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PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).
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Antineoplásicos , Arsênio , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Antineoplásicos/efeitos adversos , Arsênio/uso terapêutico , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pandemias , Resultado do TratamentoRESUMO
BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder with an incidence of approximately 1 in 5000 in the general population. It is characterized by vasodilation, which affects specific organs, such as the skin, mucous membranes, brain, lungs, gastrointestinal tract, liver, and others. However, HHT rarely involves the portal venous system to cause serious clinical complications. CASE SUMMARY: A 68-year-old woman was admitted to the emergency department due to four consecutive days of abdominal pain and bloody stool and was subsequently diagnosed with HHT. Computed tomography angiography confirmed the presence of an arteriovenous fistula (AVFs). Considering this specific manifestation, whole exome sequencing was performed. After a comprehensive evaluation, a selective superior mesenteric artery embolization was prioritized to avoid intestinal ischemia. The postoperative symptoms of the patient were quickly relieved. Unfortunately, two months post-procedure the patient died from intestinal necrosis and abdominal infection related to remaining AVFs. CONCLUSION: For patients with diffuse superior mesenteric AVFs, selective mesenteric arterial embolization may lead to positive short-term outcomes.
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Arginase has shown promising potential in treating cancers by arginine deprivation therapy; however, low enzymatic activity and stability of arginase are impeding its development. This study was aimed to improve the enzymological properties of a marine bacterial arginase by carboxymethyl chitosan (CMCS) conjugation. An arginase producing marine bacterium Priestia megaterium strain P6 was isolated and identified. The novel arginase PMA from the strain was heterologously expressed, purified, and then conjugated to CMCS by ionic gelation with calcium chloride as the crosslinking agent. Enzymological properties of both PMA and CMCS-PMA conjugate were determined. The optimum temperature for PMA and CMCS-PMA at pH 7 were 60 °C and 55 °C, respectively. The optimum pH for PMA and CMCS-PMA at 37 °C were pH 10 and 9, respectively. CMCS-PMA showed higher thermostability than PMA over 55-70 °C and higher pH stability over pH 4-11 with the highest pH stability at pH 7. At 37 °C and pH of 7, i.e., around the human blood temperature and pH, CMCS-PMA was higher than the free PMA in enzymatic activity and stability by 24% and 21%, respectively. CMCS conjugation not only changed the optimum temperature, optimum pH, and enzymatic activity of PMA, but also improved its pH stability and temperature stability, and thus made it more favorable for medical application.
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Arginase , Quitosana , Humanos , Quitosana/química , Fenômenos Químicos , Temperatura , Concentração de Íons de HidrogênioRESUMO
Background: COPD is a chronic respiratory disease with a long course and recurrent characteristics. According to relevant statistics, the global incidence of COPD is more than 30%, which seriously affects the life of patients and endangers their health. Objective: To observe the curative effect of Xiyanping in elderly patients with COPD and its influence on the expressions of growth differentiation GDF-15 and HIF-1α in serum. Methods: From August 2019 to December 2021, 86 elderly patients with acute exacerbation of COPD were admitted to our hospital. As the research objects, they were divided into the control group (n = 43) and the observation group (n = 43) randomly. The control group received the conventional treatment, while the observation group got Xiyanping on the basis of the control group. The differences in the duration of antibiotic use, expectoration, hospital stays, adverse reactions and serum-related factors, blood routine, pulmonary function, airway hyperreactivity index, COPD assessment test (CAT) score, and Borg score were made a comparison between them. Results: On the 3rd and 7th days after being treated, the sputum excretion in them was higher than before, but on the 3rd day of treatment, the sputum excretion in the observation group was higher than that in the control group, while on the 7th day of treatment, the sputum excretion was lower than that in the control group with statistically significant differences (P < 0.05). Before treatment, the serum-related factors and blood routine indexes between them were similar (P > 0.05). After treatment, GDF-15, HIF-1α, CXCL12, TNF-α, IL-8, TGF-ß, WBC, and NEU in them were significantly lower than before, and the values in the observation group were significantly lower than those in the control group with statistically significant differences (P < 0.05). There was no difference in the related indexes of pulmonary function and airway hyperreactivity between them before treatment. After being treated, FEV1, FVC, and FEV1/FVC in them were significantly higher than those before treatment. The airway resistance and lung compliance of the two groups at exhalation and inspiration were significantly lower than before, and the values in the observation group were significantly lower than those in the control group (P < 0.05). There was no difference in CAT and Borg scores between them before treatment. After treatment, the CAT score and Borg score of these patients were significantly lower than those before treatment, and the value of the observation group was significantly lower than that of the control group (P < 0.05). The duration of antibiotic use and length of stay in the observation group were significantly shorter than those of the control group, while the incidence of adverse reactions was not statistically significantly different compared with the control group (P > 0.05). Conclusion: Xiyanping can improve pulmonary function of elderly patients with acute exacerbation of COPD, reduce the response of airway hyperreactivity, and promote the excretion of sputum.
