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1.
Langmuir ; 37(37): 10979-10986, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34491749

RESUMO

Understanding the rheological behavior of materials is of great importance in science. Here, we report a microscopic foundation for optorheology by manipulating the rheological feature through light. A new phenomenon is observed in the photosynthetic bacterial suspension, that the fluid viscosity changes by light-induced electrons. Type IV pili of photosynthetic bacteria is found, and it allows the electron to transport through the exterior of cells and changes the surface potential of cells, which causes an adjustment in the spatial arrangement of cells in the suspension. When an external electric field is applied, the electric dipole of the cells is induced and their dispersion is changed. The rheological properties are measured to evaluate the internal structure of the suspension depending on the light. The photoelectrons enhance the dispersion of the photosynthetic bacteria in the solution, thus leading to a significant increment in the viscosity. We envision that this discovery will provide new applications to the interface of optics, bioengineering, and rheology.


Assuntos
Bactérias , Reologia , Suspensões , Viscosidade
2.
Arthritis Res Ther ; 23(1): 249, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565447

RESUMO

INTRODUCTION: Retroperitoneal fibrosis (RPF) is characterized by a highly fibrotic retroperitoneal mass and encompasses the idiopathic form and secondary to malignancies. Because we have limited knowledge whether RPF is associated with malignancy, we aimed to investigate the relationship between RPF and malignancy and to compare the characteristics and prognosis of cancers among patients with RPF. METHODS: Medical records of 111 patients diagnosed as having RPF were reviewed and 38 cases of cancer, confirmed by biopsy, were identified. Standardized incidence ratios (SIRs) were calculated for cancers and stratified according to cancer type and RPF-cancer diagnosis interval. Cancer characteristics and outcomes were compared between RPF-cancer diagnosis intervals. RESULTS: The average age at RPF diagnosis was 59.2 ± 15.0 years, and 69.4% of the patients were male. The cancer SIRs in patients with RPF relative to age- and sex-matched individuals in the general population was 2.2 (1.6-3.1). SIRs of renal pelvis cancer and multiple myeloma were significantly higher than in the general population. When stratified by RPF-cancer intervals, the SIR for cancer was 9.9 within 1 year of RPF diagnosis, while no significant increase in the SIR was found after 1 year from RPF diagnosis. Cancer stage was more advanced at the time of diagnosis in patients within a 1-year interval for RPF than those with cancer within a >5-year interval, with a correspondingly increased mortality in the former patients. CONCLUSIONS: RPF was significantly associated with malignancy, particularly those diagnosed within 1 year of RPF diagnosis. Cancer stages at diagnosis were more advanced and the mortality rate was higher in patients within a 1-year interval between RPF and cancer diagnosis than in those with a >5-year interval between diagnoses.

4.
Sci Rep ; 11(1): 16333, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381078

RESUMO

Circulating tumor DNA (ctDNA) may reveal dynamic tumor status during therapy. We conducted serial ctDNA analysis to investigate potential association with clinical outcome in metastatic colorectal cancer (mCRC) patients receiving chemotherapy. Tissue KRAS/NRAS wild-type mCRC patients were enrolled and treated with first-line cetuximab-containing chemotherapy. ctDNA isolated from plasma were analyzed by next generation sequencing (NGS) with 16 targeted gene panel. Among 93 patients, 84 (90.3%) had at least 1 somatic mutation in baseline ctDNA samples (average 2.74). Five patients with KRAS or NRAS hotspot mutation in the ctDNA showed significantly worse progression-free survival (PFS) (p = 0.029). Changes in average variant allele frequency (VAF) in ctDNA showed significant correlation with tumor size change at the time of first response evaluation (p = 0.020) and progressive disease (PD) (p = 0.042). Patients whose average VAF decreased below cutoff (< 1%) at the first evaluation showed significantly better PFS (p < 0.001), and the average VAF change further discriminated the PFS in the patients in partial response (p = 0.018). At the time of PD, 54 new mutations including KRAS and MAP2K1 emerged in ctDNA. ctDNA sequencing can provide mutation profile that could better reflect tumor mutation status and predict treatment outcome.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34365579

