Gut microbiota deficiency aggravates arsenic-induced toxicity by affecting bioaccumulation and biotransformation in C57BL/6J mice.

Gut microbiome can influence the arsenic metabolism in mammals. Confusingly, gut microbiome was found to both mitigate and exacerbate arsenic toxicity. In this study, the role of gut microbiota in arsenic bioaccumulation, biotransformation, and organ toxicity in C57BL/6J mice was investigated. Gut microbiota deficiency model was established by antibiotics (Ab) cocktail AVNM. Conventional and gut microbiota deficiency mice were exposed to NaAsO2 for 4 weeks. Comparing with Ab-treated mice, the total arsenic (tAs) in the tissues was significantly reduced in conventional mice, which was opposed to the results of those in feces. Interestingly, dimethyl arsenite (DMA) was the most abundant metabolite in the feces of Ab-treated mice, while arsenic acid (AsV) had the highest proportion in the feces of conventional mice with approximately 16-fold than that in Ab-treated mice, indicating the critical role of gut microbiota in metabolizing arsenious acid (AsIII) to AsV. Additionally, the liver and kidney in Ab-treated mice showed more severe pathological changes and apoptosis. The significant increased level of ionized calcium-binding adapter molecule 1 (IBA-1) was also found in the brains of Ab-treated mice. Our results indicated that gut microbiota protected the host from arsenic-induced toxicity in liver, kidney, and brain by reducing the arsenic accumulation.

Associations of arsenic exposure and arsenic metabolism with the risk of non-alcoholic fatty liver disease.

Growing evidences supported that arsenic exposure contributes to non-alcoholic fatty liver disease (NAFLD) risk, but findings were still inconsistent. Additionally, once absorbed, arsenic is methylated into monomethyl and dimethyl arsenicals. However, no studies investigated the association of arsenic metabolism with NAFLD. Our objectives were to evaluate the associations of arsenic exposure and arsenic metabolism with NAFLD prevalence. We conducted a case-control study with 1790 participants derived from Dongfeng-Tongji cohort and measured arsenic species (arsenite, arsenate, monomethylarsonate [MMA], dimethylarsinate [DMA], and arsenobetaine) in urine. Arsenic exposure (∑As) was defined as the sum of inorganic arsenic (iAs), MMA, and DMA. Arsenic metabolism was evaluated as the proportions of inorganic-related species (iAs%, MMA%, and DMA%) and methylation efficiency ratios (primary methylation index [PMI], secondary methylation index [SMI]). NAFLD was diagnosed by liver ultrasound. Logistic regression was used to evaluate the associations. The median of ∑As was 13.24 µg/g creatinine. The ∑As showed positive and nonlinear association with moderate/severe NAFLD (OR: per log-SD = 1.33, 95% CI: [1.03,1.71]; Pfor nonlinearity = 0.021). The iAs% (OR: per SD = 1.16, 95% CI: [1.03,1.30]) and SMI (OR: per log-SD = 1.16, 95% CI: [1.03,1.31]) showed positive while MMA% (OR: per SD = 0.80, 95% CI: [0.70,0.91]) and PMI (OR: per log-SD = 0.86, 95% CI: [0.77,0.96]) showed inverse associations with NAFLD. Moreover, the ORs (95% CI) of NAFLD for each 5% increase in iAs% was 1.36 (1.17,1.58) when MMA% decreased and 1.07 (1.01,1.13) when DMA% decreased; and for each 5% increase in MMA%, it was 0.74 (0.63,0.86) and 0.79 (0.69,0.91) when iAs% and DMA% decreased, respectively. The results suggest that inorganic arsenic exposure is positively associated with NAFLD risk and arsenic methylation efficiency plays a role in the NAFLD. The findings provide clues to explore potential interventions for the prevention of NAFLD. Prospective studies are needed to validate our findings.

High-Altitude Exposure and Diabetic Retinopathy: Unveiling the Impact and Mechanisms of Alleviation.

