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Radioimmunotherapy (RIT) is a novel and promising cancer treatment method, with ongoing research focusing on RIT antibody selection, radionuclides, treatment options, and benefited patient groups. As we dive into the mechanisms of tumor biology, a deeper exploration of how RIT affects tumor tissue is needed to provide new ways to improve clinical treatment outcome and patient prognosis. We labeled the anti-PD-L1 monoclonal antibody atezolizumab with iodine-131 (131I), separated and purified the labeled mAb with Sephadex G-25 medium gel filtration resin, and tested product stability. We detected the in vivo activity of 131I-PD-L1 mAb by analyzing its in vivo biodistribution and performing SPECT imaging and then set different treatment groups to study the effect of 131I-atezolizumab on the survival of tumor-bearing mice. Western blot, real-time quantitative PCR, and immunohistochemistry were used to detect the expression level of Caspase8 and Nlrp3 in tumor. TUNEL fluorescence staining was used to detect the apoptosis in the tumor. The radiopharmaceutical molecular probe 131I-atezolizumab showed high stability and in vivo biological activity. The treatment regimen adopted had a positive effect on the survival of tumor-bearing mice. 131I internal irradiation upregulated Caspase8 in tumor and ultimately inhibited solid tumor growth by activating apoptosis pathways. We also found a significant increase in the expression of NLRP3, which plays an important role in the pyroptosis pathway, in tumor. In summary, our data demonstrated that radiopharmaceuticals combined with immunotherapy affected tumor tissue by modulating relevant biological pathways, thereby achieving better antitumor effects compared with single therapy and providing new insights for promoting better patient prognosis and combination treatment strategies.
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Peritoneal dialysis(PD) is one of the most efficient methods in end-stage kidney disease, and it is very important for PD to perform well. No research has been conducted to evaluate the effect of various types of PD catheters on the prognosis of post-operative wound complications. While recent meta-analyses are in favour of straight tubing, there is still uncertainty as to whether direct or coiled PD is beneficial. The purpose of this meta-analysis was to compare the efficacy of direct and coiled PD catheters on the incidence of post-operative wound infection, bleeding and peritonitis. A comprehensive search was carried out on three databases, including PubMed and Embase, and a manual search was carried out on the links in the paper. The results showed that the incidence rate of bleeding after operation and the degree of infection among the straight and coiled pipes were compared. The results showed that there were no statistically significant differences in the incidence of post-operative wound infection among straight PD patients with coiled PD (OR, 0.79; 95% CI, 0.58-1.08 p = 0.13). No statistical significance was found in the case of PD with coiled tubing compared with that of straight PD group in wound leakage (OR, 1.17; 95% CI, 0.71-1.93 p = 0.55). No statistically significantly different rates of post-operative peritonitis were observed for coiled tubing compared with straight ones in PD patients (OR, 1.06; 95% CI, 0.78-1.45 p = 0.7). There is no statistical significance on the rate of wound infection, wound leakage and peritonitis among coiled and straight tube in PD.
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Diálisis Peritoneal , Peritonitis , Humanos , Catéteres de Permanencia/efectos adversos , Hemorragia , Diálisis Peritoneal/instrumentación , Diálisis Peritoneal/métodos , Peritonitis/epidemiología , Peritonitis/etiología , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiologíaRESUMEN
PURPOSE: Immune checkpoint inhibitors (ICIs) targeting tumor-specific PD-1/PD-L1 significantly improve the overall survival rate of patients with advanced cancer by reactivating the immune system to attack cancer cells. To explore their tumor killing effect, we used the radionuclide iodine-131 (131I) to label the anti-PD-L1 antibody Atezolizumab (131I-PD-L1 mAb). METHOD: We prepared the radioimmunoassay molecular probe 131I-PD-L1 mAb by the chloramine-T method and evaluated its affinity using Lewis lung cancer (LLC) cells. The uptake of 131I-PD-L1 mAb by transplanted tumors was examined through SPECT and its in vivo distribution. We then compared the in vitro and in vivo anti-tumor efficacy of groups treated with control, PD-L1 mAb, 131I-PD-L1 mAb, and 131I-PD-L1 mAb + PD-L1 mAb combined treatment. We performed H&E staining to examine the changes in tumor, as well as the damage in major tissues and organs caused by potential side effects. The anti-tumor mechanism of 131I-PD-L1 mAb was analyzed by Western blot, RT-qPCR and immunohistochemistry (IHC). RESULT: 131I-PD-L1 mAb was highly stable and specific, and easily penetrated into tumor. 131I-PD-L1 mAb suppressed cancer cell proliferation in vitro, and inhibited tumor growth in vivo by inducing ferroptosis, thus prolonging the survival of experimental animals while demonstrating biological safety. CONCLUSION: Therefore, our study suggested that 131I-PD-L1 mAb affected the expression of tumor-related factors through ß-rays and thus promoted ferroptosis in tumor. Combined treatment showed better anti-tumor effect compared to single ICI treatment.
