Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 53
Filtrar
1.
Insect Biochem Mol Biol ; 167: 104086, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38295885

RESUMO

Growth-blocking peptide (GBP), an insect cytokine, was first found in armyworm Mythimna separata. A functional analogue of GBP, stress-responsive peptide (SRP), was also identified in the same species. SRP gene expression has been demonstrated to be enhanced by GBP, indicating that both cytokines are organized within a hierarchical regulatory network. Although GBP1 (CG15917) and GBP2 (CG11395) have been identified in Drosophila melanogaster, immunological functions have only been characterized for GBP1. It is expected that the biological responses of two structurally similar peptides should be coordinated, but there is little information on this topic. Here, we demonstrate that GBP2 replicates the GBP1-mediated cellular immune response from Drosophila S2 cells. Moreover, the GBP2-induced response was silenced by pre-treatment with dsRNA targeting the GBP receptor gene, Mthl10. Furthermore, treatment of S2 cells with GBP2 enhanced GBP1 expression levels, but GBP1 did not affect GBP2 expression. GBP2 derived enhancement of GBP1 expression was not observed in the presence of GBP1, indicating that GBP2 is an upstream expressional regulator of a GBP1/GBP2 cytokine network. GBP2-induced enhancement of GBP1 expression was not observed in Mthl10 knockdown cells. Enhancement of GBP2 expression was observed in both Drosophila larvae and S2 cells under heat stress conditions; expressional enhancement of both GBP1 and GBP2 was eliminated in Mthl10 knockdown cells and larvae. Finally, Ca2+ mobilization assay in GCaMP3-expressing S2 cells demonstrated that GBP2 mobilizes Ca2+ upstream of Mthl10. Our finding revealed that Drosophila GBP1 and GBP2 control immune responses as well as their own expression levels through a hierarchical cytokine network, indicating that Drosophila GBP1/GBP2 system can be a simple model that is useful to investigate the detailed regulatory mechanism of related cytokine complexes.


Assuntos
Citocinas , Drosophila , Animais , Drosophila/metabolismo , Citocinas/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Transporte/metabolismo , Peptídeos/metabolismo , Imunidade
2.
BMC Cancer ; 23(1): 1046, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37904096

RESUMO

BACKGROUND: Rhabdomyosarcoma is the most common soft tissue sarcoma in children, but rare in adults. Para-meningeal rhabdomyosarcoma in head and neck (PM-HNRMS) is less applicable for surgery due to the anatomic reason. PM-HNRMS has a poor prognosis in children. However, its clinical outcomes remain unclear in adults due to the rarity. Further, there is almost no detailed data about salvage therapy. METHODS: We retrospectively examined the adult patients with PM-HNRMS treated at institutions belonging to the Kyushu Medical Oncology Group from 2009 to 2022. We evaluated the overall survival (OS) and progression-free survival (PFS) of the patients who received a first-line therapy. We also reviewed the clinical outcomes of patients who progressed against a first-line therapy and received salvage therapy. RESULTS: Total 11 patients of PM-HNRMS received a first-line therapy. The characteristics were as follows: median age: 38 years (range 25 - 63 years), histology (alveolar/spindle): 10/1, and risk group (intermediate/high): 7/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 10 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in seven patients. The median PFS was 14.2 months (95%CI: 6.0 - 25.8 months): 17.1 months (95%CI: 6.0 - not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2 - 25.8 months) for patients with stage IV. The 1-year and 3-year PFS rates were 54.5% and 11.3% for all patients. Median OS in all patients was 40.8 months (95%CI: 12.1 months-NR): 40.8 months (95%CI: 12.1 - NR) for patients with stage I-III and NR for patients with stage IV. The 5-year OS rate was 48.5% for all patients. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 4 years after completion of the last therapy. Those two patients received multi-modal therapy including local therapy for all detected lesions. CONCLUSION: The cure rate of adult PM-HNRMS is low in spite of a first-line therapy in this study. Salvage therapy might prolong the survival in patients who received the multi-modal therapy including local therapy for all detected lesions.


