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1.
J Cancer ; 15(10): 3095-3113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706901

RESUMO

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is a common gynecologic tumor and patients with advanced and recurrent disease usually have a poor clinical outcome. Angiogenesis is involved in the biological processes of tumors and can promote tumor growth and invasion. In this paper, we created a signature for predicting prognosis based on angiogenesis-related lncRNAs (ARLs). This provides a prospective direction for enhancing the efficacy of immunotherapy in CESC patients. We screened seven OS-related ARLs by univariate and multivariate regression analyses and Lasso analysis and developed a prognostic signature at the same time. Then, we performed an internal validation in the TCGA-CESC cohort to increase the precision of the study. In addition, we performed a series of analyses based on ARLs, including immune cell infiltration, immune function, immune checkpoint, tumor mutation load, and drug sensitivity analysis. Our created signature based on ARLs can effectively predict the prognosis of CESC patients. To strengthen the prediction accuracy of the signature, we built a nomogram by combining signature and clinical features.

2.
J Cancer ; 15(9): 2788-2804, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577592

RESUMO

Background: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) account for a significant proportion of gynecological malignancies and represent a major global health concern. Globally, CESC is ranked as the fourth most common cancer among women. Conventional treatment of this disease has a less favorable prognosis for most patients. However, the discovery of early molecular biomarkers is therefore important for the diagnosis of CESC, as well as for slowing down their progression process. Methods: To identify differentially expressed genes strongly associated with prognosis, univariate Cox proportional hazard analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were used. Using multiple Cox proportional hazard regression, a multifactorial model for prognostic risk assessment was then created. Results: The expression of biological clock-related genes, which varied considerably among distinct subtypes and were associated with significantly diverse prognoses, was used to categorize CESC patients. These findings demonstrate how the nomogram developed based on the 7-CRGs signature may assist physicians in creating more precise, accurate, and successful treatment plans that can aid CESC patients at 1, 3, and 5 years. Conclusions: By using machine learning techniques, we thoroughly investigated the impact of CRGs on the prognosis of CESC patients in this study. By creating a unique nomogram, we were able to accurately predict patient prognosis. At the same time, we showed new perspectives on the development of CESC and its treatment by analyzing the associations of the prognostic model with immunity, enrichment pathways, chemotherapy sensitivity, and so on. This research provides a new direction for clinical treatment.

3.
J Nanobiotechnology ; 21(1): 170, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37237294

RESUMO

BACKGROUND: Sepsis is a syndrome of physiological, pathological and biochemical abnormalities caused by infection. Although the mortality rate is lower than before, many survivors have persistent infection, which means sepsis calls for new treatment. After infection, inflammatory mediators were largely released into the blood, leading to multiple organ dysfunction. Therefore, anti-infection and anti-inflammation are critical issues in sepsis management. RESULTS: Here, we successfully constructed a novel nanometer drug loading system for sepsis management, FZ/MER-AgMOF@Bm. The nanoparticles were modified with LPS-treated bone marrow mesenchymal stem cell (BMSC) membrane, and silver metal organic framework (AgMOF) was used as the nanocore for loading FPS-ZM1 and meropenem which was delivery to the infectious microenvironments (IMEs) to exert dual anti-inflammatory and antibacterial effects. FZ/MER-AgMOF@Bm effectively alleviated excessive inflammatory response and eliminated bacteria. FZ/MER-AgMOF@Bm also played an anti-inflammatory role by promoting the polarization of macrophages to M2. When sepsis induced by cecal ligation and puncture (CLP) challenged mice was treated, FZ/MER-AgMOF@Bm could not only reduce the levels of pro-inflammatory factors and lung injury, but also help to improve hypothermia caused by septic shock and prolong survival time. CONCLUSIONS: Together, the nanoparticles played a role in combined anti-inflammatory and antimicrobial properties, alleviating cytokine storm and protecting vital organ functions, could be a potential new strategy for sepsis management.