BACKGROUND: High altitude (HA) is an extremely challenging environment for millions of people who either travel to HA regions or inhabit there permanently. SUMMARY: Significant progress has been made over the past decades in the understanding of physiological adaptations in HA conditions, and recently, more studies regarding its influence on metabolic disease have been published. However, the effect of HA on diabetic retinopathy (DR), the leading cause of blindness, remains unclear. KEY MESSAGES: The present article provides an overview of the changes in the principal physiology and clinical characteristics related to DR after HA exposure. Despite conflicting evidence, this review synthesizes the available studies and explores the potential mechanisms, such as genetic adaptations, glucose homeostasis, and related physiological changes, by which long-term exposure to HA may alleviate the progression of DR. By shedding light on this complex relationship, it also provides insights into the interplay between HA and DR, offering valuable implications for clinical practice and further research.

Epigenome-wide perspective of cadmium-associated DNA methylation and its mediation role in the associations of cadmium with lipid levels and dyslipidemia risk.

BACKGROUND: Studies demonstrated the associations of cadmium (Cd) with lipid levels and dyslipidemia risk, but the mechanisms involved need further exploration. OBJECTIVES: We aimed to explore the role of DNA methylation (DNAM) in the relationship of Cd with lipid levels and dyslipidemia risk. METHODS: Urinary cadmium levels (UCd) were measured by inductively coupled plasma mass spectrometry, serum high-density lipoprotein (HDL), total cholesterol, triglyceride, and low-density lipoprotein were measured with kits, and DNAM was measured using the Infinium MethylationEPIC BeadChip. Robust linear regressions were conducted for epigenome-wide association study. Multivariate linear and logistic regressions were performed to explore the associations of UCd with lipid levels and dyslipidemia risk, respectively. Mediation analyses were conducted to explore potential mediating role of DNAM in the associations of Cd with lipid levels and dyslipidemia risk. RESULTS: UCd was negatively associated with HDL levels (p = 0.01) and positively associated with dyslipidemia (p < 0.01). There were 92/11 DMPs/DMRs (FDR<0.05) associated with UCd. Cd-associated DNAM and pathways were connected with cardiometabolic diseases and immunity. Cg07829377 (LINC01060) mediated 42.05%/22.88% of the UCd-HDL/UCd-dyslipidemia associations (p = 0.02 and 0.01, respectively). CONCLUSIONS: Cadmium caused site-specific DNAM alterations and the associations of UCd with lipid levels and dyslipidemia risk may be partially mediated by DNAM.

Changes in the choroid detected by ultrawide-field optical coherence tomography angiography in type 2 diabetes mellitus patients without diabetic retinopathy.

AIM: The study objective was to investigate the choroidal changes in type 2 diabetes mellitus (T2DM) patients without diabetic retinopathy (DR). METHODS: This was a cross-sectional study. Controls without diabetes and T2DM patients without DR (NDR) were included. Ultrawide-field (24 × 20 mm2) optical coherence tomography angiography (OCTA) was performed to analyse choroidal thickness and vessel density. All OCTA images were divided into 3 × 3 grids. The grid centre was considered the central area, while the rest was defined as the peripheral area. RESULTS: No differences between groups were observed in the flow density of the choriocapillaris (CC), choroidal thickness (ChT) and choroidal vascular index (CVI) of the large and medium choroidal vessel (LMCV) in the central area. In the eight peripheral areas, the mean flow density of the CC did not differ between the groups, while the mean CVI and ChT were decreased in the NDR group (P< 0.05). In each peripheral area, the mean CVI and ChT were decreased in the NDR group (P< 0.05, except in the infratemporal area and nasal area for ChT and in the infratemporal area for CVI). In the correlation analysis, both mean peripheral CVI and ChT correlated with age and the duration of diabetes. CONCLUSION: Early choroidal lesions tended to be peripheral in the LMCV in patients with diabetes without DR and correlated with age and the duration of diabetes.

Urinary arsenic metabolism, genetic susceptibility, and their interaction on type 2 diabetes.

