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1.
Genes Dev ; 34(17-18): 1161-1176, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32820036

RESUMO

Medulloblastoma is a malignant childhood brain tumor arising from the developing cerebellum. In Sonic Hedgehog (SHH) subgroup medulloblastoma, aberrant activation of SHH signaling causes increased proliferation of granule neuron progenitors (GNPs), and predisposes these cells to tumorigenesis. A second, cooperating genetic hit is often required to push these hyperplastic cells to malignancy and confer mutation-specific characteristics associated with oncogenic signaling. Somatic loss-of-function mutations of the transcriptional corepressor BCOR are recurrent and enriched in SHH medulloblastoma. To investigate BCOR as a putative tumor suppressor, we used a genetically engineered mouse model to delete exons 9/10 of Bcor (BcorΔE9-10 ) in GNPs during development. This mutation leads to reduced expression of C-terminally truncated BCOR (BCORΔE9-10). While BcorΔE9-10 alone did not promote tumorigenesis or affect GNP differentiation, BcorΔE9-10 combined with loss of the SHH receptor gene Ptch1 resulted in fully penetrant medulloblastomas. In Ptch1+/- ;BcorΔE9-10 tumors, the growth factor gene Igf2 was aberrantly up-regulated, and ectopic Igf2 overexpression was sufficient to drive tumorigenesis in Ptch1+/- GNPs. BCOR directly regulates Igf2, likely through the PRC1.1 complex; the repressive histone mark H2AK119Ub is decreased at the Igf2 promoter in Ptch1+/- ;BcorΔE9-10 tumors. Overall, our data suggests that BCOR-PRC1.1 disruption leads to Igf2 overexpression, which transforms preneoplastic cells to malignant tumors.


Assuntos
Neoplasias Cerebelares/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteínas Hedgehog/metabolismo , Meduloblastoma/genética , Proteínas do Grupo Polycomb/metabolismo , Proteínas Repressoras/genética , Animais , Carcinogênese/genética , Modelos Animais de Doenças , Proteínas Hedgehog/genética , Humanos , Camundongos , Mutação , Receptor Patched-1/genética , Proteínas do Grupo Polycomb/genética , Proteínas Repressoras/metabolismo , Deleção de Sequência
2.
J Aging Phys Act ; 32(1): 1-7, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37295783

RESUMO

We investigated the association between the cross-sectional area (CSA) of the gluteus medius muscle (GMM) and activities of daily living in patients with hip fractures. This retrospective cohort study comprised 111 patients aged ≥65 years who underwent hip fracture rehabilitation. The CSA of the GMM was measured using computed tomography scans in the early stages of hospitalization. The group with decreased CSA of the GMM had a median GMI ≤17 cm2/m2 for male patients and ≤16 cm2/m2 for female patients. Patients in the group with decreased CSA of the GMM had lower functional independence measure gains than those in the control group. After adjusting for confounders, we found that decreased CSA of the GMM was significantly associated with lower functional independence measure gains (ß: -0.432, p < .001). In patients with hip fractures, decreased CSA of the GMM was associated with decreased activities of daily living.


Assuntos
Atividades Cotidianas , Fraturas do Quadril , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Coxa da Perna
3.
Int J Mol Sci ; 25(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612630

RESUMO

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases, including oral cancer. Cancer cells usually escape from the immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα, in the tumor microenvironment of oral squamous cell carcinoma (OSCC), performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating to seven immune-related factors and several clinicopathological statuses. However, the immune checkpoint-related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that the keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference in tumor immunity in the originating epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC, might be different in the originating epithelium, keratinized or non-keratinized.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Antígeno B7-H1 , Antígeno CD47 , Receptor de Morte Celular Programada 1 , Estudos Retrospectivos , Epitélio , Microambiente Tumoral
4.
J Aging Phys Act ; 31(6): 965-971, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37343947

RESUMO

This study evaluated the relationship between the muscle mass of the gluteus medius (GM) and skeletal muscle mass index (SMI) measured in patients with hip fractures. In this study, 141 patients with hip fractures were divided into those with high or low SMI. The GM index (GMI) was calculated by dividing the GM by the square of the height in meters. The correlation between GMI and SMI was subsequently analyzed, and cutoff values for determining the loss of skeletal muscle mass were calculated using the receiver operating characteristic curve. GMI and SMI showed a positive correlation for both sexes (male: r = .890, female: r = .626, p < .001). The GMI cutoff values were 19.460 cm2/m2 for males and 17.850 cm2/m2 for females. Skeletal muscle mass evaluation of the GM could contribute to hip fracture recovery by improving mobility and facilitating the early diagnosis of loss of SMM.


