Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 76
Filtrar
1.
Allergy ; 79(5): 1230-1241, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38403941

RESUMO

BACKGROUND: Identifying predictive biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to identify such biomarkers in patients with allergic rhinitis (AR) undergoing subcutaneous immunotherapy (SCIT) for house dust mite allergy. METHODS: The Tongji (discovery) cohort comprised 72 AR patients who completed 1-year SCIT follow-up. Circulating T and B cell subsets were characterized using multiplexed flow cytometry before SCIT. Serum immunoglobulin levels and combined symptom and medication score (CSMS) were assessed before and after 12-month SCIT. Responders, exhibiting ≥30% CSMS improvement, were identified. The random forest algorithm and logistic regression analysis were used to select biomarkers and establish predictive models for SCIT efficacy in the Tongji cohort, which was validated in another Wisco cohort with 43 AR patients. RESULTS: Positive SCIT response correlated with higher baseline CSMS, allergen-specific IgE (sIgE)/total IgE (tIgE) ratio, and frequencies of Type 2 helper T cells, Type 2 follicular helper T (TFH2) cells, and CD23+ nonswitched memory B (BNSM) and switched memory B (BSM) cells, as well as lower follicular regulatory T (TFR) cell frequency and TFR/TFH2 cell ratio. The random forest algorithm identified sIgE/tIgE ratio, TFR/TFH2 cell ratio, and BNSM frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort. Logistic regression analysis confirmed the predictive value of a combination model, including sIgE/tIgE ratio, TFR/TFH2 cell ratio, and CD23+ BSM frequency (AUC = 0.899 in Tongji; validated AUC = 0.893 in Wisco). CONCLUSIONS: A T- and B-cell signature combination efficiently identified SCIT responders before treatment, enabling personalized approaches for AR patients.


Assuntos
Biomarcadores , Dessensibilização Imunológica , Pyroglyphidae , Rinite Alérgica , Humanos , Rinite Alérgica/terapia , Rinite Alérgica/imunologia , Masculino , Dessensibilização Imunológica/métodos , Animais , Feminino , Adulto , Pyroglyphidae/imunologia , Resultado do Tratamento , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Pessoa de Meia-Idade , Adulto Jovem , Alérgenos/imunologia , Alérgenos/administração & dosagem , Antígenos de Dermatophagoides/imunologia , Injeções Subcutâneas , Adolescente , Prognóstico
2.
J Allergy Clin Immunol ; 153(4): 1025-1039, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38072196

RESUMO

BACKGROUND: Ectopic lymphoid tissues (eLTs) and associated follicular helper T (TFH) cells contribute to local immunoglobulin hyperproduction in nasal polyps (NPs). Follicular regulatory T (TFR) cells in secondary lymphoid organs counteract TFH cells and suppress immunoglobulin production; however, the presence and function of TFR cells in eLTs in peripheral diseased tissues remain poorly understood. OBJECTIVE: We sought to investigate the presence, phenotype, and function of TFR cells in NPs. METHODS: The presence, abundance, and phenotype of TFR cells in NPs were examined using single-cell RNA sequencing, immunofluorescence staining, and flow cytometry. Sorted polyp and circulating T-cell subsets were cocultured with autologous circulating naïve B cells, and cytokine and immunoglobulin production were measured by ELISA. RESULTS: TFR cells were primarily localized within eLTs in NPs. TFR cell frequency and TFR cell/TFH cell ratio were decreased in NPs with eLTs compared with NPs without eLTs and control inferior turbinate tissues. TFR cells displayed an overlapping phenotype with TFH cells and FOXP3+ regulatory T cells in NPs. Polyp TFR cells had reduced CTLA-4 expression and decreased capacity to inhibit TFH cell-induced immunoglobulin production compared with their counterpart in blood and tonsils. Blocking CTLA-4 abolished the suppressive effect of TFR cells. Lower vitamin D receptor expression was observed on polyp TFR cells compared with TFR cells in blood and tonsils. Vitamin D treatment upregulated CTLA-4 expression on polyp TFR cells and restored their suppressive function in vitro. CONCLUSIONS: Polyp TFR cells in eLTs have decreased CLTA-4 and vitamin D receptor expression and impaired capacity to suppress TFH cell-induced immunoglobulin production, which can be reversed by vitamin D treatment in vitro.


