Ameliorative effects of Lactobacillus against Aflatoxin B1 / Efeitos benéficos do Lactobacillus contra a Aflatoxin B1

Abstract Lactobacilli are probiotics with Aflatoxin (AF) detoxification ability, found in fermented products, GIT of animals and environment. Purpose of this study was to investigate the ability of broiler isolates of Lactobacillus against Aflatoxin B1 (AFB1). For this purpose, 5 isolates of Lactobacillus from broiler gut were incubated with 100 ppb AFB1 in aqueous environment and effect of different parameters (cell fractions, time, temperature, pH) on detoxification was determined by HPLC. The ameliorative effect of Lactobacillus salivarius (LS) against AFB1 was studied in broiler. The results revealed that LS (CR. 4) showed the best results (in vitro) as compared to other isolates (L. salivarius (CR. 3, CR, 4), L. agilis (CE. 2.1, CE. 3.1) and L. crispatus (CE. 28). Cell debris of CR. 4 showed significantly higher detoxification (P<0.05). Maximum amount of AFB1 was detoxified at 30°C (97%), pH 4.0 (99%) and 6 h (99.97%). In vivo study showed that AFB1 decreased weight gain (1,269 ± 0.04 gm/ bird), feed consumed (2,161 ± 0.08 gm/ bird), serum total protein (2.42 ± 0.34 gm/ dl), serum albumin (0.5 ± 0.2 2 gm/dl) and antibody titer (4.2 ± 0.83). Liver function enzymes were found (alanine transaminase (ALT): 32 ± 10.7 U/L) and aspartate transaminase (AST): 314.8 ± 27 U/L) elevated in AFB1 fed broilers. Treatment with 1% LS not only decreased the toxic effects of AFB1 (group D) but also improved the overall health of broilers due to its probiotic effects (p<0.05) as compared to control negative (group A). The detoxification ability of LS was better than commercial binder (CB) (0.2% Protmyc). It was concluded that detoxification of AFB1 by Lactobacillus was strain, temperature, pH and time dependent. LS has detoxification ability against AFB1 in vivo.

Resumo Os lactobacilos são probióticos com capacidade de desintoxicação da Aflatoxina (AF), encontrados em produtos fermentados, TGI de animais e meio ambiente. O objetivo deste estudo foi investigar a capacidade de isolados de frango de corte de Lactobacillus contra a Aflatoxina B1 (AFB1). Para tanto, 5 isolados de Lactobacillus de intestino de frango foram incubados com 100 ppb AFB1 em meio aquoso, e o efeito de diferentes parâmetros (frações celulares, tempo, temperatura, pH) na desintoxicação foi determinado por CLAE. O efeito melhorador de Lactobacillus salivarius (LS) contra AFB1 foi estudado em frangos de corte. Os resultados revelaram que LS (CR. 4) apresentou os melhores resultados (in vitro) em comparação com outros isolados [L. salivarius (CR. 3, CR. 4), L. agilis (CE. 2.1, CE. 3.1) e L. crispatus (CE. 28)]. Detritos celulares de CR. 4 mostraram desintoxicação significativamente maior (P < 0.05). A quantidade máxima de AFB1 foi desintoxicada a 30 °C (97%), pH 4.0 (99%) e 6 h (99,97%). O estudo in vivo mostrou que AFB1 diminuiu o ganho de peso (1,269 ± 0.04 g / ave), alimento consumido (2,161 ± 0.08 g / ave), proteína total sérica (2.42 ± 0.34 g / dl), albumina sérica (0.5 ± 0.22 gm / dl) e título de anticorpo (4.2 ± 0.83). As enzimas da função hepática foram encontradas (alanina transaminase (ALT): 32 ± 10.7 U / L) e aspartato transaminase (AST): 314.8 ± 27 U / L) elevadas em AFB1 alimentados com frangos. O tratamento com 1% LS não só diminuiu os efeitos tóxicos de AFB1 (grupo D), mas também melhorou a saúde geral dos frangos devido aos seus efeitos probióticos (p < 0.05) em comparação com o controle negativo (grupo A). A capacidade de desintoxicação do LS foi melhor do que o aglutinante comercial (CB) (0.2% Protmyc). Concluiu-se que a desintoxicação de AFB1 por Lactobacillus foi dependente da cepa, temperatura, pH e tempo. LS tem capacidade de desintoxicação contra AFB1 in vivo.

Exploring Detoxication Mechanism of Dioscoreae Bulbiferae Rhizoma Processed with Phaseoli Radiati Semen Juice Based on Target Organ Ferroptosis / 中国实验方剂学杂志