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Anticuerpos Monoclonales Humanizados , Antígeno B7-H1 , Ferroptosis , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Animales , Humanos , Ratones , Antígeno B7-H1/inmunología , Línea Celular Tumoral , Inmunohistoquímica , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/terapia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Sondas Moleculares/uso terapéutico , Radioinmunoensayo , Carcinoma Pulmonar de Lewis , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inmunoterapia , Radioisótopos de Yodo/uso terapéuticoRESUMEN
Background: To analyze individually and interactively critical risk factors, which are closely related to low bone mineral density (BMD) in patient with ankylosing spondylitis (AS). Methods: A total of 249 AS patients who visited China-Japan Friendship Hospital were included in this training set. Patients with questionnaire data, blood samples, X-rays, and BMD were collected. Logistic regression analysis was employed to identify key risk factors for low BMD in different sites, and predictive accuracy was improved by incorporating the selected significant risk factors into the baseline model, which was then validated using a validation set. The interaction between risk factors was analyzed, and predictive nomograms for low BMD in different sites were established. Results: There were 113 patients with normal BMD, and 136 patients with low BMD. AS patients with hip involvement are more likely to have low BMD in the total hip, whereas those without hip involvement are more prone to low BMD in the lumbar spine. Chest expansion, mSASSS, radiographic average grade of the sacroiliac joint, and hip involvement were significantly associated with low BMD of the femoral neck and total hip. Syndesmophytes, hip involvement and higher radiographic average grade of the sacroiliac joint increases the risk of low BMD of the femoral neck and total hip in an additive manner. Finally, a prediction model was constructed to predict the risk of low BMD in total hip and femoral neck. Conclusions: This study identified hip involvement was strongly associated with low BMD of the total hip in AS patients. Furthermore, the risk of low BMD of the femoral neck and total hip was found to increase in an additive manner with the presence of syndesmophytes, hip involvement, and severe sacroiliitis. This finding may help rheumatologists to identify AS patients who are at a high risk of developing low BMD and prompt early intervention to prevent fractures.
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Enfermedades Óseas Metabólicas , Osteoporosis , Espondilitis Anquilosante , Humanos , Espondilitis Anquilosante/complicaciones , Densidad Ósea , Osteoporosis/etiología , Enfermedades Óseas Metabólicas/complicaciones , Factores de RiesgoRESUMEN
The ecological effects of mass-flowering crops on pollinator abundance and species richness of neighbouring habitats are well established, yet the potential evolutionary consequences remain unclear. We studied effects of proximity to a mass-flowering crop on the pollination of local co-flowering plants and on patterns of natural selection on a pollination-generalised plant on the Tibetan Plateau. We recorded pollinator visitation rates and community composition at different distances (near vs. far) to oilseed rape (Brassica napus) fields in two habitat types and quantified pollinator-mediated selection on attractive traits of Trollius ranunculoides. The proximity to oilseed rape increased pollinator visitation in neighbouring alpine meadows and changed pollinator composition in neighbouring shrub meadows. Trollius ranunculoides in the alpine meadow near oilseed rape received three times more pollinator visits (mainly bees) and consequently had a 16.5% increase in seed set but also received slightly more heterospecific pollen per stigma. In contrast, pollinator visitation to T. ranunculoides in the shrub meadow near oilseed rape was three times lower (mainly flies), leading to a 10.7% lower seed despite no effect on pollen deposition. The proximity to the oilseed rape field intensified pollinator-mediated selection on flower size and weakened selection on flower height of T. ranunculoides in the alpine meadow but did not affect phenotypic selection on either trait in the shrub meadow. Our study highlights context-dependent variation in plant-pollinator interactions close to mass-flowering oilseed rape, suggesting potential effects on the evolution of flower traits of native plants through altered pollinator-mediated selection. However, context dependence may make these effects difficult to predict.