Assuntos
Pólipos Nasais , Estruturas Linfoides Terciárias , Humanos , Linfócitos T Reguladores/patologia , Linfócitos T Auxiliares-Indutores/patologia , Antígeno CTLA-4/metabolismo , Receptores de Calcitriol/metabolismo , Pólipos Nasais/patologia , Estruturas Linfoides Terciárias/patologia , Imunoglobulinas/metabolismo , Vitamina D/metabolismo
3.
Sports Med Health Sci ; 5(3): 239-244, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37753420

RESUMO

Parkinson's disease (PD) affects gait and postural stability. Tai Chi (TC) is recommended for PD for management of the condition, however biomechanical understanding to its effects on gait and postural stability is limited. This study aimed to examine the effects of an online 12-week biomechanical-based TC intervention on gait and posture in people with PD. Fifteen individuals in early-stage PD were recruited (Hoehn & Yahr stages 1-2). The TC intervention program was 60 â€‹min session, three times weekly for 12 weeks. The pre- and post-intervention test in obstacle crossing, timed-up-and-go (TUG) test, and single leg standing (SLS) with eyes open (EO) and closed (EC) were conducted. Gait speed, crossing stride length, clearance height of the heel and toe, anterior-posterior (AP) and medial-lateral (ML) displacement and velocity of the center of mass (COM) and separation of the COM-center of pressure (COP) were analyzed. The participants significantly improved their pre-vs. post-TC intervention performance on TUG test (p â€‹= â€‹0.002). During obstacle crossing, the participants significantly increased crossing stride length of the trailing foot, increased AP COM displacement and decreased ML COM-COP separation (p â€‹< â€‹0.05); the maximal dorsiflexion angle of the leading limb significantly increased and maximal plantarflexion angle of the trailing limb significantly decreased (p â€‹< â€‹0.05). A 12-week biomechanical-based online TC training was effective towards improvement of gait and postural stability among people in the early-stage of PD. The TC program and online training could be applied for management of PD.

4.
Trials ; 24(1): 241, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37386473

RESUMO

BACKGROUND: Parkinson's disease (PD) is associated with changes in gait and posture, which increases the rate of falls and injuries in this population. Tai Chi (TC) training enhances the movement capacity of patients with PD. However, the understanding of the effect of TC training on gait and postural stability in PD is lacking. This study aims to examine the effect of biomechanical-based TC training on dynamic postural stability and its relationship with walking performance. METHODS/DESIGN: A single-blind, randomized control trial of 40 individuals with early-stage PD was conducted (Hoehn and Yahr stages 1 to 3). Patients with PD will be randomly assigned to either the TC or control group. The TC group will participate in a biomechanical-based TC training program that is formed based on the movement analysis of TC and will be practiced thrice a week for 12 weeks. The control group will be required to engage in at least 60 min of regular physical activity (PA) on their own for three times per week for 12 weeks. The primary and secondary outcomes will be assessed at baseline and at 6 and 12 weeks after commencing the study protocol. The primary outcome measures will include dynamic postural stability indicated by the center of mass and center of pressure separation distance and clearance distance of the heel and toe measured during fixed-obstacle crossing. The secondary measures are gait speed, cadence, step length during level surface walking (simple task), and fixed-obstacle crossing (challenging task). The Unified Parkinson's Disease Rating Scale, single leg-stance test with eyes open and closed, and three cognitive scores (Stroop Test, Trail Making Test Part B, and the Wisconsin Card Sorting Test) were also employed. DISCUSSION: This protocol could lead to the development of a biomechanics TC training program for the improvement of gait and postural stability among individuals with PD. The program could enhance the understanding of the effect of TC training on gait and postural stability and could help improve or preserve the postural stability, self-confidence, and active participation in social activities of the participants, thus enhancing their overall quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT04644367. Registered on 25 November 2020.


Assuntos
Doença de Parkinson , Tai Chi Chuan , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Qualidade de Vida , Método Simples-Cego , Postura , Marcha , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Transl Cancer Res ; 12(1): 46-64, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36760376