ObjectiveTo investigate the attenuating effect of Dioscoreae Bulbiferae Rhizoma（DBR） processed with Phaseoli Radiati Semen（PRS） juice， and explore the attenuating mechanism based on ferroptosis of the main toxic target organ. MethodSixty male ICR mice were randomly divided into blank group， DBR group， water roasted DBR group（hereinafter referred to as water group）， PRS juice-roasted DBR group 1（DBR-PRS 10∶1， stuffy moistening for 40 min， stir-fried at 130 ℃ for 18 min， hereinafter referred to as group 1）， PRS juice-roasted DBR group 2（DBR-PRS 10∶1， stuffy moistening for 80 min， stir-fried at 100 ℃ for 14 min， hereinafter referred to as group 2）， PRS juice-roasted DBR group 3（DBR-PRS=20∶3， stuffy moistening for 40 min， stir-fried at 160 ℃ for 14 min， hereinafter referred to as group 3）. The raw and processed groups of DBR were gavaged with their corresponding 95% ethanol extract at a dose of 3 g·kg-1·d-1， while the blank group was gavaged with an equal volume of 0.5% sodium carboxymethyl cellulose， once a day for 14 consecutive days. Hematoxylin-eosin（HE） staining was used to observe the histopathological changes of mouse liver. Alanine aminotransferase（ALT） and aspartate aminotransferase（AST） levels in serum， as well as malondialdehyde（MDA）， ferrous ions（Fe2+）， reduced glutathione（GSH） and superoxide dismutase（SOD） levels in liver tissue were detected by the biochemical detection. Western blot was used to detect the expression of iron key proteins such as ferritin heavy chain 1（FTH1） and glutathione peroxidase 4（GPX4）. ResultHE staining results showed that the liver tissue structure of the blank group was clear， the morphology of hepatocytes was normal， the cytoplasms of hepatocytes in the DBR group and water group were loose and vacuolar， with obvious pathological damages， and the pathologic damages of mice in the group 1-3 were significantly improved. Compared with the blank group， the levels of ALT， AST， MDA and Fe2+ in mice from the DBR group were significantly increased（P<0.01）， while GSH and SOD levels were significantly reduced（P<0.01）， and the protein expression levels of FTH1 and GPX4 were significantly decreased（P<0.01）. Compared with the DBR group， the ALT， AST，MDA and Fe2+ levels of mice in the group 1-3 were significantly reduced（P<0.05， P<0.01）， the GSH and SOD levels and the protein expression levels of FTH1 and GPX4 were significantly increased（P<0.01）. Compared with the water group， the AST and MDA levels of mice in the group 1-3 were significantly reduced（P<0.05， P<0.01）， the SOD level significantly increased（P<0.05， P<0.01）， the FTH1 protein expression significantly increased（P<0.01）， and the serum ALT level of mice in the group 2-3 significantly reduce（P<0.01）， Fe2+ level significantly reduced（P<0.01）， GSH level significantly increased（P<0.05， P<0.01）， and GPX4 protein expression significantly increased（P<0.05， P<0.01）. Among the group 1-3， the group 3 had the best detoxification effect. ConclutionProcessing with PRS juice can reduce the liver injury induced by DBR， and the mechanism may be related to the inhibition of ferroptosis in the liver.

Study of Triptolide on Liver Injury and Detoxification Strategy / 中国实验方剂学杂志

As a commonly used traditional Chinese medicine in clinical practice， Tripterygium wilfordii has the functions of dispelling wind and removing dampness， detoxicating and destroying parasites， detumescence， pain relief， promoting blood circulation， and dredging collateral. Modern pharmacological studies show that it also has other functions such as anticancer， anti-inflammation， and immunosuppression. It has been widely used to treat autoimmune diseases， renal diseases， and tumors. T. wilfordii contains a variety of chemical components， among which triptolide （TP） can cause varying degrees of damage to human digestive， circulatory， reproductive， and other systems， with liver injury being the most common one， which greatly limits the development of TP in new drug research and industrial application. Therefore， the authors focused on the research hotspot of TP-induced liver injury and summarized relevant Chinese and international literature regarding the clinical manifestations， injury mechanisms， and detoxification strategies of TP-induced liver injury. This helps to provide a scientific basis for the clinical drug safety and scientific drug supervision of TP. The clinical manifestations of TP-induced liver injury are mostly abnormal transaminases， loss of appetite， nausea and vomiting， anorexia， yellow staining of skin and sclera， and yellow urine. The mechanisms of the above clinical manifestations involve apoptosis， oxidative stress， influence on cytochrome P450 superfamily， macrophage polarization， regulation of biological clock gene Clock， etc. Among them， cell apoptosis is related to neurogenic locus notch homolog protein 1 （Notch1）， dynamin-related protein 1 （Drp1）-cytochrome C （Cyt C）， phosphatidylinositide 3-kinases （PI3K）/protein kinase B （Akt）， mitogen-activated protein kinase （MAPK）， tumor suppressor protein 53 （p53）， Fas cell surface death receptor （Fas）/Caspase-8， and other signaling pathways. Oxidative stress is related to inhibition of nuclear factor-erythroid 2-related factor 2 （NRF2） signaling pathway， promotion of cytochrome P450 2E1 （CYP2E1） expression， and excessive accumulation of reactive oxygen （ROS）. The influence of the cytochrome P450 superfamily is manifested as reducing the substrate affinity， activity， and expression of cytochrome P450 3A （CYP3A）， cytochrome P450 2C9 （CYP2C9）， cytochrome P450 2C19 （CYP2C19）， and cytochrome P450 1A2 （CYP1A2）. Promoting the transformation of macrophages into the M1 type is related to the secretion of inflammatory factors and the accumulation of endotoxin， and the internal rhythmic regulation of the biological clock gene Clock， is related to the expression of cytochrome P450 3A11 （CYP3A11） metabolic enzyme. The detoxification strategies in the clinical application include herbs-processing detoxification strategy and drug-pairing detoxification. The traditional Chinese medicines and monomers that are helpful for detoxification include Glycyrrhiza uralensis， Paeonia lactiflora， Lysimachia christinae， Rehmannia glutinosa， saffron， and paeoniflorin. The reviews and discussion about these topics can help to provide more references for related research and clinical application of TP.