Assuntos
Neoplasias de Cabeça e Pescoço , Rabdomiossarcoma , Adulto , Humanos , Pessoa de Meia-Idade , Neoplasias de Cabeça e Pescoço/terapia , Japão , Recidiva Local de Neoplasia/terapia , Estudos Retrospectivos , Rabdomiossarcoma/patologia , Terapia de Salvação
3.
Arch Orthop Trauma Surg ; 143(10): 6339-6344, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37103607

RESUMO

BACKGROUND: Many countries are faced with aging populations. However, few studies have directly compared the clinical outcomes of medial opening-wedge high tibial osteotomy (OWHTO) and mobile-bearing unicompartmental knee arthroplasty (MB-UKA) in early elderly patients. Thus, we aimed to investigate the clinical outcomes after OWHTO and MB-UKA in early elderly patients with similar demographics and osteoarthritis (OA) severity. METHODS: Three hundred and fifteen OWHTO and 142 MB-UKA were performed for medial compartment OA by a single surgeon between August 2009 and April 2020. Among them, patients aged 65-74 years with more than two years of follow-up were enrolled. The patient-reported outcome measures (PROMs), including visual analog scale (VAS) score and Japanese Knee Osteoarthritis Measure (JKOM) score, were compared between both procedures preoperatively and at the last follow-up. The PROMs were compared between the groups by Kellgren-Lawrence (K-L) OA grades. RESULTS: Seventy-three OWHTO and 37 MB-UKA patients were enrolled. No significant differences were found in the distribution of age, gender, follow-up period, body mass index, and Tegner activity scale between the two procedures. The postoperative PROMs in patients with K-L grade 4 were better after MB-UKA than OWHTO at the mean follow-up of 5 years. No significant difference was found in PROMs in patients with K-L grades 2 and 3. CONCLUSION: ThePROMs after MB-UKA were superior to that after OWHTO in early elderly patients with severe OA. In particular, pain relief was better after MB-UKA than OWHTO with severe OA. Meanwhile, no significant difference in PROMs was found with moderate OA patients. LEVEL OF EVIDENCE: Level IVprospective cohort study.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Idoso , Humanos , Artroplastia do Joelho/métodos , Articulação do Joelho/cirurgia , Estudos de Coortes , Resultado do Tratamento , Osteoartrite do Joelho/cirurgia , Osteotomia/métodos , Estudos Retrospectivos , Medidas de Resultados Relatados pelo Paciente , Tíbia/cirurgia
4.
BMJ Open Sport Exerc Med ; 9(1): e001493, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36741788

RESUMO

Objective: Lower extremity sports injuries frequently occur during an individual's growth period. The object of the current study was to analyse the risk factors for lower extremity sports injuries for youth athletes. The secondary objective was to clarify the factors related to new injuries after a lower extremity injury. Methods: We extracted information on youth athletes (aged 10-15 years) with sports-related disorders. Background data and injury situations were collected via a specific application. During the follow-up period, new injuries were also recorded. The athletes were divided into two groups according to injury location (lower extremity or other). We performed a multiple logistic regression analysis to clarify the association between injury location and background data. Results: 1575 complaints of lower extremity disorders and 328 complaints in other body parts were registered. According to the multiple regression analysis, practice time per week was significantly shorter for the lower extremity group than the other locations group (OR 0.98; 95% CI 0.963 to 0.999). Athletes whose future goal was at the recreational level had a significantly low incidence of new injuries after experiencing lower extremity disorders. Conclusion: The practice environments and psychological factors should receive more attention to prevent lower extremity injuries.

5.
FEBS Lett ; 597(2): 288-297, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36527170

RESUMO

Mitohormesis defines the increase in fitness induced by adaptive responses to mild mitochondrial stress. Here, we show that N-acetyloxfenicine (NAO) exerted higher thermotolerance than an endogenous mitohormesis inducer, N-acetyltyrosine (NAT). This activity was not observed in armyworm larvae injected with oxfenicine, suggesting the importance of N-acetylation. NAO-induced hormetic effect was triggered by transient perturbation of mitochondria, which causes a small increase in ROS production and leads to retrograde responses including enhanced expression of antioxidant enzyme genes via activation of FoxO transcription factors. Furthermore, pretreatment with NAO significantly repressed stress-induced peroxidation of lipids in mice and growth of colorectal cancer HCT116 cells that had been transplanted into nude mice. Taken together, NAO is a potent mitohormesis inducer that is similar to NAT in terms of structure and functions.