Growing studies investigated the association of arsenic metabolism with type 2 diabetes (T2D), however, the epidemiological evidence is inconsistent. In addition, the interaction of arsenic metabolism-related genetic risk score (GRS)-arsenic on T2D risk was unclear. The present study aimed to evaluate the association of arsenic metabolism efficiency [inorganic arsenic (iAs)%, monomethylarsonic acid (MMA)%, and dimethylarsinic acid (DMA%)] with T2D risk. Moreover, the relationship of GRS and arsenic metabolism efficiency and the interaction of GRS-arsenic on T2D were investigated. Age- and sex-matched new-onset diabetes case-control study derived from the Dongfeng-Tongji cohort was conducted and 996 pairs participants were included in this study. The leave-one-out approach was used to evaluate the association of arsenic metabolism efficiency with T2D risk. The GRS and weight GRS (wGRS) were calculated based on 79 candidate SNPs. We estimated the relationship of GRS with arsenic metabolism efficiency by linear regression model. The interaction of GRS-arsenic on T2D was assessed by adding a multiplicative interaction term (GRS × arsenic) in the logistic regression models. Urinary iAs% was positively associated with T2D risk, and the OR (95% CI) was 1.06 (1.01, 1.12). MMA% and PMI were negatively associated with T2D risk, and the ORs (95% CI) were 0.87 (0.78, 0.97) and 0.64 (0.47, 0.86), respectively. Urinary DMA, As3+, and As5+ were positively associated with T2D risk. Similar relationships were found between arsenic metabolites and levels of FPG and HbA1c. Moreover, arsenic metabolism-related GRS/wGRS was positively associated with MMA% but negatively associated with DMA%. Genetic predisposition to arsenic metabolism modified the association of inorganic arsenic with T2D risk (Pinteraction = 0.033). Taken together, lower arsenic primary metabolism efficiency (higher iAs% and lower MMA%) may increase T2D risk. Genetic predisposition to arsenic metabolism was associated with arsenic metabolism efficiency, and might modify the association of inorganic arsenic with T2D risk.

Association of urinary arsenic metabolism with type 2 diabetes and glucose homeostasis: Cross-sectional and longitudinal associations.

BACKGROUND: Previous researches have assessed the relationships of urinary arsenic metabolism with type 2 diabetes (T2D) and glucose-insulin homeostasis, but the results were controversial, and potential mechanisms remain largely unclear. OBJECTIVES: This study aimed to investigate the cross-sectional and longitudinal associations of urinary arsenic metabolism with T2D prevalence and glucose changes in relatively higher arsenic exposure, and further to evaluate the underlying roles of oxidative damage in these relationships. METHODS: We included 796 participants at baseline, among them 509 participants were followed up after 2 years. Logistic regression model and leave-one-out approach were applied to evaluate the associations of arsenic metabolism with T2D prevalence. Linear mixed model was conducted to estimate the relationship of arsenic metabolism with glycemic changes over two years. The associations between arsenic metabolism and indicators of oxidative stress were assessed with a linear regression model. We further performed mediation analysis to investigate the role of oxidative stress in the associations of arsenic metabolism with 2-year change of glucose levels. RESULTS: Higher urinary MMA% increased T2D prevalence and baseline glucose levels. MMA% was positively associated with 2-year change of glucose levels. Moreover, we observed significant dose-response relationship between MMA% and 8-hydroxy-2-deoxyguanosine (8-OHdG). However, the mediating role of 8-OHdG in the association of MMA% and 2-year change of glucose levels was not observed in this population. CONCLUSIONS: In this population exposure to relatively higher arsenic levels, higher MMA% contributed to increased T2D prevalence and glucose homeostasis disorder. Arsenic metabolism also affected oxidative stress levels, especially 8-OHdG. Further studies are required to investigate the potential mechanisms.

Hydrogen-rich water treatment increased several phytohormones and prolonged the shelf life in postharvest okras.

