Expression and Prognostic Value of Glucose Transporter 3 in Diffuse Large B Cell Lymphoma.

BACKGROUND: Several reports have suggested that glucose transporter 3 (GLUT-3) promotes tumor metastasis. The aim of this study was to examine the relationship between the expression level of GLUT-3 and the prognosis of patients with diffuse large B cell lymphoma (DLBCL). METHODS: The GLUT-3 expression levels in 91 DLBCL patients were evaluated by immunohistochemistry. The relationships between GLUT-3 expression level and clinicopathological characteristics and progression-free survival (PFS) of DLBCL patients were analyzed. The use of validation cohorts confirmed the predictive value of GLUT-3 expression. The correlation between GLUT-3 and immune cell infiltration was investigated using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts system and the analysis of the infiltrating score was obtained by single sample Gene Set Enrichment Analysis. RESULTS: Expression of GLUT-3, which is highly expressed in DLBCL patients, was significantly associated with elevated serum LDH level, recurrence and Ki-67 status. Kaplan-Meier analysis showed that high GLUT-3 expression levels in DLBCL were related to poor PFS. Univariate and multivariate analyses results showed that low GLUT-3 expression level was significantly but independently associated with favorable PFS in DLBCL patients. GLUT-3 expression was also correlated with immune cell infiltration and the analysis of the infiltrating score. CONCLUSION: Our results indicate that GLUT-3 may act as a potential independent prognostic factor in DLBCL patients. The difference of the immune microenvironment in DLBCL patients may be predicted by the expression level of GLUT-3.

Long Noncoding RNA KCNMB2-AS1 Promotes SMAD5 by Targeting miR-3194-3p to Induce Bladder Cancer Progression.

PURPOSE: Bladder cancer is a common malignant tumor of the urinary system, with the fourth-highest incidence of male malignant tumors in Europe and the United States. So far, the mechanism of bladder cancer progression and metastasis has not been clarified. The aim of our study was to validate the way of long noncoding RNA (lncRNA) KCNMB2-AS1 on the metabolism and growth of bladder cancer cells by miR-3194-3p/SMAD5. PATIENTS AND METHODS: The Gene Expression was analyzed by qRT-PCR in bladder cancer tissues and cell lines, with the highly expressed KCNMB2-AS1 screened out. Cell proliferation was detected by Edu staining and clone formation assay, cell migration, and invasion by wound healing and transwell assays. Cell stemness was determined by assessing sphere-forming ability and stemness marker. Correlation between miRNA and lncRNA/gene was verified by dual-luciferase assay and RIP, and the effect of KCNMB2-AS1 on bladder cancer growth by nude mice tumor formation experiment. RESULTS: Here, we revealed the increased level of KCNMB2-AS1 in bladder cancer for the first time. Knockdown of KCNMB2-AS1 in vitro prevented the ability of proliferation, metastasis, and stemness of cancer cells. In vivo, the silencing of KCNMB2-AS1 also prevented tumor growth in vivo. Next, we revealed that KCNMB2-AS1 could interact with miR-3194-3p and uncovered that SAMD5 was a downstream target of miR-3194-3p. CONCLUSION: In conclusion, KCNMB2-AS1 mediated the bladder cancer cells progress by regulating the miR-3194-3p/SAMD5 signal pathway, which would provide a new target for bladder cancer research.

LncRNA HOTAIR induces sunitinib resistance in renal cancer by acting as a competing endogenous RNA to regulate autophagy of renal cells.

