Green mechanochemical activation of solid persulfate to remove PAHs in soil: Performance and mechanism.

Due to the high biotoxicity and persistence of polycyclic aromatic hydrocarbons (PAHs), the remediation of PAHs-contaminated soil becomes an intractable problem. Persulfate-based advanced oxidation processes are widely used to degrade PAHs in aquatic environment. However, they are not convenient for used in soil due to the heterogeneity and complexity of soil matrix. In this study, a green and convenient ball milling process is introduced to activate persulfate for the remediation of PAHs-contaminated soil. About 82.5% PAHs were removed with 10% wt. Na2S2O8 (PS) addition and ball-milling for 2 h under 500 r/min. The degradation of PAHs is attributed to the attack of radicals (SO4·- and·OH) generated from the activation of PS by mechanochemistry. Moreover, stable Si-O bonds were disrupted during ball-milling process, and formed free electron on the surface of soil particles. This facilitates the electron transfer from oxidants to contaminants. The particle size, surface element composition, functional group, and thermogravimetric analysis confirmed the slight disturbance of ball-milling-assisted PS process on the physical and chemical properties of soil. Therefore, ball-milling assisted PS approach would be a promising technology for the remediation of PAHs-contaminated soil.

Anti-inflammatory effects of brucea javanica oil via inhibition of NF-κB activation.

OBJECTIVE: As a traditional herbal medicine extracted from the seeds of Brucea javanica, Brucea javanica oil (BJO) has been clinically used to treat wart, chronic gastroenteritis and a variety of malignant tumors, including gastrointestinal cancer and lung cancer. We have recently reported the anti-tumor role and possible molecular mechanisms of BJO in treatment of lung cancer. However, it remains elusive whether BJO also has an anti-inflammatory effect. METHODS: The pneumonia-related inflammatory factors of macrophages under LPS treatment were investigated by real-time PCR and ELISA assays. LPS-induced acute pneumonia rat model was established. Hematoxylin and eosin (HE) examination was performed to detect histopathological changes in the lung tissues. Real-time PCR and ELISA assays were also used to detect the pneumonia-related inflammatory factors in lung tissues. RESULTS: LPS-induced expression and secretion of pneumonia-related inflammatory factors (TNF-α, IL-1ß, IL-6 and IL-8) were significantly suppressed by BJO in a concentration-dependent manner in RAW264.7 cells. However, BJO did not affect cell proliferation and survival rate. Further mechanistic studies revealed that BJO down-regulated the phosphorylation of IκB and p65, thereby inhibiting NF-κB pathway of macrophages and exerting its anti-inflammatory function. Western blot analysis showed that the phosphorylation levels of IκB and p65 were significantly up-regulated while the protein level of IκB was inhibited upon LPS stimulation in RAW264.7 cells and in lung tissue. Notably, LPS stimulation levels of IκB and p65 were effectively reversed under BJO co-treatment. The expression level of p65 was not influenced by LPS and BJO treatment. HE staining results showed that BJO can reduce the infiltration of inflammatory cells in lung. CONCLUSION: BJO can reduce the level of inflammatory factors in lung tissue, which provides a theoretical basis for BJO emulsion as an adjuvant therapy for pneumonia.

The HNF4α-BC200-FMR1-Positive Feedback Loop Promotes Growth and Metastasis in Invasive Mucinous Lung Adenocarcinoma.

Invasive mucinous lung adenocarcinoma (IMA) is a subtype of lung adenocarcinoma with a strong invasive ability. IMA frequently carries "undruggable" KRAS mutations, highlighting the need for new molecular targets and therapies. Nuclear receptor HNF4α is abnormally enriched in IMA, but the potential of HNF4α to be a therapeutic target for IMA remains unknown. Here, we report that P2 promoter-driven HNF4α expression promotes IMA growth and metastasis. Mechanistically, HNF4α transactivated lncRNA BC200, which acted as a scaffold for mRNA binding protein FMR1. BC200 promoted the ability of FMR1 to bind and regulate stability of cancer-related mRNAs and HNF4α mRNA, forming a positive feedback circuit. Mycophenolic acid, the active metabolite of FDA-approved drug mycophenolate mofetil, was identified as an HNF4α antagonist exhibiting anti-IMA activities in vitro and in vivo. This study reveals the role of a HNF4α-BC200-FMR1-positive feedback loop in promoting mRNA stability during IMA progression and metastasis, providing a targeted therapeutic strategy for IMA. SIGNIFICANCE: Growth and metastatic progression of invasive mucinous lung adenocarcinoma can be restricted by targeting HNF4α, a critical regulator of a BC200-FMR1-mRNA stability axis.

