[Contamination Characteristics，Detection Methods，and Control Methods of Antibiotic Resistance in Pharmaceutical Wastewater].

Pharmaceutical industry wastewater contains a large number of emerging pollutants such as antibiotics， antibiotic resistant bacteria （ARBs）， and antibiotic resistance genes （ARGs）. The present biological water treatment processes cannot effectively remove these pollutants. Eventually， they are discharged into various water bodies or penetrate into soil with the effluent， causing environmental pollution and affecting human health. Therefore， exploring the pollution characteristics of antibiotics， ARBs， and ARGs in pharmaceutical wastewater and knowing the methods to detect and control antibiotic resistance pollution in wastewater are crucial for reducing the contamination of antibiotics and ARGs and assessing the ecological risks of antibiotic resistance. Aiming at the problem of antibiotic resistance pollution in a pharmaceutical wastewater treatment plant （PWWTPs）， the pollution status of antibiotics， ARBs， and ARGs in pharmaceutical wastewater was discussed. Different assessment methods of antibiotic resistance in pharmaceutical wastewater were summarized. Finally， the wastewater treatment technologies commonly used to remove antibiotics and ARGs in PWWTPs were summarized in order to provide a theoretical basis for the ecological risk assessment and scientific control of antibiotics and ARGs in the environment.

Imbalance of T follicular helper cell subsets trigger the differentiation of pathogenic B cells in idiopathic membranous nephropathy.

OBJECTIVE: This study aims to elucidate the role of T follicular helper (Tfh) cells and their subsets in idiopathic membranous nephropathy (IMN). METHODS: The frequencies of Tfh cell subsets and B cell subsets in peripheral blood (PB) were detected in both IMN patients and healthy controls (HCs). The involvement of Tfh cells in the disease pathogenesis was examined by coculturing human Tfh cells with B cells. The dynamic changes of Tfh cells in PB or spleen were monitored in passive Heymann nephritis (PHN) rats. RESULTS: The frequencies of circulating Tfh (cTfh) cells, cTfh2 cells, and plasmablasts were enriched in the PB of patients with IMN. cTfh cells expressed higher ICOS, and lower BTLA than healthy counterparts. The frequency of ICOS + cTfh2 was associated with the severity of IMN, including 24h urine protein, IgG4 concentration and the IgG4: IgG ratio. Positive correlations were also observed between the frequency of cTfh2 cells with plasmablasts, serum IL-21 and IL-4 levels. Importantly, cTfh cells isolated from IMN patients were able to induce the differentiation of B cells to memory B cells (MBC) and plasmablasts, this process could be substantially attenuated by blocking the IL-21. Similar increases of ICOS + cTfh cells were also detected in spleen of PHN rats, concomitant with elevated urine protein levels. CONCLUSIONS: Collectively, our results demonstrate that the imbalance of cTfh cell subsets play a crucial pathogenic role in IMN by inducing the differentiation of B cells through IL-21, and cTfh2 cells might serve as useful markers to evaluate the progression of IMN.

Triptolide inhibits the proinflammatory potential of myeloid-derived suppressor cells via reducing Arginase-1 in rheumatoid arthritis.

Triptolide (TPT) is widely used in the treatment of rheumatoid arthritis (RA). However, its regulatory mechanisms are not fully understood. This study demonstrated that Myeloid-derived suppressor cells (MDSCs) were expanded in both RA patients and arthritic mice. The frequency of MDSCs was correlated with RA disease severity and T helper 17 (Th17) responses. MDSCs from RA patients promoted the polarization of Th17 cells in vitro, which could be substantially attenuated by blocking arginase-1 (Arg-1). TPT inhibited the differentiation of MDSCs, particularly the monocytic MDSCs (M-MDSCs) subsets, as well as the expression of Arg-1 in a dose dependent manner. Alongside, TPT treatment reduced the potential of MDSCs to promote the polarization of IL-17+ T cell in vitro. Consistently, TPT immunotherapy alleviated adjuvant-induced arthritis (AIA) in a mice model, and reduced the frequency of MDSCs, M-MDSCs and IL-17+ T cells simultaneously. The presented data suggest a pathogenic role of MDSCs in RA and may function as a novel and effective therapeutic target for TPT in RA.

Elevated circulating CD19+CD24hiCD38hi B cells display pro-inflammatory phenotype in idiopathic membranous nephropathy.