Assuntos
Fraturas do Quadril , Músculo Esquelético , Humanos , Masculino , Feminino , Idoso , Músculo Esquelético/fisiologia , Coxa da Perna
5.
Cancer Sci ; 112(8): 2948-2957, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34050694

RESUMO

Medulloblastoma is the most common malignant cerebellar tumor in children. Recent technological advances in multilayered 'omics data analysis have revealed 4 molecular subgroups of medulloblastoma (Wingless/int, Sonic hedgehog, Group3, and Group4). (Epi)genomic and transcriptomic profiling on human primary medulloblastomas has shown distinct oncogenic drivers and cellular origin(s) across the subgroups. Despite tremendous efforts to identify the molecular signals driving tumorigenesis, few of the identified targets were druggable; therefore, a further understanding of the etiology of tumors is required to establish effective molecular-targeted therapies. Chromatin regulators are frequently mutated in medulloblastoma, prompting us to investigate epigenetic changes and the accompanying activation of oncogenic signaling during tumorigenesis. For this purpose, we have used germline and non-germline genetically engineered mice to model human medulloblastoma and to conduct useful, molecularly targeted, preclinical studies. This review discusses the biological implications of chromatin regulator mutations during medulloblastoma pathogenesis, based on recent in vivo animal studies.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Cerebelares/patologia , Epigênese Genética , Meduloblastoma/patologia , Animais , Neoplasias Cerebelares/genética , Cromatina/genética , Regulação Neoplásica da Expressão Gênica , Engenharia Genética , Humanos , Meduloblastoma/genética , Camundongos , Mutação
6.
Genes Cells ; 25(12): 796-810, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33020978

RESUMO

A proper balance between proliferation and differentiation of cerebellar granule cell precursors (GCPs) is required for appropriate cerebellar morphogenesis. The Skp1-Cullin1-F-box (SCF) complex, an E3 ubiquitin ligase complex, is involved in polyubiquitination and subsequent degradation of various cell cycle regulators and transcription factors. However, it remains unknown how the SCF complex affects proliferation and differentiation of GCPs. In this study, we found that the scaffold protein Cullin1, and F-box proteins Skp2, ß-TrCP1 and ß-TrCP2 are expressed in the external granule layer (EGL). Knockdown of these molecules in the EGL showed that Cullin1, Skp2 and ß-TrCP2 enhanced differentiation of GCPs. We also observed accumulation of cyclin-dependent kinase inhibitor p27 in GCPs when treated with a Cullin1 inhibitor or proteasome inhibitor. Furthermore, knockdown of p27 rescued enhancement of differentiation by Cullin1 knockdown. These results suggest that the SCF complex is involved in the maintenance of the proliferative state of GCPs through p27 degradation. In addition, inhibition of Cullin1 activity also prevented cell proliferation and enhanced accumulation of p27 in Daoy cells, a cell line derived from the sonic hedgehog subtype of medulloblastoma. This suggested that excess degradation of p27 through the SCF complex causes overproliferation of medulloblastoma cells.


Assuntos
Cerebelo/citologia , Células-Tronco Neurais/metabolismo , Neurogênese , Proteínas Quinases Associadas a Fase S/metabolismo , Proteínas Contendo Repetições de beta-Transducina/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Células Cultivadas , Cerebelo/metabolismo , Proteínas Culina/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos ICR , Células-Tronco Neurais/citologia , Proteínas Quinases Associadas a Fase S/genética , Ubiquitinação
7.
Invest New Drugs ; 39(3): 846-852, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33449240