RESUMO

Background: Hepatocellular carcinoma (HCC) is a common malignancy. Ferroptosis and cuproptosis promote HCC spread and proliferation. While fewer studies have combined ferroptosis and cuproptosis to construct prognostic signature of HCC. This work attempts to establish a novel scoring system for predicting HCC prognosis, immunotherapy, and medication sensitivity based on ferroptosis-related genes (FRGs) and cuproptosis-related genes (CRGs). Methods: FerrDb and previous literature were used to identify FRGs. CRGs came from original research. The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases included the HCC transcriptional profile and clinical information [survival time, survival status, age, gender, Tumor Node Metastasis (TNM) stage, etc.]. Correlation, Cox, and least absolute shrinkage and selection operator (LASSO) regression analyses were used to narrow down prognostic genes and develop an HCC risk model. Using "caret", R separated TCGA-HCC samples into a training risk set and an internal test risk set. As external validation, we used ICGC samples. We employed Kaplan-Meier analysis and receiver operating characteristic (ROC) curve to evaluate the model's clinical efficacy. CIBERSORT and TIMER measured immunocytic infiltration in high- and low-risk populations. Results: TXNRD1 [hazard ratio (HR) =1.477, P<0.001], FTL (HR =1.373, P=0.001), GPX4 (HR =1.650, P=0.004), PRDX1 (HR =1.576, P=0.002), VDAC2 (HR =1.728, P=0.008), OTUB1 (HR =1.826, P=0.002), NRAS (HR =1.596, P=0.005), SLC38A1 (HR =1.290, P=0.002), and SLC1A5 (HR =1.306, P<0.001) were distinguished to build predictive model. In both the model cohort (P<0.001) and the validation cohort (P<0.05), low-risk patients had superior overall survival (OS). The areas under the curve (AUCs) of the ROC curves in the training cohort (1-, 3-, and 5-year AUCs: 0.751, 0.727, and 0.743), internal validation cohort (1-, 3-, and 5-year AUCs: 0.826, 0.624, and 0.589), and ICGC cohort (1-, 3-, and 5-year AUCs: 0.699, 0.702, and 0.568) were calculated. Infiltration of immune cells and immunological checkpoints were also connected with our signature. Treatments with BI.2536, Epothilone.B, Gemcitabine, Mitomycin.C, Obatoclax. Mesylate, and Sunitinib may profit high-risk patients. Conclusions: We analyzed FRGs and CRGs profiles in HCC and established a unique risk model for treatment and prognosis. Our data highlight FRGs and CRGs in clinical practice and suggest ferroptosis and cuproptosis may be therapeutic targets for HCC patients. To validate the model's clinical efficacy, more HCC cases and prospective clinical assessments are needed.

6.
Transl Cancer Res ; 12(12): 3327-3345, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38192999

RESUMO

Background: Ferroptosis and cuproptosis play a crucial role in the progression and dissemination of hepatocellular carcinoma (HCC). The primary objective of this study was to develop a unique scoring system for predicting the prognosis and immunological landscape of HCC based on ferroptosis-related genes (FRGs) and cuproptosis-related genes (CRGs). Methods: As the training cohort, we assembled a novel HCC cohort by merging gene expression data and clinical data from The Cancer Genome Atlas (TCGA) database, and Gene Expression Omnibus (GEO) database. The validation cohort consisted of 230 HCC cases taken from the International Cancer Genome Consortium (ICGC) database. Multiple genomic characteristics, such as tumor mutation burden (TMB), and copy number variations were analyzed concurrently. On the basis of the expression of CRGs and FRGs, patients were classified into cuproptosis and ferroptosis subtypes. Then, we constructed a risk model using least absolute shrinkage and selection operator (LASSO) analysis and Cox regression analysis based on ferroptosis and cuproptosis-related differentially expressed genes (DEGs). Patients were separated into two groups according to median risk score. We compared the immunophenotype, tumor microenvironment (TME), cancer stem cell index, and treatment sensitivity of two groups. Results: Three subtypes of ferroptosis and two subtypes of cuproptosis were identified among the patients. A greater likelihood of survival (P<0.05) was expected for patients in FRGcluster B and CRGcluster B. After that, a confirmed risk signature for ferroptosis and cuproptosis was developed and tested. Patients in the low-risk group had significantly higher survival rates than those in the high-risk group, according to our study (P<0.001). There was also a strong correlation between the signature and other variables including immunophenoscore, TMB, cancer stem cell index, immunological checkpoint genes, and sensitivity to chemotherapeutics. Conclusions: Through this comprehensive research, we identified a unique risk signature associated with HCC patients' treatment status and prognosis. Our findings highlight FRGs' and CRGs' significance in clinical practice and imply ferroptosis and cuproptosis may be therapeutic targets for HCC patients.

