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1.
Am J Ind Med ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980251

ABSTRACT

OBJECTIVES: Prior analyses of the Occupational Disease Surveillance System (ODSS) have compared cancer rates using internal referent groups. As an exploratory analysis, we sought to estimate cancer risk using general population reference rates to evaluate the impact that the comparison population has on findings from our surveillance program. METHODS: A cohort of approximately 2.3 million workers in Ontario, Canada with an accepted lost-time workers' compensation claim were followed for all cancer diagnoses between 1983 and 2018. Standardized incidence ratios (SIRs) and 95% confidence intervals were calculated for workers in specific occupational groups using (1) all other workers in the ODSS cohort, and (2) the general population of Ontario. RESULTS: SIRs using the general population reference group were generally equal to or modestly lower compared to SIRs using the internal reference group. Within occupation groups, SIRs had a discordant direction of association (increased rate in the internal comparison and decreased in the external comparison) for some cancer sites including urinary, prostate, and colorectal. CONCLUSIONS: Findings emphasize the importance of the choice of reference group when evaluating cancer risks in large occupational surveillance cohorts. Importantly, the magnitude of confounding and the healthy worker hire bias may depend on the occupation group and cancer site of interest.

2.
Biochim Biophys Acta Gen Subj ; 1868(8): 130651, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38825256

ABSTRACT

Cannabidiol (CBD) has antioxidant and anti-inflammatory activities. However, the anti-tumor effect of CBD on hepatocellular carcinoma (HCC) remains unclear. Here, we investigated whether CBD displays anti-tumorigenic effects in HCC cells and whether it could reduce tumorigenesis and metastases in vivo. First, this study treated HCC cells with different concentrations of CBD, followed by analyzing the changes in the proliferative, apoptotic, migratory and invasive abilities. The effects of CBD on the growth and metastasis of HCC cells in vivo were verified by tumorigenesis and metastasis assays. Subsequently, the target genes of CBD were predicted through the SwissTarget website and the genes differentially expressed in cells after CBD treatment were analyzed by microarray for intersection. The enrichment of the pathways after CBD treatment was analyzed by KEGG enrichment analysis, followed by western blot validation. Finally, rescue assays were used to validate the functions of genes as well as pathways in the growth and metastasis of HCC cells. A significant weakening of the ability of HCC cells to grow and metastasize in vitro and in vivo was observed upon CBD treatment. Mechanistically, CBD reduced GRP55 expression in HCC cells, along with increased TP53 expression and blocked MAPK signaling activation. In CBD-treated cells, the anti-tumor of HCC cells was restored after overexpression of GRP55 or deletion of TP53. CBD inhibits the MAPK signaling activation and increases the TP53 expression by downregulating GRP55 in HCC cells, thereby suppressing the growth and metastasis of HCC cells.


Subject(s)
Cannabidiol , Carcinoma, Hepatocellular , Liver Neoplasms , Receptors, Cannabinoid , Tumor Suppressor Protein p53 , Cannabidiol/pharmacology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Humans , Tumor Suppressor Protein p53/metabolism , Receptors, Cannabinoid/metabolism , Receptors, Cannabinoid/genetics , Animals , Cell Proliferation/drug effects , Cell Line, Tumor , Mice , Gene Expression Regulation, Neoplastic/drug effects , MAP Kinase Signaling System/drug effects , Apoptosis/drug effects , Cell Movement/drug effects , Phenotype , Mice, Nude
3.
Phytother Res ; 37(7): 2965-2978, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36879546

