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1.
ACS Nano ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39299912

RESUMO

The poor ambient ionic transport properties of poly(ethylene oxide) (PEO)-based SPEs can be greatly improved through filler introduction. Metal fluorides are effective in promoting the dissociation of lithium salts via the establishment of the Li-F bond. However, too strong Li-F interaction would impair the fast migration of lithium ions. Herein, magnesium aluminum fluoride (MAF) fillers are developed. Experimental and simulation results reveal that the Li-F bond strength could be readily altered by changing fluorine vacancy (VF) concentration in the MAF, and lithium salt anions can also be well immobilized, which realizes a balance between the dissociation degree of lithium salts and fast transport of lithium ions. Consequently, the Li symmetric cells cycle stably for more than 1400 h at 0.1 mA cm-2 with a LiF/Li3N-rich solid electrolyte interphase (SEI). The SPE exhibits a high ionic conductivity (0.5 mS cm-1) and large lithium-ion transference number (0.4), as well as high mechanical strength owing to the hydrogen bonding between MAF and PEO. The corresponding Li//LiFePO4 cells deliver a high discharge capacity of 160.1 mAh g-1 at 1 C and excellent cycling stability with 100.2 mAh g-1 retaining after 1000 cycles. The as-assembled pouch cells show excellent electrochemical stability even at rigorous conditions, demonstrating high safety and practicability.

2.
J Orthop Surg Res ; 19(1): 225, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576008

RESUMO

OBJECTIVE: This study was performed to investigate the effectiveness of two surgical procedures, autologous patellar tendon graft reconstruction and trans-tibial plateau pull-out repair, using a pig model. The primary focus was to assess the repair capability of medial meniscus posterior portion (MMPP) deficiency, the overall structural integrity of the meniscus, and protection of the femoral and tibial cartilage between the two surgical groups. The overall aim was to provide experimental guidelines for clinical research using these findings. METHODS: Twelve pigs were selected to establish a model of injury to the MMPP 10 mm from the insertion point of the tibial plateau. They were randomly divided into three groups of four animals each: reconstruction (autologous tendon graft reconstruction of the MMPP), pull-out repair (suture repair of the MMPP via a trans-tibial plateau bone tunnel), and control (use of a normal medial meniscus as the negative control). The animals were euthanized 12 weeks postoperatively for evaluation of the meniscus, assessment of tendon bone healing, and gross observation of knee joint cartilage. The tibial and femoral cartilage injuries were evaluated using the International Society for Cartilage Repair (ICRS) grade and Mankin score. Histological and immunohistochemical staining was conducted on the meniscus-tendon junction area, primary meniscus, and tendons. The Ishida score was used to evaluate the regenerated meniscus in the reconstruction group. Magnetic resonance imaging (MRI) was used to evaluate meniscal healing. RESULTS: All 12 pigs recovered well after surgery; all incisions healed without infection, and no obvious complications occurred. Gross observation revealed superior results in the reconstruction and pull-out repair groups compared with the control group. In the tibial cartilage, the reconstruction group had ICRS grade I injury whereas the pull-out repair and control groups had ICRS grade II and III injury, respectively. The Mankin score was significantly different between the reconstruction and control groups; histological staining showed that the structure of the regenerated meniscus in the reconstruction group was similar to that of the original meniscus. Immunohistochemical staining showed that the degree of type I and II collagen staining was similar between the regenerated meniscus and the original meniscus in the reconstruction group. The Ishida score was not significantly different between the regenerated meniscus and the normal primary meniscus in the reconstruction group. MRI showed that the MMPP in the reconstruction and pull-out repair groups had fully healed, whereas that in the control group had not healed. CONCLUSION: Autologous patellar tendon graft reconstruction of the MMPP can generate a fibrocartilage-like regenerative meniscus. Both reconstruction and pull-out repair can preserve the structural integrity of the meniscus, promote healing of the MMPP, delay meniscal degeneration, and protect the knee cartilage.