Assuntos
Nanopartículas , Sepse , Camundongos , Animais , Macrófagos/metabolismo , Antibacterianos/uso terapêutico , Sepse/tratamento farmacológico , Membrana Celular/metabolismo , Modelos Animais de Doenças
4.
Genes (Basel) ; 14(1)2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36672865

RESUMO

Pancreatic adenocarcinoma (PAAD) is a common, highly malignant, and aggressive gastrointestinal tumor. The conventional treatment of PAAD shows poor results, and patients have poor prognosis. The synthesis and degradation of proteins are essential for the occurrence and development of tumors. Aggrephagy is a type of autophagy that selectively degrades aggregated proteins. It decreases the formation of aggregates by degrading proteins, thus reducing the harm to cells. By breaking down proteins, it decreases the formation of aggregates; thus, minimizing damage to cells. For evaluating the response to immunotherapy and prognosis in PAAD patients, in this study, we developed a reliable signature based on aggrephagy-related genes (ARGs). We obtained 298 AGGLncRNAs. Based on the results of one-way Cox and LASSO analyses, the lncRNA signature was constructed. In the risk model, the prognosis of patients in the low-risk group was noticeably better than that of the patients in the high-risk group. Additionally, the ROC curves and nomograms validated the capacity of the risk model to predict the prognosis of PAAD. The patients in the low-risk and high-risk groups showed considerable variations in functional enrichment and immunological analysis. Regarding drug sensitivity, the low-risk and high-risk groups had different half-maximal inhibitory concentrations (IC50).


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , RNA Longo não Codificante , Humanos , Adenocarcinoma/genética , Macroautofagia , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/genética , Prognóstico , Neoplasias Pancreáticas
5.
Orthop Surg ; 14(8): 1778-1789, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35819087

RESUMO

OBJECTIVE: To analyze the use of packed red blood cells (PRBCs) for patients with pelvic fracture and evaluate factors associated with PRBC transfusion for patients with pelvic fracture. METHODS: This retrospective cohort study collected 551 patients with pelvic fractures from six hospitals between September 1, 2012, and June 31, 2019. The age span of patients varied from 10 to 95 years old, and they were classified into two groups based on high-energy pelvic fractures (HE-PFs) or low-energy pelvic fractures (LE-PFs). The study's outcome was the use of PRBCs, fresh frozen plasma (FFP), and albumin. Demographic data, characteristics, laboratory tests, clinical treatment details, and clinical outcomes were compared between the two groups. Factors that were statistically associated with perioperative PRBCs in univariate analyses were included to conduct an optimal scale regression to determine the independent factors for perioperative PRBCs. RESULTS: A total of 551 patients were screened from six hospitals, and after inclusion and exclusion, 319 were finally included and finished the follow-up from admission to discharge, while four patients died during hospitalization. Three hundred and nineteen patients were classified into two groups by their injury mechanisms. A total of 230/319 (72.1%) patients were classified into the HE-PF group, and 89/319 (27.8%) patients were classified into the LE-PF group. Patients in the HE-PF group were transfused with 4.5 (3-8) units of PRBCs, 300 (0-600) ml of FFP, and 0 (0-30) g of albumin, while patients in the LE-PF group were transfused with 3.5 (2-4.5) units of PRBCs, 0 (0-295) ml of FFP, and 0 (0-0) g of albumin (all P < 0.001). There were higher proportions of male patients and patients under 65 in the HE-PF group (all P < 0.001). HE-PF group patients were more severely injured and likely to take external fixation. The optimal scale regression revealed four significant factors associated with perioperative transfused PRBCs, which were patients on admission with hemorrhagic shock (importance = 0.283, P = 0.004), followed by fracture types identified by Tile classification (importance = 0.156, P < 0.001), hemoglobin levels below 70 g/L on admission (importance = 0.283, P = 0.004), followed by fracture types identified by Tile classification (importance = 0.156, P < 0.001), hemoglobin levels below 70 g/L on admission (importance = 0.148, P = 0.039), and methods of pelvic fixation (importance = 0.008, P = 0.026), ranked by the importance. CONCLUSION: Patients with HE-PFs had increased transfusions of PRBCs, FFP, and albumin, and hemorrhagic shock on admission, Tile classification, Hb levels, and stabilization methods were found to be associated with perioperative PRBCs.