ABSTRACT

Acute lung injury (ALI) caused by acute bacterial infection remains a common life-threatening lung disease. An increased inflammatory response is the basis for the occurrence and development of ALI. Most antibiotics can only reduce the bacterial load but do not protect from lung damage because of an excessive immune response. Chrysophanol (chrysophanic acid, Chr), as a natural anthraquinone extracted from Rheum palmatum L., has various biological functions, including anti-inflammatory, anti-cancer activities, and ameliorative effects on cardiovascular diseases. Considering these properties, we investigated the effect of Chr in Klebsiella pneumoniae (KP)-induced ALI mice and its potential mechanism. Our results showed that Chr had protective effects against KP-infected mice, including increased survival rate, decreased bacterial burden, reduced recruitment of immune cells, and reduced reactive oxygen species level of lung macrophages. Chr reduced the expression of inflammatory cytokines by inhibiting the toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signaling pathway and inflammasome activation and strengthening autophagy. Overactivation of the TLR4/NF-κB signaling pathway by the activator Neoseptin 3 led to Chr losing control of inflammatory cytokines in cells, resulting in increased cell death. Similarly, overactivation of the c-Jun N-terminal kinase signaling pathway using the activator anisomycin resulted in Chr losing its inhibitory effect on NOD-like receptor thermal protein domain associated protein 3 (NFRP3) inflammasome activation, and cell viability was reduced. In addition, autophagy was blocked by siBeclin1, so Chr could not reduce inflammatory factors, and cell viability was markedly inhibited. Collectively, this work unravels the molecular mechanism underpinning Chr-alleviated ALI via inhibiting pro-inflammatory cytokines. Thus, Chr is a potential therapeutic agent for KP-induced ALI.


Subject(s)
Acute Lung Injury , NF-kappa B , Mice , Animals , NF-kappa B/metabolism , Toll-Like Receptor 4/metabolism , Klebsiella pneumoniae/metabolism , Inflammasomes , Acute Lung Injury/drug therapy , Acute Lung Injury/chemically induced , Anthraquinones/pharmacology , Anthraquinones/therapeutic use , Lung , Cytokines/metabolism , Lipopolysaccharides/pharmacology
4.
Phytomedicine ; 93: 153742, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34624808

ABSTRACT

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide, yet no effective medication for this disease is available. Cochlioquinone B derivative (CoB1), purified from Salvia miltiorrhiza endophytic Bipolaris sorokiniana, affects the defense against pulmonary pathogens by regulating inflammatory responses. However, the effect of CoB1 on lung cancer and the underlying molecular mechanisms remain unknown. In the present study, we investigate the protective effects of CoB1 on lung cancer and explore its underlying mechanism. METHOD: We examined the inhibitory effect of CoB1 on lung cancer cells (A549 cells) by MTT and colony formation assay. The effect of CoB1 on cytostatic autophagy in lung cancer cells was verified by Western blot, transmission electron microscopy, and confocal microscopy. The differentially expressed miRNAs were identified using quantitative RT-PCR. Luciferase assay and Northern blot were performed to verify the correlation between miRNA-125b and Foxp3. Protein expression in autophagy-related pathways was detected by Western blot. Xenograft tumor models were constructed to explore the inhibitory effect of CoB1 and the role of miRNA-125b as a suppressor in lung cancer in vivo. RESULT: CoB1 inhibited lung cancer cell proliferation by inducing cytostatic autophagy both in vitro and in vivo. CoB1-induced autophagy was related to blocking of the PI3K/Akt1/mTOR signaling pathway. In addition, CoB1 induced miR-125b expression via activating the TAK1/MKK4/JNK/Smad axis, thereby reducing Foxp3 expression and further inducing autophagy. CONCLUSION: This study is the first to report the specific inhibitory function of CoB1 purified from Salvia miltiorrhiza endophytic Bipolaris sorokiniana in lung cancer, which may be due to the induction of autophagy. This study provides evidence and novel insights into the anticancer efficacy of CoB1.