Assuntos
Doenças das Cartilagens , Menisco , Ligamento Patelar , Animais , Doenças das Cartilagens/cirurgia , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/cirurgia , Menisco/cirurgia , Ligamento Patelar/diagnóstico por imagem , Ligamento Patelar/cirurgia , Ligamento Patelar/patologia , Suínos
3.
Cancer Biol Med ; 21(6)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38525901

RESUMO

OBJECTIVE: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B (LDHB) has been detected in breast cancer but the function of LDHB remains unknown. METHODS: Western blot was used to analyze LDHB expression in breast cancer cells. The impact of LDHB on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer (NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of LDHB in NK cell activation. RESULTS: In this study we showed that LDHB inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that LDHB-mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that LDHB in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that LDHB affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified LDHB expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some cancers. CONCLUSIONS: Our results suggest that LDHB is a promising target for activating the tumor immune microenvironment in breast cancer, where LDHB-associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of LDHB in regulating immune responses and its potential as a therapeutic target for breast cancer.


Assuntos
Neoplasias da Mama , Progressão da Doença , Células Matadoras Naturais , L-Lactato Desidrogenase , Microambiente Tumoral , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/imunologia , Humanos , Feminino , Animais , Camundongos , L-Lactato Desidrogenase/metabolismo , Microambiente Tumoral/imunologia , Linhagem Celular Tumoral , Ativação Linfocitária , Isoenzimas/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Movimento Celular , Prognóstico , Regulação Neoplásica da Expressão Gênica
4.
Biomed Pharmacother ; 172: 116267, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364739

RESUMO

Schizophrenia (SCZ) is a psychotic mental disorder characterized by cognitive, behavioral, and social impairments. However, current pharmacological treatment regimens are subpar in terms of effectiveness. This study aimed to investigate the function of Radix Bupleuri aqueous extract in SCZ in mouse models. The SCZ mouse model was established by MK-801 injection and feeding of Radix Bupleuri aqueous extract or combined antibiotics. Radix Bupleuri aqueous extract significantly improved the aberrant behaviors and neuronal damage in SCZ mice, upregulated SYP and PSD-95 expression and BDNF levels in hippocampal homogenates, down-regulated DA and 5-HT levels, and suppressed microglial activation in SCZ mice. Moreover, Radix Bupleuri aqueous extract improved the integrity of the intestinal tract barrier. The 16 S rRNA sequencing of feces showed that Radix Bupleuri extract modulated the composition of gut flora. Lactobacillus abundance was decreased in SCZ mice and reversed by Radix Bupleuri aqueous extract administration which exhibited a significant negative correlation with IL-6, IL-1ß, DA, and 5-HT, and a significant positive correlation with BDNF levels in hippocampal tissues. The abundance of Parabacteroides and Alloprevotella was increased in SCZ mice. It was reversed by Radix Bupleuri aqueous extract administration, which exhibited a positive correlation with IL-6, IL-1ß, and 5-HT and a negative correlation with BDNF. In conclusion, Radix Bupleuri aqueous extract attenuates the inflammatory response in hippocampal tissues and modulates neurotransmitter levels, exerting its neuroprotective effect in SCZ. Meanwhile, the alteration of intestinal flora may be involved in this process, which is expected to be an underlying therapeutic option in treating SCZ.


Assuntos
Bupleurum , Microbioma Gastrointestinal , Extratos Vegetais , Esquizofrenia , Humanos , Animais , Camundongos , Maleato de Dizocilpina , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo , Interleucina-6 , Serotonina , Modelos Animais de Doenças , Interleucina-1beta
5.
Cell Transplant ; 32: 9636897231196493, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37688441

RESUMO

Adipose-derived stem cells (ADSCs) are employed as a promising alternative in treating cartilage injury. Regulating the inflammatory "fingerprint" of ADSCs to improve their anti-inflammatory properties could enhance therapy efficiency. Herein, a novel injectable decorin/gellan gum hydrogel combined with ADSCs encapsulation for arthritis cartilage treatment is proposed. Decorin/gellan gum hydrogel was prepared according to the previous manufacturing protocol. The liquid-solid form transition of gellan gum hydrogel is perfectly suitable for intra-articular injection. Decorin-enriched matrix showing an immunomodulatory ability to enhance ADSCs anti-inflammatory phenotype under inflammation microenvironment by regulating autophagy signaling. This decorin/gellan gum/ADSCs hydrogel efficiently reverses interleukin-1ß-induced cellular injury in chondrocytes. Through a mono-iodoacetate-induced arthritis mice model, the synergistic therapeutic effect of this ADSCs-loaded hydrogel, including inflammation attenuation and cartilage protection, is demonstrated. These results make the decorin/gellan gum hydrogel laden with ADSCs an ideal candidate for treating inflammatory joint disorders.