RESUMO

Skin mucosal lymphoid tissues of fish are the first line of defence against pathogen invasion. We investigated the effects of Lactiplantibacillus plantarum subsp. plantarum L7, singularly or in combination with Limosilactobacillus reuteri P16, on mucosal immunity and diseases resistance of carp Cyprinus carpio. C. carpio (average weight: 26.28 ± 1.02 g) were divided into five experimental groups. Fish in each group were fed with one of the following potential probiotic-supplemented diets: control (0 - basal diet), D1 (107 CFU/g L7), D2 (108 CFU/g L7), D3 (109 CFU/g L7), and D4 (108 CFU/g L7 + 108 CFU/g P16). Eight weeks post-feeding, growth performance was higher in D4, with a final weight gain of 67.18 ± 1.47 g. Results showed a significantly higher skin mucosal lysozyme, alkaline phosphatase, mucus protein level, superoxide dismutase, and catalase activities in D2 and D4 compared to the control. However, potential probiotics had no significant effect on skin mucosal immunoglobulin level. Skin mucus of D4 exhibited stronger inhibition zones against pathogenic bacterial strains. Moreover, digestive enzyme activities (protease, lipase) were highest in D4. Intesinal lactic acid bacterial counts of fish fed combind probiotics (i.e. D4) was significantly higher than the control. Further, supplementation of potential probiotics altered the expression of IL-1ß, TNF-α, and IL-10 cytokines. Fish from D4 exhibited significantly higher relative post-challenge survival (69.7%) against Aeromonas hydrophila, followed by D2 (66.67%). Therefore, the inclusion of L. plantarum subsp. plantarum L7 at 108 CFU/g or in combination with L. reuteri P16 could enhance the growth performance, mucosal immune responses, and disease resistance of C. carpio.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34418915

RESUMO

Microscopic polyangiitis (MPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated necrotizing vasculitis, which mainly affects small vessels resulting in various organ involvement, especially the lung. The two key pulmonary manifestations, interstitial lung disease (ILD) and diffuse alveolar hemorrhage (DAH) increase the morbidity and mortality of patients with MPA. ILD is more common in MPA than in other ANCA-associated vasculitis subsets and is primarily associated with myeloperoxidase (MPO)-ANCA. Unlike alveolar hemorrhage due to pulmonary capillaritis, ILD can initially manifest as isolated pulmonary fibrosis. Of note, its most frequent radiographic pattern is the usual interstitial pneumonia pattern, similar to the characteristic pattern seen in idiopathic pulmonary fibrosis. We herein present the pathogenesis, clinical manifestations, radiographic and histopathologic features of ILD and DAH in MPA in this review. We also briefly summarize the outcome and therapeutic options for the two conditions.

7.
Nat Commun ; 12(1): 4840, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376661

RESUMO

Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both cancer cells and the tumor microenvironment (TME). We develop a 30-gene prediction model to determine the responsiveness to 5-FU and oxaliplatin-based chemotherapy and confirm the significant poor survival outcomes among cases classified as non-responder-like in three independent GC cohorts. Our study may inform clinical decision-making when designing treatment strategies.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Gástricas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Adenocarcinoma/genética , Animais , Feminino , Fluoruracila/administração & dosagem , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Oxaliplatina/administração & dosagem , Neoplasias Gástricas/genética , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética
8.
Foods ; 10(7)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34359426

RESUMO

We determined whether oral consumption of Aronia, red ginseng, shiitake mushroom, and nattokinase mixture (3.4: 4.1: 2.4: 0.1 w/w; AGM) improved glucose metabolism and insulin resistance in prediabetic adults in a 12-week randomized, double-blinded clinical trial. Participants with fasting serum glucose concentrations of 100-140 mg/dL were recruited and randomly assigned to an AGM or placebo group. Participants of the AGM group (n = 40) were given an AGM granule containing 4 g of freeze-dried Aronia, red ginseng, shiitake mushroom, and nattokinase (3.4: 4.1: 2.4: 0.1 w/w) twice daily for 12 weeks, and the placebo group participants (n = 40) were provided with corn starch granules identical in appearance, weight, and flavor for 12 weeks. Serum glucose and insulin concentrations were measured during oral-glucose tolerance tests (OGTT) after administering 75 g of glucose in a fasted state. HOMA-IR, liver damage, and inflammation indices were determined, and safety parameters and adverse reactions were assessed. As determined by OGTT, serum glucose concentrations were not significantly different between the AGM and placebo groups after the intervention. However, changes in serum insulin concentrations in the fasted state and Homeostatic model assessment-insulin resistance (HOMA-IR) index after the intervention were significantly lower in the AGM group than in the placebo group (-3.07 ± 7.06 vs. 0.05 ± 6.12, p = 0.043 for serum insulin; -0.85 ± 2.14 vs. 0.07 ± 1.92, p = 0.049 for HOMA-IR). Serum adiponectin concentrations were reduced by intervention in the placebo group but not in the AGM group. Changes in liver damage indexes, including serum activities of the γ-glutamyl transferase, alanine aminotransferase, and aspartate aminotransferase, were lower in the AGM group and significantly reduced in the AGM group more than in the placebo group (p < 0.05). Changes in serum high sensitive-C-reactive protein concentrations in AGM and placebo groups were significantly different (-0.12 ± 0.81 vs. 0.51 ± 1.95, p = 0.06). In conclusion, AGM possibly improves insulin sensitivity and ß-cell function and reduces liver damage and inflammation in prediabetic adults.