Subject(s)
Cytostatic Agents , Lung Neoplasms , MicroRNAs , Autophagy , Cell Line, Tumor , Cell Proliferation , Forkhead Transcription Factors , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , MicroRNAs/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction
5.
Mol Ther Oncolytics ; 20: 82-93, 2021 Mar 26.
Article in English | MEDLINE | ID: mdl-33575473

ABSTRACT

Lung cancer is the most frequent and fatal malignancy in humans worldwide, yet novel successful drugs for control of this disease are still lacking. Ipomoea batatas polysaccharides (IBPs) have been implicated in inhibiting diverse cancer types, but their functions in mitigating lung cancer are largely unknown. In this study, we identify a role of IBP in inhibiting lung cancer proliferation. We found that IBP significantly impedes the proliferation of lung cancer cells by inducing cytostatic macroautophagy both in vitro and in vivo. Mechanistically, IBP specifically promotes ubiquitination-mediated degradation of PAK1 (p21-activated kinase 1) and blocks its downstream Akt1/mTOR signaling pathway, leading to increased autophagic flux. In lung cancer xenografts in mice, IBP-induced cytostatic autophagy suppresses tumor development. Through site-directed mutational analysis, the underlying signaling augments ubiquitination via PAK1-ubiquitin interaction. Collectively, this work unravels the molecular mechanism underpinning IBP-induced cytostatic autophagy in lung cancer and characterizes IBP as a potential therapeutic agent for lung cancer treatment.

6.
Sci Rep ; 10(1): 20013, 2020 11 17.
Article in English | MEDLINE | ID: mdl-33203903

ABSTRACT

The study aimed to investigate the antibacterial effect and potential mechanisms of chlorogenic acid (CA) in Klebsiella pneumonia (KPN) induced infection in vitro and in vivo. 62 KPN strains were collected from the First People's Hospital of Yunnan Province. CA and CA combined Levofloxacin (LFX) were detected for KPN biofilm (BF) formation in vitro. The lung infection mice model were established by KPN. The effect of CA (500 mg/kg), LFX (50 mg/kg) and CA combined LFX (250 mg/kg + 25 mg/kg) were evaluated through the survival of mice, the changes of inflammation factors of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß and IL-6 in serum, the histopathological analysis of lung and the protein expression of NLRP3 signaling pathway in vivo. A total of 62 KPNs were isolated and identified, of which 13 (21%) strains were BF positive. 8 (13%) strains were extended spectrum ß-lactamase strains (ESBLs), and 20 (32%) strains are ESBLs biofilm positive. In vitro study, CA and LFX showed a synergistic effect on KPN biofilm formation. In vivo mice experiment, CA, especially CA + LFX treated group significantly decreased the serum levels of TNF-α, IL-1ß and IL-6, improved the survival ratio and lung pathology changes, and also reduced the protein expression of ASC, caspase 1 p20, IL-1ß and phosphor NF-κB p65. CA could effectively alleviate lung infection of KPN infected mice, and the antibacterial effection is strengthened by combined with LFX. The study provide a theroy basis for making rational and scientific antibacterial therapy strategy in clinic.


Subject(s)
Anti-Bacterial Agents/pharmacology , Chlorogenic Acid/pharmacology , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/drug effects , Levofloxacin/pharmacology , Animals , Anti-Bacterial Agents/therapeutic use , Biofilms/drug effects , Chlorogenic Acid/therapeutic use , Drug Resistance, Bacterial , Drug Synergism , Inflammation Mediators/blood , Inflammation Mediators/metabolism , Klebsiella Infections/microbiology , Klebsiella Infections/mortality , Levofloxacin/therapeutic use , Lung/drug effects , Lung/metabolism , Lung/pathology , Male , Mice , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/metabolism
7.
Front Cell Dev Biol ; 8: 552020, 2020.
Article in English | MEDLINE | ID: mdl-33240872

