Data from genome wide association studies and geoepidemiological studies established that a com-bination of genetic predisposition and environmental stimulation is required for the loss of tolerance in primary biliary...Data from genome wide association studies and geoepidemiological studies established that a com-bination of genetic predisposition and environmental stimulation is required for the loss of tolerance in primary biliary cholangitis(PBC).The serologic hallmark of PBC are the presence of high titer anti-mitochondrial autoantibodies(AMA)that recognize the lipoyl domain of the mitochondrial pyruvate dehydrogenase E2(PDC--E2)subunit.Extensive efforts have been directed to investigate the molecular basis of AMA.Recently,experimental data has pointed to the thesis that the breaking of tolerance to PDC--E2 is a pivotal event in the initial etiology of PBC,including environmental xenobiotics including those commonly found in cos-metics and food additives,suggesting that chemical modification of the PDC--E2 epitope may render its vulnerable to become a neo-antigen and trigger an immune response in genetically susceptible hosts.Here,we will discuss the natural history,genetics and immunobiology of PBC and structural constraints of PDC--E2 in AMA recognition which makes it vulnerable to chemical modification.展开更多
Experiments were conducted at Entomology division of Directorate of Rice research to study the qualitative and quantitative changes in biochemical constituents in the rice plant treated with different xenobiotics, viz...Experiments were conducted at Entomology division of Directorate of Rice research to study the qualitative and quantitative changes in biochemical constituents in the rice plant treated with different xenobiotics, viz. insecticides like deltamethrin, imidacloprid, herbicide like 2,4-Dichlorophenoxyacetic acid, fungicide like carbendazim, green manure Calotropis gigantea leaves, botanicals like Neem Seed Powder and fertilizer urea along with control plants of TN1, PTB33 and Swama varieties comprising of total 15 treatments. Application of butachlor, carbendazim, deltamethrin and excessive nitrogen fertilization resulted in increased population build up of brown plant hopper (BPH). Significantly, lower honeydew excretion (13 mme area) in the BPH nymphs was observed on resistant PTB33 variety compared to susceptible TN1 and Swarna varieties (116 and 110 mm2 respectively). In susceptible TN1 variety, the sucrose content was significantly higher (9.35 mg/g tissue) compared to BPH resistant PTB33 (5.32 mg/g tissue). The BPH resistant PTB33 variety exhibited significantly lower free amino acid content (1.23 mg/g tissue) as compared to TN1 (2.51 mg/g). The C/N ratio was comparatively high in the resistant PTB33 alone (4.32), but was low in PTB33 applied with 2,4-D + carbendazim (2.73), 2,4-D + imidacloprid ~ carbendazim (2.3), excess urea fertilizer (2.18). The total phenol contents measured in resistant PTB33 (7.5 mg/g dry wt), susceptible TN1 (5.865 mg/g dry wt) and the popular variety Swarna (5.57 mg/g dry wt) were almost same and no statistical difference was observed. Further, treatment of these varieties with different xenobiotics and botanicals also did not significantly alter their total phenol content. However, the phenol content of the resistant PTB 33 alone and treated with xenobiotics was higher compared to the susceptible TN 1 and Swarna varieties alone and treated with xenobiotics. The plant biochemical constituents such as free amino acids, sucrose were lower in untreated resistant PTB33 compared to susceptible TN1, and PTB33 treated with urea and deltamethrin. The high feeding rate and population build up on the susceptible variety TN1 is positively correlated with high quantities of sucrose, free amino acids and lower quantities of phenols and low C/N ratio.展开更多
With the use of over 100,000 industrially produced chemicals, there have been several concerns on human health and environment. Most of these chemicals are exposed into the natural environment during the life cycles o...With the use of over 100,000 industrially produced chemicals, there have been several concerns on human health and environment. Most of these chemicals are exposed into the natural environment during the life cycles of their production, transportation, storage, consumption, and as by-products and wastes. The rising rates of cancer, obesity, and infertility suggests that there are compounds recently introduced to the environment that have altered the chemistry of the human body, and it is only with the monitoring of xenobiotics such as Bisphenol A (BPA), nonyphenols, estrogen (natural and synthetic) and other endocrine-disrupting compounds (EDCs) that patterns and links could be drawn. This paper investigates the safety, environmental and health (SHE) impacts caused by BPA, nonyphenols and estrogens. Derived from petroleum, bisphenol A is used in manufacturing plastic consumer products, including certain water bottles, in dental sealants for children's teeth, and in resins used to line tin cans. Nonyphenol is one of the by-products of alkylphenolpolyethoxilates which is widely used as nonionic surfactants. Synthetic estrogen used for birth control pills as well as natural estrogen excreted by women through urine enters the domestic wastewater streams. These compounds are considered to be EDCs and have severe SHE concerns. In this paper, the challenges of entry of these compounds (xenobiotics) into nature, health and environmental issues and their remediation have been reviewed in detail.展开更多
A conceptual treatment of the mechanisms involved in the process of toxicosis by diverse agents in different tissues indicate a likely unspecific, common, central process in addition to specific precipitating factors ...A conceptual treatment of the mechanisms involved in the process of toxicosis by diverse agents in different tissues indicate a likely unspecific, common, central process in addition to specific precipitating factors acting on a particular site in a cascade of events. Free radicals, membrane functions and calcium functions appear to be links in the common pathway. Such a central mechanism could be interrelated with immunological defenses as well as genotoxic changes at different sites, suggesting parallel or related evolution of these antistress mechanisms. Many radical scavengers, antioxidants, membrane stabilizers, nutritional supplements and calcium modulators have proved beneficial either in reducing toxic impact, delaying the development of lesions or even reversing the effects. Similarly, recent evidences show that some immunomodulators can act as antioxidants and antigenotoxicants. Thus, the status of body defenses which may vary from one individual to the other have a role in deciding the effects under the same quantified risks with varying relative responses. Whether modulation of physiological defenses against stress could help in developing prophylactic measures remains an open question.展开更多
Stroke is devastating and the second leading cause of disability and death worldwide.The pathophysiology of stroke is intricate involving oxidative stress,ionic imbalance,and excitotoxicity leading to cell death.The c...Stroke is devastating and the second leading cause of disability and death worldwide.The pathophysiology of stroke is intricate involving oxidative stress,ionic imbalance,and excitotoxicity leading to cell death.The current therapeutic strategies for ischemic stroke primarily aim to restore cerebral blood flow by removing clots using intravenous thrombolysis and mechanical thrombectomy.However,hemorrhagic stroke requires different therapeutic interventions,where intravenous thrombolysis worsens the persistent condition.Nevertheless,the present treatment strategies do not provide effective neuroprotection as they have limitations such as narrow time window,specialized clinics and personnel,and higher expense.Therefore,studies on novel therapeutic strategies that can render neuroprotection over an extended time with minimum adverse effects are solicited.Xenobiotics are agents that are foreign to the biological system but can regulate their metabolism by binding to different xenobiotic receptors(XRs)to produce toxic substances.Modulation of XRs in different preclinical studies have shown benefits in the stroke outcome.Therefore,targeting XRs may be a future therapeutic strategy for stroke intervention.The present review briefly discusses various implications of xenobiotics and their receptors to evolve as a potential therapeutic target for prospective use as an adjunctive therapy for stroke.展开更多