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Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Antibacterianos , Fator 15 de Diferenciação de Crescimento , Interleucina-8 , Fator de Crescimento Transformador beta , Fator de Necrose Tumoral alfa , IdosoRESUMO
Cardiovascular diseases have become one of the leading causes of mortality worldwide. Stents and artificial grafts have been used to treat cardiovascular diseases. Thrombosis and restenosis seriously impact the clinical outcome of stents and artificial vascular grafts. For the purpose of antithrombosis and anti-restenosis, numerous strategies have been developed to construct highly hemocompatible surfaces, enhance endothelialization, and inhibit intimal hyperplasia. Rapid endothelialization and inhibited intimal hyperplasia play an important role in artery repair after stent implantation and coronary artery bypass graft surgery. This review focuses on the recently developed strategies for improving the hemocompatibility and endothelialization of cardiovascular devices. We also introduce drug, gene and RNA delivery technologies for inhibiting intimal hyperplasia. The challenges and future perspectives about promoting endothelialization are also briefly discussed with the hope to help inspire further innovations.
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Doenças Cardiovasculares , Sistema Cardiovascular , Prótese Vascular , Humanos , Hiperplasia , StentsRESUMO
OBJECTIVE: To investigate whether genomic instability (GI)-derived long non-coding RNAs (lncRNAs) have a prognostic impact on the patients with endometrial cancer. MATERIAL AND METHODS: Patients with Uterine Corpus Endometrial Carcinoma (UCEC) were selected from The Cancer Genome Atlas (TCGA) database. Systematic bioinformatics analyses were performed, including Pearson correlations, GO and KEGG enrichment analysis, bivariate and multiple logistic regression analysis, and Kaplan-Meier (KM) method. RESULTS: A total of 552 UCEC samples were included in the study. The differentially expressed lncRNAs (DELs) were identified, including 79 down-regulated lncRNAs and 31 up-regulated lncRNAs. Bivariate logistic regression analysis showed that 19 GI-derived lncRNAs were prognostic factors. By further multivariate logistic regression analysis, AC005256.1 (estimated coefficient = -0.474), AC026336.3 (estimated coefficient = -0.030), AL161618.1 (estimated coefficient = -1.661), and BX322234.1 (estimated coefficient = 1.511) were used to construct a prognostic risk model. In the train set and test set, the risk model was shown to have both a high prognostic and a diagnostic value. CONCLUSION: We developed a novel GI-derived 4-lncRNA signature for the diagnosis and prognosis of patients with endometrial cancer. These findings offered a novel perspective in the clinical management of endometrial cancer.