ABSTRACT

BACKGROUND: Salmonella typhimurium (ST) causes several intestinal diseases. Polyphenols including chlorogenic acid (CGA) inhibit pathogenesis. OBJECTIVE: This study aimed to investigate the mechanisms of CGA in ST infection. METHODS: The intestinal pathological changes and survival rate of ST-infected mice were measured to verify the protection of CGA on ST infection. The antibacterial effects of CGA in vitro on the invasion to intestinal epithelial cells and autophagy was evaluated. The relationships among GAS5, miR-23a, and PTEN were verified. Expression of inflammation- and autophagy-related proteins was detected. RESULTS: CGA treatment alleviated pathological damage, improved the secretion disturbance of intestinal cytokines caused by ST infection, and reduced the mortality of mice. Intestinal GAS5 was upregulated after CGA treatment. LncRNA GAS5 competitively bound to miR-23a to upregulate PTEN and inhibit the p38 MAPK pathway. CGA regulated the p38 MAPK pathway through lncRNA GAS5/miR-23a/PTEN axis to promote autophagy in ST infection. The functional rescue experiments of miR-23a and PTEN further identified these effects. CONCLUSION: CGA promotes autophagy and inhibits ST infection through the GAS5/miR-23a/PTEN axis and the p38 MAPK pathway.

9.
J Immunol ; 205(5): 1293-1305, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32747503

ABSTRACT

Owing to multiple antibiotic resistance, Pseudomonas aeruginosa causes the most intractable infections to human beings worldwide, thus exploring novel drugs to defend against this bacterium remains of great importance. In this study, we purified a novel cochlioquinone B derivative (CoB1) from Salvia miltiorrhiza endophytic Bipolaris sorokiniana and reveal its role in host defense against P. aeruginosa infection by activating cytoprotective autophagy in alveolar macrophages (AMs) both in vivo and in vitro. Using a P. aeruginosa infection model, we observed that CoB1-treated mice manifest weakened lung injury, reduced bacterial systemic dissemination, decreased mortality, and dampened inflammatory responses, compared with the wild type littermates. We demonstrate that CoB1-induced autophagy in mouse AMs is associated with decreased PAK1 expression via the ubiquitination-mediated degradation pathway. The inhibition of PAK1 decreases the phosphorylation level of Akt, blocks the Akt/mTOR signaling pathway, and promotes the release of ULK1/2-Atg13-FIP200 complex from mTOR to initiate autophagosome formation, resulting in increased bacterial clearance capacity. Together, our results provide a molecular basis for the use of CoB1 to regulate host immune responses against P. aeruginosa infection and indicate that CoB1 is a potential option for the treatment of infection diseases.


Subject(s)
Autophagy/drug effects , Benzoquinones/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/drug effects , TOR Serine-Threonine Kinases/metabolism , p21-Activated Kinases/metabolism , Animals , Cells, Cultured , Macrophages, Alveolar/drug effects , Macrophages, Alveolar/metabolism , Mice , Mice, Inbred C57BL , Pseudomonas Infections/metabolism , Signal Transduction/drug effects , Ubiquitination/drug effects
10.
Colloids Surf B Biointerfaces ; 185: 110616, 2020 Jan 01.
Article in English | MEDLINE | ID: mdl-31740323

ABSTRACT

Multidrug-resistant (MDR) bacterial strains have led to notable heathy threats to human beings. The demand for the development of effective antibacterial materials is increasing. Silver nanoparticles (AgNPs) and graphene-based nanomaterials are two major types of nanomaterials that are studied to inhibit and/or kill bacteria. In this study, by combining the excellent photothermal effect of graphene and antibacterial activity of AgNPs, we have applied reduced graphene oxide/silver (RGO/Ag) nanocomposite to destroy the MDR bacteria. The antibacterial activity of the RGO/Ag nanocomposite was systematically investigated using a regular bacterium of Escherichia coli (E. coli) and an MDR bacterium of Klebsiella pneumoniae (Kp). Compared with AgNPs, graphene oxide (GO) and RGO, the RGO/Ag nanocomposite showed significant higher antibacterial efficiency for both regular bacteria and MDR bacteria. Under a near-infrared (NIR) irradiation (0.30 W/cm2 for 10 min), the RGO/Ag nanocomposite demonstrated an enhanced synergetic antibacterial activity through the photothermal effect. Nearly 100 % of E. coli and Kp were killed by the treatment of 15 µg/mL and 30 µg/mL of RGO/Ag nanocomposite, respectively. Moreover, a membrane integrity assay and a reactive oxygen species (ROS) assay demonstrated that the RGO/Ag nanocomposite under NIR irradiation induced the cell membrane disruption and generation of ROS, providing possible mechanisms for their high antibacterial activity besides the photothermal effect. Finally, the cytotoxicity of the RGO/Ag nanocomposites toward different mammalian cells was studied, the cell viabilities retained above 60 % at higher concentrations of RGO/Ag, indicating that the RGO/Ag nanocomposites may be a low cytotoxic, efficient antibacterial agent with the irradiation.