Aldo-keto reductases(AKRs)are a superfamily of enzymes that play crucial roles in various cellular processes,including the metabolism of xenobiotics,steroids,and carbohydrates.A growing body of evidence has unveiled t...Aldo-keto reductases(AKRs)are a superfamily of enzymes that play crucial roles in various cellular processes,including the metabolism of xenobiotics,steroids,and carbohydrates.A growing body of evidence has unveiled the involvement of AKRs in the development and progression of various cancers.AKRs are aberrantly expressed in a wide range of malignant tumors.Dysregulated expression of AKRs enables the acquisition of hallmark traits of cancer by activating oncogenic signaling pathways and contributing to chemoresistance.AKRs have emerged as promising oncotherapeutic targets given their pivotal role in cancer development and progression.Inhibition of aldose reductase(AR),either alone or in combination with chemotherapeutic drugs,has evolved as a pragmatic therapeutic option for cancer.Several classes of synthetic aldo-keto reductase(AKR)inhibitors have been developed as potential anticancer agents,some of which have shown promise in clinical trials.Many AKR inhibitors from natural sources also exhibit anticancer effects.Small molecule inhibitors targeting specific AKR isoforms have shown promise in preclinical studies.These inhibitors disrupt the activation of oncogenic signaling by modulating transcription factors and kinases and sensitizing cancer cells to chemotherapy.In this review,we discuss the physiological functions of human AKRs,the aberrant expression of AKRs in malignancies,the involvement of AKRs in the acquisition of cancer hallmarks,and the role of AKRs in oncogenic signaling,and drug resistance.Finally,the potential of aldose reductase inhibitors(ARIs)as anticancer drugs is summarized.展开更多
Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expr...Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used drugs.This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide chemotherapy.DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy individuals.The presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed up.The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT vs.GG,OR=5.4,p<0.001)models.Following cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian patients.This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.展开更多
Plant surfaces are covered by a layer of cuticle, which functions as a natural barrier to protect plants from mechanical damage, desiccation, and microbial invasion. Results presented in this report show that the epic...Plant surfaces are covered by a layer of cuticle, which functions as a natural barrier to protect plants from mechanical damage, desiccation, and microbial invasion. Results presented in this report show that the epicuticular wax and the cuticle of plant leaves also play an important role in resisting xenobiotic invasion. Although the epicuticular wax is impermeable to hydrophilic xenobiotics, the cuticle not only restricts the penetration of hydrophilic compounds into leaf cells, but also traps lipophilic ones. The role of the epidermal cells of plant leaves in resisting xenobiotic invasion has been neglected until now. The present study shows, for the first time, that the epidermal cells may reduce or retard the transport of lipophilic xenobiotics into the internal tissues through vacuolar sequestration. Although the guard cells appear to be an easy point of entry for xenobiotics, only a very small proportion of xenobiotics present on the leaf surface actually moves into leaf tissues via the guard cells .展开更多
The gastrointestinal barrier is constantly exposed to numerous environmental substrates that are foreign and potentially harmful. These xenobiotics can cause shifts in the intestinal microbiota composition, affect muc...The gastrointestinal barrier is constantly exposed to numerous environmental substrates that are foreign and potentially harmful. These xenobiotics can cause shifts in the intestinal microbiota composition, affect mucosal immune responses, disturb tissue integrity and impair regeneration. The multidrug transporter ABCB1/MDR1 p-glycoprotein (p-gp) plays a key role at the front line of host defence by efficiently protecting the gastrointestinal barrier from xenobiotic accumulation. This Editorial discusses how altered expression and function of ABCB1/MDR1 p-gp may contribute to the development and persistence of chronic intestinal inflammation in inflammatory bowel diseases (IBD). Recent evidence implies multiple interactions between intestinal microbiota, innate immunity and xenobiotic metabolism via p-gp. While decreased efflux activity may promote disease susceptibility and drug toxicity, increased efflux activity may confer resistance to therapeutic drugs in IBD. Mice deficient in MDR1 A develop spontaneously chronic colitis, providing a highly valuable murine IBD model for the study of intestinal epithelial barrier function, immunoregulation, infectious co-triggers and novel therapeutic approaches. Possible associations of human ABCB1 gene polymorphisms with IBD susceptibility have been evaluated, but results are inconsistent. Future studies must focus on further elucidation of the pathophysiological relevance and immunological functions of p-gp and how its ambiguous effects could be therapeutically targeted in IBD.展开更多
The wastewater discharged from tanneries lack biodegradability due to the presence of recalcitrant compounds at significant concentration. The focal theme of the present investigation was to use chemo-autotrophic acti...The wastewater discharged from tanneries lack biodegradability due to the presence of recalcitrant compounds at significant concentration. The focal theme of the present investigation was to use chemo-autotrophic activated carbon oxidation(CAACO) reactor, an immobilized cell reactor using chemoautotrophs for the treatment of tannery wastewater. The treatment scheme comprised of anaerobic treatment, sand filtration, and CAACO reactor, which remove COD, BOD, TOC, VFA and sulphides respectively by 86%, 95%, 81%, 71% and 100%. Rice bran mesoporous activated carbon prepared indigenously and was used for immobilization of chemoautotrophs. The degradation of xenobiotic compounds by CAACO was confirmed through HPLC and FT-IR techniques.展开更多
Vitamin K(VK), which was originally identified as a cofactor involved in the production of functional coagulation factors in the liver, has been shown to be involved in various aspects of physiological and pathologica...Vitamin K(VK), which was originally identified as a cofactor involved in the production of functional coagulation factors in the liver, has been shown to be involved in various aspects of physiological and pathological events, including bone metabolism, cardiovascular diseases and tumor biology. The mechanisms and roles of VK are gradually becoming clear. Several novel enzymes involved in the VK cycle were identified and have been shown to be linked to tumorigenesis. The VKs have been shown to suppress liver cancer cell growth through multiple signaling pathways via the transcription factors and protein kinases. A VK2 analog was applied to the chemoprevention of hepatocellular carcinoma(HCC) recurrence after curative therapy and was shown to have beneficial effects, both in the suppression of HCC recurrence and in patient survival. Although a large scale randomized control study failed to demonstrate the suppression of HCC recurrence, a meta-analysis suggested a beneficial effect on the long-term survival of HCC patients. However, the beneficial effects of VK administration alone were not sufficient to prevent or treat HCC in clinical settings. Thus its combination with other anti-cancer reagents and the development of more potent novel VK derivatives are the focus of ongoing research which seeks to achieve satisfactory therapeutic effects against HCC.展开更多