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Carcinoma Endometrioide/genética , Neoplasias do Endométrio/genética , Instabilidade Genômica , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Bases de Dados Genéticas , Intervalo Livre de Doença , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Genoma , Humanos , Estimativa de Kaplan-Meier , Prognóstico , Fatores de RiscoRESUMO
The development of upper tract urothelial carcinoma (UTUC) has been associated with the ingestion of aristolochic acid (AA) in Chinese herbs. The tumors are more malignant and patients have a worse prognosis in China compared with that in Western countries. Recently, whole-genome and exome sequencing of AA-associated UTUCs found that the most frequently mutated gene was lysine demethylase 6A (KDM6A). However, its biological role and clinical significance have not yet been defined in patients with UTUC in China. A total of 108 surgically resected UTUC samples were obtained. Using immunohistochemistry, the protein expression level of KDM6A in the tumors was investigated together with the clinical and pathological characteristics of the patients, including survival times. In the present study, the expression level of KDM6A was significantly lower in UTUC specimens compared with that in samples from the normal urothelium. Lower KDM6A expression was also found to be significantly associated with a higher tumor grade and shorter cancer-specific and disease-free survival times (P=0.023 and P=0.033, respectively). In addition, using immunohistochemical analysis, no positive association was found between KDM6A expression and the expression of H3K27me3 or histone-lysine N-methyltransferase EZH2, a histone methyltransferase that generates H3K27me3. The results of the present study indicated that decreased KDM6A expression level was significantly associated with tumor grade and decreased survival time in UTUC, suggesting that KDM6A expression could be used as a prognostic marker in patients with UTUC in China.
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The anti-inflammatory active ingredients of Zhi-Shi-Zhi-Zi-Chi-Tang (ZSZZCT), a traditional Chinese medicine formula, were predicted and identified using an approach based on activity index, LC-MS, semi-preparative LC and NMR. Firstly, the whole extract of ZSZZCT was analyzed using liquid chromatography-quadrupole time of flight-mass spectrometry (LC-Q-TOF-MS) and liquid chromatography - ion trap mass spectrometry (LC-IT-MS), 79 constituents were detected and 39 constituents were identified unambiguously or tentatively. Subsequently, the whole extract of the formula was separated into multiple components and the activity index method was used to calculate index values of the 79 constituents by integrating the chemical and pharmacological information of multiple components. Four polymethoxyl flavones were predicted as the major active constituents according to the activity index values. Furthermore, three polymethoxyl flavones were prepared using the strategy with semi-preparative LC guided by LC-MS, and their anti-inflammatory activities were validated. The results show that three polymethoxyl flavones with higher positive index values, i.e., 3, 5, 6, 7, 8, 3', 4'-heptamethoxyflavone, 3-hydroxynobiletein and tangeretin had significant anti-inflammatory effects. In conclusion, the predicted results indicated that the activity index method is feasible for the accurate prediction of active constituents in TCM formulae.
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Anti-Inflamatórios/química , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Flavonas/química , Flavonas/isolamento & purificação , Flavonas/farmacologia , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Células RAW 264.7RESUMO
Stress impacts the reproductive axis at the level of the hypothalamus and the pituitary gland, which exert an effect on the ovary. Menstruation is regulated by the hypothalamic-pituitary-ovary (HPO) axis. However, the role of stress in menstruation remains unclear. The objective of this study was to explore the role of stress in endometrial breakdown and shedding, using the pseudopregnant mouse menstrual-like model. Female mice were mated with vasectomized males and labeled day 0.5, upon observation of a vaginal seminal plug. On day 3.5, decidualization was induced in pseudopregnant mice using arachis oil. On day 5.5, pseudopregnant mice with artificial decidualization were placed in restraint tubes for 3 h. The findings indicated that acute restraint stress resulted in the disintegration of the endometrium. While corticosterone concentration in the serum increased significantly due to restraint stress, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and progesterone (P4) levels in the serum decreased significantly. An endometrial histology examination indicated that progesterone implants may rescue P4 decline caused by acute stress and block endometrium breakdown and shedding. In addition, mice were treated with metyrapone, an inhibitor of corticosterone synthesis, 1 h prior to being subjected to restraint stress. Interestingly, metyrapone not only inhibited stress-induced endometrium breakdown and shedding, but also prevented stress-induced reduction of P4, LH and FSH. Furthermore, real-time PCR and western blot showed that mRNA and protein expression of CYP11A1 (cytochrome P450, family 11, subfamily A, polypeptide 1) and steroidogenic acute regulatory protein (StAR), the two rate-limiting enzymes for progesterone synthesis in the ovary, decreased following acute stress. But metyrapone prevented the reduction of StAR expression induced by restraint stress. Overall, this study revealed that acute stress results in an increase in corticosterone, which may inhibit LH and FSH release in the serum and CYP11A1 and StAR expression in the ovary, which finally leads to the breakdown and shedding of the endometrium. These experimental findings, based on the mouse model, may enable further understanding of the effects of stress on menstruation regulation and determine the potential factors affecting stress-associated menstrual disorders.