7.
J Allergy Clin Immunol ; 150(3): 727-735.e6, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35460727

RESUMO

BACKGROUND: Although metabolomics provides novel insights into disease mechanisms and biomarkers, the metabolic alterations in local tissues affected by chronic rhinosinusitis (CRS) are unknown. OBJECTIVE: This study aimed to determine the metabolomic profiles of sinonasal tissues associated with different types of CRS and their treatment outcomes. METHODS: Untargeted metabolomic profiling was performed on sinonasal tissues obtained from patients with eosinophilic CRS with nasal polyps (CRSwNP), noneosinophilic CRSwNP or CRS without nasal polyps (CRSsNP), and controls. The messenger RNA (mRNA) levels of inflammatory cytokines in nasal tissues were detected by quantitative real-time reverse transcriptase PCR. Nasal polyp tissues were cultured ex vivo and treated with glutathione. RESULTS: Distinct metabolomic profiles were observed for the CRS subtypes. Eosinophilic CRSwNP had profoundly enhanced unsaturated fatty acid oxidization, which correlated with mucosal eosinophil numbers and IL-5 mRNA levels. Noneosinophilic CRSwNP was characterized by uric acid accumulation. Increased uric acid levels were positively correlated with mucosal neutrophil numbers and IFN-γ, IL-17A, IL-1ß, and IL-8 mRNA levels. Disrupted purine metabolism was specifically detected in CRSsNP. Reduced levels of amino acid metabolites were found in eosinophilic CRSwNP and CRSsNP, and were inversely associated with mucosal total inflammatory cell numbers and inflammatory cytokines. Compared to non-difficult-to-treat CRS, difficult-to-treat CRS had higher glutathione disulfide levels, which were positively correlated with IL-8 mRNA levels. Glutathione treatment reduced IL-8 mRNA expression in cultured nasal polyp tissues. CONCLUSIONS: Specific metabolic signatures are associated with different types of CRS, inflammatory patterns, and disease outcomes, which may provide novel insights into pathophysiologic mechanisms, subtype-specific biomarkers, and treatment targets of CRS.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Biomarcadores , Doença Crônica , Citocinas/metabolismo , Glutationa , Humanos , Interleucina-8 , Pólipos Nasais/metabolismo , RNA Mensageiro , Rinite/metabolismo , Sinusite/metabolismo , Ácido Úrico
8.
Sports Med Health Sci ; 4(4): 245-252, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36600972

RESUMO

This study examined the maximum joint angles and moments, and electromyography (EMG) activity of the lower limbs in an experienced Tai Chi (TC) practitioner in performing four dynamic (Repulse Monkey, Wave-hand in Clouds, Brush Knee Twist Step, and Lateral Forward Step) and three static TC movements (Starting Form, Hero Touch Sky, and Push Hand Back) and compared them with the measures from walking. Integrated EMG (iEMG) and peak EMG of the rectus femoris, adductor longus, tibialis anterior, semitendinosus, erector spinae, gluteus medius, tensor fasciae latae, medial and lateral gastrocnemius muscles were analyzed. One-way analysis of variance showed that compared with walking, TC presented 1) significantly larger hip flexion (71.4° vs. 42.2°) and abduction angles (11.9° vs. 5.3°), smaller knee flexion (45.2° vs. 71.1°) and abduction angles (13.0° vs. 27.7°), larger ankle dorsiflexion (41.4° vs. 11.3°) and abduction angles (8.8° vs. 7.2°); 2) hip flexion moment and knee flexion and abduction moment were significantly larger. Ankle dorsiflexion moment were significantly smaller, whereas ankle abduction moment was significantly larger in two TC movements; and 3) the EMG activity of the muscles in TC varied from 10% to 610% of walking. The knee extensors, hip adductors and abductors had significantly higher peak EMG (430% â€‹± â€‹40%, 240% â€‹± â€‹30%, and 320% â€‹± â€‹90%) and iEMG values (610% â€‹± â€‹30%, 311% â€‹± â€‹30%, and 1.4% â€‹± â€‹20%), respectively. The findings suggested that these TC movements could be a good option for the improvement of muscle strength and range of motion of the lower limbs.

9.
Res Sports Med ; 29(6): 586-592, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34477036

RESUMO

This study examined the biomechanics of the lower limbs during four typical Tai Chi (TC) movements: wave hand in cloud, leaning fly side, repulse monkey, and brush knee and twist step, in order to provide biomechanical evidence-based recommendations for patients with knee osteoarthritis (OA) practicing TC. Joint angles and joint moments of the hip, knee, and ankle in frontal and sagittal plane as well as ground reaction forces were examined while performing TC and regular walking in an experienced 38 years old TC master. The results showed that relative to walking, the four TC movements are characterized by a wide motion range of lower limbs, slow increase in joint loading, and strong muscle activity during performance. Therefore, these TC movements could be suitable for patients with knee OA to practice for improving the muscle strength of their lower limbs and functional ability.


