RESUMO
Metagenomic studies show that diverse resident viruses inhabit the healthy gut; however, little is known about the role of these viruses in the maintenance of gut homeostasis. We found that mice treated with antiviral cocktail displayed more severe dextran sulfate sodium (DSS)-induced colitis compared with untreated mice. DSS-induced colitis was associated with altered enteric viral abundance and composition. When wild-type mice were reconstituted with Toll-like receptor 3 (TLR3) or TLR7 agonists or inactivated rotavirus, colitis symptoms were significantly ameliorated. Mice deficient in both TLR3 and TLR7 were more susceptible to DSS-induced experimental colitis. In humans, combined TLR3 and TLR7 genetic variations significantly influenced the severity of ulcerative colitis. Plasmacytoid dendritic cells isolated from inflamed mouse colon produced interferon-ß in a TLR3 and TLR7-dependent manner. These results imply that recognition of resident viruses by TLR3 and TLR7 is required for protective immunity during gut inflammation.
Assuntos
Colite/imunologia , Trato Gastrointestinal/virologia , Interferon beta/imunologia , Glicoproteínas de Membrana/imunologia , Rotavirus/imunologia , Receptor 3 Toll-Like/imunologia , Receptor 7 Toll-Like/imunologia , Animais , Antivirais/farmacologia , Colite/induzido quimicamente , Células Dendríticas/imunologia , Sulfato de Dextrana , Microbioma Gastrointestinal , Trato Gastrointestinal/imunologia , Humanos , Inflamação/imunologia , Interferon beta/biossíntese , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , RNA Ribossômico 16S/genética , Receptor 3 Toll-Like/genética , Receptor 7 Toll-Like/genéticaRESUMO
INTRODUCTION: We aimed to investigate the clinical significance of loudness discomfort level (LDL) test in tinnitus patients and its relationship with pure-tone audiometry, tinnitogram and questionnaires. METHODS: We retrospectively reviewed the medical records of 320 tinnitus patients who visited a tertiary university hospital's tinnitus clinic and completed LDL tests between March 2020 and December 2022. Epidemiological data and psychoacoustic test results were collected. RESULTS: LDL showed no significant differences between frequencies for both ears. Mean LDL did not correlate with mean pure-tone average or hearing thresholds at each frequency. The hearing loss group had higher LDL at 8 kHz compared to the normal hearing group (p<0.01). Objective sound intolerance was found in a quarter, correlating with subjective hyperacusis, anxiety, and depression. Weak negative correlations were found between most of questionnaire's scores and LDL on the left side. Tinnitus loudness weak negatively correlated with LDL at most frequencies, except 8 kHz. DISCUSSION/CONCLUSION: Our findings suggest a notable association between LDL levels and emotional factors in tinnitus patients, rather than with auditory thresholds. While lateralized differences in LDL responses were observed, specifically on the left side, these preliminary results do not confirm a causal link and thus do not warrant changes to current clinical testing protocols without further research.
RESUMO
OBJECTIVES: This study aimed to explore the electrophysiological characteristics of patients with chronic tinnitus through electrocochleography (ECochG) findings and determine if these findings correlate with specific audiological patterns that could differentiate tinnitus patients from those without this condition. MATERIALS AND METHODS: A retrospective analysis of medical records from patients who visited a tinnitus clinic at a tertiary university hospital between March 2020 and December 2023 was conducted. Inclusion criteria were non-pulsatile subjective tinnitus lasting over three months, and ECochG performed at initial evaluation. Audiological assessments and ECochG results were analyzed, with the SP/AP ratio being a focal point. RESULTS: Among 256 patients, an elevated SP/AP ratio was observed in 37.5 % of patients. No significant difference in ECochG outcomes was noted based on tinnitus laterality. Patients with an elevated SP/AP ratio reported more sleep disturbances, higher depression scores, attention problems, and aural fullness. These patients also exhibited lower loudness discomfort levels and low-frequency hearing losses. Significant correlations were found between elevated SP/AP ratios and DPOAE responses. CONCLUSIONS: The findings highlight the SP/AP ratio in ECochG as a valuable biomarker for assessing clinical and psychological aspects of tinnitus, indicating its potential utility in tailoring treatment strategies. Elevated SP/AP ratios were associated with sleep disturbances, depression, attention problems, aural fullness, hyperacusis, and low-frequency hearing loss, suggesting a complex interplay between cochlear pathology and tinnitus perception. This study underscores the need for a nuanced understanding of ECochG results in the clinical evaluation of tinnitus, potentially guiding more personalized management approaches.