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Corticosterona/sangue , Endométrio/patologia , Progesterona/sangue , Estresse Fisiológico/fisiologia , Estresse Psicológico/patologia , Animais , Endométrio/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Metirapona/farmacologia , Camundongos , Progesterona/farmacologia , Restrição FísicaRESUMO
AIM: To analyze the epidemiological features of colorectal diverticulum (CRD) in China. METHODS: We retrospectively analyzed CRD patients in 8 tertiary hospitals located in 5 regions of China from 2000 to 2016. The detection rates, number and distribution, demographic information, concomitant disorders, and their associations were investigated. RESULTS: Of 3,446,118 cases, 7,964 (2.3%) were CRD with a mean age of 56 years (11-92 years). The detection rate increased yearly and with increasing age. Males had a higher detection rate than females (3.0 vs. 1.47%, p < 0.01) and 1.8-times higher increase rate. The detection rate increased with age; however, females of > 60 years had a 2.8-times increasing rate than males. CRD occurred most frequently in the right-side colon, followed by rectum. Multiple diverticula were common in males and increased with age, with a 3-times higher increase rate than single lesion. Single-segment CRD occurred more frequently in males than in females (80.1 vs. 76.4%, p < 0.01). Concurred colon polyps were seen in 51.05% cases. CONCLUSION: CRD detection rates increased annually and with age, particularly in senior females in China. Multiple diverticula were common in males and increased with age. CRD was predominant in the right-side colon. Polyps are the most common comorbidity associated with CRD.
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Divertículo do Colo/epidemiologia , Reto/patologia , Caracteres Sexuais , Adulto , Fatores Etários , Idoso , China/epidemiologia , Comorbidade , Divertículo do Colo/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
One of the most common head and neck cancers is laryngeal squamous cell carcinoma (LSCC). LSCC exhibits high mortality rates and has a poor prognosis. The molecular mechanisms leading to the development and progression of LSCC are not entirely clear despite genetic and therapeutic advances and increased survival rates. In this study, a total of 116 differentially expressed genes (DEGs), including 11 upregulated genes and 105 downregulated genes, were screened from LSCC samples and compared with adjacent noncancerous. Statistically significant differences (log 2-fold difference > 0.5 and adjusted P-valueâ<â.05) were found in this study in the expression between tumor and nontumor larynx tissue samples. Nine cancer hub genes were found to have a high predictive power to distinguish between tumor and nontumor larynx tissue samples. Interestingly, they also appear to contribute to the progression of LSCC and malignancy via the Jak-STAT signaling pathway and focal adhesion. The model could separate patients into high-risk and low-risk groups successfully when only using the expression level of mRNA signatures. A total of 4 modules (blue, gray, turquoise, and yellow) were screened for the DEGs in the weighted co-expression network. The blue model includes cancer-specific pathways such as pancreatic cancer, bladder cancer, nonsmall cell lung cancer, colorectal cancer, glioma, Hippo signaling pathway, melanoma, chronic myeloid leukemia, prostate cancer, and proteoglycans in cancer. Endocrine resistance (CCND1, RAF1, RB1, and SMAD2) and Hippo signaling pathway (CCND1, LATS1, SMAD2, and TP53BP2) could be of importance in LSCC, because they had high connectivity degrees in the blue module. Results from this study provide a powerful biomarker discovery platform to increase understanding of the progression of LSCC and to reveal potential therapeutic targets in the treatment of LSCC. Improved monitoring of LSCC and resulting improvement of treatment of LSCC might result from this information.