Assuntos
Extremidade Inferior/fisiologia , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/reabilitação , Amplitude de Movimento Articular/fisiologia , Tai Chi Chuan/métodos , Caminhada/fisiologia , Suporte de Carga/fisiologia , Adulto , Fenômenos Biomecânicos , Humanos , Cinética , Masculino
10.
Appl Bionics Biomech ; 2021: 7464719, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422111

RESUMO

This study was aimed at exploring the biomechanical characteristics of the lower extremity amongst three typical yoga manoeuvres. A total of thirteen experienced female yoga practitioners were recruited in the current study; they were all certified with the Yoga Alliance. A three-dimensional motion capture system with 10 cameras combined with four synchronised force plates was used to collect kinematics of the lower extremity and ground reactive force whilst the participants performed the crescent lunge pose, warrior II pose, and triangle pose. One-way repeated ANOVA was used in exploring the differences amongst the three yoga movements, and the significance was set to alpha < 0.05. The triangle pose performed the largest range of motion (ROM) of the hip (90.5° ± 22.9°), knee (68.8° ± 23.1°), and ankle (46.4° ± 11.3°) in the sagittal plane and the hip (54.8° ± 6.5°), knee (42.4° ± 12.8°), and ankle (4.8° ± 1.7°) in the frontal plane amongst the three manoeuvres (P < 0.05). No significant difference was found for the hip and ankle joint moment amongst the three manoeuvres (P > 0.05). Knee joint travelled into 9.5° of extension and slight adduction of 1.94° whilst expressing the largest knee joint adduction moments (0.30 ± 0.22 Nm/kg) in the triangle pose. The distribution of the angular impulse of the lower limb joints indicated that the hip joint contributed significantly the most in the sagittal and frontal planes of the three yoga manoeuvres (P < 0.05), ranging from 51.67% to 70.56%. Results indicated that triangle pose may be superior to the other two manoeuvres, which improved hip joint ROM, strength, and dynamic stability. However, knee injuries such as osteoarthritis (OA) should be considered because of the large knee extensor angle and adductor moments.

11.
Environ Toxicol ; 36(8): 1694-1701, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33978285

RESUMO

Hexavalent chromium (Cr (VI)), which is a recognized human carcinogen, is widely used in industrial production of raw materials. Evidence verifies that environmental contaminants in the urine can induce malignant transformation in the urinary bladder tract, and our data indicate that Cr (VI) could promote the proliferation and migration and inhibit the apoptosis of bladder cancer (BLCA) cells. However, the molecular mechanism remains ambiguous. We find that Filamin A (FLNA) is overexpressed in BLCA, and Cr (VI) promotes epithelial-to-mesenchymal transition by regulating FLNA in BLCA. Thus, inhibiting the expression of FLNA may be a prospective method for limiting the BLCA progression caused by Cr (VI) exposure.


Assuntos
Neoplasias da Bexiga Urinária , Cromo , Filaminas , Humanos , Estudos Prospectivos
12.
Sports Med Health Sci ; 3(3): 165-170, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35784519

RESUMO

The effects of body mass and sex on lower limb biomechanics during ascent and descent were examined in participants aged 50 to 75 with normal weight (n â€‹= â€‹19), overweight (n â€‹= â€‹18), and obese (n â€‹= â€‹8). Peak joint angles and joint moment of the lower limb were analyzed with the VICON motion analysis system. Results from multivariate analysis of variance showed that during descent, the overweight participants had significantly higher knee extensor moment (0.98 â€‹± â€‹0.30 â€‹N∙m/kg-1) than the normal-weight participants (0.70 â€‹± â€‹0.29 â€‹N∙m/kg-1). The obese group had significantly higher ankle abductor moment (0.21 â€‹± â€‹0.11 â€‹N∙m/kg-1) than the normal weight (0.12 â€‹± â€‹0.08 â€‹N∙m/kg-1) and overweight groups (0.09 â€‹± â€‹0.06 â€‹N∙m/kg-1). During ascent, the obese participants had significant higher hip flexor moment (0.42 â€‹± â€‹0.20 â€‹N∙m/kg-1) than overweight participants (0.22 â€‹± â€‹0.17 â€‹N∙m/kg-1). Significant sex differences were found in knee extension angles (4.2 â€‹± â€‹3.4° vs 7.0 â€‹± â€‹3.3°) during descent, plantar flexion angles during ascent (23.7 â€‹± â€‹5.3° vs 15.6 â€‹± â€‹3.7°) and descent (29.9 â€‹± â€‹5.0° vs 22.1 â€‹± â€‹7.9°), and ankle adduction angles (6.8 â€‹± â€‹4.8° vs 2.5 â€‹± â€‹2.5°) during ascent. It is concluded that body mass has significant impact on joint loading of lower limbs during stair walking. Being overweight and obese increased hip joint loading during ascent, and knee and ankle joint loading during descent in older adults. Sex difference in joint kinematics was presented during stair walking regardless of the body mass.

