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2.
ACS Pharmacol Transl Sci ; 7(2): 421-431, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38357273

RESUMO

In traditional Chinese medicine, Radix Astragali has played a vital role in treating progressive fibrotic diseases. One of its main active components, astragaloside IV, is a promising anti-fibrotic treatment despite its extremely low bioavailability. Our study aimed to optimize sodium astragalosidate (SA) by salt formation to improve solubility and oral absorption for anti-fibrotic therapy in vivo. Isoproterenol-induced myocardial fibrosis rat models and obese BKS-db mice presenting diabetic kidney fibrosis were used in this study. Daily oral administration of SA (20 mg/kg) for 14 days ameliorated cardiac fibrosis by reducing collagen accumulation and fibrosis-related inflammatory signals, including TNF-α, IL-1ß, and IL-6. In db/db mice, SA (5,10, and 20 mg/kg per day for 8 weeks) dose-dependently alleviated lipid metabolism impairment and renal dysfunction when administered orally. Furthermore, Western blot and immunohistochemistry analyses demonstrated that SA treatment inhibited renal fibrosis by suppressing TGF-ß1/Smads signaling. Taken together, our findings provide the oral-route medication availability of SA, which thus might offer a novel lead compound in preclinical trial-enabling studies for developing a long-term therapy to treat and prevent fibrosis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-37971580

RESUMO

BACKGROUND: Pulmonary fibrosis (PF) is a progressive lung disorder with a poor prognosis. GBE50 is a new standardized Ginkgo biloba extract that has been widely used in cardiovascular diseases. However, the protective mechanism of GBE50 against PF remains to be elucidated. METHODS: C57BL/6J mice were treated with bleomycin (Bleo) to induce PF in the presence or absence of GBE50. Protein content in bronchoalveolar lavage fluid (BALF) and wet weight/dry weight ratio were examined for analysis of pulmonary edema. Hematoxylin-eosin staining and Masson trichrome staining were used for histopathological observation of murine lung tissues. Ashcroft score was used for semi-quantitation of lung fibrosis degree. RT-qPCR was utilized for assessing mRNA levels of pro-fibrotic mediators in lung tissues. TUNEL staining was implemented for cell apoptosis assessment. The levels of oxidative stress- and inflammation-related markers were evaluated by corresponding commercial assay kits. Western blotting was used to evaluate levels of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling- and transforming growth factor (TGF)-ß1/SMAD signaling-related proteins. RESULTS: GBE50 alleviated lung injury and severity of fibrosis, reduced collagen deposition and cell apoptosis in lung tissues, and suppressed inflammatory response and oxidative stress injury in Bleo-stimulated PF mice. GBE50 activated Nrf2 signaling pathway and inactivated TGF-ß1/SMAD signaling pathway in the lungs of Bleo-induced PF mice. Inhibition of Nrf2 signaling reversed GBE50-mediated inactivation of TGF-ß1/SMAD signaling and attenuation of inflammation and oxidative stress in Bleo-induced PF mice. CONCLUSION: GBE50 protects against Bleo-induced PF in mice by mitigating fibrosis, inflammation and oxidative stress via Nrf2 and TGF-ß1/SMAD signaling pathways.

4.
Materials (Basel) ; 16(20)2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37895702

RESUMO

QBe2.0 strips were used to fabricate spiral tubes and actuators for controlled extension (STACERs) through the winding and stabilization method, which is a novel technique for obtaining STACERs. The raw strips and the STACERs were investigated using tensile tests and SEM for the mechanical properties and fractography observation, employing specialized test equipment for service performance, and via XRD, EBSD, and TEM were used to test the residual stress and microstructure evolution. The tensile strength/elongation for raw strips was 485.8 MPa/60%, while for STACERs, tensile strength increased by 834.67 MPa to 646 MPa, and the elongation rate decreased by 12% to 19.3%. The fractography showed that the fracture mode was ductile. The service performance tests indicated that STACERs obtained under 320 °C had a higher driving force, good pointing accuracy, and high bending stiffness, while the residual stress of raw strips was τxy = -6 MPa; for STACERs obtained between 290 °C and 350 °C, τxy decreased from -5 MPa to -74 MPa, then increased from -74 MPa to 21 MPa, and the optimum fabricating parameter was 320 °C + 2 h. The EBSD results showed that LABs and HABs for raw strips and STACERs at 320 °C + 2 h accounted for 3-97% and 24.5-75.5%, the grain sizes were 7.07 µm and 3.67 µm, and the twin fraction decreased from 57.3% to 31.8%, respectively. The KAM and Schmid factor maps indicated that the STACER was prone to recovering and recrystallizing. Coupled with the EBSD results, the TEM results indicated that the strengthening mechanism for raw strips is twinning strengthening, while that for STACER is grain-refining strengthening with a precipitation of the γ″ phase. It is a meaningful novelty that the relationship between the macro properties and microstructure has been elucidated.