BACKGROUND: Cell autophagy has been proposed to be involved in drug resistance therapy. However, how the long non-coding RNA (lncRNA) reduces risks of drug resistance in renal cancer (RC) cells needs a thorough inquiry. This study was assigned to probe the effect and mechanism of HOTAIR on sunitinib resistance of RC. METHODS: Clinical RC tissues and para-carcinoma tissues were obtained to detect the expressions of miR-17-5p, HOTAIR and Beclin1. Sunitinib-resistant cells (786-O-R and ACHN-R) were constructed using parental RC cells (786-O and ACHN). The resistance of 786-O-R and ACHN-R cells to sunitinib was examined. Western blot and qRT-PCR were assayed to obtain the expressions of miR-17-5p, HOTAIR and Beclin1. The effects of HOTAIR knockdown or miR-17-5p overexpression/knockdown on cell autophagy and sunitinib resistance were measured by MDC staining, immunofluorescence and Western blot. The sensitivity of RC cells to sunitinib and change in cell clone formation after sunitinib treatment were assessed by CCK-8 assay and colony formation assay, respectively. The relationships among HOTAIR, miR-17-5p and Beclin1 were verified by dual-luciferase reporter gene and RIP assay. The role of HOTAIR knockdown in sunitinib resistance was verified in nude mice. RESULTS: HOTAIR expression in sunitinib-resistant cells is higher than that in parental cells. Knockdown of HOTAIR in sunitinib-resistant cells lead to refrained sunitinib resistance and cell autophagy both in vivo and in vitro. Activation of autophagy could raise resistance to sunitinib in RC cells, while inhibition of autophagy could improve the sensitivity of sunitinib-resistant cells to sunitinib. HOTAIR could compete with miR-17-5p to regulate Beclin1 expression. Knockdown of miR-17-5p in parental cells increases cell resistant to sunitinib, and overexpression of miR-17-5p in sunitinib-resistant cells increases cell sensitive to sunitinib. CONCLUSION: HOTAIR negatively targets miR-17-5p to activate Beclin1-mediated cell autophagy, thereby enhancing sunitinib resistance in RC cells.

Total pelvic exenteration and a new model of diversion for giant primitive neuroectodermal tumor of prostate: A case report and review of the literature.

The present study reports a rare primitive neuroectodermal tumor (PNET) of prostate. A 27-year-old male was admitted to Harbin Medical University Cancer Hospital (Harbin, China) for dysuria and dyschezia. Magnetic resonance imaging (MRI) revealed a large mass that may involve the bladder and rectum next to the prostate. Histopathological analysis of biopsy of prostate indicated mesenchymal origin tumor, and immunohistochemistric staining confirmed diagnosis of PNET of prostate. En bloc total pelvic exenteration and double barrel sigmoidostomy were performed. Double stomas in the skin incision were used for fecal and urinary diversion, respectively. Short-term outcome is satisfactory, while long-term efficacy remains to be poor. Clinical features of PNET of prostate should be paid much more attention and radical surgery and adjuvant chemotherapy should be recommended.

A Two-Sequence, Four-Period, Crossover, Replicate Study to Demonstrate Bioequivalence of Warfarin Sodium Tablet in Healthy Chinese Subjects Under Fasting and Fed Conditions.

Warfarin is a narrow therapeutic index anticoagulant drug, and several generic formulations have been approved worldwide. However, there has been no report evaluating the bioequivalence of warfarin sodium according to US Food and Drug Administration draft guidance. We designed a 2-sequence and 4-period crossover study to compare the pharmacokinetic profile and assess bioequivalence between the test warfarin sodium tablet and reference product Coumadin (2.5 mg) in 56 healthy Chinese subjects under fasting and fed conditions. The plasma concentration of warfarin was analyzed by a validated liquid chromatography-tandem mass spectrometry assay, and the reference-scaled procedure was used to determine bioequivalence for the pharmacokinetics parameters. The results showed that the point estimate of geometric mean ratios of Cmax and AUC0-t for warfarin were 103.21% and 99.31%, respectively, in the fasting condition and 100.62% and 98.98%, respectively, in the fed condition, and the 90% confidence intervals were all within the range of 90.00%-111.11%. The upper limit of the 90% confidence interval of estimated within-subject variation ratios of the test and reference products was 1.33 for Cmax and 2.22 for AUC0-t under the fasting condition and 1.68 for Cmax and 2.15 for AUC0-t under the fed condition. Overall, bioequivalence of the 2 warfarin sodium products was demonstrated.

Impact factors on the production of ß-methylamino-L-alanine (BMAA) by cyanobacteria.

