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1.
J Gen Intern Med ; 39(6): 960-968, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38277022

RESUMO

BACKGROUND: Empathy with patients improves clinical outcomes. Although previous studies have shown no significant differences in empathy levels between physicians and nurses, investigations have not considered differences in cultural backgrounds and related factors of healthcare providers at the individual level. OBJECTIVE: This study compares empathy between physicians and nurses in Japan and identifies relevant factors that contribute to these differences. DESIGN: A cross-sectional survey design was used in the study. The online survey was conducted using the Nikkei Medical Online website. PARTICIPANTS: A total of 5441 physicians and 965 nurses in Japan who were registered as members of Nikkei Medical Online were included. MAIN MEASURES: Empathy was measured by the Jefferson Scale of Empathy (JSE). KEY RESULTS: Cronbach's α was 0.89. The mean JSE score for Japanese physicians was significantly lower at 100.05 (SD = 15.75) than the mean score of 110.63 (SD = 12.25) for nurses (p<0.001). In related factors, higher age (increasing by one year) (+0.29; 95% CI 0.25 to 0.32; p<0.001), self-identified female gender (+5.45; 95% CI 4.40 to 6.49; p<0.001), having children (+1.20; 95% CI 0.30 to 2.10; p=0.009), and working at a hospital with 20-99 beds (+1.73; 95% CI 0.03 to 3.43; p=0.046) were significantly associated with higher scores, whereas those whose mother is a physician (-6.65; 95% CI -8.82 to -4.47; p<0.001) and father is a nurse (-9.53; 95% CI -16.54 to -2.52; p=0.008) or co-medical professional (-3.85; 95% CI -5.49 to -2.21; p<0.001) were significantly associated with lower scores. CONCLUSIONS: Physicians had significantly lower scores on the JSE than nurses in Japan. Higher age, self-identified female gender, having children, working at a small hospital, having a mother who is a physician, and having a father who is a nurse or co-medical professional were factors associated with the level of empathy.


Assuntos
Empatia , Enfermeiras e Enfermeiros , Médicos , Humanos , Estudos Transversais , Feminino , Masculino , Japão , Adulto , Pessoa de Meia-Idade , Médicos/psicologia , Enfermeiras e Enfermeiros/psicologia , Inquéritos e Questionários , Atitude do Pessoal de Saúde , Relações Médico-Paciente
2.
Int Immunol ; 35(7): 303-312, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-36719100

RESUMO

Dupuytren's contracture (DC) is an inflammatory fibrosis characterized by fibroproliferative disorders of the palmar aponeurosis, for which there is no effective treatment. Although several genome-wide association studies have identified risk alleles associated with DC, the functional linkage between these alleles and the pathogenesis remains elusive. We here focused on two single nucleotide polymorphisms (SNPs) associated with DC, rs16879765 and rs17171229, in secreted frizzled related protein 4 (SFRP4). We investigated the association of SRFP4 with the IL-6 amplifier, which amplifies the production of IL-6, growth factors and chemokines in non-immune cells and aggravates inflammatory diseases via NF-κB enhancement. Knockdown of SFRP4 suppressed activation of the IL-6 amplifier in vitro and in vivo, whereas the overexpression of SFRP4 induced the activation of NF-κB-mediated transcription activity. Mechanistically, SFRP4 induced NF-κB activation by directly binding to molecules of the ubiquitination SFC complex, such as IkBα and ßTrCP, followed by IkBα degradation. Furthermore, SFRP4 expression was significantly increased in fibroblasts derived from DC patients bearing the risk alleles. Consistently, fibroblasts with the risk alleles enhanced activation of the IL-6 amplifier. These findings indicate that the IL-6 amplifier is involved in the pathogenesis of DC, particularly in patients harboring the SFRP4 risk alleles. Therefore, SFRP4 is a potential therapeutic target for various inflammatory diseases and disorders, including DC.