Assuntos
Fraturas Ósseas , Choque Hemorrágico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas , Transfusão de Componentes Sanguíneos/métodos , Criança , Eritrócitos , Feminino , Fraturas Ósseas/cirurgia , Hemoglobinas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
Front Chem ; 9: 522708, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796503

RESUMO

Zirconia nanoparticles (ZrO2 NPs) are commonly used in the field of biomedical materials, but their antitumor activity and mechanism is unclear. Herein, we evaluated the anti-tumor activity of ZrO2 NPs and explored the anti-tumor mechanism. The results of in vitro and in vivo experiments showed that the level of intracellular reactive oxygen species (ROS) in HeLa cells was elevated after ZrO2 NPs treatment. Transmission electron microscopy (TEM) showed that after treatment with ZrO2 NPs, the mitochondria of HeLa cells were swollen, accompanied with the induction of autophagic vacuoles. In addition, flow cytometry analysis showed that the apoptotic rate of HeLa cells increased significantly by Annexin staining after treatment with ZrO2 NPs, and the mitochondrial membrane potential (MMP) was reduced significantly. The proliferation of HeLa cells decreased as indicated by reduced Ki-67 labeling. In contrast, TUNEL-positive cells in tumor tissues increased after treatment with ZrO2 NPs, which is accompanied by increased expression of mitochondrial apoptotic proteins including Bax, Caspase-3, Caspase-9, and Cytochrome C (Cyt C) and increased expression of autophagy-related proteins including Atg5, Atg12, Beclin-1, and LC3-II. Treating HeLa cells with N-acetyl-L-cysteine (NAC) significantly reduced ROS, rate of apoptosis, MMP, and in vivo anti-tumor activity. In addition, apoptosis- and autophagy-related protein expressions were also suppressed. Based on these observations, we conclude that ZrO2 NPs induce HeLa cell death through ROS mediated mitochondrial apoptosis and autophagy.

7.
J Nanobiotechnology ; 19(1): 8, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407527

RESUMO

BACKGROUND: Non-Hodgkin's lymphoma (NHL) possesses great heterogeneity in cytogenetics, immunophenotype and clinical features, and chemotherapy currently serves as the main treatment modality. Although employing monoclonal antibody targeted drugs has significantly improved its overall efficacy, various patients continue to suffer from drug resistance or recurrence. Chinese medicine has long been used in the treatment of malignant tumors. Therefore, we constructed a low pH value sensitivity drug delivery system based on the cancer cell membrane modified mesoporous silica nanoparticles loaded with traditional Chinese medicine, which can reduce systemic toxicity and improve the therapeutic effect for the targeted drug delivery of tumor cells. RESULTS: Accordingly, this study put forward the construction of a nano-platform based on mesoporous silica nanoparticles (MSNs) loaded with the traditional Chinese medicine isoimperatorin (ISOIM), which was camouflaged by the cancer cell membrane (CCM) called CCM@MSNs-ISOIM. The proposed nano-platform has characteristics of immune escape, anti-phagocytosis, high drug loading rate, low pH value sensitivity, good biocompatibility and active targeting of the tumor site, blocking the lymphoma cell cycle and promoting mitochondrial-mediated apoptosis. CONCLUSIONS: Furthermore, this study provides a theoretical basis in finding novel clinical treatments for lymphoma.


