RESUMEN
Ovarian cancer is one of the most lethal gynecological malignancies, because of metastatic dissemination with poor late clinical therapy. Maggots have been used in traditional Chinese medicine, where they are also known as 'Wu Gu Chong'. Previous studies have indicated that maggot extract (ME) was beneficial for the treatment of gastric cancer when combined with other drugs, but the effect on anti-ovarian cancer and the underlying mechanism remains unclear. The aim of this study was to investigate the effects of ME on suppressing the proliferation and migration of ovarian cancer cells, and to clarify the underlying mechanism. In this research, Cell Counting Kit-8 (CCK-8), colony formation assay, and luciferase-positive cell quantification assay were employed to identify the inhibitory effects of ME on cell proliferation. Then, the pro-apoptosis and anti-metastasis effects of ME were explored by Western blot, dual annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assay, immunofluorescent staining, and wound-healing assay. We further established a xenograft model by subcutaneously or intraperitoneally injecting BALB/c nude mice with SKOV3 cells stably expressing luciferase, and the mice were treated with ME. The results showed that ME therapy effectively restrained the growth and metastasis of ovarian tumors in vivo. Furthermore, the mRNA levels of cancer factors including heat shock protein 90 alpha family class B member 1 (HSP90AB1), MYC, and insulin like growth factor 1 receptor (IGF1R) were analyzed by quantitative real-time PCR assay to explore the possible antitumor mechanisms of ME. Next, HSP90 ATPase activity was inhibited by geldanamycin in A2780, and the cell viability was shown to be dramatically reduced, decreasing further with the combination of ME and cisplatin. In turn, HSP90AB1 overexpression effectively inhibited the effect of ME in suppressing capability for cell viability and migration. In addition, HSP90AB1 overexpression limited the ability of ME to inhibit expression of MYC and IGF1R, while the opposite effect was observed for expression of pro-apoptosis protein caspase3 and BAX. Therefore, this study confirmed the potential roles and mechanisms of ME in inhibiting the growth and metastasis of ovarian tumors and promoting apoptosis of ovarian cancer cells by inhibiting overexpression of HSP90AB1.
RESUMEN
Ulcerative colitis (UC) is a common chronic remitting disease but without satisfactory treatment. Maggots are known as a traditional Chinese medicine named as 'wu gu chong'. The aim of the present study was to investigate the therapeutic effect of the maggot protein on dextran sulphate sodium (DSS)-induced colitis in C57BL/6 mice. In the present study, female C57BL/6 mice were given sterile water containing 3% DSS to establish the model of UC. Mice were randomly divided into five groups: control group (sterile water), model group (DSS), treatment group (DSS + maggot protein), mesalazine group (DSS + mesalazine), and maggot protein group (sterile water + maggot protein). The mental state, defecate traits, and changes in body weights were recorded daily. The disease activity index (DAI) as a disease severity criterion was calculated based on body weights and stool consistency and bleeding. All the mice were killed on the 12th day. Colon length, colon histological changes, and other inflammatory factors were analyzed and evaluated. The results showed that colitis models of mice were established successfully. Administration of maggot protein markedly suppressed the severity of UC compared with the DSS model group. Furthermore, maggot protein potently ameliorated DSS-induced weight loss, colon shortening, and colon histological injury. Moreover, the maggot protein exerted anti-inflammatory effects via inhibition of the activation of the nuclear factor κB (NFκB) signaling pathway. In summary, treatment by maggot protein was able to improve not only the symptoms of colitis, but also the microscopic inflammation in mice with DSS-induced colitis. The present study may have implications for developing an effective therapeutic strategy for inflammatory bowel diseases (IBDs).
Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Proteínas de Insectos/administración & dosificación , Larva/química , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/patología , Colon/efectos de los fármacos , Colon/patología , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Humanos , Inflamación/inducido químicamente , Inflamación/patología , Proteínas de Insectos/química , Medicina Tradicional China , Ratones , Transducción de Señal/efectos de los fármacosRESUMEN
Stroke is the third most common cause of death in most industrialized countries. Polygonum multiflorum (He-Shou-Wu, HSW) is one of the traditional Chinese medicines with multiple pharmacological activities which is widely used in Chinese recipe. This study aims to explore the protective effect of HSW on ischemic stroke rat model and to elucidate the underlying mechanisms. The mortality rate, neurological deficit, cerebral infarct size, histopathology, immunohistochemistry, biochemical parameters, quantitative real-time polymerase chain reaction and western blotting were used to access the treatment effects of HSW on ischemic stroke. Proton nuclear magnetic resonance (1H NMR) based metabolomics analysis disclosed that HSW could relieve stroke rats suffering from the ischemia/reperfusion injury by ameliorating the disturbed energy and amino acids metabolisms, alleviating the oxidative stress from reactive oxygen species and reducing the inflammation. HSW treatment increased levels of cellular antioxidants that scavenged reactive oxygen species during ischemia-reperfusion via the nuclear erythroid 2-related factor 2 signaling pathway, and exert anti-inflammatory effect by decreasing the levels of inflammatory factors such as cyclooxygenase-2, interleukin-1ß, interleukin-6 and tumor necrosis factor-α. The integrated metabolomics approach showed its potential in understanding mechanisms of HSW in relieving ischemic stroke. Further study to develop HSW as an effective therapeutic agent to treat ischemic stroke is warranted.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Medicamentos Herbarios Chinos/farmacología , Fallopia multiflora/química , Fármacos Neuroprotectores/farmacología , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/metabolismo , Animales , Antioxidantes/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/química , Masculino , Medicina Tradicional China/métodos , Metabolómica/métodos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Espectroscopía de Protones por Resonancia Magnética/métodos , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismoRESUMEN
BACKGROUND: This study was conducted to evaluate the prevalence of iron-deficiency anemia (IDA) after Roux-en-Y gastric bypass (RYGB) in Chinese obese patients with type 2 diabetes (T2DM). Furthermore, we evaluate potential predicting factors for onset of IDA after RYGB. METHODS: A total of 184 obese T2DM individuals who underwent RYGB were enrolled in the study. Patients were divided into three groups: male, premenopausal female, and postmenopausal female. Hematologic parameters were obtained prior to and after surgery on standardized time intervals up to 24 months postoperatively. RESULTS: At baseline, 6.0 % of patients were anemic, with similar percentages of anemic patients in each group. The relative decrease in the mean hemoglobin (Hb) level was significantly more pronounced for premenopausal female than for postmenopausal female or male. The percentage of anemia in male group had increased to 15.2 and 17.0 % at 6 and 12 months, respectively, and then decreased to 4.5 % at 24-month visit. In postmenopausal female group, the percentages of anemia constantly increase to 34.0 % at 6-month follow-up. Then, it decreased gradually to 25.0 and 26.7 % at 12- and 24-month visits, respectively. In premenopausal female group, the anemia percentages dramatically increased to 62.5 % at 24-month follow-up. Multiple logistic regression indicated that lower serum ferritin level preoperative and female were associated with higher possibility to suffer IDA 2 years after RYGB. CONCLUSIONS: Iron-deficiency and IDA are extremely frequent after RYGB in Chinese obese patients with T2DM. Premenopausal female presents unexpectedly high incidence of IDA during the 2-year observation.
Asunto(s)
Anemia Ferropénica/epidemiología , Diabetes Mellitus Tipo 2/cirugía , Suplementos Dietéticos , Derivación Gástrica/efectos adversos , Obesidad/cirugía , Adulto , Anemia Ferropénica/etiología , Anemia Ferropénica/prevención & control , Pueblo Asiatico , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Estudios de Seguimiento , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Prevalencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Sinomenine is originally derived from medicinal herb and used preferentially in treatment of rheumatoid diseases in Far East regions. SIN has strong anti-inflammatory and immune-regulatory properties, acting mainly through inhibiting NF-kB signaling. Although the upstream target through which SIN affects NF-kB activity is unknown, evidence suggests that SIN might regulate inflammation through Nrf2 signaling. In this study we explored the role of Nrf2 in mediating SIN's anti-inflammation and kidney protection in a mouse model of obstructive nephropathy. We found that SIN is an activator of Nrf2 signaling. It markedly increased Nrf2 protein level, Nrf2 nuclear translocation, Nef2 transcription capacity, and the downstream protein expression. We further demonstrated that SIN activation of Nrf2 is likely due to its repression of the Nrf2 inhibitor Keap1 since it drastically reduced Keap1 protein through the PKC-sensitive ubiquitination-proteasomal degradation. SIN treatment of nephropathy mice effectively reduced the kidney damage and inflammatory responses, balanced renal oxidative stress, and improved the pathological protein expression in an Nrf2 dependent manner. In addition, SIN also Nrf2-dependently modulated macrophage M1/M2 polarization and inhibited the IkBα phosphorylation and NF-kB nuclear translocation, hence revealing an important upstream event that contributed to its anti-inflammation and tissue protection. Taken together our study has identified a novel pathway through which SIN exerts its anti-inflammation and renal protective functions, and provided a molecular basis for SIN potential applications in the treatment of kidney and other inflammatory disorders.