Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 215
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-34554903

RESUMO

Stem cell therapy is widely regarded as a promising strategy in regenerative medicine, yet the therapeutic effects of stem cells in vivo are limited by many factors when applied without additional factors, such as poor cell engraftment, uncontrolled differentiation, and unclear cell fates and niches. The emergence of nanotechnology has provided several solutions for these problems. Nanomaterial-based cell labeling and tracking have been extensively investigated in recent decades, and many innovative and multifunctional nanomaterials have been used to reveal the fate of stem cells, allowing more efficient, sensitive, and accurate imaging/tracking strategies for stem cells to be achieved. Nanomaterials enhance stem cell therapy by incorporating or integrating with stem cells and, as scaffolds or substrates, nanomaterials with antioxidant properties that can be used as graft coatings show great promise for clinical transformation. However, current reviews on the subject tend to focus on the various effects of nanomaterials on stem cells and are less concerned with their application to stem cell therapy. Accordingly, we herein present a review of progress in the application of nanomaterials in stem cell therapy over the last three years, which we hope will be of benefit to a comprehensive understanding of nanomaterial-mediated stem cell therapy from lab to pre-clinical practice.

2.
Medicine (Baltimore) ; 100(32): e26884, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397908

RESUMO

ABSTRACT: High tibial osteotomy (HTO) is a promising surgery that can treat osteoarthritis of the medial septum of the knee. However, the extensive release of soft tissue and the osteotomy gap may produce intraoperative and postoperative bone bleeding. Tranexamic acid (TXA) is an effective blood management strategy, as it competitively inhibits the activation process of plasminogen and prevents fibrinolytic enzymes from degrading fibrin. Therefore, we compared the operative bone bleeding of patients who underwent HTO who received either intravenous (IV) or topical TXA in this research.The medical records of a total of 191 patients (including 72 who received IV TXA, 64 who received topical TXA and 55 control patients) who received open-wedge HTO were retrospectively reviewed from January 2016 to August 2019. There were no obvious demographic differences between the groups. Here, we used independent parameters to assess the efficacy of topical and IV TXA in reducing blood loss.Compared with the IV TXA group, patients receiving topical TXA therapy had greater blood loss (622 ±â€Š231 ml versus 451 ±â€Š231 ml, mean difference 171 mL [95% CI, 87-254]; p < 0.001). The hemoglobin concentration of the IV TXA group was obviously higher than that of the topical medication group. No patients had thromboembolic complications during the entire study period.In our study, it seemed that either IV or topical use of TXA might reduce blood loss after open-wedge HTO, and the blood loss and amount of drainage in the IV TXA group showed huge decreases compared to those in the topical group.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Osteotomia/métodos , Hemorragia Pós-Operatória/prevenção & controle , Tíbia/cirurgia , Ácido Tranexâmico/administração & dosagem , Administração Tópica , Adulto , Idoso , Antifibrinolíticos/administração & dosagem , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
3.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3402-3409, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396761

RESUMO

This study aimed to investigate the effect and the possible mechanism of Shenlian( SL) extract on tumor necrosis factor-α( TNF-α)-induced ECV304 injury. After the establishment of TNF-α-induced ECV304 cells injure model,MTT assay was used to detect cell viability and the level of reactive oxygen species( ROS) was measured by flow cytometry. The contents of superoxide dismutase( SOD),malondialdehyde( MDA),nitric oxide( NO),endothelin-1( ET-1) and interleukin-1ß( IL-1ß) in the supernatant were detected by biochemical method and enzyme linked immunosorbent assay( ELISA). The expression levels of apoptosis-related proteins B-lymphoma-2 gene( Bcl-2),Bcl-2 associated X protein( Bax),caspase-3,caspase-9 and nuclear factor E2 associated factor2( Nrf2)/Kelch like epichlorohydrin associated protein-1( Keap1) signaling pathway related proteins Nrf2,Keap1,quinone oxidoreductase( NQO1) and heme oxygenase 1( HO-1) were detected by Western blot. The results showed that 50 µg·L-1 TNF-α significantly damaged ECV304 cells,induced the impairment of cell viability( P<0. 01),the increase of ROS production,the decrease of SOD activity,and the increase of MDA,NO,ET-1 and IL-1ß( P<0. 01),meanwhile,it caused the up-regulation of Keap1,caspase-9 and Bax protein expression,and down-regulation of NQO1 and Bcl-2 protein expression( P<0. 05) compared with the control group.Compared with the model group,SL extract reduced the damage of ECV304 cells induced by TNF-α,improved cell viability,reduced ROS production,increased SOD activity and decreased MDA,NO,ET-1,IL-1ß content( P<0. 01 or P<0. 05). In addition,SL extract also down-regulated the protein expression levels of Keap1,caspase-3,caspase-9 and Bax,and increased the protein expressions of Nrf2,NQO1,HO-1 and Bcl-2( P<0. 01 or P<0. 05). The above results indicate that SL extract can provide protective effect on ECV304 cells injury induced by TNF-α,alleviate oxidative stress injury,inflammation and apoptosis,and its mechanism may be related to regulating Nrf2/Keap1 signaling pathway.


