The m6A-ncRNAs axis in diabetes complications: novel mechanism and therapeutic potential.

Diabetes, a multifaceted metabolic disorder, poses a significant global health burden with its increasing prevalence and associated complications, such as diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, and diabetic angiopathy. Recent studies have highlighted the intricate interplay between N6-methyladenosine (m6A) and non-coding RNAs (ncRNAs) in key pathways implicated in these diabetes complications, like cell apoptosis, oxidative stress, and inflammation. Thus, understanding the mechanistic insights into how m6A dysregulation impacts the expression and function of ncRNAs opens new avenues for therapeutic interventions targeting the m6A-ncRNAs axis in diabetes complications. This review explores the regulatory roles of m6A modifications and ncRNAs, and stresses the role of the m6A-ncRNA axis in diabetes complications, providing a therapeutic potential for these diseases.

Anticancer effect of hUC-MSC-derived exosome-mediated delivery of PMO-miR-146b-5p in colorectal cancer.

Antisense oligonucleotide (ASO) is a novel therapeutic platform for targeted cancer therapy. Previously, we have demonstrated that miR-146b-5p plays an important role in colorectal cancer progression. However, a safe and effective strategy for delivery of an ASO to its targeted RNA remains as a major hurdle in translational advances. Human umbilical cord mesenchymal cell (hUC-MSC)-derived exosomes were used as vehicles to deliver an anti-miR-146b-5p ASO (PMO-146b). PMO-146b was assembled onto the surface of exosomes (e) through covalent conjugation to an anchor peptide CP05 (P) that recognized an exosomal surface marker, CD63, forming a complex named ePPMO-146b. After ePPMO-146b treatment, cell proliferation, uptake ability, and migration assays were performed, and epithelial-mesenchymal transition progression was evaluated in vitro. A mouse xenograft model was used to determine the antitumor effect and distribution of ePPMO-146b in vivo. ePPMO-146b was taken up by SW620 cells and effectively inhibited cell proliferation and migration. The conjugate also exerted antitumor efficacy in a xenograft mouse model of colon cancer by systematic administration, where PPMO-146b was enriched in tumor tissue. Our study highlights the potential of hUC-MSC-derived exosomes anchored with PPMO-146b as a novel safe and effective approach for PMO backboned ASO delivery.

Biodegradable Hollow Polydopamine@manganese Dioxide as an Oxygen Self-Supplied Nanoplatform for Boosting Chemo-photodynamic Cancer Therapy.

Photodynamic therapy (PDT) has attracted extensive attention in the clinical treatment of malignant tumor. However, the acidic and hypoxic conditions of the tumor microenvironment (TME) limit the further application of PDT in the clinic. Herein, we fabricate a new nanoplatform─HPDA@MnO2@Ce6/DOX@PEG-RGD (HPMRCD)─by means of coating hollow polydopamine nanoparticles (HPDA) with manganese dioxide (MnO2), which is modified by cyclic RGD functionalized poly(ethylene glycol) (PEG) and further co-loaded with a photosensitizer, Chlorin e6 (Ce6), and a chemotherapy drug, doxorubicin (DOX). This nanoplatform could be enriched in tumor tissues, then instantly dissociated under an acidic and H2O2-rich TME. The dual-responsive release of Mn2+ ions and oxygen (O2) can relieve tumor hypoxia, which can be used as a magnetic resonance contrast agent and the latter can enhance the PDT effect. Furthermore, the degradation of HPMRCD leads to an efficient loaded therapeutic molecule release, thus yielding a potential therapy to enhance tumor suppression by adopting the combined chemo-photodynamic therapy.

Near infrared II laser controlled free radical releasing nanogenerator for synergistic nitric oxide and alkyl radical therapy of breast cancer.

