RESUMEN
BACKGROUND: Mitochondrial myopathies (MMs) are a group of multi-system diseases caused by abnormalities in mitochondrial DNA (mtDNA) or mutations of nuclear DNA (nDNA). The diagnosis of mitochondrial myopathy (MM) is reliant on the combination of history and physical examination, muscle biopsy, histochemical studies, and next-generation sequencing. Patients with MMs have diverse clinical manifestations. In the contemporary literature, there is a paucity of reports on cardiac structure and function in this rare disease. We report a Chinese man with MM accompanied with both acute right heart failure and left ventricular hypertrophy. CASE PRESENTATION: A 49-year-old man presented with clinical features suggestive of MM, i.e., ophthalmoparesis, weakness of the pharyngeal and extremity muscles, and respiratory muscles which gradually progressed to respiratory insufficiency. He had a family history of mitochondrial myopathy. He had increased levels of serum creatine kinase and lactate. Muscle biopsy of left lateral thigh revealed 8% ragged red fibers (RRF) and 42% COX-negative fibers. Gene sequencing revealed a novel heterozygote TK2 variant (NM_001172644: c.584T>C, p.Leu195Pro) and another heterozygous variant (NM_004614.4:c.156+958G>A; rs1965661603) in the intron of TK2 gene. Based on these findings, we diagnosed the patient as a case of MM. Echocardiography revealed right heart enlargement, pulmonary hypertension, left ventricular hypertrophy, and thickening of the main pulmonary artery and its branches. The patient received non-invasive ventilation and coenzyme Q10 (CoQ10). The cardiac structure and function were restored at 1-month follow-up. CONCLUSIONS: This is the first report of reversible cardiac function impairment and left ventricular hypertrophy in a case of adult-onset MM, nocturnal hypoxia is a potential mechanism for left ventricular hypertrophy in patients with MM.
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Hipertrofia Ventricular Izquierda , Miopatías Mitocondriales , Adulto , Masculino , Humanos , Persona de Mediana Edad , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/genética , Pueblos del Este de Asia , Corazón , Miopatías Mitocondriales/complicaciones , Miopatías Mitocondriales/diagnóstico , Miopatías Mitocondriales/genética , CardiomegaliaRESUMEN
OBJECTIVE: Although there have been improvements in targeted therapy and immunotherapy, the majority of lung adenocarcinoma (LUAD) patients still lack effective therapies. Consequently, it is urgent to screen for new diagnosis biomarkers and pharmacological targets. Junctional adhesion molecule-like protein (JAML) was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD. Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD. However, the effect of kaempferol on JAML is still unknown. METHODS: Small interfering RNA was used to knockdown JAML expression. The cell viability was determined using the cell counting kit-8 assay. The proliferation of LUAD cells was evaluated using the 5-ethynyl-2'-deoxyuridine incorporation assay. The migration and invasion of LUAD cells were evaluated by transwell assays. Molecular mechanisms were explored by Western blotting. RESULTS: JAML knockdown suppressed proliferation, migration and invasion of LUAD cells, and JAML deficiency restrained epithelial-mesenchymal transition (EMT) via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Using a PI3K activator (740Y-P), rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway. Kaempferol also inhibited proliferation, migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway. Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells. Kaempferol exerted anticancer effects by targeting JAML. CONCLUSION: JAML is a novel target for kaempferol against LUAD cells. Please cite this article as: Wu Q, Wang YB, Che XW, Wang H, Wang W. Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma. J Integr Med. 2023; 21(3): 268-276.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Moléculas de Adhesión de Unión/genética , Moléculas de Adhesión de Unión/metabolismo , Quempferoles/farmacología , Línea Celular Tumoral , Movimiento Celular/genética , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proliferación Celular , Regulación Neoplásica de la Expresión GénicaRESUMEN
OBJECTIVES: To investigate the prevalence of sleep disturbance, sleep patterns, sleep-related factors, and medical demands among university and college students in Chongqing, China. METHODS: Demographic data and responses to the sleep problem questionnaire (SPQ) were collected from 1973 students from 11 universities and 10 colleges between November 2022 and January 2023. RESULTS: The prevalence of sleep disturbance in university and college students was different in different periods (58.17% during campus lockdown and 40.30% after the lifting of lockdown). The combined prevalence was 49.72%. The prevalence of the 6 types of sleep disturbance showed the same trend. The average sleep latency was 32.79 minutes and the average sleep duration was 7.53 hours. Male, university students, upper-class students, history of depression, academic stress, major life events, bad bedroom environment, and campus lockdown were factors related to sleep disturbance among respondents. Most of the respondents (52.09%) had no medical care requests, and the major reasons were a lack of access to medical care (75.15%), economic pressure (68.49%), concerns regarding curative effects (58.51%), and academic pressure (56.56%). CONCLUSION: The prevalence of sleep disturbance for university and college students was obviously improved after the lifting of campus lockdown, and the major factors related to sleep disturbance were study, life, mental health, and sleep environment. The students examined herein reported relatively low medical care requests when they experience sleep disturbance.