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AIM: Ankylosing spondylitis (AS) is a chronic inflammatory disease. However, the key inflammatory cytokines disrupted in this disease are not well defined. In this study, we performed protein array and multiple protein quantification to investigate the differentially expressed cytokines in plasma between AS patients and healthy subjects. METHOD: In the discovery cohort, 5 AS patients who never underwent biologic therapy and 5 gender- and age-matched healthy subjects were enrolled in the protein array analysis. Another 40 AS patients and 20 healthy participants were recruited in the validation stage. In addition, the messenger RNA and protein levels of osteogenesis-related genes were quantified in hFOB1.19 cells in an in vitro osteoblast model. RESULTS: Of the 318 cytokines found to be differentially expressed by protein array, leukemia inhibitor factor (LIF) was significantly increased in AS patients as compared to controls. The "signaling by interleukins" pathway was the most enriched pathway in AS patients, and "signaling by interleukins"-related cytokines, including LIF, interleukin (IL)-6, IL-23, and IL-31, were significantly differentially expressed in the validation stage. Additionally, we correlated the expression of LIF with C-reactive protein (CRP) and inflammation of magnetic resonance imaging lesions in the spine (MRI-SPINE) in AS patients. We further analyzed the effects of LIF in hFOB cells and found that LIF promoted the growth factor receptor-bound protein 2 / phospho-extracellular signal-regulated kinase / runt-related transcription factor 2 / alkaline phosphatase pathway at the protein level and activated several osteogenesis-related genes (RUNX2 and BGLAP). CONCLUSION: LIF was increased in the plasma of AS patients as compared with healthy subjects and significantly correlated with inflammation indices (CRP and MRI-SPINE) in AS patients. Thus, LIF may play a critical role in the pathogenesis of AS via promoting osteogenic differentiation.
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Osteogénesis , Espondilitis Anquilosante , Humanos , Inflamación/metabolismo , Interleucina-6/metabolismo , Factor Inhibidor de Leucemia/genética , Factor Inhibidor de Leucemia/metabolismo , Factor Inhibidor de Leucemia/farmacología , Osteoblastos/patología , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/genéticaRESUMEN
OBJECTIVES: A cross-sectional study was conducted in 270 Chinese patients with ankylosing spondylitis (AS) in order to identify potential risk factors for severity of spinal structural damage. METHODS: Two hundred seventy AS patients fulfilled the Modified New York Criteria. Computed tomography (CT) was used to scan sacroiliac and hip joints, and radiography was used to scan anteroposterior and lateral lumbar spine, as well as lateral cervical spine. Bath Ankylosing Spondylitis Radiology Index and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) were scored in duplicate. RESULTS: One hundred eighty-three patients had low mSASSS (mSASSS, <10), and 87 patients had high mSASSS (mSASSS, ≥10). Univariate analysis revealed that AS age of onset, body mass index (BMI), smoking duration, duration of symptoms, diagnostic delay, hip involvement, and sacroiliitis grade were significantly associated with the risk of having high mSASSS after adjustment (all p's < 0.05). Hip involvement interacted significantly with BMI and smoking duration in a graded manner. Particularly, relative to patients with low BMI-negative hip involvement, those with high BMI-negative hip involvement, low BMI-positive hip involvement, and high BMI-positive hip involvement had a 1.94-fold, 3.29-fold, and 5.07-fold increased risk of high mSASSS (95% confidence interval, 0.84-4.47, 1.37-7.89, and 1.97-13.06, p = 0.118, 0.008, and 0.001, respectively). Finally, a nomogram graph based on 7 significant risk factors was generated with substantial prediction accuracy (concordance index, 0.906). CONCLUSIONS: We have identified 7 potential risk factors for the severity of spinal structural damage in Chinese AS patients. Importantly, positive hip involvement, combined with high BMI or long smoking duration, was associated with a remarkably increased risk of having severe spinal structural damage.
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Espondilitis Anquilosante , Vértebras Cervicales , China/epidemiología , Estudios Transversales , Diagnóstico Tardío , Progresión de la Enfermedad , Humanos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Columna Vertebral , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/epidemiologíaRESUMEN
Wangbi Tablets are widely used in the treatment of rheumatoid arthritis, knee osteoarthritis and other diseases at pre-sent. Long-term clinical application and research have shown that this drug has a good effect in reducing the pain of related diseases and improving symptoms. Due to the lack of guidance in the instructions and currently no relevant norms to guide the clinical application of Wangbi Tablets, in order to further improve clinicians' understanding of the drug and fully tap the clinical advantages of the drug, the Professional Committee of Orthopedics and Traumatology Drug Research of China Association of Chinese Medicine organized experts in the fields of rheumatism, orthopedics, pharmacy and methodology in Chinese and western medicine to develop expert consensus on Chinese patent medicines in accordance with the relevant requirements of the consensus methodology. Based on full consideration of clinical research evidence and expert experience, the clinical issues were summarized in the consensus, and for those clinical problems supported by evidences, the internationally recognized recommendation evaluation and formulation method GRADE was used to evaluate the evidence and form recommendations; for those clinical issues not supported by evidences, a consensus was reached through the nominal group method to form consensus recommendations. The consensus adopted a concise and clear format to form re-commendations or reach consensus suggestions on the medication regimen, medication characteristics, intervention timing, usage and dosage, course of use and safety issues for the treatment of rheumatoid arthritis and knee osteoarthritis with Wangbi Tablets. It is suggested that its application will better improve the efficacy of Wangbi Tablets in the treatment of rheumatoid arthritis and knee osteoarthritis, at the same time provide a reference for clinicians to use Wangbi Tablets in a standardized, reasonable and safe manner.