Hydrogen-rich water (HRW) treatment has been reported to delay the softening and senescence of postharvest okras, but its regulatory mechanism remains unclear. In this paper, we investigated the effects of HRW treatment on the metabolism of several phytohormones in postharvest okras, which act as regulatory molecules in fruit ripening and senescence processes. The results showed that HRW treatment delayed okra senescence and maintained fruit quality during storage. The treatment upregulated all of the melatonin biosynthetic genes such as AeTDC, AeSNAT, AeCOMT and AeT5H, contributing to the higher melatonin content in the treated okras. Meanwhile, increased transcripts of anabolic genes but lower expression of catabolic genes involved in indoleacetic acid (IAA) and gibberellin (GA) metabolism were observed in okras when treated with HRW, which was related to the enhanced levels of IAA and GA. However, the treated okras experienced lower abscisic acid (ABA) content as compared to the non-treated fruit due to the down-regulation of its biosynthetic genes and up-regulation of the degradative gene AeCYP707A. Additionally, there was no difference in γ-aminobutyric acid between the non-treated and HRW-treated okras. Collectively, our results indicated that HRW treatment increased levels of melatonin, GA and IAA, but decreased ABA content, which ultimately delayed fruit senescence and prolonged shelf life in postharvest okras.

Discovery and Characterization of the Key Constituents in Ginkgo biloba Leaf Extract With Potent Inhibitory Effects on Human UDP-Glucuronosyltransferase 1A1.

Human UDP-glucuronosyltransferase 1A1 (hUGT1A1) is one of the most essential phase II enzymes in humans. Dysfunction or strong inhibition of hUGT1A1 may result in hyperbilirubinaemia and clinically relevant drug/herb-drug interactions (DDIs/HDIs). Recently, a high-throughput fluorescence-based assay was constructed by us to find the compounds/herbal extracts with strong inhibition against intracellular hUGT1A1. Following screening of over one hundred of herbal products, the extract of Ginkgo biloba leaves (GBL) displayed the most potent hUGT1A1 inhibition in HeLa-UGT1A1 cells (Hela cells overexpressed hUGT1A1). Further investigations demonstrated that four biflavones including bilobetin, isoginkgetin, sciadopitysin and ginkgetin, are key constituents responsible for hUGT1A1 inhibition in living cells. These biflavones potently inhibit hUGT1A1 in both human liver microsomes (HLM) and living cells, with the IC50 values ranging from 0.075 to 0.41 µM in living cells. Inhibition kinetic analyses and docking simulations suggested that four tested biflavones potently inhibit hUGT1A1-catalyzed NHPN-O-glucuronidation in HLM via a mixed inhibition manner, showing the K i values ranging from 0.07 to 0.74 µM. Collectively, our findings uncover the key constituents in GBL responsible for hUGT1A1 inhibition and decipher their inhibitory mechanisms against hUGT1A1, which will be very helpful for guiding the rational use of GBL-related herbal products in clinical settings.

Cu-Doped Boron Nitride Nanosheets for Solid-Phase Extraction and Determination of Rhodamine B in Foods Matrix.

Cu-doped boron nitride nanosheets (Cu-BNNS) were first reported as promising adsorbents for the solid-phase extraction and determination of rhodamine B (RhB) dye in a food matrix. Different characterizations, including XRD, FTIR, XPS, SEM, and TEM, were performed to confirm the formation of the adsorbent. Then, the adsorption performance of Cu-BNNS was investigated by adsorption kinetics, isotherms, and thermodynamics. Multiple extraction parameters were optimized by single-factor experiments. Under optimized conditions, the recoveries in the food matrix were in the range of 89.8-95.4%, with the spiked levels of 100 ng/mL and 500 ng/mL, respectively. This novel system was expected to have great potential to detect RhB in a wide variety of real samples.

Stock prediction based on bidirectional gated recurrent unit with convolutional neural network and feature selection.

With the development of recent years, the field of deep learning has made great progress. Compared with the traditional machine learning algorithm, deep learning can better find the rules in the data and achieve better fitting effect. In this paper, we propose a hybrid stock forecasting model based on Feature Selection, Convolutional Neural Network and Bidirectional Gated Recurrent Unit (FS-CNN-BGRU). Feature Selection (FS) can select the data with better performance for the results as the input data after data normalization. Convolutional Neural Network (CNN) is responsible for feature extraction. It can extract the local features of the data, pay attention to more local information, and reduce the amount of calculation. The Bidirectional Gated Recurrent Unit (BGRU) can process the data with time series, so that it can have better performance for the data with time series attributes. In the experiment, we used single CNN, LSTM and GRU models and mixed models CNN-LSTM, CNN-GRU and FS-CNN-BGRU (the model used in this manuscript). The results show that the performance of the hybrid model (FS-CNN-BGRU) is better than other single models, which has a certain reference value.