CD19+CD24hiCD38hi regulatory B cells exert immunosuppressive functions by producing IL-10, but their role in idiopathic membranous nephropathy (IMN) remains elusive. Here, we investigated the frequency and functional changes of circulating CD19+CD24hiCD38hi B cells and evaluated the correlation of CD19+CD24hiCD38hi B cells with clinical features and T helper cell subsets in IMN patients. Compared with healthy controls (HCs), IMN patients showed an increased frequency of CD19+CD24hiCD38hi B cells, but a significant reduction in the percentage of CD19+CD24hiCD38hi B cells was observed 4 weeks after cyclophosphamide treatment. The frequency of CD19+CD24hiCD38hi B cells was positively correlated with the levels of 24h urinary protein, but negatively correlated with serum total protein and serum albumin, respectively. CD19+CD24hiCD38hi B cells in IMN patients displayed a skewed pro-inflammatory cytokine profile with a higher level of IL-6 and IL-12, but a lower concentration of IL-10 than their healthy counterparts. Accompanied by upregulation of Th2 and Th17 cells in IMN patients, the percentage of CD19+CD24hiCD38hi B cell subset was positively associated with Th17 cell frequency. In conclusion, CD19+CD24hiCD38hi B cells were expanded but functionally impaired in IMN patients. Their altered pro-inflammatory cytokine profile may contribute to the pathogenesis of IMN.

Influence of organic cosolvents on hexabromobenzene degradation in solution by montmorillonite-templated subnanoscale zero-valent iron.

Organic cosolvents are commonly used to increase the dissolution of poorly water-soluble organic pollutants into aqueous solutions during environmental remediation. In this study, the influences of five organic cosolvents on hexabromobenzene (HBB) degradation catalyzed by one typical reactive material montmorillonite-templated subnanoscale zero-valent iron (CZVI) were investigated. The results demonstrated that all cosolvents promoted HBB degradation but the degree of promotion was different for different cosolvents, which was associated with inconsistent solvent viscosities, dielectric constant properties, and the extent of interactions between cosolvents with CZVI. Meanwhile, HBB degradation was highly dependent on the volume ratio of cosolvent to water, which increased in the range of 10%-25% but persistently decreased in the range of more than 25%. This might be due to the fact that the cosolvents increased HBB dissolution at low concentrations but reduced the protons supplied by water and the contact between HBB with CZVI at high concentrations. In addition, the freshly-prepared CZVI had higher reactivity to HBB than the freeze-dried CZVI in all water-cosolvent solutions, probably because freeze-drying reduced the interlayer space of CZVI and thus the contact probability between HBB and active reaction sites. Finally, the CZVI-catalyzed HBB degradation mechanism was proposed as the electron transfer between zero-valent iron and HBB, which led to the formation of four debromination products. Overall, this study provides helpful information for the practical application of CZVI in the remediation of persistent organic pollutants in the environment.

Bacterial community assembly and antibiotic resistance genes in soils exposed to antibiotics at environmentally relevant concentrations.

Understanding how bacterial community assembly and antibiotic resistance genes (ARGs) respond to antibiotic exposure is essential to deciphering the ecological risk of anthropogenic antibiotic pollution in soils. In this study, three loam soils with different land management (unmanured golf course, dairy-manured pasture, and swine-manured cornfield) were spiked with a mixture of 11 antibiotics at the initial concentration of 100 and 1000 µg kg-1 for each antibiotic and incubated over 132 days, mimicking a scenario of pulse disturbance and recovery in soils, with unspiked soil samples as the control treatment. The Infer Community Assembly Mechanisms by Phylogenetic-bin-based null model (iCAMP) analysis demonstrated that drift and dispersal limitation contributed to 57%-65% and 16%-25%, and homogeneous selection 12%-16% of soil bacterial community assembly. Interestingly, antibiotic exposure to 1000 µg kg-1 level significantly increased the contribution of drift to community assembly, largely due to the positive response from Acidobacteria-6 in the golf course and pasture soils and from Chthoniobacteraceae in the cornfield soil to the antibiotic exposure. However, ARG abundance and diversity in the three soils exhibited antibiotics-independent temporal fluctuations, but were associated with the changes in soil bacterial communities over time. This study provides the first insight into the relative contributions of different bacterial community assembly processes in soils upon antibiotic exposure at environmentally relevant concentrations.