Assuntos
Antioxidantes , Mitocôndrias , Animais , Camundongos , Camundongos Nus , Mitocôndrias/metabolismo , Antioxidantes/metabolismo , Transdução de Sinais , Insetos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
6.
J Orthop Sci ; 28(5): 1074-1081, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36175252

RESUMO

BACKGROUND: No study thus far has compared tunnel enlargement between double-bundle and triple-bundle anterior cruciate ligament reconstruction. We compared tibial tunnel enlargement and rate of tibial tunnel coalition between these two reconstructions, hypothesizing that tibial tunnel enlargement in triple-bundle reconstruction is less than that in double-bundle reconstruction, and that the tunnel coalition rate is equal between the two procedures. METHODS: This prospective randomized clinical trial included 25 patients who underwent computed tomography 2 weeks and 1 year postoperatively. Eleven patients underwent double-bundle anterior cruciate ligament reconstruction and 14 underwent triple-bundle anterior cruciate ligament reconstruction. Tunnel positions and tunnel coalition at the tibial tunnel aperture were assessed using three-dimensional computed tomography. Tunnel enlargement rate was calculated by measuring the sagittal and axial widths of the tibial bone tunnel 10 mm from the tibial tunnel aperture. These parameters were then compared between the groups. RESULTS: The changes in tunnel positions and tunnel coalitions between groups were not significantly different. On both sagittal and axial views, the tunnel enlargement rates of the medial and lateral sections of the anteromedial bundle in the triple-bundle group were significantly smaller than those in the double-bundle group (sagittal view, p = 0.02 and < 0.01, respectively; axial view, p = 0.02 and ≤ 0.05, respectively). The groups did not differ significantly in terms of posterolateral tunnel enlargement. CONCLUSION: Tunnel widening in the medial and lateral sections of the anteromedial bundle-associated tibial tunnel in triple-bundle anterior cruciate ligament reconstruction was smaller than that of double-bundle reconstruction. The tunnel coalition rates between the two reconstructions were not significantly different.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Humanos , Ligamento Cruzado Anterior/cirurgia , Fêmur/cirurgia , Estudos Prospectivos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Lesões do Ligamento Cruzado Anterior/cirurgia , Articulação do Joelho/cirurgia
7.
Cells ; 11(19)2022 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-36231128

RESUMO

The repair of wounded cell membranes is essential for cell survival. Upon wounding, actin transiently accumulates at the wound site. The loss of actin accumulation leads to cell death. The mechanism by which actin accumulates at the wound site, the types of actin-related proteins participating in the actin remodeling, and their signaling pathways are unclear. We firstly examined how actin accumulates at a wound site in Dictyostelium cells. Actin assembled de novo at the wound site, independent of cortical flow. Next, we searched for actin- and signal-related proteins targeting the wound site. Fourteen of the examined proteins transiently accumulated at different times. Thirdly, we performed functional analyses using gene knockout mutants or specific inhibitors. Rac, WASP, formin, the Arp2/3 complex, profilin, and coronin contribute to the actin dynamics. Finally, we found that multiple signaling pathways related to TORC2, the Elmo/Doc complex, PIP2-derived products, PLA2, and calmodulin are involved in the actin dynamics for wound repair.


Assuntos
Actinas , Dictyostelium , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Calmodulina/metabolismo , Dictyostelium/genética , Dictyostelium/metabolismo , Forminas , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Fosfolipases A2/metabolismo , Profilinas/genética , Profilinas/metabolismo , Transdução de Sinais
8.
J Pers Med ; 12(10)2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36294880

RESUMO

A two-stage surgical procedure involving labioplasty and palatoplasty is a common surgical modality performed in children with cleft lip and palate. Additionally, an alveolar cleft bone graft is performed prior to the eruption of the canine teeth. These three surgeries impose the burden of general anesthesia separately for each procedure, and the formation of scar tissue from the procedure inhibits maxillary growth. We adopted a single-stage surgical procedure to overcome these drawbacks. To date, there have been no reports comparing the treatment outcomes of alveolar morphology and maxillary growth and development in children who underwent single-stage surgery with those who underwent two-stage surgery using plaster casts and cephalograms. Twenty children aged 5-7 years were equally divided into two groups based on whether they had undergone a two- or single-stage procedure. Cephalometric analysis and analysis of dentition models were conducted. The results showed that the single-stage surgery exhibited significant differences in the sella-nasion angle, point A to McNamara line, maxillary length, mandibular body length, and posterior arch width and length compared with the two-stage surgery. Therefore, it was suggested that the single-stage surgery had a favorable effect on maxillary growth compared with the two-stage surgery.