Cyanobacteria produce a series of secondary metabolites, one of which is beta-N-methylamino-l-alanine (BMAA). BMAA is considered to be the cause of human neurodegeneration. Compared with other cyanotoxins, the role of BMAA in cyanobacteria remains unclear. To investigate this question, six strains of cyanobacteria were cultured and tested in this experiment with an optimized and validated BMAA determination method. The results show that four strains can produce BMAA. The effects of nutrient levels on the production of BMAA by Anabaena sp. FACHB-418 were studied by changing the initial concentrations of nitrate (NaNO3) and phosphate (K2HPO4) in mediums. Bound BMAA was detected in all samples and the concentrations were within 50-100 ng/g. Free BMAA was presence when the concentration of nitrogen was lower than 1.7 mg/L (121.43 µM). Free BMAA was released from the dead and ruptured cells during the cell decline period, so dissolved BMAA cannot be detectable in the adaptation and logarithmic periods, but could be abundant in the decline periods. Statistical analyses show that free BMAA concentrations were negatively correlated with nitrogen strongly (p = 2.334 × 10-10 and r = -0.842), but positively correlated with phosphorus weakly (p = 0.016 and r = 0.405). Moreover, the results of culture experiments indicated that exogenous BMAA could inhibit the growth of cyanobacteria that cannot produce BMAA, and the effect was enhanced as the concentration of exogenous BMAA increased. This phenomenon implies that the production of BMAA may be the stress response by some cyanobacteria to low nitrogen conditions to kill other cyanobacteria, i.e., their competitors.

Effects and mechanism on the removal of neurotoxin ß-N-methylamino-l-alanine (BMAA) by chlorination.

ß-N-Methylamino-l-alanine (BMAA), a new cyanobacterial toxin, is found in different aquatic ecosystems worldwide and is to threaten the human nervous system. Therefore, it is important for water plants to develop feasible methods to counter the effects of BMAA. In this study, the removal of BMAA by chlorine, as well as its intermediate products, at different pH values and the mechanism of pH on the removal BMAA were investigated. The results showed that the chlorination of BMAA is in accordance with the second-order kinetics model. The reaction rate of chlorinated BMAA increased with the increase in the concentration of chlorine. The pH of the solution significantly affected the reaction rate. The apparent kinetic constant (kapp) decreased from 6.00 × 103 M-1·min-1 to 35.5 M-1·min-1 when the pH increased from 4.5 to 9 in the chlorine concentration of 32.23 µM. It is probable that the species distribution and proportion of BMAA and chlorine at different pH values were the main causes of this phenomenon. Additionally, the chlorination reaction consisted of four elementary reactions and hydrogen ions were beneficial to the reaction. The temperature also affected the reaction rate and the activation energy of the reaction was 16.6 ± 1.99 kJ·M-1. A variety of degradation products were detected and the path of degradation was speculated. Chlorination, dechlorination, and decarboxylation were the main processes of oxidative degradation. Furthermore, the composition of the degradation products was the same at different pH values.

A bio-inspired, one-step but versatile coating onto various substrates with strong antibacterial and enhanced osteogenesis.

It is of great interest to prepare osteogenic and antibacterial coatings for successful implants. Current coating techniques suffer from being time-consuming, substrate material or shape dependence, expensive equipment, environmental pollution, low stability, processes that are difficult to control, etc. Herein, inspired by mussels, we report a one-step and versatile method to fabricate a dual functional coating. The coating is finished in minutes independently of materials or dimensions of substrates. Thus, our coatings exhibit strong antibacterial ability against both Gram-positive bacteria S. aureus, and Gram-negative bacteria E. coli, support the proliferation of dental pulp stem cells (DPSCs), and are powerful for inducing osteogenic differentiation. The universality, facility, rapidness, and mildness of our coating process, which is also environmentally-friendly and cost-effective, points towards potential applications in bone or dental implants.

Formation kinetics of disinfection byproducts in algal-laden water during chlorination: A new insight into evaluating disinfection formation risk.

It is necessary and important to investigate the formation of disinfection byproducts (DBPs) in water treatment systems for the management of disinfection formation risk. In the present study, the formation potential of trichloromethane (TCM) and haloacetic acids in different algal metabolites were compared, and the formation kinetics of these DBPs were investigated. The results indicated that DBP formation potential, the traditional index widely used to evaluate the disinfection formation risk, can represent neither the total precursors of DBPs nor the possible generated amounts of DBPs in drinking water systems. Kinetic analyses showed that the formation of DBPs could be well described by a classical second-order reaction kinetic model and that the actual concentrations of DBPs during chlorination were predictable with the model. The formation of DBPs in drinking water treatment systems was highly dependent on the total precursors of DBPs in water and the formation rate of DBPs with chlorine; the latter is usually underestimated in previous studies. Because of their high reactivity, TCM in hydrophilic extracellular organic matter and trichloroacetic acid in all algal metabolites should be serious considerations in the management of disinfection formation risk.