Tetracycline photolysis revisited: Overlooked day-night succession of the parent compound and metabolites in natural surface waters and associated ecotoxicity.

Despite the extensive study of tetracycline photolysis in aquatic environments, the phototransformation of tetracycline and its metabolites under natural day-night succession has not been examined. In this study, we investigated tetracycline photolysis and associated ecotoxicity in two natural surface waters and one artificial ultrapure water under simulated day/night cycling over two days. Previously unrecognized and highly pH- and temperature-dependent dark interconversions of tetracycline metabolites were observed. The liquid chromatography-mass spectrometry/mass spectrometry analysis identified a range of isomerized, hydroxylated, demethylated, deaminated, and open-ring photoproducts. The hydrolysis of tetracycline, isotetracycline, and several intermediate products was proposed as the major mechanism for the observed dark transformations. Exposure studies employing Escherichia coli indicated that although the tetracycline degradation products had lower bacterial toxicities than the parent compound, increasing toxicity with irradiation time after the near-complete degradation of the parent compound in natural waters implied that product mixtures retain ecotoxicity. The dark transformations also affected the bacterial toxicity and fluorescence properties of irradiated tetracycline solutions. Overall, this study provides new insights into the photochemical behavior of tetracycline and its associated ecological risk in aquatic environments.

Biodegradable Microplastics: A Review on the Interaction with Pollutants and Influence to Organisms.

Biodegradable plastics attract public attention as promising substitutes for traditional nondegradable plastics which have caused the serious white pollution problem due to their persistence. However, even for biodegradable plastics, natual conditions for the rapid and complete degradation are rare. Even more serious is that biodegradable plastics might be disintegrated into microplastics more rapidly than tranditional plastics, emerging as another threat to the environment. Similar to traditional microplastics, biodegradable microplastics could adsorb many pollutants by various physicochemical effects and release additives. Biodegradable microplastics have been confirmed to be toxic to the organisms as particle matter and the vector as pollutants. Under some conditions, biodegradable microplastics may pose more severe negative impacts on the organisms. With the fierely increasing trend to replace the nondegradable plastic commodities with biodegradable ones, it is necessary to evaluate whether biodegradable plastics and the generated microplastics would alleviate plastic pollution or induce greater ecological impacts.

NaCl salinity enhances tetracycline bioavailability to Escherichia coli on agar surfaces.

Soil salinity is a worldwide problem and is damaging soil functions. Meanwhile, increasing amounts of anthropogenic antibiotics are discharged to agricultural soils. Little is known about how soil salinity (e.g., NaCl) could influence the bioavailability of antibiotics to bacteria. In this study, a tetracycline-responsive Escherichia coli bioreporter grew on the surfaces of agar microcosms at the same tetracycline concentration (200 µg/L), but various NaCl concentrations (0.5-19.2 g/L) with estimated osmotic potential of -0.18 to -1.80 MPa, and agar content (0.3%-5%) with estimated intrinsic permeability of 38 to 32,928 nm2. These agar microcosms mimicked very fine textured soils with a range of NaCl salinity. Increasing agar content lowered the intrinsic permeability hence decreasing tetracycline bioavailability to E. coli, due likely to the reduced mass transfer of tetracycline via water flow. Intriguingly, tetracycline bioavailability increased with increasing NaCl concentration which caused the increase in osmotic stress. This is contradictory to the notion that osmotic stress reduces bacterial chemical uptake. Further analysis of E. coli membrane integrity demonstrated that the enhanced tetracycline bioavailability to bacteria could result from the compromised cell membranes and enhanced membrane permeability at higher NaCl salinity. Overall, this study suggests that high soil salinity (NaCl) may enhance the selection pressure exerted by antibiotics on bacteria.

Dioxin-like compounds formation mediated by Fe3+-montmorillonite: The substituent effects of halophenols.