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Carcinoma de Células Escamosas/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Laríngeas/genética , Transdução de Sinais/genética , Biomarcadores Tumorais/genética , Progressão da Doença , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Laringe/metabolismo , Metanálise em Rede , RNA Mensageiro/genética , Taxa de SobrevidaRESUMO
AIM: To investigate whether mesenchymal stem cells (MSCs) from adipose-derived stromal cells (ADSCs) and bone marrow stromal cells (BMSCs) have similar hepatic differentiation potential. METHODS: Mouse ADSCs and BMSCs were isolated and cultured. Their morphological and phenotypic characteristics, as well as their multiple differentiation capacity were compared. A new culture system was established to induce ADSCs and BMSCs into functional hepatocytes. Reverse transcription polymerase chain reaction, Western blot, and immunofluorescence analyses were performed to identify the induced hepatocyte-like cells. CM-Dil-labeled ADSCs and BMSCs were then transplanted into a mouse model of CCl4-induced acute liver failure. Fluorescence microscopy was used to track the transplanted MSCs. Liver function was tested by an automatic biochemistry analyzer, and liver tissue histology was observed by hematoxylin and eosin (HE) staining. RESULTS: ADSCs and BMSCs shared a similar morphology and multiple differentiation capacity, as well as a similar phenotype (with expression of CD29 and CD90 and no expression of CD11b or CD45). Morphologically, ADSCs and BMSCs became round and epithelioid following hepatic induction. These two cell types differentiated into hepatocyte-like cells with similar expression of albumin, cytokeratin 18, cytokeratin 19, alpha fetoprotein, and cytochrome P450. Fluorescence microscopy revealed that both ADSCs and BMSCs were observed in the mouse liver at different time points. Compared to the control group, both the function of the injured livers and HE staining showed significant improvement in the ADSC- and BMSC-transplanted mice. There was no significant difference between the two MSC groups. CONCLUSION: ADSCs share a similar hepatic differentiation capacity and therapeutic effect with BMSCs in an acute liver failure model. ADSCs may represent an ideal seed cell type for cell transplantation or a bio-artificial liver support system.
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Tecido Adiposo/citologia , Diferenciação Celular , Hepatócitos/transplante , Células-Tronco Mesenquimais , Cultura Primária de Células/métodos , Animais , Hepatócitos/citologia , Masculino , Camundongos Endogâmicos BALB CRESUMO
OBJECTIVE: Transplantation of adipose-derived stem cells (ADSCs) is associated with potential risks of late complications including tumorigenesis due to the active proliferation of the cells. We aimed to test the effect of transplantation of ADSCs with suppressed proliferation by gamma irradiation in the treatment of thin endometrium in rats. METHODS: ADSCs were isolated from female SD rats and identified by detecting the surface antigens with flow cytometry. After exposure to gamma irradiation at 0, 5 Gy and 10 Gy, the cells were examined for changes in colony-forming ability. Twenty-four female rats with chemically induced thin endometrium were randomized into 4 equal groups and at 6-8 h after modeling, the rats received intrauterine injection of non-irradiated ADSCs (group I), 5 Gy irradiated ADSCs (group II), 10 Gy irradiated ADSCs (group III), or PBS only (group IV). Endometrial pathology was analyzed with HE staining in these rats in the third estrus phase following the cell transplantation. RESULTS: The ADSCs showed a complete loss of proliferative capacity after exposure to 10 Gy irradiation. After the cell transplantation, the endometrium thickness was thicker in group I and II than in group IV (P<0.01), but there was no significant difference between groups III and IV. CONCLUSIONS: Gamma irradiation impairs the proliferative capacity of ADSCs in vitro. Exposure to 10 Gy irradiation causes a total loss of proliferation capacity of the ADSCs, which have no therapeutic potential; 5 Gy irradiation causes partial loss of proliferation capacity of the cells, which still retain the activity to promote endometrial cell regeneration.