Methylophiopogonanone A is a naturally occurring broad-spectrum inhibitor against human UDP-glucuronosyltransferases: Inhibition behaviours and implication in herb-drug interactions.

Methylophiopogonanone A (MOA) is an abundant homoisoflavonoid in the Chinese herb Ophiopogonis Radix. Recent investigations revealed that MOA inhibited several human cytochrome P450 enzymes (CYPs) and stimulated OATP1B1. However, the inhibitory effects of MOA on phase II drug-metabolizing enzymes, such as human UDP-glucuronosyltransferases (hUGTs), have not been well investigated. Herein, the inhibition potentials of MOA on hUGTs were assessed. The results clearly demonstrated that MOA dose-dependently inhibited all tested hUGTs including UGT1A1 (IC50 = 1.23 µM), one of the most important detoxification enzymes in humans. Further investigations showed that MOA strongly inhibited UGT1A1-catalysed NHPH-O-glucuronidation in a range of biological settings including hUGT1A1, human liver microsomes (HLM) and HeLa cells overexpressing UGT1A1. Inhibition kinetic analyses demonstrated that MOA competitively inhibited UGT1A1-catalysed NHPH-O-glucuronidation in both hUGT1A1 and HLM, with Ki values of 0.52 and 1.22 µM, respectively. Collectively, our findings expanded knowledge of the interactions between MOA and human drug-metabolizing enzymes, which would be very helpful for guiding the use of MOA-related herbal products in clinical settings.

A broad-spectrum substrate for the human UDP-glucuronosyltransferases and its use for investigating glucuronidation inhibitors.

Strong inhibition of the human UDP-glucuronosyltransferase enzymes (UGTs) may lead to undesirable effects, including hyperbilirubinaemia and drug/herb-drug interactions. Currently, there is no good way to examine the inhibitory effects and specificities of compounds toward all the important human UGTs, side-by-side and under identical conditions. Herein, we report a new, broad-spectrum substrate for human UGTs and its uses in screening and characterizing of UGT inhibitors. Following screening a variety of phenolic compound(s), we have found that methylophiopogonanone A (MOA) can be readily O-glucuronidated by all tested human UGTs, including the typical N-glucuronidating enzymes UGT1A4 and UGT2B10. MOA-O-glucuronidation yielded a single mono-O-glucuronide that was biosynthesized and purified for structural characterization and for constructing an LC-UV based MOA-O-glucuronidation activity assay, which was then used for investigating MOA-O-glucuronidation kinetics in recombinant human UGTs. The derived Km values were crucial for selecting the most suitable assay conditions for assessing inhibitory potentials and specificity of test compound(s). Furthermore, the inhibitory effects and specificities of four known UGT inhibitors were reinvestigated by using MOA as the substrate for all tested UGTs. Collectively, MOA is a broad-spectrum substrate for the human UGTs, which offers a new and practical tool for assessing inhibitory effects and specificities of UGT inhibitors.

A fluorescence-based microplate assay for high-throughput screening and evaluation of human UGT inhibitors.

Human UDP-glucuronosyltransferase enzymes (hUGTs), one of the most important classes of conjugative enzymes, are responsible for the glucuronidation and detoxification of a variety of endogenous substances and xenobiotics. Inhibition of hUGTs may cause undesirable effects or adverse drug-drug interactions (DDI) via modulating the glucuronidation rates of endogenous toxins or the drugs that are primarily conjugated by the inhibited hUGTs. Herein, to screen hUGTs inhibitors in a more efficient way, a novel fluorescence-based microplate assay has been developed by utilizing a fluorogenic substrate. Following screening of series of 4-hydroxy-1,8-naphthalimide derivatives, we found that 4-HN-335 is a particularly good substrate for a panel of hUGTs. Under physiological conditions, 4-HN-335 can be readily O-glucuronidated by ten hUGTs, such reactions generate a single O-glucuronide with a high quantum yield (Ф = 0.79) and bring remarkable changes in fluorescence emission. Subsequently, a fluorescence-based microplate assay is developed to simultaneously measure the inhibitory effects of selected compound(s) on ten hUGTs. The newly developed fluorescence-based microplate assay is time- and cost-saving, easy to manage and can be adapted for 96-well microplate format with the Z-factor of 0.92. We further demonstrate the utility of the fluorescence-based assay for high-throughput screening of two compound libraries, resulting in the identification of several potent UGT inhibitors, including natural products and FDA-approved drugs. Collectively, this study reports a novel fluorescence-based microplate assay for simultaneously sensing the residual activities of ten hUGTs, which strongly facilitates the identification and characterization of UGT inhibitors from drugs or herbal constituents and the investigations on UGT-mediated DDI.