Toxic dioxin or/and dioxin-like compounds could be naturally formed from the reaction of halophenols on Fe3+-montmorillonite minerals under ambient conditions. Given that the toxicities and productions of dioxin or/and dioxin-like compounds are largely determined by the number, species, and position of the carried halogen atoms, it is necessary to explore the substituent effects on the reaction of halophenols with Fe3+-montmorillonite. Herein, Fe3+-montmorillonite catalyzed polymerizations of six halophenols were examined in a wide range of relative humidity (10%∼80%) using combinations of mass spectrometry identifications and density functional theory calculations. Results show that both the position and species of the substituents substantially impact the reaction rate, product species, and transformation pathways. In general, regardless of humidity ortho-substituted chlorophenols are more reactive than meta-substituted chlorophenols, which is also supported by the density functional theory calculations indicating that the ortho positions are more likely to be attacked. Regarding substituent species, bromophenols are slightly more reactive and also more easily affected by humidities than chlorophenols, which is due to the weaker electron absorbing ability of the bromine atom than the chlorine atom. Hydroxylated polyhalogenated diphenyl ethers are more frequently detected polymerization products, although hydroxylated polyhalogenated biphenyls are greater quantity of products. Overall, this study provides useful information for understanding the natural formation of dioxin or/and dioxin-like compounds mediated by clay minerals and underlying reaction mechanisms.

PEG-PEI/siROCK2 inhibits Aß42-induced microglial inflammation via NLRP3/caspase 1 pathway.

OBJECTIVES: There is an urgent need to develop therapeutic strategies to improve the treatment outcome of Alzheimer's disease. The treatment strategy of gene therapy mediated by nanocarrier systems brings new hope for the treatment of Alzheimer's disease. ROCK2 is involved in various pathological processes of Alzheimer's disease and may be a potential target for the treatment of Alzheimer's disease. Our previous study indicated that PEG-PEI/siROCK2 [polyethyleneglycol-polyethyleneimine deliver ROCK2-siRNA, (PPSR)] prevented Aß42-induced neurotoxicity and showed a promising prospect for the treatment of Alzheimer's disease. However, whether PPSR has an effect on the microglial inflammation in Alzheimer's disease is still unclear. MATERIALS AND METHODS: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay was used to detect the cytotoxicity of PEG-PEI and PPSR in primary microglial cells. Real-time PCR and western blotting were used to assess the expression of ROCK2 and nucleotide oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)/caspase 1 pathway in primary microglial cells. ELISA assay was used to measure the effect of PPSR on attenuating the lipopolysaccharide (LPS) + Aß-induced increase in IL-1ß. RESULTS: PEG-PEI concentration less than 20 µg/ml and the N/P (molar ratio of PEG-PEI amino/siRNA phosphate) ratio of PPSR less than 50 showed no significant cytotoxicity in primary microglia cells. PPSR could effectively inhibit the expression of ROCK2 in primary microglial cells. A further study revealed that PPSR attenuates the LPS+Aß-induced increase in IL-1ß without affecting cell viability. In addition, we found that PPSR suppressed the Aß-induced NLRP3/caspase 1 pathway in primary microglial cells. CONCLUSION: PPSR inhibits Aß42-induced microglial inflammation via NLRP3/caspase 1 pathway.

Halide salts induced the photodegradation of a fat-burning compound 2, 4-dinitrophenol by iron-montmorillonite.

Natural montmorillonite clay and anthropogenic organic pollutants frequently coexist in the estuarine environment where freshwater from rivers mixes with saltwater from the ocean. In this environment, the sharply changed aqueous chemistry especially salt content could significantly alter the photochemical behaviors of pollutants. However, this process was rarely investigated. In this study, the photodegradation of a representative anthropogenic weight-loss compound 2,4-dinitrophenol in the presence of Fe3+-montmorillonite and different halide salts was systematically investigated. Results show that 2,4-dinitrophenol was resistant to photodegradation by Fe3+-montmorillonite alone, but the presence of NaCl, NaBr, and sea salts in the system can evoke significant 2,4-dinitrophenol degradation. The enhancement effect was further elucidated as the replacement reaction between the clay associated Fe3+ and Na + which leads to the release of more interlayer Fe3+ from montmorillonite, resulting in increased production of high active hydroxyl radicals (˙OH) that can substantially damage 2,4-dinitrophenol molecule. In addition, halogen radicals from the reaction of halide ions with ˙OH were also confirmed to participate in 2,4-dinitrophenol degradation. Overall, this study implied that the changed salty condition in the estuarine water could induce the rapid transformation of organic pollutants that move from freshwater and have relatively stable photochemical properties.

Ikzf2 Regulates the Development of ICOS+ Th Cells to Mediate Immune Response in the Spleen of S. japonicum-Infected C57BL/6 Mice.