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Tecido Adiposo/citologia , Endométrio/citologia , Raios gama , Transplante de Células-Tronco , Células-Tronco/efeitos da radiação , Animais , Proliferação de Células/efeitos da radiação , Células Cultivadas , Feminino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , RegeneraçãoRESUMO
OBJECTIVE: To investigate the effect of storage time on accumulation of platelet-related growth factors in the supernatant of leukoreduced packed red blood cells (LR-pRBC) and on tumor cell proliferation in vitro. METHODS: LR-pRBC were quartered and stored at 2 °C-6 °C. The supernatant of pRBC was obtained by centrifugation with 1 006 × g for 10 min at day 0, 14, 21 and 35 d. The enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of platelet-derived growth factor(PDGF) and vascular endothelial growth factor (VEGF). After HepG2 cells was cultured with the supernatant of LR pRBC at day 0 and day 35 together for 48 hours, methylthiazoliltetracolium (MTT) method was used to measure the proliferation of tumor cells in vitro. RESULTS: The concentrations of 2 cytokines were still increased with the storage time prolonging. As compared to LR-pRBC at day 0 [611.84 (95%CI, 356.45-867.23) pg/ml], the level of VEGF reached 900.16 (95% CI, 552.26-1248.07) pg/ml (P<0.05). There was a similar tendency in PDGF level with less increment in the supernatant of LR pRBC at day 35 [2.23 (95% CI, 0-5.37) ng/L vs 5.66 (95% CI, 0-12.48), P=0.073], but there was no significant statistical difference. Likewise, in vitro study of HepG2 cell proliferation showed that the LR-pRBC at day 35 promoted more proliferation of tumor cells with OD value 0.40 (95% CI, 0.38-0.42) (P<0.05). CONCLUSION: The residual platelets in LR-pRBC were activated, disintegrated and released the dense granules and α-granules which induce the accumulation of VEGF and PDGF. It seemed that the supernatant of LR-pRBC promoted the proliferation of tumor cells in vitro.
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Plaquetas , Preservação de Sangue , Proliferação de Células , Citocinas , Ensaio de Imunoadsorção Enzimática , Humanos , Técnicas In Vitro , Fator de Crescimento Derivado de Plaquetas , Fatores de Tempo , Fator A de Crescimento do Endotélio VascularRESUMO
Nine new terpenoids (1-3, 5-10), including three cyclolanostane triterpenoids (1-3) and six isopimarane diterpenoids (5-10), along with six known terpenoids (4, 11-15), were isolated from the leaves and twigs of Dysoxylum gotadhora. Compound 1 represents a class of rare natural 21,24-epoxy cyclolanostane-type triterpenoids, and compounds 2 and 3 are the first examples of 21,25-epoxy cyclolanostane-type triterpenoids. Compounds 1, 2, 4, 8, and 15 exhibited noteworthy inhibition of nitric oxide production induced by lipopolysaccharide in RAW 264.7 cells with IC50 values of 25.5, 41.5, 27.4, 14.5, and 45.2 µM, respectively.
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Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Meliaceae/química , Terpenos/isolamento & purificação , Terpenos/farmacologia , Animais , Anti-Inflamatórios/química , Diterpenos/farmacologia , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , Componentes Aéreos da Planta/química , Terpenos/química , Triterpenos/farmacologiaRESUMO
OBJECTIVE: This study was to investigate whether prestorage leukoreduction could decrease the accumulative concentration of tumor-associated cytokines in supernatant of stored packed red blood cells (pRBC) and to study the effect of prestorage leukoreduction on proliferation of HepG2 tumor cells by in vitro. The leukoreduced (LR) and non-leukoreduced (NLR) pRBC were equally obtained from one donation and were stored under 2 °C-6°C. The supernatants of pRBC in these two group were performed by centrifugation with 1 006×g for 10 min at day 0 and 35 d. The enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of normal T cells and secretory factor (RANTES/CCL5), as well as the accumulative concentrations of tumor-necrosis factor (TNF-α), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) in pRBC supernantant of above-mentioned two groups. After HepG2 cells was cultured with the supernatant of NLR-pRBC and LR-pRBC at the end of day 35 together for 48 hours, the methyl thiazolil tetracolium (MTT) method was used to measure the proliferation of tumor cells in vitro. RESULTS: The accumulative concentration of 5 cytokines in supernatants of above menthioned two groups increased in different degrees along with the prolongation of storage time,that is, the accumulative concentrations of 5 cytokines at 35 d were higher than that at day 0, in which the change of VEGF accumu-lative concentration showed statistical significance, its accumulative concentration in NLR group at day 35 elevated to 549.61 ± 299.43 pg/ml, and was higher than that in LR group (95.46 ± 110.87 pg/ml) (P < 0.05). The experiment of HepG2 cell proliferation indicated that the supernatant of LR pRBC group produced less proliferation of tumor cells with OD value 0.40 (95% CI, 0.38-0.42) than that of NLR pRBC group with OD value 0.49 (95% CI, 0.43-0.55) (P < 0.05). CONCLUSION: The prestorage leukoreduction has been confirmed to decrease the accumulative level of cytokines, particalarly decrease the accumulative level of VEGF, moreover, it may be a factor for inhibiting the proliferation of tumor cells in vitro.
