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1.
BMC Musculoskelet Disord ; 25(1): 29, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166887

RESUMO

BACKGROUND: To evaluate the outcome of shoulder arthroscopy-assisted implantation of three-dimensional (3D)-printed titanium pads for recurrent shoulder dislocation with glenoid bone defects. METHODS: From June 2019 to May 2020, the clinical efficacy of 3D printed titanium pad implantation assisted by shoulder arthroscopy, for the treatment of recurrent shoulder dislocations with shoulder glenoid defects was retrospectively analyzed. The American Shoulder and Elbow Surgeons (ASES) shoulder, Rowe, and Constant scores were recorded before surgery and at 3 months, 6 months, 1 year, and 2 years after surgery. 3D computed tomography (CT) and magnetic resonance imaging were used to evaluate the location of the glenoid pad, bone ingrowth, joint degeneration, and osteochondral damage. RESULTS: The mean age of the 12 patients was 21.4 (19-24) years and the mean follow-up time was 27.6 (24-35) months. The Visual Analog Scale score significantly improved from 5.67 ± 1.98 preoperatively to 0.83 ± 0.58 postoperatively (p = 0.012). The postoperative ASES score was significantly increased to 87.91 ± 3.47 compared with preoperative ASES score (46.79 ± 6.45) (p < 0.01). Rowe and Constant scores also improved from 22.5 ± 12.34 and 56.58 ± 7.59 preoperatively to 90.83 ± 4.69 and 90.17 ± 1.89 at 2 years postoperatively, respectively. CT performed 2 years after surgery showed that the pad perfectly replenished the bone-defective part of the shoulder glenoid and restored the articular surface curvature of the shoulder glenoid in the anterior-posterior direction, and the bone around the central riser of the pad was tightly united. Magnetic resonance imaging 2 years after surgery showed that the humeral head osteochondral bone was intact, and there was no obvious osteochondral damage. CONCLUSIONS: 3D printed titanium pads are a reliable, safe, and effective surgical procedure for treating recurrent shoulder dislocations with glenoid bone defects.


Assuntos
Instabilidade Articular , Luxação do Ombro , Articulação do Ombro , Humanos , Adulto Jovem , Adulto , Luxação do Ombro/diagnóstico por imagem , Luxação do Ombro/cirurgia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Titânio , Seguimentos , Estudos Retrospectivos , Instabilidade Articular/cirurgia , Artroscopia/métodos , Impressão Tridimensional , Recidiva
2.
J Am Chem Soc ; 145(51): 28085-28095, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38032206

RESUMO

The creation of full stereoisomers of an organic compound comprising multiple contiguous stereocenters with simultaneous control over both relative and absolute configurations remains a significant challenge in synthetic chemistry. Using a cooperative catalysis strategy, we established an N-heterocyclic carbene/nickel-catalyzed enantio- and diastereodivergent propargylation reaction to access 3,3'-disubstituted oxindoles, enabling the incorporation of internal alkyne functionality and the introduction of a single quaternary or vicinal quaternary/tertiary stereogenic center. By selecting the appropriate combination of catalyst chirality, all four potential stereoisomers of α-quaternary propargylated oxindoles were synthesized in a predictable and precise way with remarkable yields, diastereoselectivities, and enantioselectivities from identical starting materials. The synthetic utility of this method was demonstrated in the concise asymmetric total synthesis of (-)-debromoflustramine B and (-)-C(ß-Me)-debromoflustramine B.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33685899

RESUMO

Acanthamoeba spp. are free-living protozoan that cause a serious human eye disease called Acanthamoeba keratitis (AK). Several new and effective medical therapy for AK patients remains highly debated and therefore, CHG is still considered one of the first lines of treatment for AK patients. We hypothesized that ocular microenvironmental factors are responsible for Acanthamoeba drug resistance and clinical AK treatment failure. To investigate the influence of the ocular surface on CHG treatment, we tested the effect of several ocular elements on the anti-amoeba activity of CHG. The suspected inhibitory elements, including mucin, albumin, human and amoeba cell lysates, live and heat-killed bacteria, and cornea, were added to the amoebicidal activity platform, where amoeba was incubated with CHG at varying concentrations. Mucin showed a significant inhibitory effect on CHG activity against Acanthamoeba castellanii In contrast, albumin did not affect CHG treatment. Furthermore, human and amoeba cell lysates as well as live and heat-killed bacterial suspensions also significantly inhibited CHG activity. Additionally, we found that pig corneas also reduced CHG activity. In contrast, dry eye drops and their major component, propylene glycol, which is commonly used as eyewash material, did not have an impact on CHG activity. Our results demonstrate the effect of ocular microenvironmental factors on CHG activity and suggest that these factors may play a role in the development of amoeba resistance to CHG and treatment failure.