9.
J Insect Physiol ; 131: 104225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33736983

RESUMO

Insect cytokine growth blocking peptide (GBP) is synthesized as an inactive precursor, termed proGBP, that is normally present in a significant concentration in the hemolymph of non-stressed animals (Hayakawa, 1990, 1991). Under stress conditions, proGBP is instantly processed to active GBP by a serine protease and this is thought to be an important initial step for insects to cope with stress-induced adverse effects via GBP-induced physiological changes. However, the detailed mechanism underlying proteolytic processing of hemolymph proGBP in insects under stress conditions remains unknown. Here we demonstrated that proGBP processing requires ROS-induced release of a proteinaceous factor from hemocytes that activates the inactive proGBP processing enzyme. The release of the activator protein from hemocytes is initiated by an elevation of the cytoplasmic Ca2+ concentration induced by ROS. Therefore, we concluded that stress-induced activation of proGBP requires ROS-dependent stimulation of an intracellular calcium signaling pathway in hemocytes, followed by release of the hemocyte proteinaceous factor that specifically activates the proGBP processing enzyme.


Assuntos
Citocinas/metabolismo , Hemócitos/metabolismo , Proteínas de Insetos/metabolismo , Mariposas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico , Animais , Sinalização do Cálcio
10.
Arthrosc Tech ; 10(2): e353-e357, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33680766

RESUMO

With improvement in arthroscopic techniques, partial meniscectomy with repair for symptomatic discoid lateral meniscus (DLM) has been the preferred treatment to restore meniscal function. It was reported that DLM exhibited deformation and extrusion shortly after saucerization with repair. Therefore it is desirable to minimize removal of the DLM. The anterior zone of the DLM is often tighter than that of the normal meniscus and anatomic variant. It is considered that the anterior and anterocentral dislocation types in the majority of symptomatic DLM can be related to both peripheral instability and anterior tightness. We present a technique that, first, the inside-out repair technique is applied from the posterior to middle segment of the DLM; next, the tension of the anterior zone during knee flexion-extension is confirmed to determine the released amount of that part; and, finally, all sutures are tied to reproduce the normal meniscus movement. Meniscus repair with anterior cord release without any meniscectomy could resolve peripheral instability of DLM and prevent degeneration of the articular cartilage.

11.
Arch Insect Biochem Physiol ; 106(2): e21758, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33145828

RESUMO

Stress enhances the concentration of reactive oxygen species (ROS) in animal plasma. Increased ROS alter various physiological functions, such as development and the immune response, but excessive increases could be harmful. In this study, we tested the hypothesis that abnormally increased plasma ROS levels are associated with animal death. Injection of the nematode Caenorhabditis elegans into insect larvae caused high mortality in Galleria mellonella, and the plasma ROS concentration was four times higher than M9 buffer-injected larvae. There was no difference in plasma antioxidant activity after nematode injection. However, coinjecting nematodes with an antioxidant (ascorbic acid or N-acetylcysteine) suppressed increases in ROS concentrations by the nematodes and increases in the number of nematodes in the larvae, which increased G. mellonella survival. These results suggest that the abnormal elevation of ROS associated with the stress caused by nematode propagation is lethal for G. mellonella.