Assuntos
Artrite , Hidrogéis , Camundongos , Animais , Hidrogéis/farmacologia , Decorina/farmacologia , Cartilagem , Injeções Intra-Articulares , Células-Tronco , Inflamação/terapia , Autofagia
6.
Cell Signal ; 105: 110604, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36669606

RESUMO

Articular osteochondral injury is a common and frequently occurring disease in orthopedics that is caused by aging, disease, and trauma. The cytokine interleukin-1ß (IL-1ß) is a crucial mediator of the inflammatory response, which exacerbates damage during chronic disease and acute tissue injury. Human Wharton's jelly mesenchymal stem cell (HWJMSC) extracellular vesicles (HWJMSC-EVs) have been shown to promote cartilage regeneration. The study aimed to investigate the influence and mechanisms of HWJMSC-EVs on the viability, apoptosis, and cell cycle of IL-1ß-induced chondrocytes. HWJMSC-EVs were isolated by Ribo™ Exosome Isolation Reagent kit. Nanoparticle tracking analysis was used to determine the size and concentration of HWJMSC-EVs. We characterized HWJMSC-EVs by western blot and transmission electron microscope. The differentiation, viability, and protein level of chondrocytes were measured by Alcian blue staining, Cell Counting Kit-8, and western blot, respectively. Flow cytometer was used to determine apoptosis and cell cycle of chondrocytes. The results showed that HWJMSCs relieved IL-1ß-induced chondrocyte injury by inhibiting apoptosis and elevating viability and cell cycle of chondrocyte, which was reversed with exosome inhibitor (GW4869). HWJMSC-EVs were successfully extracted and proven to be uptake by chondrocytes. HWJMSC-EVs ameliorate IL-1ß-induced chondrocyte injury by inhibiting cell apoptosis and elevating viability and cycle of cell, but these effects were effectively reversed by knockdown of transferrin receptor (TFRC). Notably, using bone morphogenetic protein 2 (BMP2) pathway agonist and inhibitor suggested that HWJMSC-EVs ameliorate IL-1ß-induced chondrocyte injury through activating the BMP2 pathway via up-regulation TFRC. Furthermore, over-expression of runt-related transcription factor 2 (RUNX2) reversed the effects of BMP2 pathway inhibitor promotion of IL-1ß-induced chondrocyte injury. These results suggested that HWJMSC-EVs ameliorate IL-1ß-induced chondrocyte injury by regulating the BMP2/RUNX2 axis via up-regulation TFRC. HWJMSC-EVs may play a new insight for early medical interventions in patients with articular osteochondral injury.


Assuntos
Vesículas Extracelulares , Geleia de Wharton , Humanos , Condrócitos/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Regulação para Cima , Interleucina-1beta/farmacologia , Interleucina-1beta/metabolismo , Proteína Morfogenética Óssea 2/metabolismo , Vesículas Extracelulares/metabolismo , Receptores da Transferrina/metabolismo
7.
Br J Pharmacol ; 180(6): 701-720, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36368726

RESUMO

BACKGROUND AND PURPOSE: Artesunate, approved by the Food and Drug Administration in 2020 as a new treatment for severe malaria, also shows anti-tumour activity against acute myeloid leukaemia (AML). However, the underlying molecular mechanism(s) of artesunate-induced apoptosis and differentiation of AML is not clearly elucidated. EXPERIMENTAL APPROACH: The biological effects of artesunate on AML were explored in vitro, using cells from AML patients and leukaemia cell lines, and in vivo, using female C57BL/6 or nude nu/nu BALB/c mice. Underlying mechanisms in vitro were examined with the Trypan blue dye exclusion assay, western blotting and flow cytometry. Effects of artesunate in C57BL/6 mice intravenously injected with murine AML cells (C1498-GFP) were assessed by numbers of AML cells and by survival. KEY RESULTS: In vitro, artesunate promoted apoptosis and differentiation in both leukaemia cell lines and patient-derived primary leukaemia cells. Mechanistically, artesunate promoted cell apoptosis by triggering reactive oxygen species (ROS) production and increasing expression of the pro-apoptotic protein Bim. Interestingly, transferrin receptor 1 (TFRC)-mediated regulation of intracellular iron homeostasis also played an essential role in AML cell differentiation induced by artesunate. In vivo, artesunate slowed AML progression and prolonged survival in a mouse leukaemia model. Notably, artesunate displayed no apparent toxicity towards healthy haematopoietic stem cells, bone marrow mononuclear cells or experimental animals. CONCLUSION AND IMPLICATIONS: Artesunate is a safe agent with significant anti-leukaemia effects in mice and may serve as a promising chemotherapeutic strategy for patients with AML, based on two different mechanisms, targeting the ROS/Bim and the TFRC/Fe2+ pathways.