Subject(s)
Anti-Bacterial Agents/pharmacology , Graphite/pharmacology , Hyperthermia, Induced , Nanocomposites/chemistry , Phototherapy , Silver/pharmacology , Bacteria/drug effects , Cell Death/drug effects , Cell Line, Tumor , Drug Synergism , Humans , Microbial Sensitivity Tests , Microbial Viability/drug effects , Oxidation-Reduction , Reactive Oxygen Species/metabolism
11.
mBio ; 10(4)2019 07 23.
Article in English | MEDLINE | ID: mdl-31337721

ABSTRACT

Pseudomonas aeruginosa, one of the most common pathogens in hospital-acquired infections, is tightly controlled by a multilayered regulatory network, including the quorum sensing system (QS), the type VI secretion system (T6SS), and resistance to host immunity. We found that the P. aeruginosa 3880 (PA3880) gene, which encodes an unknown protein, acts as a regulator of anaerobic metabolism in response to oxidative stress and virulence in P. aeruginosa More than 30 PA3880 homologs were found in other bacterial genomes, indicating that PA3880 is widely distributed in the Bacteria kingdom as a highly conserved gene. Deletion of the PA3880 gene changed the expression levels of more than 700 genes, including a group of virulence genes, under both aerobic and anaerobic conditions. To further study the mechanisms of PA3880-mediated regulation in virulence, we utilized a bacterial two-hybrid assay and found that the PA3880 protein interacted directly with QS regulator MvfR and anaerobic regulator Anr. Loss of the PA3880 protein significantly blunted the pathogenicity of P. aeruginosa, resulting in increased host survival, decreased bacterial burdens, reduced inflammatory responses, and fewer lung injuries in challenged mice hosts. Mechanistically, we found that Cys44 was a critical site for the full function of PA3880 in influencing alveolar macrophage phagocytosis and bacterial clearance. We also found that AnvM directly interacted with host receptors Toll-like receptor 2 (TLR2) and TLR5, which might lead to activation of the host immune response. Hence, we gave the name AnvM (anaerobic and virulence modulator) to the PA3880 protein. This characterization of AnvM could help to uncover new targets and strategies to treat P. aeruginosa infections.IMPORTANCE Infections by Pseudomonas aeruginosa, one of the most frequently isolated human pathogens, can create huge financial burdens. However, knowledge of the molecular mechanisms involved in the pathogenesis of P. aeruginosa remains elusive. We identified AnvM as a novel regulator of virulence in P. aeruginosa Deletion of anvM altered the expression levels of more than 700 genes under aerobic and anaerobic conditions, including quorum sensing system genes and oxidative stress resistance genes. AnvM directly interacted with MvfR and Anr, thus regulating their downstream genes. More importantly, AnvM directly bound to TLR2 and TLR5, which turn on the host immune response. These findings provide insights into the significance of AnvM homologs in pathogenic bacteria and suggest a potential drug target against bacterial infection.