Assuntos
Fator 2 Relacionado a NF-E2 , Fator de Necrose Tumoral alfa , Apoptose , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Extratos Vegetais , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética
4.
J Int Med Res ; 49(8): 3000605211035889, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34463564

RESUMO

OBJECTIVE: To investigate the effect of drug treatment combined with interventional cavity therapy for cavitary pulmonary tuberculosis. METHODS: One-hundred thirty patients who underwent transbronchial tuberculosis cavity plugging (TTCP) combined with drug therapy from 2012 to 2018 were selected as the observation group, and 130 patients with cavitary tuberculosis who underwent treatment with drugs only were selected as the control group. Changes in cavity size and sputum tests were compared between the two groups. In addition, adverse reactions were monitored. RESULTS: The number of cases with cavity closure was significantly higher in the observation group than in the control group at different time points. The number and proportion of negative sputum samples in the observation group were significantly higher than those in the control group. The treatment success rate was 98.46% in the observation group and 92.3% in the control group. No recurrence was observed in the observation group, and 8.3% of cases in the control group showed recurrence. CONCLUSIONS: TTCP for the treatment of cavity tuberculosis showed good outcomes, with limited side effects and minimal complications.


Assuntos
Tuberculose Pulmonar , Tuberculose , Antituberculosos/uso terapêutico , Humanos , Recidiva , Escarro , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico
5.
Technol Cancer Res Treat ; 20: 15330338211034291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34308689

RESUMO

BACKGROUND: The objective of this study was to assess the prognostic value of pretreatment platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-white blood cell ratio (LWR) of CRC patients who received neoadjuvant chemotherapy. METHODS: We analyzed the peripheral blood routine parameters and other clinical data of 145 patients with colorectal cancer who had undergone neoadjuvant chemotherapy between January 2011 and February 2014. Pretreatment blood parameters of 145 patients were collected, and PLR, NLR, and LWR were calculated. The utility of PLR, NLR, and LWR in predicting treatment efficacy and patient survival was statistically evaluated using the chi-square test, log-rank test, Kaplan-Meier curves and logistic regression models, and Cox regression models. RESULTS: Receiver operating characteristic curve showed that the best cutoff values of PLR, NLR, and LWR were 154.31, 3.01, and 0.22, respectively. In univariate analysis, tumor location (P = 0.044), differentiation degree (P = 0.001), lymph node metastasis (P = 0.020), and high PLR (P = 0.042) were significantly correlated with a lower overall response rate (ORR). In addition, clinical stage, lymph node metastasis, and high PLR were correlated with short OS (P < 0.01) and DFS (P < 0.01). Moreover, WBC count was correlated with a short OS. Multivariate analysis showed that tumor location (P = 0.013), differentiation degree (P = 0.001), and lymph node metastasis (P = 0.033) were independent predictors of ORR. In addition, lymph node metastasis independently predicted a shorter OS (P = 0.011). Lymph node metastasis (P = 0.013) and high PLR (P = 0.022) were independent prognostic factors for short DFS. CONCLUSIONS: For CRC patients who received NAC, clinical pathological stage and lymph node metastasis were correlated with lower ORR and survival, while a high PLR that may be of prognostic relevance in CRC patients receiving NAC.