Assuntos
Contratura de Dupuytren , Humanos , Contratura de Dupuytren/genética , Contratura de Dupuytren/patologia , Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla , NF-kappa B/metabolismo , Interleucina-6/metabolismo , Fibroblastos/metabolismo , Inflamação/genética , Inflamação/metabolismo , Proteínas Proto-Oncogênicas/metabolismo
3.
Biochem Biophys Res Commun ; 682: 223-243, 2023 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-37826946

RESUMO

Skeletal muscle myogenesis represents one of the most intensively and extensively examined systems of cell differentiation, tissue formation, and regeneration. Muscle regeneration provides an in vivo model system of postnatal myogenesis. It comprises multiple steps including muscle stem cell (or satellite cell) quiescence, activation, migration, myogenic determination, myoblast proliferation, myocyte differentiation, myofiber maturation, and hypertrophy. A variety of extracellular signaling and subsequent intracellular signal transduction pathways or networks govern the individual steps of postnatal myogenesis. Among them, MAPK pathways (the ERK, JNK, p38 MAPK, and ERK5 pathways) and PI3K-Akt signaling regulate multiple steps of myogenesis. Ca2+, cytokine, and Wnt signaling also participate in several myogenesis steps. These signaling pathways often control cell cycle regulatory proteins or the muscle-specific MyoD family and the MEF2 family of transcription factors. This article comprehensively reviews molecular mechanisms of the individual steps of postnatal skeletal muscle myogenesis by focusing on signal transduction pathways or networks. Nevertheless, no or only a partial signaling molecules or pathways have been identified in some responses during myogenesis. The elucidation of these unidentified signaling molecules and pathways leads to an extensive understanding of the molecular mechanisms of myogenesis.


Assuntos
Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Diferenciação Celular/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Desenvolvimento Muscular/fisiologia , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia
4.
Cell Mol Neurobiol ; 43(5): 2165-2178, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36222946

RESUMO

Although evidence has accumulated to indicate that Schwann cells (SCs) differentiate into repair SCs (RSCs) upon injury and that the unique phenotype of these cells allow them to provide support for peripheral nerve regeneration, the details of the RSCs are not fully understood. The findings of the current study indicate that the RSCs have enhanced adherent properties and a greater capability to promote neurite outgrowth and axon regeneration after peripheral nerve injury, compared to the non-RSCs. Further, transcriptome analyses have demonstrated that the molecular signature of the RSCs is distinctly different from that of the non-RSCs. The RSCs upregulate a group of genes that are related to inflammation, repair, and regeneration, whereas non-RSCs upregulate genes related to myelin maintenance, Notch, and aging. These findings indicate that the RSCs have markedly different cellular, regenerative, and molecular characteristics compared to the non-RSCs, even though the RSCs were just derived from non-RSCs upon injury, thus providing the basis for understanding the mechanisms related to SC mediated repair after peripheral nerve injury.


Assuntos
Traumatismos dos Nervos Periféricos , Humanos , Traumatismos dos Nervos Periféricos/genética , Traumatismos dos Nervos Periféricos/terapia , Axônios , Regeneração Nervosa/fisiologia , Células de Schwann/fisiologia , Nervos Periféricos
5.
Exp Physiol ; 108(4): 621-635, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36852508

RESUMO

NEW FINDINGS: What is the central question of this study? Although fibroblasts are involved in the regenerative process associated with peripheral nerve injury, detailed information regarding their characteristics is largely lacking. What is the main finding and its importance? Nerve-derived fibroblasts have a greater neurite-promoting effect than skin-derived fibroblasts, and epineurium-derived fibroblasts can promote neurite outgrowth more effectively than parenchyma-derived fibroblasts. The epineurium-derived fibroblasts and parenchyma-derived fibroblasts have distinctly different molecular profiles, including genes of soluble factors to promote axonal growth. Fibroblasts are molecularly and functionally different depending on their localization in nerve tissue, and epineurium-derived fibroblasts might be involved in axon regeneration after peripheral nerve injury more than previously thought. ABSTRACT: Although fibroblasts (Fb) are components of a peripheral nerve involved in the regenerative process associated with peripheral nerve injury, detailed information regarding their characteristics is largely lacking. The objective of the present study was to investigate the capacity of Fb derived from peripheral nerves to stimulate the outgrowth of neurites from adult dorsal root ganglion neurons and to clarify their molecular characteristics. Fibroblasts were prepared from the epineurium and parenchyma of rat sciatic nerves and skin. The Fb derived from epineurium showed the greatest effect on neurite outgrowth, followed by the Fb derived from parenchyma, indicating that Fb derived from nerves promote neurite outgrowth more effectively than skin-derived Fb. Although both soluble and cell-surface factors contributed evenly to the neurite-promoting effect of nerve-derived Fb, in crush and transection injury models, Fb were not closely associated with regenerating axons, indicating that only soluble factors from Fb are available to regenerating axons. A transcriptome analysis revealed that the molecular profiles of these Fb were distinctly different and that the gene expression profiles of soluble factors that promote axonal growth are unique to each Fb. These findings indicate that Fb are molecularly and functionally different depending on their localization in nerve tissue and that Fb derived from epineurium might be involved more than was previously thought in axon regeneration after peripheral nerve injury.