Glutathione S-transferases(GSTs) from Liposcelis bostrychophila Badonnel and L.entomophila(Enderlein)(Psocoptera:Liposcelididae) were purified by glutathione-agarose affinity chromatography,and characterized su...Glutathione S-transferases(GSTs) from Liposcelis bostrychophila Badonnel and L.entomophila(Enderlein)(Psocoptera:Liposcelididae) were purified by glutathione-agarose affinity chromatography,and characterized subsequently by their Michaelis-Menten kinetics toward the artificial substrates 1-chloro-2,4-dinitrobenzene(CDNB) and reduced glutathione(GSH),respectively.The specific activity of the purified GST toward CDNB was 2.3-fold higher in L.bostrychophila than in L.entomophila.Though the specific activities of purified enzymes varied between the two species,the purification yields were similar.SDS-PAGE revealed one band at 23 kDa for both the species.GSTs of L.entomophila exhibited higher Michaelis-Menten constants(Km) but lower maximal velocity(Vmax) values than those of L.bostrychophila.The optimum pH for CDNB conjugation of L.bostrychophila and L.entomophila GSTs was 7.0 and 7.5,and optimum temperature was 35 and 40°C,respectively.Inhibition kinetics showed that cibacron blue,curcumin,bromosulfalein,ethacrynic acid,and carbosulfan had excellent inhibitory effects on GSTs in both species,but the inhibitory effects of beta-cypermethrin,fenpropathrin,tetraethylthiuram disulfide,and diethyl maleate were not significant.展开更多
AIM: To evaluate the effects of frying oil and Houttuynia cordata Thunb (H. cordata), a vegetable traditionally consumed in Taiwan, on the xenobiotic-metabolizing enzyme system of rodents. METHODS: Forty-eight Sprague...AIM: To evaluate the effects of frying oil and Houttuynia cordata Thunb (H. cordata), a vegetable traditionally consumed in Taiwan, on the xenobiotic-metabolizing enzyme system of rodents. METHODS: Forty-eight Sprague-Dawley rats were fed with a diet containing 0%, 2% or 5% H. cordata powder and 15% fresh soybean oil or 24-h oxidized frying oil (OFO) for 28 d respectively. The level of microsomal protein, total cytochrome 450 content (CYP450) and enzyme activities including NADPH reductase, ethoxyresorufin 0-deethylase (EROD), pentoxyresorufin 0-dealkylase (PROD), aniline hydroxylase (ANH), aminopyrine demethylase (AMD), and quinone reductase (QR) were determined. QR represented phase Ⅱ enzymes, the rest of the enzymes tested represented phase Ⅰ enzymes. RESULTS: The oxidized frying oil feeding produced a significant increase in phase Ⅰ and Ⅱ enzyme systems, including the content of CYP450 and microsomal protein, and the activities of NADPH reductase, EROD, PROD, ANH, AMD and QR in rats (P<0.05). In addition, the activities of EROD, ANH and AMD decreased and QR increased after feeding with H. cordata in OFO-fed group (P<0.05). The feeding with 2% H. cordata diet showed the most significant effect. CONCLUSION: The OFO diet induces phases I and II enzyme activity, and the 2% H. cordata diet resulted in a better regulation of the xenobiotic-metabolizing enzyme system.展开更多
The susceptibility of individuals to obesity has been reported in many developed countries with predisposition of humans to obesity associated with high calorie diets and unhealthy lifestyles. Obesity may closely be i...The susceptibility of individuals to obesity has been reported in many developed countries with predisposition of humans to obesity associated with high calorie diets and unhealthy lifestyles. Obesity may closely be involved in cell suicide in various organ diseases with the importance of accelerated aging that requires early intervention with drug therapy to prevent diseases such as non alcoholic fatty liver disease (NAFLD) that has increased in children and reached to approx. 40% of the global population. Obesity is induced by various diets and lifestyle factors such as stress, anxiety and depression which are important to consider with the global increase in obesity and are possibly linked to the rise in individuals with brain disorders that involve neurodegeneration. Xenobiotics such as the endocrine disruptor chemicals that have increased in the environment in various developed countries lead to various chronic endocrine diseases as populations divert towards unhealthy diets and lifestyles with induction of NAFLD and obesity. The amount and nature of food intake that improves and increases liver lipid and xenobiotic metabolism in obese individuals have become important to decrease the risk for increased adiposity in man. High fibre or protein diets that contain leucine may improve liver glucose, lipid and xenobiotic metabolism and require further investigation with xenobiotics such as endocrine disruptors involved in appetite dysregulation and metabolic disorders in developed countries. The use of anti-obese drugs that reduce food intake and improve hypercholesterolemia and cardiovascular disease has been assessed in obesity with drug therapy closely involved either in the prevention or induction of NAFLD and obesity in man.展开更多
Pregnane and Xenobiotic Receptor (PXR; or Steroid and Xenobiotic Receptor, SXR), a new member of the nuclear receptor superfamily, is thought to modulate a network of genes that are involved in xenobiotic metabolism a...Pregnane and Xenobiotic Receptor (PXR; or Steroid and Xenobiotic Receptor, SXR), a new member of the nuclear receptor superfamily, is thought to modulate a network of genes that are involved in xenobiotic metabolism and elimination. To further explore the role of PXR in body’s homeostatic mechanisms, we for the first time, report successful prokary- otic expression and purification of full-length PXR and preparation of polyclonal antibody against the whole protein. The full-length cDNA encoding a 434 amino acids protein was sub-cloned into prokaryotic expression vector, pET-30b and transformed into E. coli BL21(DE3) cells for efficient over expression. The inclusion body fraction, containing the expressed recombinant protein, was purified first by solubilizing in sarcosine extraction buffer and then by affinity column chromatography using Ni-NTA His-Bind matrix. The efficacy of anti-PXR antibody was confirmed by immunocytology, Western blot analysis, EMSA and immunohistochemistry. The antibody obtained was capable of detecting human and mouse PXR with high specificity and sensitivity. Immunofluorescence staining of COS-1 cells transfected with human or mouse PXR showed a clear nuclear localization. Results from immunohistochemistry showed that level of PXR in liver sections is immunologically detectable in the nuclei. Similar to exogenously transfected PXR, Western blot analysis of cell extract from HepG2 and COLO320DM cells revealed a major protein band for endogenous PXR having the expected molecular weight of 50 kDa. Relevance of other immunodetectable bands with reference to PXR isoforms and current testimony are evaluated. Advantages of antibody raised against full-length PXR protein for functional characterization of receptor is discussed and its application for clinical purposes is envisaged.展开更多
AIM To analyze the association between oncohematological diseases and GSTT1 /GSTM1 /CYP1A1 polymorphisms, dietary habits and smoking, in an argentine hospitalbased case-control study.METHODS This hospital-based case-c...AIM To analyze the association between oncohematological diseases and GSTT1 /GSTM1 /CYP1A1 polymorphisms, dietary habits and smoking, in an argentine hospitalbased case-control study.METHODS This hospital-based case-control study involved 125 patients with oncohematological diseases and 310 control subjects. A questionnaire was used to obtain sociodemographic data and information about habits. Blood samples were collected, and DNA was extracted using salting out methods. Deletions in GSTT1 and GSTM1 (null genotypes) were addressed by PCR. CYP1A1 MspI polymorphism was detected by PCR-RFLP. Odds ratio(OR) and 95%CI were calculated to estimate the association between each variable studied and oncohematological disease.RESULTS Women showed lower risk of disease compared to men(OR 0.52, 95%CI: 0.34-0.82, P = 0.003). Higher levels of education(> 12 years) were significantly associated with an increased risk, compared to complete primary school or less(OR 3.68, 95%CI: 1.82-7.40, P < 0.001 adjusted for age and sex). With respect to tobacco, none of the smoking categories showed association with oncohematological diseases. Regarding dietary habits, consumption of grilled/barbecued meat 3 or more times per month showed significant association with an increased risk of disease(OR 1.72, 95%CI: 1.08-2.75, P = 0.02). Daily consumption of coffee also was associated with an increased risk(OR 1.77, 95%CI: 1.03-3.03, P = 0.03). Results for GSTT1, GSTM1 and CYP1A1 polymorphisms showed no significant association with oncohematological diseases. When analyzing the interaction between polymorphisms and tobacco smoking or dietary habits, no statistically significant associations that modify disease risk were found. CONCLUSION We reported an increased risk of oncohematological diseases associated with meat and coffee intake. We did not find significant associations between genetic polymorphisms and blood cancer.展开更多