RESUMO

A retrospective cohort study was performed to investigate the effectiveness of preemptive postsurgical therapy with cetuximab for patients with a major risk of recurrence or metastasis after clinical complete resection of primary oral squamous cell carcinoma (OSCC). The study period was from 2007 to 2019 for patients treated at the Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine. OSCC patients with major risk (n = 88) in the follow-up period were divided into groups with no postsurgical treatment (NP group), with standard postsurgical treatment (SP group), and with postsurgical treatment including cetuximab (CP group), and prognosis were compared among those groups. The 5-year overall survival rate was significantly higher in patients who received postsurgical treatment with cetuximab (CP) compared to that in the other two groups ((CP vs. NP, p = 0.028; CP vs. SP, p = 0.042). Furthermore, we performed multivariate analysis to evaluate the effects of the main components of the treatment. Among CDDP, radiotherapy, and cetuximab, only cetuximab significantly contributed to improved survival by univariate analysis (crude HR:0.228, 95%CI:0.05-0.968, p = 0.045). cetuximab also showed the same tendency in multivariate analysis, although p value did not reach significant level (Adjusted HR: 0.233, 95%CI: 0.053-1.028, p = 0.054). The results suggest that the postsurgical treatment with cetuximab as a preemptive postsurgical therapy after complete surgical resection of a visible tumor is considerably effective for OSCC patients with major risk, in other words, invisible dormant metastasis.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Terapia Combinada , Receptores ErbB/antagonistas & inibidores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Estudos Retrospectivos , Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Resultado do Tratamento
8.
Int J Mol Sci ; 22(20)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34681573

RESUMO

TSC-22 (TGF-ß stimulated clone-22) has been reported to induce differentiation, growth inhibition, and apoptosis in various cells. TSC-22 is a member of a family in which many proteins are produced from four different family genes. TSC-22 (corresponding to TSC22D1-2) is composed of 144 amino acids translated from a short variant mRNA of the TSC22D1 gene. In this study, we attempted to determine the intracellular localizations of the TSC22D1 family proteins (TSC22D1-1, TSC-22 (TSC22D1-2), and TSC22(86) (TSC22D1-3)) and identify the binding proteins for TSC22D1 family proteins by mass spectrometry. We determined that TSC22D1-1 was mostly localized in the nucleus, TSC-22 (TSC22D1-2) was localized in the cytoplasm, mainly in the mitochondria and translocated from the cytoplasm to the nucleus after DNA damage, and TSC22(86) (TSC22D1-3) was localized in both the cytoplasm and nucleus. We identified multiple candidates of binding proteins for TSC22D1 family proteins in in vitro pull-down assays and in vivo binding assays. Histone H1 bound to TSC-22 (TSC22D1-2) or TSC22(86) (TSC22D1-3) in the nucleus. Guanine nucleotide-binding protein-like 3 (GNL3), which is also known as nucleostemin, bound to TSC-22 (TSC22D1-2) in the nucleus. Further investigation of the interaction of the candidate binding proteins with TSC22D1 family proteins would clarify the biological roles of TSC22D1 family proteins in several cell systems.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Histonas/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Processamento Alternativo , Diferenciação Celular , Linhagem Celular , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Dano ao DNA , Células HEK293 , Humanos , Espectrometria de Massas , Mitocôndrias/metabolismo , Ligação Proteica , Mapas de Interação de Proteínas
9.
Biol Pharm Bull ; 41(9): 1480-1484, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30175783

RESUMO

Natural killer (NK) cells play an important role in tumor immunity and infection control. The natural cytotoxicity receptors (NCRs) NKp46, NKp44 and NKp30 are involved in the control of the activation of NK cells. Few reports have investigated the ligands of NCRs. We previously reported the NCRs binding affinity to heparin and glycosaminoglycans. We also showed that multimeric sialyl Lewis X-expressing transferrin, secreted by human hepatoma HepG2 cells, binds to NKp46 and NKp44, but not to NKp30. In this study, we investigated the binding between NCRs and glycolipids. The possible binding of glycolipids to NCRs was screened by microarray, using the recombinant extracellular domain of NKp46, NKp44 and NKp30 tagged with 6×His (rNKp46, rNKp44 and rNKp30). We found that rNKp44 binds to Globo-A. However, we did not detect the interaction between rNKp46 or rNKp30 and any of the glycolipids investigated. Direct binding assays supported the results of the microarray screening. Therefore, we concluded that Globo-A is a novel ligand for NKp44 but not NKp46 and NKp30, and showed differences in the ligand selectivity of NCRs.