Ameliorative effects of Lactobacillus against Aflatoxin B1

Abstract Lactobacilli are probiotics with Aflatoxin (AF) detoxification ability, found in fermented products, GIT of animals and environment. Purpose of this study was to investigate the ability of broiler isolates of Lactobacillus against Aflatoxin B1 (AFB1). For this purpose, 5 isolates of Lactobacillus from broiler gut were incubated with 100 ppb AFB1 in aqueous environment and effect of different parameters (cell fractions, time, temperature, pH) on detoxification was determined by HPLC. The ameliorative effect of Lactobacillus salivarius (LS) against AFB1 was studied in broiler. The results revealed that LS (CR. 4) showed the best results (in vitro) as compared to other isolates (L. salivarius (CR. 3, CR, 4), L. agilis (CE. 2.1, CE. 3.1) and L. crispatus (CE. 28). Cell debris of CR. 4 showed significantly higher detoxification (P 0.05). Maximum amount of AFB1 was detoxified at 30°C (97%), pH 4.0 (99%) and 6 h (99.97%). In vivo study showed that AFB1 decreased weight gain (1,269 ± 0.04 gm/ bird), feed consumed (2,161 ± 0.08 gm/ bird), serum total protein (2.42 ± 0.34 gm/ dl), serum albumin (0.5 ± 0.2 2 gm/dl) and antibody titer (4.2 ± 0.83). Liver function enzymes were found (alanine transaminase (ALT): 32 ± 10.7 U/L) and aspartate transaminase (AST): 314.8 ± 27 U/L) elevated in AFB1 fed broilers. Treatment with 1% LS not only decreased the toxic effects of AFB1 (group D) but also improved the overall health of broilers due to its probiotic effects (p 0.05) as compared to control negative (group A). The detoxification ability of LS was better than commercial binder (CB) (0.2% Protmyc). It was concluded that detoxification of AFB1 by Lactobacillus was strain, temperature, pH and time dependent. LS has detoxification ability against AFB1 in vivo.

Resumo Os lactobacilos são probióticos com capacidade de desintoxicação da Aflatoxina (AF), encontrados em produtos fermentados, TGI de animais e meio ambiente. O objetivo deste estudo foi investigar a capacidade de isolados de frango de corte de Lactobacillus contra a Aflatoxina B1 (AFB1). Para tanto, 5 isolados de Lactobacillus de intestino de frango foram incubados com 100 ppb AFB1 em meio aquoso, e o efeito de diferentes parâmetros (frações celulares, tempo, temperatura, pH) na desintoxicação foi determinado por CLAE. O efeito melhorador de Lactobacillus salivarius (LS) contra AFB1 foi estudado em frangos de corte. Os resultados revelaram que LS (CR. 4) apresentou os melhores resultados (in vitro) em comparação com outros isolados [L. salivarius (CR. 3, CR. 4), L. agilis (CE. 2.1, CE. 3.1) e L. crispatus (CE. 28)]. Detritos celulares de CR. 4 mostraram desintoxicação significativamente maior (P 0.05). A quantidade máxima de AFB1 foi desintoxicada a 30 °C (97%), pH 4.0 (99%) e 6 h (99,97%). O estudo in vivo mostrou que AFB1 diminuiu o ganho de peso (1,269 ± 0.04 g / ave), alimento consumido (2,161 ± 0.08 g / ave), proteína total sérica (2.42 ± 0.34 g / dl), albumina sérica (0.5 ± 0.22 gm / dl) e título de anticorpo (4.2 ± 0.83). As enzimas da função hepática foram encontradas (alanina transaminase (ALT): 32 ± 10.7 U / L) e aspartato transaminase (AST): 314.8 ± 27 U / L) elevadas em AFB1 alimentados com frangos. O tratamento com 1% LS não só diminuiu os efeitos tóxicos de AFB1 (grupo D), mas também melhorou a saúde geral dos frangos devido aos seus efeitos probióticos (p 0.05) em comparação com o controle negativo (grupo A). A capacidade de desintoxicação do LS foi melhor do que o aglutinante comercial (CB) (0.2% Protmyc). Concluiu-se que a desintoxicação de AFB1 por Lactobacillus foi dependente da cepa, temperatura, pH e tempo. LS tem capacidade de desintoxicação contra AFB1 in vivo.