4.
Opt Lett ; 48(23): 6108-6111, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039203

RESUMO

Polarization-sensitive photodetectors in the ultraviolet (UV) region have been favored for their great meaning in the field of military and civilian. UV photodetectors based on GaN have aroused much attention due to high photocurrent and high sensitivity. However, the dependence on external power sources and the limited sensitivity to polarized UV light significantly impede the practical application of these photodetectors in UV-polarized photodetection. Herein, a polarization-sensitive UV photodetector based on ReSe2/GaN mixed-dimensional van der Waals (vdWs) heterojunction is proposed. Owing to the high-quality junction and type-II band alignment, the responsivity and specific detectivity reach values of 870 mA/W and 6.8 × 1011 Jones, under 325 nm illumination, respectively. Furthermore, thanks to the strong in-plane anisotropy of ReSe2, the device is highly sensitive to polarized UV light with a photocurrent anisotropic ratio up to 6.67. The findings are expected to bring new opportunities for the development of highly sensitive, high-speed and energy-efficient polarization-sensitive photodetectors.

5.
Gynecol Oncol ; 170: 25-31, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36608384

RESUMO

OBJECTIVE: To assess the actual clinical application of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in Chinese patients with recurrent ovarian cancer, and to explore prognostic factors associated with progression-free survival (PFS). METHODS: We retrospectively assessed real-world clinical data from our hospital using the inclusion and exclusion criteria of representative randomized controlled trials, analyzed the prognosis, and performed univariate and multivariate analyses of prognostic factors. RESULTS: Between 2019 and 2022, the proportion of platinum-sensitive recurrence ovarian cancer patients who received PARPi maintenance therapy increased to 29.6%, 53.3%, 43.8% and 62.2%, respectively, each year. A total of 48 patients were included in the prognostic analysis, of which 32 and 16 received olaparib and niraparib, respectively. Using the criteria of the Study19 and SOLO2 studies, the olaparib group in our patients had coincidence rates of 56.3% and 18.8%, respectively. Using the criteria of the NOVA and NORA studies, the niraparib group had coincidence rates of 31.3% and 37.5%, respectively. Median PFS was 26.1 months (95% CI 20.2-32.1). Response to primary therapy was an independent prognostic factor for PFS (relative risk, 3.248; 95% CI 1.081-9.757, P = 0.036). CONCLUSIONS: PARPi maintenance therapy was also effective in real world applications. Complete response (CR) to primary therapy was an independent factor favorably affecting PFS. Therefore, primary treatment choices aimed at optimal cytoreduction during primary surgery and improving the CR rate should still be considered, which positively affects the long-term prognosis of patients in the new treatment mode.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma Epitelial do Ovário/tratamento farmacológico
6.
Biogerontology ; 24(5): 783-799, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36683095

RESUMO

Atherosclerosis threatens human health by developing cardiovascular diseases, the deadliest disease world widely. The major mechanism contributing to the formation of atherosclerosis is mainly due to vascular endothelial cell (VECs) senescence. We have shown that 17ß-estradiol (17ß-E2) may protect VECs from senescence by upregulating autophagy. However, little is known about how 17ß-E2 activates the autophagy pathway to alleviate cellular senescence. Therefore, the aim of this study is to determine the role of estrogen receptor (ER) α and ß in the effects of 17ß-E2 on vascular autophagy and aging through in vitro and in vivo models. Hydrogen peroxide (H2O2) was used to establish Human Umbilical Vein Endothelial Cells (HUVECs) senescence. Autophagy activity was measured through immunofluorescence and immunohistochemistry staining of light chain 3 (LC3) expression. Inhibition of ER activity was established using shRNA gene silencing and ER antagonist. Compared with ER-ß knockdown, we found that knockdown of ER-α resulted in a significant increase in the extent of HUVEC senescence and senescence-associated secretory phenotype (SASP) secretion. ER-α-specific shRNA was found to reduce 17ß-E2-induced autophagy, promote HUVEC senescence, disrupt the morphology of HUVECs, and increase the expression of Rb dephosphorylation and SASP. These in vitro findings were found consistent with the in vivo results. In conclusion, our data suggest that 17ß-E2 activates the activity of ER-α and then increases the formation of autophagosomes (LC3 high expression) and decreases the fusion of lysosomes with autophagic vesicles (P62 low expression), which in turn serves to decrease the secretion of SASP caused by H2O2 and consequently inhibit H2O2-induced senescence in HUVEC cells.