Assuntos
Antimaláricos , Leucemia Mieloide Aguda , Feminino , Animais , Camundongos , Artesunato/farmacologia , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Apoptose , Linhagem Celular Tumoral , Receptores da Transferrina/uso terapêutico
8.
Pediatr Res ; 93(1): 72-77, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35414668

RESUMO

BACKGROUND: The underlying mechanisms for infantile bronchopneumonia development remain unknown. METHODS: Peripheral blood mononuclear cell (PBMCs) and serum derived from severe and mild infantile bronchopneumonia were obtained, and the expression of various molecules was detected with enzyme-linked immunosorbent assay and quantitative PCR. Such molecules were also detected in granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced bone marrow-derived NFκB2-/- dendritic cells (DCs) or NIK SMI1 (NF-κB-inducing kinase inhibitor) administrated DCs. RESULTS: The relative mRNA expression levels of type I interferons (IFNs) (IFN-α4, IFN-ß), Th17 cell-associated markers (interleukin-17A, retinoic-acid-receptor-related orphan nuclear receptor gamma, and GM-CSF), and non-canonical NF-κB member (NFκB2) were significantly up-regulated in PBMCs and DCs derived from infantile bronchopneumonia compared with healthy controls. However, compared with Th17 cell-associated markers and non-canonical NF-κB molecules, the expression of IFN-α4 and IFN-ß was significantly inhibited in severe infantile bronchopneumonia compared with mild infantile bronchopneumonia. The relative protein expression of the above molecules also showed a similar expression pattern in the PBMCs or serum. NF-κB2 knockout or NIK SMI1 administration could reverse the diminished expression of IFN-ß in GM-CSF-induced bone marrow-derived DCs. CONCLUSIONS: GM-CSF-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in DCs contributes to the development of severe bronchopneumonia in infant. IMPACT: Granulocyte-macrophage colony-stimulating factor-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in dendritic cells is critical for the development of infantile bronchopneumonia. Our findings reveal a possible mechanism underlying the development of severe infantile bronchopneumonia. The results could provide therapeutic molecular target for the treatment of such disease.


Assuntos
Broncopneumonia , Interferon Tipo I , Humanos , Lactente , Fator Estimulador de Colônias de Granulócitos e Macrófagos , NF-kappa B , Leucócitos Mononucleares
9.
Org Biomol Chem ; 20(40): 7963-7971, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-36190455

RESUMO

Novel all-hydrocarbon cross-linked aza-stapled peptides were designed and synthesized for the first time by ring-closing metathesis between two aza-alkenylglycine residues. Three aza-stapled peptidic analogues based on the peptide dual inhibitor of p53-MDM2/MDMX interactions were synthesized and screened for biological activities. Among the three aza-stapled peptides, aSPDI-411 displayed increased anti-tumor activity, binding affinities to both MDM2 and MDMX, and cell membrane permeability compared to its linear peptide counterpart.


Assuntos
Proteínas Proto-Oncogênicas c-mdm2 , Proteína Supressora de Tumor p53 , Proteína Supressora de Tumor p53/química , Sequência de Aminoácidos , Peptídeos/química , Ligação Proteica , Hidrocarbonetos
10.
Am J Transl Res ; 14(8): 5263-5279, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105051

