RESUMEN
OBJECTIVE: The aim of the study was to investigate the safety and antiviral efficacy of a Chinese multiherb extract-based tincture (GWK) on a population of patients with high-risk human papilloma (hrHPV) infections and hrHPV-caused cervical low-grade squamous intraepithelial lesions (LSILs). PATIENTS AND METHODS: Patients with persistent hrHPV infection were enrolled in Group A, including A1 subjects, who received the intervention, and A2 subjects, who received the control. Patients with hrHPV infection causing cervical LSIL were enrolled in Group B, which included B1 subjects, who received the intervention, and B2 subjects, who served as the control. For Groups A1 and B1, hrHPV was tested at 3 months (M3) and 6 months (M6) after the intervention. The side effects were also analyzed. RESULTS: At baseline (D0), a total of 99 patients were enrolled in Group A, with 50 subjects in Group A1 and 49 subjects in Group A2. A total of 91 patients were enrolled in Group B, with 45 subjects in Group B1 and 46 subjects in Group B2. There was no significant difference in the characteristics, including average age, age stratification, and HPV genotype. At M6, both Group A1 and Group B1 had a higher hrHPV clearance rate than the control group (A1/A2: 80.0% vs. 20.4%; B1/B2: 64.4% vs. 15.2%, p<0.001). At M6, the effective rates of Group A1 and Group B1 were 84% (42/50) and 68.9% (31/45), respectively. The side effect rates of Groups A1 and B1 were 11.5% (6/52) and 11.1% (5/45), respectively. Most adverse reactions involved local discomfort, including vulvar erythema, vulvar itch, increased vaginal discharge, cervical bleeding, and mild pain in the lower abdomen. Univariate logistic regression analysis showed that the intervention had an OR of 12 (95% CI 4.431-32.50) for clearing persistent HPV infection (p<0.001). For cervical LSIL, the intervention had an OR of 10.1 for clearing persistent HPV infection (95% CI 3.68-27.7) (p<0.001). CONCLUSIONS: The results of this study suggest that the Chinese multiherb extract-based tincture GWK is safe and well tolerated. Furthermore, this preliminary study showed that this Chinese multiherb extract-based tincture is helpful for promoting HPV clearance in cases of persistent HPV and HPV-induced LSIL.
Asunto(s)
Medicamentos Herbarios Chinos , Infecciones por Papillomavirus , Femenino , Humanos , China , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Pueblos del Este de Asia , Papillomaviridae/efectos de los fármacos , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/tratamiento farmacológico , Infecciones por Papillomavirus/virología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/efectos adversos , Extractos Vegetales/uso terapéutico , Estudios Prospectivos , Displasia del Cuello del Útero/tratamiento farmacológico , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Frotis VaginalRESUMEN
Despite abundant data supporting c-Src as a metastasis-promoting oncogene, activating mutations of c-Src are rare. This suggests that trans-interacting proteins may have a critical role in regulating c-Src activation. Here, we first report the discovery of Src homology 3 (SH3) domain-binding glutamic acid-rich-like protein (SH3BGRL), a novel c-Src activator in mice. Ectopic expression of murine SH3BGRL (mSH3BGRL) strongly promoted both tumor cell invasion and lung metastasis. Molecularly, mSH3BGRL specifically bound the inactive form of c-Src phosphorylated at Tyr527, promoting Tyr416 phosphorylation of c-Src and subsequent FAK-mediated activation of ERK and AKT signaling pathways. Targeting endogenous c-Src alone was sufficient to abolish mSH3BGRL-induced cancer metastasis in vivo. Unexpectedly, human SH3BGRL (hSH3BGRL) in turn suppressed tumorigenesis and metastasis in nature. We attempted site-specific reversion of hSH3BGRL amino-acid sequence to mSH3BGRL and found V108A substitution sufficient to restore SH3BGRL function as a c-Src activator and metastasis promoter. Notably, the somatic mutation R76C of hSH3BGRL can similarly act as hSH3BGRL-V108A and mSH3BGRL in tumorigenesis and metastasis. Our results uncover an evolutionarily controversial role of SH3BGRL in driving tumor metastasis through c-Src activation, and suggests that hSH3BGRL mutation status could be relevant to cancer diagnosis and therapy.
