação/etiologia , Contagem de Leucócitos , Estudos Retrospectivos
15.
J Clin Invest ; 130(6): 2827-2844, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32338640

RESUMO

Inherited bone marrow failure syndromes (IBMFSs) are a heterogeneous group of disorders characterized by defective hematopoiesis, impaired stem cell function, and cancer susceptibility. Diagnosis of IBMFS presents a major challenge due to the large variety of associated phenotypes, and novel, clinically relevant biomarkers are urgently needed. Our study identified nuclear interaction partner of ALK (NIPA) as an IBMFS gene, as it is significantly downregulated in a distinct subset of myelodysplastic syndrome-type (MDS-type) refractory cytopenia in children. Mechanistically, we showed that NIPA is major player in the Fanconi anemia (FA) pathway, which binds FANCD2 and regulates its nuclear abundance, making it essential for a functional DNA repair/FA/BRCA pathway. In a knockout mouse model, Nipa deficiency led to major cell-intrinsic defects, including a premature aging phenotype, with accumulation of DNA damage in hematopoietic stem cells (HSCs). Induction of replication stress triggered a reduction in and functional decline of murine HSCs, resulting in complete bone marrow failure and death of the knockout mice with 100% penetrance. Taken together, the results of our study add NIPA to the short list of FA-associated proteins, thereby highlighting its potential as a diagnostic marker and/or possible target in diseases characterized by hematopoietic failure.


Assuntos
Síndrome Congênita de Insuficiência da Medula Óssea , Proteína do Grupo de Complementação D2 da Anemia de Fanconi , Células-Tronco Hematopoéticas/metabolismo , Proteínas Nucleares , Animais , Síndrome Congênita de Insuficiência da Medula Óssea/genética , Síndrome Congênita de Insuficiência da Medula Óssea/metabolismo , Síndrome Congênita de Insuficiência da Medula Óssea/patologia , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genética , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Células-Tronco Hematopoéticas/patologia , Camundongos , Camundongos Knockout , Proteínas Nucleares/deficiência , Proteínas Nucleares/metabolismo , Ligação Proteica
16.
Biochem Biophys Res Commun ; 525(4): 889-894, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171527

RESUMO

A sophisticated and delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts regulates bone metabolism. Optineurin (OPTN) is a gene involved in primary open-angle glaucoma and amyotrophic lateral sclerosis. Although its function has been widely studied in ophthalmology and neurology, recent reports have shown its possible involvement in bone metabolism through negative regulation of osteoclast differentiation. However, little is known about the role of OPTN in osteoblast function. Here, we demonstrated that OPTN controls not only osteoclast but also osteoblast differentiation. Different parameters involved in osteoblastogenesis and osteoclastogenesis were assessed in Optn-/- mice. The results showed that osteoblasts from Optn-/- mice had impaired alkaline phosphatase activity, defective mineralized nodules, and inability to support osteoclast differentiation. Moreover, OPTN could bind to signal transducer and activator of transcription 1 (STAT1) and regulate runt-related transcription factor 2 (RUNX2) nuclear localization by modulating STAT1 levels in osteoblasts. These data suggest that OPTN is involved in bone metabolism not only by regulating osteoclast function but also by regulating osteoblast function by mediating RUNX2 nuclear translocation via STAT1.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Osteoblastos/citologia , Osteogênese/fisiologia , Fator de Transcrição STAT1/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Diferenciação Celular/fisiologia , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Proteínas de Membrana Transportadoras/genética , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Osteoclastos/citologia , Osteoclastos/metabolismo
17.
J Bone Miner Metab ; 38(4): 442-455, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31970478