Assuntos
Receptor alfa de Estrogênio , Peróxido de Hidrogênio , Humanos , Receptor alfa de Estrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Células Cultivadas , Estradiol/farmacologia , Células Endoteliais da Veia Umbilical Humana , Autofagia
7.
J Transl Med ; 20(1): 496, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316782

RESUMO

BACKGROUND: Aberrant sialoglycans on the surface of tumor cells shield potential tumor antigen epitopes, escape recognition, and suppress activation of immunocytes. α2,3/α2,6Gal- and α2,6GalNAc (Gal/GalNAc)-linked sialic acid residues of sialoglycans could affect macrophage galactose-type lectins (MGL) mediated-antigen uptake and presentation and promote sialic acid-binding immunoglobulin-like lectins (Siglecs) mediated-immunosuppression. Desialylating sialoglycans on tumor cells could present tumor antigens with Gal/GalNAc residues and overcome glyco-immune checkpoints. Thus, we explored whether vaccination with desialylated whole-cell tumor vaccines (DWCTVs) triggers anti-tumor immunity in ovarian cancer (OC). METHODS: Sialic acid (Sia) and Gal/GalNAc residues on OC A2780, OVCAR3, and ID8 cells treated with α2-3 neuraminidase (α2-3NA) and α2-6NA, and Sigec-9 or Siglec-E and MGL on DCs pulsed with desialylated OC cells were identified using flow cytometry (FCM); RT-qPCR determined IFNG expression of T cells, TRBV was sequenced using Sanger sequencing and cytotoxicity of αß T cells was measured with LDH assay; Anti-tumor immunity in vivo was validated via vaccination with desialylated whole-cell ID8 vaccine (ID8 DWCTVs). RESULTS: Gal/GalNAc but not Sia residues were significantly increased in the desialylated OC cells. α2-3NA-modified DWCTV increased MGL but decreased Siglec-9 or Siglec E expression on DCs. MGLbright/Siglec-9dim DCs significantly up-regulated IFNG expression and CD4/CD8 ratio of T cells and diversified the TCR repertoire of αß T-cells that showed enhanced cytotoxic activity. Vaccination with α2-3NA-modified ID8 DWCTVs increased MGLbright/Siglec-Edim DCs in draining lymph nodes, limited tumor growth, and extended survival in tumor-challenged mice. CONCLUSION: Desialylated tumor cell vaccine could promote anti-tumor immunity and provide a strategy for OC immunotherapy in a clinical setting.


Assuntos
Vacinas Anticâncer , Neoplasias Ovarianas , Humanos , Camundongos , Animais , Feminino , Epitopos , Ácido N-Acetilneuramínico/metabolismo , Linhagem Celular Tumoral , Apoptose , Neoplasias Ovarianas/terapia , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Antígenos , Galactose/metabolismo
8.
Virol J ; 19(1): 90, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35619167