9.
Ann Surg Oncol ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196861

RESUMO

BACKGROUND: Because no prior studies have evaluated the chronological trends of ductal carcinoma in situ (DCIS) despite the increasing number of surgeries performed for DCIS, this study analyzed how the clinical, radiologic, and pathologic characteristics of DCIS changed during a 10-year period. METHODS: Of 7123 patients who underwent primary breast cancer surgery at a single institution from 2006 to 2015, 792 patients with pure DCIS were included in this study. The chronological trends of age, symptoms, method for detecting either mammography or ultrasonography, tumor size, nuclear grade, comedonecrosis, and molecular markers were calculated using Poisson regression for all patients and asymptomatic patients. RESULTS: During 10 years, DCIS surgery rates significantly increased (p < 0.001). Despite the high percentage of DCIS detected on mammography, the detection rate for DCIS by mammography significantly decreased (97.3% in 2006 to 67.6% in 2015; p = 0.025), whereas the detection rate by ultrasound significantly increased (2.7% to 31.0%; p < 0.001). Conservation surgery rates (odds ratio [OR], 1.058), low-to-intermediate nuclear grade rates (OR, 1.069), and the absence of comedonecrosis (OR, 1.104) significantly increased over time (all p < 0.05). Estrogen receptor (ER) negativity (OR, 0.935) and human epidermal growth factor receptor 2 (HER2) positivity rates (OR, 0.953) significantly decreased (all p < 0.05). The same trends were observed for the 613 asymptomatic patients. CONCLUSION: The rate of DCIS detected on ultrasound only significantly increased during 10 years. Low-to-intermediate nuclear grade rates significantly increased, whereas ER negativity and HER2 positivity rates significantly decreased during the same period. These findings suggest that DCIS detected on screening ultrasound is less aggressive than DCIS detected on mammography.

10.
Pediatr Rheumatol Online J ; 19(1): 100, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193198

RESUMO

BACKGROUND: Dermatomyositis is an inflammatory muscle disease caused by immune-mediated muscle injury, and central core disease (CCD) is a congenital myopathy associated with disturbed intracellular calcium homeostasis and excitation-contraction coupling. To date, CCD has not been reported to have autoantibodies or coexist with inflammatory myopathy. CASE PRESENTATION: Here, we described the case of a 25-year-old woman who had progressive proximal muscle weakness, myalgia, pruritic macular rash, skin ulcers, and calcinosis. Dermatomyositis was initially suspected based on the clinical symptoms accompanied by elevated muscle enzyme levels, electromyography abnormalities, and a positive antinuclear antibody test. However, the patient's muscle biopsy revealed the characteristic findings of both dermatomyositis and CCD, suggesting that dermatomyositis occurred in this patient with previously asymptomatic CCD. The patient did not have any pathogenic gene mutations associated with congenital myopathy, including RYR1 and SEPN1 in targeted next-generation sequencing. She received high-dose glucocorticoid therapy and azathioprine with a significant improvement in muscle strength. CONCLUSIONS: We present a case of rare coexistence of dermatomyositis and CCD. Clinicians should be aware that patients with CCD may have inflammatory myopathy that responds well to immunosuppressive therapy.