13.
Allergy ; 76(5): 1416-1431, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33022771

RESUMO

BACKGROUND: Although the importance of ectopic lymphoid tissues (eLTs) in the pathophysiology of nasal polyps (NPs) is increasingly appreciated, the mechanisms underlying their formation remain unclear. OBJECTIVE: To study the role of interleukin (IL)-17A, C-X-C motif chemokine ligand 13 (CXCL13) and lymphotoxin (LT) in eLT formation in NPs. METHODS: The expression levels of CXCL13 and LT and their receptors, in addition to the phenotypes of stromal cells in NPs, were studied by flow cytometry, immunostaining, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Purified nasal stromal cells and B cells were cultured, and a murine model of nasal type 17 inflammation was established by intranasal curdlan challenge for the mechanistic study. RESULTS: The excessive CXCL13 production in NPs correlated with enhanced IL-17A expression. Stromal cells, with CD31- Pdpn+ fibroblastic reticular cell (FRC) expansion, were the major source of CXCL13 in NPs without eLTs. IL-17A induced FRC expansion and CXCL13 production in nasal stromal cells. In contrast, B cells were the main source of CXCL13 and LTα1 ß2 in NPs with eLTs. CXCL13 upregulated LTα1 ß2 expression on B cells, which in turn promoted CXCL13 production in nasal B cells and stromal cells. LTα1 ß2 induced expansion of FRCs and CD31+ Pdpn+ lymphoid endothelial cells, which were the predominant stromal cell types in NPs with eLTs. IL-17A knockout and CXCL13 and LTßR blockage diminished nasal eLT formation in the murine model. CONCLUSION: We identified an important role of IL-17A-induced stromal cell remodeling in the initiation and crosstalk between B and stromal cells via CXCL13 and LTα1 ß2 in the enlargement of eLTs in NPs.


Assuntos
Pólipos Nasais , Estruturas Linfoides Terciárias , Animais , Linfócitos B , Células Endoteliais , Camundongos , Células Estromais
14.
J Allergy Clin Immunol ; 147(5): 1692-1703, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33340608

RESUMO

BACKGROUND: Stimulator of interferon genes (STING) activation favors effective innate immune responses against viral infections. Its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unknown. OBJECTIVE: Our aim was to explore the expression, regulation, and function of STING in CRSwNP. METHODS: STING expression in sinonasal mucosal samples was analyzed by means of quantitative RT-PCR, immunohistochemistry, flow cytometry, and Western blotting. Regulation and function of STING expression were explored by using cultured primary human nasal epithelial cells (HNECs) and cells of the line BEAS-2B in vitro. RESULTS: STING expression was reduced in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues. STING was predominantly expressed by epithelial cells in nasal tissue and was downregulated by IL-4 and IL-13 in a signal transducer and activator of transcription 6 (STAT6)-dependent manner. HNECs derived from eosinophilic polyps displayed compromised STING-dependent type I interferon production but heightened IL-13-induced STAT6 activation and CCL26 production as compared with HNECs from noneosinophilic polyps and control tissues, which were rescued by exogenous STING overexpression. Knocking down or overexpressing STING decreased or enhanced expression of suppressor of cytokine signaling 1 (SOCS1) in BEAS-2B cells, respectively, independent of the canonic STING pathway elements TBK1 and IRF3. Knocking down SOCS1 abolished the inhibitory effect of STING on IL-13 signaling in BEAS-2B cells. STING expression was positively correlated with SOCS1 expression but negatively correlated with CCL26 expression in nasal epithelial cells from patients with CRSwNP. CONCLUSIONS: Reduced STING expression caused by the type 2 milieu not only impairs STING-dependent type I interferon production but also amplifies IL-13 signaling by decreasing SOCS1 expression in nasal epithelial cells in eosinophilic CRSwNP.


Assuntos
Eosinofilia/imunologia , Interleucina-13/imunologia , Proteínas de Membrana/imunologia , Pólipos Nasais/imunologia , Rinite/imunologia , Sinusite/imunologia , Adulto , Células Cultivadas , Doença Crônica , Células Epiteliais/imunologia , Feminino , Proteínas Fetais/genética , Técnicas de Silenciamento de Genes , Humanos , Fator Regulador 3 de Interferon/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mucosa Nasal/citologia , Proteínas Tirosina Quinases/genética , Proteína 1 Supressora da Sinalização de Citocina/genética
15.
PeerJ ; 8: e10239, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194420