RESUMO

BACKGROUND: Persistent HPV16 infection is the leading risk factor for developing cervical cancer. Anti-L1 antibodies against HPV16 produced in HPV16 infections play diverse roles in the clearance of virus infection and prevention of persistence. It has been implicated that the cervicovaginal squamous epithelial cells actually express TRIM21 and that some HPV16 particles could escape leaky endosomal compartment into the cytosol and that Fc receptor TRIM21 directly neutralize infection by targeting antibody-opsonized viruses for proteasomal degradation. We explored whether anti-L1 antibody opsonized HPV16 pseudovirus (PsV) entered into the cytosol could be neutralized by TRIM21-mediated activation of a proteasomal pathway to reduce the chance of persistent HPV16 infection. METHODS: HPV16 PsV were generated and extracted in HEK 293FT cells co-transfected with pcDNA3.1-eGFP and p16sheLL plasmids according to the standard protocol. The HPV16 PsV with capsid protein L1 was characterized by fluorescence microscopy and western blot, and the HPV16 PsV titer and anti-L1-bound PsV entry efficiency were detected by flow cytometry. The expressions of transcription factors (TF) and cytokines elicited by the TRIM21-activated proteasomal pathway were confirmed by dual-luciferase reporter assay and RT-qPCR. The changes in HPV16 PsV load with or without inhibitors in the infected HEK 293FT cells were determinated by qPCR. RESULTS: Simultaneous transfection with pcDNA3.1-eGFP and p16sheLL plasmids into the HEK 293FT cells resulted in the self-assembly of HPV16 PsV with capsid protein L1. Both HPV16 PsV and anti-L1-bound HPV16 PsV could infect HEK 293FT cells. Anti-L1-bound PsV up-regulated TRIM21 mediated-activation of proteasome and increased expressions of TF and cytokines in the infected cells where HPV16 PsV load reduced by ~ 1000-fold in the presence of anti-L1 antibody, but inhibition of proteasomal activity increased HPV16 PsV load. CONCLUSION: Our preliminary results indicate that anti-L1 antibody entered with HPV16 PsV into the cells could mediate degradation of HPV16 PsV by TRIM21-activated proteasomal pathway intracellularly, giving anti-capsid protein L1 antibody a role in host defense of persistent HPV16 infection.


Assuntos
Infecções por Papillomavirus , Vírus de RNA , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Citocinas , Papillomavirus Humano 16/genética , Humanos
9.
Exp Cell Res ; 406(1): 112742, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34302857

RESUMO

BACKGROUND: Mutations at sites crucial for the interaction between RAD51 and BRC domains impair the ability of BRCA2 homologous recombination. We aimed to clarify whether BRCA2 BRC domain-associated mutation correlates with sensibility of platinum-based chemotherapy and survival in high-grade serous ovarian cancer (HGSOC). METHODS: We identified BRCA2 BRC domain mutations by sequencing PCR-amplified amplicons of genomic DNA isolated from tumor tissues and peripheral blood leukocytes (PBL)in 113 patients with advanced EOC, and assessed platinum-free interval (PFI), progression-free survival (PFS) and overall survival (OS). RESULTS: 21.23% (24 of 113) cases with somatic missense mutation but not germline mutation were identified. Among 24 cases with mutation, 33.3% (8 of 24) cases with nonsense mutation (C-terminal truncation) significantly prolonged median PFI (37 vs 8 months,P = 0.000), PFS (43 vs 14 months, p = 0.000) and OS (56 vs 31 months, P = 0.002); 66.7% (16 of 24) cases with missense mutation also prolonged median PFI (15 vs 8 months, P = 0.044), PFS (21 vs 14 months, P = 0.049) and OS (38 vs 31 months, P = 0.037), compared to those without any mutation. CONCLUSIONS: Somatic mutations in BRCA2 BRC domain confer a higher sensitivity to platinum-based therapy and are associated with a favourable survival in HGSOC.


Assuntos
Proteína BRCA2/genética , Cisplatino/uso terapêutico , Cistadenocarcinoma Seroso/genética , Mutação , Neoplasias Ovarianas/genética , Rad51 Recombinase/genética , Adulto , Sequência de Aminoácidos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteína BRCA2/metabolismo , Sequência de Bases , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Rad51 Recombinase/metabolismo , Transdução de Sinais , Análise de Sobrevida
10.
Exp Parasitol ; 239: 108312, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35738459