RESUMO

OBJECTIVE: Inhibin B (INHB) is one of the TGF-ß superfamily member, consisting of α (INHA) and ßB (INHBB) subunits. Studies have found that TGF-ß receptor 3 (TGFBR3) binds to a convex α subunit on the surface of INHB, and enhances the binding affinity of activin receptor type-2 (ACVR2A/B) to INHß subunit. This study tried to evaluate the roles of INHB subunits and its receptors (INHA, ACVR2A, ACVR2B, INHBB, TGFBR3) as prognostic biomarkers and therapeutic targets for the effective treatment of lung adenocarcinoma (LUAD). METHODS: We analyzed INHB subunits and its receptors' expression and the influence of LUAD from Oncomine, GEPIA, HCMDB, CancerSEA, TIMER databases and so on. Then, 41 cases of cancer tissue and 41 cases of adjacent epithelium were detected in LUAD patients by immunohistochemistry. RESULTS: INHA, ACVR2A, ACVR2B, INHBB were up-regulated while TGFBR3 was down-regulated in LUAD. INHA, ACVR2A and TGFBR3 were found to be strongly associated with high-grade malignancies and advanced TNM, only TGFBR3 expression was negatively correlated with LUAD metastasis probably mainly through cell adhesion molecules and the PI3K-Akt signaling pathway, univariate and multivariate analysis suggested that overall survival was lower in LUAD cases with low TGFBR3 levels. Further analysis revealed that low TGFBR3 expression was related to reduced infiltration of immune cells into the LUAD, promoting metastasis of LUAD cells. TGFBR3 expression negatively correlates with lymphatic metastasis and clinical stage in patients with LUAD. CONCLUSION: TGFBR3 could be a potential new metastatic biomarker for LUAD, with potential application as a prognostic marker and for immunotherapy of LUAD.

11.
Pharmacol Res ; 182: 106306, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35714823

RESUMO

As a broad-spectrum oral small molecule inhibitor targeting multikinase, sorafenib is currently approved for the clinical treatment of several types of cancer as a single agent. A considerable number of clinical trial results have indicated that combination therapies involving sorafenib have been shown to improve treatment efficacy and may lead to novel therapeutic applications. Ursolic acid (UA), a natural pentacyclic triterpene compound extracted from a great variety of traditional medicinal plants and most fruits and vegetables, exhibits a wide range of therapeutic potential, including against cancer, diabetes, brain disease, liver disease, cardiovascular diseases, and sarcopenia. In the present study, we investigated the antitumor effects of sorafenib in combination with ursolic acid and found that the two agents displayed significant synergistic antitumor activity in in vitro and in vivo tumor xenograft models. Sorafenib/UA induced selective apoptotic death and ferroptosis in various cancer cells by evoking a dramatic accumulation of intracellular lipid reactive oxygen species (ROS). Mechanistically, the combination treatment promoted Mcl-1 degradation, which regulates apoptosis. However, decreasing the protein level of SLC7A11 plays a critical role in sorafenib/UA-induced cell ferroptosis. Therefore, these results suggest that the synergistic antitumor effects of sorafenib combined with ursolic acid may involve the induction of Mcl-1-related apoptosis and SLC7A11-dependent ferroptosis. Our findings may offer a novel effective therapeutic strategy for tumor treatment.


Assuntos
Ferroptose , Neoplasias , Sistema y+ de Transporte de Aminoácidos , Apoptose , Linhagem Celular Tumoral , Humanos , Neoplasias/tratamento farmacológico , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Triterpenos , Ácido Ursólico
12.
Am J Pathol ; 190(1): 57-67, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610172

RESUMO

Acetaminophen (APAP) overdose-induced hepatotoxicity is the leading cause of drug-induced liver injury worldwide. The related injury pathogenesis is mainly focused on the liver. Here, the authors report that gut barrier disruption may also be involved in APAP hepatotoxicity. APAP administration led to gut leakiness and colonic epithelial chemokine (C-C motif) ligand 7 (CCL7) up-regulation. Intestinal epithelial cell (IEC)-specific CCL7 transgenic mice (CCL7tgIEC mice) showed markedly increased myosin light chain kinase phosphorylation, and elevated gut permeability and bacterial translocation into the liver compared to wild-type mice. Global transcriptome analysis revealed that the expression of hepatic proinflammatory genes was enhanced in CCL7tgIEC mice compared with wild-type animals. Moreover, CCL7 overexpression in intestinal epithelial cells significantly augmented APAP-induced acute liver injury. These data provide new evidence that dysfunction of CCL7-mediated gut barrier integrity may be an important contributor to APAP-induced hepatotoxicity.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Quimiocina CCL7/metabolismo , Células Epiteliais/patologia , Regulação da Expressão Gênica , Intestinos/fisiopatologia , Animais , Translocação Bacteriana , Permeabilidade da Membrana Celular , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Quimiocina CCL7/genética , Células Epiteliais/metabolismo , Perfilação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
13.
J Mater Chem B ; 7(2): 265-276, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-32254551