Assuntos
Glicolipídeos/metabolismo , Receptores Desencadeadores da Citotoxicidade Natural/metabolismo , Linhagem Celular , Humanos , Ligantes , Análise em Microsséries , Proteínas Recombinantes/metabolismo
10.
Clin Nutr ESPEN ; 63: 378-383, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971405

RESUMO

BACKGROUND & AIMS: The extracellular water-to-total body water ratio (ECW/TBW) increases with age and after fractures. A high ECW/TBW may hinder improvements in physical function and skeletal muscle mass. However, the effects of ECW/TBW improvement have not been properly investigated. The aim of this study was to investigate the factors associated with ECW/TBW improvement in older adults with hip fractures. METHODS: This retrospective cohort study included 203 patients with hip fractures who were admitted to a convalescent rehabilitation ward. ECW/TBW and skeletal muscle mass index (SMI) were measured using bioelectrical impedance analysis. The patients were classified into two groups: those with an improvement in ECW/TBW (n = 123) and those without an improvement (n = 80). Decision tree analysis was performed to examine the factors associated with ECW/TBW improvement. As a secondary objective, a multiple regression analysis was performed to identify the factors associated with SMI gain. RESULTS: Decision tree analysis identified rehabilitation volume and protein intake as the first and second factors most significantly associated with an improvement in ECW/TBW, respectively. Multiple regression analysis showed that improved ECW/TBW (ß: 0.400, p < 0.001) was significantly associated with SMI gain. CONCLUSIONS: Rehabilitation volume and protein intake are clinically important for improving ECW/TBW in older adults with hip fractures.

11.
Ann Geriatr Med Res ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38952334

RESUMO

Background: Recent studies have reported an association between sarcopenia and depression symptoms. To date, no reports have investigated the association between sarcopenia and depression symptoms evaluated using the Geriatric Depression Screening Scale (GDS)-15 in patients with stroke. Therefore, this study aimed to investigate the association between sarcopenia and its components and the improvement of depression symptoms in patients with stroke admitted to a convalescent rehabilitation ward. Methods: Patients with stroke aged ≥65 years admitted to a convalescent rehabilitation ward were included in the study. Participants were categorized into sarcopenia and non-sarcopenia groups based on the 2019 Asian Working Group for Sarcopenia. Here, depression symptoms were evaluated using the GDS-15, in addition to demographic characteristics. This study's primary outcome was the GDS change from admission to discharge. Multiple regression analysis was performed to investigate the association between GDS change and sarcopenia and its components. Results: Overall, 118 participants were included, with a mean age of 78.7±8.1, and 58 (49%) were classified in the sarcopenia group. Multiple regression analysis showed that sarcopenia (ß: -0.283, 95% confidence interval [CI]: -1.140 to -0.283, p < 0.001) and handgrip strength (ß: -0.317, 95% CI: -0.162 to -0.014, p = 0.021) were independently associated with GDS change. Conclusion: Sarcopenia and handgrip strength were significantly associated with improved depression symptoms in patients with stroke admitted to a convalescent rehabilitation ward. However, further prospective studies should investigate the association between sarcopenia and depression symptoms in patients with stroke.