Assuntos
Axônios , Traumatismos dos Nervos Periféricos , Ratos , Animais , Axônios/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Gânglios Espinais/metabolismo , Regeneração Nervosa/fisiologia , Neurônios/metabolismo , Nervo Isquiático/metabolismo , Fibroblastos/metabolismo , Crescimento Neuronal , Células Cultivadas
6.
Cell Mol Life Sci ; 79(6): 289, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35536429

RESUMO

Accumulating evidences suggest that M2 macrophages are involved with repair processes in the nervous system. However, whether M2 macrophages can promote axon regeneration by directly stimulating axons nor its precise molecular mechanism remains elusive. Here, the current study demonstrated that typical M2 macrophages, which were generated by IL4 simulation, had the capacity to stimulate axonal growth by their direct effect on axons and that the graft of IL4 stimulated macrophages into the region of Wallerian degeneration enhanced axon regeneration and improved functional recovery after PNI. Importantly, uPA (urokinase plasminogen activator)-uPA receptor (uPAR) was identified as the central axis underlying the axon regeneration effect of IL4 stimulated macrophages. IL4 stimulated macrophages secreted uPA, and its inhibition abolished their axon regeneration effect. Injured but not intact axons expressed uPAR to be sensitive to uPA. These results unveil a cellular and molecular mechanism underlying the macrophage related axon regeneration and provide a basis of a novel therapy for PNI.


Assuntos
Traumatismos dos Nervos Periféricos , Ativador de Plasminogênio Tipo Uroquinase , Axônios/fisiologia , Humanos , Interleucina-4/farmacologia , Macrófagos/fisiologia , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/terapia , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética
7.
Neuropathology ; 43(5): 413-420, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36942363

RESUMO

Somatic mosaicism of isocitrate dehydrogenase 1/2 (IDH1/2) mutation is a cause of Ollier disease (OD), characterized by multiple enchondromatosis. A 35-year-old woman who was diagnosed with OD at age 24 underwent resection surgery for multifocal tumors located at the right and left frontal lobes that were discovered incidentally. No apparent spatial connection was observed on preoperative magnetic resonance imaging. Pathological examinations revealed tumor cells with a perinuclear halo in the left frontal lobe tumor, whereas astrocytic tumor cells were observed in the right frontal lobe tumor. Based on positive IDH1 R132H immunostaining and the result of 1p/19q fluorescent in situ hybridization, pathological diagnoses were IDH mutant and 1p/19q-codeleted oligodendroglioma in the right frontal lobe tumor and IDH mutant astrocytoma in the left frontal lobe tumor, respectively. The DNA sequencing revealed IDH1 R132H mutation in the peripheral blood sample and frontal lobe tumors. This case suggested that in patients with OD, astrocytoma and oligodendroglioma can co-occur within the same individual simultaneously, and IDH1 R132H mutation was associated with supratentorial development of gliomas.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Encondromatose , Glioma , Oligodendroglioma , Feminino , Humanos , Adulto Jovem , Adulto , Oligodendroglioma/genética , Oligodendroglioma/patologia , Encondromatose/complicações , Encondromatose/genética , Encondromatose/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Hibridização in Situ Fluorescente , Isocitrato Desidrogenase/genética , Glioma/genética , Astrocitoma/genética , Astrocitoma/patologia , Mutação
8.
Postgrad Med J ; 99(1178): 1258-1265, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37742090