RESUMO

Acanthamoeba castellanii is a free-living protozoan that causes several severe human parasitic diseases such as Acanthamoeba keratitis and granulomatous encephalitis. A. castellanii feeds on bacteria, yeasts, and other organic particles as food sources, but the mechanisms of digestion in acanthamoebal cells are unclear. Rab GTPases participate in endosomal delivery in eukaryotes after phagocytosis. This study aimed to determine the potential functions of A. castellanii Rab7 (AcRab7), which is involved in phagocytosis, and the relationship between AcRab7 and further cellular physiological phenomena. In this study, the inhibitor CID1067700 (CID) was used to specifically inhibit the binding of nucleotides to confirm the potential functions of AcRab7. Cellular proliferation and ATP assays were also used to detect underlying cellular physiological functions after blocking the phagocytosis pathway. We found that AcRab7 expression increased as the co-culture time with Escherichia coli increased. Immunofluorescence staining showed that AcRab7 colocalized with lysosomes in its GTP-activating form. In addition, AcRab7 inhibition resulted in a reduction in cell proliferation and ATP levels. Our results suggest that AcRab7 participates in endosomal delivery and dominates energy production and cell growth.


Assuntos
Ceratite por Acanthamoeba , Acanthamoeba castellanii , Ceratite por Acanthamoeba/parasitologia , Acanthamoeba castellanii/fisiologia , Trifosfato de Adenosina , Escherichia coli , Humanos , Fagocitose
11.
Environ Toxicol ; 37(2): 349-361, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34741589

RESUMO

Ionizing radiation (IR) brings many health problems to humans, causing damage to the digestive system, hematopoietic system, and immune system. Natural compounds derived from plants have attracted widespread attention due to their low toxicity. Here, we found that 3,4,5-O-tricaffeoylquinic acid (tCQA) extracted from natural plant Azolla imbricata could significantly alleviate the systemic damage in mice caused by IR. In order to further explore the molecular mechanism of the radioprotective effect of tCQA, in vitro experiments confirmed that tCQA could attenuate the cytotoxic effect of IR on the colonic epithelial cell line NCM460 and alleviate the IR-induced mitochondrial dysfunction characterized by the decrease of mitochondrial transmembrane potential, ROS production, and caspase-dependent apoptosis. In addition, the generation of ROS induced by H2 O2 could also be reversed by tCQA. Then, Western blot demonstrated that tCQA could reverse the MAPK signaling pathway activated by IR. However, the inhibitory effect of tCQA on JNK and P38 levels activated by the JNK agonist anisomycin is not obvious; meanwhile, tCQA could inhibit the activation of JNK/P38 induced by H2 O2 , which suggests that tCQA might inhibit the JNK/P38 signaling pathway by reducing ROS. In short, tCQA inhibits the generation of ROS caused by IR, and then regulates the activity of caspase in the mitochondrial pathway by inhibiting the JNK/P38 signaling pathway, thereby alleviating the apoptosis of NCM460. This research provides an experimental basis for the development of new types of radioprotective agents for medical diagnosis and radiotherapy.


Assuntos
Sistema de Sinalização das MAP Quinases , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Apoptose , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Potencial da Membrana Mitocondrial , Camundongos , Radiação Ionizante , Espécies Reativas de Oxigênio , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
Phytochem Anal ; 33(2): 239-248, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34390060

RESUMO

INTRODUCTION: The roots of Stephania succifera are used in traditional medicine for the treatment of several diseases. Research on this plant has mainly focused on bioactive alkaloids from the roots, and no previous work on compounds from the abundant leaves has yet been reported. OBJECTIVE: To identify and compare alkaloidal compounds in S. succifera roots and leaves and to predict the potential bioactivity of some alkaloids. METHODS: High-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF-MS/MS) was employed to identify alkaloidal compounds from S. succifera. The potential targets and bioactivities of most alkaloids were predicted using the PharmMapper server. RESULTS: Fifty-six alkaloidal compounds, including protoberberine-, aporphine-, proaporphine-, benzylisoquinoline-, and lactam-type alkaloids, were identified or tentatively identified in S. succifera roots and leaves based on the HPLC-MS data. Forty-one compounds have not been previously reported in S. succifera and eight of them have not been previously reported in the literature. Twenty-four alkaloidal compounds were found in both roots and leaves. Twelve potential targets with different indications were predicted for some alkaloids. CONCLUSION: Comparison of chemical constituents and their potential bioactivities for S. succifera roots and leaves indicated that diverse bioactive alkaloids were present in the leaves as well as the roots. PharmMapper provided new directions for bioactivity screening. This study will be helpful for further understanding the medicinal components of S. succifera and the rational utilisation of plant resources.