RESUMO

The clinical application of SN38 (7-ethyl-10-hydroxy-camptothecin) is severely restricted by its extremely low water solubility. Nanoaggregates formed by amphiphilic SN38 prodrugs have been widely used for the delivery of SN38. In this study, we used a hydrophobized SN38 prodrug, rather than a typical SN38 amphiphile, to construct rod-shaped nanoaggregates for efficient SN38 delivery. The hydrophobized SN38 was synthesized by conjugating SN38 with oleic acid using disulfanyl-ethyl carbonate as the linker. Interestingly, the resulting prodrug self-assembled into nanorods with high drug loading capacity (45%) and colloidal stability. Moreover, these nanorods displayed an impressively high redox-sensitivity to release 100% SN38 within 1 h in 10 mM DTT, versus 1% in phosphate buffer (pH 7.4). The efficient drug release resulted in an uncompromised in vitro cytotoxicity, which was comparable to free SN38 and nearly 93-fold more potent than CPT-11. Most importantly, these novel prodrug nanoaggregates exhibited potent antitumor activity in the CT26 colorectal cancer xenograft. The nanoaggregates of such redox-hypersensitive hydrophobized SN38 represent an effective alternative strategy for developing novel SN38 nanomedicines.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Irinotecano/farmacologia , Nanopartículas/uso terapêutico , Nanotubos , Pró-Fármacos/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Irinotecano/análogos & derivados , Irinotecano/síntese química , Masculino , Camundongos Endogâmicos BALB C , Nanomedicina , Solubilidade
14.
Sci Rep ; 6: 24996, 2016 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-27138292

RESUMO

Ionization potential (IP) is defined as the amount of energy required to remove the most loosely bound electron of an atom, while electron affinity (EA) is defined as the amount of energy released when an electron is attached to a neutral atom. Both IP and EA are critical for understanding chemical properties of an element. In contrast to accurate IPs and structures of neutral atoms, EAs and structures of negative ions are relatively unexplored, especially for the transition metal anions. Here, we report the accurate EA value of Fe and fine structures of Fe(-) using the slow electron velocity imaging method. These measurements yield a very accurate EA value of Fe, 1235.93(28) cm(-1) or 153.236(34) meV. The fine structures of Fe(-) were also successfully resolved. The present work provides a reliable benchmark for theoretical calculations, and also paves the way for improving the EA measurements of other transition metal atoms to the sub cm(-1) accuracy.

15.
PLoS One ; 10(6): e0126944, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26030771

RESUMO

BACKGROUND: Studies have indicated that statins influence the risks and mortality rates of several types of solid tumors. However, the association between statin use and survival in patients with colorectal cancer (CRC) remains unclear. METHODS: We searched the PubMed and Embase databases for relevant studies published up to September 2014 that assessed statin use and CRC prognosis. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). The secondary outcomes were disease-free survival (DFS) and recurrence-free survival (RFS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled with Mantel-Haenszel random-effect modeling. All statistical tests were two-sided. RESULTS: Four studies on post-diagnosis statin therapy and five studies on pre-diagnosis statin use were included in our meta-analysis of 70,608 patients. Compared with the non-users, the patients with post-diagnosis statin use gained survival benefits for OS (HR 0.76; 95% CI: 0.68 to 0.85, P<0.001) and CSS (HR 0.70; 95% CI: 0.60 to 0.81, P<0.001). In addition, we observed that pre-diagnosis statin use prolonged the survival of patients with CRC for OS (HR 0.70; 95% CI: 0.54 to 0.91, P=0.007) and CSS (HR 0.80; 95% CI: 0.74 to 0.86, P<0.001). However, we did not observe a survival benefit for DFS (HR 1.13; 95% CI: 0.78 to 1.62, P=0.514) or RFS (HR 0.98; 95% CI: 0.36 to 2.70, P=0.975) in the CRC patients with post-diagnosis statin use. CONCLUSIONS: Statin use before or after cancer diagnosis is related to reductions in overall and cancer-specific mortality in colorectal cancer survivors.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias Colorretais/diagnóstico , Humanos , Viés de Publicação , Análise de Sobrevida
16.
Artigo em Chinês | MEDLINE | ID: mdl-25916529