Determination of Knowledge Based on Aflatoxin Poisoning among Broiler Farmers in Nairobi City County, Kenya

Background: There is a scarcity of information concerning knowledge of aflatoxin contamination of feeds among farmers even in aflatoxin-prone regions in Kenya. Thus, knowledge of aflatoxins in feeds among poultry farmers is of paramount importance in designing plans to minimize risks of aflatoxin exposure. Therefore, this study sought to assess the Determinants of Knowledge on Aflatoxin Among Broiler farmers in Nairobi City County, Kenya. Methodology: The study utilized an analytical cross-sectional study design. A total of 240 farmers were sampled from a population of 600 farmers within Nairobi City County. A structured questionnaire was administered to farmers within Nairobi City County. SPSS version 26 was used to analyze the data descriptively. Results were presented in tables and figures. Ethical approval was sought from relevant authorities and parties before the commencement of the study. Results: Results from the study show that the majority of the farmers (58.2%) had knowledge of aflatoxin. There was a significant association (p<0.05) between the socio-demographic characteristics of farmers and knowledge of aflatoxin. Conclusion: The study concludes that the farmers had adequate knowledge of aflatoxin occurrence in feeds and methods to reduce the contamination. There is a need for continuous sensitization of farmers on aflatoxin, particularly on feed management practices by the Ministry of Agriculture and Ministry of Health Division of Public Health in Kenya.

Analysis of Aflatoxin Levels in Broiler Chicken Feed from Selected Farms in Nairobi City County, Kenya

Aflatoxin levels in animal feed should be observed from the farm to the table to ensure the safety of the feed to animals and humans. The contamination of cereals and other agricultural supplies used in animal feed production could happen in the farm in the pre-harvest phase or in the post-harvest phase. The study sought to determine Aflatoxin levels in broiler feed from selected farms in Nairobi City County. A total of 42 feed samples were collected. Samples were analyzed using the LCMS/MS technique. Results from the study show that Aflatoxin levels in broiler starter were; B1(17.26±3.07 ppb), B2 (2.44±0.84 ppb), G1 (8.87±2.41 ppb), G2 (0.9±0.44 ppb) and Total AF (29.47±6.13 ppb). Aflatoxin levels in broiler finisher were B1 (17.17±3.09 ppb), B2 (2.68±1.18 ppb), G1 (9.25±2.7 ppb), G2 (1±0.45 ppb) and Total AF (30.1±6.88 ppb). Results from analysis of feed samples showed that AFB1 levels in both broiler starter and broiler finisher were above the KEBS limit but were below the EAC, EU and WHO/FAO limit. Total Aflatoxin levels were above the KEBS limit but below the EAC limit. There is need to enhance the capacity of feed surveillance and monitoring in the country through various laboratory analysis techniques among various agencies in the feed value chain to ensure feed safety.

Insecticide resistance levels and associated mechanisms in three Aedes aegypti populations from Venezuela

BACKGROUND The massive use of insecticides in public health has exerted selective pressure resulting in the development of resistance in Aedes aegypti to different insecticides in Venezuela. Between 2010 and 2020, the only insecticides available for vector control were the organophosphates (Ops) fenitrothion and temephos which were focally applied. OBJECTIVES To determine the state of insecticide resistance and to identify the possible biochemical and molecular mechanisms involved in three populations of Ae. aegypti from Venezuela. METHODS CDC bottle bioassays were conducted on Ae. aegypti collected between October 2019 and February 2020 in two hyperendemic localities for dengue in Aragua State and in a malaria endemic area in Bolívar State. Insecticide resistance mechanisms were studied using biochemical assays and polymerase chain reaction (PCR) to detect kdr mutations. FINDINGS Bioassays showed contrasting results among populations; Las Brisas was resistant to malathion, permethrin and deltamethrin, Urbanización 19 de Abril was resistant to permethrin and Nacupay to malathion. All populations showed significantly higher activity of mixed function oxidases and glutathione-S-transferases (GSTs) in comparison with the susceptible strain. The kdr mutations V410L, F1534C, and V1016I were detected in all populations, with F1534C at higher frequencies. MAIN CONCLUSION Insecticide resistance persists in three Ae. aegypti populations from Venezuela even in the relative absence of insecticide application.

Optimization of parameters for stir-frying of Kansui Radix with vinegar based on conversion of toxic components / 中国中药杂志

This study aims to optimize the parameters for stir-frying of Kansui Radix with vinegar based on the conversion of representative toxic diterpenes, which is expected to serve as a reference for the standardized production of Kansui Radix stir-fried with vinegar. To be specific, the toxic components [3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol(3-O-EZ), kansuiphorin C(KPC)] in Kansui Radix and the products(ingenol, 20-deoxyingenol) after the stir-frying with vinegar were selected. The toxicity to intestine and water-draining activity were evaluated with NCM460(normal human colon mucosal epithelial cell line) and HT-29(a human colorectal adenocarcinoma cell line). An HPLC method was then developed to assess the conversion of toxic components. On this basis, temperature, time, and amount of vinegar for the processing of Kansui Radix were optimized with the Box-Behnken design and the content of ingenol and 20-deoxyingenol as evaluation index. The results showed that after the stir-frying of Kansui Radix with vinegar, 3-O-EZ and KPC were first converted to monoester 3-O-(2'E,4'Z-decadienoyl)ingenol(3-EZ) and 5-O-benzoyl-20-deoxyingenol(5-O-Ben) and finally to almost non-toxic ingenol and 20-deoxyingenol, respectively. Meanwhile, the water-draining activity was retained. Six compounds had a good linear relationship with the peak area in the corresponding concentration ranges(R~2≥0.999 8), and the average recovery fell in the range of 98.20%-102.3%(RSD≤2.4%). The content of representative diterpenes and intermediate products was 14.78%-24.67% lower in the Kansui Radix stir-fried with vinegar than in the Kansui Radix, while the content of the conversed products was 14.37%-71.37% higher. Among the process parameters, temperature had significant influence on the total content of products, followed by time. The optimal parameters were 210 ℃, 15 min, and 30% vinegar. The relative error between the experimental results and the predicted values was 1.68%, indicating that the process was stable and reproducible. The strategy of screening optimal parameters for stir-frying of Kansui Radix with vinegar based on the transformation of toxic components can help improve the production stability, reduce the toxicity, and ensure the efficacy of Kansui Radix stir-fried with vinegar, which can serve as a reference for the process optimization of similar toxic Chinese medicinals.