Assuntos
Interações Hospedeiro-Parasita , Mariposas/parasitologia , Nematoides/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Larva/crescimento & desenvolvimento , Larva/parasitologia , Mariposas/crescimento & desenvolvimento , Plasma/parasitologia
12.
Knee ; 27(5): 1293-1299, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33010741

RESUMO

BACKGROUND: The purpose of this study was to investigate postoperative tunnel widening after rectangular tunnel bone-patellar-tendon-bone graft anterior cruciate ligament reconstruction using newer-generation bioabsorbable interference screws. METHODS: Forty-six patients who had undergone primary rectangular tunnel bone-patellar-tendon-bone graft anterior cruciate ligament reconstruction using MILAGRO bioabsorbable interference screws (DePuy Synthes, Warsaw, IN, USA) for femoral fixation and for whom computed tomography was performed at two weeks and one year postoperatively were included in this prospective study. To assess the tunnel widening, the cross-sectional area of the femoral tunnel aperture (compared between two weeks and one year postoperatively) was assessed using computed tomography. Cyst formation, postoperative screw breakage, screw migration, and graft migration were also evaluated using computed tomography one year postoperatively. RESULTS: Mean tunnel widening was 1.9%, and the cross-sectional area of the femoral tunnel aperture was not significantly different between two weeks and one year postoperatively. Postoperative cyst formation, screw breakage, screw migration, and graft migration were not observed in any patient. CONCLUSIONS: After rectangular tunnel bone-patellar-tendon-bone graft anterior cruciate ligament reconstruction using bioabsorbable interference screws for femoral fixation, tunnel widening was not observed via computed tomography analysis at two weeks and one year postoperatively.


Assuntos
Implantes Absorvíveis , Reconstrução do Ligamento Cruzado Anterior/métodos , Parafusos Ósseos , Enxertos Osso-Tendão Patelar-Osso , Adulto , Feminino , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Humanos , Masculino , Estudos Prospectivos , Tomografia Computadorizada por Raios X
13.
EMBO Rep ; 21(5): e49211, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32118349

RESUMO

Under stress conditions, mitochondria release low levels of reactive oxygen species (ROS), which triggers a cytoprotective response, called "mitohormesis". It still remains unclear how mitochondria respond to stress-derived stimuli and release a low level of ROS. Here, we show that N-acetyl-l-tyrosine (NAT) functions as a plausible intrinsic factor responsible for these tasks in stressed animals. NAT is present in the blood or hemolymph of healthy animals, and its concentrations increase in response to heat stress. Pretreatment with NAT significantly increases the stress tolerance of tested insects and mice. Analyses using Drosophila larvae and cultured cells demonstrate that the hormetic effects are triggered by transient NAT-induced perturbation of mitochondria, which causes a small increase in ROS production and leads to sequential retrograde responses: NAT-dependent FoxO activation increases in the gene expression of antioxidant enzymes and Keap1. Moreover, we find that NAT represses tumor growth, possibly via the activation of Keap1. In sum, we propose that NAT is a vital endogenous molecule that could serve as a triggering factor for mitohormesis.


Assuntos
Mitocôndrias , Fator 2 Relacionado a NF-E2 , Animais , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Camundongos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tirosina/análogos & derivados
14.
Artigo em Inglês | MEDLINE | ID: mdl-32042597

RESUMO

BACKGROUND: The aim of the study was to investigate the effects of navigation-based varus or axial rotational alignment through knee flexion on patient reported outcomes or the maximum flexion angle of unicompartmental knee arthroplasty (UKA). METHODS: Data were retrospectively collected from 46 knees that underwent UKA for medial unicompartmental knee osteoarthritis. An image-free knee navigation system was used in all cases, and intraoperative varus and axial rotational alignment at every knee flexion angle were recorded before and after implantation. All patients completed the Knee injury and Osteoarthritis Outcome Score (KOOS) at final follow-up. By varus or valgus at 0° knee flexion, the knees were subdivided into two groups (varus at 0° group, varus above the median value; neutral at 0° group, varus equal to or below the median value). By varus or valgus at 90° knee flexion, patients were similarly subdivided into two groups (varus at 90° group; neutral at 90° group). The maximum knee flexion angle was measured 3 months after surgery. RESULTS: There were no differences in the KOOS between the neutral at 0° group and the varus at 0° group. However, the KOOS activity score (79 ± 17 vs 69 ± 16, p = 0.02) and the KOOS total score (72 ± 17 vs 65 ± 15, p = 0.03) of the neutral at 90° group were better than those of the varus at 90° group. The alignment and the maximum knee flexion angle 3 months after surgery were not correlated. CONCLUSION: Varus at 0° knee flexion and axial rotational alignment did not affect the clinical outcomes of UKA. Patient reported outcomes was better for the neutral knees with less varus at 90° knee flexion than for varus knees.