Design, synthesis and biological evaluation of novel chalcone-like compounds as potent and reversible pancreatic lipase inhibitors.

Pancreatic lipase (PL), a crucial enzyme responsible for hydrolysis of dietary lipids, has been validated as a key therapeutic target to prevent and treat obesity-associated metabolic disorders. Herein, we report the design, synthesis and biological evaluation of a series of chalcone-like compounds as potent and reversible PL inhibitors. Following two rounds of structural modifications at both A and B rings of a chalcone-like skeleton, structure-PL inhibition relationships of the chalcone-like compounds were studied, while the key substituents that would be beneficial for PL inhibition were revealed. Among all tested chalcone-like compounds, compound B13 (a novel chalcone-like compound bearing two long carbon chains) displayed the most potent PL inhibition activity, with an IC50 value of 0.33 µM. Inhibition kinetic analyses demonstrated that B13 could potently inhibit PL-mediated 4-MUO hydrolysis in a mixed inhibition manner, with the Ki value of 0.12 µM. Molecular docking simulations suggested that B13 could tightly bind on PL at both the catalytic site and a non-catalytic site that was located on the surface of PL, which was consistent with the mixed inhibition mode of this agent. In addition, B13 displayed excellent stability in artificial gastrointestinal fluids and good metabolic stability in human liver preparations. Collectively, our findings suggested that chalcone-like compounds were good choices for design and development of orally administrated PL inhibitors, while B13 could be served as a promising lead compound to develop novel anti-obesity agents via targeting on PL.

ICT-modulated NIR water-soluble fluorescent probe with large Stokes shift for selective detection of cysteine in living cells and zebrafish.

The fluorescent probes with good water-solubility, long-wavelength emission and large Stokes shift are greatly desirable for in vivo detection. Herein, we designed a novel 1,8-naphthalimide-based near-infrared (NIR) optical and fluorescent probe (NTC) for sensing cysteine (Cys). Using acrylate as the recognition site, the probe demonstrated high selectivity and sensitivity for Cys with a low detection limit (0.093 µM) in aqueous buffer solution due to the excellent water-solubility. Upon the reaction with Cys, the recovery of intramolecular charge transfer (ICT) in the probe led to about 40-fold fluorescence enhancement. Furthermore, the reaction result was investigated by 1H NMR, and HRMS analyses, and the sensing mechanism was validated by quantum calculations. Finally, NTC was applied to image exogenous and endogenous Cys in HeLa cells and zebrafish selectively, implying that the probe possessed great potential application in biological fluorescence sensing.

An ultra-sensitive and easy-to-use assay for sensing human UGT1A1 activities in biological systems.

The human UDP-glucuronosyltransferase 1A1 (UGT1A1), one of the most essential conjugative enzymes, is responsible for the metabolism and detoxification of bilirubin and other endogenous substances, as well as many different xenobiotic compounds. Deciphering UGT1A1 relevance to human diseases and characterizing the effects of small molecules on the activities of UGT1A1 requires reliable tools for probing the function of this key enzyme in complex biological matrices. Herein, an easy-to-use assay for highly-selective and sensitive monitoring of UGT1A1 activities in various biological matrices, using liquid chromatography with fluorescence detection (LC-FD), has been developed and validated. The newly developed LC-FD based assay has been confirmed in terms of sensitivity, specificity, precision, quantitative linear range and stability. One of its main advantages is lowering the limits of detection and quantification by about 100-fold in comparison to the previous assay that used the same probe substrate, enabling reliable quantification of lower amounts of active enzyme than any other method. The precision test demonstrated that both intra- and inter-day variations for this assay were less than 5.5%. Furthermore, the newly developed assay has also been successfully used to screen and characterize the regulatory effects of small molecules on the expression level of UGT1A1 in living cells. Overall, an easy-to-use LC-FD based assay has been developed for ultra-sensitive UGT1A1 activities measurements in various biological systems, providing an inexpensive and practical approach for exploring the role of UGT1A1 in human diseases, interactions with xenobiotics, and characterization modulatory effects of small molecules on this conjugative enzyme.