5.
Heliyon ; 9(8): e19155, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37664700

RESUMO

Introduction: Bufei Huayu Decoction (BFHY) is a clinical prescription with reported efficacy in enhancing the therapeutic outcomes of chemotherapeutic agents for non-small cell lung cancer (NSCLC). However, the underlying metabolic mechanism of BFHY's action remains unexplored. Objective: The objective of this study is to investigate the global metabolic effects of cisplatin and cisplatin plus BFHY on NSCLC. Methods: Three groups (NSCLC, cisplatin, and cisplatin + BFHY) underwent a serum metabolomics procedure based on UHPLC-QE-MS. Then, a pathway analysis was carried out using MetaboAnalyst 3.0 to elucidate the therapeutic action routes of cisplatin and cisplatin plus BFHY in NSCLC. Results: In the subcutaneous NSCLC model, both cisplatin and cisplatin + BFHY reduced the tumor volume and caused cell death. In comparison to cisplatin alone, cisplatin + BFHY showed a stronger tumor-suppressing impact. Furthermore, the same 16 metabolic signaling pathways were shared by the cisplatin and cisplatin + BFHY treatments. These typical metabolites are mainly involved in amino acid metabolism, lipid mobilization, nucleic acid metabolism and carbohydrate metabolites. Conclusions: Potential biomarkers and metabolic networks of cisplatin and cisplatin + BFHY's anti-tumor actions are revealed in our investigation.

6.
Int J Genomics ; 2023: 3568416, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37252635

RESUMO

Aim: We sought to profile gut microbiota's role in combination of Bu Fei Hua Yu (BFHY) with cisplatin treatment. Methods: Non-small cell lung cancer (NSCLC) mice model were constructed followed by treatment with cisplatin alone or combined with BFHY. Mice weight and tumor volume were measured during the experiment. And mice cecum were detected by hematoxylin and eosin, cecum contents were collected for Enzyme Linked ImmuneSorbent Assay, and stool were profiled for metagenomic sequencing. Results: Combination of BFHY with cisplatin treatment decreased the tumor growth and relieved the damage of cecum. Expressions of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), monocyte chemotactic protein 1 (MCP), and interferon-γ (IFN-γ) were decreased compared with cisplatin treatment alone. Linear discriminant analysis effect size analysis showed that g_Parabacteroides was downregulated and g_Escherichia and g_Blautia were upregulated after cisplatin treatment. After combination with BFHY, g_Bacteroides and g_Helicobacter were decreased. g_Klebsiella, g_Unclssified_Proteobacteria, and g_Unclssified_Clostridiates were increased. Moreover, heatmap results showed that Bacteroides abundance was increased significantly after cisplatin treatment; BFHY combination treatment reversed this state. Function analysis revealed that multiple functions were slightly decreased in cisplatin treatment alone and increased significantly after combination with BFHY. Conclusion: Our study provided evidence of an efficacy of combination of BFHY with cisplatin on treatment of NSCLC and revealed that gut microbiota plays a role in it. The above results provide new ideas on NSCLC treatment.

