Porous polymeric support membranes with outstanding organic solvent resistance are highly required for fabricating thin-film composite (TFC) organic solvent nanofiltration (OSN) membranes. In this ...work, we report the fabrication of a high-permeance TFC-OSN membrane by the use of a polytetrafluoroethylene (PTFE) microfiltration membrane loaded with single-walled carbon nanotubes coated by a polydopamine (PD/SWCNT) network film (named the PD/SWCNT/PTFE composite membrane) as the support. Through interfacial polymerization between m-phenylenediamine and trimesoyl chloride, a polyamide (PA) thin film has successfully grown on the surface of the PD/SWCNT/PTFE composite membrane. The resulting PA TFC-OSN membrane exhibits a high methanol permeance up to 13.2 L m–2 h–1 bar–1 with a rejection rate of 89.6% to 6-hydroxy-2-naphthalenesulfonic acid sodium salt (HNSA, M w = 246.21). Moreover, the rejection rates of the PA TFC-OSN membrane to various dyes remain unchanged before and after DMF activation, indicating that it possesses an excellent resistance to organic solvents.
Oxidative stress causes endothelial death while underlying mechanisms remain elusive. Herein, the pro-death effect of tert-butyl hydroperoxide (t-BHP) was investigated with low concentration (50μM) ...of t-BHP (t-BHPL) and high concentration (500μM) of t-BHP (t-BHPH). Both t-BHPL and t-BHPH induced endothelial cell death was determined. T-BHPL induced caspase-dependent apoptosis and reactive oxygen species (ROS) generation, which was inhibited by N-acetyl-L-cysteine (NAC). Furthermore, NADPH oxidase inhibitor diphenyleneiodonium (DPI), NOX4 siRNA, and NOX4 inhibitor GKT137831 reduced t-BHPL-induced ROS generation while mitochondrial respiratory chain inhibitors rotenone (Rot), 2-thenoyltrifluoroacetone (TTFA), and antimycin A (AA) failed to do so. NOX4 overexpression resulted in increased ROS generation and Akt expression but decreased sensitivity to t-BHPL. In contrast, T-BHPH induced LDH release, PI uptake, and cell translucent cytoplasm. RIP1 inhibitor necrostatin-1 (Nec-1), MLKL inhibitor necrosulfonamide (NSA) and silencing RIP1, RIP3, and MLKL inhibited t-BHPH-induced cell death while pan-caspase inhibitor Z-VAD-FMK showed no effect. T-BHPH-induced ROS production was inhibited by TTFA, AA and Rot while DPI showed no effect. T-BHPH induced RIP1/RIP3 interaction, which was decreased by Rot, TTFA, and AA. Silence RIP1 and RIP3 but not MLKL inhibited t-BHPH-induced mitochondrial membrane potential (MMP) decrease and ROS production. Moreover, P38MAPK inhibitor SB203580 reversed both t-BHPL and t-BHPH-induced cell death while inhibitors for ERKs and JNKs showed no obvious effect. These data suggested that t-BHP induced both apoptosis and necroptosis in endothelial cells which was mediated by ROS and p38MAPK. ROS derived from NADPH oxidase and mitochondria contributed to t-BHPL and t-BHPH-induced apoptosis and necroptosis, respectively.
Doxorubicin (DOX) is a widely used antineoplastic agent in clinics. However, its clinical application is largely limited by its cardiotoxicity. Diethyl blechnic (DB) is a novel compound isolated from
...Bunge. Here, we study the effect of DB on DOX-induced cardiotoxicity and its underlying mechanisms. Cellular viability was tested by 3--4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) and protein level was evaluated by Western blotting. 5,5’,6,6’-tetrachloro-1,1’,3,3’-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining was performed to determine the mitochondrial membrane potential (MMP). Hoechst 33342 staining and TUNEL staining was performed to test the apoptosis. Reactive oxygen species (ROS) generation was investigated by using flow cytometry. DB significantly inhibited DOX-induced apoptosis in H9c2 cells and primary cultured cardiomyocytes. Moreover, DB decreased cell apoptotic morphological changes and reversed the mitochondrial membrane potential induced by DOX. Meanwhile, pre-treatment with DB increased the expression levels of B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra-large (Bcl-xl), and survivin and reduced the expression levels of Bcl-2-associated X protein (Bax), p-p53, cytochrome c (cyt c), and cleaved-caspase 3, 7, 8, 9 in the protein levels in DOX-treated H9c2 cells. Furthermore, DB suppressed ROS generation. The DB-mediated protective effects were accompanied by increased c-Jun N-terminal kinase1/2 (JNK1/2) expression. In addition, SP600125, the inhibitor of JNK1/2, abolished the protective effect of DB. We concluded that DB protected cardiomyocytes against DOX-induced cytotoxicity by inhibiting ROS and activating the JNK1/2 pathway. Therefore, DB is a promising candidate as a cardioprotective agent against DOX-induced cardiotoxicity.