RESUMO
Traumatic neuroma is the reparative proliferation of axons and Schwann cells at the proximal end of a severed nerve following injury or surgery. Traumatic neuromas with or without clinical symptoms have rarely been reported in the external auditory canal. A 50-year-old woman with a history of trauma visited our otorhinolaryngology clinic with a 7 × 5-mm mass localized on the anterior wall of the external auditory canal. The mass was easily removed via surgical excision and was histopathologically diagnosed as a neuroma. No signs of recurrence were observed after excision. Herein, the authors present this case, along with a review of the literature.
RESUMO
OBJECTIVES: The Tinnitus Handicap Inventory (THI) and Numerical Rating Scale (NRS) for awareness, annoyance, loudness, and effect on life are two of the most commonly used questionnaires for patients with tinnitus. This study aimed to determine whether these two questionnaires can comprehensively evaluate the patient's condition and which questionnaire is better as a primary endpoint for tinnitus. MATERIALS AND METHODS: Data from 90 patients who visited a university hospital with subjective, non-pulsatile tinnitus and without a history of any psychiatric disorders were reviewed between March 2020 and May 2022. The patients' medical histories, audiological profiles, questionnaires including the THI and NRS, Beck Depression Inventory (BDI), Beck Anxiety Depression (BAI), Hospital Anxiety-Depression Scale (HAD), and the Brief Encounter Psychosocial Instrument (BEPSI) were analyzed. RESULTS: The THI had a moderately positive correlation with the NRS for effect on life, annoyance, and loudness. It also had a low positive correlation with the BDI, HAD-A, BEPSI, and BAI. Considering annoyance and loudness, the NRS did not correlate with the other questionnaires, except for the THI (p > 0.05). The NRS for tinnitus awareness correlated with most audiological profiles. The ROC curve analysis revealed that the THI significantly predicted depression, anxiety, and stress. Conversely, none of the four NRS items significantly predicted these psychiatric problems (p > 0.05). CONCLUSIONS: Using the THI as a primary endpoint after interventions rather than the NRS is more reasonable because the THI covers the emotional, functional, and catastrophic aspects of tinnitus, although not the audiological status. To compensate for this, the auxiliary use of NRS for awareness should also be considered.
Assuntos
Zumbido , Humanos , Depressão/diagnóstico , Depressão/etiologia , Depressão/psicologia , Emoções , Ansiedade/diagnóstico , Ansiedade/etiologia , Inquéritos e QuestionáriosRESUMO
In studies that assessed the accuracy of implant surgical guides, evaluations were based on the placement position of the implant by using a manufactured surgical guide. However, such assessments could involve errors that may occur during implant placement. Therefore, evaluating the 3-dimensional accuracy of the fabrication of the implant surgical guide itself is not enough. In the evaluation method described in this article, location-related information is obtained by connecting a scan body to the sleeve of the surgical guide instead of directly placing the implant. This helps to evaluate the accuracy of the surgical guide without errors in the placement of an implant.