Caspase-10, matrix metalloproteinase-9 and total laminin are correlated with the tumor malignancy of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common malignant kidney tumor, the pathogenesis of which remains unclear. The aim of the present study was to investigate whether caspase-10, matrix metalloproteinase-9 (MMP-9) and total laminin (LM) were involved into the pathogenesis of ccRCC. The levels of caspase-10, MMP-9 and total LM were analyzed by ELISA in tumor tissues and adjacent non-malignant tissues of 27 patients with ccRCC. The results revealed that caspase-10 levels in the tumor tissues were significantly higher than those in the adjacent non-malignant tissues (P<0.05). The MMP-9 levels in the tumor tissues were significantly lower than those in adjacent non-malignant tissues (P<0.01). The total LM levels in tumor tissues revealed no statistical difference with those in the adjacent non-malignant tissues (P=0.757). Additionally, caspase-10 levels were positively correlated with MMP-9 levels (P<0.001), but negatively correlated with total LM levels (P<0.05) in tumor tissues. Correlation analyses with clinical data of patients with ccRCC, revealed that caspase-10 levels (P<0.05) and MMP-9 levels (P<0.001) in tumor tissues were positively correlated with tumor grades of ccRCC, whereas total LM levels were positively correlated with tumor size (P<0.05). The results of the present study suggested that interactions between caspase-10, MMP-9 and LM are likely involved in the pathogenesis of ccRCC. A deeper understanding of the correlation between caspase-10, MMP-9 and LM would aid the clarification of pathogenesis of ccRCC.

Overexpression of ATP citrate lyase in renal cell carcinoma tissues and its effect on the human renal carcinoma cells in vitro.

ATP citrate lyase (ACLY) is a key enzyme of lipogenesis in cells. However, ACLY expression in renal cell carcinoma (RCC) and its association with clinicopathological parameters remain unclear. The present study aimed to evaluate ACLY expression levels in RCC and adjacent normal tissues. This study included 33 patients with clear cell RCC (ccRCC). ACLY protein was assayed using immunohistochemistry and western blotting methods. ACLY mRNA expression was determined by reverse transcription-quantitative polymerase chain reaction. Serum ACLY concentrations were measured using the ELISA. Compared with adjacent normal tissues, significantly higher levels of ACLY protein expression were observed in all of the ccRCC tissues (P<0.05). ACLY protein levels were positively associated with the T stage and nuclear grade of RCC. ACLY immunostaining was located in the cytoplasm and nucleus. ACLY protein levels and ACC1 mRNA expression in RCC tissues were significantly higher compared with that in adjacent normal tissues (P<0.05). There were no significant differences in serum ACLY concentrations between patients with RCC and health controls (P>0.05). Preliminary evaluation of ACLY function showed that ACLY small interfering RNA downregulation inhibited RCC cell proliferation and migration, but promoted RCC cell apoptosis. ACLY may be a novel biomarker for the evaluation of biological aggressiveness and may be a potential target for RCC treatment.

Clinicopathological significance of galectin-1 expression and percentage of galectin-1-expressing T cells in clear-cell renal cell carcinoma.