Assuntos
Alcaloides , Stephania , Alcaloides/análise , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Folhas de Planta/química , Stephania/química , Espectrometria de Massas em Tandem/métodos
13.
Sensors (Basel) ; 22(11)2022 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35684917

RESUMO

Micro-expressions are rapid and subtle facial movements. Different from ordinary facial expressions in our daily life, micro-expressions are very difficult to detect and recognize. In recent years, due to a wide range of potential applications in many domains, micro-expression recognition has aroused extensive attention from computer vision. Because available micro-expression datasets are very small, deep neural network models with a huge number of parameters are prone to over-fitting. In this article, we propose an OF-PCANet+ method for micro-expression recognition, in which we design a spatiotemporal feature learning strategy based on shallow PCANet+ model, and we incorporate optical flow sequence stacking with the PCANet+ network to learn discriminative spatiotemporal features. We conduct comprehensive experiments on publicly available SMIC and CASME2 datasets. The results show that our lightweight model obviously outperforms popular hand-crafted methods and also achieves comparable performances with deep learning based methods, such as 3D-FCNN and ELRCN.


Assuntos
Fluxo Óptico , Face , Expressão Facial , Redes Neurais de Computação , Reconhecimento Psicológico
15.
Bioconjug Chem ; 31(8): 2008-2020, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32628454

RESUMO

Paclitaxel (PTX) resistance in most epithelial ovarian cancers (EOCs) with increasing membrane expression of mucin 16 (MUC16) is mediated by the Toll-like receptor-myeloid differentiation factor 2/myeloid differentiation factor 88 (TLR4-MD2/MyD88) signaling pathway. 6-Shogaol (6S), an α,ß-unsaturated carbonyl compound with lipophilic property, can block PTX-induced formation of the TLR4-MD2 complex that activates the MyD88/NF-κB signaling pathway. Herein, to improve the effectiveness of 6S, augment the sensibility of PTX, and enhance the targeting ability of PTX-resistant cancer therapies, we report a class of 6S-loaded phase transition nanobubbles conjugated with the MUC16 antibody (6S@NBs-MUC16A), which can enhance the sensitivity of PTX to EOC cells through ultrasound-controlled targeted-delivery of 6S. The 6S@NB-MUC16A could enhance the targeting efficiency and organizational distribution of 6S in MyD88+ EOC area, and the 1 MHz ultrasound can be used as an initiator to trigger the "explosion" of nanobubbles and promote the 6S release. Furthermore, in vivo assessment results indicate that ultrasound-augmented 6S@NB-MUC16A can significantly improve the response of EOC to PTX and the inhibition ratio of tumor growth compared to the control-treated with PTX alone, and exhibit less toxicity to the critical organs. The ultrasound-augmented 6S@NB-MUC16A with less cytotoxicity could be a potentially useful nanosystem to surmount PTX resistance in EOC, which provides potential possibilities for the applications in the biological field.


Assuntos
Antineoplásicos/farmacologia , Catecóis/farmacologia , Paclitaxel/farmacologia , Transição de Fase , Animais , Catecóis/administração & dosagem , Catecóis/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Camundongos , Camundongos Nus , Fator 88 de Diferenciação Mieloide , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
BMC Cancer ; 20(1): 315, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293355