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Artritis Reumatoide , Medicamentos Herbarios Chinos , Osteoartritis de la Rodilla , Artritis Reumatoide/tratamiento farmacológico , Consenso , Humanos , Medicina Tradicional China , Osteoartritis de la Rodilla/tratamiento farmacológico , ComprimidosRESUMEN
This study was aimed to investigate the effect of piceatannol (PIC) on the proliferation and apoptosis of bladder cancer cell line EJ, and the underlying mechanism. Bladder cancer cell line EJ was incubated with different concentrations of PIC, and CCK-8 method was used to determine the effect of the treatment on cell proliferation. The effect of PIC on cell cycle, apoptosis and the expressions of related signal pathway proteins were determined using Western blotting. Flow cytometry showed that PIC inhibited the proliferation of EJ cells in a concentration- and time-dependent fashion. Moreover, EJ cells were significantly blocked in G0/G1 phase, when compared with the blank control group (p < 0.05). In addition, PIC enhanced apoptosis of EJ cells in a concentration-dependent manner (p < 0.05). Results from western blotting showed that, compared with the control group, PIC upregulated the protein expression of PTEN, but downregulated Akt protein phosphorylation, relative to control cells. PIC significantly inhibits the proliferation of EJ cells and enhances their apoptosis through a mechanism related to the activation of PTEN/Akt signaling pathway.
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Apoptosis/efectos de los fármacos , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Estilbenos/farmacología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Transducción de Señal/efectos de los fármacosRESUMEN
Rheumatoid arthritis (RA) is a common immune-mediated chronic inflammatory joint disease of unknown etiology. While tumor necrosis factor-α(TNF-α) blockers have proven to be a beneficial treatment option for many patients, not all respond to such treatments. In the present study, we investigate the role of the recently discovered zinc-sensing G protein-couple receptor GPR39. To our knowledge, this study is the first to investigate the role of GPR39 in the context of RA using human fibroblast-like synoviocytes (FLS). We found that agonism of GPR39 using its specific agonist TC-G 1008 significantly ameliorated important markers of RA, including oxidative stress, mitochondrial dysfunction, expression of proinflammatory cytokines including interleukin-1ß (IL-1ß), IL-6, and monocyte chemoattractant protein 1 (MCP-1), and secretion of key matrix metalloproteinases (MMPs) including MMP-1, MMP-3 and MMP-13. Furthermore, we demonstrate that these may be mediated via the Janus-kinase (JNK), activating protein 1 (AP-1), and nuclear factor-κB (NF-κB) cellular signaling pathways. Our findings demonstrate for the first time the potential of GPR39 to mediate synovial inflammation, pannus invasion, and enzymatic degradation of articular extracellular matrix.