INTRODUCTION: This study investigates the clinical significance of galectin-1 expression in carcinoma tissues, plasma, and lymphocytes of patients with clear-cell renal cell carcinoma (RCC). METHODS: Galectin-1 expression was investigated, using immunohistochemistry, in 91 clear-cell RCC tissue sections, five angioleiolipomas tissue sections, and three oncocytomas tissue sections. As controls, normal tissue sections adjacent to each tumour and six benign renal tumour sections were examined. Plasma galectin-1 levels as measured by ELISA were compared in 39 patients. Proportions of galectin-1 expressing CD4+ and galectin-1 expressing CD8+ T lymphocytes in peripheral blood of these patients were detected by flow cytometry. RESULTS: The positive expression rate of galetin-1 in 91 clear-cell RCC tissues sections by immunohistochemistry was 87 (95.6%), with weak expression rate of 35.2 (32/91), moderate expression rate of 51.6% (47/91), and strong expression rate of 13.2% (12/91); whereas 25% (2/8) of renal benign tumour sections showed weak galectin-1 expression, 91.2% (83/91) of non-tumor tissues adjacent to carcinomas had negative expression of galectin-1, and another six (75%) renal benign tumour sections had negative galectin-1 expression. Plasma galectin-1 levels between patients with clear-cell RCC and with benign tumours were not significantly difference (p>0.05). In patients with clear-cell RCC, we found a significantly higher proportion of galectin-1-expressing CD4+ lymphocytes (p<0.05) and galectin-1-expressing CD8+ lymphocytes (p<0.05) than in patients with benign tumours. Moreover, the level of galectin-1 expression was positively associated with stage and Fuhrman grade of clear-cell RCC. CONCLUSIONS: Our results suggest that high level of galectin-1 expression in clear-cell RCC tissues may be a useful marker for clear-cell RCC. Our findings also reveal a new clinical significance of galectin-1 - that high proportions of galectin-1-expressing CD4+ and CD8+ lymphocytes were positively associated with poor clinicopathological features.

Increased expression of GGN promotes tumorigenesis in bladder cancer and is correlated with poor prognosis.

Bladder cancer has shown great challenge for people's life. Traditional therapeutics against bladder cancer including surgery could not bring much benefit for patients, particularly for the late stage patients. So it is necessary to keep in mind why and how bladder cancer cells survive in our body. In this study, we explored the function and the molecular mechanism of GGN gene in bladder cancer. GGN was shown to be expressed at a high level in bladder cancer tissues compared to the control and was associated with the unsatisfactory survival rate of patients. GGN was also expressed abundantly in bladder cancer cell lines such as T24, 5637 and BIU87. Then GGN was knocked down in 5637 cells and T24 cells at both RNA and protein level. In accordance, aberrant growth and proliferation were demonstrated in bladder cancer cells. The ability of migration and invasion of bladder cancer cells was also inhibited. The in vivo data further proved that the xenograft tumor growth was dramatically suppressed by GGN knockdown. Then we demonstrated that the level of IκB, bax and truncated caspase3 was upregulated after GGN was knocked down in 5637 cells. In contrast, expression level of NFκB, IKK, c-Myc, cyclin D1 and Bcl-2 was reduced. Further, the phosphorylation level of IκB was also downregulated. These data suggest that NFκB/caspase3-mediated apoptosis signaling was regulated by GGN. Conclusively, GGN played a tumor-promoting role in bladder cancer through regulation of NFκB/caspase3-mediated apoptosis signaling. This study provides a new clue for the treatment of patients with bladder cancer.

Performance of selective catalytic reduction of NO with NH3 over natural manganese ore catalysts at low temperature.

Natural manganese ore catalysts for selective catalytic reduction (SCR) of NO with NH3 at low temperature in the presence and absence of SO2 and H2O were systematically investigated. The physical and chemical properties of catalysts were characterized by X-ray diffraction, Brunauer-Emmett-Teller (BET) specific surface area, NH3 temperature-programmed desorption (NH3-TPD) and NO-TPD methods. The results showed that natural manganese ore from Qingyang of Anhui Province had a good low-temperature activity and N2 selectivity, and it could be a novel catalyst in terms of stability, good efficiency, good reusability and lower cost. The NO conversion exceeded 85% between 150°C and 300°C when the initial NO concentration was 1000 ppm. The activity was suppressed by adding H2O (10%) or SO2 (100 or 200 ppm), respectively, and its activity could recover while the SO2 supply is cut off. The simultaneous addition of H2O and SO2 led to the increase of about 100% in SCR activity than bare addition of SO2. The formation of the amorphous MnOx, high concentration of lattice oxygen and surface-adsorbed oxygen groups and a lot of reducible species as well as adsorption of the reactants brought about excellent SCR performance and exhibited good SO2 and H2O resistance.

Optimization of the Determination Method for Dissolved Cyanobacterial Toxin BMAA in Natural Water.