Enhancing the atrazine tolerance of Pennisetum americanum (L.) K. Schum by inoculating with indole-3-acetic acid producing strain Pseudomonas chlororaphis PAS18.

Atrazine as a kind of herbicide could cause damage to the sensitive plants. Though plant growth promoting rhizobacteria (PGPR) have been proven with the potential to enhance the resistance of plants against various abiotic stresses, whether it could alleviate phytotoxicity caused by atrazine is sill unclear. In present study, the effects of strain Pseudomonas chlororaphis PAS18, a kind of PGPR enable to produce indole-3-acetic acid (IAA), on the growth and physiological responses of Pennisetum americanum (L.) K.Schum seedlings were investigated under three different levels (0, 20 and 100 mg kg-1) of atrazine in pot experiment. The results suggest that strain PAS18 could alleviate the growth and physiological interference caused by 20 mg kg-1 of atrazine. Physiological analysis showed strain PAS18 could further decrease the damaged extent of photosystem II, superoxide radical level and malondialdehyde content of test plant via up-regulating psbA expression, enhancing superoxide dismutase activity and reducing atrazine accumulation in the test plant. Moreover, ion flux measurements suggest that IAA could alleviate the Ca2+ exflux state of the test plant which caused by atrazine stress. Hence, it is plausible that strain PAS18 could alleviate atrazine-induced stress to P. americanum by enhancing the photosystem II repair and antioxidant defense ability as well as balancing the Ca2+ flux.

Interactions of drug-metabolizing enzymes with the Chinese herb Psoraleae Fructus.

Psoraleae Fructus (the dried fruits of Psoralea corylifolia), one of the most frequently used Chinese herbs in Asian countries, has a variety of biological activities. In clinical settings, Psoraleae Fructus or Psoraleae Fructus-related herbal medicines frequently have been used in combination with a number of therapeutic drugs for the treatment of various human diseases, such as leukoderma, rheumatism and dysentery. The use of Psoraleae Fructus in combination with drugs has aroused concern of the potential risks of herb-drug interactions (HDI) or herb-endobiotic interactions (HEI). This article reviews the interactions between human drug-metabolizing enzymes and the constituents of Psoraleae Fructus; the major constituents in Psoraleae Fructus, along with their chemical structures and metabolic pathways are summarized, and the inhibitory and inductive effects of the constituents in Psoraleae Fructus on human drug-metabolizing enzymes (DMEs), including target enzyme(s), its modulatory potency, and mechanisms of action are presented. Collectively, this review summarizes current knowledge of the interactions between the Chinese herb Psoraleae Fructus and therapeutic drugs in an effort to facilitate its rational use in clinical settings, and especially to avoid the potential risks of HDI or HEI through human DMEs.

Highly Sensitive and Selective Fluorescent Probe for Detection of Fe3+ Based on Rhodamine Fluorophore.

A simple rhodamine-based fluorescent probe L1, which exhibits good response to Fe3+ in CH3CN/Tris-HCl buffer (v:v = 9:1, pH 7.00) solution. With the experimental conditions optimized, the probe L1 could be used as a fluorescent and colorimetric probe for Fe3+ with the detection limit as low as 0.29 µM. The binding constant (Ka) of Fe3+ binding to the probe L1 were calculated to be 1.4 × 1010 M-2, respectively from a Benesi-Hildebrand plot. With the addition of Fe3+, the CH3CN/Tris-HCl buffer (v:v = 9:1, pH 7.00) solution of the probe L1 exhibited a obviously color change from transparent to pink with distinctive changes. More importantly, the recognition process of the probe L1 for Fe3+ was chemically reversible on the addition AcO-. Graphical Abstract.