Recently, alkyl radicals have attracted much attention in cancer therapy due to their oxygen-independent generation property. For the first time, alkyl radical and nitric oxide (NO) combined therapy is demonstrated as an effective strategy for tumor inhibition. As a proof of concept, a biocompatible free radical nanogenerator with near-infrared (NIR) II laser-induced simultaneous NO and alkyl radical release property was elaborately fabricated. In particular, an NIR II molecule (IR 1061), NO donor (BNN6) and alkyl radical initiator (AIPH) were firstly encapsulated in a natural lecithin stabilized phase change material, and then further functionalized by an amphiphile of DSPE-PEG-RGD with specific tumor targeting ability, finally obtaining biocompatible P(IR/BNN6/AIPH)@Lip-RGD. Upon NIR II laser irradiation, the photothermal effect generated from IR 1061 could trigger the phase change of the nanogenerator by releasing the encapsulated BNN6 and AIPH, and subsequently decompose them to generate highly active NO and alkyl radicals. Remarkably, NO and alkyl radical release profiles of P(IR/BNN6/AIPH)@Lip-RGD could be precisely controlled using intermittent NIR II laser irradiation. Moreover, P(IR/BNN6/AIPH)@Lip-RGD displayed a synergistic NO and alkyl radicals' anticancer effect by significantly inhibiting the growth of breast tumors, upon NIR II laser exposure. Furthermore, an in depth mechanistic study revealed that synergistic NO and alkyl radical effect induced cancer cell apoptosis through a mitochondria-mediated apoptotic pathway. The synergistic effect jointly caused a burst generation of mitochondrial ROS, which significantly down-regulated Bcl-2 protein expression, accelerated cytochrome c release and triggered a cascade of apoptosis-related proteins of Caspase-3 and Caspase-9.

A Panel of Plasma Exosomal miRNAs as Potential Biomarkers for Differential Diagnosis of Thyroid Nodules.

Background: A liquid biopsy using circulating exosomal genetic materials provides new insights for thyroid cancer diagnosis. This study aimed to identify plasma-derived exosomal biomarkers that could be used for early detection of papillary thyroid carcinoma (PTC). Method: Exosomal miRNAs in plasma were isolated from patients with benign thyroid nodules and patients with PTC. Profiling of exosomal miRNA was performed using RNA sequencing (RNA-seq) to identify miRNA candidates and differentiate the benign from malignant. The validation cohort consisted of 30 patients with benign thyroid nodules, 35 PTC patients, and 31 healthy individuals. Real-time PCR was used to quantify the expression of miRNA candidates. The diagnostic potential of the candidates was evaluated by receiver operating characteristic (ROC) curves. Results: After RNA-seq, eight plasma exosomal miRNAs were selected as candidates. Further validation indicated that the levels of exosomal miR-16-2-3p, miR-223-5p, miR-34c-5p, miR-182-5p, miR-223-3p, and miR-146b-5p were significantly lower in nodules compared to healthy controls (p < 0.0001), whereas miR-16-2-3p and miR-223-5p were significantly higher in the PTC cases than in those with benign nodules (p < 0.05). ROC analyses revealed that the above six miRNAs were potent indicators for detection of thyroid nodules. Meanwhile, miR-16-2-3p and miR-223-5p can be utilized for detecting PTC from benign nodules. Additionally, combined miRNA panels showed increased diagnostic sensitivities and specificities compared to single miRNA markers. Conclusion: Six aberrantly expressed plasma exosomal miRNAs may be used as diagnostic biomarkers to differentiate thyroid nodules from healthy individuals. The panel consisting of miR-16-2-3p, miR-223-5p, miR-101-3p, and miR-34c-5p are eligible for discriminating benign from malignant thyroid nodules.

The versatile roles and clinical implications of exosomal mRNAs and microRNAs in cancer.