Assuntos
Implantes Dentários , Cirurgia Assistida por Computador , Desenho Assistido por Computador , Tomografia Computadorizada de Feixe Cônico , Implantação Dentária Endóssea/métodos , Imageamento TridimensionalRESUMO
PURPOSE/OBJECTIVES: Dental students experience difficulties during the transition from preclinical to clinical curriculum. In order to help the students to adapt to the clinical education programme, a simulated practice using patient-based customised models was introduced in this study to prepare for their first clinical practice. METHODS: This study included 45 third-year predoctoral students (D3 students) who were about to perform the preparation of a single crown abutment on their first patient. After practicing abutment preparation using simulated models and providing the actual treatment to their own patient, the students were surveyed to investigate their perceptions on the simulated practice using the 3D-printed customised typodont model. The statistical analysis of the quantitative data and the thematic analysis of the qualitative data were conducted. RESULTS: Regarding this simulation, more than 80% of the students gave positive feedback on their practice of (a) operative positions and postures, (b) finger rest, (c) occlusal reduction, (d) axial reduction and (e) proximal reduction. Student responses on the open-ended questions about how they perceived the usefulness of this simulation were categorised as "First clinical case," "Patient-based model" and "Realistic simulation environment." In addition, a number of improvements of the simulation were also suggested by the students including the typodont and the manikin. CONCLUSIONS: This study gives insights into the significance of simulated practice using patient-based customised typodonts as a transitional education tool and its direction of development in the field of restorative treatments accompanied by irreversible tooth preparations.
Assuntos
Educação em Odontologia , Estudantes de Odontologia , Coroas , Humanos , Manequins , Preparo do DenteRESUMO
We present a method to extend the axial range of digital holographic microscopy based on the optimal modified lateral shearing interferometer (MLSI). The proposed system can extend the axial range by using a dual optical plate. The interference pattern with two spatial wavelengths is generated by the plate with different thicknesses. These spatial wavelengths transfer a dual spatial frequency into the Fourier plane by using FFT. Two phases are extracted by a dual spatial frequency and combined to create a synthetic wavelength, which is applied to measure the micrometer-scale object without phase unwrapping. Also, the noise-reducing algorithm is used to reduce phase noise caused by the amplified noise of the synthetic wavelength. The experimental result confirms the feasibility of the optimal MLSI by using a dual optical plate.
RESUMO
PURPOSE: Thunderbeat (TB) is an integrated energy device incorporating ultrasonic and bipolar technology that provides rapid cut and precision dissection and reliable vessel sealing compared with conventional electrosurgery (ES). The present study compared the surgical outcomes of TB and ES for harvesting the anterolateral thigh free flap (ALTFF). PATIENTS AND METHODS: The present prospective cohort study compared TB and ES in patients who had undergone head and neck reconstruction using ALTFFs. The baseline characteristics, including age, gender, body mass index, primary tumor site (recipient site), and T stage, were measured. Patients who had undergone reconstruction after previous unsuccessful head and neck cancer treatment using radiation were included in the salvage surgery group. The primary outcome variables were the harvesting time, blood loss, and flap failure. The interval until the start of an oral diet and the percutaneous endoscopic gastrostomy (PEG) insertion rate were analyzed to compare the functional outcomes. After identifying the confounding variables, multivariate approaches were used to adjust for the confounding variables. RESULTS: No significant differences were found in the demographics and disease-related factors such as age, gender, body mass index, anatomic distribution, and T stage of the primary disease, between the 2 groups. The operation time and bleeding volume were reduced by 32.4 and 33.1%, respectively, in the TB group compared with those in the control group. The postoperative drainage volume, duration, flap failure rate, and intensive care unit and total hospital stays were nearly identical between the 2 groups. No statistically significant differences were found in the functional outcomes (PEG insertion and oral diet start day) between the 2 groups. CONCLUSIONS: The results of the present study have shown that TB is a useful supportive tool for head and neck reconstruction surgery because it decreases the operation time with surgical outcomes comparable to those with conventional ES.