There is a serious dispute on the existence of ß-N-methylamino-l-alanine (BMAA) in water, which is a neurotoxin that may cause amyotrophic lateral sclerosis/Parkinson's disease (ALS/PDC) and Alzheimer' disease. It is believed that a reliable and sensitive analytical method for the determination of BMAA is urgently required to resolve this dispute. In the present study, the solid phase extraction (SPE) procedure and the analytical method for dissolved BMAA in water were investigated and optimized. The results showed both derivatized and underivatized methods were qualified for the measurement of BMAA and its isomer in natural water, and the limit of detection and the precision of the two methods were comparable. Cartridge characteristics and SPE conditions could greatly affect the SPE performance, and the competition of natural organic matter is the primary factor causing the low recovery of BMAA, which was reduced from approximately 90% in pure water to 38.11% in natural water. The optimized SPE method for BMAA was a combination of rinsed SPE cartridges, controlled loading/elution rates and elution solution, evaporation at 55 °C, reconstitution of a solution mixture, and filtration by polyvinylidene fluoride membrane. This optimized method achieved > 88% recovery of BMAA in both algal solution and river water. The developed method can provide an efficient way to evaluate the actual concentration levels of BMAA in actual water environments and drinking water systems.

Oxidative Stress Mediated Hippocampal Neuron Apoptosis Participated in Carbon Disulfide-Induced Rats Cognitive Dysfunction.

Occupational exposure to carbon disulfide (CS2) exhibits central nervous systems toxicity. But the mechanism is unclear. The present study was designed to investigate the relationship between the CNS damage and cognitive dysfunction caused by CS2, and eventually reveal the possible oxidative-related mechanism of hippocampus pathological changes in CS2 exposed rats. Male Wistar rats were administrated with CS2 at dosage of 200, 400 and 600 mg/kg for consecutive 20 days, respectively. Cognitive performances were evaluated by Morris water maze tests. Thionin and immunohistochemical analysis were used to investigate the hippocampal neuron damage, and the expression of apoptosis related proteins (cleaved-caspase 3, Bax and Bcl-2) were detected to explore the possible mechanisms of neuronal loss. Oxidative stress parameters were checked by commercial assay kits. Rats exposed to CS2 displayed cognitive dysfunction manifested as decreased spatial learning ability and memory lesion. Pathological changes and significant neuron loss were observed in hippocampus, especially in CA1 and CA3 sub-regions. Mitochondria-dependent apoptosis pathway was implicated in the CS2-induced neuronal loss which was demonstrated by the up-regulation of cleaved-caspase 3 and Bax accompanied with down-regulation of Bcl-2. Furthermore, extensive oxidative stress induced by CS2 was also revealed by the measurement of ROS, RNS, MDA, GSH&GSSG and antioxidant enzymes (CAT, T-SOD, and GSH-Px). Our study suggested that oxidative stress mediated hippocampal neuron apoptosis might play an important role in CS2 induced CNS damage and cognitive dysfunction.

Evaluation of drinking water treatment combined filter backwash water recycling technology based on comet and micronucleus assay.

Based on the fact that recycling of combined filter backwash water (CFBW) directly to drinking water treatment plants (WTP) is considered to be a feasible method to enhance pollutant removal efficiency, we were motivated to evaluate the genotoxicity of water samples from two pilot-scale drinking water treatment systems, one with recycling of combined backwash water, the other one with a conventional process. An integrated approach of the comet and micronucleus (MN) assays was used with zebrafish (Danio rerio) to investigate the water genotoxicity in this study. The total organic carbon (TOC), dissolved organic carbon (DOC), and trihalomethane formation potential (THMFP), of the recycling process were lower than that of the conventional process. All the results showed that there was no statistically significant difference (P>0.05) between the conventional and recycling processes, and indicated that the genotoxicity of water samples from the recycling process did not accumulate in 15 day continuous recycling trial. It was worth noting that there was correlation between the concentrations of TOC, DOC, UV254, and THMFPs in water and the DNA damage score, with corresponding R(2) values of 0.68, 0.63, 0.28, and 0.64. Nevertheless, both DNA strand breaks and MN frequency of all water samples after disinfection were higher than that of water samples from the two treatment units, which meant that the disinfection by-products (DBPs) formed by disinfection could increase the DNA damage. Both the comet and MN tests suggest that the recycling process did not increase the genotoxicity risk, compared to the traditional process.