Extracellular vesicles (EVs), which include exosomes, microvesicles, and apoptotic bodies, are nanosized structures that are secreted by various cells and act as important mediators in intercellular communication. Recent studies have shown that exosomes carrying bioactive molecules are generated from multivesicular bodies and are present in various body fluids. mRNAs and microRNAs (miRNAs) are encapsulated in exosomes and have been found to be involved in multiple pathophysiological processes. Here, we provide a review of tumor-associated exosomal mRNAs and miRNAs and their roles in metastasis and drug resistance. In particular, we emphasize their clinical application potential as diagnostic and prognostic biomarkers of cancer and in cancer therapy.

Construction of a combined enzyme system of graphene oxide and manganese peroxidase for efficient oxidation of aromatic compounds.

Manganese peroxidase (MnP) from Irpex lacteus F17 has potential use as a biocatalyst in the field of environmental biotechnology because of its unique properties and ability to decompose harmful aromatic compounds. However, its requirement of harsh acidic reaction conditions and its insufficient catalytic activity restrict its practical applications. Here, we combine graphene oxide (GO) and MnP to construct an efficient enzyme system (GO-MnP) with improved catalytic efficiencies and a wide pH range for the oxidation of aromatic substances and dye decolorization. We found that the Michaelis constant (Km) of GO-MnP for Mn2+ was 2.8 times lower and the catalytic efficiency (kcat/Km) of GO-MnP was 4.5 times higher than those of MnP, and that the decolorization of various dyes by GO-MnP was significantly improved over the pH range of 4.5-5.5. A comparison of the midpoint redox potentials also reflects the strong oxidation ability of GO-MnP. Furthermore, we demonstrated that, in the GO-MnP system, the MnP activity is mainly determined by the amounts of epoxy and carboxyl groups in GO, based on an analysis of the functional group changes in GO and reduced GO associated with different reduction degrees as shown by X-ray photoelectron spectroscopy.

A uPAR targeted nanoplatform with an NIR laser-responsive drug release property for tri-modal imaging and synergistic photothermal-chemotherapy of triple-negative breast cancer.

In the present work, an iridium (Ir) complex loaded theranostic nanoplatform was designed for high-efficiency triple-negative breast cancer (TNBC) therapy. For this purpose, the Ir complex was firstly loaded on a photothermal agent of gold nanostars (GNS) by simply mixing followed by functionalization using a urokinase-type plasminogen activator receptor (uPAR) targeted polyetherimide-AE105 peptide conjugate (P-AE105) with the formation of GNS@Ir@P-AE105. It was demonstrated that the resultant GNS@Ir@P-AE105 was a multifunctional nanoplatform with advantages of (1) NIR laser controlled release of the Ir complex; (2) precise delivery of the Ir complex to TNBC cells; (3) excellent photothermal (PT)/photoacoustic (PA)/X-ray computed tomography (CT) tri-modal imaging ability; and (4) a synergistic photothermal-chemotherapeutic effect. An in-depth investigation of the mechanism revealed that binding forces of the Ir complex-GNS and P-AE105-GNS were significantly diminished upon NIR laser irradiation, which conferred an NIR laser-responsive Ir complex release property to the nanoplatform. Moreover, the nanoplatform exerted high efficiency anti-TNBC effects via a ROS-induced p53 apoptotic pathway. Specifically, combinational photothermal-chemotherapeutic treatments stimulated intracellular ROS generation, which significantly up-regulated apoptotic-relative p53 gene expression either by causing severe DNA damage or inducing an arrest effect on the sub-G1 phase of the cell cycle. Taken together, our work provides a novel theranostic nanoplatform for efficient and simultaneous diagnosis and therapy of TNBC.

PEP06 polypeptide 30 exerts antitumour effect in colorectal carcinoma via inhibiting epithelial-mesenchymal transition.