Assuntos
Transtorno Bipolar , Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos de Cirurgia Plástica , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , UltrassomRESUMO
BACKGROUND: Aquafilling filler is used for breast and buttock augmentation, which are the most commonly performed cosmetic surgery procedures. However, complications after using Aquafilling filler for breast augmentation have been reported, and there are concerns regarding its use in large areas, such as the buttocks. We provide our experience with complications after breast augmentation and buttock augmentation using Aquafilling filler. METHODS: This observational cohort study analyzed the data of 399 patients treated for filler-related complications at our institutes from September 2015 to November 2019. Of these patients, 146 underwent surgery to remove Aquafilling filler from the breast or buttock. RESULTS: The mean time between Aquafilling filler use and complication onset was 38.5 ± 10.2 months. The average amount of filler material removed from one side of the breast or buttock was 285.5 ± 95.8 mL (range 150-750 mL). The most common complications were induration and masses (83.6%), followed by pain (52.1%), firmness (24.7%), asymmetry (10.3%), migration (8.2%), mastitis (6.8%), dimpling (6.2%), fever (3.4%), and sepsis (n = 1). After treatment, there was no recurrence of infection, and the patient satisfaction level based on the visual analogue scale was 8.0 ± 0.9. CONCLUSIONS: Although Aquafilling filler is easily injectable and has long-term clinical effects, complications can occur. Furthermore, there are concerns regarding its toxicity and influence on the surrounding tissues. Hence, further research studies on Aquafilling filler and evidence regarding its long-term safety are needed. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Assuntos
Mamoplastia , Mama , Nádegas , Estética , Feminino , Humanos , Mamoplastia/efeitos adversos , Reoperação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
To simulate the current oral status of patients, including maxillofacial defects, the digital method described uses a method based on multisource data. These include data recorded from scans made with and without wearing an obturator and data obtained by scanning the surgical or interim obturator. This method eliminates the need for preliminary impressions and complex border-molding steps during the process of creating a definitive obturator, thereby greatly simplifying the fabrication process.
Assuntos
Implantes Dentários , Obturadores Palatinos , Humanos , BocaRESUMO
BACKGROUND: Target enrichment is a critical component of targeted deep next-generation sequencing for the cost-effective and sensitive detection of mutations, which is predominantly performed by either hybrid selection or PCR. Despite the advantages of efficient enrichment, PCR-based methods preclude the identification of PCR duplicates and their subsequent removal. Recently, this limitation was overcome by assigning a unique molecular identifier(UMI) to each template molecule. Currently, several commercial library construction kits based on PCR enrichment are available for UMIs, but there have been no systematic studies to compare their performances. In this study, we evaluated and compared the performances of five commercial library kits from four vendors: the Archer® Reveal ctDNA™ 28 Kit, NEBNext Direct® Cancer HotSpot Panel, Nugen Ovation® Custom Target Enrichment System, Qiagen Human Comprehensive Cancer Panel(HCCP), and Qiagen Human Actionable Solid Tumor Panel(HASTP). RESULTS: We evaluated and compared the performances of the five kits using 50 ng of genomic DNA for the library construction in terms of the library complexity, coverage uniformity, and errors in the UMIs. While the duplicate rates for all kits were dramatically decreased by identifying unique molecules with UMIs, the Qiagen HASTP achieved the highest library complexity based on the depth of unique coverage indicating superb library construction efficiency. Regarding the coverage uniformity, the kits from Nugen and NEB performed the best followed by the kits from Qiagen. We also analyzed the UMIs, including errors, which allowed us to adjust the depth of unique coverage and the length required for sufficient complexity. Based on these comparisons, we selected the Qiagen HASTP for further performance evaluations. The targeted deep sequencing method based on PCR target enrichment combined with UMI tagging sensitively detected mutations present at a frequency as low as 1% using 6.25 ng of human genomic DNA as the starting material. CONCLUSION: This study is the first systematic evaluation of commercial library construction kits for PCR-based targeted deep sequencing utilizing UMIs. Because the kits displayed significant variability in different quality metrics, our study offers a practical guideline for researchers to choose appropriate options for PCR-based targeted sequencing and useful benchmark data for evaluating new kits.