12.
Clin Nutr ESPEN ; 63: 508-514, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39053700

RESUMO

BACKGROUND & AIMS: Depression symptoms are both prevalent and associated with poor prognosis in patients with convalescent stroke. Therefore, the improvement of depression symptoms is important for patients with convalescent stroke. This study aimed to examine whether malnutrition diagnosed using the Global Leadership Initiative on Malnutrition (GLIM) criteria and its components are associated with improvements in depression symptoms in patients with stroke undergoing rehabilitation. METHODS: This was a retrospective cohort study of older adult patients with convalescent stroke. Inclusion criteria comprised patients aged ≥65 years experiencing their first occurrence of stroke and admitted for rehabilitation therapy. Patients were classified into either the malnutrition or normal nutrition groups based on the diagnosis of malnutrition using the GLIM criteria. The Geriatric Depression Screening Scale (GDS)-15 was used to evaluate depression symptoms. The primary outcome of the study was the change in depression symptoms, indicating a change in GDS score from admission to discharge. The association between malnutrition diagnosed using the GLIM criteria and change in depression symptoms was assessed using multiple regression analysis. Additionally, associations with the constructs of the GLIM criteria were investigated. RESULTS: The malnutrition group comprised 64 (45%) patients, with a mean age of 78.2 years; 77 (54%) and 66 (46%) were males and females, respectively. Multiple regression analysis showed that malnutrition, diagnosed using the GLIM criteria (ß: -0.306, p < 0.001), was independently associated with changes in depression symptoms. Moreover, the GLIM criterion component of reduced muscle mass (ß: -0.235, p < 0.001) demonstrated a negative association with a change in depression symptoms. CONCLUSION: Malnutrition and reduced muscle mass, diagnosed using the GLIM criteria in patients with stroke undergoing convalescent rehabilitation, were found to suppress the improvement of depression symptoms.

13.
Clin Nutr ESPEN ; 60: 11-16, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38479898

RESUMO

BACKGROUND & AIMS: This study aimed to investigate the association between trunk muscle mass and muscle quality, as evaluated by bioelectrical impedance analysis (BIA), and the ability to walk independently in patients with hip fractures. Cutoff values for quantitative and qualitative indicators of the trunk muscles were also calculated. METHODS: This study included 181 patients with hip fractures who were admitted to a convalescent rehabilitation ward. Trunk muscle mass and phase angle of the participants were evaluated on admission. The phase angle in this study was defined as the trunk muscle quality index (TMQI). Patients were classified into the independent (functional independence measure [FIM]-walk score ≥6; n = 101) and non-independent (FIM-walk score ≤5; n = 80) walking groups according to the FIM mobility scores at discharge. RESULTS: The independent group had a higher FIM gain than the non-independent group (37.0 ± 13.6 vs. 27.1 ± 13.5, p < 0.001). Logistic regression analysis showed that the trunk muscle mass index (TMI) and TMQI were associated with the ability to walk independently. Furthermore, cutoff values of TMI and TMQI for male and female to estimate the ability to walk independently were 6.5 kg/m2 and 5.7 kg/m2, and 4.5° and 3.4°, respectively. CONCLUSION: TMI and TMQI are related to the ability to walk independently in patients with hip fractures. These results suggest the importance of improving trunk muscle mass and muscle quality during rehabilitation of patients with hip fractures.


Assuntos
Atividades Cotidianas , Fraturas do Quadril , Humanos , Masculino , Feminino , Caminhada , Músculo Esquelético , Hospitalização
14.
Ophthalmol Glaucoma ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38823680

RESUMO

PURPOSE: To evaluate the agreement between 24-2 visual field (VF) test results obtained using the gaze analyzing perimeter (GAP; Findex) and the Humphrey field analyzer (HFA; Carl Zeiss Meditec). DESIGN: Cross-sectional study. PARTICIPANTS: Patients underwent HFA 24-2 for suspected or confirmed VF loss and were treated at the Kyoto University Hospital between December 2022 and July 2023. METHODS: Patients underwent consecutive VF tests on the same eye using HFA and GAP 24-2 tests. Bland-Altman analysis was used to compare GAP and HFA results. Examination points where the sensitivity measured using GAP was ≥ 10 dB higher than that measured using HFA were re-evaluated by referring back to the original gaze data; 2 ophthalmologists assessed whether the gaze moved linearly toward the new test target. MAIN OUTCOME MEASURES: Mean deviation (MD) and elapsed time on an individual basis and sensitivity on an examination point basis. RESULTS: Forty-seven eyes of 47 patients were analyzed. The correlation coefficient of the MD using HFA and GAP was 0.811 (95% confidence interval [CI]: 0.683-0.891). Bland-Altman analysis showed good agreement between HFA and GAP tests. The mean difference (95% limits of agreement) in MD between HFA and GAP results was -0.63 dB (-5.81 to 4.54 dB). Although no statistically significant differences were observed in the elapsed time (P = 0.99), measurements completed within 200 seconds were observed only in the GAP group (11 cases, 23.4%), who had significantly better HFA MD value than others (P = 0.001). On an examination point basis for sensitivity, the correlation coefficient between HFA and GAP was 0.691 (95% limits of agreement, 0.670-0.711). Original gaze data assessment revealed that the gaze moved linearly toward the new test target for 70.2% of the examination points with a sensitivity discrepancy. CONCLUSIONS: The results indicate that the GAP provides VF assessment outcomes comparable to those of the HFA. The GAP exhibited advantages in terms of testing time, particularly in patients with minimal VF impairment. Furthermore, the GAP records all eye movements, enabling the objective determination of VF abnormalities based on gaze patterns and facilitating easy posthoc verification. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