Thoughts and Analysis on Regulating Tumor Pre-Metastatic Niche by Regulating Qi and Detoxifying / 中医杂志

Based on the concept of “imbalance of qi movement with the latent cancer toxin”， it is believed that the development process of tumor pre-metastatic niche （PMN） could be summarized as tumor derived secretory factors， exosomes and other “cancer toxin”， which latent in the body， were diffusion-prone by means of meridians and membrane-sources. Besides， the latent toxin induced the imbalance of qi movement， especially the distant weakest qi， and the local sweat pore and collateral vessels were blocked， which resulted in phlegm and blood stasis， and the cross-aggregation of poison. We also proposed therapeutic principles of PMN as first regulating qi and then clearing and expelling toxin， and tried to discuss the theoretical model of traditional Chinese medicine for PMN based on the theory of qi regulation and detoxification， aimed at providing ideas for the future theory construction of traditional Chinese medicine prevention and treatment for malignant tumor metastasis.

Effect of lime water processing of Pinelliae Rhizoma Praeparatum on toxic component lectin protein / 中国中药杂志

The present study investigated the effect of immersion in the excipient lime water on the toxic component lectin protein and explained the scientific connotation of lime water detoxication during the processing of Pinelliae Rhizoma Praeparatum. Western blot was used to investigate the effects of immersion in lime water with different pH(pH 10, 11, and 12.4), saturated sodium hydroxide, and sodium bicarbonate solution on the content of lectin protein. The protein compositions of the supernatant and the precipitate after immersing lectin protein in lime water of different pH were determined by the SDS-PAGE method combined with the silver staining technique. The MALDI-TOF-MS/MS technique was used to detect the molecular weight distribution of peptide fragments in the supernatant and precipitate after immersing lectin protein in lime water of different pH, and circular dichroism spectroscopy was used to detect the ratio changes in the secondary structure of lectin protein during the immersion. The results showed that immersion in lime water at pH>12 and saturated sodium hydroxide solution could significantly reduce the content of lectin protein, while immersion in lime water at pH<12 and sodium bicarbonate solution had no significant effect on lectin protein content. The corresponding lectin protein bands and molecular ion peaks were not detected at the 12 kDa position in the supernatant and precipitate after immersing the lectin protein in lime water at pH>12, which was attributed to the fact that lime water immersion at pH>12 could significantly change the ratio of the secondary structure of lectin protein, resulting in irreversible denaturation, while lime water immersion at pH<12 did not change the ratio of the secondary structure of lectin protein. Therefore, pH>12 was the key condition for the detoxication of lime water during the processing of Pinelliae Rhizoma Praeparatum. Lime water immersion at pH>12 could cause irreversible denaturation of lectin protein, resulting in a significant decrease in the inflammatory toxicity of Pinelliae Rhizoma Praeparatum, which played a key role in detoxification.

Main ways and target prediction of detoxification mechanism of Euphorbia kansui after stir-frying with vinegar / 中国药房

OBJECTIVE To study main way and target of Euphorbia kansui after stir-frying with vinegar. METHODS Twenty-four SPF grade SD rats were randomly divided into blank group， E. kansui group （850 mg/kg） and vinegar stir-fried E. kansui group （850 mg/kg）， with 8 rats in each group. Blank group was given 0.5% sodium carboxymethyl cellulose solution intragastrically， and E. kansui group and vinegar stir-fried E. kansui group were given relevant test sample for consecutive 20 d. The rats’ urine of 12 hours was collected on the 20th day. The urine samples of rats in each group were determined by UPLC-Q- Exactive-MS. The data was pre-processed by Compound Discoverer 3.0 software， and the metabolite structure was identified by BioCyc， HMDB and other databases. Whether different groups presented their own clustering phenomenon was observed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）， etc. Based on the pathway analysis of MetaboAnalyst， the potential targets of detoxification mechanism of E. kansui after stir-frying with vinegar were predicted. RESULTS Twenty significantly differential endogenous metabolites were identified， of which 10 target metabolites， such as N-acetyl-L-aspartate and 3-phosphonooxypyruvic acid， were targets of detoxification mechanism of E. kansui after stir- frying with vinegar. The main metabolic pathways included arginine biosynthesis， alanine， aspartic acid and glutamic acid metabolism， cysteine and methionine metabolism， and arginine and D-ornithine metabolism. The biological significance of all related metabolites in the pathways was analyzed and speculated； after stir-frying with vinegar， E. kansui may alleviate neurotoxicity by reducing the level of N-acetyl-L-aspartic acid； E. kansui had a protective effect on cardio-cerebrovascular system by increasing the level of L-high arginine. CONCLUSIONS After stir-frying with vinegar， E. kansui can significantly improve the adverse factors in terms of nervous system， cardio-cerebrovascular system， immune system and energy metabolism. The most concentrated metabolic pathway related to its detoxification mechanism is arginine biosynthesis.