7.
J Pharm Biomed Anal ; 231: 115414, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37141677

RESUMO

Radix Astragali (RA) is commonly used in Asian herbal therapy or food supply, and astragalosides and flavonoids are its major components with diverse pharmaceutical effects. To provide new information on the potential cardiovascular benefits of RA administered orally, the bioaccessibility of these compounds with relevant in vitro digestion parameters was determined for four digestion phases (oral, gastric, small and large intestines) by ultrahigh-performance liquid chromatography quadrupole time-of-flight-mass spectrometry (UPLC-Q-TOF/MS). Meanwhile, we compared the effects of digestion products on advanced glycation end products (AGEs)-induced intracellular reactive oxygen species (ROS) levels in a human arterial endothelial cells (HAECs) model, and studied the potential of RA against oxidative stress-related cardiovascular disease. The changes of saponins and flavonoids composition and antioxidant activity after digestion in intestines were mainly due to the astragaloside IV (AS-IV) biosynthesis involving saponins acetyl isomerization and deacetylation, and the flavonoid glycosides converted to aglycone by deglycosylation processes. All these results suggest that acetyl biotransformation of RA in small intestine directly influenced the response to oxidative stress, and might provide a reference for elucidation of the multi-component action after oral RA in cardiovascular health care.


Assuntos
Medicamentos de Ervas Chinesas , Saponinas , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Células Endoteliais/química , Saponinas/química , Medicamentos de Ervas Chinesas/química , Flavonoides/análise , Biotransformação , Digestão
8.
Materials (Basel) ; 16(8)2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37109806

RESUMO

The Co40NiCrMo alloy, used for STACERs fabricated by the CSPB (compositing stretch and press bending) process (cold forming) and the winding and stabilization (winding and heat treatment) method, was investigated with regard to its tensile property, residual stress, and microstructure. The Co40NiCrMo STACER prepared by the winding and stabilization method was strengthened with lower ductility (tensile strength/elongation: 1562 MPa/5%) compared to that prepared by CSPB (tensile strength/elongation: 1469 MPa/20.4%). The residual stress of the STACER prepared by winding and stabilization (τxy = -137 MPa) showed consistency with that obtained through CSPB (τxy = -131 MPa). Combined with the driving force and pointing accuracy performances, the optimum heat treatment parameters for the winding and stabilization method were determined as 520 °C + 4 h. The HABs in the winding and stabilization STACER (98.3%, of which 69.1% were Σ3 boundaries) were much higher than those in the CSPB STACER (34.6%, of which 19.2% were Σ3 boundaries), while deformation twins and h.c.p ε-platelet networks were present in the CSPB STACER, and many more annealing twins appeared in the winding and stabilization STACER. It was concluded that the strengthening mechanism in the CSPB STACER is the combined action of deformation twins and h.c.p ε-platelet networks, while for the winding and stabilization STACER, annealing twins play the dominant role.

9.
Front Pharmacol ; 13: 987882, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36210826

RESUMO

LS-102 is a new derivative of astragaloside IV (AGS IV) that has been shown to possess potentially significant cardioprotective effects. However, there are no reports concerning its interaction with human serum albumin (HSA) and toxicology in vertebrates. The present investigation was undertaken to characterize the interaction of AGS IV and LS-102 with HSA using equilibrium dialysis and UHPLC-MS/MS methods, along with computational methods. Notably, the effects of AGS IV and LS-102 were studied in vivo using the zebrafish embryo model. Markers related to embryonic cardiotoxicity and thrombosis were evaluated. We showed that the plasma protein binding rate of AGS IV (94.04%-97.42%) was significantly higher than that of LS-102 (66.90%-69.35%). Through site marker competitive experiments and molecular docking, we found that AGS IV and LS-102 were located at the interface of subdomains IIA and IIIA, but the site I might be the primary binding site. Molecular dynamics revealed that AGS IV showed a higher binding free energy mainly due to the stronger hydrophobic and hydrogen bonding interactions. Moreover, the secondary structure implied no obvious effect on the protein structure and conformation during the binding of LS-102. LS-102 significantly ameliorated the astramizole-induced heart rate slowing, increased SV-BA spacing, and prevented arachidonic acid-induced thrombosis in zebrafish. To our knowledge, we are the first to reveal that LS-102 binds to HSA with reversible and moderate affinity, indicating its easy diffusion from the circulatory system to the target tissue, thereby providing significant insights into its pharmacokinetic and pharmacodynamic properties when spread in the human body. Our results also provide a reference for the rational clinical application of LS-102 in the cardiovascular field.

