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Radiation-related nasopharyngeal necrosis (RRNN) is a rare and often fatal complication in patients with nasopharyngeal carcinoma (NPC). Currently, no standard treatments are recommended for RRNN. The effects of traditional conservative treatments are suboptimal, and surgery for RRNN cannot be performed by inexperienced doctors. In the present study, the use of Endostar in two patients with RRNN was evaluated. Two patients with RRNN were treated at the Department of Oncology, Panyu Central Hospital (Guangzhou, China). Endostar was administrated (15 mg/day from day 1 to day 7, every three weeks) intravenously for four and seven cycles in a male and a female patient, respectively. The effects of Endostar were assessed using magnetic resonance imaging (MRI) and a nasopharyngoscope. The symptoms of RRNN in both patients were relieved after treatment with Endostar. MRI and nasopharyngoscope analysis revealed that necrosis of the nasopharynx was substantially decreased and nasopharyngeal ulcers were healed. Endostar has the potential to be a novel, effective therapy for the treatment of patients with RRNN. However, clinical trials are required to confirm the results of the present study.
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Bacterial cellulose (BC) is a bio-produced nanostructure material widely used in biomedical, food, and paper-manufacturing industries. However, low production efficiency and high-cost have limited its industrial applications. This study aimed to examine the level of improvement in BC production by co-culturing Bacillus cereus and Komagataeibacter xylinus. The BC yield in corn stover enzymatic hydrolysate was found to be obviously enhanced from 1.2 to 4.4 g/L after the aforementioned co-culturing. The evidence indicated that acetoin (AC) and 2,3-butanediol (2,3-BD) produced by B. cereus were the key factors dominating BC increment. The mechanism underlying BC increment was that AC and 2,3-BD increased the specific activity of AC dehydrogenase and the contents of adenosine triphosphate (ATP) and acetyl coenzyme A (acetyl-CoA), thus promoting the growth and energy level of K. xylinus. Meanwhile, the immobilization of BC could also facilitate oxygen acquisition in B. cereus under static conditions. This study was novel in reporting that the co-culture could effectively enhance BC production from the lignocellulosic enzymatic hydrolysate.
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Gluconacetobacter xylinus , Nanoestruturas , Bacillus cereus , Celulose/química , Técnicas de CoculturaRESUMO
BACKGROUND: In order to design compounds with fresh molecular skeleton to break through the limitation of available agrochemicals, a series of 36 novel selenenyl sulfide compounds were chemically synthesized, and their biological activities were fully evaluated against tobacco mosaic virus (TMV), 14 plant pathogenic fungi, three insect species and plant acetohydroxyacid synthase (AHAS). RESULTS: All the target compounds were characterized by proton nuclear magnetic resonance (1 H-NMR), carbon-13 (13 C)-NMR, selenium-77 (77 Se)-NMR, and high-resolution mass spectrometry (HRMS). The crystal structure of 10j indicated that the Se-S bond was successfully constructed. Compounds 10d, 10h, 10s, 10u, 10aa, 10ac, 10ae, 10ag, and 10ai exhibited 40%, 43%, 39%, 41%, 47%, 46%, 47%, 42%, and 39% anti-TMV activities at 500 mg L-1 , better than that of ribavirin. The median effective concentration (EC50 ) against Sclerotinia sclerotiorum of 10ac was 6.69 mg L-1 and EC50 values against Physalospora piricola and Pyricularia grisea of 10z were 12.25 mg L-1 and 15.27 mg L-1 , respectively, superior to the corresponding values of chlorothalonil. Compounds 10c and 10v demonstrated 100% larvicidal activity against Culex pipiens pallens at 5 mg L-1 , while 10a displayed 100% insecticidal activity against Mythimna separata at 200 mg L-1 . Compounds 10c, 10j, and 10o showed > 60% inhibitions against plant AHAS at 10 µmol L-1 . From the quantum calculation, highest occupied molecular orbital (HOMO) was considered as a factor that affects the anti-TMV activity. CONCLUSION: The preliminary results suggested that more efforts should be devoted to exploring the selenenyl sulfides for the discovery of new leads of antiviral agent, fungicide, insecticide or AHAS inhibitors as potential agrochemicals for crop protection. © 2023 Society of Chemical Industry.