Objective: Since the ban of antibiotics as growth promoting feed additives in the EU in 2006 research in alternatives has gained importance. Phytogenic feed additives represent a heterogenous class of different plant ...Objective: Since the ban of antibiotics as growth promoting feed additives in the EU in 2006 research in alternatives has gained importance. Phytogenic feed additives represent a heterogenous class of different plant derived substances that are discussed to improve the health of farm animals by direct and indirect antioxidant effects and by influencing microbial eubiosis in the gastrointestinal tract. Consequently our study aimed to investigate the influence of broccoli extract and the essential oils of tur- meric, oregano, thyme and rosemary, as selected individual additives, on intestinal and faecal microflora, on xenobiotic enzymes, and on the antioxidant system of piglets. Methods: 48 four weeks old male weaned piglets were assigned to 6 groups of 8. The piglets were housed individually in stainless steel pens with slatted floor. The control group (Con) was fed a diet without an additive for 4 weeks. The diet of group BE contained 0.15 g/kg sulforaphane in form of a broccoli extract. 535, 282, 373 and 476 mg/kg of the essential oils of turmeric (Cuo), oregano (Oo), thyme (To) and rosemary (Ro) were added to the diets of the remaining 4 groups to stan-dardise supplementation to 150 mg/kg of the oils’ key terpene compounds ar-turmerone, carvacrol, thymol and 1,8-cineole. The composition of bacterial microflora was examined by cultivating samples of jejeunal and colonic mucosa and of faeces under specific conditions. The mRNA expression of xenobiotic and antioxidant enzymes was determined by reversing transcrip- tase real time detection PCR (RT-PCR). Total antioxidant status was assayed using the Trolox Equivalent Antioxidant Capacity (TEAC), and lipid peroxidation was determined by measuring thiobarbioturic acid reactive substances (TBA- RS). Results: Compared to Con piglets all additives positively influenced weight gain and feed conversion in week 1. Over the whole trial period no significant differences in performance parameters existed between the experimental groups. Compared to group Con performance of Ro piglets was, however, slightly impaired. Com- pared to Con piglets Cuo, Oo and To increased the ratio of Lactobacilli:E. coli attached to the jejunal mucosa, whereas BE and Ro impaired this ratio slightly. In contrast in colonic mucosa Ro improved Lactobacilli:E. coli ratio. In faecal samples an improvement of Lactobacilli:E. coli ratio could be analysed for To and Ro. Ro was the only additive that reduced the incidence rate of piglets tested positive for enterotoxic E. coli (ETEC). All additives significantly increased jejunal TEAC and reduced TBA-RS. In the liver BE, Cuo, Oo and To increased TEAC in tendency and Ro significantly. Liver TBA-RS were slightly reduced by all additives compared to Con piglets. Whereas the influence of BE, To and Ro on jejunal TEAC mainly was derived from the induction of xenobiotic and antioxidant enzymes (indirect antioxidant effects), Cuo and Oo influenced TEAC by direct antioxidant effects. Discussion and Conclusions: Our results have shown: That within the labiatae oils Oo and To have the potential to improve performance slightly. That phytogenic substances have a small but not sig- nificant influence on intestinal microflora. That phytogenic feed additives up-regulate the anti- oxidant system of piglets either by direct or by indirect antioxidant effects and that they may thereby improve health status. That within the labiatae oils Oo has a high direct antioxidant potential whereas Ro potently induces xenobiotic and antioxidant enzymes. That broccoli extract is an attractive new phytogenic additive, improving antioxidant status by indirect antioxidant effects. That defined combinations of selected phytogenic substances may produce additive effects. That health promoting effects of phytogenic additives in the future should be studied systematically under the challenge with pathogenic microorganisms or food derived to-xins.展开更多
Surfactants are the major active ingredients of laundry detergents. Therefore, special attention should be focused on the treatment and disposal of laundry wastewater. The aim of this study was to characterise the was...Surfactants are the major active ingredients of laundry detergents. Therefore, special attention should be focused on the treatment and disposal of laundry wastewater. The aim of this study was to characterise the wastewater from a commercial laundry over 30 days. Physicochemical analyses were performed, monitoring the content of nitrogen, phosphate, heavy metals, linear alkylbenzene sulphonate (LAS), volatile organic acids and alcohols. The pH was approximately 5.6 and the COD approximately 4800 mg·L-1. The average concentrations of sulphate, sulphide, N-ammoniacal organic nitrogen compounds and heavy metals were below the maximum limit, in accordance with local and national environmental legislation, and the average total suspended solids was 0.08 g·L-1. Among the metals analysed, iron was observed with the highest concentrations (0.037 mg·L-1 and 0.72 mg·L-1). Phosphate was detected in 93% of samples (94.65 mg·L-1 average). LAS was detected in all samples (12.24 mg·L-1 to 1023.7 mg·L-1). Thirty-three different xenobiotic organic compounds were identified in the laundry wastewater with the qualitative screening. The major groups of the compounds were fragrances, preservatives, solvents and some surfactants. Although the characterisation indicated low values for many parameters, this does not eliminate the need for specific treatment before its disposal at the sewage system.展开更多
In this experiment carried out on Caribbean chili pepper plants(Capsicum chinensis),the bio-insecticide azadirachtin in combination with an NPK fertilizer proved to have a greater lethal impact on the larvae of Aedes ...In this experiment carried out on Caribbean chili pepper plants(Capsicum chinensis),the bio-insecticide azadirachtin in combination with an NPK fertilizer proved to have a greater lethal impact on the larvae of Aedes albopictus than each substance on its own.This synergistic effect is noticeably important when both inputs are sprayed directly on the leaves of the plant(foliar application).While the plants treated with azadirachtin or NPK alone cause a 33.6%and 36.4%mortal-ity respectively of the Ae.albopictus larvae,the combination of the two inputs induces a 74.4%mortality on the mosquito larvae.To account for this synergistic effect phenomenon inside the plant,the azadirachtin+NPK combination most likely interacts with the capsaicinoid compounds naturally produced by the plant.Not only does this study carried out on azadirachtin reveal major results but the methodology itself offers a most interesting approach on how to boost the agricultural inputs within the plants.As a matter of fact,this research axis demands developing since the control of pests harmful to men has been dramatically lacking insecticide molecules acting on new targets over the past three decades.展开更多
基金Supported by National Institutes of Health grants (in part), DK39588, DK090019 and DK067003
文摘Data from genome wide association studies and geoepidemiological studies established that a com-bination of genetic predisposition and environmental stimulation is required for the loss of tolerance in primary biliary cholangitis(PBC).The serologic hallmark of PBC are the presence of high titer anti-mitochondrial autoantibodies(AMA)that recognize the lipoyl domain of the mitochondrial pyruvate dehydrogenase E2(PDC--E2)subunit.Extensive efforts have been directed to investigate the molecular basis of AMA.Recently,experimental data has pointed to the thesis that the breaking of tolerance to PDC--E2 is a pivotal event in the initial etiology of PBC,including environmental xenobiotics including those commonly found in cos-metics and food additives,suggesting that chemical modification of the PDC--E2 epitope may render its vulnerable to become a neo-antigen and trigger an immune response in genetically susceptible hosts.Here,we will discuss the natural history,genetics and immunobiology of PBC and structural constraints of PDC--E2 in AMA recognition which makes it vulnerable to chemical modification.