Asunto(s)
Neoplasias/genética , Oncogenes/genética , Proteínas/genética , Proteínas Supresoras de Tumor/genética , Secuencia de Aminoácidos , Animales , Western Blotting , Células CHO , Línea Celular Tumoral , Movimiento Celular/genética , Cricetinae , Cricetulus , Humanos , Células MCF-7 , Ratones Desnudos , Mutación , Metástasis de la Neoplasia , Neoplasias/metabolismo , Neoplasias/patología , Unión Proteica , Proteínas/metabolismo , Proteínas Proto-Oncogénicas pp60(c-src)/genética , Proteínas Proto-Oncogénicas pp60(c-src)/metabolismo , Interferencia de ARN , Homología de Secuencia de Aminoácido , Transducción de Señal/genética , Trasplante HeterólogoRESUMEN
Angiostrongylus cantonensis (A. cantonensis) infection causes eosinophilic meningitis in humans. Eosinophilia and a Th2-type immune response are the crucial immune mechanisms for eosinophilic meningitis. CD4+CD25+ regulatory T cells (Treg) are involved in the pathogenesis of A. cantonensis. Diammonium glycyrrhizinate (DG) is a compound related to glycyrrhizin (GL), a triterpene glycoside extracted from liquorice root. We investigated the curative effects and probable mechanisms of therapy involving a combination of albendazole and DG in BALB/c mice infected with A. cantonensis, and compared these with therapy involving albendazole and dexamethasone. We analysed survival time, body weight, signs, eosinophil numbers, immunoglobulin E (IgE), interleukin-5 (IL-5), and eotaxin concentrations, numbers and Foxp3 expression of CD4+CD25+ Treg, worm recovery and histopathology. The present results demonstrated that the combination of albendazole and DG could increase survival time more efficiently and relieve neurological dysfunction; decrease weight loss, eosinophil numbers, concentrations of IgE, IL-5 and eotaxin, the number and expression of Foxp3 of CD4+CD25+ Treg; and improve worm recovery and histopathology changes in treated animals, compared with the combination of albendazole and dexamethasone. The observations presented here suggest that the albendazole and dexamethasone combination could be replaced by the combination of albendazole and DG.
Asunto(s)
Albendazol/administración & dosificación , Angiostrongylus cantonensis/efectos de los fármacos , Antihelmínticos/administración & dosificación , Eosinofilia/tratamiento farmacológico , Ácido Glicirrínico/administración & dosificación , Meningitis/tratamiento farmacológico , Infecciones por Strongylida/tratamiento farmacológico , Angiostrongylus cantonensis/patogenicidad , Animales , Peso Corporal , Dexametasona/administración & dosificación , Modelos Animales de Enfermedad , Eosinofilia/parasitología , Femenino , Humanos , Inmunoglobulina E/sangre , Recuento de Leucocitos , Meningitis/parasitología , Ratones , Ratones Endogámicos BALB C , Infecciones por Strongylida/parasitología , Análisis de Supervivencia , Linfocitos T Reguladores/inmunología , Resultado del TratamientoRESUMEN
Vocal cord dysfunction (VCD) is an uncommon condition which often mimics asthma in presentation and severity. We present nine- and 11-year-old female siblings with vocal cord dysfunction, which is a dysfunction of the larynx involving unintentional paradoxical adduction of the vocal cords during inspiration. We evaluated the use of exercise testing in conjunction with pulmonary function testing in suspected vocal cord dysfunction. Although normal pulmonology function tests were elicited with the patient at rest, exercise testing revealed blunting of the expiratory loop with attenuation of the inspiratory loop unique to VCD. The child underwent video laryngoscopy in the specialised voice clinic, which confirmed vocal cord dysfunction. Exercise testing is a rapid and noninvasive means of diagnosing vocal cord dysfunction in a small subset of patients, but video laryngoscopy, with training manoeuvres to elicit paradoxical vocal cord movements in VCD, remains the gold standard of diagnosis of VCD.
Asunto(s)
Asma Inducida por Ejercicio/diagnóstico , Disnea/etiología , Enfermedades de la Laringe/diagnóstico , Trastornos Respiratorios/diagnóstico , Ruidos Respiratorios/etiología , Pliegues Vocales/patología , Niño , Diagnóstico Diferencial , Prueba de Esfuerzo , Femenino , Humanos , Enfermedades de la Laringe/complicaciones , Pruebas de Función RespiratoriaRESUMEN
BACKGROUND: Food allergy seems to be increasing in Asia as well as world-wide. Our aim was to characterize food protein sensitization patterns in a population of Asian children with possible food allergy. METHODS: Children presenting to our allergy clinic over 3 years with symptomatic allergic disease and at least one specific food allergen sensitization documented on skin prick testing were included in the analysis. RESULTS: Two hundred and twenty-seven patients fulfilled inclusion criteria. Ninety (40%) of the positive skin tests were positive to egg, 87 (39%) to shellfish, 62 (27.3%) to peanut, 30 (13.2%) to fish, 27 (11.8%) to cow's milk, 21 (9.3%) to sesame, 13 (3.7%) to wheat and eight (3.2%) to soy. Peanut sensitization was the third most common sensitizing allergen, and seen mostly in young atopic children with multiple food hypersensitivities and a family history of atopic dermatitis. The median reported age of first exposure to fish and shellfish was 6 and 12 months, respectively. The mean age at presentation of children with shellfish hypersensitivity was at 6.7 years of age. The likelihood of shellfish sensitization was increased in children with concomitant sensitization to cockroaches. CONCLUSIONS: In contrast to previously reported low peanut allergy rates in Asia, in our review, peanut sensitization is present in 27% (62/227) of food-allergic children, mostly in patients with multiple food protein sensitizations. Temporal patterns of first exposure of infants to fish and shellfish are unique to the Asian diet. Shellfish are a major sensitizing food source in Asian children, especially in allergic rhinitis patients sensitized to cockroaches.