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Fungicidas Industriais , Inseticidas , Mariposas , Vírus do Mosaico do Tabaco , Animais , Relação Estrutura-Atividade , Fungicidas Industriais/química , Antivirais , Inseticidas/química , Sulfetos/farmacologia , Estrutura Molecular , Desenho de FármacosRESUMO
Objectives: To investigate the clinical effects of TP-based hyperthermic intraperitoneal chemotherapy (HIPEC) on the levels of antigen cluster protein 133 (CD133) and human epididymal secretory protein 4 (HE4) in patients with advanced epithelial ovarian cancer (EOC). Methods: A total of 104 patients with advanced EOC hospitalized in Affiliated Hospital of Hebei Engineering University from April 2015 to December 2018 were assigned to two groups using a random number table. A control group (n =52) treated by the conventional postoperative TP regimen and an observation group (n =52) receiving HIPEC in addition to the conventional postoperative TP regimen. CD133 and HE4 expression in serum, overall response rate (ORR), long-term efficacy, and incidence of drug toxicity were measured for comparative analysis. Results: The serum levels of CD133 and HE4 expression in the observation group were lower than in the control group (P < 0.005, respectively); the observation group surpassed the control group in ORR, 2-year survival, and progression-free survival (PFS) (P < 0.005, respectively); however, the two groups had no statistically significant difference in the incidence of drug toxicity (P > 0.05). Conclusions: TP-based HIPEC can effectively inhibit CD133 and HE4 expression in advanced EOC, which thereby improves the clinical efficacy and encourages longer survival.
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Objective: To analyze the effects of carboplatin combined with paclitaxel-based intraperitoneal hyperthermic perfusion chemotherapy (IPCH) on serum levels of human epididymis protein 4 (HE4) and mitogen-dependent oncogene-1 (DJ-1) in patients with advanced recurrent ovarian cancer (OC). Methods: From July 2019 to July 2020, patients with advanced recurrent OC (n=92) treated in Affiliated Hospital of Hebei Engineering University were selected as study subjects. According to the random number table method, patients were divided into control group and observation group. Patients in the control group were treated with carboplatin combined with paclitaxel-based intravenous chemotherapy, and patients in the observation group were treated with carboplatin combined with paclitaxel-based IPCH. The therapeutic effects, serum levels of HE4, DJ-1 and human kallikrein 10 (HK-10), peripheral blood immune indexes and adverse reactions of patients were compared between the two groups. Results: The response rate of the observation group was significantly higher than that of the control group (p<0.05); after treatment, the indexes of HE4, DJ-1 and HK-10 in the two groups were significantly decreased, while the indexes of CD3+CD4+, CD3+CD56+ and CD3+CD4+/CD3+CD8+ were significantly increased; moreover, significantly lower indexes of HE4, DJ-1 and HK-10 and significantly higher indexes of CD3+CD4+, CD3+CD56+ and CD3+CD4+/CD3+CD8+ were found in the observation group when compared with the control group (p<0.05). The severity of myelosuppression, nausea and vomiting in the observation group was significantly lower than that in the control group, and the total tumor metastasis rate in the observation group was significantly lower than that in the control group (p<0.05). Conclusions: Carboplatin combined with paclitaxel IPCH had obvious inhibitory effects on HE4, DJ-1 and other serum tumor markers in patients with advanced recurrent OC, with a more prominent clinical effect, and could further significantly reduce the risk of adverse reactions and metastasis.
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Type 1 insulin-like growth factor receptor (IGF-1R) is a promising therapeutic target for cancer treatment. A single-chain variable fragment (scFv) against human IGF-1R forms inclusion body when expressed in periplasmic space of E. coli routinely. Here, we described that co-expression of appropriate disulfide bonds (Dsb) proteins known to catalyze the formation and isomerization of Dsb can markedly recover the soluble expression of target scFv in E. coli. A 50 % recovery in solubility of the scFv was observed upon co-expression of DsbC alone, and a maximum solubility (80 %) was obtained when DsbA and DsbC were co-expressed in combination. Furthermore, the soluble scFv present full antigen-binding activity with IGF-1R, suggesting its correct folding. This study also suggested that the selection of Dsb proteins should be tested case-by-case if the approach of co-expression of Dsb system is adopted to address the problem of insoluble expression of proteins carrying Dsb.
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Biotecnologia/métodos , Proteínas de Escherichia coli/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo , Anticorpos de Cadeia Única/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Ligação Proteica , Dobramento de Proteína , Receptores de Somatomedina/imunologia , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/genética , SolubilidadeRESUMO
A new molecular mechanism is proposed to explain the opposite effects of fever on cancers and Alzheimer's disease (AD). The proposal is based on the experimental discovery that the fever stress interferes the structure and the activity of Pin1, which plays uniquely opposite roles in the pathogenesis of cancers and AD. Pin1 is the only known cis-trans isomerase that specifically isomerizes the pSer/pThr-Pro motifs in proteins, facilitating kinds of signaling pathways. The up-regulation of Pin1 can amplify multiple oncogenic signaling pathways, resulting in cancers, while the down-regulation of Pin1 can cause many pathological characteristics of AD. Recently, we found that Pin1 is sensitive to heat treatment, and heating can gradually damage both of the structure and the function of Pin1. So, we hypothesize that the fever stress, which is usually induced by febrile diseases or hyperthermia treatment, may lead to the damaged structure of Pin1 and the decreased activity of it in vivo, resulting in the decreased risk of cancers and the increased risk of AD. Numerous epidemiological and experimental researches on cancers and AD support the hypothesis. The hypothesis not only provides new insights into the opposite effects of fever on cancers and AD, but also gives new clues for understanding the interacting effects of the environmental and the genetic factors in the complicated pathogenesis of cancers and AD.