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Trastornos del Sueño-Vigilia , Humanos , Masculino , Universidades , Estudios Transversales , Trastornos del Sueño-Vigilia/epidemiología , China/epidemiología , Sueño , Estudiantes/psicologíaRESUMEN
A composite fluorescent nanoprobe based on metal enhanced fluorescence (MEF) effect of gelatin-coated silver nanoparticles (AgNPs@gel) was developed for selective and sensitive detection of dopamine (DA). The characteristic fluorescence of Tb(III) was using as the detection signal and AgNPs@gel served as substrates of the MEF. Gelatin with rich amine and carboxylic groups was used not only as a co-ligand of Tb(III) complex, but also as a bridging substance and a spacing material for improving the MEF of AgNPs@gel on the intrinsic luminescent intensity of Tb(III). Under the optimal conditions, the increment of the fluorescence intensity (measured at 307/544 nm as excitation/emission wavelength) of the system increased linearly with the concentration of DA in the range of 0.80-100 nM (R2 = 0.9937) and 100-1000 nM (R2 = 0.9978). The fluorescent probe greatly improved Tb(III) luminescence, which paved the way for sensitive detection with a low detection limit of 0.54 nM. It also showed good selectivity among other neurotransmitters. This work was successfully applied to the determination of DA in human serum samples with recoveries ranging from 99.8 to 102.2%. We believe that the Tb(III)-DA-AgNPs@gel composite fluorescent probe can be developed as a new approach for DA detection.
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Dopamina/análisis , Nanopartículas del Metal , Plata , Terbio , Fluorescencia , Gelatina , Humanos , Límite de Detección , Espectrometría de FluorescenciaRESUMEN
OBJECTIVE: To explore the effect of ligustrazine injection (LI) on serum levels of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) in patients with bronchial asthma and determine the mechanism of action of LI in preventing and treating asthma. METHODS: Sixty-eight patients with mild or moderate bronchial asthma were assigned to two groups equally according to their sequence number, odd or even. The conventional treatment was administered to both groups, and LI was given to the treatment group by ultrasonic spray inhalation twice a day but not to the control group. The therapeutic course for all was 2 weeks. Further, 30 healthy subjects who had no history of smoking were enrolled as the normal control group. The clinical condition scores, frequency of attacks and dosage of Terbutaline inhaled were scored and recorded on the first day of hospitalization (before treatment) and after treatment. At the same time, the indexes of lung function, including forced expiratory volume in one second (FEV1), forced expiratory volume in one second to forced vital capacity ratio (FEV1%) and the peak expiratory flow (PEF) were determined before treatment. The levels of IL-4 and IFN-gamma in peripheral blood were detected by ELISA before and after treatment, and compared with that of the healthy control group. RESULTS: After treatment, the clinical condition scores were found to be lower, indexes of lung function were elevated, but serum level of IL-4 and ratio of IL-4/IFN-gamma were reduced in both groups, showing significant differences as compared to those before treatment (P<0.05). However, the changes in all the indexes were more significant in the treatment group than in the control group, also showing statistical significance (P<0.05). No significant difference was revealed when IFN-gamma levels were compared before and after treatment in both groups, though a lowering trend could be seen, significant difference could not be found in the comparison of IFN-gamma levels between groups after treatment (P>0.05). CONCLUSION: LI shows good clinical effect in treating bronchial asthma, and its mechanism might be related to the suppression of the synthesis of IL-4, thus leading to the inhibition of TH2 cell subset preponderant response and immune equilibrium regulation.