11.
Transl Oncol ; 14(10): 101180, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34274801

RESUMO

OBJECTIVES: To assess the additive prognostic value of MR-based radiomics in predicting progression-free survival (PFS) in patients with nasopharyngeal carcinoma (NPC) METHODS: Patients newly diagnosed with non-metastatic NPC between June 2006 and October 2019 were retrospectively included and randomly grouped into training and test cohorts (7:3 ratio). Radiomic features (n=213) were extracted from T2-weighted and contrast-enhanced T1-weighted MRI. The patients were staged according to the 8th edition of American Joint Committee on Cancer Staging Manual. The least absolute shrinkage and selection operator was used to select the relevant radiomic features. Univariate and multivariate Cox proportional hazards analyses were conducted for PFS, yielding three different survival models (clinical, stage, and radiomic). The integrated time-dependent area under the curve (iAUC) for PFS was calculated and compared among different combinations of survival models, and the analysis of variance was used to compare the survival models. The prognostic performance of all models was validated using a test set with integrated Brier scores. RESULTS: This study included 81 patients (training cohort=57; test cohort=24), and the mean PFS was 57.5 ± 43.6 months. In the training cohort, the prognostic performances of survival models improved significantly with the addition of radiomics to the clinical (iAUC, 0.72-0.80; p=0.04), stage (iAUC, 0.70-0.79; p=0.001), and combined models (iAUC, 0.76-0.81; p<0.001). In the test cohort, the radiomics and combined survival models were robustly validated for their ability to predict PFS. CONCLUSION: Integration of MR-based radiomic features with clinical and stage variables improved the prediction PFS in patients diagnosed with NPC.

12.
Mol Psychiatry ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253863

RESUMO

Heterogeneity in the etiopathology of autism spectrum disorders (ASD) limits the development of generic remedies, requires individualistic and patient-specific research. Recent progress in human-induced pluripotent stem cell (iPSC) technology provides a novel platform for modeling ASDs for studying complex neuronal phenotypes. In this study, we generated telencephalic induced neuronal (iN) cells from iPSCs derived from an ASD patient with a heterozygous point mutation in the DSCAM gene. The mRNA of DSCAM and the density of DSCAM in dendrites were significantly decreased in ASD compared to control iN cells. RNA sequencing analysis revealed that several synaptic function-related genes including NMDA receptor subunits were downregulated in ASD iN cells. Moreover, NMDA receptor (R)-mediated currents were significantly reduced in ASD compared to control iN cells. Normal NMDA-R-mediated current levels were rescued by expressing wild-type DSCAM in ASD iN cells, and reduced currents were observed by truncated DSCAM expression in control iN cells. shRNA-mediated DSCAM knockdown in control iN cells resulted in the downregulation of an NMDA-R subunit, which was rescued by the overexpression of shRNA-resistant DSCAM. Furthermore, DSCAM was co-localized with NMDA-R components in the dendritic spines of iN cells whereas their co-localizations were significantly reduced in ASD iN cells. Levels of phospho-ERK1/2 were significantly lower in ASD iN cells, suggesting a potential mechanism. A neural stem cell-specific Dscam heterozygous knockout mouse model, showing deficits in social interaction and social memory with reduced NMDA-R currents. These data suggest that DSCAM mutation causes pathological symptoms of ASD by dysregulating NMDA-R function.

13.
Mol Cancer Ther ; 20(10): 1846-1857, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34315764

RESUMO

PTC596 is an investigational small-molecule tubulin-binding agent. Unlike other tubulin-binding agents, PTC596 is orally bioavailable and is not a P-glycoprotein substrate. So as to characterize PTC596 to position the molecule for optimal clinical development, the interactions of PTC596 with tubulin using crystallography, its spectrum of preclinical in vitro anticancer activity, and its pharmacokinetic-pharmacodynamic relationship were investigated for efficacy in multiple preclinical mouse models of leiomyosarcomas and glioblastoma. Using X-ray crystallography, it was determined that PTC596 binds to the colchicine site of tubulin with unique key interactions. PTC596 exhibited broad-spectrum anticancer activity. PTC596 showed efficacy as monotherapy and additive or synergistic efficacy in combinations in mouse models of leiomyosarcomas and glioblastoma. PTC596 demonstrated efficacy in an orthotopic model of glioblastoma under conditions where temozolomide was inactive. In a first-in-human phase I clinical trial in patients with cancer, PTC596 monotherapy drug exposures were compared with those predicted to be efficacious based on mouse models. PTC596 is currently being tested in combination with dacarbazine in a clinical trial in adults with leiomyosarcoma and in combination with radiation in a clinical trial in children with diffuse intrinsic pontine glioma.