文摘Experiments were conducted at Entomology division of Directorate of Rice research to study the qualitative and quantitative changes in biochemical constituents in the rice plant treated with different xenobiotics, viz. insecticides like deltamethrin, imidacloprid, herbicide like 2,4-Dichlorophenoxyacetic acid, fungicide like carbendazim, green manure Calotropis gigantea leaves, botanicals like Neem Seed Powder and fertilizer urea along with control plants of TN1, PTB33 and Swama varieties comprising of total 15 treatments. Application of butachlor, carbendazim, deltamethrin and excessive nitrogen fertilization resulted in increased population build up of brown plant hopper (BPH). Significantly, lower honeydew excretion (13 mme area) in the BPH nymphs was observed on resistant PTB33 variety compared to susceptible TN1 and Swarna varieties (116 and 110 mm2 respectively). In susceptible TN1 variety, the sucrose content was significantly higher (9.35 mg/g tissue) compared to BPH resistant PTB33 (5.32 mg/g tissue). The BPH resistant PTB33 variety exhibited significantly lower free amino acid content (1.23 mg/g tissue) as compared to TN1 (2.51 mg/g). The C/N ratio was comparatively high in the resistant PTB33 alone (4.32), but was low in PTB33 applied with 2,4-D + carbendazim (2.73), 2,4-D + imidacloprid ~ carbendazim (2.3), excess urea fertilizer (2.18). The total phenol contents measured in resistant PTB33 (7.5 mg/g dry wt), susceptible TN1 (5.865 mg/g dry wt) and the popular variety Swarna (5.57 mg/g dry wt) were almost same and no statistical difference was observed. Further, treatment of these varieties with different xenobiotics and botanicals also did not significantly alter their total phenol content. However, the phenol content of the resistant PTB 33 alone and treated with xenobiotics was higher compared to the susceptible TN 1 and Swarna varieties alone and treated with xenobiotics. The plant biochemical constituents such as free amino acids, sucrose were lower in untreated resistant PTB33 compared to susceptible TN1, and PTB33 treated with urea and deltamethrin. The high feeding rate and population build up on the susceptible variety TN1 is positively correlated with high quantities of sucrose, free amino acids and lower quantities of phenols and low C/N ratio.
文摘With the use of over 100,000 industrially produced chemicals, there have been several concerns on human health and environment. Most of these chemicals are exposed into the natural environment during the life cycles of their production, transportation, storage, consumption, and as by-products and wastes. The rising rates of cancer, obesity, and infertility suggests that there are compounds recently introduced to the environment that have altered the chemistry of the human body, and it is only with the monitoring of xenobiotics such as Bisphenol A (BPA), nonyphenols, estrogen (natural and synthetic) and other endocrine-disrupting compounds (EDCs) that patterns and links could be drawn. This paper investigates the safety, environmental and health (SHE) impacts caused by BPA, nonyphenols and estrogens. Derived from petroleum, bisphenol A is used in manufacturing plastic consumer products, including certain water bottles, in dental sealants for children's teeth, and in resins used to line tin cans. Nonyphenol is one of the by-products of alkylphenolpolyethoxilates which is widely used as nonionic surfactants. Synthetic estrogen used for birth control pills as well as natural estrogen excreted by women through urine enters the domestic wastewater streams. These compounds are considered to be EDCs and have severe SHE concerns. In this paper, the challenges of entry of these compounds (xenobiotics) into nature, health and environmental issues and their remediation have been reviewed in detail.
文摘A conceptual treatment of the mechanisms involved in the process of toxicosis by diverse agents in different tissues indicate a likely unspecific, common, central process in addition to specific precipitating factors acting on a particular site in a cascade of events. Free radicals, membrane functions and calcium functions appear to be links in the common pathway. Such a central mechanism could be interrelated with immunological defenses as well as genotoxic changes at different sites, suggesting parallel or related evolution of these antistress mechanisms. Many radical scavengers, antioxidants, membrane stabilizers, nutritional supplements and calcium modulators have proved beneficial either in reducing toxic impact, delaying the development of lesions or even reversing the effects. Similarly, recent evidences show that some immunomodulators can act as antioxidants and antigenotoxicants. Thus, the status of body defenses which may vary from one individual to the other have a role in deciding the effects under the same quantified risks with varying relative responses. Whether modulation of physiological defenses against stress could help in developing prophylactic measures remains an open question.
文摘Stroke is devastating and the second leading cause of disability and death worldwide.The pathophysiology of stroke is intricate involving oxidative stress,ionic imbalance,and excitotoxicity leading to cell death.The current therapeutic strategies for ischemic stroke primarily aim to restore cerebral blood flow by removing clots using intravenous thrombolysis and mechanical thrombectomy.However,hemorrhagic stroke requires different therapeutic interventions,where intravenous thrombolysis worsens the persistent condition.Nevertheless,the present treatment strategies do not provide effective neuroprotection as they have limitations such as narrow time window,specialized clinics and personnel,and higher expense.Therefore,studies on novel therapeutic strategies that can render neuroprotection over an extended time with minimum adverse effects are solicited.Xenobiotics are agents that are foreign to the biological system but can regulate their metabolism by binding to different xenobiotic receptors(XRs)to produce toxic substances.Modulation of XRs in different preclinical studies have shown benefits in the stroke outcome.Therefore,targeting XRs may be a future therapeutic strategy for stroke intervention.The present review briefly discusses various implications of xenobiotics and their receptors to evolve as a potential therapeutic target for prospective use as an adjunctive therapy for stroke.