Pancreatic cancer is the seventh leading cause of cancer-related death worldwide and is known as "the king of cancers". Currently, gemcitabine (GEM) as the clinical drug of choice for chemotherapy of ...advanced pancreatic cancer has poor drug sensitivity and ineffective chemotherapy. Nardoguaianone L (G-6) is a novel guaiane-type sesquiterpenoid isolated from
DC., and it exhibits anti-tumor activity. Based on the newly discovered G-6 with anti-pancreatic cancer activity in our laboratory, this paper aimed to evaluate the potential value of the combination of G-6 and GEM in SW1990 cells, including cell viability, cell apoptosis, colony assay and tandem mass tags (TMT) marker-based proteomic technology. These results showed that G-6 combined with GEM significantly inhibited cell viability, and the effect was more obvious than that with single drug. In addition, the use of TMT marker-based proteomic technology demonstrated that the AGE-RAGE signaling pathway was activated after medication-combination. Furthermore, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) assays were used to validate the proteomic results. Finally, apoptosis was detected by flow cytometry. In conclusion, G-6 combined with GEM induced an increase in ROS level and a decrease in MMP in SW1990 cells through the AGE-RAGE signaling pathway, ultimately leading to apoptosis. G-6 improved the effect of GEM chemotherapy and may be used as a potential combination therapy for pancreatic cancer.
•Platycodins represent the main bioactive components of Platycodonis Radix.•More than 70 platycodins have been identified from Platycodonis Radix.•The platycodins possess various pharmacological ...activities.•Toxicology and pharmacokinetics of the platycodins have been summarized.
Platycodonis Radix, the root of Platycodon grandiflorum (Jacq.) A. DC., is a well-known edible herbal medicine. It is a common vegetable used for the preparation of side dish, kimchi, dessert, and tea. Besides, it has been used to treat respiratory disease including cough, excessive phlegm, and sore throat for a long history. In the past decades, the bioactive components and the pharmacological activities of Platycodonis Radix have been widely investigated. Thereinto, platycodins, the oleanane-type triterpenoid saponins were demonstrated to be the main bioactive components in Platycodonis Radix, and more than 70 platycodins have been identified up to date. This paper mainly reviewed the phytochemistry, pharmacological activities (apophlegmatic, anti-tussive, anti-inflammatory, anti-cancer, anti-obesity, anti-diabetic, immunomodulatory, cardiovascular protective, and hepatoprotective activities, etc.), toxicology and pharmacokinetics of platycodins isolated from Platycodonis Radix, aiming to promote further investigation on therapeutic potential of these platycodins.
Alzheimer's disease (AD) is a common human neurodegenerative disease, which is characterized by the progressive loss of memory and the cognitive impairment. Since the etiology of AD is still unknown, ...it is extremely difficult to develop the effective drugs for preventing or slowing the AD process. The major characteristics of AD such as amyloid β plaques, neurofibrillary tangles, mitochondrial dysfunction, and autophagy dysfunction are commonly used as the important indicators for evaluating the effects of potential candidate drugs. The rhizome of
(known as 'Danshen' in Chinese), a famous traditional Chinese medicine, which is widely used for the treatment of hyperlipidemia, stroke, cardiovascular and cerebrovascular diseases. Increasing evidences suggest that the bioactive components of Danshen can improve cognitive deficits in mice, protect neuronal cells, reduce tau hyperphosylation, prevent amyloid-β fiber formation and disaggregation. Here we briefly summarize the studies regarding the effects of bioactive component from Danshen on those major characteristics of AD in preclinical studies, as well as explore the potential of these Danshen component in the treatment of AD.
Abstract
Trade-off between permeability and nanometer-level selectivity is an inherent shortcoming of membrane-based separation of molecules, while most highly porous materials with high adsorption ...capacity lack solution processability and stability for achieving adsorption-based molecule separation. We hereby report a hydrophilic amidoxime modified polymer of intrinsic microporosity (AOPIM-1) as a membrane adsorption material to selectively adsorb and separate small organic molecules from water with ultrahigh processing capacity. The membrane adsorption capacity for Rhodamine B reaches 26.114 g m
−2
, 10–1000 times higher than previously reported adsorptive membranes. Meanwhile, the membrane achieves >99.9% removal of various nano-sized organic molecules with water flux 2 orders of magnitude higher than typical pressure-driven membranes of similar rejections. This work confirms the feasibility of microporous polymers for membrane adsorption with high capacity, and provides the possibility of adsorptive membranes for molecular separation.