RESUMO

INTRODUCTION: Mesenchymal stem cells (MSCs) can differentiate into various types of cells and can thus be used for periodontal regenerative therapy. However, the mechanism of differentiation is still unclear. Transplanted MSCs are, via their transcription factors or microRNAs (miRNAs), affected by periodontal cells with direct contact or secretion of humoral factors. Therefore, transplanted MSCs are regulated by humoral factors from human gingival fibroblasts (HGF). Moreover, insulin-like growth factor (IGF)-1 is secreted from HGF and regulates periodontal regeneration. To clarify the regulatory mechanism for MSC differentiation by humoral factors from HGF, we identified key genes, specifically miRNAs, involved in this process, and determined their function in MSC differentiation. MATERIALS AND METHODS: Mesenchymal stem cells were indirectly co-cultured with HGF in osteogenic or growth conditions and then evaluated for osteogenesis, undifferentiated MSC markers, and characteristic miRNAs. MSCs had their miRNA expression levels adjusted or were challenged with IGF-1 during osteogenesis, or both of which were performed, and then, MSCs were evaluated for osteogenesis or undifferentiated MSC markers. RESULTS: Mesenchymal stem cells co-cultured with HGF showed suppression of osteogenesis and characteristic expression of ETV1, an undifferentiated MSC marker, as well as miR-101-3p. Over-expression of miR-101-3p regulated osteogenesis and ETV1 expression as well as indirect co-culture with HGF. IGF-1 induced miR-101-3p and ETV1 expression. However, IGF-1 did not suppress osteogenesis. CONCLUSIONS: Humoral factors from HGF suppressed osteogenesis in MSCs. The effect was regulated by miRNAs and undifferentiated MSC markers. miR-101-3p and ETV1 were the key factors and were regulated by IGF-1.


Assuntos
Fibroblastos/metabolismo , Gengiva/citologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Osteogênese/genética , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Humanos , Fator de Crescimento Insulin-Like I/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , MicroRNAs/genética , Osteogênese/efeitos dos fármacos , Fatores de Transcrição/metabolismo
20.
J Periodontol ; 86(3): 456-64, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25494830

RESUMO

BACKGROUND: The purpose of this study is to evaluate whether ß-tricalcium phosphate (ß-TCP) could be a promising modality to help augment alveolar bone in periodontal tissue regeneration by bone marrow mesenchymal stem cells (BMMSCs). METHODS: Expanded BMMSCs and atelocollagen (Col) were mixed together (MSC/Col). A combination of ß-TCP with MSC/Col was also prepared (MSC/Col/TCP). MSC/Col/TCP or MSC/Col was transplanted into experimental periodontal Class III furcation defects that had been exposed to inflammation in beagle dogs. Periodontal tissue regeneration was evaluated by histologic and morphometric analyses at 4 and 8 weeks after transplantation. RESULTS: MSC/Col and MSC/Col/TCP enhanced periodontal tissue regeneration compared to Col and TCP/Col according to hematoxylin and eosin staining. The percentage of new cementum length in the MSC/Col/TCP group was not significantly different from that in the MSC/Col group at 4 and 8 weeks. On the other hand, the percentage of new bone area in the MSC/Col/TCP group was much higher than that in the MSC/TCP group at 4 weeks. However, at 8 weeks, no significant difference in new bone area was found between the two groups. In the MSC/Col/TCP group, ß-TCP was surrounded by newly formed bone. Multinucleated cells, which were positive for osteopontin and tartrate-resistant acid phosphatase, were present in the interconnected macropores of ß-TCP. CONCLUSION: These findings suggest that ß-TCP is applicable as a scaffold for BMMSCs transplantation and helps augment alveolar bone without impairing regeneration of cementum.


Assuntos
Processo Alveolar/patologia , Fosfatos de Cálcio/uso terapêutico , Cementogênese/fisiologia , Colágeno Tipo I , Regeneração Tecidual Guiada Periodontal/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Alicerces Teciduais , Fosfatase Ácida/análise , Animais , Regeneração Óssea/fisiologia , Técnicas de Cultura de Células , Colágeno/química , Colágeno Tipo I/química , Cemento Dentário/patologia , Modelos Animais de Doenças , Cães , Feminino , Defeitos da Furca/cirurgia , Células Gigantes/patologia , Isoenzimas/análise , Tamanho do Órgão , Osteogênese/fisiologia , Osteopontina/análise , Fosfatase Ácida Resistente a Tartarato , Alicerces Teciduais/química , Anquilose Dental/patologia , Raiz Dentária/patologia
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