10.
ACS Appl Mater Interfaces ; 14(25): 28781-28791, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35709472

RESUMO

Organic cocrystal exhibits excellent photothermal conversion (PTC), but how the intermolecular interactions of cocrystals regulate the PTC is obscure. Here, two isomeric donor molecules (phenanthrene and anthracene) and two electron-withdrawing molecules (7,7,8,8,8-tetracyanodimethylquinone and 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinone dimethane) are self-assembled into the four cocrystals (PTQ, PFQ, ATQ, and AFQ). By changing the molecular configuration of the donor and the electron-withdrawing ability of the acceptor, the intrinsic influencing factors of the intermolecular interaction on the PTC were explored. Under near-infrared laser (808 nm) irradiation, the PTC efficiencies of PTQ, PFQ, AFQ, and ATQ are 35.85, 44.74, 57.00, and 60.53%, respectively. Based on the single-crystal X-ray diffraction, ultrafast time-resolved transient absorption, and excited-state theoretical calculations, we found that the π-π stacking in ATQ and AFQ is conducive to promoting the near-infrared light-harvesting ability and the p-π interaction of cocrystals can regulate the nonradiative rotation of -C(C≡N)2 groups, resulting in a tunable near-infrared PTC via the isomeric cocrystals. Accordingly, the evaporation rate of the porous polyurethane-AFQ foam can reach 1.33 kg·m-2·h-1 in the simulated solar-driven water evaporation system. This work provides a strategy to boost the PTC by the intermolecular interactions of cocrystal materials.

11.
Bioengineered ; 12(2): 10176-10186, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34874810

RESUMO

MicroRNA-506 (miR-506), a miRNA, has been proven to act as a tumor suppressor gene in nonsmall-cell lung cancer (NSCLC); Tubby-like protein 3 (TULP3) is a potential target gene of miR-506. This study investigates whether miR-506 can prevent NSCLC progression by mediating TULP3. In vivo and in vitro experiments were performed to explore the function and potential regulatory relationship of miR-506 and TULP3 in NSCLC. Our results revealed that miR-506 is high expression in NSCLC cell lines, and the overexpression of miR-506 could inhibit cell viability and enhance cell apoptosis in H1299 and A549 cells. Pro-apoptotic related protein (cytochrome C, Bax, and cleaved caspase-9) expression increased while anti-apoptotic related protein (BCL-2 and BCL-XL) expression decreased after miR-506 was overexpression. Meanwhile, the overexpression of miR-506 could notably downregulate TULP3. Additionally, silence of TULP3 inhibited cell viability and promoted cell apoptosis. At the same time, pro-apoptotic related protein expression was promoted while anti-apoptotic related protein expression was inhibited. Furthermore, TULP3 overexpression could markedly reverse the inhibitory effect of miR-506 on the proliferation and induction of mitochondrial apoptosis in H1299 and A549 cells. In vivo tumor formation experiments also exhibited consistent results indicating that the functions of TULP3 might be correlated with the promotion of tumorigenesis. In conclusion, we firstly found that miR-506 can be involved in the processes of NSCLC and exert a suppressive effect on tumorigenesis by regulating TULP3 expression.


Assuntos
Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Animais , Apoptose/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular/genética , Progressão da Doença , Inativação Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , MicroRNAs/genética , Mitocôndrias/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Med Sci Monit ; 26: e922634, 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32799214