RESUMO

PURPOSE OF STUDY: A physician's ability to empathize is crucial for patient health outcomes, and this differs according to speciality, personal characteristics, and environmental factors. This study aimed to examine the empathy levels among physicians based on their specialities and to identify the influencing factors. STUDY DESIGN: A nationwide, online, cross-sectional survey was conducted using the Nikkei Business Publication online physician member homepage. Participants were 5441 physicians in Japan registered as members of Nikkei Medical Online across 20 specialities. We used the Jefferson Scale of Empathy (JSE) to measure the physicians' empathy levels. Cronbach's alpha was 0.84. RESULTS: The mean JSE score was 100.05, SD = 15.75. Multivariate analyses showed that the highest JSE scores were for general medicine [+5.58, 95% confidence interval (CI) 2.60-8.56], general surgery (+3.63, 95% CI 0.97-6.28), psychiatry (+3.47, 95% CI 1.76-5.17), and paediatrics (+1.92, 95% CI 0.11-3.73). Factors associated with higher JSE scores were being female (+5.86, 95% CI 4.68-7.04), managers (+1.11, 95% CI 0.16-2.07), working in a small hospital (+2.19, 95% CI 0.23-4.15), and with children (+3.32, 95% CI 2.29-4.36). CONCLUSIONS: A significant decrease in the empathy levels was found when the parent of the participant was also a medical provider. Being a general medicine physician or a female physician in a high position who has children was positively and significantly correlated with high empathy levels.


Assuntos
Medicina Geral , Clínicos Gerais , Médicas , Humanos , Feminino , Criança , Masculino , Estudos Transversais , Empatia
9.
J Pediatr Orthop ; 43(3): e244-e248, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36476945

RESUMO

BACKGROUND: Surgery for polydactyly of the foot aims to achieve good cosmesis and improve shoe fitting. An accurate understanding of toe morphology will help to minimize the skin incision or optimize the surgical plan before incision. However, it is difficult to determine the shape of the articular surface using radiographs of children with immature bone. We performed arthrography during surgery for postaxial polydactyly of the foot to assess the cartilaginous structures. The purpose of this study was to investigate the usefulness of arthrography in postaxial polydactyly of the foot. METHODS: We included 36 digits of 31 patients (16 males and 15 females), including 5 bilateral cases. The age at surgery ranged from 9 to 75 months (mean, 20 mo). Intraoperative arthrography was performed and all radiographs and arthrograms were reviewed and classified by 3 observers using the Watanabe classification. The absolute percentage agreement between the observers was calculated. The senior author assigned the arthrograms as the reference. The types determined by the other 2 observers using radiographs and arthrograms were compared with the reference. RESULTS: Full agreement occurred in 66.7% of the radiographs and in 75% of arthrograms. The mean kappa coefficient was 0.58, indicating fair agreement, between the reference and the radiologic assessment, while it was 0.81, indicating excellent or almost perfect agreement, in the evaluation using arthrograms. CONCLUSIONS: Intraoperative arthrography is an easy and reliable diagnostic method that can be used to determine the detailed articular shape. LEVEL OF EVIDENCE: Level III.


Assuntos
Polidactilia , Sindactilia , Masculino , Criança , Feminino , Humanos , Lactente , Pré-Escolar , Artrografia , , Polidactilia/cirurgia
10.
Macromol Rapid Commun ; 43(9): e2200014, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35142042

RESUMO

The synthesis of acrylates with an isocyanurate substituent that show significant volume expansion on radical photo-polymerization is reported. The acrylate consisting of benzyl bisurethane moieties exhibits the largest volume expansion among them and contributes to restrict volume change upon its radical photo-copolymerization with a diacrylate exhibiting volume shrinkage. Furthermore, a correlation is revealed between the volume change behavior and the polymer structure through the radical photo-polymerization of the isocyanurate core-based diacrylate with benzyl bisurethane moieties under various concentration conditions.