Background: Th cells (helper T cells) have multiple functions in Schistosoma japonicum (S. japonicum) infection. Inducible co-stimulator (ICOS) is induced and expressed in activated T lymphocytes, which enhances the development of B cells and antibody production through the ICOS/ICOSL pathway. It remains unclear about the role and possible regulating mechanism of ICOS+ Th cells in the spleen of S. japonicum-infected C57BL/6 mice. Methods: C57BL/6 mice were infected with cercariae of S. japonicum through the abdomen. The expression of ICOS, activation markers, and the cytokine production on CD4+ ICOS+ Th cells were detected by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR). Moreover, the differentially expressed gene data of ICOS+ and ICOS- Th cells from the spleen of infected mice were obtained by mRNA sequencing. Besides, Western blot and chromatin immunoprecipitation (ChIP) were used to explore the role of Ikzf2 on ICOS expression. Results: After S. japonicum infection, the expression of ICOS molecules gradually increased in splenic lymphocytes, especially in Th cells (P < 0.01). Compared with ICOS- Th cells, more ICOS+ Th cells expressed CD69, CD25, CXCR5, and CD40L (P < 0.05), while less of them expressed CD62L (P < 0.05). Also, ICOS+ Th cells expressed more cytokines, such as IFN-γ, IL-4, IL-10, IL-2, and IL-21 (P < 0.05). RNA sequencing results showed that many transcription factors were increased significantly in ICOS+ Th cells, especially Ikzf2 (P < 0.05). And then, the expression of Ikzf2 was verified to be significantly increased and mainly located in the nuclear of ICOS+ Th cells. Finally, ChIP experiments and dual-luciferase reporter assay confirmed that Ikzf2 could directly bind to the ICOS promoter in Th cells. Conclusion: In this study, ICOS+ Th cells were found to play an important role in S. japonicum infection to induce immune response in the spleen of C57BL/6 mice. Additionally, Ikzf2 was found to be one important transcription factor that could regulate the expression of ICOS in the spleen of S. japonicum-infected C57BL/6 mice.

Characterization of γδT cells in lung of Plasmodium yoelii-infected C57BL/6 mice.

BACKGROUND: Malaria has high morbidity and mortality rates in some parts of tropical and subtropical countries. Besides respiratory and metabolic function, lung plays a role in immune system. γδT cells have multiple functions in producing cytokines and chemokines, regulating the immune response by interacting with other cells. It remains unclear about the role of γδT cells in the lung of mice infected by malaria parasites. METHODS: Flow cytometry (FCM) was used to evaluate the frequency of γδT cells and the effects of γδT cells on the phenotype and function of B and T cells in Plasmodium yoelii-infected wild-type (WT) or γδTCR knockout (γδT KO) mice. Haematoxylin-eosin (HE) staining was used to observe the pathological changes in the lungs. RESULTS: The percentage and absolute number of γδT cells in the lung increased after Plasmodium infection (p < 0.01). More γδT cells were expressing CD80, CD11b, or PD-1 post-infection (p < 0.05), while less γδT cells were expressing CD34, CD62L, and CD127 post-infection (p < 0.05). The percentages of IL-4+, IL-5+, IL-6+, IL-21+, IL-1α+, and IL-17+ γδT cells were increased (p < 0.05), but the percentage of IFN-γ-expressing γδT cells decreased (p < 0.05) post-infection. The pathological changes in the lungs of the infected γδT KO mice were not obvious compared with the infected WT mice. The proportion of CD3+ cells and absolute numbers of CD3+ cells, CD3+ CD4+ cells, CD3+ CD8+ cells decreased in γδT KO infected mice (p < 0.05). γδT KO infected mice exhibited no significant difference in the surface molecular expression of T cells compared with the WT infected mice (p > 0.05). While, the percentage of IFN-γ-expressing CD3+ and CD3+ CD8+ cells increased in γδT KO infected mice (p < 0.05). There was no significant difference in the absolute numbers of the total, CD69+, ICOS+, and CD80+ B cells between the WT infected and γδT KO infected mice (p > 0.05). CONCLUSIONS: The content, phenotype, and function of γδT cells in the lung of C57BL/6 mice were changed after Plasmodium infection. γδT cells contribute to T cell immune response in the progress of Plasmodium infection.