6.
Water Res ; 202: 117453, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34320444

RESUMO

The anaerobic ammonium oxidation (anammox) process is regarded as a promising approach to treat antibiotic-containing wastewater. Therefore, it is urgent to elucidate the effects of various antibiotics on the anammox process. Moreover, the mechanism of extracellular polymeric substance (EPS) as protective barriers to relieve antibiotic stress remain unclear. Therefore, the single and combined effects of erythromycin (ETC) and sulfamethoxazole (SMZ), and interactions between EPS and antibiotics were investigated in this study. Based on a 228-day continuous flow experiment, high concentrations of ETC and SMZ had significant inhibitory effects on the nitrogen removal performance of the anammox process, with the abundances of corresponding antibiotic resistance genes (ARGs) increasing. In addition, the combined inhibitory effect of the two antibiotics on the anammox process was more significant and longer-lasting than that of the single. However, the anammox process was able to quickly recover from deterioration. The tolerance of anammox granules to the stress of low-concentration antibiotics was probably attributed to the increase in ARGs and secretion of EPS. Molecular docking simulation results showed that proteins in EPS could directly bind with SMZ and ETC at the sites of GLU-307, HYS-191, ASP-318 and THR-32, respectively. These findings improved our understanding of various antibiotic effects on the anammox process and the interaction mechanism between antibiotics and proteins in EPS.


Assuntos
Antibacterianos , Matriz Extracelular de Substâncias Poliméricas , Antibacterianos/farmacologia , Reatores Biológicos , Resistência Microbiana a Medicamentos/genética , Simulação de Acoplamento Molecular , Nitrogênio , Oxirredução , Esgotos , Águas Residuárias
7.
J Nanobiotechnology ; 19(1): 220, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294083

RESUMO

Chirality is a fundamental characteristic of natural molecules and a crucial factor in the biochemical reactions of living cells and organisms. Recently, researchers have successfully introduced chiral molecules to the surfaces of nanomaterials, creating chiral nanomaterials that exhibit an upscaling of chiral behavior from the molecular scale to the nanoscale. These chiral nanomaterials can selectively induce autophagy, apoptosis, and photothermal ablation in tumor cells based on their chirality, making them promising for application in anti-tumor therapy. However, these interesting and important phenomena have hitherto received little attention. Accordingly, we herein present a review of recent research progress in the field of chiral nanomaterials for tumor therapy along with brief looks at the mechanistic details of their actions. Finally, the current challenges and future perspectives of chiral nanomaterials in terms of maximizing their potential in tumor therapy are discussed. Thus, this review provides a helpful introduction to the design of chiral nanomaterials and will hopefully highlight the importance of chirality in tumor therapy.

8.
J Radiat Res ; 62(5): 744-751, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34179986

RESUMO

In order to respond to nuclear or radiological emergencies effectively and protect the physical and mental health of the public, the national-, provincial-, municipal- and county-level public health response systems for nuclear or radiological emergencies had been established in China by the end of twentieth century. The health administrative departments at all levels have established professional emergency response teams, continue to improve their own level of emergency response systems and operating mechanisms, enhance the capabilities of radiation injury treatment, radiation monitoring and protection through training and exercises and also pay attention to the logistical support for emergency response. In this article the organizations, management system and capabilities of public health response to nuclear or radiological emergencies in China are briefly introduced. We try to strengthen information exchange and cooperation with foreign counterparts in this field in the future, so as to jointly promote the development of preparedness and response for nuclear or radiological emergencies.