15.
Nat Commun ; 11(1): 889, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060352

RESUMO

Idiopathic inflammatory myopathies cause progressive muscle weakness and degeneration. Since high-dose glucocorticoids might not lead to full recovery of muscle function, physical exercise is also an important intervention, but some exercises exacerbate chronic inflammation and muscle fibrosis. It is unknown how physical exercise can have both beneficial and detrimental effects in chronic myopathy. Here we show that senescence of fibro-adipogenic progenitors (FAPs) in response to exercise-induced muscle damage is needed to establish a state of regenerative inflammation that induces muscle regeneration. In chronic inflammatory myopathy model mice, exercise does not promote FAP senescence or resistance against tumor necrosis factor-mediated apoptosis. Pro-senescent intervention combining exercise and pharmacological AMPK activation reverses FAP apoptosis resistance and improves muscle function and regeneration. Our results demonstrate that the absence of FAP senescence after exercise leads to muscle degeneration with FAP accumulation. FAP-targeted pro-senescent interventions with exercise and pharmacological AMPK activation may constitute a therapeutic strategy for chronic inflammatory myopathy.


Assuntos
Terapia por Exercício , Células-Tronco Mesenquimais/citologia , Músculo Esquelético/fisiopatologia , Doenças Musculares/terapia , Regeneração , Envelhecimento , Animais , Apoptose , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Músculo Esquelético/imunologia , Doenças Musculares/imunologia , Doenças Musculares/fisiopatologia
16.
J Insect Physiol ; 117: 103889, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31136741

RESUMO

Armyworm Mythimna separata larvae show changes in cuticle darkening depending on population densities and are roughly categorized into two phenotypes, a pale brown solitary type and black-colored gregarious type. Although the color difference in both larval types is apparent, it remains ambiguous whether any change in physiological traits accompanies the cuticle darkening. To answer this query, we repeated genetic selection of the blackness phenotype over one hundred generations in our laboratory colony and produced a black-colored (BL) strain. Comparison between non-selected control (CTL) and BL strains revealed an increased fecundity and adult life span in the BL strain compared with the CTL strain. In contrast, BL strain larvae were found to be significantly more sensitive to heat stress than those in the CTL strain. Hemolymph reactive oxygen species (ROS) levels were higher in the BL strain than in the CTL strain under both non-stress and heat stress conditions. Antioxidant activities of the hemolymph were not significantly different between the two strains under non-stress condition, but the activities increased to higher levels in the CTL strain than those in the BL strain after heat stress. Activities and gene expression levels of antioxidant enzymes such as catalase and superoxide dismutase (SOD) in the fat body were significantly higher in CTL strain larvae than in BL strain larvae after heat treatment. Thermal stress tolerance of the offspring of crossings between the two strains showed a tolerance level almost equivalent to the maternal one: the cross between CTL females and BL males produced offspring with the higher tolerance compared with the oppositely crossed offspring. Expression levels of the antioxidant enzyme genes of the former offspring were found to be similar to those of CTL strain. These results indicate a trade-off between reproductive activity and stress resistance: the BL strain had acquired high reproductivity but had lost stress tolerance through repeated genetic selection. Furthermore, the present genetic analyses demonstrated that the phenotype of stress tolerance is derived from the maternal parent.


Assuntos
Mariposas , Pigmentação , Seleção Genética , Animais , Antioxidantes/metabolismo , Feminino , Hemolinfa/metabolismo , Larva , Masculino , Estresse Oxidativo
17.
Front Immunol ; 10: 241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30828336