BACKGROUND AND PURPOSE: PEP06, a polypeptide modified from endostatin, was investigated for its antitumour effects on colorectal cancer (CRC) and the possible mechanisms of this antitumour activity were examined in in vitro and in vivo models. EXPERIMENTAL APPROACH: After PEP06 treatment, cell proliferation and migration assays were performed in CRC cells. Epithelial-mesenchymal transition (EMT) progression was determined by Western blotting, immunofluorescent staining and immunohistochemistry in vitro and in a residual xenograft model. MiRNAs regulated by PEP06 were identified by miRNA microarray and verified by in situ hybridization and quantitative real-time PCR. The interactions between PEP06 and integrin αvß3 were determined with Biacore SA biochips. The cellular function of miR-146b-5p was validated by gain-of-function and loss-of-function approaches. A mouse model of lung metastasis was used to determine the effect of PEP06 on metastatic growth. KEY RESULTS: PEP06 did not affect cell viability but reduced migration and EMT in SW620 and HCT116 cells. PEP06 significantly repressed the expression of miR-146b-5p in these two cell lines through binding to integrin αvß3. MiR-146b-5p was shown to increase EMT by targeting Smad4, and the miR-146b-5p-Smad4 cascade regulated EMT in CRC. PEP06 also suppressed CRC pulmonary metastasis, increased survival of mice and hampered residual tumour growth by inhibiting EMT through down-regulating miR-146b-5p. CONCLUSIONS AND IMPLICATIONS: PEP06 is a polypeptide that inhibits the growth and metastasis of colon cancer through its RGD motif binding to integrin αvß3, thereby down-regulating miR-146b-5p to inhibit EMT in vitro and in vivo. It might have potential as a therapeutic for CRC.

A Rapid Method for Antigen-Specific Hybridoma Clone Isolation.

Using an enzyme-linked immunosorbent assay (ELISA) and limited dilution methods to screen and clone antigen-specific hybridoma cells is extremely time-consuming and labor-intensive. This work features a simple and rapid cell surface fluorescence immunosorbent assay (CSFIA), designed for the detection and isolation of antigen-specific hybridoma clones. In this assay, antigens are first anchored to the hybridoma cell surface through a dual-functioning molecular Oleyl-PEG4000-NHS. Specific antibodies secreted from hybridoma cells are then captured by the antigens on the cell surface. Positive hybridoma cells are stained using a fluorescently labeled anti-mouse IgG-Fc antibody. After the addition of a methylcellulose semisolid medium, positive clones are easily picked using a pipet. These positive cell clones can be used to produce monoclonal antibodies after direct expansion. Using this method, positive hybridoma clones against both malachite green and porcine epidemic diarrhea virus are selected with high efficiency. Compared to the ELISA-based method, the CSFIA-based method achieved the capability of isolating >2-fold more hybridoma clones in <25% of the corresponding processing time. In brief, the CSFIA-based method is highly efficient and inexpensive with a simple and direct operation, which is an excellent candidate method for antigen-specific positive clone isolation in a monoclonal antibody preparation.

Posterolateral Approach With Buttress Plates and Cannulated Screw Fixation for Large Posterior Malleolus Fractures.

The present study retrospectively reviewed the clinical efficacy of open reduction and internal fixation with buttress plates and cannulated screws via a posterolateral approach for the treatment of large posterior malleolus fractures. From July 2009 to April 2012, 34 patients (15 males and 19 females; mean age 41.2 years) with posterior malleolus fractures involving >25% of the distal articular tibia, were treated by cannulated screw and buttress plate fixation. All the patients were followed for ≥24 months. The outcome measures included the radiographic appearance of the reduction and bone union and the Baird-Jackson score. The average operation time was 105.6 (range 78 to 145) minutes. Radiologic examination showed all fractures achieved anatomic reduction and primary bone union at a mean of 3.8 (range 3 to 7) months after surgery. After an average follow-up period of 32.7 (range 24 to 44) months, no displacement, loosening, or breakage of internal fixation was observed. However, mild posttraumatic arthritis was present in 3 patients. According to the Baird-Jackson scoring system, the outcomes were rated as excellent in 11 cases, good in 17, fair in 5, and poor in only 1 case, for an excellent and good rate of 82.3%. An association analysis indicated age and injury mechanism might be factors influencing the intraoperative and postoperative outcomes. A posterolateral approach with buttress plate and cannulated screw internal fixation could be an effective technique for reduction and fixation of large posterior malleolus fragments.