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Preservação de Sangue , Proliferação de Células , Eritrócitos , Neoplasias , Citocinas , Ensaio de Imunoadsorção Enzimática , Humanos , Técnicas In Vitro , Leucócitos , Fator de Crescimento Derivado de Plaquetas , Fator A de Crescimento do Endotélio VascularRESUMO
OBJECTIVE: The study was to understand the incidence of traumatic coagulopathy and the clinical blood transfusion in hospitalized trauma patients so as to provide a reference for guiding scientific component transfusion in trauma or surgical patients. METHODS: By using a software "clinical transfusion database" developed by our department, 1 766 trauma cases who suffered traumatic injury and required hospital admission between 2001 and 2012 were retrieved, and out of them 1 211 patients were given transfusion, and the transfusion-related indicators of the patients such as coagulation, hemoglobin levels before transfusion, trauma situation, massive blood transfusion and total blood transfusion were retrospectively analyzed. According total volume of blood usage during hospitalization,1 211 cases with transfusion were divided into three groups: low volume transfusion group ( ≤ 5 U, n = 471), moderate volume transfusion group (5-10 U, n = 449) and high volume transfusion group (>10 U, n = 291), then the difference of indicators among the 3 groups was compared, and the risk factors of high volume transfusion were analyzed. RESULTS: There were 33 cases of coagulopathy and 52 cases of massive transfusion in trauma patients with transfusion. The transfusion rate of trauma patients was about 68.6%. There was no association between the total amount of blood transfusion and surgical grade or whether surgery. The most patients were transfused using two components (plasma and red blood cell), the ratio of plasma to RBC transfused in patients with coagulopathy was approximately 1.0. In high volume transfusion group, there were more younger and male patients with more serious injury, their infection and death were significantly higher than that in other two groups (P < 0.01). CONCLUSION: There were approximately 69% of hospitalized trauma patients require transfusion, the patients in high volume transfusion group have two populations such as middle-aged and young men who was vulnerable to severe trauma mainly caused by accident injury or fall injury and older women who was vulnerable to osteoporotic hip fractures mainly caused by fall injuries. The coagulation disorders in the patients with trauma coagulopathy should be corrected by transfusion with high ratios of plasma to RBC. Massive transfusion (OR = 95.22), hemorrhagic shock (OR = 17.2), trauma coagulopathy (OR = 4.52) are risk factors of high volume transfusion > 10 U, and massive transfusion also is a risk factor of trauma coagulopathy (OR = 16.257). The routine dynamic monitoring of coagulation should be performed for trauma or surgical patients to guide the clinical transfusion scientifically.
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Transfusão de Sangue , Choque Hemorrágico , Transtornos da Coagulação Sanguínea , Feminino , Hospitalização , Humanos , Masculino , Estudos RetrospectivosRESUMO
Calycosin, which is a kind of typical phytoestrogen, can bind with estrogen receptor and produce estrogen-like effects. Calycosin were reported to have antioxidant, anti-osteoporosis, anti-tumor and immunomodulating activities. This review covers biological activities and its mechanism of calycosin. It will provide a useful reference for clinical research and rational utilization of monomericompound.