RESUMO

BACKGROUND: The enrichment of cancer stem cell-like cells (CSCs) has been considered to be responsible for tumor progression after an initial response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung adenocarcinoma (NSCLC/ADC). CSCs with ALDH1A1bright /CD44high expression contribute to the TKIs resistance in NSCLC/ADC cells. All-trans retinoic acid (ATRA) has been shown to be a potential targeted therapy against CSCs due to its ability to inhibit ALDH1A1 activity. We therefore investigated whether ATRA could circumvent the resistance to improve the response to gefitinib in NSCLC/ADC cells. METHODS: Treatment of NSCLC/ADC A549 and H1650 cells with gefitinib enriched the gefitinib surviving cells (GSCs). The expression of ALDH1A1 and CD44 and the IC50 values for gefitinib were determined by flow cytometry (FCM) and crystal violet assay in GSCs and ATRA-treated GSCs, respectively. Using DEAB as the positive control, direct inhibitory effect of ATRA on ALDH1A1 activity was determined by ALDEFLUOR assay, RESULTS: GSCs showed higher expression of ALDH1A1 and CD44 and IC50 values for gefitinib than their respective parental cells, suggesting that gefitinib can lead to propagation of CSC-enriched gefitinib-resistant cells. Treatment with ATRA was found to significantly reduce the increased expression of ALDH1A1 and CD44 and the IC50 values for gefitinib in A549GSC and H1650GSC cells, and ATRA could directly inhibit active ALDH1A1 as compared to DEAB. CONCLUSION: Our findings suggest that combination treatment with ATRA prevents gefitinib-induced enrichment of ALDH1A1bright/CD44high CSCs and enhances gefitinib-induced growth inhibition of NSCLC/ADC cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Gefitinibe/farmacologia , Neoplasias Pulmonares/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Tretinoína/farmacologia , Células A549 , Família Aldeído Desidrogenase 1/genética , Família Aldeído Desidrogenase 1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Concentração Inibidora 50 , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Células-Tronco Neoplásicas/metabolismo , Retinal Desidrogenase/genética , Retinal Desidrogenase/metabolismo , Regulação para Cima/efeitos dos fármacos
17.
Biogerontology ; 21(5): 549-557, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32172411

RESUMO

17ß-estradiol (17ß-E2) has been implicated in inhibiting the senescence of vascular endothelial cells (VEC) and slowing down the process of atherosclerosis. However, the underlying molecular mechanisms are still unknown. In this study, we examined the roles of SIRT3 in 17ß-E2-induced autophagy and 17ß-E2-mediated inhibition of hydrogen peroxide (H2O2)-induced senescence in Human umbilical vein endothelial cells (HUVEC). Cellular senescence was measured by immunoblot analysis with antibodies against phosphorylated Rb and senescence-associated ß-galactosidase staining. Immunoblot analysis with antibodies against LC3 and p62 was performed to determine autophagy flux. Our findings show that 17ß-E2 activates SIRT3 promoter and upregulates SIRT3 gene expression in HUVEC cells. siRNA-mediated silencing of SIRT3 gene expression inhibits 17ß-E2-induced processing of LC3-I to LC3-II and degradation of p62, two widely-used makers of autophagy. SIRT3 knockdown also blocks 17ß-E2-induced inhibition of cellular senescence triggered by H2O2. Our data further reveal that SIRT3 knockdown impairs 17ß-E2-induced co-localization of LC3 and VDAC1, a marker protein on mitochondria, when HUVEC cells were co-treated with H2O2. Together, our findings suggest that 17ß-E2 upregulates SIRT3 gene expression by activating SIRT3 promoter and then promotes autophagy, which in turn serves to remove dysfunctional mitochondria caused by H2O2 and consequently inhibit H2O2-induced senescence in HUVEC cells.


Assuntos
Autofagia , Senescência Celular , Estradiol/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Sirtuína 3/metabolismo , Inativação Gênica , Humanos , Peróxido de Hidrogênio , Mitocôndrias/patologia
18.
Mol Biol Rep ; 47(3): 2197-2203, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32078092

RESUMO

Stephania is a medicinal plants-rich genus of Menispermaceae. However, the identification of morphologically-similar species in Stephania is difficult using the currently reported methods. The indiscriminate overexploitation of Stephania plants has resulted in clinical misuse and endangerment of many species, which necessitates the development of an efficient and reliable method for species authentication. Therefore, six candidate DNA barcode sequences (ITS, ITS2, psbA-trnH, matK, rbcL, and trnL-F) were tested for their capacity to identify Stephania species. The barcodes were analyzed either as a single region or in combination by tree-based [neighbor-joining (NJ) and Bayesian inference (BI)], distance-based (PWG-distance), and sequence similarity-based (TaxonDNA) methods. Amplification and sequencing success rates were 100% for all six candidate barcodes. A comparison of six barcode regions showed that ITS exhibited the highest number of variable and informative sites (182/179), followed by psbA-trnH (173/162). DNA barcoding gap assessment showed that interspecific distances of the six barcodes were greater than intraspecific distances. The identification results showed that species discrimination rates of combination barcodes were higher than those of single-region barcodes. Based on best match and best close match methods, the ITS+psbA-trnH combination exhibited the highest discrimination power (93.93%). Further, all Stephania species could be resolved in the phylogenetic trees based on ITS+psbA-trnH (NJ, BI). This study demonstrates that DNA barcoding is an efficient method to identify Stephania species and recommends that the ITS+psbA-trnH combination is the best DNA barcode for the identification of Stephania species.