15.
Dev Cell ; 59(17): 2302-2319.e12, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-38834071

RESUMO

Normal cells coordinate proliferation and differentiation by precise tuning of gene expression based on the dynamic shifts of the epigenome throughout the developmental timeline. Although non-mutational epigenetic reprogramming is an emerging hallmark of cancer, the epigenomic shifts that occur during the transition from normal to malignant cells remain elusive. Here, we capture the epigenomic changes that occur during tumorigenesis in a prototypic embryonal brain tumor, medulloblastoma. By comparing the epigenomes of the different stages of transforming cells in mice, we identify nuclear factor I family of transcription factors, known to be cell fate determinants in development, as oncogenic regulators in the epigenomes of precancerous and cancerous cells. Furthermore, genetic and pharmacological inhibition of NFIB validated a crucial role of this transcription factor by disrupting the cancer epigenome in medulloblastoma. Thus, this study exemplifies how epigenomic changes contribute to tumorigenesis via non-mutational mechanisms involving developmental transcription factors.


Assuntos
Epigenoma , Meduloblastoma , Fatores de Transcrição NFI , Meduloblastoma/genética , Meduloblastoma/patologia , Meduloblastoma/metabolismo , Animais , Fatores de Transcrição NFI/metabolismo , Fatores de Transcrição NFI/genética , Camundongos , Humanos , Regulação Neoplásica da Expressão Gênica , Progressão da Doença , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Epigênese Genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Proliferação de Células/genética , Diferenciação Celular/genética
16.
J Med Ultrason (2001) ; 50(2): 237-243, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36961646

RESUMO

PURPOSE: Anterior knee pain (AKP) may occur after anterior cruciate ligament (ACL) reconstruction. The present study investigated the relationship between the change in infrapatellar fat pad (IFP) thickness assessed using ultrasonography (US) and AKP on squatting in patients after ACL reconstruction. METHODS: Patients were enrolled 3 months after ACL reconstruction using the bone-tendon-bone (BTB) technique. Subjects were divided into the AKP group (numerical rating scale [NRS] score ≥ 1) and control group (NRS score < 1) using a NRS of pain on squatting, and intergroup comparisons were performed. On US evaluation, measurement angles of the knee joint were 0° and 30° in the supine position. The IFP between the femoral intercondylar notch and patellar tendon was measured on short-axis images. The changes in IFP thickness were calculated from values measured at different angles of the knee joint. RESULTS: Twenty-one patients (mean age 24.9 ± 9.3 years) were included in the present study: 12 in the AKP group (9 males, 3 females) and nine in the control group (5 males, 4 females). A significant difference in the change in IFP thickness at 3 months was observed between the AKP and control groups (0.67 ± 0.44 mm vs. 1.84 ± 0.34 mm, p < 0.001). There was a negative correlation between the change in IFP thickness and the NRS score (r = - 0.720, p < 0.001) in reconstructed knees. CONCLUSION: A smaller change in IFP thickness assessed using US after ACL reconstruction was identified as a factor contributing to AKP on squatting.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Lesões do Ligamento Cruzado Anterior/cirurgia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Dor , Tecido Adiposo/diagnóstico por imagem , Ultrassonografia
17.
Nutrients ; 15(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37447315

RESUMO

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become pertinent problems. The prevalence of comorbidities is a major problem in countries with aged populations as elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. All of these diseases are associated with sarcopenia and frailty, and they frequently cause falls, fractures, and a decline in activities of daily living. Fractures in the elderly people are associated with bone fragility, which is influenced by diabetes and chronic kidney disease. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood glucose level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solve the health-related problems in super-aging societies.