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Fibroblastos/patología , Pirimidinas/farmacología , Receptores Acoplados a Proteínas G/agonistas , Sulfonamidas/farmacología , Sinoviocitos/efectos de los fármacos , Sinoviocitos/patología , Factor de Necrosis Tumoral alfa/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Quimiocina CCL2/biosíntesis , Citoprotección/efectos de los fármacos , Femenino , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Masculino , Metaloproteinasa 13 de la Matriz/biosíntesis , Metaloproteinasa 13 de la Matriz/metabolismo , Persona de Mediana Edad , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Estrés Oxidativo/efectos de los fármacos , Pirimidinas/uso terapéutico , Receptores Acoplados a Proteínas G/deficiencia , Receptores Acoplados a Proteínas G/genética , Transducción de Señal/efectos de los fármacos , Sulfonamidas/uso terapéutico , Sinoviocitos/metabolismoRESUMEN
BACKGROUND: There is limited experience about transcatheter closure of doubly committed subarterial ventricular septal defects with Amplatzer ductal occluder. METHODS: Between March, 2015 and July, 2017, a total of 22 patients with doubly committed subarterial ventricular septal defects received transcatheter closure using Amplatzer ductal occluder and underwent clinical follow-up for at least 6 months. RESULTS: Device implantation was finally successful in 21 (95.4%) patients despite failed occlusion in one patient and intra-procedural replacement of unsuitable occluders in four (19.0%) patients. In mean 12.3 months of follow-up, there were no major complications (death, aortic valve or sinus rupture, device dislocation or embolisation, grade 2 new-onset aortic regurgitation, etc.), resulting in clinical occlusion success of 95.4%. Mechanical haemolysis occurred in one patient and resolved with medication. Residual shunt was observed in 11 (52.4%) patients (9 mild, 2 moderate-severe) post-procedurally, 14 (66.7%) patients (12 mild, 2 moderate-severe) in hospital stay, and 2 (9.5%) patients (2 mild, 0 moderate-severe) at the last follow-up. Device-induced new-onset aortic regurgitation was found in nine (42.8%) patients (9 mild, 0 moderate-severe) post-procedurally and in hospital stay, which was resolved in two (9.5%) patients and unchanged in seven (33.3%) patients at the last follow-up. Another four (19.0%) patients newly developed mild aortic regurgitation during follow-up. CONCLUSIONS: Transcatheter closure of doubly committed subarterial ventricular septal defects with Amplatzer ductal occluder is technically feasible in the selected patients. However, further study is needed to confirm its long-term clinical outcomes.
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Defectos del Tabique Interventricular/cirugía , Dispositivo Oclusor Septal , Adolescente , Adulto , Insuficiencia de la Válvula Aórtica/etiología , Cateterismo Cardíaco , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Selección de Paciente , Dispositivo Oclusor Septal/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: We quantified the expression of six well-characterized microRNAs (miRNAs) in peripheral blood mononuclear cells to see whether they can predispose to syndesmophytes in ankylosing spondylitis (AS) patients. METHODS: This is a cross-sectional study involving 46 AS patients (23/23 with/without syndesmophytes) and 22 healthy controls. miRNAs expression was quantified by real-time PCR. RESULTS: Six examined miRNAs were comparably expressed between AS patients without syndesmophytes and healthy controls (p > .05). Relative to AS patients without syndesmophytes, patients with syndesmophytes had significantly higher levels of miR-29a, miR-335-5p, miR-27a and let-7i (p = .001, .002, .013 and .029, respectively). Nine significant contributors associated with syndesmophytes in AS, including smoking, AS duration, human leukocyte antigen B27, erythrocyte sedimentation rate, C-reactive protein, miR-335-5p, miR-27a, miR-218 and sacroiliitis, were identified. The addition of miR-335-5p, miR-27a and miR-218 can significantly improve the accuracy of baseline risk factors. Based on the nine significant contributors, a nomogram was constructed, with good prediction accuracy (C-index: 0.86, p < .001). CONCLUSION: We provide evidence for the predisposition of miR-335-5p, miR-27a and miR-218 to syndesmophytes in AS patients, indicating a contributory role of miRNAs in the pathogenesis of syndesmophytes. Further validation is warranted.
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MicroARNs/sangre , Espondilitis Anquilosante/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , China , Femenino , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , MicroARNs/genética , Espondilitis Anquilosante/genéticaRESUMEN
Disorder in circadian rhythm has been revealed as a risk factor for coronary heart disease. Several studies in molecular biology established a gene interaction network using coronary heart susceptibility genes and the circadian rhythm pathway. However, cross talk between genes was mostly discovered in single gene pairs. There might be combination sets of genes intergraded as a unit to regulate the network. To resolve multiple variables in coronary heart susceptibility genes controlling circadian rhythm pathways, a multiple correlation analysis was applied to the transcriptome. Nine genes, including CUGBP, Elav-like family member (CELF); sodium leak channel, nonselective (NALCN); protein phosphatase 2 regulatory subunit B gamma (PPP2R2C); tubulin alpha 1c (TUBA1C); microtubule-associated protein 4 (MAP4); cofilin 1 (CFL1); myosin heavy chain 7 (MYH7); QKI, KH domain containing RNA binding (QKI); and maternal embryonic leucine zipper kinase (MELK), from coronary heart susceptibility were identified to predict the outcome of a linear combination of circadian rhythm pathway genes with R factor more than 0.7. G protein subunit alpha o1 (GNAO1), protein kinase C gamma (PRKCG), RBX, and G protein subunit beta 1 (GNB1) in the circadian rhythm pathway are characterized as combination variables to coexpress with coronary heart susceptibility genes.