RESUMO

OBJECTIVE: To compare the efficacy and safety of subcutaneous immunotherapy with dermatophagoides pteronyssinus standardized extract given in conventional and cluster immunotherapy schedules for persistent allergic rhinitis. METHODS: One hundred and ten patients with moderate to severe allergic rhinitis caused by dust mites, in accordance with the immunotherapy inclusion criteria, were allocated to receive conventional immunotherapy as group A (n = 57) or cluster immunotherapy as group B (n = 53). In group A, 7 cases were lost to follow-up, the expulsion rate of group A was 12.28%; in group B, 1 case was lost to follow-up, the expulsion rate of group B was 1.89%. Nasal symptom scores, medicine scores and mini rhinoconjunctivitis quality of life questionnaire (Mini RQLQ) were recorded and compared before and after 7 weeks, 15 weeks, 1.0 year, 1.5 years, 2.0 years. All the scores were assessed to evaluate the clinical efficacy, and also the incidence of local and systemic adverse reactions were registered to evaluate the safety. SPSS 19.0 software was used to analyze the data. RESULTS: Nasal symptom scores, medicine scores and Mini RQLQ of both groups were significant lower than those before the treatment (all P < 0.05). Mini RQLQ and nasal symptom scores in cluster group (0.55 ± 0.21,0.57 ± 0.27) were more significantly declined than the conventional group after 7 weeks and 2.0 years of observation (all PMini RQLQ<0.05;nasal symptom scores: 1.41 ± 0.65, 0.83 ± 0.30, t value was 11.344, 5.649, both P < 0.05). The clinical efficiency rate in cluster group (86.5%, 94.2%) were more significantly highter than those (60.0%, 80.0%) in the conventional group after 7 weeks and 2 years of observation (χ(2) value was 9.224, 4.642, both P < 0.05). The medicine scores in cluster group (0.11 ± 0.04) was more significantly declined than conventional group (0.47 ± 0.11) after 7 weeks (t = 27.665, P < 0.05). The incidence of local and systemic adverse reactions during the incremental-dose phase and maintenance-dose phase compared with conventional immunotherapy were not significantly different (P > 0.05). CONCLUSION: The cluster immunotherapy is a safe treatment method which is more effective and faster than conventional immunotherapy to the dust mites caused allergic rhinitis.


Assuntos
Imunoterapia , Rinite Alérgica/terapia , Animais , Dermatophagoides pteronyssinus , Feminino , Humanos , Perda de Seguimento , Masculino , Medicina , Pyroglyphidae , Qualidade de Vida , Padrões de Referência , Rinite Alérgica/imunologia , Segurança , Inquéritos e Questionários
17.
Artigo em Chinês | MEDLINE | ID: mdl-22932134

RESUMO

OBJECTIVE: To investigate the complications of hyoid suspension with Repose system on obstructive sleep apnea hypopnea syndrome (OSAHS) and to find out the effective prevention strategies. METHODS: Forty four patients diagnosed by polysomnography as OSAHS were received hyoid suspension with Repose system from June 2005 to July 2009. The intraoperative and postoperative complications were analyzed retrospectively. The patients who reported abnormal swallowing were evaluated with water drinking test and video fluorography swallow study to assess biomechanical changes in swallowing. RESULTS: Incidence rate of perioperative titanium nial amotio was 15.9% (7/44). It was avoided by implanting titanium nial again. No perioperative complications occurred such as injury of superior laryngeal nerve, blood vessel and thyrohyoid membrane, fracture of hyoid bone, suture break. All patients developed dysfunctions of pronunciation and swallowing, edema of mouth floor, dysfunctions of movement of tongue that could relieved gradually after three days on most patients. No postoperative complications occurred such as titanium nial amotio, fat liquoring, edema of mouth floor, hematoma, infection, foreign body reaction, injury of root apex of anterior tooth, dysfunctions of movement and sensation of tongue, suture break and death. All patients had over 2 year postoperative follow up. Incidence rate of dysfunctions of pronunciation and swallowing was 4.5% (2/44) and 15.9% (7/44) respectively. Main situation for dysfunctions of pronunciation was speaking ambiguity. Major manifestations of swallowing abnormalities were occasional aspiration, food going down the wrong tube, food becoming stuck in the throat, deglutition with bowing head. Seven patients who had abnormal swallowing possessed normal water drinking test and occurred asynersis of hyoid movement and laryngeal elevation, but aspiration were not observed. Three patients presented obvious stagnation in epiglottic vallecula and sinus piriformis. CONCLUSIONS: Most complications of hyoid suspension with Repose system may be avoided or recovered on short term. Postoperative dysfunctions of pronunciation and swallowing may exist for a long time.