9.
Bioresour Technol ; 333: 125186, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33892423

RESUMO

Two types of anaerobic ammonium oxidation (anammox) seed sludge were selected to evaluate their responses to copper nanoparticles (CuNPs) exposure. Antibiotic-exposed anammox granules (R1) were more likely to be inhibited by 5.0 mg L-1 CuNPs than the normal anammox granules (C1). The nitrogen removal efficiency (NRE) of C1 decreased by 9.00% after two weeks of exposure to CuNPs, whereas that of R1 decreased by 20.32%. Simultaneously, the abundance of Candidatus. Kuenenia decreased by 27.65% and 36.02% in C1 and R1 under CuNPs stress conditions, respectively. Generally, R1 was more susceptible to CuNPs than C1. The correlation analysis indicated that the horizontal transfer of antibiotic resistance genes and copA triggered by intI1 facilitated the generation of multiresistance in the anammox process. Moreover, the potential multiresistance mechanism of anammox bacteria was hypothesized based on previous results. The results will generate new ideas for the treatment of complex wastewater using the anammox process.


Assuntos
Compostos de Amônio , Nanopartículas , Anaerobiose , Antibacterianos/farmacologia , Reatores Biológicos , Cobre , Nitrogênio , Oxirredução , Esgotos
10.
Int J Mol Sci ; 22(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669867

RESUMO

RIDR-PI-103 is a novel reactive oxygen species (ROS)-induced drug release prodrug with a self-cyclizing moiety linked to a pan-PI3K inhibitor (PI-103). Under high ROS, PI-103 is released in a controlled manner to inhibit PI3K. The efficacy and bioavailability of RIDR-PI-103 in breast cancer remains unexplored. Cell viability of RIDR-PI-103 was assessed on breast cancer cells (MDA-MB-231, MDA-MB-361 and MDA-MB-453), non-tumorigenic MCF10A and fibroblasts. Matrigel colony formation, cell proliferation and migration assays examined the migratory properties of breast cancers upon treatment with RIDR-PI-103 and doxorubicin. Western blots determined the effect of doxorubicin ± RIDR-PI-103 on AKT activation and DNA damage response. Pharmacokinetic (PK) studies using C57BL/6J mice determined systemic exposure (plasma concentrations and overall area under the curve) and T1/2 of RIDR-PI-103. MDA-MB-453, MDA-MB-231 and MDA-MB-361 cells were sensitive to RIDR-PI-103 vs. MCF10A and normal fibroblast. Combination of doxorubicin and RIDR-PI-103 suppressed cancer cell growth and proliferation. Doxorubicin with RIDR-PI-103 inhibited p-AktS473, upregulated p-CHK1/2 and p-P53. PK studies showed that ~200 ng/mL (0.43 µM) RIDR-PI-103 is achievable in mice plasma with an initial dose of 20 mg/kg and a 10 h T1/2. (4) The prodrug RIDR-PI-103 could be a potential therapeutic for treatment of breast cancer patients.


Assuntos
Antraciclinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Dano ao DNA , Fosfatidilinositol 3-Quinases/metabolismo , Pró-Fármacos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Animais , Antraciclinas/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colágeno , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Combinação de Medicamentos , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Furanos/farmacocinética , Furanos/farmacologia , Furanos/uso terapêutico , Humanos , Laminina , Camundongos Endogâmicos C57BL , Pró-Fármacos/farmacologia , Proteoglicanas , Piridinas/farmacocinética , Piridinas/farmacologia , Piridinas/uso terapêutico , Pirimidinas/farmacocinética , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico
11.
J Environ Manage ; 286: 112267, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33667820

RESUMO

Antibiotic pollution is becoming increasingly severe due to its extensive use. The potential application of the anaerobic ammonium oxidation (anammox) process in the treatment of wastewater containing antibiotics has attracted much attention. As common antibiotics, spiramycin (SPM) and streptomycin (STM) are widely used to treat human and animal diseases. However, their combined effects on the anammox process remain unknown. Therefore, this study systematically evaluated the response of the anammox process to both antibiotics. The half maximal inhibitory concentrations of SPM and STM were determined. The continuous-flow anammox system could adapt to SPM and STM at low concentrations, while antibiotics at high concentrations exhibited inhibitory effects. When the concentrations reached 5 mg L-1 SPM and 50 mg L-1 STM, the nitrogen removal efficiency dramatically decreased and then rapidly recovered within 8 days. Correspondingly, the abundances of dominant bacteria and genes also changed with antibiotic concentrations. In general, the anammox process showed a stable performance and a high resistance to SPM and STM, suggesting that acclimatization by elevating the concentrations was beneficial for the anammox process to obtain resistance to different antibiotics with high concentrations. This study provides guidance for the stable operation of anammox-based biological treatment of antibiotics containing wastewater.