Assuntos
Código de Barras de DNA Taxonômico , Stephania/classificação , Stephania/genética , Biologia Computacional/métodos , DNA de Plantas , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
19.
Macromol Rapid Commun ; 41(10): e2000038, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32285525

RESUMO

Streoregular poly(vinyl alcohol) is hard to obtain because vinyl alcohol is unstable relative to its tautomer acetaldehyde, and the monomer precursor vinyl ester is poisonous to the coordination catalyst. Herein, the coordination polymerization of 2-vinyl-2,1-borazanaphthalene (BN2VN) is reported by the linked or unlinked half-sandwich ligands attached scandium precursors ((FluSiMe3 )Sc(CH2 SiMe3 )2 (THF) (THF = tetrahydrofuran, 1), (FluCH2 CH2 -NHC-R)Sc(CH2 SiMe3 )2 (THF) (R = mesityl 2, i Pr 3, Me 4), and (FluCH2 Py)Sc(CH2 SiMe3 )2 (5) for the first time. Among these precursors, complex 5 converts 600 equivalents of BN2VN into polymer within 5 min to reach an activity as high as 8.99 × 105 g molSc -1 h-1 . The resultant products show excellent syndiotacticity and melting temperatures above 300 °C, which can be transferred to syndiotactic poly(vinyl alcohol) with 90% rr triad content by postpolymerization oxidation.


Assuntos
Naftalenos/química , Álcool de Polivinil/síntese química , Complexos de Coordenação/química , Estrutura Molecular , Polimerização , Álcool de Polivinil/química , Escândio/química , Estereoisomerismo
20.
Health Qual Life Outcomes ; 18(1): 269, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758237

RESUMO

BACKGROUND: The original version of Victorian Institute of Sport Assessment-Patella Questionnaire (VISA-P) is developed in English, and aimed to assess the severity of patellar tendinopathy symptoms. Before used in China, it should be translated to Chinese version. OBJECTIVES: Our aim is to make a translation/cross-culturally adaption for the VISA-P into simplified Chinese version (VISA-PC). And primarily validate the VISA-PC in Chinese speaking population. METHODS: The translation process of VISA-P questionnaire into simplified Chinese version (VISP-PC) followed the International recognized guideline. Cross-cultural adaptation was carried out with a clinical measurement study. A total of 128 projects which consisted 33 healthy students, 39 patients with patellar tendinopathy and 56 military students (receive military training as at-risk population) were included into this study. Internal consistency was evaluated with Cronbach's alpha, and test-retest reliability was assessed with intraclass correlation coefficients (ICCs). Construct validity and floor and ceiling effects were also tested. RESULTS: The scores were 95.84 ± 5.97 of healthy group, 91.87 ± 9.03 of at-risk group, 62.49 ± 11.39 of pathological group. There is no ceiling and floor effect of VISA-PC. The Cronbach's alpha (0.895) and ICC (0.986) values showed good internal consistency and reliability. There were high correlations between VISA-PC and Kujala patellofemoral score (r = 0.721). VISA-PC score also had good correlation with the relevant SF-36 items. CONCLUSION: The VISA-PC was well translated into simplified Chinese version (VISA-PC), which is reliable and valid for Chinese-speaking patients with patellar tendinopathy. LEVEL OF EVIDENCE: II.


Assuntos
Ligamento Patelar/fisiopatologia , Inquéritos e Questionários/normas , Tendinopatia/fisiopatologia , Adaptação Fisiológica , Adulto , Traumatismos em Atletas/fisiopatologia , Estudos de Casos e Controles , China , Comparação Transcultural , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Reprodutibilidade dos Testes , Tendinopatia/diagnóstico , Adulto Jovem
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