Assuntos
Antineoplásicos/administração & dosagem , Membrana Celular , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Linfoma/tratamento farmacológico , Nanopartículas/química , Animais , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis , Proliferação de Células , Modelos Animais de Doenças , Furocumarinas/farmacologia , Humanos , Medicina Tradicional Chinesa , Camundongos Nus , Espécies Reativas de Oxigênio , Dióxido de Silício
8.
Mater Sci Eng C Mater Biol Appl ; 119: 111648, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33321684

RESUMO

Lymphoma is a well-known malignant tumor in the human body. Although many anticancer drugs have been developed to improve the survival rate of patients, about 40% of patients continue to be recurrent or refractory, a key issue needing remedy. Therefore, it is necessary to identify alternative treatments to reduce the disease's mortality. To this effect, a new type of anti-lymphoma nanocomplex FA@RBCm-AgNPs was prepared using AgNPs as the core of nanoparticles along with the targeting molecule folic acid inserted erythrocyte membrane as the shell. The biomimetic properties of red blood cell membrane (RBCm) endow F-RAN with good biocompatibility as well as the ability to evade clearance of the reticuloendothelial system. In addition, F-RAN was modified with folic acid to actively and selectively identify tumor cells. In vivo and in vitro experiments demonstrate that F-RAN can inhibit lymphoma cells and induce apoptosis of stem cells while promoting apoptosis of lymphoma with no obvious side effects. Hence, F-RAN may serve as a new treatment for lymphoma.


Assuntos
Linfoma , Nanopartículas Metálicas , Nanopartículas , Apoptose , Biomimética , Linhagem Celular Tumoral , Humanos , Linfoma/tratamento farmacológico , Prata
9.
Front Chem ; 8: 565, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32766207

RESUMO

Jolkinolide B (JB) is a bioactive compound isolated from a Chinese herbal medicine that exerts antitumor activity. However, the anti-lymphoma effect of JB and its mechanism are yet to be revealed. Because free JB has poor pharmacokinetics and weak antitumor efficacy, we opted to use black phosphorus quantum dot (BPQD) nanomaterials as a drug loading platform to synthesize a nano-traditional Chinese medicine (nano-TCM) called BPQDs@JB. Compared with free JB, Raji cells administrated with BPQDs@JB exhibited the cell viability of 19.85 ± 1.02%, and the production of intracellular reactive oxygen species (ROS) was promoted. Likewise, BPQDs@JB was capable of rising the apoptosis rate of Raji cells to 34.98 ± 1.76%. In nude mice transplanted tumor model administrated with BPQDs@JB, the tumor tissue sections administrated with BPQDS@JB achieved a conspicuous red fluorescence, demonstrating the presence of most ROS production in the BPQDS@JB. TUNEL achieved a number of positive (brown) nuclei in vivo, revealing that BPQDS@JB could significantly induce tumor tissue apoptosis. As revealed from the mentioned results, BPQDs@JB can generate considerable ROS and interfere with the redox state to inhibit tumor. In brief, BPQDs@JB may be adopted as a treatment option for lymphoma.

10.
Front Chem ; 8: 377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32457875

RESUMO

Zirconia nanoparticles (ZrO2 NPs) are widely applied in the field of biomedicine. In this study, we constructed a nanoplatform of ZrO2 NPs coated with a platelet membrane (PLTm), named PLT@ZrO2. PLTm nanovesicles camouflage ZrO2 NPs, prevent nanoparticles from being cleared by macrophage, and target tumor sites. Compared to ZrO2 alone, PLT@ZrO2 is better at inhibiting the invasion and metastasis of Hela cells in vitro and in vivo. In vitro, PLT@ZrO2 inhibited the growth and proliferation of Hela cells. Scratch-wound healing recovery assay demonstrated that PLT@ZrO2 inhibited Hela cells migration. Transwell migration and invasion assays showed that PLT@ZrO2 inhibited Hela cells migration and invasion. In vivo, PLT@ZrO2 inhibited the tumor growth of Xenograft mice and inhibited the lung and liver metastasis of Hela cells. Immunofluorescence and Western blotting results showed that anti-metastasis protein (E-cadherin) was upregulated and pro-metastasis proteins (N-cadherin, Smad4, Vimentin, E-cadherin,ß-catenin, Fibronectin, Snail, Slug, MMP2, Smad2) were down-regulated. Our study indicated that PLT@ZrO2 significantly inhibits tumor growth, invasion, and metastasis.