Assuntos
Biomarcadores/análise , DNA/análise , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Reação em Cadeia da Polimerase/métodos , Kit de Reagentes para Diagnóstico/normas , DNA/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala/normas , Humanos , Reação em Cadeia da Polimerase/normasRESUMO
The twigs of Cinnamomum cassia, commonly referred to as Cinnamomi Ramulus, are widely used as one of the primary ingredients in Chinese/Korean traditional medicines that have anticancer effects. However, the active constituents responsible for its anticancer effects and their molecular mechanisms still remain to be elucidated. Caffeic acid phenethyl ester (CAPE) and caffeic acid (CA) were isolated for the first time from C. cassia using LC-MS-guided phytochemical isolation methods. CAPE significantly suppressed EGF- and TPA-induced cell transformation of JB6 P+ cells at sub-micromolar concentrations, whereas CA, a structurally similar compound to CAPE, had no such effect. The antiproliferative and chemopreventive activity of CAPE was found to arise through the inhibition of AP-1 transcriptional activity via the promotion of c-Fos degradation. These findings demonstrate that CAPE may contribute to the chemopreventive/chemotherapeutic effects of C. cassia through downregulating c-Fos.
Assuntos
Anticarcinógenos/isolamento & purificação , Anticarcinógenos/farmacologia , Ácidos Cafeicos/isolamento & purificação , Ácidos Cafeicos/farmacologia , Cinnamomum aromaticum/química , Álcool Feniletílico/análogos & derivados , Caules de Planta/química , Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos , Anticarcinógenos/química , Ácidos Cafeicos/química , Estrutura Molecular , Álcool Feniletílico/química , Álcool Feniletílico/isolamento & purificação , Álcool Feniletílico/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , República da Coreia , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismoRESUMO
Transparent optical components, which are required for high-precision and high-performance, are made by a plastic injection molding method. This can cause inner defects to appear because of the difference in cooling rate and pressure. However, submicron inner defects, caused by the refractive index error, are extremely difficult to determine. Thus, digital holographic microscopy based on an optimal modified lateral shearing interferometer is proposed. This is to measure submicron defects in transparent objects, such as a defective microlens. In addition, the optimal lateral shearing distance is proposed to efficiently remove duplicate images. Optical experiments using the suggested lateral shearing interferometer are presented, and the experimental results with a test microlens confirm the feasibility of the proposed method.
RESUMO
Bioactive phytochemicals can suppress the growth of malignant cells, and investigation of the mechanisms responsible can assist in the identification of novel therapeutic strategies for cancer therapy. Ginger has been reported to exhibit potent anti-cancer effects, although previous reports have often focused on a narrow range of specific compounds. Through a direct comparison of various ginger compounds, we determined that gingerenone A selectively kills cancer cells while exhibiting minimal toxicity toward normal cells. Kinase array screening revealed JAK2 and S6K1 as the molecular targets primarily responsible for gingerenone A-induced cancer cell death. The effect of gingerenone A was strongly associated with relative phosphorylation levels of JAK2 and S6K1, and administration of gingerenone A significantly suppressed tumor growth in vivo. More importantly, the combined inhibition of JAK2 and S6K1 by commercial inhibitors selectively induced apoptosis in cancer cells, whereas treatment with either agent alone did not. These findings provide rationale for dual targeting of JAK2 and S6K1 in cancer for a combinatorial therapeutic approach.
Assuntos
Apoptose/efeitos dos fármacos , Diarileptanoides/farmacologia , Inibidores Enzimáticos/farmacologia , Janus Quinase 2/antagonistas & inibidores , Proteínas Quinases S6 Ribossômicas 70-kDa/antagonistas & inibidores , Linhagem Celular Tumoral , Humanos , Janus Quinase 2/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismoRESUMO
OBJECTIVE: To examine the effects of pelvic floor muscle training (PFMT) on the contractility of pelvic floor muscle and lower urinary tract symptoms in female stroke patients. DESIGN: Randomized, single-blind controlled study. SETTING: Outpatient rehabilitation hospital. SUBJECTS: Thirty one female patients who were more than three months post-stroke and stress urinary incontinence. INTERVENTIONS: The subjects were randomized to either a PFMT group (n = 16), or a control group (n = 15). Both groups received general rehabilitation exercise for 6 weeks, but the PFMT group additionally received PFMT for 6 weeks. MAIN MEASURES: Vaginal function test using a perineometer (maximal vaginal squeeze pressure) and intra-vaginal electromyography (activity of pelvic floor muscle), and urinary symptoms and quality of life using a Bristol Female Lower Urinary Tract Symptom questionnaire. RESULTS: After intervention, the maximal vaginal squeeze pressures for the PFMT and control groups were 18.35 (5.24) and 8.46 (3.50) mmHg, respectively. And the activities of pelvic floor muscle of the PFMT and control groups was 12.09 (2.24) 㶠and 9.33 (3.40) ã¶, respectively. After intervention, the changes of scores for inconvenience in the activity of daily living of the PFMT and control groups were -15.00 (6.25) and -0.17 (1.59), respectively. In addition, the changes of score for lower urinary tract symptom was improved more in the PFMT group (-4.17 (4.00)) than in the control group (-0.25 (1.29)) (P < 0.05). CONCLUSIONS: These findings suggest that PFMT is beneficial for the management of urinary incontinence in female stroke patients.