Discussion on the Treatment of Malignant Tumors by the Method of Counteracting Toxin with Toxin / 中医杂志

Cancer toxin is the key pathogenesis of malignant tumors. The basic principle of cancer treatment is “dispelling pathogen and resolving toxins， reinforcing healthy qi and reinforcing the foundation”. As one of the “eight methods of anticancer and detoxification”， the counteracting toxin with toxin therapy is a commonly used clinical treatment of malignant tumors. This paper discussed the method of counteracting toxin with toxin and its application in the prevention and treatment of malignant tumors from the aspects of history tracing， academic connotation， application principles and clinical application. Toxic Chinese medicinals with anticancer function are required to eliminate cancer toxins based on the principles of excessive cancer toxicity and plentiful healthy qi， as well as in accordance with the various stages and classifications of tumors， thereby improving the theoretical connotation of the method of counteracting toxin with toxin， and promoting the popularization and application of the pathogenesis theory of cancer toxin in the prevention and treatment of malignant tumors.

Decolourization and Detoxification of Azo Dye, Malachite Green by Pseudomonas monteilii Strain RZT1, a Bacterium Isolated from Textile Wastewater

Discharge of textile industrial effluent without proper treatment has become a severe hazard for the animal health and environment worldwide. Therefore, this study was designed to isolate azo dye-degrading bacteria from textile wastewater and evaluate their ability to biodegrade reactive dyes into non-toxic products. The potent bacterial strain which was isolated from textile wastewater was identified as Pseudomonas monteilii strain RZT1 on the basis of 16S rDNA sequence. The isolated bacterial strain exhibited good decolorization ability with yeast extract supplementation as cosubstrate in static conditions for Malachite Green dye. The optimal condition for the decolorization of Malachite Green dye by P. monteilii strain RZT1 were at pH 7.0 and 28癈. Decolorization rates of Malachite Green dye by P. monteilii strain RZT1 were varied with initial dye concentration as follow: 84.8%, 75.4%, 63.4% and 45.5% decolorization for 100ppm, 200ppm, 300ppm and 400ppm initial dye concentration respectively. We investigated the effects of dyes used in the textile industry on the seed germination of Five crops - Rice (Oryza sativa), Wheat (Triticum aestivum L.), Khesari (Lathyrus sativus), Mustard (Brassica nigra) and Bitter Melon (Momordica charantia). It was found that textile dye Malachite Green had negative effect on seed germination and seedling growth in test cultures. The harmful effects of dye on seed germination and early seedling growth parameters were augmented with increase of dye concentration. Interestingly, treatment of the Malachite Green dye with isolated bacteria reduced the adverse effects of that dye on seed germination and seedling growth. Thus, it indicated the potentiality of P. monteilii strain RZT1 for bioremediation of textile effluents into a non-toxic form for plants.

Fibrina rica en plaquetas aplicada en conjunto con biomodificación alveolar en la regeneración ósea guiada. Reporte de caso / Platelet rich fibrin applied in conjunction with alveolar biomodification in guided bone regeneration. Case report

Resumen Debido a los diferentes problemas existentes a la hora de realizar procedimientos implantológicos por la calidad del remanente óseo y el estado de los tejidos periodontales en la zona a rehabilitar, existen opciones de regeneración ósea inducida que muestran tasas de éxito considerablemente favorables al ser empleadas en casos donde es necesario una regeneración ósea extensa capaz de soportar un implante dental. El objetivo del presente estudio es describir el éxito en la regeneración ósea por medio de alternativas combinadas de fibrina rica en plaquetas y modificación biológica con tetraciclina. Reporte del caso clínico: paciente femenina de 67 años que consulta por inflamación, supuración y dolor en la zona antero-superior. Es diagnosticada como absceso periapical crónico, se hace cirugía de extracción de órganos dentales, posterior a eso se hace descontaminación y adaptación de los alveolos con tetraciclina para realizar la regeneración ósea guiada con fibrina rica en plaquetas, hueso tipo Lumina Bone Porous y Lumina Coat, luego se espera el proceso de evolución para colocación de implantes dentales. El éxito obtenido con el uso de fibrina rica en plaquetas y la biomodificacion ósea como coadyuvante en la desinfección de la zona a tratar, logró mostrar resultados altamente favorables en el proceso de regeneración ósea guiada.