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Ritmo Circadiano , Biología Computacional/métodos , Enfermedad Coronaria/genética , Perfilación de la Expresión Génica/métodos , Algoritmos , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad , Células HEK293 , Humanos , Análisis por MicromatricesRESUMEN
Chitin deacetylases (CDAs) are enzymes that catalyze the conversion of chitin into chitosan, thereby influence the mechanical and permeability properties of structures such as the cuticle and peritrophic matrices. The full length cDNAs of chitin deacetylase2 (CDA2) genes from Hyphantria cunea were fully cloned by PCR amplification. Two cDNA sequences of HcCDA2 were searched from transcriptome of H. cunea and named as HcCDA2a and HcCDA2b. The deduced protein sequences showed that HaCDA2a and HaCDA2b are synthesized as preproteins of 524 and 518 amino acid residues with an 18-amino acid signal peptide, respectively. HcCDA2a and HcCDA2b contained a chitin-binding domain (ChBD), a low-density lipoprotein receptor class A domain (LDLa) and a polysaccharide deacetylase-like catalytic domain (CDA). Gene expression analyses results showed that HcCDA2a and HcCDA2b were both expressed at the head, integument, foregut, midgut, hindgut, Malpighian tubules and fat body, as well as the 1st to 5th days of fifth instar larvae. Western blot analyses revealed that HcCDA2 protein was highly abundant in the head and integument, and the developmental expression result in the fifth instars showed that HcCDA2 was highly present at the first two days. Besides, RT-PCR results showed that HcCDA2a and HcCDA2b were both expressed in integument and head, whether in molting stage or feeding stage. No visiable phenotypic changes were observed after injection of dsHcCDA2b, while lethal phenotypes of cuticle shedding failure and high mortality were resulted from injection of dsHcCDA2a. The silence of HcCDA2a leads to the ecdysis failure and death of H. cunea. These results suggest that HcCDA2 plays an important role during insect development, and provide new candidate targets and basis for developing environment-friendly pesticides.
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Amidohidrolasas/genética , Amidohidrolasas/metabolismo , Mariposas Nocturnas/enzimología , Amidohidrolasas/química , Animales , Sitios de Unión , Clonación Molecular , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Mariposas Nocturnas/genética , Mariposas Nocturnas/crecimiento & desarrollo , Unión Proteica , Distribución TisularRESUMEN
The fall webworm, Hyphantria cunea (Drury) is a major invasive pest in China. Aminopeptidase N (APN) isoforms in lepidopteran larvae midguts are known for their involvement in the mode of action of insecticidal crystal (Cry) proteins from Bacillus thuringiensis. In the present work, we identified a putative Cry1Ab toxin-binding protein, an APN isoform designated HcAPN3, in the midgut of H. cunea by ligand blot and mass spectrometry. HcAPN3 was highly expressed throughout all larval developmental stages and was abundant in the midgut and hindgut tissues. HcAPN3 was down-regulated at 6 h, then was up-regulated significantly at 12 h and 24 h after Cry1Ab toxin treatment. We expressed HcAPN3 in insect cells and detected its interaction with Cry1Ab toxin by ligand blot assays. Furthermore, RNA interference (RNAi) against HcAPN3 using oral delivery and injection of double-stranded RNA (dsRNA) resulted in a 61-66% decrease in transcript level. Down-regulating of the expression of HcAPN3 was closely associated with reduced susceptibility of H. cunea to Cry1Ab. In addition, the HcAPN3E fragment peptide expressed in Escherichia coli enhanced Cry1Ab toxicity against H. cunea larvae. This work represents the first evidence to suggest that an APN in H. cunea is a putative binding protein involved in Cry1Ab susceptibility.