11.
BMC Musculoskelet Disord ; 23(1): 821, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36042450

RESUMO

BACKGROUND: Although total wrist arthroplasty (TWA) has become a common treatment option for wrists with damage due to rheumatoid arthritis (RA), the optimal implant axial alignment for TWA has been inadequately studied. This study was performed to investigate the relationships between implant alignment and carpal rotational alignment and the wrist range of motion (ROM) following TWA. METHODS: This study included 18 patients who underwent TWA using a DARTS® Total Wrist System (Teijin Nakashima Medical, Okayama, Japan) for wrist RA. Pre- and 6-month postoperative computed tomography scans were performed, including the radial volar line (Rv), capitohamate axis (CH), and Rv-CH angle in axial scans. The wrist ROM was also measured. The relationship between the Rv-CH angle and ROM was examined. RESULTS: The mean Rv-CH angle showed significant wrist pronation from 73.0° to 83.4° postoperatively. We observed a significant positive correlation (0.58) between the postoperative Rv-CH angle and extension and a significant negative correlation (- 0.56) between the postoperative Rv-CH angle and flexion. CONCLUSIONS: Implantation of the DARTS® TWA prosthesis resulted in pronation of the carpal axial alignment, which was correlated with postoperative wrist extension. The volar cortex of the distal radius can be a novel reference axis for adequate implant placement.


Assuntos
Artrite Reumatoide , Artroplastia de Substituição , Ossos do Carpo , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/cirurgia , Artroplastia de Substituição/efeitos adversos , Humanos , Amplitude de Movimento Articular , Punho/cirurgia , Articulação do Punho/diagnóstico por imagem , Articulação do Punho/cirurgia
12.
Exp Cell Res ; 397(1): 112342, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33130177

RESUMO

The Ras family of small GTPases comprises about 36 members in humans. M-Ras is related to classical Ras with regard to its regulators and effectors, but solely constitutes a subfamily among the Ras family members. Although classical Ras strongly binds Raf and highly activates the ERK pathway, M-Ras less strongly binds Raf and moderately but sustainedly activates the ERK pathway to induce neuronal differentiation. M-Ras also possesses specific effectors, including RapGEFs and the PP1 complex Shoc2-PP1c, which dephosphorylates Raf to activate the ERK pathway. M-Ras is highly expressed in the brain and plays essential roles in dendrite formation during neurogenesis, in contrast to the axon formation by R-Ras. M-Ras is also highly expressed in the bone and induces osteoblastic differentiation and transdifferentiation accompanied by calcification. Moreover, M-Ras elicits epithelial-mesenchymal transition-mediated collective and single cell migration through the PP1 complex-mediated ERK pathway activation. Activating missense mutations in the MRAS gene have been detected in Noonan syndrome, one of the RASopathies, and MRAS gene amplification occurs in several cancers. Furthermore, several SNPs in the MRAS gene are associated with coronary artery disease, obesity, and dyslipidemia. Therefore, M-Ras carries out a variety of cellular, physiological, and pathological functions. Further investigations may reveal more functions of M-Ras.


Assuntos
Diferenciação Celular , Movimento Celular , Minerais/metabolismo , Músculos/metabolismo , Síndrome de Noonan/patologia , Proteínas ras/metabolismo , Humanos , Síndrome de Noonan/genética , Síndrome de Noonan/metabolismo , Proteínas ras/genética
13.
Exp Cell Res ; 387(2): 111775, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31843497

RESUMO

The Ras-ERK pathway regulates a variety of cellular and physiological responses, including cell proliferation, differentiation, morphogenesis during animal development, and homeostasis in adults. Deregulated activation of this pathway leads to cellular transformation and tumorigenesis as well as RASopathies. Several negative regulators of this pathway have been documented. Each of these proteins acts at particular points of the pathway, and they exert specific cellular and physiological functions. Among them, DA-Raf1 (DA-Raf), which is a splicing isoform of A-Raf and contains the Ras-binding domain but lacks the kinase domain, antagonizes the Ras-ERK pathway in a dominant-negative manner. DA-Raf induces apoptosis, skeletal myocyte differentiation, lung alveolarization, and fulfills tumor suppressor functions by interfering with the Ras-ERK pathway. After the findings of DA-Raf, several kinase-domain-truncated splicing variants of Raf proteins have also been reported. The family of these truncated proteins represents the concept that alternative splicing can generate antagonistic proteins to their full-length counterparts.