Assuntos
Osso Hioide/cirurgia , Complicações Intraoperatórias , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Complicações Pós-Operatórias , Apneia Obstrutiva do Sono/cirurgia , Adulto , Feminino , Humanos , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos
18.
Ultrason Sonochem ; 18(2): 553-61, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21036653

RESUMO

A simple ultrasound-assisted co-precipitation method in combination with a calcination treatment was developed to prepare magnetic Mg-Al layered double hydroxides composite as an adsorbent material to remove fluoride ions from aqueous solutions. The application of ultrasound in the preparation process promoted the formation of the hydrotalcite-like phase and drastically shortened the time being required for preparation of the crystalline composite. It was found that the ultrasound irradiation assistance decreased the size of the composite particles and increased the specific surface area, being favorable to the improvement of the adsorption capacity. The composite prepared under the ultrasound irradiation exhibited fairly high maximum adsorption capacity of fluoride (47.7 mg g(-1)), which was 60% higher than that of the composite prepared without the ultrasound irradiation assistance with the same aging time. The thermodynamic and kinetic studies demonstrated that the adsorption of fluoride ions involved the reconstruction of the layered structure in the composite. In addition, the magnetic composite can be effectively and simply separated by using an external magnetic field, and then regenerated by desorption and calcination.


Assuntos
Alumínio/química , Fluoretos/isolamento & purificação , Hidróxidos/química , Magnésio/química , Magnetismo , Ultrassom , Adsorção , Precipitação Química , Fluoretos/química , Concentração de Íons de Hidrogênio , Cinética , Temperatura , Termodinâmica , Difração de Raios X
19.
Artigo em Chinês | MEDLINE | ID: mdl-21055056

RESUMO

OBJECTIVE: To investigate the complications of tongue base reduction with radiofrequency tissue ablation on patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and find out the effective prevention strategies. METHODS: One hundred and ninety three OSAHS patients diagnosed by polysomnography were received tongue base reduction with radiofrequency tissue ablation between March 2008 and December 2009. The intraoperative and postoperative complications including bleeding, hematoma of tongue base, abscess of tongue base, altered taste, tongue numbness, deviation of tongue extension movement, dysfunctions of pronunciation and swallowing as well as the managements were analyzed retrospectively. RESULTS: No perioperative complications occurred. There were 186 cases with postoperative pain (96.4%), 155 cases with submandibular edema (80.3%). Nocturnal sudden cardiac death was encountered in 1 case and secondary bleeding in 1 case. There was no ulceration of tongue base mucose, hematoma or abscess of tongue base, altered taste, tongue numbness, tongue deviations, speech, swallowing and taste disorder after operation. The scale of postoperative pain claimed by patients was ranged between mild to moderate. Diclofenac suppository had analgesic effect for these patients. The quantity of bleeding in patient with secondary hemorrhage was so little that after proper treatment the bleeding was stopped and never happened again. Patient with nocturnal sudden cardiac death occurred at thirty-seven hours after operation, because of swelling and pain of tongue base aggravated sleep apnea and night hypoxemia inducing fatal arrhythmia. CONCLUSIONS: Postoperative pain and submandibular edema were 2 most common postoperative complications which can be easily controlled by antibiotics, Glucocorticoids and Diclofenac suppository. For those severe OSAHS patients accompanied by cardiopulmonary diseases, the tongue base reduction with radiofrequency tissue ablation can induce nocturnal sudden cardiac death. It is important to pay more attention on arrhythmias at night in severe OSAHS patients.


Assuntos
Ablação por Cateter/efeitos adversos , Complicações Pós-Operatórias , Apneia Obstrutiva do Sono/cirurgia , Língua/cirurgia , Adulto , Edema/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/patologia
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