Epithelial-mesenchymal transition (EMT), the transdifferentiation of epithelial cells into mesenchymal cells, has been implicated in the metastasis and provides novel strategies for cancer therapy. ...Osthole (OST), a dominant active constituent of Chinese herb Cnidium monnieri, has been reported to inhibit cancer metastasis while the mechanisms remains unclear. Here, we studied the inhibitory effect and mechanisms of OST on TGF-β1-induced EMT in A549 cells. Cells were treated with TGF-β1 in the absence and presence of OST. The morphological alterations were observed with a microscopy. The protein and mRNA expressions were determined by Western blotting and real-time PCR. The protein localization was detected with immunofluorescence. The adhesion, migration, and invasion were determined by Matrigel, wound-healing, and Transwell assays. TGF-β1 treatment induced spindle-shaped alterations of cells, upregulation of N-cadherin, Vimentin, NF-κB p65, and downregulation of E-cadherin. Dysregulated membrane expression and mRNA expression of E-cadherin and N-cadherin were observed after TGF-β1 treatment. TGF-β1 increased abilities of migration and invasion and triggered the nuclear translocation of NF-κB p65. These alterations were dramatically inhibited by OST. Furthermore, PDTC, a NF-κB inhibitor, showed similar effects. In addition, TGF-β1-induced expression of Snail was significantly inhibited by OST and silenced Snail partially reversed TGF-β1-induced EMT biomarkers without affecting NF-κB p-65. In conclusion, OST inhibited TGF-β1-induced EMT, adhesion, migration, and invasion through inactivation of NF-κB-Snail pathways in A549 cells. This study provides novel molecular mechanisms for the anti-metastatic effect of OST.
Chemoresistance, the major obstacle in breast cancer chemotherapy, results in unnecessary chemotherapy and wasting of medical resources. No feasible method has been available to predict ...chemoresistance before chemotherapy. In our previous study, elevated expression of transient receptor potential channel TRPC5 was found to be an essential element for chemoresistance in breast cancer cells, and it was determined that it could be transferred to chemosensitive breast cancer cells through releasing extracellular vesicles (EV) containing TRPC5 from chemoresistant cells, resulting in acquired chemoresistance. Exosomes, a type of EV, are secreted membrane‐enclosed vesicles of 50–150‐nm diameter. In this study we found that circulating exosomes in peripheral blood from breast cancer patients carried TRPC5. In the present study, circulating exosome‐carrying TRPC5 (cirExo‐TRPC5) level was significantly correlated with TRPC5 expression level in breast cancer tissues and tumor response to chemotherapy. Furthermore, increased cirExo‐TRPC5 level after chemotherapy preceded progressive disease (PD) based on imaging examination and strongly predicted acquired chemoresistance. Taken together, our study demonstrated that cirExo‐TRPC5 might act as a noninvasive chemoresistance marker and might serve as an adjuvant to the current imaging examination‐based chemoresistance.
Increased cirExo‐TRPC5 level after chemotherapy was preceding progressive disease (PD) based on imaging examination and strongly predicted acquired chemoresistance. CrExo‐TRPC5 might act as a noninvasive chemoresistance marker and might serve as an adjuvant to the current imaging examination‐based chemoresistance.
Inhibition of autophagy is a promising strategy for non-small cell lung cancer (NSCLC) treatment, which is in the clinical trials. However, only chloroquine is used in clinic as an autophagic ...inhibitor and the inhibitory effect of chloroquine on autophagy is finite. Therefore, the development of an alternative autophagic inhibitor for NSCLC therapy becomes necessary. In the present study, cepharanthine (CEP), an alkaloid extracted from Stephania cepharantha Hayata, was identified as a novel autophagic inhibitor in NSCLC cells. The potential mechanism of the CEP-inhibited autophagy was by blockage of autophagosome-lysosome fusion and inhibition of lysosomal cathepsin B and cathepsin D maturation. Furthermore, we found for the first time that dacomitinib (DAC), a second-generation epidermal growth factor receptor inhibitor that in the phase III clinical trials for NSCLC treatment, induced a protective autophagy to decrease its anti-cancer effect. Combined treatment with CEP increased the anti-proliferative and apoptotic effects of DAC in vitro and enhanced the anti-cancer effect of DAC in NCI-H1975 xenograft mice. Collectively, CEP might be further developed as an autophagic inhibitor, and combined treatment of CEP and DAC could offer an effective strategy for NSCLC treatment.
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•Cepharanthine (CEP) is identified as a novel autophagic inhibitor in NSCLC cells.•Dacomitinib (DAC) induces a protective autophagy in NSCLC cells.•CEP enhances the anti-cancer effect of DAC both in vitro and in vivo.•Combined treatment of CEP and DAC may be an effective strategy for NSCLC treatment.
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