Assuntos
Compostos de Amônio , Macrolídeos , Aminoglicosídeos , Anaerobiose , Animais , Antibacterianos , Reatores Biológicos , Humanos , Nitrogênio , Oxirredução , Águas Residuárias
12.
Bioanalysis ; 13(5): 395-407, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33661021

RESUMO

Background: To support the clinical studies of cabiralizumab, an immunogenicity assay for detecting anti-cabiralizumab antibodies is required. Results: Strategies were developed to overcome two major bioanalytical challenges: poor drug tolerance of the anti-drug antibodies assay and very low cut point observed in the screening and confirmatory assays. By using acid dissociation (400 mM glycine solution at pH 2.0), drug tolerance of 200 µg/ml drug was achieved for both the screening and confirmatory assays. Effects of biological matrix (disease state vs normal serum) and assay conditions (capture/detector reagent concentration, minimum required dilution, acid pretreatment) on assay cut points were systematically evaluated. Conclusion: A bridging immunogenicity assay for detecting anti-cabiralizumab antibodies in human serum has been successfully developed, validated and applied to clinical studies.

13.
Molecules ; 26(3)2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33494216

RESUMO

Rare-earth labeling in biological apatite could provide critical information for the pathologic transition (osteoclastic) and physiologic regeneration (osteogenesis) of bone and teeth because of their characteristic site-sensitive fluorescence in different coordinative conditions of various tissues in many biological processes. However, the rare-earth labeling method for biological apatites, i.e., carbonated-hydroxyapatite, has been rarely found in the literature. In this paper, we report a Pourbaix-diagram guided mineralizing strategy to controllable carbonation and doping of rare-earth ions in the hydroxyapatite (HA) lattice. The carbonation process of hydroxyapatite was achieved by controllable mineralization in hydrothermal condition with K2CO3 as the carbonate source, which results into the pure B-type carbonated hydroxyapatite (CHA) with tunable carbonate substitution degree. All of the as-synthesized materials crystalized into P63/m (No. 176) space group with the lattice parameter of a decreases and c increases with the increasing of carbonate content in the reactants. Structural refinement results revealed that the substitution of planar CO32- is superimposed on one of the faces of PO43- tetrahedral sub-units with a rotation angle of 30° in reference to c-axis. All of the hydrothermally synthesized CHA nanocrystals show hexagonal rod-like morphology with the length of 70-110 nm and diameter of 21-35 nm, and the decreasing length/diameter ratio from 3.61 to 2.96 from low to high carbonated level of the samples. Five rare-earth cations, of Pr3+, Sm3+, Eu3+, Tb3+, and Ho3+, were used as possible probe ions that can be doped into either HA or CHA lattice. The site-preference of Tb3+ doping is the same in the crystallographic site of HA and CHA according to characteristic emission peaks of 5D4-7Fj (j = 3-6) transitions in their photoluminescent spectroscopy. Our work provides a controllable carbonation method for rare-earth labeling hydroxyapatite nanomaterials with potential biologically active implant powders for bone repair and tissue regeneration.


Assuntos
Substitutos Ósseos/química , Durapatita/química , Metais Terras Raras/química , Nanopartículas/química , Animais , Substitutos Ósseos/farmacologia , Linhagem Celular , Durapatita/farmacologia , Medições Luminescentes , Metais Terras Raras/farmacologia , Camundongos
14.
Trends Immunol ; 42(3): 209-227, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33495077

RESUMO

V-domain Ig suppressor of T cell activation (VISTA) is a B7 family member that maintains T cell and myeloid quiescence and is a promising target for combination cancer immunotherapy. During inflammatory challenges, VISTA activity reprograms macrophages towards reduced production of proinflammatory cytokines and increased production of interleukin (IL)-10 and other anti-inflammatory mediators. The interaction of VISTA with its ligands is regulated by pH, and the acidic pH ~6.0 in the tumor microenvironment (TME) facilitates VISTA binding to P-selectin glycoprotein ligand 1 (PSGL-1). Targeting intratumoral pH might be a way to reduce the immunoinhibitory activity of the VISTA pathway and enhance antitumor immune responses. We review differences among VISTA therapeutics under development as candidate immunotherapies, focusing on VISTA binding partners and the unique structural features of this interaction.