RESUMO

BACKGROUND The aim of this study was to show whether the standardized Ginkgo biloba extract EGb761, a traditional Chinese medicine, has a therapeutic effect on pulmonary fibrosis (PF). MATERIAL AND METHODS Bleomycin (BLM) was used for establishing the PF mouse model. The mice were treated with a gradient of EGb761 for 28 days to determine an appropriate drug dose. On day 28, the effect of EGb761 on lung injury and inflammation was confirmed by hematoxylin and eosin and Masson staining and evaluated by pulmonary alveolitis and Ashcroft score. The balance of M1/M2 macrophages was evaluated with the respective markers inducible nitric oxide synthase and and interleukin-10 by real-time polymerase chain reaction. Furthermore, the expressions of fibrosis-associated protein alpha-smooth muscle actin (SMA), related inflammatory protein transforming growth factor (TGF)-ß1, the apoptosis-related proteins B-cell lymphoma-associated X protein (Bax), B-cell lymphoma (Bcl)-2, caspase-3, caspase-9, and phosphorylated nuclear factor (NF)-kappaB (p65) were assessed by western blot. RESULTS On day 28, PF was induced by treating with BLM, whereas EGb761 suppressed the PF of lung tissue. The BLM-induced imbalance of M1/M2 macrophages was reduced by EGb761. Furthermore, the increasing amounts of alpha-SMA and TGF-ß1 induced by BLM were suppressed by EGb761. In addition, the protein or messenger ribonucleic acid expression levels of phosphorylated NF-kappaB (p65), caspase-3, and caspase-9 were upregulated, whereas Bax and Bcl-2 were downregulated. Treatment with EGb761 restored the levels of these proteins except for caspase-9. CONCLUSIONS This study illustrated the protective effect of EGb761 on BLM-induced PF by regulating the balance of M1/M2 macrophages and NF-kappaB (p65)-mediated apoptosis. The results demonstrated the potential clinical therapeutic effect of EGb761, providing a novel possibility for curing PF.


Assuntos
Apoptose/efeitos dos fármacos , Bleomicina/toxicidade , Ginkgo biloba/química , Macrófagos Alveolares/efeitos dos fármacos , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Fibrose Pulmonar/prevenção & controle , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/imunologia
13.
Exp Ther Med ; 19(5): 3425-3431, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32269608

RESUMO

Lung and systemic inflammation are associated with impaired lung function and increased mortality in patients with chronic obstructive pulmonary disease (COPD). Theophylline and glucocorticoids have been shown to have an anti-inflammatory effect in some respiratory diseases. However, corticosteroid insensitivity is a major barrier to the anti-inflammatory management of COPD. This study aimed to explore whether a combined treatment of theophylline and dexamethasone (Dex) could decrease cigarette smoke extract (CSE)-induced inflammation via prevention of a reduction in histone deacetylase 2 (HDAC2) expression and through inhibition of the PI3K/Akt pathway, which may be related to corticosteroid sensitivity. The half-maximal inhibitory concentration (IC50) of Dex (IC50-Dex) was used to as a marker of corticosteroid sensitivity. IC50-Dex was determined through observation of Dex inhibition of tumor necrosis factor-α (TNF-α)-induced interleukin (IL)-8 release. Using reverse transcription quantitative PCR and western blotting, U937 cells treated with CSE were assessed for HDAC2 expression levels and phosphorylation levels of Akt. Theophylline and Dex pre-treatment was shown to significantly reduce the CSE-induced release of IL-8 and TNF-α. The combination of theophylline and Dex pretreatment also reversed corticosteroid insensitivity in CSE-induced U937 cells and inhibited the PI3K/AKT pathway to a greater extent than theophylline treatment alone. CSE-treated U937 cells showed a reduction in HDAC2 mRNA and protein expression compared with the control group. However, this effect was reduced after pre-incubation with the combined therapy or theophylline alone. In conclusion, pretreatment with theophylline and Dex decreased CSE-induced inflammation via inhibition of the PI3K/Akt pathway and increase in HDAC2 protein expression.

14.
J Photochem Photobiol B ; 202: 111676, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31837583

RESUMO

Wounds origins serious complications of lives of human beings which may leads to death. The important issue for the problem is infection during wound care management which delays wound healing process. These kinds of infections may be caused by the overuse or misuse of antibiotics, antidotes, usage of new drugs, not properly sterilized surgical instruments, not appropriate for pH level and imperfect wound dressing etc. during or after surgery. Hence in this report, antimicrobial action of pH responsive TA/KA composited hydrogel crosslinked with GO-QDs (TA/KA-GOQDs) using citric acid as cross-linker has been reported by demonstrating in-vitro and in-vivo studies for wound care management. The prepared samples of GOQDs, TA/KA hydrogel and TA/KA-GOQDs were characterized using FT-IR, XRD, SEM and TEM techniques. pH responsive hydrogel property of TA/KA was evaluated by swelling studies. In-vitro antibacterial studies was carried out by direct contact test method. Further, the prepared samples were tested in a wound healing model of rate with the wound of size 1.5 cm2 for in-vivo studies. After 16 days of treatment, the prepared samples for wound healing causes 100% wound areas closure. Histological observations were made by MT and HE staining process which proves keratinocytes proliferation by biocompatible and biocomposited TA/KA-GOQDs. The pH responsive TA/KA-GOQDs proved as efficient wound healing agent by faster keratinocytes proliferation within a compact period.