Assuntos
Diabetes Mellitus , Fragilidade , Insuficiência Renal Crônica , Sarcopenia , Idoso , Humanos , Sarcopenia/epidemiologia , Sarcopenia/prevenção & controle , Sarcopenia/complicações , Fragilidade/epidemiologia , Fragilidade/prevenção & controle , Fragilidade/complicações , Idoso Fragilizado , Atividades Cotidianas , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações
18.
Prog Rehabil Med ; 8: 20230036, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37854311

RESUMO

Objectives: This study aimed to investigate the relationship between trunk muscle mass index (TMI), appendicular skeletal muscle mass index (ASMI), and walking independence in patients aged 65 years and older undergoing rehabilitation for hip fracture. Methods: This retrospective, observational study was conducted in a convalescent rehabilitation ward and included 314 patients (aged ≥65 years) with hip fracture. The patients were classified into the independence group [functional independence measure (FIM)-walk score ≥6] or the non-independence group (FIM-walk score ≤5) according to the mobility item score among the motor FIM items at the time of discharge. Age, sex, TMI, ASMI, and Mini Nutritional Assessment-Short Form (MNA-SF) data were also extracted. Between-group and multivariate analyses were performed to evaluate the factors associated with walking independence. Results: The independence group had higher TMI (males: 6.6±0.9 vs. 5.6±1.0 kg/m2, P <0.001; females: 6.1±0.8 vs. 5.7±1.0 kg/m2, P <0.001), ASMI (males: 6.7±1.1 vs. 5.9±1.3 kg/m2, P=0.004; females: 5.3±0.9 vs. 4.7±0.8 kg/m2, P <0.001), MMSE-J (21.5±4.9 vs. 16.4±4.5 points, P <0.001), and MNA-SF [median (interquartile range): 8 (6-9) vs. 7 (5-8) points, P <0.001] than the non-independence group. Multivariate analysis showed that TMI at admission was significantly associated with walking independence (odds ratio: 1.86, 95% confidence interval: 1.28-2.72, P <0.001). Conclusions: This study suggests that a higher TMI at admission was important for acquiring walking independence in patients with hip fracture and shows the importance of early evaluation of TMI during hospitalization of patients with hip fracture.

19.
J Int Med Res ; 51(3): 3000605231161223, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36942446

RESUMO

The main symptom in primary syphilis is a small, painless, sore or ulcer called a chancre on the penis, vagina, or around the anus, although chancres can sometimes appear in the mouth or on the lips, fingers, or buttocks. We present the case of a man in his early 60 s with a chief complaint of a painful tongue ulcer. An ulcerated, indurated, and hemorrhagic lesion (23 × 14 mm) was found on the ventral tongue surface, near the oral floor. Palpation identified several swollen, mobile, elastic cervical lymph nodes, with no tenderness. We initially diagnosed tongue cancer; however, during a subsequent detailed examination for a malignant tumor, including biopsy and obtaining additional history, his disease was finally identified as primary syphilis with multiple swollen cervical lymph nodes. Oral amoxicillin and probenecid were started, and after 14 days, there was partial reduction in the size of the submandibular lymph nodes and the ulcer on the left tongue margin. The number of patients with syphilis in Japan increased by eight times from 2012 to 2018. We suggest that dentists consider primary syphilis as a differential diagnosis for oral refractory ulcer with induration and obtain a detailed patient history.


Assuntos
Sífilis , Doenças da Língua , Neoplasias da Língua , Masculino , Feminino , Humanos , Neoplasias da Língua/diagnóstico , Neoplasias da Língua/patologia , Úlcera/diagnóstico , Úlcera/patologia , Sífilis/diagnóstico , Sífilis/patologia , Doenças da Língua/diagnóstico , Doenças da Língua/patologia , Língua/patologia
20.
Chem Commun (Camb) ; 59(72): 10801-10804, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37594189

RESUMO

A multi-component coordination compound, in which ruthenium antenna complexes are connected to a polyoxotungstate core is presented. This hybrid cluster effectively promotes the electrochemical conversion of CO2 to C1 feedstocks, the selectivity of which can be controlled by the acidity of the media.

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