Toxicogenomics of iron oxide nanoparticles in the nematode C. elegans.

We present a mechanistic study of the effect of iron oxide nanoparticles (SPIONs) in Caenorhabditis elegans combining a genome-wide analysis with the investigation of specific molecular markers frequently linked to nanotoxicity. The effects of two different coatings were explored: citrate, an anionic stabilizer, and bovine serum albumin, as a pre-formed protein corona. The transcriptomic study identified differentially expressed genes following an exposure to SPIONs. The expression of genes involved in oxidative stress, metal detoxification response, endocytosis, intestinal integrity and iron homeostasis was quantitatively evaluated. The role of oxidative stress was confirmed by gene expression analysis and by synchrotron Fourier Transform infrared microscopy based on the higher tissue oxidation of NP-treated animals. The observed transcriptional modulation of key signaling pathways such as MAPK and Wnt suggests that SPIONs might be endocytosed by clathrin-mediated processes, a putative mechanism of nanotoxicity which deserves further mechanistic investigations.

d-Amino Acid Position Influences the Anticancer Activity of Galaxamide Analogs: An Apoptotic Mechanism Study.

Galaxamide, an extract from Galaxaura filamentosa, is a cyclic pentapeptide containing five l-leucines. Due to the particular cyclic structure and the excellent anticancer activity, synthesis of Galaxamide and its analogs and their subsequent bio-applications have attracted great attention. In the present work, we synthesized six Galaxamide analogs by replacing one of the l-leucines with phenylalanine and varying the d-amino acid position. The anticancer effect of the synthesized Galaxamide analogs was tested against four in vitro human cancer cell lines, human hepatocellular cells (HepG2), human breast cancer cell (MCF-7), human breast adenocarcinoma cells (MDA-MB-435) and a human cervical carcinoma cell line (Hela). Results showed that Galaxamide analogs with different d-amino acid positions displayed distinct anticancer potential. The Galaxamide analog containing d-amino acid at position 5 (Analog-6) presented the strongest anticancer activity. The mechanism study revealed that Analog-6 could cause the early apoptosis of HepG2 cells by inhibiting their growth in the sub-G1 stage of the cell cycle and induce the chromatin condensation and fragmentation, which can be seen as 68% of HepG2 cells inhibited in the sub-G1 stage. Moreover, a mitochondria-mediated pathway was found to be involved in the apoptotic process of Analog-6 on HepG2 cells.

Bio-identity and fate of albumin-coated SPIONs evaluated in cells and by the C. elegans model.