Assuntos
Materiais Biocompatíveis/farmacologia , Grafite/química , Hidrogéis/química , Queratinas/química , Pontos Quânticos/química , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Proliferação de Células/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Queratinócitos/citologia , Queratinócitos/metabolismo , Ratos , Pele/patologia , Staphylococcus aureus/efeitos dos fármacos
15.
Appl Opt ; 58(6): 1475-1484, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30874032

RESUMO

In this paper, we investigate the effects of shape distribution of aerosol particles on the volumetric scattering properties, as well as the radiance and polarization distributions of skylight, by numerical simulations. The results demonstrate that the shape distribution indeed exerts a significant influence on the skylight degree of linear polarization. The skylight polarization calculated assuming the microscope-measured shape distributions is distinct from that using the inversion-based shape distributions. The significant effects will influence the retrieval of the sphericity of aerosols based on the sun-sky radiometer measurements. Our results suggest that using representative shape distributions obtained by direct microscopic observations of aerosol samples captured in the natural atmosphere has a high potential to improve the retrieval of the aerosol shape parameter.

16.
Langmuir ; 34(35): 10426-10433, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30091934

RESUMO

Bubble-driven micromotors have attracted substantial interest due to their remarkable self-motile and cargo-delivering abilities in biomedical or environmental applications. Here, we developed a hollow micromotor that experiences fast self-propulsion underneath an air-liquid interface by periodic bubble growth and collapse. The collapsing of a single microbubble induces a ∼1 m·s-1 impulsive jetting flow that instantaneously pushes the micromotor forward. Unlike previously reported micromotors propelled by the recoiling of bubbles, cavitation-induced jetting further utilizes the energy stored in the bubble to propel the micromotor and thus enhances the energy conversion efficiency by 3 orders of magnitude. Four different modes of propulsion are, for the first time, identified by quantifying the dependence of propulsion strength on microbubble size. Meanwhile, the vertical component of the jetting flow counteracts the buoyancy of the micromotor-bubble dimer and facilitates counterintuitive hovering underneath the air-liquid interface. This work not only enriches the understanding of the propulsion mechanism of bubble-driven micromotors but also gives insight into the physical aspects of cavitation bubble dynamics near the air-liquid interface on the microscale.

17.
Opt Express ; 25(16): A813-A823, 2017 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-29041048

RESUMO

Particle shape is crucial to the properties of light scattered by atmospheric aerosol particles. A method of fluorescence microscopy direct observation was introduced to determine the aspect ratio distribution of aerosol particles. The result is comparable with that of the electron microscopic analysis. The measured aspect ratio distribution has been successfully applied in modeling light scattering and further in simulation of polarization measurements of the sun/sky radiometer. These efforts are expected to improve shape retrieval from skylight polarization by using directly measured aspect ratio distribution.

18.
PLoS One ; 11(9): e0162133, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27626799

RESUMO

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines) and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis activation in lung cancer cells, which was evidenced by TRAIL/death receptor-5 (DR5) induction and caspase-8 activation. The caspase-8 inhibitor or TRAIL/DR5 siRNA knockdown alleviated ONC201's cytotoxicity against lung cancer cells. Molecularly, ONC201 in-activated Akt-S6K1 and Erk signalings in lung cancer cells, causing Foxo3a nuclear translocation. For the in vivo studies, intraperitoneal injection of ONC201 at well-tolerated doses significantly inhibited xenografted A549 tumor growth in severe combined immunodeficient (SCID) mice. Further, ONC201 administration induced TRAIL/DR5 expression, yet inactivated Akt-S6K1 and Erk in tumor tissues. These results of the study demonstrates the potent anti-lung cancer activity by ONC201.