Assuntos
Terapia por Exercício , Contração Muscular , Diafragma da Pelve , Acidente Vascular Cerebral/complicações , Incontinência Urinária/etiologia , Incontinência Urinária/reabilitação , Idoso , Eletromiografia , Feminino , Humanos , Pessoa de Meia-Idade , Força Muscular , Qualidade de Vida , Método Simples-Cego , Resultado do TratamentoRESUMO
Combination chemotherapy for the treatment of pancreatic cancer commonly employs gemcitabine with an EGFR inhibitor such as erlotinib. Here, we show that the retinoic acid derivative, ABPN, exhibits more potent anticancer effects than erlotinib, while exhibiting less toxicity toward noncancerous human control cells. Low micromolar concentrations of ABPN induced apoptosis in BxPC3 and HPAC pancreatic cancer cell lines, concomitant with a reduction in phosphorylated EGFR as well as decreased ErbB3, Met and BRUCE protein levels. The degradation of ErbB3 is a result of proteasomal degradation, possibly due to the ABPN-dependent upregulation of Nrdp1. Administration of ABPN showed significant reductions in tumor size when tested using a mouse xenograft model, with higher potency than erlotinib at the same concentration. Analysis of the tumors demonstrated that ABPN treatment suppressed ErbB3 and Met and induced Nrdp1 in vivo. The data suggest that ABPN may be more suitable in combination chemotherapy with gemcitabine than the more widely used EGFR inhibitor, erlotinib.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Retinoides/farmacologia , Ativação Transcricional/efeitos dos fármacos , Ubiquitina-Proteína Ligases/genética , Animais , Apoptose , Linhagem Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Sinergismo Farmacológico , Cloridrato de Erlotinib/farmacologia , Fluoruracila/farmacologia , Humanos , Masculino , Camundongos Nus , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptor ErbB-3/metabolismo , Transdução de Sinais , Tretinoína/farmacologia , Carga Tumoral/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , GencitabinaRESUMO
Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms. Our study revealed that mice with genetic deficiency of caspase-7 are highly susceptible to SSL-induced skin carcinogenesis. Epidermal hyperplasia, tumor volume and the average number of tumors were significantly increased in caspase-7 knockout (KO) mice compared with SKH1 wild-type mice irradiated with SSL. The expression of cell proliferation markers, such as survivin and Ki-67, was elevated in SSL-irradiated skin of caspase-7 KO mice compared with those observed in SSL-exposed wild-type SKH1 mouse skin. Moreover, SSL-induced apoptosis was abolished in skin from caspase-7 KO mice. Two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization-time-of-flight analysis of skin tissue lysates from SSL-irradiated SKH1 wild-type and caspase-7 KO mice revealed an aberrant induction of keratin-17 in caspase-7 KO mice. Immunohistochemical analysis of skin tumors also showed an increase of keratin-17 expression in caspase-7 KO mice compared with SKH1 wild-type mice. The expression of keratin-17 was also elevated in SSL-irradiated caspase-7 KO keratinocytes as well as in human basal cell carcinomas. The in vitro caspase activity assay showed keratin-17 as a substrate of caspase-7, but not caspase-3. Overall, our study demonstrates that genetic loss of caspase-7 promotes SSL-induced skin carcinogenesis by blocking caspase-7-mediated cleavage of keratin-17.