11.
ACS Appl Mater Interfaces ; 12(20): 22687-22701, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32330381

RESUMO

Toxicity and drug resistance caused by chemotherapeutic drugs have become bottlenecks in treating tumors. The delivery of anticancer drugs based on nanocarriers is regarded as an ideal way to solve the aforementioned problems. In this study, a new antilymphoma nanodrug CD20 aptamer-RBCm@Ag-MOFs/PFK15 (A-RAMP) is designed and constructed, and it consists of two parts: (1) metal-organic frameworks Ag-MOFs (AM) loaded with tumor aerobic glycolysis inhibitor PFK15 (P), forming a core part (AMP); (2) targeted molecule CD20 aptamer (A) is inserted into the red blood cell membrane (RBCm) to form the shell part (A-R). A-RAMP under the guidance of CD20 aptamer actively targets B-cell lymphoma both in vitro and in vivo. As a result, A-RAMP not only significantly inhibits the effect on tumor growth but also shows no obvious side effects on the treated nude mice, indicating that A-RAMP can accurately target tumor cells, reprogram aerobic glycolysis, and exert synergistic antitumor effect by Ag+ and PFK 15. Furthermore, the antitumor mechanism of A-RAMP in vivo by apoptotic pathway and targeting metabonomics are explored. These results suggest that A-RAMP has a promising application prospect as an smart, safe, effective, and synergistic antilymphoma agent.


Assuntos
Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Glicólise/efeitos dos fármacos , Linfoma de Células B/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Nanocompostos/química , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Aptâmeros de Nucleotídeos/química , Sequência de Bases , Materiais Biomiméticos/química , Membrana Eritrocítica/química , Humanos , Células K562 , Estruturas Metalorgânicas/química , Camundongos , Camundongos Endogâmicos BALB C , Piridinas/uso terapêutico , Quinolinas/uso terapêutico , Células RAW 264.7 , Prata/química , Prata/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Onco Targets Ther ; 13: 473-486, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021291

RESUMO

BACKGROUND: Isatin derivatives have extensive biological activities, such as antitumor. IF203, a novel isatin derivative, has not previously been reported to have antitumor activity. METHODS: Acid phosphatase assays (APAs) and Ki-67 immunohistochemistry were used to detect the proliferation of HepG2 cells. Transmission electron microscope (TEM) was applied to detect ultrastructural changes. Flow cytometry (FCM) was used to detect cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) of HepG2 cells in vitro. TUNEL, MMP and ROS immunofluorescence assays were applied to assess apoptosis, MMP, and ROS of HepG2 cells in vivo. Western Blotting was applied to assess the levels of apoptosis- and autophagy-related proteins. RESULTS: In this study, in vivo and in vitro experiments showed that IF203 possesses antitumor activity. The results of APAs and Ki-67 immunohistochemistry demonstrated that IF203 could inhibit the proliferation of HepG2 cells. Cell cycle assays, downregulation of Cyclin B1 and Cdc2, and upregulation of P53 suggested that IF203 could lead to G2/M cell cycle arrest. In addition, ultrastructural changes, apoptosis assays, TUNEL immunofluorescence results, upregulated expression of Bax, and downregulated expression of Bcl-2 suggest that IF203 can induce apoptosis in HepG2 cells. After IF203 treatment, intracellular ROS levels increased, MMP decreased, JC-1 green fluorescence was enhanced, and the levels of Caspase-9, Caspase-3 and Cytochrome C expression were upregulated, suggesting that IF203 could induce apoptosis of HepG2 cells through the mitochondrial apoptosis pathway. Moreover, characteristic apoptotic ultrastructural changes were accompanied by the appearance of many autophagy bubbles and upregulation of Atg5, Atg12, ULK1, Beclin-1 and LC3-II proteins, suggesting that IF203 could induce autophagy in HepG2 cells. CONCLUSION: This study showed that IF203 leads to the death of HepG2 cells through cell cycle arrest, apoptotic induction, and autophagy promotion.