15.
Cancer Sci ; 112(9): 3732-3743, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34118099

RESUMO

Colorectal cancer (CRC) is a recurring cancer that is often resistant to conventional therapies and therefore requires the development of molecular-based therapeutic approaches. Dopamine receptor D2 (DRD2) is associated with the growth of many types of tumors, but its oncogenic role in CRC is unclear. Here, we observed that elevated DRD2 expression was associated with a poor survival rate among patients with CRC. Depletion of DRD2 suppressed CRC cell growth and motility by downregulating ß-catenin/ZEB signaling in vitro and in vivo, whereas overexpression of DRD2 promoted CRC cell progression. Inhibition of DRD2 by the antagonist pimozide inhibited tumor growth and lymph node metastasis in vivo and enhanced the cytotoxic effects of conventional agents in vitro. Taken together, our findings indicate that targeting the DRD2/ß-catenin/ZEB1 signaling axis is a potentially promising therapeutic strategy for patients with CRC.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Progressão da Doença , Receptores de Dopamina D2/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , beta Catenina/metabolismo , Idoso , Animais , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Antagonistas de Dopamina/farmacologia , Feminino , Células HCT116 , Células HT29 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Pimozida/farmacologia , Interferência de RNA , Receptores de Dopamina D2/genética , Transdução de Sinais , Taxa de Sobrevida , Transfecção , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Sci Rep ; 11(1): 13439, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34188123

RESUMO

The high-flow nasal cannula (HFNC) is a useful treatment modality for acute hypoxemic respiratory failure (AHRF) in children. We compared the ability of the oxygen saturation to fraction of inspired oxygen ratio (S/F) and arterial oxygen partial pressure to fraction of inspired oxygen ratio (P/F) to predict HFNC outcomes in children with AHRF. This study included children treated with HFNC due to AHRF from April 2013 to March 2019 at the Severance Children's Hospital. HFNC failure was defined as the need for mechanical ventilation. Trends of S/F and P/F during HFNC were analyzed. To predict HFNC outcomes, a nomogram was constructed based on predictive factors. A total of 139 patients with arterial blood gas data were included in the S/F and P/F analyses. S/F < 230 at initiation showed high prediction accuracy for HFNC failure (area under the receiver operating characteristic curve: 0.751). Univariate analyses identified S/F < 230 at HFNC initiation and < 200 at 2 h (odds ratio [OR] 12.83, 95% CI 5.06-35.84), and hemato-oncologic disease (OR 3.79, 95% CI 1.12-12.78) as significant predictive factors of HFNC failure. The constructed nomogram had a highly predictive performance, with a concordance index of 0.765 and 0.831 for the exploratory and validation groups, respectively. S/F may be used as a predictor of HFNC outcomes. Our nomogram with S/F for HFNC failure within 2 h may prevent delayed intubation in children with AHRF.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34068352

RESUMO

The aim of this study was to evaluate the muscle activities and subjective discomfort according to the heights of tasks and the lower-limb exoskeleton CEX (Chairless EXoskeleton), which is a chair-type passive exoskeleton. Twenty healthy subjects (thirteen males and seven females) participated in this experiment. The independent variables were wearing of the exoskeleton (w/ CEX, w/o CEX), working height (6 levels: 40, 60, 80, 100, 120, and 140 cm), and muscle type (8 levels: upper trapezius (UT), erector spinae (ES), middle deltoid (MD), triceps brachii (TB), biceps brachii (BB), biceps femoris (BF), rectus femoris (RF), and tibialis anterior (TA)). The dependent variables were EMG activity (% MVC) and subjective discomfort rating. When wearing the CEX, the UT, ES, RF, and TA showed lower muscle activities at low working heights (40-80 cm) than not wearing the CEX, whereas those muscles showed higher muscle activities at high working heights (100-140 cm). Use of the CEX had a positive effect on subjective discomfort rating at lower working heights. Generally, lower discomfort was reported at working heights below 100 cm when using the CEX. At working heights of 100-140 cm, the muscle activity when wearing the CEX tended to be greater than when not wearing it. Thus, considering the results of this study, the use of the lower-limb exoskeleton (CEX) at a working height of 40-100 cm might reduce the muscle activity and discomfort of whole body and decrease the risk of related disorders.


Assuntos
Exoesqueleto Energizado , Eletromiografia , Ergonomia , Feminino , Humanos , Extremidade Inferior , Masculino , Músculo Esquelético , Postura
18.
Laryngoscope ; 131(10): 2332-2340, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34156095