Assuntos
Processamento Alternativo/genética , Sistema de Sinalização das MAP Quinases/genética , Proteínas Proto-Oncogênicas A-raf/genética , Proteínas ras/genética , Animais , Humanos , Transdução de Sinais/genética
14.
Exp Cell Res ; 376(2): 168-180, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30742807

RESUMO

Ras-activated ERK pathway (Raf-MEK-ERK phosphorylation cascade) regulates a variety of cellular responses including cell proliferation, differentiation, survival, and apoptosis. DA-Raf1 (DA-Raf) is a splicing variant of A-Raf and contains the Ras-binding domain but lacks the kinase domain. Accordingly, DA-Raf antagonizes the Ras-ERK pathway in a dominant-negative manner. Here we show that DA-Raf plays essential roles in skeletal myocyte differentiation including myoblast fusion and in apoptosis, which are suppressed by the Ras-ERK pathway. Expression of DA-Raf was highly induced in C2C12 skeletal myocytes in a low serum concentration of differentiation condition and in NIH3T3 fibroblasts under a serum starvation apoptosis-inducing condition. Stable knockdown of DA-Raf resulted in suppression of muscle-specific gene expression, myoblast fusion, and apoptosis. In contrast, exogenous overexpression of DA-Raf prominently caused apoptosis. DA-Raf induces apoptosis by preventing ERK-RSK-mediated inhibitory phosphorylation of Bad. Although it has been reported that apoptosis triggers myoblast fusion, DA-Raf-induced apoptosis was not involved in myoblast fusion in C2C12 cells. These results imply that suppression of the Ras-ERK pathway by DA-Raf is essential for both myocyte differentiation including myoblast fusion and apoptosis but that apoptosis is not a prerequisite for myoblast fusion.


Assuntos
Diferenciação Celular/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Fibras Musculares Esqueléticas/citologia , Proteínas Proto-Oncogênicas A-raf/fisiologia , Animais , Apoptose , Fusão Celular , Linhagem Celular , Células HEK293 , Humanos , Camundongos , Células NIH 3T3 , Proteínas ras/metabolismo
15.
Exp Physiol ; 104(10): 1447-1454, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31294871

RESUMO

NEW FINDINGS: What is the central question of this study? Although the factors secreted from Schwann cells that promote axonal growth in the peripheral nervous system have been well studied, the effect of cell-contact factors on Schwann cells remains to be determined. What is the main finding and its importance? This study demonstrates that Schwann cells stimulate neurite outgrowth by direct contact with neurites and by secreting factors. Notably, the effect of cell-contact factors in neurite outgrowth is comparable to that of secreted factors, indicating that the identification of cell surface molecules on Schwann cells that promote neurite outgrowth could lead to development of a new therapy for peripheral nervous system injury. ABSTRACT: Schwann cells (SCs) play a variety of roles in the regeneration process after injury to the peripheral nervous system. The factors secreted from SCs that promote axonal growth have been well studied. However, the involvement of cell-contact factors on SCs remains to be determined. Here, we demonstrate a significant contribution of a cell-contact mechanism in the effect of SCs on promotion of neuronal outgrowth. Neurite outgrowth of adult sensory neurons from dorsal root ganglia was quantified during co-culture with adult SCs. Direct contact of SCs with neurons was eliminated by culturing SCs on an insert placed in the same well; this resulted in a 51% reduction in the length of neurite outgrowth. In addition, when dorsal root ganglion neurons were cultured on sparsely seeded SCs, neurons that made contact with SCs on their neurites had 118% longer neurites than neurons that lacked contacts with SCs. Collectively, these findings provide evidence that SCs stimulate neurite outgrowth via direct contact with neurites in addition to secreting factors. The identification of cell surface molecules on SCs that promote neurite outgrowth could lead to development of a new therapy for peripheral nervous system injury.