13.
J Cell Mol Med ; 23(11): 7651-7663, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31565849

RESUMO

Diabetic cardiomyopathy is characterized by diabetes-induced myocardial abnormalities, accompanied by inflammatory response and alterations in inflammation-related signalling pathways. Kirenol, isolated from Herba Siegesbeckiae, has potent anti-inflammatory properties. In this study, we aimed to investigate the cardioprotective effect of kirenol against DCM and underlying the potential mechanisms in a type 2 diabetes mellitus model. Kirenol treatment significantly decreased high glucose-induced cardiofibroblasts proliferation and increased the cardiomyocytes viability, prevented the loss of mitochondrial membrane potential and further attenuated cardiomyocytes apoptosis, accompanied by a reduction in apoptosis-related protein expression. Kirenol gavage could affect the expression of pro-inflammatory cytokines in a dose-dependent manner but not lower lipid profiles, and only decrease fasting plasma glucose, fasting plasma insulin and mean HbA1c levels in high-dose kirenol-treated group at some time-points. Left ventricular dysfunction, hypertrophy, fibrosis and cell apoptosis, as structural and functional abnormalities, were ameliorated by kirenol administration. Moreover, in diabetic hearts, oral kirenol significantly attenuated activation of mitogen-activated protein kinase subfamily and nuclear translocation of NF-κB and Smad2/3 and decreased phosphorylation of IκBα and both fibrosis-related and apoptosis-related proteins. In an Electrophoretic mobility shift assay, the binding activities of NF-κB, Smad3/4, SP1 and AP-1 in the nucleus of diabetic myocardium were significantly down-regulated by kirenol treatment. Additionally, high dose significantly enhanced myocardial Akt phosphorylation without intraperitoneal injection of insulin. Kirenol may have potent cardioprotective effects on treating for the established diabetic cardiomyopathy, which involves the inhibition of inflammation and fibrosis-related signalling pathways and is independent of lowering hyperglycaemia, hyperinsulinemia and lipid profiles.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/tratamento farmacológico , Diterpenos/uso terapêutico , Inflamação/tratamento farmacológico , Animais , Biomarcadores/metabolismo , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colágeno/biossíntese , Citocinas/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/fisiopatologia , Diterpenos/administração & dosagem , Diterpenos/química , Diterpenos/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Glucose/toxicidade , Inflamação/sangue , Inflamação/complicações , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Inibidor de NF-kappaB alfa/metabolismo , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Proteínas Smad/metabolismo , Remodelação Ventricular/efeitos dos fármacos
14.
Iran J Public Health ; 48(5): 841-848, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31523640

RESUMO

BACKGROUND: We aimed to establish the reference range of thrombelastogram (TEG) for Chinese healthy volunteers and pregnant women and analyze the influence factors. METHODS: Blood samples were collected from healthy volunteers and pregnant women at five tertiary hospitals (the Third Xiangya Hospital of Central South University, the Second Xiangya Hospital of Central South University, Hunan Provincial People's Hospital, Hunan Cancer Hospital and Changsha Central Hospital) in 2016. The effects of age, gender, blood type, and full-term pregnancy on the reference range of normal TEG for healthy volunteers and pregnant women were studied. The specificity of TEG in detecting coagulation disorder. RESULTS: For healthy volunteers, the normal ranges of TEG parameters were as follows: R, 4.3-9.3 min; K, 1.2-3.2 min; α, 50.2-71.2°; MA, 54.1-71.3 mm; LY30: 0%-2.2%; CI, -3.8-2.4. At least one parameter exceeded the normal range specified by the manufacturer in 20.3% of the healthy volunteers; about 7.6% healthy volunteers were diagnosed as coagulation disorder by the above standards; the specificity of detection was 79.7%. There were significant differences in R, K, α, MA and CI between males and females (P<0.01). For pregnant women, the normal ranges of TEG were as follows: R, 3.9-7.5 min; K, 1.0-2.4 min; α, 57.6-74.9°; MA, 55.7-75.7 mm; LY30, 0%-0.56%; CI, -0.97-3.6. Pregnant women having O blood group had a dramatically prolonged R. Full-term pregnancy had no significant impact on TEG results. CONCLUSION: Compared with pregnant women having non-O blood group, those having O blood group had a dramatically prolonged R and showed greater tendency to hemorrhage during and after parturition.