RESUMO

OBJECTIVES/HYPOTHESIS: Tinnitus can develop due to, or be aggravated by, stress in a rat model. To investigate stress as a possible causal factor in the development of tinnitus, we designed an animal study that included tinnitus behavior and excitatory/inhibitory neurotransmitter expression after noise exposure as well as restraint stress. STUDY DESIGN: An experimental animal study. METHODS: Wistar rats were grouped according to single or double exposure to noise and restraint stress. The noise exposure (NE) group was subjected to 110 dB sound pressure level (SPL) of 16 kHz narrow-band noise (NBN) for 1 hour, and the restraint stress (RS) group was restrained for 1 hour with or without noise exposure. Gap prepulse inhibition of the acoustic startle (GPIAS) reflex was measured at an NBN of 16 kHz to investigate tinnitus development. Various immunohistopathologic and molecular biologic studies were undertaken to evaluate possible mechanisms of tinnitus development after noise and/or restraint stress. RESULTS: The RS-only group showed a reduced GPIAS response, which is a reliable sign of tinnitus development. In the double-stimulus groups, more tinnitus-development signs of reduced GPIAS responses were observed. The expression of γ-aminobutyric acid A receptor α1 (GABAAR α1) in the hippocampus decreased in the NE│RS group. Increased N-methyl-d-aspartate receptor1 intensities in the NE│RS group and decreased GABAAR α1 intensities in the RS and NE│RS groups were observed in the CA3 region of the hippocampus. CONCLUSIONS: Tinnitus appeared to develop after stress alone in this animal study. An imbalance in excitatory and inhibitory neurotransmitters in the hippocampus may be related to the development of tinnitus after acute NE and/or stress. LEVEL OF EVIDENCE: NA Laryngoscope, 131:2332-2340, 2021.


Assuntos
Região CA3 Hipocampal/patologia , Ruído/efeitos adversos , Estresse Psicológico/complicações , Zumbido/etiologia , Estimulação Acústica/efeitos adversos , Estimulação Acústica/métodos , Animais , Modelos Animais de Doenças , Humanos , Masculino , Ratos , Receptores de GABA-A/análise , Receptores de GABA-A/metabolismo , Receptores de N-Metil-D-Aspartato/análise , Receptores de N-Metil-D-Aspartato/metabolismo , Reflexo de Sobressalto , Estresse Psicológico/psicologia , Zumbido/diagnóstico , Zumbido/patologia , Zumbido/psicologia
19.
Pediatr Allergy Immunol Pulmonol ; 34(2): 83-87, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34143683

RESUMO

Background: Myhre syndrome is a rare connective tissue disorder caused by heterozygous pathogenic variants in the SMAD4 gene. Although recognizing Myhre syndrome in early childhood is challenging, it is important to manage airway stenosis in patients with Myhre syndrome. Case Presentation: We report the case of a 2-month-old boy who initially presented with severe multilevel airway stenosis, dysmorphic face, and multiple abnormalities. Lung fibrosis and mild aortic valve stenosis were additionally observed on follow-up examinations. A heterozygous missense variant, c.1499T>C (p.Ile500Thr), in SMAD4 was identified through exome sequencing. Tracheostomy was performed, and the patient has maintained stable respiration through a customized tracheostomy tube with a home ventilator. Conclusions: Patients who have dysmorphic face, airway stenosis, and cardiovascular anomalies that do not fit the diagnosis of common syndromes should be evaluated for rare diseases, including Myhre syndrome. Since respiratory complications can be life threatening, early diagnosis and suitable intervention are necessary.

20.
Sensors (Basel) ; 21(10)2021 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-34065710

RESUMO

Olfactory receptors (ORs) account for 49% of all G protein-coupled receptors (GPCRs), which are important targets for drug discovery, and hence ORs may also be potential drug targets. Various ORs are expressed in breast cancer cells; however, most of them are orphan receptors, and thus, their functions are unknown. Herein, we present an experimental strategy using a surface plasmon resonance (SPR) system and a cell-based assay that allowed the identification of orphan OR6M1 as a new anticancer target in the MCF-7 breast cancer cell line. After the construction of stable OR6M1-expressing cells, the SPR-based screening of 108 chemicals for ligand activity was performed against OR6M1-expressing whole cells (primary screening) or membrane fragments (secondary screening). As a result, anthraquinone (AQ) and rutin were discovered to be new OR6M1 ligands. Based on calcium imaging in OR6M1-expressing Hana3A cells, AQ and rutin were classified as an OR6M1 agonist and antagonist, respectively. Cell viability and live/dead assays showed that AQ induced the death of MCF-7 cells, which was inhibited by rutin. Therefore, OR6M1 may be considered an anticancer target, and AQ may be considered a chemotherapeutic agent. This combined method can be widely used to discover the ligands and functions of other orphan GPCRs.


Assuntos
Receptores Odorantes , Ressonância de Plasmônio de Superfície , Antraquinonas , Descoberta de Drogas , Humanos , Ligantes , Células MCF-7 , Receptores Odorantes/genética , Rutina
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