UNLABELLED: Nanoparticles which surface adsorb proteins in an uncontrolled and non-reproducible manner will have limited uses as nanomedicinal products. A promising approach to avoid nanoparticle non-specific interactions with proteins is to design bio-hybrids by purposely pre-forming a protein corona around the inorganic cores. Here, we investigate, in vitro and in vivo, the newly acquired bio-identity of superparamagnetic iron oxide nanoparticles (SPIONs) upon their functionalization with a pre-formed and well-defined bovine serum albumin (BSA) corona. Cellular uptake, intracellular particle distribution and cytotoxicity were studied in two cell lines: adherent and non-adherent cells. BSA decreases nanoparticle internalization in both cell lines and protects the iron core once they have been internalized. The physiological response to the nanoparticles is then in vivo evaluated by oral administration to Caenorhabditis elegans, which was selected as a model of a functional intestinal barrier. Nanoparticle biodistribution, at single particle resolution, is studied by transmission electron microscopy. The analysis reveals that the acidic intestinal environment partially digests uncoated SPIONs but does not affect BSA-coated ones. It also discloses that some particles could enter the nematode's enterocytes, likely by endocytosis which is a different pathway than the one described for the worm nutrients. STATEMENT OF SIGNIFICANCE: Unravelling meaningful relationships between the physiological impact of engineered nanoparticles and their synthetic and biological identity is of vital importance when considering nanoparticles biomedical uses and when establishing their nanotoxicological profile. This study contributes to better comprehend the inorganic nanoparticles' behavior in real biological milieus. We synthesized a controlled pre-formed BSA protein corona on SPIONs to lower unspecific cell uptake and decrease nanoparticle fouling with other proteins. Such findings may be of relevance considering clinical translation and regulatory issues of inorganic nanoparticles. Moreover, we have advanced in the validation of C. elegans as a simple animal model for assessing biological responses of engineering nanomaterials. The physiological response of BSA coated SPIONs was evaluated in vivo after their oral administration to C. elegans. Analyzing ultra-thin cross-sections of the worms by TEM with single-particle precision, we could track NP biodistribution along the digestive tract and determine unambiguously their translocation through biological barriers and cell membranes.

Downregulation of miR-21 is involved in direct actions of ursolic acid on the heart: implications for cardiac fibrosis and hypertrophy.

PURPOSE: Myocardial fibrosis contributes to cardiac remodeling and loss of cardiac function in myocardial infarction and heart failure. This study used in vitro and in vivo models to examine the effects of ursolic acid (UA) on myocardial fibrosis and to explore its potential mechanism. METHODS: Transverse aortic constriction (TAC) surgery was performed in mice to induce cardiac hypertrophy and fibrosis. UA was orally administered 1 week prior to TAC. Two weeks after TAC, myocardial pathology was detected using Masson's trichrome staining and transmission electron microscopy, and heart-to-body weight ratio was measured. For in vitro studies, cultured cardiac fibroblasts were treated with serum in the presence or absence of UA. The relative levels of miR-21 and p-ERK/ERK, collagen content and cell viability were measured. RESULTS: Ursolic acid attenuated pathological cardiac hypertrophy and myocardial fibrosis in vivo induced by TAC. Downregulation of miR-21 and p-ERK/ERK were observed in myocardial fibroblasts treated with UA in a dose-dependent manner compared with the control group both in vitro and in vivo. CONCLUSIONS: Our study demonstrates that UA can inhibit myocardial fibrosis both in vitro and in vivo, and the effects of UA on myocardial fibrosis may be due to the inhibition of miR-21/ERK signaling pathways.

Protective Effects of Bovine Serum Albumin on Superparamagnetic Iron Oxide Nanoparticles Evaluated in the Nematode Caenorhabditis elegans.

Nanomaterials give rise to unique biological reactivity that needs to be thoroughly investigated. The quest for enhanced magnetic nanomaterials of different shapes, magnetic properties, or surface coatings continues for applications in drug delivery, targeting therapies, biosensing, and magnetic separation. In this context, the use of simple in vivo models, such as Caenorhabditis elegans, to biologically evaluate nanoparticles is currently in increasing demand as it offers low-cost and information-rich experiments. In this work, we evaluated how surface modification (citrate- and protein-coated) of superparamagnetic iron oxide nanoparticles (C-SPIONs and BSA-SPIONs, respectively) induces changes in their toxicological profile and biodistribution using the animal model C. elegans and combining techniques from materials science and biochemistry. The acute toxicity and nanoparticle distribution were assessed in two populations of worms (adults and larvae) treated with both types of SPIONs. After 24 h treatment, nanoparticles were localized in the alimentary system of C. elegans; acute toxicity was stronger in adults and larvae exposed to C-SPIONs rather than BSA-SPIONs. Adult uptake was similar for both SPION types, whereas uptake in larvae was dependent on the surface coating, being higher for BSA-SPIONs. Nanoparticle size was evaluated upon excretion, and a slight size decrease was found. Interestingly, all results indicate the protective effects of the BSA to prevent degradation of the nanoparticles and decrease acute toxicity to the worms, especially at high concentrations. We argue that this relevant information on the chemistry and toxicity of SPIONs in vivo could not be gathered using more classical in vitro approaches such as cell culture assays, thus endorsing the potential of C. elegans to assess nanomaterials at early stages of their synthetic formulations.