15.
ACS Appl Mater Interfaces ; 11(31): 28254-28266, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31291079

RESUMO

Hederagenin (HED) has poor anticancer activity whose mechanism remains unclear and unsystematic. Free drugs for cancer treatment exhibit disadvantages such as poor targeting and efficacy. To address this problem, we constructed a nanoplatform of black phosphorus quantum dots (BPQDs) camouflaged with a platelet membrane (PLTm) carrying HED, termed PLT@BPQDs-HED. PLTm vesicles serve as a shell to encapsulate multiple high-efficiency drug-loaded nanocores, which can target tumor sites and significantly improve antitumor activity. Compared with free HED, this platform significantly reduced tumor cell viability and the mitochondrial membrane potential (MMP), while increasing the production of intracellular reactive oxygen species (ROS). The platform also significantly increased the amounts of terminal deoxyribonucleotide transferase mediated dUTP nick-end-labeling (TUNEL)-positive cells and decreased the number of Ki-67-positive cells. In addition, the platform upregulated proapoptotic factor Bax, downregulated the anti-apoptotic molecule Bcl-2, activated Caspase-9 and Caspase-3, and stimulated Cytochrome C release. Moreover, the platform promoted the formation of autophagosomes, upregulated Beclin-1, and promoted LC3-I conversion into LC3-II. This study demonstrated that the above platform significantly enhances tumor targeting and promotes mitochondria-mediated cell apoptosis and autophagy in tumor cells.


Assuntos
Antineoplásicos , Apoptose/efeitos dos fármacos , Morte Celular Autofágica/efeitos dos fármacos , Plaquetas , Neoplasias da Mama/tratamento farmacológico , Membrana Celular , Fósforo , Pontos Quânticos , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Células MCF-7 , Camundongos , Fósforo/química , Fósforo/farmacocinética , Fósforo/farmacologia , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Células RAW 264.7 , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Artif Cells Nanomed Biotechnol ; 47(1): 968-979, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30880468

RESUMO

Conventional anti-tumour chemotherapy is facing the challenges of poor specificity, high toxicity and drug resistance. Tumour microenvironment (TME) plays a critical role in tumour development and drug resistance. To address this problem, we constructed a novel anti-tumour nanoparticle platform RBC@BPQDs-DOX/KIR, black phosphorus nanoparticle quantum dots (BPQDs) with one of the chemotherapeutics (doxorubicin, DOX) and an anti-inflammatory traditional Chinese medicine active component (Kirenol, KIR). Red blood cell membrane (RBCm) vesicles were used as the shell to envelop several nanocores. The combination of DOX and KIR may promote therapeutic efficacy, at which the anti-apoptotic effect of the tumour cells was inhibited (by downregulating Bcl-2 and upregulating Bax) and the tumour progression-related inflammatory factors, such as tumour necrosis factor α (TNF-α) and interleukin-6 (IL-6) were downregulated. Furthermore, TME was remodelled and the anti-tumour effect of DOX was magnified. RBCm imparts high biocompatibility and enhanced permeability and retention (EPR) effects to RBC@BPQDs-DOX/KIR, thus enhancing its tumour passively targetability. Overall, the RBCm-camouflaged drug delivery system RBC@BPQDs-DOX/KIR as a promising therapy for targeted chemotherapeutics and anti-inflammatory therapeutics may provide a specific and highly efficient anti-tumour treatment choice.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Membrana Eritrocítica/química , Fósforo/química , Pontos Quânticos/química , Animais , Anti-Inflamatórios/farmacocinética , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/farmacocinética , Diterpenos/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Feminino , Humanos , Teste de Materiais , Camundongos , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
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