Subject(s)
Bacterial Proteins/metabolism , Host-Pathogen Interactions , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/pathogenicity , Virulence Factors/metabolism , Anaerobiosis , Animals , Bacterial Proteins/genetics , Female , Gene Expression Regulation, Bacterial , Mice , Mice, Inbred C57BL , Oxidative Stress , Quorum Sensing , Toll-Like Receptor 5/metabolism , Toll-Like Receptors/metabolism , Virulence , Virulence Factors/genetics
12.
Breast Cancer ; 26(6): 766-775, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31172425

ABSTRACT

BACKGROUND: Icariin is a major component isolated from Epimedium brevicornum Maxim and has been reported to exhibit anti-tumor activity. However, whether icariin could reverse the acquired drug resistance in breast cancer remains largely unclear. Therefore, this study was designed to explore the antitumor effects of icariin and its underlying mechanisms in a tamoxifen-resistant breast cancer cell line MCF-7/TAM. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Lactate dehydrogenase (LDH) assay were performed to determine the effects of icariin on cell viability and cell death. Cell cycle progression and apoptosis were detected by flow cytometry analysis. Transmission electron microscopy (TEM) assay was utilized to observe cell autophagy. The downstream protein levels were measured using western blotting. RESULTS: Here, we observed that icariin treatment not only inhibited the growth of MCF-7 but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Moreover, icariin significantly induced cell cycle G0/G1 phase arrest and apoptosis, as well as suppressed autophagy. At molecular levels, icariin treatment remarkably down-regulated the expression levels of CDK2, CDK4, Cyclin D1, Bcl-2, LC3-1, LC3-II, AGT5, Beclin-1, but upregulated the expression levels of caspase-3, PARP and p62. Most importantly, we found inhibition of autophagy via 3-MA treatment could significantly enhance the effects of icariin on cell viability and apoptosis. Enhanced autophagy via autophagy related 5 (ATG5) overexpression could partially reverse the effects of icariin on cell viability and apoptosis. CONCLUSION: These results revealed that icariin might potentially be useful as an adjuvant agent in cancer chemotherapy to enhance the effect of tamoxifen through suppression of autophagy in vitro and provide insight into the therapeutic potential of icariin for the treatment of chemo-resistant breast cancer.


Subject(s)
Apoptosis/drug effects , Autophagy/drug effects , Breast Neoplasms/pathology , Drug Resistance, Neoplasm/drug effects , Flavonoids/pharmacology , Plant Extracts/pharmacology , Tamoxifen/adverse effects , Autophagy-Related Protein 5/genetics , Autophagy-Related Protein 5/metabolism , Breast Neoplasms/drug therapy , Caspase 3/metabolism , Cell Cycle Checkpoints/drug effects , Cell Survival/drug effects , Epimedium/chemistry , Female , Humans , MCF-7 Cells , Poly(ADP-ribose) Polymerases/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Selective Estrogen Receptor Modulators/adverse effects , Selective Estrogen Receptor Modulators/therapeutic use , Signal Transduction/drug effects , Tamoxifen/therapeutic use , Transfection
13.
Mol Med Rep ; 19(3): 2057-2064, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30664158

ABSTRACT

The present study aimed to investigate the anti­arthritic effects of curculigoside isolated from the rhizome of Curculigo orchioides Gaertn in vivo and in vitro, as well as to determine the potential underlying mechanisms. A rat model of arthritis was induced with type II collagen. Arthritic rats were treated with curculigoside (50 mg/kg) and blood samples were collected to determine serum levels of tumor necrosis factor (TNF)­α, interleukin (IL)­1ß, IL­6, IL­10, IL­12 and IL­17A. Furthermore, indices of the thymus and spleen were determined. The anti­proliferative effects of curculigoside were detected with Cell Counting kit­8 assays in rheumatoid arthritis­derived fibroblast­like synoviocyte MH7A cells. In addition, expression levels of Janus kinase (JAK)1, JAK3, signal transducer and activator of transcription (STAT)3, nuclear factor (NF)­κB p65 and its inhibitor (IκB) were determined by western blotting. The results revealed that curculigoside inhibited paw swelling and arthritis scores in type II collagen­induced arthritic (CIA) rats. Additionally, curculigoside decreased serum levels of TNF­α, IL­1ß, IL­6, IL­10, IL­12 and IL­17A in CIA rats. Curculigoside also significantly inhibited MH7A cell proliferation in a time and concentration­dependent manner. Furthermore, treatment downregulated the expression of JAK1, JAK3 and STAT3, and upregulated cytosolic nuclear factor (NF)­κB p65 and IκB. In conclusion, the results of the present study indicated that curculigoside exhibited significant anti­arthritic effects in vivo and in vitro, and the molecular mechanism may be associated with the JAK/STAT/NF­κB signaling pathway.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Benzoates/administration & dosage , Glucosides/administration & dosage , Janus Kinase 1/genetics , Janus Kinase 3/genetics , STAT3 Transcription Factor/genetics , Animals , Arthritis, Rheumatoid/chemically induced , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/pathology , Cell Proliferation/drug effects , Collagen Type II/toxicity , Disease Models, Animal , Gene Expression/drug effects , Humans , I-kappa B Proteins/genetics , Interleukins/genetics , Rats , Signal Transduction , Synoviocytes/drug effects , Transcription Factor RelA/genetics , Tumor Necrosis Factor-alpha/genetics
14.
Int J Clin Exp Pathol ; 12(6): 2075-2083, 2019.
Article in English | MEDLINE | ID: mdl-31934029