Matrine Reverses the Warburg Effect and Suppresses Colon Cancer Cell Growth via Negatively Regulating HIF-1α.

The Warburg effect is a peculiar feature of cancer's metabolism, which is an attractive therapeutic target that could aim tumor cells while sparing normal tissue. Matrine is an alkaloid extracted from the herb root of a traditional Chinese medicine, Sophora flavescens Ait. Matrine has been reported to have selective cytotoxicity toward cancer cells but with elusive mechanisms. Here, we reported that matrine was able to reverse the Warburg effect (inhibiting glucose uptake and lactate production) and suppress the growth of human colon cancer cells in vitro and in vivo. Mechanistically, we revealed that matrine significantly decreased the messenger RNA (mRNA) and protein expression of HIF-1α, a critical transcription factor in reprogramming cancer metabolism toward the Warburg effect. As a result, the expression levels of GLUT1, HK2, and LDHA, the downstream targets of HIF-1α in regulating glucose metabolism, were dramatically inhibited by matrine. Moreover, this inhibitory effect of matrine was significantly attenuated when HIF-1α was knocked down or exogenous overexpressed in colon cancer cells. Together, our results revealed that matrine inhibits colon cancer cell growth via suppression of HIF-1α expression and its downstream regulation of Warburg effect. Matrine could be further developed as an antitumor agent targeting the HIF-1α-mediated Warburg effect for colon cancer treatment.

Correlated low IGF2BP1 and FOXM1 expression predicts a good prognosis in lung adenocarcinoma.

IGF2BP1 and FOXM1 are shown to be critical in the regulation of caner progression. However, the prognostic value of IGF2BP1 in lung adenocarcinoma and its relationship with FOXM1 still remains unclear. In this study, the expression and biological significance of both IGF2BP1 and FOXM1 were evaluated in 188 lung adenocarcinoma, at mRNA and protein levels. We showed that mRNA and protein levels of IGF2BP1 and FOXM1 were upregulated in lung adenocarcinoma compared to adjacent non-cancerous tissues. High IGF2BP1 expression was correlated with a poor prognosis for lung adenocarcinoma patients. Moreover, IGF2BP1 expression was positively associated with FOXM1 expression. Meanwhile, the findings indicated that low IGF2BP1 combined with low FOXM1 expression, was negatively correlated with pathological stage and lymph node metastasis, predicted good outcomes for lung adenocarcinoma patients. Additionally, low IGF2BP1 and FOXM1 expression status, is an independent prognostic factor for lung adenocarcinoma after surgical resection. We demonstrate that low IGF2BP1 and FOXM1 expression can serve as a potential factor for the clinical diagnosis and prognosis of lung adenocarcinoma, and targeted inhibition of IGF2BP1 and FOXM1 might be an alternative strategy for the management of lung adenocarcinoma.

Co-outbreak of multidrug resistance and a novel ST3006 Klebsiella pneumoniae in a neonatal intensive care unit: A retrospective study.

The outbreak of carbapenem-resistant Klebsiella pneumoniae is a serious public health problem, especially in the neonatal intensive care unit (NICU).Fifteen K. pneumoniae strains were isolated from 7 neonates during June 3 to 28, 2017 in an NICU. Antimicrobial susceptibility was determined by the Vitek 2 system and microbroth dilution method. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were used to analyze the genetic relatedness of the isolates. Whole-genome sequencing and gene function analysis were performed to investigate pathogenicity and drug resistance and screen genomic islands.Three clones of K. pneumoniae were identified from 7 neonates: 7 strains of ST37, 7 of novel ST3006, and 1 of ST1224. Gene sequencing showed that the kpn1343 (ST37) strain harbored 12 resistance genes (OXA-33, TEM-1, SHV-11, AAC (6')-IId, AAC (3)-IIa, AAC (6')-Ib-cr, catB3, arr-3, sul1, oqxB, oqxA, CRP, and catB3) and included 15 genomic islands and 205 reduced virulence genes. The kpn1344 (ST3006) strain harbored 4 antibiotic-resistant genes (TEM-1, CTX-M-3, vgaC, and CRP) and included 19 genomic islands and 209 reduced virulence genes. MLST and PFGE showed that 15 strains of K. pneumoniae were divided into 3 groups with a high level of homology. ST1224 (kpn1362) was isolated on June 28, 2017, which was 10 days after the last isolate (kpn1359, June 18, 2017); thus, we speculated that ST1224 was not the clone that caused the outbreak.This co-outbreak of K. pneumoniae involved 2 clones: ST37 and ST3006. ST37 carried the multidrug-resistant genes, such as OXA-33, TEM-1, and SHV-11, and ST3006 was a novel K. pneumoniae ST typing. Whole-genome sequencing may be an effective method for screening bacterial-resistant genes and their functions.