Assuntos
Gânglios Espinais/crescimento & desenvolvimento , Neuritos/fisiologia , Crescimento Neuronal/fisiologia , Células de Schwann/fisiologia , Células Receptoras Sensoriais/fisiologia , Animais , Comunicação Celular/fisiologia , Tamanho Celular , Técnicas de Cocultura , Feminino , Gânglios Espinais/citologia , Regeneração Nervosa , Neuritos/ultraestrutura , Ratos , Ratos Endogâmicos Lew
16.
Exp Cell Res ; 362(1): 111-120, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29129563

RESUMO

Activating mutations of RAS genes, particularly KRAS, are detected with high frequency in human tumors. Mutated Ras proteins constitutively activate the ERK pathway (Raf-MEK-ERK phosphorylation cascade), leading to cellular transformation and tumorigenesis. DA-Raf1 (DA-Raf) is a splicing variant of A-Raf and contains the Ras-binding domain (RBD) but lacks the kinase domain. Accordingly, DA-Raf antagonizes the Ras-ERK pathway in a dominant-negative fashion and suppresses constitutively activated K-Ras-induced cellular transformation. Thus, we have addressed whether DA-Raf serves as a tumor suppressor of Ras-induced tumorigenesis. DA-Raf(R52Q), which is generated from a single nucleotide polymorphism (SNP) in the RBD, and DA-Raf(R52W), a mutant detected in a lung cancer, neither bound to active K-Ras nor interfered with the activation of the ERK pathway. They were incapable of suppressing activated K-Ras-induced cellular transformation and tumorigenesis in mice, in which K-Ras-transformed cells were transplanted. Furthermore, although DA-Raf was highly expressed in lung alveolar epithelial type 2 (AE2) cells, its expression was silenced in AE2-derived lung adenocarcinoma cell lines with oncogenic KRAS mutations. These results suggest that DA-Raf represents a tumor suppressor protein against Ras-induced tumorigenesis.


Assuntos
Genes ras/genética , Sistema de Sinalização das MAP Quinases/genética , Proteínas Proto-Oncogênicas A-raf/genética , Proteínas Supressoras de Tumor/genética , Proteínas ras/genética , Células A549 , Adenocarcinoma/genética , Adenocarcinoma de Pulmão , Animais , Células COS , Carcinogênese/genética , Linhagem Celular , Linhagem Celular Tumoral , Chlorocebus aethiops , Cães , Células HCT116 , Células HL-60 , Células HeLa , Humanos , Neoplasias Pulmonares/genética , Células Madin Darby de Rim Canino , Camundongos , Células NIH 3T3
17.
BMC Musculoskelet Disord ; 20(1): 207, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077175

RESUMO

BACKGROUND: Low back pain (LBP) is a common complaint in the elderly Japanese population. Although previous studies showed that height loss was associated with LBP, it remains unclear whether LBP is associated with body composition. The objective of the present study was to investigate whether body composition and physical characteristics, including height loss, were associated with LBP. METHODS: The present study is retrospectively registered, and the participants were 2212 community-dwelling Japanese people aged over 60 years who participated in the Shimane CoHRE study in 2016. We investigated the presence of LBP, body composition parameters (muscle, fat, body weight, and bone mass), physical characteristics (body height and height loss), chronic diseases, history of fall, smoking, and drinking habits. We examined the relationships of body composition parameters and physical characteristics with point prevalence of LBP using multivariate logistic regression. RESULTS: The point prevalence of LBP was 43.2% in women and 39.5% in men. Logistic regression models showed that body height and body composition were not significantly associated with LBP; however, height loss was associated significantly with LBP in women and men (OR: 1.14, 95% CI: 1.08-1.20 and OR: 1.13, 95% CI: 1.06-1.21, respectively). Hypertension (OR: 1.32, 9 5% CI: 1.04-1.69) and chronic heart disease (OR: 1.57, 95% CI: 1.01-2.43) in women and history of fall (OR: 1.70, 95% CI: 1.13-2.56) and cerebrovascular disease (OR: 1.88, 95% CI: 1.05-3.34) in men were significantly associated with LBP. However, body composition was not associated with LBP in either gender. CONCLUSIONS: The present study demonstrated that height loss, but not body composition, was related to LBP in community-dwelling elderly people. To elucidate the cause of LBP, it is important to consider the relationship with height loss.