ABSTRACT

This study aimed to investigate the therapeutic effects and mechanism of action of curcumin against a MRL/lpr lupus model. Eight-week-old female MRL/lpr mice were used to establish the lupus nephritis model. Histologic and immunohistochemical analysis was conducted for lupus nephritis. Anti-dsDNA IgG and BAFF level were detected by ELISA. Cells directly isolated from the spleen were used to detect macrophage subsets and activation status by FACS. Curcumin reduced the total IgG and anti-dsDNA IgG levels in blood and reduced the activation of B cells in MRL/lpr mice. Moreover, curcumin prevented activation of macrophages in MRL/lpr mice. Levels of BAFF in serum, spleens and kidneys were also reduced in curcumin-treated MRL/lpr mice. In vitro experiments showed that curcumin reduced the activation of macrophage and leaded to the decrease of BAFF from them upon toll like receptor (TLR) 4 stimulation. Curcumin attenuates lupus nephritis in MRL/lpr mice by inhibiting macrophages activation and their secreting BAFF, which may be a potential therapeutic candidate for the treatment of SLE.

15.
Int J Clin Exp Pathol ; 11(1): 76-87, 2018.
Article in English | MEDLINE | ID: mdl-31938089

ABSTRACT

BACKGROUND: Lung epithelial cell dysfunction induced by hyperoxia-associated oxidative stress is a prominent feature involved in the development of acute lung injury (ALI). How the underlying molecular mechanisms contributed to this process are poorly defined. In the present study, we sought to identify the role of miR-124 in hyperoxia-induced cell apoptosis and excessive inflammatory response in pulmonary epithelial cell. METHODS: The miR-124 levels in pulmonary epithelial cell were assayed by qRT-PCR. MiR-124 mimics and inhibitors were transfected to gain or loss of miR-124 function. Cell proliferation was analyzed by CCK8 assay. Cell apoptosis was analyzed by flow cytometry. The targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. The protein levels were assayed by western blotting. RESULTS: The results showed that miR-124 was significantly down-regulated in Beas2B cells and primary LECs upon hyperoxia exposure conditions. However, overexpression of miR-124 dramatically attenuated hyperoxia-provoked TLR4, NF-κB and pro-inflammatory cytokines production. In vitro, the cell viability and apoptosis was significantly reversed following transfection with miR-124 mimics in the presence of hyperoxia. Furthermore, the 3'-untranslated region (3'-UTR) of CCL2 was bound by miR-124. CONCLUSION: It was concluded that miR-124 inhibited hyperoxia-induced apoptosis and excessive inflammatory response in Beas2B cells and primary LECs, at least partially, through the inhibition of TLR4/NF-κB/CCL2 signaling cascades.