基金SN and GBR are supported by grants from the Science and Engineering Research Board,Government of India(EMR/2016/001984)Indian Council of Medical Research.
文摘Aldo-keto reductases(AKRs)are a superfamily of enzymes that play crucial roles in various cellular processes,including the metabolism of xenobiotics,steroids,and carbohydrates.A growing body of evidence has unveiled the involvement of AKRs in the development and progression of various cancers.AKRs are aberrantly expressed in a wide range of malignant tumors.Dysregulated expression of AKRs enables the acquisition of hallmark traits of cancer by activating oncogenic signaling pathways and contributing to chemoresistance.AKRs have emerged as promising oncotherapeutic targets given their pivotal role in cancer development and progression.Inhibition of aldose reductase(AR),either alone or in combination with chemotherapeutic drugs,has evolved as a pragmatic therapeutic option for cancer.Several classes of synthetic aldo-keto reductase(AKR)inhibitors have been developed as potential anticancer agents,some of which have shown promise in clinical trials.Many AKR inhibitors from natural sources also exhibit anticancer effects.Small molecule inhibitors targeting specific AKR isoforms have shown promise in preclinical studies.These inhibitors disrupt the activation of oncogenic signaling by modulating transcription factors and kinases and sensitizing cancer cells to chemotherapy.In this review,we discuss the physiological functions of human AKRs,the aberrant expression of AKRs in malignancies,the involvement of AKRs in the acquisition of cancer hallmarks,and the role of AKRs in oncogenic signaling,and drug resistance.Finally,the potential of aldose reductase inhibitors(ARIs)as anticancer drugs is summarized.
文摘Cytochromes P450(CYPs)play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75%of the total metabolism of commercially available drugs,including chemotherapeutics.The gene expression and enzyme activity of CYPs are variable between individuals,which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics,as well as differences in the efficacy and toxicity of clinically used drugs.This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients,as well as the clinical outcome after receiving cyclophosphamide chemotherapy.DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex-and age-matched healthy individuals.The presence of the CYP2B6*9(G516T)polymorphism was examined by PCR-based allele specific amplification(ASA).Patients were further indicated for receiving chemotherapy,and then they were followed up.The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models,comprising allelic(T-allele vs.G-allele,OR=4.8,p<0.001)and dominant(GT+TT vs.GG,OR=5.4,p<0.001)models.Following cyclophosphamide chemotherapy,we found that the patients with variant genotypes(GT+TT)were less likely to achieve remission compared to those with the wild-type genotype(GG),with a response percentage of(37.5%vs.83%,respectively).In conclusion,our findings showed that the CYP2B6*9(G516T)polymorphism is associated with B-CLL susceptibility among Egyptian patients.This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.
基金Publication of this paper is supported by the National Natural Science Foundation of China (30424813) and Science Publication Foundation of the Chinese Academy of Sciences.
文摘Plant surfaces are covered by a layer of cuticle, which functions as a natural barrier to protect plants from mechanical damage, desiccation, and microbial invasion. Results presented in this report show that the epicuticular wax and the cuticle of plant leaves also play an important role in resisting xenobiotic invasion. Although the epicuticular wax is impermeable to hydrophilic xenobiotics, the cuticle not only restricts the penetration of hydrophilic compounds into leaf cells, but also traps lipophilic ones. The role of the epidermal cells of plant leaves in resisting xenobiotic invasion has been neglected until now. The present study shows, for the first time, that the epidermal cells may reduce or retard the transport of lipophilic xenobiotics into the internal tissues through vacuolar sequestration. Although the guard cells appear to be an easy point of entry for xenobiotics, only a very small proportion of xenobiotics present on the leaf surface actually moves into leaf tissues via the guard cells .
基金Supportedby the Deutsche Forschungsgemeinschaft,No.CA226/4-3 to Cario E
文摘The gastrointestinal barrier is constantly exposed to numerous environmental substrates that are foreign and potentially harmful. These xenobiotics can cause shifts in the intestinal microbiota composition, affect mucosal immune responses, disturb tissue integrity and impair regeneration. The multidrug transporter ABCB1/MDR1 p-glycoprotein (p-gp) plays a key role at the front line of host defence by efficiently protecting the gastrointestinal barrier from xenobiotic accumulation. This Editorial discusses how altered expression and function of ABCB1/MDR1 p-gp may contribute to the development and persistence of chronic intestinal inflammation in inflammatory bowel diseases (IBD). Recent evidence implies multiple interactions between intestinal microbiota, innate immunity and xenobiotic metabolism via p-gp. While decreased efflux activity may promote disease susceptibility and drug toxicity, increased efflux activity may confer resistance to therapeutic drugs in IBD. Mice deficient in MDR1 A develop spontaneously chronic colitis, providing a highly valuable murine IBD model for the study of intestinal epithelial barrier function, immunoregulation, infectious co-triggers and novel therapeutic approaches. Possible associations of human ABCB1 gene polymorphisms with IBD susceptibility have been evaluated, but results are inconsistent. Future studies must focus on further elucidation of the pathophysiological relevance and immunological functions of p-gp and how its ambiguous effects could be therapeutically targeted in IBD.
文摘The wastewater discharged from tanneries lack biodegradability due to the presence of recalcitrant compounds at significant concentration. The focal theme of the present investigation was to use chemo-autotrophic activated carbon oxidation(CAACO) reactor, an immobilized cell reactor using chemoautotrophs for the treatment of tannery wastewater. The treatment scheme comprised of anaerobic treatment, sand filtration, and CAACO reactor, which remove COD, BOD, TOC, VFA and sulphides respectively by 86%, 95%, 81%, 71% and 100%. Rice bran mesoporous activated carbon prepared indigenously and was used for immobilization of chemoautotrophs. The degradation of xenobiotic compounds by CAACO was confirmed through HPLC and FT-IR techniques.
文摘Vitamin K(VK), which was originally identified as a cofactor involved in the production of functional coagulation factors in the liver, has been shown to be involved in various aspects of physiological and pathological events, including bone metabolism, cardiovascular diseases and tumor biology. The mechanisms and roles of VK are gradually becoming clear. Several novel enzymes involved in the VK cycle were identified and have been shown to be linked to tumorigenesis. The VKs have been shown to suppress liver cancer cell growth through multiple signaling pathways via the transcription factors and protein kinases. A VK2 analog was applied to the chemoprevention of hepatocellular carcinoma(HCC) recurrence after curative therapy and was shown to have beneficial effects, both in the suppression of HCC recurrence and in patient survival. Although a large scale randomized control study failed to demonstrate the suppression of HCC recurrence, a meta-analysis suggested a beneficial effect on the long-term survival of HCC patients. However, the beneficial effects of VK administration alone were not sufficient to prevent or treat HCC in clinical settings. Thus its combination with other anti-cancer reagents and the development of more potent novel VK derivatives are the focus of ongoing research which seeks to achieve satisfactory therapeutic effects against HCC.