RESUMO

BACKGROUND: High heel shoes (HHS) can affect human postural control because elevated heel height (HH) may result in plantar flexed foot and limit ankle joint range of motion during walking. Effects of HH and HHS wearing experience on postural stability during self-initiated and externally triggered perturbations are less examined in the literature. Hence, the objective of the present study is to investigate the influences of HH on human postural stability during dynamic perturbations, perceived stability, and functional mobility between inexperienced and experienced HHS wearers. METHODS: A total of 41 female participants were recruited (21 inexperienced HHS wearers and 20 experienced HHS wearers). Sensory organization test (SOT), motor control test (MCT), and limits of stability (LOS) were conducted to measure participant's postural stability by using computerized dynamic posturography. Functional reach test and timed up and go test were performed to measure functional mobility. The participants' self-perceived stability was assessed by visual analog scale. Four pairs of shoes with different HH (i.e., 0.8, 3.9, 7.0, and 10.1 cm) were applied to participants randomly. Repeated measures analysis of variance was conducted to detect the effects of HH and HHS wearing experience on each variable. RESULTS: During self-initiated perturbations, equilibrium score remarkably decreased when wearing 10.1 cm compared with flat shoes and 3.9 cm HHS. The contribution of vision to postural stability was larger in 10.1 cm HHS than in flat shoes. The use of ankle strategy worsened when HH increased to 7 cm. Similarly, the directional control of the center of gravity (COG) decreased for 7 cm HHS in LOS. Experienced wearers showed significantly higher percentage of ankle strategy and COG directional control than novices. Under externally triggered perturbations, postural stability was substantially decreased when HH reached 3.9 cm in MCT. No significant difference was found in experienced wearers compared with novices in MCT. Experienced wearers exhibited considerably better functional mobility and perceived stability with increased HH. CONCLUSIONS: The use of HHS may worsen dynamic postural control and functional mobility when HH increases to 3.9 cm. Although experienced HHS wearers exhibit higher proportion of ankle strategy and COG directional control, the experience may not influence overall human postural control. Sensory organization ability, ankle strategy and COG directional control might provide useful information in developing a safety system and prevent HHS wearers from falling.

16.
J Am Podiatr Med Assoc ; 110(4)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32997764

RESUMO

BACKGROUND: Wearing high-heeled shoes and carrying asymmetrical loads are common in ladies. However, knowledge of the effects of wearing high-heeled shoes on balance and lower-extremity biomechanics in experienced and novice high-heeled shoe wearers is lacking. The study aims to examine the effects of high-heeled shoes and asymmetrical load carrying on joint kinematics and kinetics of the lower extremity during walking as well as balance in experienced and novice high-heeled shoe wearers. METHODS: Fifteen experienced and 15 novice high-heeled shoes wearers participated in this study. Using a motion analysis system, kinematic and kinetic data were collected while participants walked at their preferred speed in six conditions created from two types of shoes (9-cm high-heeled shoes and flat-heeled shoes) and three weights of symmetrical load (0%, 5%, and 10% of body weight). Stride time and length, step length, double support time, peak joint angles, and joint moments in a sagittal plane were analyzed. Single-leg and tandem-leg stance tests were performed in each condition. RESULTS: Compared with experienced high-heeled shoe wearers, novice high-heeled shoe wearers had longer double support time and shorter stride length during 10% of body weight asymmetrical load walking; walked with greater knee flexion angle, smaller knee range of motion, and smaller ankle dorsiflexor moment; and scored lower in the single-leg and tandem-leg stance tests. CONCLUSIONS: Novice high-heeled shoe wearers need to alter their lower-limb joint angles and moments to adjust to high-heeled shoes to achieve balance during gait while carrying an asymmetrical load.


Assuntos
Sapatos , Caminhada , Fenômenos Biomecânicos , Marcha , Calcanhar , Humanos , Articulação do Joelho , Extremidade Inferior
17.
Res Sports Med ; 28(4): 572-587, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32954802

RESUMO

The aim of this review was to examine the effects of shoes and insoles on low back pain (LBP). Seven electronic databases were searched from their inception to May 2020. The methodological quality of the 14 included studies was assessed by PEDro scale. Quality of evidence was assessed using GRADE. Moderate evidence on the disability questionnaire score (SMD, 0.52; 95% CI, 0.28 to 0.77; P < 0.001) and pain score (SMD, 0.61; 95% CI, 0.36 to 0.85; P < 0.001) of the custom-made orthotics for chronic LBP compared with no orthotics/insoles intervention was found. Meta-analysis results also showed moderate evidence on the disability questionnaire score (SMD, 0.44; 95% CI, 0.05 to 0.82; P =0.03) in patients who wore unstable shoes compared with regular shoes. Pain and life quality scores showed low-quality evidence of unstable shoes for chronic LBP. Custom-made orthotics and unstable shoes can be recommended to patients as a management option of chronic LBP.