Abstract As the different problems that exist when carrying out implant procedures due to the quality of the bone remnant and the state of the existing periodontal tissues in the area to be rehabilitated, there are induced bone regeneration options that show considerably favorable success rates as they are used in cases where extensive bone regeneration is necessary to support a dental implant. The objective of the present study is to describe the success in bone regeneration using combined alternatives of platelet-rich fibrin and biological modification with tetracycline. Report of the clinical case: 67-year-old female patient consulted for inflammation and suppuration and pain in the upper antero-superior area, she was diagnosed as chronic periapical abscess, dental organ extraction surgery was performed, after that decontamination and adaptation of the alveoli was performed with tetracycline to perform guided bone regeneration with platelet-rich fibrin, Coat membrane and Lumina bone criteria, then wait for the evolution process to place dental implants. The success obtained with the use of FRP and bone biomodification as an adjuvant in the disinfection of the area to be treated achieved to show highly favorable results in the guided bone regeneration process.

Managing acute opioid withdrawal with tramadol during COVID-19 lockdown in a peri-urban setting

Background: The coronavirus disease 2019 (COVID-19) has highlighted the scope of heroin dependence and need for evidence-based treatment amongst marginalised people in South Africa. Acute opioid withdrawal management without maintenance therapy carries risks of increased morbidity and mortality. Due to the high costs of methadone, Tshwane's Community Oriented Substance Use Programme (COSUP) used tramadol for opioid withdrawal management during the initial COVID-19 response. Aim: To describe demographics, route of heroin administration and medication-related experiences amongst people accessing tramadol for treatment of opioid withdrawal.Setting: Three community-based COSUP sites in Mamelodi (Tshwane, South Africa). Methods: A retrospective cross-sectional study was conducted. Data were collected using an interviewer-administered paper-based tool between April and August 2020. Descriptive statistics were used to analyse data. Results: Of the 220 service users initiated onto tramadol, almost half (n = 104, 47%) were not contactable. Fifty-eight (26%) people participated, amongst whom most were male (n = 55, 95%). Participants' median age was 32 years. Most participants injected heroin (n = 36, 62.1%). Most participants experienced at least one side effect (n = 47, 81%) with 37 (64%) experiencing two or more side effects from tramadol. Insomnia occurred most frequently (n = 26, 45%). One person without a history of seizures experienced a seizure. Opioid withdrawal symptoms were experienced by 54 participants (93%) whilst taking tramadol. Over half (n = 38, 66%) reported using less heroin whilst on tramadol. Conclusion: Tramadol reduced heroin use but was associated with withdrawal symptoms and unfavourable side effects. Findings point to the limitations of tramadol as opioid withdrawal management to retain people in care and the importance of access to first-line opioid agonists.

Research advances in toxicity of uranium in vivo and its new chelators / 中国辐射卫生

Uranium is an important radioactive actinide in nature and an important nuclear material in nuclear industry. After uranium is accidentally released into the environment, it enters the body through the respiratory tract, the digestive tract, and other ways, then enters the circulation system through blood, and is finally mainly deposited in the kidney and bone, causing a certain degree of toxicity. Therefore, efficient low-toxicity chelators are an important way to reduce radionuclide pollution, radiation damage, and chemical toxicity. This article reviews uranium deposition and harm, the detoxification mechanism of uranium chelators, and the research advances in uranium chelators and points out the development trend of uranium chelators.

Progress in lipid emulsions as antidotes to reverse drug poisoning / 中国药科大学学报

@#Due to their good safety, wide application scope and quick onset time, lipid emulsions are full of promise to reverse drug poisoning. In this review, a number of clinical case reports were summarized to analyze the detoxification effect of lipid emulsions on local anesthetic, antiarrhythmic, psychotropic and organophosphate poisoning, as well as the possible adverse reactions of lipid emulsions therapy.Meanwhile, the mechanisms underlying lipid emulsions therapy, such as lipid sink theory, enhanced body basal metabolism and positively affected cardiovascular function, were fully interpreted.Besides, a few potential solutions to the problems still existing in lipid emulsions therapy were proposed, in order to consolidate the understanding of lipid emulsions therapy and promote its rational application in reversing drug poisoning.

Metabolomic study on clinical staging of methamphetamine detoxification by LC-QTOF-MS / 中国药科大学学报

@#At present , methamphetamine has become a major hidden danger in global public health safety. In order to judge methamphetamine addicts and methamphetamine abstainers more scientifically and reliably, this study analyzed the endogenous metabolites in plasma, serum and urine of methamphetamine addicts, methamphetamine abstainers and healthy volunteers by highly sensitive high-throughput liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) analytical instrument. The obtained metabolomic data were processed by univariate analysis (t-test) and multivariate analysis (PLS-DA and OPLS-DA) and eligible potential biomarkers were then screened.The identified biomarkers set enrichment analysis to find the connection between metabolites and metabolic pathways.Multivariate statistical results showed that methamphetamine acute group, recovery group and healthy group were clearly separated.3, 18 and 6 regulated metabolites were identified in serum, plasma and urine, respectively, suggesting that lipid metabolism was abnormal in methamphetamine acute group, and that fatty acid metabolism, sulfate/sulfite metabolism and sex hormone metabolism were abnormal in methamphetamine recovery group.The selected potential biomarkers in this study provide the possibility for scientific judgment of the clinical stage of methamphetamine detoxification.