基金funded in part by the National Natural Sciences Foundation of China (30871631)the Specialized Research Fund for the Doctoral Program of Higher Education of China to Prof. Wang Jinjun(200806350009)+1 种基金the Doctoral Program of Southwest University of China (SWU109023)the Fundamental Research Funds for the Central Universities,China(XDJK2009C112)
文摘Glutathione S-transferases(GSTs) from Liposcelis bostrychophila Badonnel and L.entomophila(Enderlein)(Psocoptera:Liposcelididae) were purified by glutathione-agarose affinity chromatography,and characterized subsequently by their Michaelis-Menten kinetics toward the artificial substrates 1-chloro-2,4-dinitrobenzene(CDNB) and reduced glutathione(GSH),respectively.The specific activity of the purified GST toward CDNB was 2.3-fold higher in L.bostrychophila than in L.entomophila.Though the specific activities of purified enzymes varied between the two species,the purification yields were similar.SDS-PAGE revealed one band at 23 kDa for both the species.GSTs of L.entomophila exhibited higher Michaelis-Menten constants(Km) but lower maximal velocity(Vmax) values than those of L.bostrychophila.The optimum pH for CDNB conjugation of L.bostrychophila and L.entomophila GSTs was 7.0 and 7.5,and optimum temperature was 35 and 40°C,respectively.Inhibition kinetics showed that cibacron blue,curcumin,bromosulfalein,ethacrynic acid,and carbosulfan had excellent inhibitory effects on GSTs in both species,but the inhibitory effects of beta-cypermethrin,fenpropathrin,tetraethylthiuram disulfide,and diethyl maleate were not significant.
基金Supported by Grant From the National Science Council of Taiwan, No. NSC 90-2320-13-038-038
文摘AIM: To evaluate the effects of frying oil and Houttuynia cordata Thunb (H. cordata), a vegetable traditionally consumed in Taiwan, on the xenobiotic-metabolizing enzyme system of rodents. METHODS: Forty-eight Sprague-Dawley rats were fed with a diet containing 0%, 2% or 5% H. cordata powder and 15% fresh soybean oil or 24-h oxidized frying oil (OFO) for 28 d respectively. The level of microsomal protein, total cytochrome 450 content (CYP450) and enzyme activities including NADPH reductase, ethoxyresorufin 0-deethylase (EROD), pentoxyresorufin 0-dealkylase (PROD), aniline hydroxylase (ANH), aminopyrine demethylase (AMD), and quinone reductase (QR) were determined. QR represented phase Ⅱ enzymes, the rest of the enzymes tested represented phase Ⅰ enzymes. RESULTS: The oxidized frying oil feeding produced a significant increase in phase Ⅰ and Ⅱ enzyme systems, including the content of CYP450 and microsomal protein, and the activities of NADPH reductase, EROD, PROD, ANH, AMD and QR in rats (P<0.05). In addition, the activities of EROD, ANH and AMD decreased and QR increased after feeding with H. cordata in OFO-fed group (P<0.05). The feeding with 2% H. cordata diet showed the most significant effect. CONCLUSION: The OFO diet induces phases I and II enzyme activity, and the 2% H. cordata diet resulted in a better regulation of the xenobiotic-metabolizing enzyme system.
文摘The susceptibility of individuals to obesity has been reported in many developed countries with predisposition of humans to obesity associated with high calorie diets and unhealthy lifestyles. Obesity may closely be involved in cell suicide in various organ diseases with the importance of accelerated aging that requires early intervention with drug therapy to prevent diseases such as non alcoholic fatty liver disease (NAFLD) that has increased in children and reached to approx. 40% of the global population. Obesity is induced by various diets and lifestyle factors such as stress, anxiety and depression which are important to consider with the global increase in obesity and are possibly linked to the rise in individuals with brain disorders that involve neurodegeneration. Xenobiotics such as the endocrine disruptor chemicals that have increased in the environment in various developed countries lead to various chronic endocrine diseases as populations divert towards unhealthy diets and lifestyles with induction of NAFLD and obesity. The amount and nature of food intake that improves and increases liver lipid and xenobiotic metabolism in obese individuals have become important to decrease the risk for increased adiposity in man. High fibre or protein diets that contain leucine may improve liver glucose, lipid and xenobiotic metabolism and require further investigation with xenobiotics such as endocrine disruptors involved in appetite dysregulation and metabolic disorders in developed countries. The use of anti-obese drugs that reduce food intake and improve hypercholesterolemia and cardiovascular disease has been assessed in obesity with drug therapy closely involved either in the prevention or induction of NAFLD and obesity in man.
文摘Pregnane and Xenobiotic Receptor (PXR; or Steroid and Xenobiotic Receptor, SXR), a new member of the nuclear receptor superfamily, is thought to modulate a network of genes that are involved in xenobiotic metabolism and elimination. To further explore the role of PXR in body’s homeostatic mechanisms, we for the first time, report successful prokary- otic expression and purification of full-length PXR and preparation of polyclonal antibody against the whole protein. The full-length cDNA encoding a 434 amino acids protein was sub-cloned into prokaryotic expression vector, pET-30b and transformed into E. coli BL21(DE3) cells for efficient over expression. The inclusion body fraction, containing the expressed recombinant protein, was purified first by solubilizing in sarcosine extraction buffer and then by affinity column chromatography using Ni-NTA His-Bind matrix. The efficacy of anti-PXR antibody was confirmed by immunocytology, Western blot analysis, EMSA and immunohistochemistry. The antibody obtained was capable of detecting human and mouse PXR with high specificity and sensitivity. Immunofluorescence staining of COS-1 cells transfected with human or mouse PXR showed a clear nuclear localization. Results from immunohistochemistry showed that level of PXR in liver sections is immunologically detectable in the nuclei. Similar to exogenously transfected PXR, Western blot analysis of cell extract from HepG2 and COLO320DM cells revealed a major protein band for endogenous PXR having the expected molecular weight of 50 kDa. Relevance of other immunodetectable bands with reference to PXR isoforms and current testimony are evaluated. Advantages of antibody raised against full-length PXR protein for functional characterization of receptor is discussed and its application for clinical purposes is envisaged.