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Agonistas Adrenérgicos beta/uso terapéutico , Asma/sangre , Asma/tratamiento farmacológico , Interferón gamma/sangre , Interleucina-4/sangre , Pirazinas/administración & dosificación , Pirazinas/uso terapéutico , Agonistas Adrenérgicos beta/administración & dosificación , Anciano , Anciano de 80 o más Años , Asma/fisiopatología , Estudios de Casos y Controles , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Terbutalina/uso terapéuticoRESUMEN
OBJECTIVE: To investigate the effects of ligustrazine (LTZ) on airway inflammation in a mouse model of neutrophilic asthma (NA). METHODS: Forty healthy C57BL/6 female mice were randomly divided into 4 groups using a random number table, including the normal control, NA, LTZ and dexamethasone (DXM) groups, with 10 rats in each group. The NA mice model was established by the method of ovalbumin combined with lipopolysaccharide sensitization. At 0.5 h before each challenge, LTZ and DXM groups were intraperitoneally injected with LTZ (80 mg/kg) or DXM (0.5 mg/kg) for 14 d, respectively, while the other two groups were given the equal volume of normal saline. After last challenge for 24 h, the aerosol inhalation of methacholine was performed and the airway reactivity was measured. The bronchoalveolar lavage fluid (BALF) was collected. The Wright-Giemsa staining was used for total white blood cells and differential counts. The levels of cytokines interleukin (IL)-17 and IL-10 were detected by enzyme-linked immunosorbent assay. The pathological change of lung tissue was observed by hematoxylin eosin staining. RESULTS: The airway responsiveness of the NA group was signifificantly higher than the normal control group (P<0.05), while those in the LTZ and DXM groups were signifificantly lower than the NA group (P<0.05). The neutrophil and eosinophil counts in the LTZ and DXM groups were signifificantly lower than the NA group (P<0.05), and those in the LTZ group were signifificantly lower than the DXM group (P<0.05). There were a large number of peribronchiolar and perivascular inflammatory cells in fifiltration in the NA group. The airway inflflammation in the LTZ and DXM groups were signifificantly alleviated than the NA group. The infifiltration in the LTZ group was signifificantly reduced than the DXM group. Compared with the normal control group, the IL-17 level in BALF was signifificantly increased and the IL-10 level in BALF was signifificantly decreased in the NA group (P<0.05). LTZ and DXM treatment signifificantly decreased IL-17 levels and increased IL-10 levels compared with the NA group (P<0.05), and the changes in the above indices were more signifificant in the LTZ group (P<0.05). CONCLUSION: LTZ could alleviate the airway inflflammation in the NA mice model through increasing the IL-10 level and decreasing the IL-17 level.
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Asma/tratamiento farmacológico , Asma/patología , Neutrófilos/patología , Neumonía/tratamiento farmacológico , Pirazinas/uso terapéutico , Animales , Asma/sangre , Asma/complicaciones , Líquido del Lavado Bronquioalveolar/citología , Modelos Animales de Enfermedad , Femenino , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Recuento de Leucocitos , Pulmón/efectos de los fármacos , Pulmón/patología , Ratones Endogámicos C57BL , Neutrófilos/efectos de los fármacos , Neumonía/sangre , Neumonía/complicaciones , Neumonía/patología , Pirazinas/farmacología , Hipersensibilidad Respiratoria/sangre , Hipersensibilidad Respiratoria/complicaciones , Hipersensibilidad Respiratoria/tratamiento farmacológico , Hipersensibilidad Respiratoria/patologíaRESUMEN
OBJECTIVE: To study the morbidity of cough variant asthma (CVA) among patients with chronic cough syndrome and its relative risk factors. METHODS: Patients were recruited with detailed history on their illness. Data were collected on physical examination, chest X-ray, eosinophil cell counts, pulmonary ventilation with histamine stimulating test and bronchi dilation test. According to available data, diagnosis of CVA was confirmed and the relative factors Questionnaire form was completed for each patient. RESULTS: Among 473 patients with chronic cough, 95 (44 male and 51 female) were confirmed to be CVA (20.08%). Analysis of the relative factors suggested that CVA was associated with multiple factors. Morbidity of CVA was associated with season, personal histories on allergy and family history on asthma. CVA could be induced by upper respiratory tract infection, inhale of oil vapor, acrimony air, over-burdened physical exercises etc. CONCLUSION: For patients with chronic cough symptom, clear diagnosis of CVA, avoid of passable risk factors and timely medical intervention when necessary, would be helpful in controlling clinical courses and improving the prognosis of the disease.