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease caused by inflammation of the synovium and characterized by chronic polyarthritis that destroys bone and cartilage. Fibroblast-like synoviocytes (FLSs) in the synovium of patients with RA can promote cartilage and bone destruction by producing proteins such as matrix metalloproteinases and receptor activator of NF-κB ligand, thereby representing an important therapeutic target for RA. FLSs have several phenotypes depending on which cell surface proteins and adhesion factors are expressed. Identifying the cellular functions associated with different phenotypes and methods of controlling them are considered essential for developing therapeutic strategies for RA. In this study, synovial tissue was collected from patients with RA and control subjects who required surgery due to ligament injury or fracture. Immunohistological analysis was used to investigate the rates of positivity for phosphorylated platelet-derived growth factor receptor-αß (pPDGFRαß) and cadherin-11 (CDH11) expression, and apoptosis-related markers were assessed for each cell phenotype. Next, FLSs were isolated in vitro and stimulated with tumor necrosis factor-α (TNF-α) in addition to a combination of PDGF and transforming growth factor (2GF) to investigate pPDGFRαß and CDH11 expression and the effects of the inhibition of TNF and cyclin-dependent kinase (CDK) 4/6 on FLSs. Immunohistological analysis showed a large percentage of pPDGFRαß+CDH11- cells in the sub-lining layer (SL) of patients with RA. These cells exhibited increased B-cell lymphoma-2 expression, reduced TNF receptor-1 expression, resistance to cell death, and abnormal proliferation, suggesting a tendency to accumulate in the synovium. Further, in vitro 2GF stimulation of FLSs lowered, whereas 2GF + TNF stimulation increased the pPDGFRαß/CDH11 ratio. Hypothesizing that FLSs stimulated with 2GF + TNF would accumulate in vivo in RA, we determined the therapeutic effects of TNF and CDK4/6 inhibitors. The TNF inhibitor lowered the pPDGFRαß/CDH11 ratio, whereas the CDK4/6 inhibitor suppressed cell proliferation. However, a synergistic effect was not observed by combining both the drugs. We observed an increase in pPDGFRαß+CDH11- cells in the SL of the RA synovium and accumulation of these cells in the synovium. We found that the TNF inhibitor suppressed FLS activity and the CDK4/6 inhibitor reduced cell proliferation.


Assuntos
Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Artrite Reumatoide/patologia , Proliferação de Células , Células Cultivadas , Progressão da Doença , Feminino , Fibroblastos , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Fenótipo , Membrana Sinovial , Sinoviócitos , Fator de Necrose Tumoral alfa , Adulto Jovem
18.
Arthroscopy ; 35(3): 896-905, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30733036

RESUMO

PURPOSE: The first objective of our cadaveric study was to perform a biomechanical comparison of single-bundle (SB), double-bundle (DB), and triple-bundle (TB) anterior cruciate ligament (ACL) reconstructions using a hamstring tendon graft to determine the laxity match pre-tension (LMP) value, which is the tension within the graft required to re-create the same anterior laxity as the ACL-intact knee. The second objective was to determine the anterior laxity and force distribution during the application of both an anterior force and a simulated pivot-shift test. METHODS: Eleven fresh-frozen cadaveric knees were tested using a robotic/universal force-moment sensor system in the intact state, TB-reconstructed knee, DB-reconstructed knee, and SB-reconstructed knee. The LMP in each reconstruction was recorded. Each reconstructed knee was tested with an external load of 100-N anterior drawer and combined rotatory loads of 10-Nm valgus moment and 5-Nm internal rotation. The anterior tibial translation and tensile forces of each graft bundle were measured. RESULTS: The LMP values for the TB reconstruction were 1.7 N for the anteromedial-medial graft, 1.7 N for the anteromedial-lateral graft, and 3.4 N for the posterolateral graft (PLG). The LMP value was 5.6 N for the anteromedial graft and PLG in the DB reconstruction. The LMP value was 26.3 N for the whole graft in the SB reconstruction. No statistically significant difference in stability was found between TB and DB reconstructions during the anterior load and the combined rotatory load test. For force distribution, the PLG tension in the TB reconstruction was statistically lower than that in the DB reconstruction. CONCLUSIONS: Anatomic TB ACL reconstruction with the lowest initial tension on the graft stabilized the knee equally to DB or SB reconstruction, which required greater initial tension. CLINICAL RELEVANCE: Although SB, DB, and TB ACL reconstructions through the anatomic tunnel position could equally restore stability, the initial tension on the graft required to restore stability was less in the latter 2 multi-tunnel reconstructions.