Assuntos
Dor Crônica/reabilitação , Órtoses do Pé , Dor Lombar/reabilitação , Sapatos , Atividades Cotidianas , Fenômenos Biomecânicos , Desenho de Equipamento , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Autoavaliação (Psicologia) , Inquéritos e Questionários
18.
J Exerc Sci Fit ; 18(2): 89-93, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32636890

RESUMO

OBJECTIVES: This study aimed to compare the plantar loads between habitual rearfoot strike (RFS) and non-RFS (NRFS) during running under the participant's preferred speed. METHODS: A total of 66 (36 RFS, 30 NRFS) healthy amateur male runners were included in our study. In-shoe pressure sensors were utilised to the test plantar loads when participants were running using their preferred foot strike pattern and running speed (RFS: 3.2 ± 0.3 m/s; NRFS: 3.4 ± 0.4 m/s). RESULTS: Results indicated that running speed has a significant effect on the total contact area [F (1, 64) = 7.061, P = 0.01, η 2  = 0.101], which also affects midfoot and forefoot regions. No significant difference was found on the total maximum force, force-time-integral, peak pressure (PP) and pressure-time-integral (PTI), but the total contact area of RFS was higher than that of NRFS runners [F (1, 64) = 77.406, P < 0.001, η 2  = 0.551]. Plantar loads were mainly focused on the heel and midfoot for RFS runners in all variables, and NRFS runners experienced increased PP and PTI in medial forefoot regions. CONCLUSION: Habitual runners tend to adjust their contact area according to the running speed through midfoot and forefoot regions. RFS runners remain susceptible to high impact force on the heel and midfoot, and NRFS runners experience high impact force in the first metatarsal regions. Therefore, runners should note this situation to avoid running-related injuries.

19.
Res Sports Med ; 28(4): 553-562, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32686490

RESUMO

We examined the effects of long-term exercise on age-related decline in static balance control through centre-of-pressure (CoP) measurements of four groups of participants: older controls, younger controls, older Tai Chi exercisers and older joggers. The participants stood quietly in a tandem stance on a force platform for 30 s with eyes open (EO) and eyes closed (EC). The older controls showed remarkably larger CoP and EC/EO ratios than younger controls and older Tai Chi exercisers. The EC/EO ratios of velocity in the mediolateral direction of older joggers were significantly smaller than those of older controls. Results suggest that the static balance of older controls showed a significant decline caused by age-related changes. Long-term Tai Chi and jogging, particularly the former, contributed to static balance control in older people. Older adults relied more on visual information in static postural control than young people. Tai Chi would be an ideal exercise for improving static balance in older people.


Assuntos
Exercício Físico/fisiologia , Corrida Moderada/fisiologia , Equilíbrio Postural/fisiologia , Tai Chi Chuan , Adulto , Idoso , Envelhecimento/fisiologia , Estudos Transversais , Humanos , Masculino , Fatores de Tempo , Percepção Visual/fisiologia , Adulto Jovem
20.
Allergy Asthma Immunol Res ; 12(2): 274-291, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32009322

RESUMO

PURPOSE: Plasma cells and immunoglobulins (Igs) play a pivotal role in the induction and maintenance of chronic inflammation in nasal polyps. During secondary immune responses, plasma cell survival and Ig production are regulated by the local environment. The purpose of the present study was to investigate the presence of long-lived plasma cells (LLPCs) and specific survival niches for LLPCs in human nasal polyps. METHODS: Nasal mucosal samples were cultured with an air-liquid interface system and the Ig levels in culture supernatants were analyzed by enzyme-linked immunosorbent assay. The characteristics of LLPCs in nasal polyps were determined by immunohistochemistry and immunofluorescence. The expression of neurotrophins as well as their receptors was detected by quantitative real-time polymerase chain reaction, immunohistochemistry, immunofluorescence, and Western blotting. RESULTS: The numbers of CD138⁺ total plasma cells and BCL2⁺ plasma cells were increased in both eosinophilic and non-eosinophilic nasal polyps compared with those in normal tissues. The production of IgG, IgA, and IgE was detected in culture supernatants even after a 32-day culture of nasal polyps. Although the total numbers of plasma cells were decreased in nasal polyps after culture, the numbers of BCL2⁺ plasma cells remained stable. The expression of nerve growth factor (NGF) as well as tropomyosin receptor kinase (Trk) A, a high-affinity receptor for NGF, was upregulated in both eosinophilic and non-eosinophilic nasal polyps. In addition, BCL2⁺ plasma cell numbers were positively correlated with NGF and TrkA mRNA expression in nasal mucosal tissues. Polyp plasma cells had the expression of TrkA. CONCLUSIONS: Human nasal polyps harbor a population of LLPCs and NGF may be involved in their prolonged survival. LLPCs may be a novel therapeutic target for suppressing the local Ig production in nasal polyps.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...