基金Supported by The "Consejo Nacional de Investigaciones Científicas y Técnicas"(PIP-634 to Richard S and Scholarship Grant to Cerliani MB)the "Instituto Nacional del Cáncer"(grant No.R.M.493:Asistencia financiera a proyectos de investigación en cáncer de origen nacional Ⅱ,to Pavicic W)
文摘AIM To analyze the association between oncohematological diseases and GSTT1 /GSTM1 /CYP1A1 polymorphisms, dietary habits and smoking, in an argentine hospitalbased case-control study.METHODS This hospital-based case-control study involved 125 patients with oncohematological diseases and 310 control subjects. A questionnaire was used to obtain sociodemographic data and information about habits. Blood samples were collected, and DNA was extracted using salting out methods. Deletions in GSTT1 and GSTM1 (null genotypes) were addressed by PCR. CYP1A1 MspI polymorphism was detected by PCR-RFLP. Odds ratio(OR) and 95%CI were calculated to estimate the association between each variable studied and oncohematological disease.RESULTS Women showed lower risk of disease compared to men(OR 0.52, 95%CI: 0.34-0.82, P = 0.003). Higher levels of education(> 12 years) were significantly associated with an increased risk, compared to complete primary school or less(OR 3.68, 95%CI: 1.82-7.40, P < 0.001 adjusted for age and sex). With respect to tobacco, none of the smoking categories showed association with oncohematological diseases. Regarding dietary habits, consumption of grilled/barbecued meat 3 or more times per month showed significant association with an increased risk of disease(OR 1.72, 95%CI: 1.08-2.75, P = 0.02). Daily consumption of coffee also was associated with an increased risk(OR 1.77, 95%CI: 1.03-3.03, P = 0.03). Results for GSTT1, GSTM1 and CYP1A1 polymorphisms showed no significant association with oncohematological diseases. When analyzing the interaction between polymorphisms and tobacco smoking or dietary habits, no statistically significant associations that modify disease risk were found. CONCLUSION We reported an increased risk of oncohematological diseases associated with meat and coffee intake. We did not find significant associations between genetic polymorphisms and blood cancer.
文摘Objective: Since the ban of antibiotics as growth promoting feed additives in the EU in 2006 research in alternatives has gained importance. Phytogenic feed additives represent a heterogenous class of different plant derived substances that are discussed to improve the health of farm animals by direct and indirect antioxidant effects and by influencing microbial eubiosis in the gastrointestinal tract. Consequently our study aimed to investigate the influence of broccoli extract and the essential oils of tur- meric, oregano, thyme and rosemary, as selected individual additives, on intestinal and faecal microflora, on xenobiotic enzymes, and on the antioxidant system of piglets. Methods: 48 four weeks old male weaned piglets were assigned to 6 groups of 8. The piglets were housed individually in stainless steel pens with slatted floor. The control group (Con) was fed a diet without an additive for 4 weeks. The diet of group BE contained 0.15 g/kg sulforaphane in form of a broccoli extract. 535, 282, 373 and 476 mg/kg of the essential oils of turmeric (Cuo), oregano (Oo), thyme (To) and rosemary (Ro) were added to the diets of the remaining 4 groups to stan-dardise supplementation to 150 mg/kg of the oils’ key terpene compounds ar-turmerone, carvacrol, thymol and 1,8-cineole. The composition of bacterial microflora was examined by cultivating samples of jejeunal and colonic mucosa and of faeces under specific conditions. The mRNA expression of xenobiotic and antioxidant enzymes was determined by reversing transcrip- tase real time detection PCR (RT-PCR). Total antioxidant status was assayed using the Trolox Equivalent Antioxidant Capacity (TEAC), and lipid peroxidation was determined by measuring thiobarbioturic acid reactive substances (TBA- RS). Results: Compared to Con piglets all additives positively influenced weight gain and feed conversion in week 1. Over the whole trial period no significant differences in performance parameters existed between the experimental groups. Compared to group Con performance of Ro piglets was, however, slightly impaired. Com- pared to Con piglets Cuo, Oo and To increased the ratio of Lactobacilli:E. coli attached to the jejunal mucosa, whereas BE and Ro impaired this ratio slightly. In contrast in colonic mucosa Ro improved Lactobacilli:E. coli ratio. In faecal samples an improvement of Lactobacilli:E. coli ratio could be analysed for To and Ro. Ro was the only additive that reduced the incidence rate of piglets tested positive for enterotoxic E. coli (ETEC). All additives significantly increased jejunal TEAC and reduced TBA-RS. In the liver BE, Cuo, Oo and To increased TEAC in tendency and Ro significantly. Liver TBA-RS were slightly reduced by all additives compared to Con piglets. Whereas the influence of BE, To and Ro on jejunal TEAC mainly was derived from the induction of xenobiotic and antioxidant enzymes (indirect antioxidant effects), Cuo and Oo influenced TEAC by direct antioxidant effects. Discussion and Conclusions: Our results have shown: That within the labiatae oils Oo and To have the potential to improve performance slightly. That phytogenic substances have a small but not sig- nificant influence on intestinal microflora. That phytogenic feed additives up-regulate the anti- oxidant system of piglets either by direct or by indirect antioxidant effects and that they may thereby improve health status. That within the labiatae oils Oo has a high direct antioxidant potential whereas Ro potently induces xenobiotic and antioxidant enzymes. That broccoli extract is an attractive new phytogenic additive, improving antioxidant status by indirect antioxidant effects. That defined combinations of selected phytogenic substances may produce additive effects. That health promoting effects of phytogenic additives in the future should be studied systematically under the challenge with pathogenic microorganisms or food derived to-xins.
基金The authors gratefully acknowledge the Laboratório de Processos Biológicos-LPB/EESC/USP Sao Paulo,Research Foundation(FAPESP)(No 2010/11531-9)the National Council for Scientific and Technological Development for their financial support.
文摘Surfactants are the major active ingredients of laundry detergents. Therefore, special attention should be focused on the treatment and disposal of laundry wastewater. The aim of this study was to characterise the wastewater from a commercial laundry over 30 days. Physicochemical analyses were performed, monitoring the content of nitrogen, phosphate, heavy metals, linear alkylbenzene sulphonate (LAS), volatile organic acids and alcohols. The pH was approximately 5.6 and the COD approximately 4800 mg·L-1. The average concentrations of sulphate, sulphide, N-ammoniacal organic nitrogen compounds and heavy metals were below the maximum limit, in accordance with local and national environmental legislation, and the average total suspended solids was 0.08 g·L-1. Among the metals analysed, iron was observed with the highest concentrations (0.037 mg·L-1 and 0.72 mg·L-1). Phosphate was detected in 93% of samples (94.65 mg·L-1 average). LAS was detected in all samples (12.24 mg·L-1 to 1023.7 mg·L-1). Thirty-three different xenobiotic organic compounds were identified in the laundry wastewater with the qualitative screening. The major groups of the compounds were fragrances, preservatives, solvents and some surfactants. Although the characterisation indicated low values for many parameters, this does not eliminate the need for specific treatment before its disposal at the sewage system.
文摘In this experiment carried out on Caribbean chili pepper plants(Capsicum chinensis),the bio-insecticide azadirachtin in combination with an NPK fertilizer proved to have a greater lethal impact on the larvae of Aedes albopictus than each substance on its own.This synergistic effect is noticeably important when both inputs are sprayed directly on the leaves of the plant(foliar application).While the plants treated with azadirachtin or NPK alone cause a 33.6%and 36.4%mortal-ity respectively of the Ae.albopictus larvae,the combination of the two inputs induces a 74.4%mortality on the mosquito larvae.To account for this synergistic effect phenomenon inside the plant,the azadirachtin+NPK combination most likely interacts with the capsaicinoid compounds naturally produced by the plant.Not only does this study carried out on azadirachtin reveal major results but the methodology itself offers a most interesting approach on how to boost the agricultural inputs within the plants.As a matter of fact,this research axis demands developing since the control of pests harmful to men has been dramatically lacking insecticide molecules acting on new targets over the past three decades.