Mechanism of Aconiti Kusnezoffii Radix Processed with Chebulae Fructus Against H9c2 Cardiomyocyte Toxicity Based on TRPV1 Channel / 中国实验方剂学杂志

ObjectiveTo explore the role of transient receptor potential vanilloid 1 （TRPV1） channel in reducing cardiomyocyte toxicity of Aconiti Kusnezoffii Radix processed with Chebulae Fructus. MethodH9c2 cardiomyocytes cultured in vitro were used as a model to assess cell viability by methyl thiazolyl tetrazolium （MTT） assay， the expression of TRPV1 mRNA was detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the leakage rate of lactate dehydrogenase （LDH）， the changes of nucleus， reactive oxygen species （ROS）， mitochondrial membrane potential and Ca2+ contents were detected by enzyme linked immunosorbent assay （ELISA）. ResultCompared with the blank group， when the concentration was ≥0.5 g·L-1， the cell viability was significantly decreased （P<0.01）， the leakage rate of LDH， the release of ROS and Ca2+ were increased， the mitochondrial membrane potential was decreased， and the nucleus was pyknosis or even broken in raw Aconiti Kusnezoffii Radix and Aconiti Kusnezoffii Radix processed with Chebulae Fructus groups. When the concentration was ≥0.5 g·L-1， compared with the same mass concentration of raw Aconiti Kusnezoffii Radix group， the cell viability increased significantly （P<0.01）， the leakage rate of LDH， the release of ROS and Ca2+ decreased， the mitochondrial membrane potential increased， and the nuclear morphology improved in Aconiti Kusnezoffii Radix processed with Chebulae Fructus group. Application of the same mass concentration of raw Aconiti Kusnezoffii Radix to H9c2 cardiomyocytes pretreated with the TRPV1 inhibitor BCTC significantly increased cell viability， decreased leakage rate of LDH， ROS and Ca2+ release， increased mitochondrial membrane potential and improved nuclear pyknosis compared with untreated H9c2 cardiomyocytes. Application of the same mass concentration of Aconiti Kusnezoffii Radix processed with Chebulae Fructus to H9c2 cardiomyocytes pretreated with BCTC decreased cell viability， increased LDH leakage rate， ROS and Ca2+ release， reduced mitochondrial membrane potential compared with untreated H9c2 cardiomyocytes. Real-time PCR results showed that both raw Aconiti Kusnezoffii Radix and Chebulae Fructus decoction could increase the expression of TRPV1 mRNA in cardiomyocytes in a concentration dependent manner. ConclusionRaw Aconiti Kusnezoffii Radix can induce cardiomyocyte apoptosis and cardiotoxicity by activating TRPV1 channel， while Aconiti Kusnezoffii Radix processed with Chebulae Fructus can attenuate the toxicity through TRPV1 channel， which may be related to the synergistic effect of acid components in Chebulae Fructus and alkaloids in Aconiti Kusnezoffii Radix on TRPV1 channel.

Preliminary exploration of detoxification mechanism of processing methods on cardiotoxicity induced by radix Tripterygium wilfordii in mice via Nrf2/HO-1 pathway / 中国中药杂志

This study aims to investigate the detoxification effects of different processing methods on the cardiotoxicity induced by radix Tripterygium wilfordii, and preliminarily explore the detoxification mechanism via the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1) pathway. The raw and processed products [stir-fried product, product stir-fried with Lysimachiae Herba(JQC), product stir-fried with Phaseoli Radiati Semen(LD), product stir-fried with Paeoniae Radix Alba(BS), product stir-fried with Glycyrrhizae Radix et Rhizoma(GC), and product stir-fried with vinegar(CZ)] of radix T. wilfordii were administrated to mice by gavage at a dose of 2 g·kg~(-1)(based on crude drugs) for 28 days. Twenty-four hours after the last administration, we measured the serum biochemical indexes of mice to evaluate the detoxification effect. Furthermore, we determined the expression of key proteins of Nrf2/HO-1 pathway in mouse heart tissue by Western blot and some oxidation/antioxidation-related indexes by corresponding kits to explore the detoxification mechanism. The administration of the raw product elevated the levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde, a product of cardiac lipid peroxidation(P<0.01), down-regulated the protein levels of Nrf2 and HO-1(P<0.01), and reduced the levels of total superoxide dismutase, glutathione, glutathione peroxidase, and glutathione S-transferase(P<0.01). However, after the administration of the products stir-fried with JQC, LD, BS, GC, and CZ, the abnormalities of the above indexes induced by the raw product were recovered(P<0.05 or P<0.01). In particular, the product stir-fried with JQC showed the best performance. Taken all together, the cardiotoxicity induced by radix T. wilfordii could be attenuated by stir-frying with JQC, LD, BS, GC, and CZ, and the stir-frying with JQC showed the best detoxification effect. The mechanism might be associated with the cardiac antioxidant defense and oxidative damage mitigation mediated by the up-regulated Nrf2.