Assuntos
Morte Celular/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Neoplasias Pulmonares/patologia , Ligante Indutor de Apoptose Relacionado a TNF/biossíntese , Animais , Apoptose , Linhagem Celular Tumoral , Feminino , Xenoenxertos , Humanos , Imidazóis , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos SCID , Proteínas Quinases/metabolismo , Piridinas , Pirimidinas
19.
Am J Physiol Lung Cell Mol Physiol ; 309(2): L139-46, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25957293

RESUMO

Corticosteroid insensitivity, which is induced by cigarette smoke extract (CSE), is a significant barrier when treating chronic obstructive pulmonary disease (COPD). Erythromycin (EM) has been shown to have an anti-inflammatory role in some chronic airway inflammatory diseases, particularly diffuse panbronchiolitis and cystic fibrosis. Here, we explored whether the combination therapy of EM and dexamethasone (Dex) reverses corticosteroid insensitivity and investigated the molecular mechanism by which this occurs. We demonstrated that the combination of EM and Dex restored corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) from COPD patients and U937 cells after CSE exposure. Moreover, pretreatment with 10, 50, or 100 µg/ml EM reversed the HDAC2 protein reduction induced by CSE exposure in a dose-dependent manner. U937 cells exposed to CSE show a reduction in histone deacetylase (HDAC) activity, which was potently reversed by EM or combination treatment. Although 10 and 17.5% CSE increased phosphorylated Akt (PAkt) expression in a concentration-dependent manner, preapplication of EM and the combination treatment in particular blocked this PAkt increase. Total Akt levels were unaffected by CSE or EM treatments. Furthermore, the combination treatment enhanced glucocorticoid receptor (GR)α expression. Our results demonstrate that the combination therapy of EM and Dex can restore corticosteroid sensitivity through inhibition of the PI3K-δ/Akt pathway and enhancing GRα expression.


Assuntos
Corticosteroides/farmacologia , Dexametasona/farmacologia , Eritromicina/farmacologia , Leucócitos Mononucleares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Glucocorticoides/metabolismo , Fumar/efeitos adversos , Anti-Inflamatórios/farmacologia , Western Blotting , Estudos de Casos e Controles , Quimioterapia Combinada , Fármacos Gastrointestinais/farmacologia , Histona Desacetilase 2/metabolismo , Humanos , Interleucina-8/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Células U937
20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 30(4): 384-7, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-24721407

RESUMO

OBJECTIVE: To investigate the effect of erythromycin (EM) on corticosteroid insensitivity of human THP-1 cells induced by cigarette smoke extract (CSE) and its mechanism. METHODS: THP-1 cells were treated with EM followed by CSE stimulation. Histone deacetylase-2 (HDAC2) short interference RNA (HDAC2-siRNA) was transfected into the cells using Lipofectamine(TM); 2000. Interleukin-8 (IL-8) level in supernatants was measured by ELISA and HDAC2 expression was determined by real-time quantitative PCR (qRT-PCR) and Western blotting. RESULTS: The inhibition ratio of IL-8 in the EM group was significantly higher than that in the CSE group, but lower than that in the control group (P<0.05). The half-maximal inhibitory concentration of dexamethasone (IC50;-Dex) in the EM group was lower than that in the CSE group, but higher than that in the control group (P<0.05). The expression of HDAC2 protein in the EM group was higher than that in the CSE group, but lower than that in the control group (P<0.05). Besides, HDAC2 mRNA and HDAC2 protein expressions were lower in the HDAC2-siRNA group than in the scrambled oligonucleotide (SC) group. EM could reverse HDAC2 mRNA and HDAC2 protein reduction induced by HDAC2-siRNA (P<0.05). CONCLUSION: Corticosteroid sensitivity of THP-1 cells could be reduced by CSE. EM could reverse the corticosteroid insensitivity by up-regulating the expression of HDAC2 protein.


Assuntos
Corticosteroides/farmacologia , Eritromicina/farmacologia , Histona Desacetilase 2/genética , Histona Desacetilase 2/metabolismo , Monócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Humanos , Monócitos/citologia , Monócitos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fumaça/efeitos adversos , Nicotiana/química
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