Assuntos
Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Ligamento Cruzado Anterior/fisiologia , Tendões dos Músculos Isquiotibiais/transplante , Idoso , Idoso de 80 Anos ou mais , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/fisiopatologia , Fenômenos Biomecânicos , Cadáver , Feminino , Humanos , Articulação do Joelho/cirurgia , Masculino , Rotação
19.
Clin Biomech (Bristol, Avon) ; 60: 121-126, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30342380

RESUMO

BACKGROUND: Suture-button (SB) fixation has been widely performed for syndesmosis injuries, but it has been reported unstable in some biomechanical studies. The purpose of this study was to evaluate the stability of the syndesmosis using SB fixation with anterior inferior tibiofibular ligament augmentation using suture-tape (ST). METHODS: Eight normal fresh-frozen cadaveric legs were used. After initial tests of intact and injured models, SB fixation, SB fixation with ST augmentation, ST augmentation alone, and screw fixation were performed sequentially for each specimen. Loading tests stimulating dorsiflexion, inversion, and external rotation of the ankle joint were performed for each model. The tibiofibular diastasis (TFD) and the fibular rotational angle related to the tibia (FRA) were measured using a magnetic tracking system. FINDINGS: In the injured model, both TFD and FRA increased significantly compared with the intact model in all directions (P < .05). In the SB fixation model, TFD and FRA generally showed significant increases (P < .05, except for TFD in external rotation). In the SB fixation with ST augmentation model and ST augmentation alone, TFD and FRA were not significantly different compared with the intact model (P > .05). In the screw fixation model, FRA with inversion force at the ankle was significantly decreased compared with the intact model (P = .027). INTERPRETATION: SB fixation alone did not provide stability of the syndesmosis, and screw fixation became too rigid compared with the intact model. Using ST augmentation achieved dynamic stability similar to the intact model for syndesmotic injuries.


Assuntos
Traumatismos do Tornozelo/cirurgia , Parafusos Ósseos , Fíbula/cirurgia , Ligamentos Laterais do Tornozelo/cirurgia , Suturas , Tíbia/cirurgia , Idoso , Idoso de 80 Anos ou mais , Articulação do Tornozelo/cirurgia , Fenômenos Biomecânicos , Cadáver , Feminino , Humanos , Masculino , Rotação , Estresse Mecânico , Técnicas de Sutura
20.
J Orthop Sci ; 23(6): 1000-1004, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30017713

RESUMO

BACKGROUND: Hypermobile lateral meniscus (HLM) is one of the causes of knee pain and a locking sensation. It is thought that disruption of the popliteomeniscle fascicles lead to hypermobility of the lateral meniscus in adults. In cases of HLM, the posterior portion of the lateral meniscus shows forward abnormal translation with knee flexion and backward translation with knee extension. We refer to this phenomenon as paradoxical motion. The purpose of this study was to report an arthroscopic HLM stabilization and evaluate the midterm clinical outcomes. METHODS: Twenty consecutive HLM patients (21 knees) who underwent arthroscopic surgery were included. The mean age at the time of surgery was 37.7 (19-63) years. Mean duration from surgery to final follow-up was 37 (24-68) months. Meniscus movement according to the knee flexion and extension was observed by diagnostic arthroscopy. We performed arthroscopic inside-out vertical stacked suturing of disrupted popliteomeniscle fascicles. The number of suturing and details of meniscal movement were assessed. The Tegner activity level score and Lysholm knee scores were determined preoperatively and at 2 years postoperatively. Clinical outcomes included locking sensation, recurrences and complications reported at the final follow-up. RESULTS: Paradoxical motion of the lateral meniscus was observed in all patients. We performed an average of 5.0 (2-8) vertical stacked sutures of the disrupted popliteomeniscal fascicles. Physiological motion of the lateral meniscus was observed after meniscus repairs. The mean Tegner activity level scales before and after surgery were 4.6 (2-8) and 4.7 (2-8), respectively. The mean Lysholm knee scores significantly improved from 72.0 (48-85) preoperatively to 97.8 (78-100) at 2 years postoperatively. There were no complications or recurrences of locking symptoms at the final follow-up. CONCLUSIONS: Use of arthroscopic inside-out vertical sutures for disrupted popliteomeniscle fascicles improved the clinical outcomes for HLM patients without complications.


Assuntos
Artroscopia , Instabilidade Articular/prevenção & controle , Articulação do Joelho , Técnicas de Sutura , Lesões do Menisco Tibial/cirurgia , Adulto , Estudos de Coortes , Feminino , Humanos , Instabilidade Articular/etiologia , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Lesões do Menisco Tibial/complicações , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...