Assuntos
Carcinoma de Células Escamosas/enzimologia , Caspase 7/genética , Queratinas/fisiologia , Lesões Experimentais por Radiação/enzimologia , Neoplasias Cutâneas/enzimologia , Luz Solar/efeitos adversos , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Caspase 7/metabolismo , Células Cultivadas , Epiderme/enzimologia , Epiderme/patologia , Epiderme/efeitos da radiação , Feminino , Técnicas de Inativação de Genes , Queratinócitos/enzimologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteólise , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Carga TumoralRESUMO
To examine the effects of high-fat diet (HFD) on melanoma progression, HFD-fed C57BL/6N mice were subcutaneously injected with syngeneic B16F10 melanoma cells. At 3 weeks post-injection, the tumors were resected; the mice were then sacrificed at 2 weeks post-resection. HFD stimulated melanoma growth and lymph node (LN) metastasis as well as tumor and LN lymphangiogenesis. Lipid vacuoles in the tumor and M2-macrophage (MΦ)s in the adipose and tumor tissues were increased in HFD-fed mice. CCL19 and CCL21 contents were higher in LNs than in tumors. HFD increased both CCL19 and CCL21 levels in LNs and CCR7 in tumors. Adipose tissue-conditioned media (CM) from HFD-fed mice enhanced lymphangiogenesis, and mature adipocyte (MA)/M2-MΦ co-culture CM markedly stimulated the tube formation of lymphatic endothelial cell (LEC)s and B16F10 migration. Monocyte migration was moderately stimulated by B16F10 or MA CM, but tremendously stimulated by B16F10/M2-MΦ co-culture CM, which was enhanced by MA/B16F10/M2-MΦ co-culture CM. The co-culture results revealed that MAs increased CCL2, M-CSF and CCR7 mRNAs in B16F10s; vascular endothelial growth factor (VEGF)-D mRNA in M2-MΦs; and CCL19, CCL21 and VEGF receptor (VEGFR)3 mRNA in LECs. M2-MΦs increased CCL2, M-CSF and VEGF-A mRNAs in B16F10s, whereas B16F10s increased VEGF-C mRNAs in M2-MΦs and VEGFR3 mRNA in LECs. These results indicate that in HFD-fed mice, MA-induced CCL2 and M-CSF in tumor cells increase M2-MΦs in tumor; the crosstalk between tumor cells and M2-MΦs further increases cytokines and angiogenic and lymphangiogenic factors. Additionally, MA-stimulated CCL19, CCL21/CCR7 axis contributes to increased LN metastasis in HFD-fed mice.
Assuntos
Adipócitos/patologia , Dieta Hiperlipídica/efeitos adversos , Linfangiogênese , Macrófagos/patologia , Melanoma Experimental/patologia , Obesidade/etiologia , Adipócitos/metabolismo , Aloenxertos , Animais , Apoptose , Western Blotting , Proliferação de Células , Quimiocinas/metabolismo , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Leptina/fisiologia , Metástase Linfática , Macrófagos/metabolismo , Masculino , Melanoma Experimental/genética , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Patológica , Obesidade/fisiopatologia , Análise Serial de Proteínas , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptor Tipo 4 de Melanocortina/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Microambiente TumoralRESUMO
[Purpose] The aim of the study was to assess the effect of an 8-week balance exercise program for enhancement of gait function on temporal and spatial parameters of school aged children with intellectual disabilities. [Subjects] Forty young people with intellectual disabilities were assigned either to the balance exercise program for enhancement of gait function group (BG group, n=19) or the control group (n=21). [Methods] The BG group attended an 8-week balance exercise program for enhancement of gait function consisting of two sessions a week. Gait was assessed using temporal and spatial parameters. [Results] The balance exercise program resulted in significant improvements in participant performance in temporal and spatial parameters. [Conclusion] A balance exercise program for enhancement of gait function can be an effective intervention for improving functional outcomes and can be recommended as an alternative mode of physical activity programming for improving balance and gait.