18.
Oncol Rep ; 38(2): 611-624, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28627697

ABSTRACT

Nanomaterials are increasingly used as drug carriers for cancer therapy. Nanomaterials also appeal to researchers in the areas of cancer diagnosis and biomarker discovery. Several antitumor nanodrugs are currently being tested in preclinical and clinical trials and show promise in therapeutic and other settings. We review the development of nanomaterial drug carriers, including liposomes, polymer nanoparticles, dendritic polymers, and nanomicelles, for the diagnosis and treatment of various cancers. The prospects of nanomaterials as drug carriers for future clinical applications are also discussed.


Subject(s)
Drug Delivery Systems/trends , Nanotechnology/trends , Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Dendrimers/therapeutic use , Humans , Liposomes/therapeutic use , Nanoparticles/therapeutic use
19.
Colloids Surf B Biointerfaces ; 157: 1-9, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28554055

ABSTRACT

Graphene is a novel two-dimensional nanomaterial with a growing number of practical applications across numerous fields. In this work, we explored potential biomedical applications of graphene oxide (GO) by systematically studying antibacterial capacity of GO in both macrophages and animal models. Three types of bacteria, including Klebsiella pneumoniae (Kp), Escherichia coli (E. coli) and P. aeruginosa (Pa) were used for in vitro study. Kp was also selected as a representative multidrug resistant (MDR) bacterium for in vivo study. In in vitro study, GO effectively eradicated Kp in agar dishes and thus protected alveolar macrophages (AM) from Kp infection in the culture. In the in vivo evaluation, GO were introduced intranasally into mouse lungs followed by testing organ tissue damage including lung, liver, spleen, and kidneys, polymorphonuclear neutrophil (PMN) penetration, bacterial dissemination, and mortality in Kp-infected mice. We found that GO can prohibit the growth and spread of Kp both in vitro and in vivo, resulting in significantly increased cell survival rate, less tissue injury, subdued inflammatory response, and prolonged mice survival. These findings indicate that GO could be a promising biomaterial for effectively controlling MDR pathogens.


Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Graphite/pharmacology , Graphite/therapeutic use , Nanostructures/chemistry , Animals , Anti-Bacterial Agents/chemistry , Drug Resistance, Multiple, Bacterial , Escherichia coli/drug effects , Female , Graphite/chemistry , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/pathogenicity , Mice , Mice, Inbred C57BL , Microbial Sensitivity Tests , Pseudomonas aeruginosa/drug effects
20.
J Immunol ; 198(8): 3205-3213, 2017 04 15.
Article in English | MEDLINE | ID: mdl-28258192

ABSTRACT

Sepsis is a severe and complicated syndrome that is characterized by dysregulation of host inflammatory responses and organ failure, with high morbidity and mortality. The literature implies that autophagy is a crucial regulator of inflammation in sepsis. In this article, we report that autophagy-related protein 7 (Atg7) is involved in inflammasome activation in Pseudomonas aeruginosa abdominal infection. Following i.p. challenge with P. aeruginosa, atg7fl/fl mice showed impaired pathogen clearance, decreased survival, and widespread dissemination of bacteria into the blood and lung tissue compared with wild-type mice. The septic atg7fl/fl mice also exhibited elevated neutrophil infiltration and severe lung injury. Loss of Atg7 resulted in increased production of IL-1ß and pyroptosis, consistent with enhanced inflammasome activation. Furthermore, we demonstrated that P. aeruginosa flagellin is a chief trigger of inflammasome activation in the sepsis model. Collectively, our results provide insight into innate immunity and inflammasome activation in sepsis.


Subject(s)
Autophagy-Related Protein 7/immunology , Inflammasomes/immunology , Pseudomonas Infections/immunology , Pyroptosis/immunology , Sepsis/immunology , Animals , Autophagy-Related Protein 7/deficiency , Disease Models, Animal , Immunity, Innate/immunology , Immunoblotting , Inflammasomes/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Confocal , Pseudomonas Infections/metabolism , Pseudomonas aeruginosa/immunology , Sepsis/metabolism
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