Assuntos
Composição Corporal/fisiologia , Estatura/fisiologia , Vida Independente/estatística & dados numéricos , Dor Lombar/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Japão/epidemiologia , Dor Lombar/fisiopatologia , Masculino , Prevalência , Fatores de Risco , Fatores Sexuais
18.
J Biol Chem ; 292(8): 3201-3212, 2017 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-28082682

RESUMO

Stress-induced activation of p53 is an essential cellular response to prevent aberrant cell proliferation and cancer development. The ubiquitin ligase MDM2 promotes p53 degradation and limits the duration of p53 activation. It remains unclear, however, how p53 persistently escapes MDM2-mediated negative control for making appropriate cell fate decisions. Here we report that TBP-like protein (TLP), a member of the TBP family, is a new regulatory factor for the p53-MDM2 interplay and thus for p53 activation. We found that TLP acts to stabilize p53 protein to ensure long-lasting p53 activation, leading to potentiation of p53-induced apoptosis and senescence after genotoxic stress. Mechanistically, TLP interferes with MDM2 binding and ubiquitination of p53. Moreover, single cell imaging analysis shows that TLP depletion accelerates MDM2-mediated nuclear export of p53. We further show that a cervical cancer-derived TLP mutant has less p53 binding ability and lacks a proliferation-repressive function. Our findings uncover a role of TLP as a competitive MDM2 blocker, proposing a novel mechanism by which p53 escapes the p53-MDM2 negative feedback loop to modulate cell fate decisions.


Assuntos
Mapas de Interação de Proteínas , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Semelhantes à Proteína de Ligação a TATA-Box/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Apoptose , Células HCT116 , Células HeLa , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Estabilidade Proteica , Proteólise , Proteínas Proto-Oncogênicas c-mdm2/análise , Proteínas Semelhantes à Proteína de Ligação a TATA-Box/análise , Proteína Supressora de Tumor p53/análise , Ubiquitinação
19.
J Am Chem Soc ; 140(3): 884-887, 2018 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-29313331

RESUMO

Multifunctional 6-membered cyclic carbonates (6-CCs) comprising acetal structures have been synthesized via phosgene-free routes and utilized for the fabrication of reworkable networked poly(acetal-hydroxyurethane) (PAHU) films. Dibenzoyl-protected di(trimethylolpropane) (DTMP) reacts with multifunctional aldehydes derived from nonexpensive alcohols to afford protected multifunctional DTMPs. After deprotection, the multifunctional DTMPs can react with diphenyl carbonate to efficiently form multifunctional 6-CCs. The polyaddition of the 6-CCs and diamines effectively proceeds in DMF to give networked PAHU films with good transparency and flexibility. These films possess the reworkability based on acid-catalyzed reversibility of acetal linkages. In particular, the film fabricated using large amounts of hexa-functional 6-CCs can reform reproducibly with maintaining to some degree its mechanical properties.

20.
Biomacromolecules ; 19(7): 3067-3076, 2018 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-29750865

RESUMO

A novel catechol-bearing polypeptide (CtP) was synthesized and used as a component of electrochemical biosensor involving both enzymatic activity and affinity-based sensing systems. Glucose oxidase (GOx) and anti-immunoglobulin G (Anti-IgG) were selected as model biorecognition elements for the selective analysis of glucose and IgG. Step-by-step surface modifications were followed using various techniques such as cyclic voltammetry (CV) and electrochemical impedance spectrometry (EIS) as well as X-ray photoelectron spectroscopy (XPS). Additionally, contact angles were measured in order to observe surface properties. Amperometric measurements using the GOx biosensor were performed at -0.7 V by following the oxygen consumption due to the enzymatic reaction in different glucose concentrations. Affinity-based interactions via IgG sensor were monitored using the differential pulse voltammetry (DPV) technique. As the "surface design with CtP" approach employed herein is generally applicable and easily adaptable to obtain functional matrices for biomolecule immobilization, CtP-coated surfaces can be promising platforms for the fabrication of various biobased sensing systems.


Assuntos
Técnicas Biossensoriais/métodos , Catecóis/química , Glucose/análise , Imunoglobulina G/análise , Peptídeos/química , Anticorpos Anti-Idiotípicos/química , Anticorpos Anti-Idiotípicos/metabolismo , Glucose Oxidase/química , Glucose Oxidase/metabolismo , Propriedades de Superfície
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