Assuntos
Antígenos B7 , Neoplasias , Humanos , Imunoterapia , Ativação Linfocitária , Neoplasias/terapia , Linfócitos T , Microambiente Tumoral
17.
J Hazard Mater ; 410: 124645, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33257124

RESUMO

The release of asbestos fibers in old buildings, during demolition, or remodeling is associated with severe public health risks to building occupants and workers. In Korea, asbestos was used in several building materials during the 20th century. Although the use of asbestos is currently banned, its widespread earlier use and the current government initiatives to revitalize dilapidated areas make it essential to accurately evaluate the location and status of asbestos-containing materials (ACMs). This study surveyed buildings in an area of deteriorated dwellings targeted for renewal and determined the status and distribution of ACMs in that area. Asbestos distribution maps were generated and asbestos characteristics were analyzed. In addition, the risk posed by the identified ACMs was assessed using four international methods (the Korean Ministry of Environment, US Environmental Protection Agency, American Society for Testing and Materials, and UK Health and Safety Executive methods), and the results were compared. Notable differences between the assessment results were identified and were found to reflect the specific characteristics of buildings in the study area. These findings suggest ACM risk assessments should be specifically tailored to the regions in which they are applied, thereby improving ACM management and promoting both worker and occupant health.


Assuntos
Asbestos , Asbestos/análise , Asbestos/toxicidade , Materiais de Construção , Humanos , Saúde Pública , República da Coreia , Medição de Risco , Estados Unidos
18.
J Integr Med ; 19(2): 144-157, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33353843

RESUMO

OBJECTIVE: The present study investigated how mild moxibustion treatment affects the intestinal microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis (IM) induced with 5-fluorouracil (5-Fu). METHODS: Forty male Sprague-Dawley rats were randomly divided into control, chemotherapy, moxibustion and probiotics groups. The IM rat model was established by intraperitoneal injection of 5-Fu. Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days. Tissue morphology, serum levels of inflammatory factors and the expression levels of tight junction proteins, caspase-1, gasdermin D and NLRP3 were evaluated in colon tissue, through hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay, Western blotting, quantitative real-time reverse transcription polymerase chain reaction and immunofluorescence. Gut microbiome profiling was conducted through 16S rRNA amplicon sequencing. RESULTS: Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins, reduced cell apoptosis and the expression levels of caspase-1, gasdermin D and NLRP3; they also decreased the serum levels of tumor necrosis factor-α, interleukin (IL)-6, IL-1ß and IL-18, while increasing serum levels of IL-10. Moxibustion and probiotic treatments also corrected the reduction in α-diversity and ß-diversity in IM rats, greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapy-treated rats to levels observed in healthy animals. We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors. Finally, moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors. CONCLUSION: Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation. Moreover, moxibustion modulates the gut microbiota, likely via decreasing the expression levels of the NLRP3 inflammasome.


Assuntos
Microbioma Gastrointestinal , Moxibustão , Mucosite , Animais , Fluoruracila , Inflamassomos , Mucosa Intestinal , Masculino , Mucosite/induzido quimicamente , Mucosite/terapia , Proteína 3 que Contém Domínio de Pirina da Família NLR , RNA Ribossômico 16S , Ratos , Ratos Sprague-Dawley
19.
Aging (Albany NY) ; 13(1): 450-459, 2020 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-33257598