PD-1 Polymorphisms Are Associated with Susceptibility of Acute Anterior Uveitis in Chinese Population.

Acute anterior uveitis (AAU) is an ordinary type of uveitis, which is an autoimmune disease produced by T cells. Programmed apoptosis protein 1 (PD-1) is a vital negative regulatory protein of immune tolerance. We detect the single nucleotide polymorphisms (SNPs) rs41386349, rs10204525, and rs2227982 of PD-1 to investigate the correlation between PD-1 polymorphisms and AAU. A total of 166 AAU patients and 263 controls were recruited in this case-control study. Compared with controls, the frequencies of the GG genotypes were higher in rs10204525 in AAU patients (p = 0.012). There were obvious increases in frequencies of the TT genotypes in rs2227982 and the GG genotypes in rs10204525 in human leukocyte antigen (HLA)-B27-negative AAU patients compared with controls (p = 0.03; p = 0.015, respectively). There were also increases in frequencies of TT genotypes in rs2227982 and the GG genotypes in rs10204525 in the patients without ankylosing spondylitis (AS) when compared with controls (p = 0.021; p = 0.003, respectively). Furthermore, the frequencies of TT genotypes in rs2227982 were higher in female patients diagnosed with AAU than with control group (p = 0.033). Our results showed that SNPs rs2227982 and rs10204525 were interrelated to AAU; the influence on AAU could be related with gender, HLA-B27, and AS status.

Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3ß/ß-catenin signaling pathways.

Sulforaphane is a common antioxidant selectively abundant in cruciferous plants, which exhibits effective anti-cancer actions in control of tumorigenesis or progression of various cancers. A recent study has shown that sulforaphane attenuates the EGFR signaling pathway in non-small cell lung cancer (NSCLC), suggesting its potential anti-metastatic effects. In this study we assessed the involvement of sulforaphane and miR-616-5p in epithelial-mesenchymal transition (EMT) and NSCLC metastasis. Sulforaphane suppressed the cell proliferation in human NSCLC cell lines H1299, 95C and 95D with IC50 values of 9.52±1.23, 9.04±1.90 and 17.35±2.03 µmol/L, respectively. At low concentrations (1-5 µmol/L), sulforaphane dose-dependently inhibited the migration and invasion of 95D and H1299 cells with relatively high metastatic potential. The anti-metastatic action of sulforaphane was confirmed in 95D and H1299 cell xenografts in vivo. In fresh NSCLC tissue samples from 179 patients, miR-616-5p levels were upregulated in late-stage NSCLCs, and strongly correlated with risk of NSCLC recurrence and metastasis. Consistent with the clinic observation, miR-616-5p levels in the 3 NSCLC cell lines were correlated with their metastatic ability, and were decreased by sulforaphane treatment. Silencing miR-616-5p markedly suppressed the migration and invasion of 95D cells in vitro and NSCLC metastasis in vivo. Further studies revealed that miR-616-5p directly targeted GSK3ß and decreased its expression, whereas sulforaphane decreased miR-616-5p levels by histone modification, and followed by inactivation of the GSK3ß/ß-catenin signaling pathway and inhibition of EMT, which was characterized by loss of epithelial markers and acquisition of a mesenchymal phenotype in NSCLC cells. Our findings suggest that sulforaphane is a potential adjuvant chemotherapeutic agent for the prevention of NSCLC recurrence and metastasis, and miR-616-5p can be clinically utilized as a biomarker or therapeutic target to inhibit metastasis.