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Bacillus thuringiensis/metabolismo , Proteínas Portadoras/metabolismo , Animales , Bacillus thuringiensis/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Antígenos CD13/genética , Antígenos CD13/metabolismo , Proteínas Portadoras/genética , Insecticidas , Larva , Espectrometría de Masas , Mariposas Nocturnas , Interferencia de ARNRESUMEN
Objective To observe the effect of Bushen Qiangdu Recipe (BQR) on the entheses ossification histomorphology of articular ligament of DBA/1 mice with spontaneous ankylosing spondylitis (AS) , and to study its mechanism for prevention and treatment of AS. Methods Thirty 12-week old male DBA/1 mice were randomly divided into the model group, the positive drug group, low, medium, high dose BQR groups, 6 in each group. Another 6 C57BLE mice of the same age were recruited as a blank control group. BQR containing 11. 25, 22. 50, 45.00 g/kg crude drugs was respectively adminis- tered to mice in low, medium, high dose BQR groups by gastrogavage, 0. 2 mL for each mouse, once per day. Celecoxib Capsule (0. 2 mL/0. 8 mg for each mouse, once per day) was administered to mice in the positive drug group by gastrogavage. Equal volume of normal saline was administered to mice in the model group and the blank control group by gastrogavage. All mice were fed and intragastically adminis- tered for 12 successive weeks. Body weight, diet, stools, and hair were routinely observed. Signs of ar- thritis were evaluated once per two weeks. Mice were sacrifice, and then general observation of achilles tendon was performed. The achilles tendon tissue was HE stained. Protein expressions of alkaline phos- phatase (ALP) , bone gamma-carboxyglutamic-acid-containing proteins (BGP) , Dickkopfl (DKK1) , and Wnt5a in the achilles tendon were detected using immunohistochemical method. Results Compared with the blank control group, the scoring of arthritis obviously increased in the model group (P <0. 05). But the scoring of arthritis was obviously lower in the 3 BQR groups and the positive drug group than in the model group (P <0. 05). Histopathological results of achilles tendon tissue showed that no infiltration of inflammatory cells or fibroblasts occurred in the normal group. Their histomorphological structures were normal. Cartilage formation and bone formation at various degrees occurred in the model group. Filtration of fibroblast-like cells occurred in inflammatory cells and attachment points. Scattered lymphocyte infiltra- tion was often seen in the achilles tendon tissue of each medicated group. Cartilage formation and bone formation were rarely seen. Compared with the blank control group, the scoring of arthritis increased in the model group (P <0. 05). Compared with the model group, the scoring of arthritis was decreased in the 3 BQR groups and the positive drug group (P <0. 05). Compared with the blank control group, protein expression of DKK1 decreased and protein expression of Wnt5a increased in the model group (P <0. 05). Compared with the model group, protein expression of DKK1 increased and protein expression of Wnt5a decreased in middle and high dose BQR groups (P <0. 05). Conclusion BQR could delay the occur- rence and development of arthritis and ossification in DBA/1 mice of spontaneous AS model possibly by inhibiting classical Wnt pathway.
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Medicamentos Herbarios Chinos , Vía de Señalización Wnt , Animales , Medicamentos Herbarios Chinos/farmacología , Masculino , Ratones , Ratones Endogámicos DBA , Ratas Sprague-Dawley , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
OBJECTIVE: To evaluate the short-term efficacy and safety of Bushen Shuji Granule (BSG) in treating ankylosing spondylitis (AS) patients. METHODS: A prospective randomized controlled clinical trial was carried out in 62 active stage AS patients with Shen deficiency Du-channel cold syndrome (SDDCS), who were randomly assigned to the BSG group (treated with BSG) and the control group (treated with Celecoxib Capsule). Twelve weeks consisted of one therapeutic course. Therapeutic effects were evaluated by ASAS20 and ASAS40 (set by Assessments in Ankylosing Spondylitis working group) , BASDA150, Chinese medical (CM) syndrome efficacy evaluation standards. BASDAI, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath AS Metrology Index (BASMI), scores for spine pain, scores for pain at night, patient global assessment (PGA) , erythrocyte sedimentation rate (ESR) , and C reactive protein (CRP) were observed before and after treatment. RESULTS: After three-month treatment by BSG, ASAS20 standard rate was 63. 33% (19/30 cases) in the BSG group and 66.67% (20/30 cases) in the control group with no significant difference between the two groups (χ2 = 0.073, P > 0.05). The efficacy for CM syndromes was 70.00% (21/30 cases) in the BSG group, higher than that in the control group [40.00% (12/30 cases), χ2 = 5.455, P < 0.05]. Scores for CM syndromes, BASDAI, night pain index, spinal pain index, PGA, CRP were improved in the BSG group (P < 0.05, P < 0.01). The incidence of adverse events in the BSG group was lower than that of the control group. CONCLUSION: BSG based on Shen supplementing, Du-channel strengthening, blood activating, and channels dredging method had good short-term clinical efficacy and safety in treating AS.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Pueblo Asiatico , Investigación Biomédica , Sedimentación Sanguínea , Proteína C-Reactiva , Humanos , Dolor , Estudios Prospectivos , SeguridadRESUMEN