RESUMO

BACKGROUND: Breast cancer is the most commonly diagnosed cancer and is the leading cause of cancer death in women worldwide. Both talazoparib and olaparib are approved by the US Food and Drug Administration for treating BRCA (breast cancer 1, early onset)-mutated HER2 (human epidermal growth factor receptor 2)-negative metastatic or advanced breast cancer. However, the optimal choice of first-line treatment has not been determined. OBJECTIVE: To compare the efficacy, safety, and acceptability of single-agent poly (ADP-ribose) polymerase (PARP) inhibitors for patients with BRCA-mutated HER2-negative metastatic or advanced breast cancer. RESULTS: We included two trials comprising 733 participants. Compared with talazoparib, olaparib was not associated with improved PFS (HR = 1.08, 95% CrI = 0.34-3.45) or OS (HR = 1.18, 95% CrI = 0.61-2.31). Compared with talazoparib, olaparib was associated with non-significantly improved ORR (OR = 0.83, 95% CrI = 0.05-12.64). Regarding safety, olaparib had reduced risk for both grade 3-4 anemia (OR = 0.34, 95% CrI = 0.003-34.94) and any-grade anemia (OR = 0.37, 95% CrI = 0.02-6.81) compared with talazoparib. Olaparib also showed a low risk for grade 3-4 neutropenia (OR = 0.57, 95% CrI = 0.06-5.75) compared with talazoparib. Both talazoparib and olaparib were not associated with high risk of treatment discontinuation (OR = 0.95, 95% CrI = 0.21-4.47). Regarding time to QoL deterioration, olaparib was associated with short time to clinically meaningful QoL deterioration (HR = 1.16, 95% CrI = 0.19-7.17) compared to talazoparib. CONCLUSION: Both talazoparib and olaparib have similar efficacy, safety, and acceptability in patients with BRCA-mutated HER2-negative metastatic or advanced breast cancer. Well-designed head-to-head randomized controlled trials with large samples are suggested to determine the optimal treatment choice. METHODS: We performed a systematic review and network meta-analysis. We performed a systematic search of Web of Science, Embase, PubMed, Medline, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials, and the World Health Organization International Clinical Trials Registry Platform, and international registers for published and unpublished double-blind randomized controlled trials from database inception to July 20, 2019. The pooled estimates of hazard ratios (HR) with 95% credible intervals (CrIs) were calculated for PFS, OS, and the time to deterioration of quality of life (QoL). The pooled estimates of odds ratio (OR) with 95% CrIs were calculated for ORR, AEs, and treatment discontinuation. This study is registered with PROSPERO (CRD42019138939).


Assuntos
Neoplasias da Mama/tratamento farmacológico , Genes BRCA1 , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Anemia/induzido quimicamente , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Mutação , Metástase Neoplásica , Metanálise em Rede , Neutropenia/induzido quimicamente , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Qualidade de Vida , Receptor ErbB-2/metabolismo , Taxa de Sobrevida , Resultado do Tratamento
20.
Cancer Control ; 27(1): 1073274820960481, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32951460

RESUMO

This study aimed to establish and validate a comprehensive nomogram for predicting the cause-specific survival (CSS) probability in tonsillar squamous cell carcinoma (TSCC). We screened and extracted data from the SEER (Surveillance, Epidemiology, and End Results) database for the period 2004 to 2016. We randomly divided the 7243 identified patients into a training cohort (70%) for constructing the model and a validation cohort (30%) for evaluating the model using R software. Multivariate Cox stepwise regression was used to select predictive variables. The concordance index (C-index), the area under the time-dependent receiver operating characteristics curve (AUC), the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA) were used to evaluate the model. The multivariate Cox stepwise regression analysis successfully established a nomogram for the 1-, 3-, and 5-year CSS probabilities for TSCC patients. The C-index, AUC, NRI, and IDI were all showed that the model has good discrimination. The calibration plots were very close to the standard lines, indicating that the model has a good degree of calibration, and the DCA curve further illustrated that the model has good clinical validity. We have established the first nomogram for predicting the 1-, 3-, and 5-year CSS probabilities for TSCC based on a large retrospective sample. Our rigorous validation and evaluation indicated that the model can provide useful guidance to clinical workers making clinical decisions about individual patients.


Assuntos
Carcinoma de Células Escamosas/patologia , Nomogramas , Programa de SEER/estatística & dados numéricos , Neoplasias Tonsilares/patologia , Idoso , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Tonsilares/terapia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...