Seed Oil of Brucea javanicaInduces Cell Cycle Arrest and Apoptosis via Reactive Oxygen Species-Mediated Mitochondrial Dysfunction in Human Lung Cancer Cells.

Brucea javanica oil (BJO), a traditional herbal medicine extracted from the seeds of B. javanica, has been clinically used to treat non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in combination with chemotherapy or radiotherapy in China. However, how BJO exerts this antitumor effect is still largely unknown. Here, effects of BJO on the growth of NSCLC and SCLC cell lines were investigated by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenytetrazolium Bromide (MTT) assay, and the results showed that BJO inhibited the proliferation of A549 cells (NSCLC) and H446 cells (SCLC). Further studies revealed that BJO induced G0/G1 arrest partly via regulating p53 and cyclin D1 in these two cell lines. BJO also has pro-apoptotic effect on H446 and A549 cells through mitochondria/caspase-mediated pathway, which was initiated by the accumulation of intracellular reactive oxygen species (ROS). These findings thus revealed the molecular mechanisms underlying the antitumor effect of BJO on SCLC and NSCLC, which may benefit the further clinical application of BJO.

[Effects of Xiangsha Liujunzi decoction on TLR signal pathway in gastric mucosa tissues of rats with Helicobacter pylori-induced chronic atrophic gastritis].

To explore the effects and mechanism of Xiangsha Liujunzi decoction on TLR signal pathway in gastric mucosa tissues of rats with Helicobacter pylori-related gastritis, sixty SD rats were randomly divided into control group, model group, high concentration of Xiangsha Liujunzi decoction group, moderate concentration of Xiangsha Liujunzi decoction group, low concentrations of Xiangsha Liujunzi decoction group and SB203580-treated group, with 10 rats in each group. SD rats of Hp-associated chronic atrophic gastritis models were established by intragastric gavage of Helicobacter pylori (HP) suspension. Changes in the gastric mucosa of rats were assessed by histopathology. ELISA was applied to detect the expressions of TNF-α and IL-6 in the serum, and the activity of iNOS in gastric mucosa. The content of NO in the gastric mucosa was tested by nitrate reductive enzymatic. The expressions of TLR2, TLR4, P38MAPK, NF-κB were detected by QPCR and Western-blot. The results indicated that the clinical symptoms of rats and pathological changes of gastric mucosa were improved in Xiangsha Liujunzi decoction group. Compared with normal control group, the protein expressions of TLR2, TLR4, p-P38MAPK and NF-κB in gastric mucosa of model group rats increased (P<0.01) with the levels of TNF-α and IL-6 in the serum, and the activity of iNOS and the content of NO in gastric mucosa increased. Compared with model group, the expressions decreased in Xiangsha Liujunzi decoction group, especially in the high concentration of Xiangsha Liujunzi decoction group(P<0.01), with gradually increased rate of HP eradication and decreased pathological grades of chronic atrophic gastritis. The serum level of TNF-α and IL-6 decreased from (24.313±2.261) µg•L ⁻¹ to (15.195±1.235) µg•L-1(P<0.01) and from (77.416±8.095) µg•L ⁻¹ to (33.150±2.532) µg•L ⁻¹ (P<0.01), and the activity of iNOS and the content of NO in gastric mucosa decreased from (1.530±0.206) U•mg ⁻¹ to (0.802±0.091) U•mg ⁻¹ (P<0.01) and from (0.907±0.032) mmol•g ⁻¹ to (0.335±0.026) mmol•g ⁻¹ (P<0.01) after the treatment of high concentration of Xiangsha Liujunzi decoction. All the effects increased with the increasing dosage of Xiangsha Liujunzi decoction from 0.324 g•mg ⁻¹ to 1.296 g•mg ⁻¹. The protein expressions of NF-κB decreased in the gastric mucosa after treated with P38MAPK specific inhibitor-SB203580. In the rats model, HP infection results in chronic atrophic gastritis through the activation of TLR2, TLR4/MAPK/NF-κB/iNOS/NO signal pathway. Xiangsha Liujunzi decoction can eradicate H. pylori and alleviate chronic atrophic gastric mucosal inflammation. The treatment is effective and safe to cure HP-induced chronic atrophic gastritis.

[The application of loop-mediated isothermal amplification for detection of common pathogenic bacteria in lower respiratory tract infections].