Tripterygium wilfordii Hook F. (TwHF) based therapy has been proved as effective in treating rheumatoid arthritis (RA), yet the predictors to its response remains unclear. A two-stage trial was designed to identify and verify the baseline symptomatic predictors of this therapy. 167 patients with active RA were enrolled with a 24-week TwHF based therapy treatment and the symptomatic predictors were identified in an open trial; then in a randomized clinical trial (RCT) for verification, 218 RA patients were enrolled and classified into predictor positive (P+) and predictor negative (P-) group, and were randomly assigned to accept the TwHF based therapy and Methotrexate and Sulfasalazine combination therapy (M) for 24 weeks, respectively. Five predictors were identified (diuresis, excessive sweating, night sweats for positive; and yellow tongue-coating, thermalgia in the joints for negative). In the RCT, The ACR 20 responses were 82.61% in TwHF/P+ group, significantly higher than that in TwHF/P- group (P = 0.0001) and in M&S/P+ group (P < 0.05), but not higher than in M&S/P- group. Similar results were yielded in ACR 50 yet not in ACR 70 response. No significant differences were detected in safety profiles among groups. The identified predictors enable the TwHF based therapy more efficiently in treating RA subpopulations.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Tripterygium/química , Adulto , Anciano , Antirreumáticos/farmacología , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Extractos Vegetales/farmacología , Pronóstico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
The conventional transcatheter closure of patent ductus arteriosus (PDA) requires femoral artery puncture and angiography for duct anatomic and shunting estimation. If such estimation can be replaced by transthoracic echocardiography (TTE), the procedure will be further simplified, with fewer invasions. This study aimed to examine whether TTE can serve as an alternative to aorta angiography and as a major guidance for transcatheter duct closure. The study enrolled 298 consecutive patients (71 males and 227 females) with PDA. In the study, TTE with combined two-dimensional echocardiography (2DE) imaging and color-coded flow imaging (CDFI) was performed to measure the minimal shunting width (MSW) as the estimated minimal duct size for selection of an Amplatzer duct occluder (ADO) and to monitor the transcatheter duct closure intraprocedurally. The MSW was validated against the duct-stretched diameter (SDD), against the minimal waist diameter of the conical part of a released occluder measured by X-ray spot picture after successful duct closure (SDC), and against the size of the finally used ADO (SADO). Good correlation was found between MSW and SDD [SDD (mm) = 1.31 MSW; r = 0.89; p < 0.01] and between MSW and SADO [SADO (mm) = 1.71 MSW; r = 0.88; p < 0.01]. Of 296 patients who received occlusion using MSW as the reference for selection of the occluder, SDC was attained in 288 (97.3%), 5 (1.7%), and 2 (0.7%) patients, respectively, at the first, second (1 ADO replacement), and third (2 ADO replacements) occluding attempt. Acute occluder dislodgement occurred in one patient (0.3%). At the 12-month follow-up assessment, no major complications were found, and the total immediate or 12-month SDC was 99.7%. Echocardiography as an alternative major guidance to angiography for transcatheter duct closure is technically feasible, and TTE guidance can further simplify the procedure, with fewer invasions and potential complications.
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Cateterismo Cardíaco , Conducto Arterioso Permeable/cirugía , Ecocardiografía , Adolescente , Adulto , Niño , Preescolar , Angiografía Coronaria , Conducto Arterioso Permeable/diagnóstico por imagen , Femenino , Fluoroscopía , Humanos , Lactante , Masculino , Persona de Mediana Edad , Dispositivo Oclusor Septal , Resultado del TratamientoRESUMEN
This study is designed to compare the efficacy and safety of traditional Chinese medicine (TCM) with western medicine (WM) in the management of rheumatoid arthritis (RA). This is a 24-week, randomized, multicenter, single-blind study comparing TCM with WM (as used in China) carried out between June 2002 and December 2004 in nine research centers in China, involving 489 patients. Patients were randomized to receive TCM (n = 247), MTX and SSZ (n = 242). MTX was started at a dose of 5 mg to a final dose of 7.5-15 mg weekly. The maintenance dose was 2.5-7.5 mg weekly. The starting dose of SSZ was 0.25 g bid, increasing by 0.25 g a day once a week to a final dose of 0.5-1 g qid. The maintenance dose was 0.5 g tid to qid. Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria (ACR20) at weeks 24. At 24 weeks, ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group, (P < 0.001) at 24 weeks. ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group, (P = 0.01). ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group, (P = 0.14). Side effects were observed more frequently in WM group. In this study, ACR20, ACR50 responses at 24 weeks were significantly better in the WM treated group, by intention to treat (ITT) and per protocol analysis. The ACR 70 response showed no significant difference between the two groups. TCM, while effective in treating RA, appears to be less effective than WM in controlling symptoms, but TCM is associated with fewer side effects.