MiR-451 inhibits synovial fibroblasts proliferation and inflammatory cytokines secretion in rheumatoid arthritis through mediating p38MAPK signaling pathway.

Rheumatoid arthritis is an autoimmune disease characterized as joint synovial inflammation. MicroRNA is a group of small noncoding RNA molecules discovered in recent years that can posttranscriptional regulate mRNA expression and involved in a variety processes of immune cell activation and differentiation. There is still lack of study about the role of miR-451 in rheumatoid arthritis. Synovial fibroblasts isolated from rheumatoid arthritis patients were cultured in vitro. Chemical synthesized miR-451 was lipo-transfected, real-time RT-PCR was applied to detect miR-451 expression level, and MTT method was used to detect the effect of miR-451 on synovial fibroblasts proliferation. Enzyme-linked immunosorbent assay was used to detect tumor necrosis factor TNF-α, IL-1ß, and IL-6 level in the supernatant. Western blot was applied to test target protein p38 MAPK expression level. Our study found that synovial fibroblasts expressed higher miR-451 mRNA level in miR-451 treatment group. MiR-451 treatment significantly decreased cell proliferation ability (P < 0.05). Compared with the control, p38 MAPK protein expression reduced obviously in the miR-451 treatment group (P < 0.05). MiR-451 transfected synovial fibroblasts secreted lower levels of TNF-α (198 ± 12 pg/ml vs 124 ± 13 pg/ml, P < 0.01), IL-1ß (352 ± 43 pg/ml vs 165 ± 87 pg/ml, P < 0.01), and IL-6 (487 ± 84 pg/ml vs 257 ± 92 pg/ml, P < 0.01). The results proved that miR-451 can down-regulate p38 MAPK protein expression, and reduce synovial fibroblasts proliferation and cytokine expression level.

[Protective effect and mechanism of Ecliptae Herba on cigarette smoke extract-induced cytotoxicity of NHBE cells].

OBJECTIVE: To investigate the protective effect and mechanism of Ecliptae Herba extract on cigarette smoke extract-induced cytotoxicity. METHOD: The effect of Ecliptae Herba extract on CSE-induced NHBE cell proliferation was detected by MTT assay. GSH content was determined by DTNB colorimetry. GST activity was measured by CDNB colorimetric assay. NQO1 activity was detected by NADPH and DCIP. The protein expression was determined by Western blot assay. RESULT: Ecliptae Herba extract reduced CSE's inhibitory effect on NHBE cells, recover the decrease in intracellular GSH caused by CSE and reduce the CSE-induced activity of GST and NQO1 and NQO1 protein expression. CONCLUSION: Ecliptae Herba extract can reduce CSE-induced injury on NHBE cells, which may be related to phase II detoxification enzymes.

Ursolic acid inhibits cigarette smoke extract-induced human bronchial epithelial cell injury and prevents development of lung cancer.

Cigarette smoking is the main cause of chronic obstructive pulmonary disease and lung cancer. The present study was aimed to explore the chemopreventive effect of ursolic acid (UA) on these diseases. In the CSE treated normal human bronchial epithelial cell model, UA alleviated cytotoxicity caused by CSE, recovered the intracellular redox balance, and relieved the stimulation of external deleterious factors as well. UA mitigated CSE-induced DNA damage through the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway. Moreover, UA inhibited lung cancer development in the model established by A549 cells in nude mice in vivo. For the first time, our results indicate that UA could be developed as a potential lung cancer chemopreventive agent.