OBJECTIVE: To investigate the spectrum of common pathogenic bacteria of low respiratory tract infection by loop-mediated isothermal amplification (LAMP) of nucleic acid test and to prove the clinical significance of this method. METHODS: A total of 289 qualified sputum samples from patients with lower respiratory tract infections in Fujian Province were detected by LAMP technique, and then the distribution of pathogenic bacteria was analyzed. The positive cases (the patients whose specific bacterial copies in their sputum samples > 1×10(3) copies/ml) were divided into 2 groups according to whether their treatment had covered this pathogen or not. The underlying diseases, duration of anti-bacterial treatment, the hospital days, and the effectiveness of initial treatment and cure rate were compared. RESULTS: The culture method in the 289 patients showed that 44 (15.2%) were positive. Tests by the LAMP method with a bacteria concentration > 1×10(3) copies/ml as cutoff value, showed positive results in 124 patients (43.0%). The lower respiratory tract pathogens included 144 strains of bacteria (77.8%), and 41 strains of atypical pathogens (22.2%). Gram-negative bacteria were the predominant pathogens, such as Pseudomonas aeruginosa, H. influenzae, Klebsiella pneumoniae, and Streptococcus pneumoniae. In 95 cases the initial therapy had covered the pathogens, while in 29 cases the initial therapy had not. The effectiveness of the initial treatment (χ(2) = 31.0, P < 0.01) and the total days of hospital stay (t = -2.083, P = 0.039) in the group whose antibiotics had covered the pathogens were significantly higher than those of the other group. However, there were no significant difference in duration of anti-bacterial treatment (t = -1.073, P = 0.285)and cure rates (χ(2) = 0.6, P = 0.4) between the 2 groups. CONCLUSIONS: LAMP method can detect the nuclear acid of the bacteria in the sputum much more rapidly and sensitively than the routine culture method. LAMP technique may be helpful to know the pathogenic bacteria before treatment, and therefore may improve the choice of initial antibiotic therapy.

Serological and molecular capsular typing, antibiotic susceptibility and multilocus sequence typing of Streptococcus pneumoniae isolates from invasive and non-invasive infections.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a major causative agent of severe infections, including sepsis, pneumonia, meningitis, and otitis media, and has become a major public health concern. We report the pneumococcal serotype and sequence type (ST) distribution, and antimicrobial resistance of 39 S. pneumoniae strains from seven hospitals in China. METHODS: Blood/cerebrospinal fluid (CSF) and sputum isolates from patients were analyzed to determine S. pneumoniae serotypes by polymerase chain reaction (PCR) and the Neufeld Quellung reaction, the multilocus sequence types (MLST) by PCR and sequencing, and susceptibility to antimicrobial agents by the VITEK Gram Positive Susceptibility Card. RESULTS: A total of 39 isolates were collected including 21 blood/CSF and 18 sputum isolates. Conventional serotyping by the Quellung reaction required 749 reactions. In contrast, PCR based typing needed only 106 PCR reactions. The most frequent serotypes from the blood/CSF isolates were 14 (38.1%), 19A (14.3%), 23F (9.5%), and 18C (9.5%). In the sputum isolates the most frequent serotypes were 19F (33.3%), 23F (16.7%), 19A (11.1%), and 3 (11.1%). The incidence of penicillin resistance in the blood/CSF and sputum isolates was 66.7% and 55.6%, respectively. Statistical analysis showed that patients = 5 years old had a higher resistance to penicillin when they compared with the patients = 65 years old (P = 0.011). Serotypes 14, 19A and 19F were significantly associated with penicillin resistance (P < 0.001). ST320, ST271, and ST876 isolates showed high resistant rates to several antibiotics including penicillin (P = 0.006). All of the isolates of serotype 19A were resistant to both penicillin and erythromycin, and they were all multi-drug resistant (MDR) isolates. CONCLUSIONS: The specificity and sensitivity of multiplex-PCR are good, and this method represents a substantial savings of time and money, and can be widely used in the laboratory and clinical practice. Data from this research showed an extremely high prevalence of penicillin resistance and an increasing prevalence of multi-drug resistant (MDR) rate in S. pneumoniae. A distinctive emergence of serotype 19A was observed which was also associated with the increasing prevalence of antimicrobial resistance. Therefore, nationwide surveillance of pneumococcal resistance and serotypes is strongly warranted.