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Doença de Alzheimer/fisiopatologia , Febre/fisiopatologia , Modelos Teóricos , Neoplasias/fisiopatologia , Peptidilprolil Isomerase/química , Peptidilprolil Isomerase/fisiologia , Doença de Alzheimer/complicações , Regulação para Baixo , Medicina Baseada em Evidências , Febre/complicações , Humanos , Peptidilprolil Isomerase de Interação com NIMA , Neoplasias/complicações , Transdução de Sinais , Regulação para CimaRESUMO
OBJECTIVES: This study aimed to compare the NERS (New Risk Stratification) and SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) scores for prognostication after stenting of unprotected left main stenosis in a "real-world" setting. BACKGROUND: In contrast to existing systems, the NERS score encompasses clinical, procedural, and angiographic characteristics. METHODS: The NERS score was derived from 260 patients with unprotected left main stenosis who underwent percutaneous coronary intervention and tested in 337 patients in a consecutive left main registry (66.55 +/- 10.49 years, 78.9% men) undergoing percutaneous coronary intervention in a prospective, multicenter trial. Six-month clinical and angiographic follow-up was obtained in 100% and 88.9% of patients, respectively. The primary end point was major adverse cardiac events (MACE), encompassing myocardial infarction, all-cause death, and target vessel revascularization. Receiver-operator characteristic (ROC) curve was generated for the comparison of NERS versus SYNTAX scores. RESULTS: The NERS score consisted of 54 variables (17 clinical, 4 procedural, and 33 angiographic). A NERS score > or =25 demonstrated a sensitivity and specificity of 92.0% and 74.1% (MACE as state variable), respectively, significantly higher than SYNTAX intermediate risk (20.5% and 25.4%) or SYNTAX higher risk (70.5% and 35.2%, p for all <0.001). At follow-up, myocardial infarction, cardiac death, and target vessel revascularization occurred in 3.0%, 5.6%, and 13.1% of patients, respectively, for a composite MACE of 26.0%. A NERS score > or =25 (hazard ratio: 1.13; 95% confidence interval [CI]: 1.11 to 1.16; p < 0.001) was the only independent predictor of cumulative MACE and stent thrombosis at follow-up (odds ratio: 31.04; 95% CI: 19.36 to 67.07; p < 0.001). CONCLUSIONS: The NERS score was more predictive of MACE than the SYNTAX score was. Further study is needed to address their relative roles in assessment for appropriateness of coronary artery bypass graft versus percutaneous coronary intervention for unprotected left main coronary artery stenosis.
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Angioplastia Coronária com Balão/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Ponte de Artéria Coronária , Estenose Coronária/terapia , Stents Farmacológicos , Indicadores Básicos de Saúde , Paclitaxel/administração & dosagem , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/mortalidade , Distribuição de Qui-Quadrado , China , Angiografia Coronária , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/mortalidade , Estenose Coronária/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Razão de Chances , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Desenho de Prótese , Curva ROC , Sistema de Registros , Medição de Risco , Fatores de Risco , Trombose/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The safety of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions in remote hospitals without surgical facilities remains unknown. This study aimed to evaluate three-year outcomes after CTO for PCI in ten centers around China where no on-site coronary artery bypass grafting (CABG) support was available. METHODS: A total of 152 patients from 10 Chinese hospitals without on-site surgical facilities were prospectively studied. Intra-procedural and in-hospital events were assessed. Angiographic follow-up was indexed eight months after the initial procedure. Clinical follow-up was extended to three years. The primary outcome was the rate of major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction and target-vessel revascularization (TVR). RESULTS: The incidence of CTO was 7.9% in patients who underwent PCI. Successful recanalization was achieved in 132 patients (86.8%). Compared with patients in the PCI success group, patients with PCI procedural failure had longer lesion lengths ((42.32 +/- 22.08) mm vs (27.61 +/- 22.85) mm, P = 0.023), a higher rate of perforation (25.0% vs 0, P = 0.014), and a greater need for pericardial puncture. There were significant differences in MACE in-hospital and at one year and three years between the failure (10.0%, 30.0% and 35.0%) and the success (3.0%, 12.1% and 14.4%) groups (P = 0.037, 0.034 and 0.040, respectively). These led to a significant decrease in the MACE-free survival rate at one and three years in the failure group, compared with the success group (P = 0.031 and 0.023, respectively). Stump was the only predictor of recanalization success (HR 0.158, 95% CI 0.041-0.612, P = 0.008), whereas procedural failure (OR 13.023, 95% CI 6.67-13.69, P = 0.002), incomplete revascularization (OR 9.71, 95% CI 2.93-5.59, P = 0.005), and total stent length (OR 6.02, 95% CI 1.55-11.93, P = 0.027) were three independent predictors of MACE. CONCLUSIONS: PCI for CTO was unsafe in remote hospitals without CABG facilities. Paying attention to coronary perforation is important for successful procedures.