RTKN2 is Associated with Unfavorable Prognosis and Promotes Progression in Non-Small-Cell Lung Cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. However, the molecular mechanism of NSCLC remains unknown. Accumulating data show that Rhotekin 2 (RTKN2) functions as a novel crucial regulator of diverse biological processes; however, its pathological role in NSCLC remains unclear. METHODS: In this study, we investigated the function of RTKN2 in NSCLC. The expression of RTKN2 mRNA was analyzed in tumor tissues and paired adjacent tissues from patients by qRT-PCR. The role of RTKN2 in cell proliferation, apoptosis, migration, and invasion was investigated. The potential mechanisms were explored. RESULTS: We found that the level of RTKN2 mRNA was up-regulated in NSCLC tissues and cell lines. RTKN2 knockout inhibited the proliferation of human NSCLC cell lines A549 via inducing apoptosis by increasing the level of Bax and decreasing the level of Bcl-2. Furthermore, silencing of RTKN2 reduced the migration and invasion of A549 cells through up-regulated matrix metalloproteinase-9 (MMP9) and MMP2 expression. CONCLUSION: These data suggest that RTKN2 may not only be a prognostic biomarker candidate but also provide a potential therapeutic target for NSCLC diagnosis and treatment.

CD19+CD24hiCD38hi B Cell Dysfunction in Primary Biliary Cholangitis.

CD19+CD24hiCD38hi B cells are immature transitional B cells that, in normal individuals, exert suppressive effects by IL-10 production but are quantitatively altered and/or functionally impaired in individuals with various autoimmune diseases. Primary biliary cholangitis (PBC), an autoimmune disease, clinically presents as chronic cholestasis and nonsuppurative destructive cholangitis. A role for CD19+CD24hiCD38hi B cells in PBC is unknown. This study investigated the frequency and functional variation of circulating CD19+CD24hiCD38hi B cells in PBC patients. Flow cytometry was employed to quantify the percentage of CD19+CD24hiCD38hi B cells in peripheral blood samples. Correlations between CD19+CD24hiCD38hi B cells and routine laboratory parameters were assessed. Levels of IL-10, TNF-α, IL-6 and IL-12, and Tim-1 in CD19+CD24hiCD38hi B cells from PBC patients were analyzed. The effect of CD19+CD24hiCD38hi B cells on CD4+T cell differentiation was evaluated. The percentage of CD19+CD24hiCD38hi B cells in PBC patients was significantly higher than in healthy controls and was positively correlated with liver cholestasis. After activation by anti-B cell receptor and CpG, the production of IL-10 was decreased and the production of IL-6 and IL-12 was increased in CD19+CD24hiCD38hi B cells from PBC patients. Moreover, Tim-1 levels were significantly downregulated in CD19+CD24hiCD38hi B cells from PBC patients. Coculture showed that PBC-derived CD19+CD24hiCD38hi B cells were less capable of CD4+T cell inhibition, but promoted Th1 cell differentiation. In conclusion, PBC patients have expanded percentages, but impaired CD19+CD24hiCD38hi B cells, which correlate with disease damage. In PBC patients, this B cell subset has a skewed proinflammatory cytokine profile and a decreased capacity to suppress immune function, which may contribute to the pathogenesis of PBC.

Transformation and toxicity of environmental contaminants as influenced by Fe containing clay minerals: a review.

Clay minerals are ubiquitous in soil and sediments, and play important roles in environmental processes. Virtually all clay minerals contain some Fe, either in the crystal structure or adsorbed at the surface of the clay minerals, which could promote many reactions on the clay minerals. The interaction between Fe containing clay mineral and its surrounding contaminants would greatly affect the transformation and toxicity of the contaminants. While it is certain that the Fe plays important roles in the fate of the contaminants, relative qualitative and quantitative assessment of these processes is limited. Based on the overall toxicity variation, this paper reviews the active areas of the researches on the interactions between Fe containing clay mineral and contaminants, and provides perspectives for future work.

Rheumatoid arthritis synovial fibroblasts promote TREM-1 expression in monocytes via COX-2/PGE2 pathway.

BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) is inducible on monocyte/macrophages and neutrophils and amplifies the inflammatory response. The aim of this study was to determine whether rheumatoid arthritis synovial fibroblasts (RASF) promote the expression of TREM-1 in monocytes and its potential regulatory mechanism. METHODS: Synovial fluid and paired peripheral blood from rheumatoid arthritis (RA) patients were analyzed using flow cytometry. Expression of TREM-1 in monocytes was detected after co-culture with RASF, with or without pre-treatment with toll-like receptor (TLR) ligands. Whether RASF-regulated TREM-1 level in monocytes require direct cell contact or soluble factors was evaluated by transwell experiment. COX-2 expression and PGE2 secretion in RASF were determined by quantitative PCR (qPCR) and ELISA. RASF, with and without TLR ligand stimulation, were treated with COX-2 inhibitors, COX-2 siRNA (siCOX-2) or EP1-4 antagonists, and the resulting TREM-1 level in CD14+ monocytes was measured using flow cytometry. RESULTS: TREM-1 was highly expressed in CD14+ cells from peripheral blood and especially synovial fluid from RA patients. The expression of TREM-1 in monocytes was increased by co-culture with RASF. TLR-ligand-activated RASF further elevated TREM-1 level. Transwell assay indicated that soluble factors played a key role in RASF-promoted expression of TREM-1 in monocytes. RASF, with or without stimulation by TLR ligands, increased secretion of PGE2 in a cyclooxygenase (COX)-2-dependent manner. PGE2 enhanced the increase in TREM-1 level in monocytes. Finally, studies using COX-2 inhibitors, COX-2 siRNA (siCOX-2) and EP1-4 antagonists, showed that RASF promotion of TREM-1 expression in monocytes was mediated by COX-2/PGE2/EP2,4 signaling. CONCLUSIONS: Our data is the first report to reveal the critical role of RASF in upregulating TREM-1 expression in monocytes, which indicates that TREM-1 might be a novel target for RA therapy.

Detection of T lymphocyte subsets and related functional molecules in follicular fluid of patients with polycystic ovary syndrome.

Immune responses play an important role in the pathogenesis of polycystic ovary syndrome (PCOS). However, the characteristics of T lymphocyte subsets in PCOS remain insufficiently understood. In this study, lymphocytes of follicular fluid (FF) were obtained from oocyte retrieval before in-vitro fertilization (IVF) in infertile women with or without PCOS. The levels of cluster of differentiation 25 (CD25), CD69, programmed death 1 (PD-1), interferon-γ (IFN-γ), interleukin 17A (IL-17A) and IL-10 in T lymphocytes were determined by flow cytometry. Our results showed that the percentage of FF CD8+ T cells was significantly decreased in infertile patients with PCOS (P < 0.05). Furthermore, the levels of CD69 and IFN-γ were significantly decreased and the level of PD-1 was increased in both CD4+ and CD8+ T cells from infertile patients with PCOS (P < 0.05). Moreover, the expression of PD-1 on CD4+ or CD8+ T cells was positively correlated with the estradiol (E2) levels in the serum and reversely correlated with the expression of IFN-γ in CD4+ or CD8+ T cells in infertile patients with PCOS. These results suggested that T cell dysfunction may be involved in the pathogenesis of PCOS.

Transformation of gaseous 2-bromophenol on clay mineral dust and the potential health effect.

Iron-bearing clays are ubiquitously distributed as mineral dusts in the atmosphere. Bromophenols were reported as the major products from thermal decomposition of the widely used brominated flame retardants (BFRs). However, little information is available for the reactivity of iron associated with mineral dusts to interact with the atmospheric bromophenols and the subsequent toxic effects. Herein, three common clay minerals (montmorillonite, illite and kaolinite) were used to simulate mineral dusts, and the reactions with gaseous 2-bromophenol were systematically investigated under environmentally relevant atmospheric conditions. Our results demonstrate that structural Fe(III) in montmorillonite and Fe(III) from iron oxide in illite mediated the dimerization of 2-bromophenol to form hydroxylated polybrominated biphenyl and hydroxylated polybrominated diphenyl ether. The surface reaction is favored to occur at moisture environment, since water molecules formed complex with 2-bromophenol and the reaction intermediates via hydrogen bond to significantly lower the reaction energy and promote the dimerization reaction. More importantly, the formed dioxin-like products on clay mineral dust increased the toxicity of the particles to A549 lung cell by decreasing cell survival and damaging cellular membrane and proteins. The results of this study indicate that not only mineral dust itself but also the associated surface reaction should be fully considered to accurately evaluate the toxic effect of mineral dust on human health.