Identify Melatonin as a Novel Therapeutic Reagent in the Treatment of 1-Bromopropane(1-BP) Intoxication.

1-Bromopropane (1-BP) has been used as an alternative for fluoride compounds and 1-BP intoxication may involve lung, liver, and central neural system (CNS). Our previous studies showed that 1-BP impaired memory ability by compromising antioxidant cellular defenses. Melatonin is a powerful endogenousantioxidant, and the objective of this study was to explore the therapeutic role of melatonin in the treatment of 1-BP intoxication. Rats were intragastrically treated with 1-BP with or without melatonin, and then sacrificed on 27th day after 1-BP administration. The Morris water maze (MWM) test was used to evaluate the spatial learning and memory ability of the experimental animals, and NeuN staining was performed to assess neuron loss in hippocampus. We found that rats treated with 1-BP spent more time and swam longer distance before landing on the hidden platform with a comparable swimming speed, which was markedly mitigated by the pretreatment with melatonin in a concentration-dependent manner. In addition, 1-BP-induced notable decrease in neuron population in hippocampus by promoting apoptosis, and melatonin pretreatment attenuated those changes in brain. The GSH/GSSG ratio was proportionately decreased and heme oxygenase 1 was increased in the rats exposed to 1-BP (Figure 6), and administration of melatonin restored them. Meanwhile, MDA, the level of lipid peroxidation product, was significantly increased upon exposed to 1-BP, which was significantly attenuated by melatonin pretreatment, indicating that administration of 1-BP could interfere with redox homeostasis of brain in rat, and such 1-BP-induced biomedical changes were reversed by treatment with melatonin.We conclude that treatment with melatonin attenuates 1-BP-induced CNS toxicity through its ROS scavenging effect.

Evaluation of the oxidation of enrofloxacin by permanganate and the antimicrobial activity of the products.

Permanganate [Mn(VII)] oxidation of the fluoroquinolone (FQ) antibiotic enrofloxacin (ENR) was investigated with respect to kinetics and mechanisms, and the products were evaluated for residual antibacterial activity. The degradation of ENR by Mn(VII) obeyed second-order kinetics. A modern liquid chromatography coupled to a hybrid quadrupole time-of-flight mass spectrometer (LC-Q-TOF) was used to determine the accurate mass of the measured degradation products. The structures of nine oxidation products were identified at a neutral pH, one of which was an N-oxide product formed from the oxidation of tertiary amines. One proposed plausible reaction pathway was that the oxidation occurred on the piperazine ring; the C-H adjacent to the amine group was attacked by Mn(VII). The identified products from ENR arose through four pathways involving two mechanisms of N-dealkylation, C-hydroxylation and the reactions of amine oxides. The quinolone core remained intact for all of the products. The residual antibacterial activity of the oxidative reaction byproducts against the nonresistant Escherichia coli (G(-)) reference strain DH5ɑ was evaluated by quantifying the bacterial colonies. The oxidation products exhibited reduced antibacterial activity compared with their parent compound.

The occurrence and removal of selected fluoroquinolones in urban drinking water treatment plants.

Fluoroquinolones (FQs) are a widely prescribed group of antibiotics. They enter the aqueous environment, where they are frequently detected, and can lead to a threat to human health. Drinking water treatment plants (DWTPs) play a key role in removing FQs from potable water. This study investigated the occurrence and removal of four selected FQs (norfloxacin (NOR), ciprofloxacin (CIP), enrofloxacin (ENR), and ofloxacin (OFL)) in three urban DWTPs in China. The treatment efficacy for each system was simultaneously evaluated. Two of the examined DWTPs used conventional treatment processes. The third used conventional processes followed by additional treatment processes (ozonation-biologically activated carbon (ozonation-BAC) and membrane technology). The average concentrations of the four FQs in the source water and the finished water ranged from 51 to 248 ng/L and from <5 to 46 ng/L, respectively. Based on residual concentrations, the conventional treatment system had a low removal of FQs. In contrast, the addition of advanced treatment processes such as the ozonation-BAC and membranes, substantially improved the removal of FQs. The finding of this study has important implications: even though coagulation-sedimentation and chlorination treatment processes can remove most target FQs, the typical practice of advanced treatment processes is necessary for the further removal.