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RESUMEN Perú generó 8.215.355 t de residuos sólidos municipales en el 2021; de este, 57,64 % corresponde a residuos orgánicos (RO) y 61,28 % son dispuestos en rellenos sanitarios con múltiples deficiencias de gestión, lo que exige buscar alternativas para tratar de manera segura los RO. Frente a esta situación, el compostaje permite la biotransformación, la reducción y la obtención de biofertilizantes, que se pueden aplicar como sustrato o enmienda. El objetivo de la investigación fue evaluar indicadores de procesamiento y calidad de compost derivado de residuos sólidos orgánicos urbanos, en Leoncio Prado, región Huánuco, Perú. Se evaluaron los tipos de residuos, basados en la normativa peruana para caracterización de residuos, los indicadores del proceso (temperatura y pH), la caracterización fisicoquímica y calidad en base a las normas internacionales. Los resultados muestran diferencia significativa para pH, nitrógeno, calcio, potasio, cobre y zinc; contrariamente, la materia orgánica, el % de cenizas, la conductividad eléctrica, el sodio y el fósforo no mostraron diferencias, siendo lo más destacado los altos niveles de pH, además, la calidad del compost es de "Clase B", según la norma chilena 2880. Los compost producidos son de calidad media y se recomienda su uso como sustrato o enmienda en la agricultura, previo tratamiento para corregir los altos niveles de pH.
ABSTRACT Peru generated 8,215,355 t of municipal solid waste in 2021, of which 57.64% corresponds to organic waste (OW) and 61.28% is disposed of in landfills with multiple management deficiencies, which makes it necessary to seek alternatives to safely treat OW. In view of this situation, composting allows biotransformation, reduction and obtaining biofertilizers that can be applied as a substrate or amendment. The objective of the research was to evaluate the processing indicators and quality of compost derived from urban organic solid waste in Leoncio Prado, Huánuco-Peru. Waste types were evaluated based on Peruvian regulations for waste characterization, process indicators (temperature and pH), physicochemical characterization and quality based on international standards. The results show significant differences for pH, nitrogen, calcium, potassium, copper and zinc; on the contrary, organic matter, % ash, electrical conductivity, sodium and phosphorus showed no differences, the most outstanding being the high pH levels, and the quality of the compost is "Class B" according to Chilean standard 2880. The compost produced is of medium quality and is recommended for use as a substrate or amendment in agriculture after treatment to correct the high pH levels.
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Objective To investigate the mechanism of Gentianopsis paludosa xanthone(GPX)combined with probiotics in the intervention of colon inflammation-tumor transformation in rats by regulating TGF-β1/Smads pathway and inflammatory factors.Methods Ninety rats were divided into the normal group,the model group[drinking sodium dextran sulfate(DSS)for 3 days]and the intervention group by random number table method.The model group was subdivided into the inflammatory stage group,the pre-inflammatory cancer group(DMH injection for 4 weeks),the intermediate inflammatory cancer group(DMH injection for 13 weeks)and the advanced inflammatory cancer group(DMH injection for 21 weeks).The administration group was subdivided into the groups(after the first day of drinking DSS,drugs for each group were given by gavage once a day for 8 weeks)on the basis of the advanced inflammatory cancer group,including the GPX group(GPX 69.3 mg/kg),the probiotic group,the combined group(GPX+probiotics 400 mg/kg)and the thalidomide group(thalidomide 13.5 mg/kg).The disease activity index(DAI),colon length and wet mass index were compared between all groups.Characteristics of colon tumors were observed,and pathological changes of colon were observed by HE staining.The expression levels of transforming growth factor(TGF)-β1,Smad4,Smad7,interleukin(IL)-6 and tumor necrosis factor(TNF)-α were detected by Western blot assay and enzyme-linked immunosorbent assay,respectively.Results Compared with the advanced inflammatory cancer group,the administration groups showed an increase in colon length,the expression levels of TGF-β1 and Smad4 protein,a decrease in colon wall thickness,wet mass index,maximum tumor diameter,the levels of Smad7,IL-6,TNF-α,and DAI score decreased in the GPX group and the combined group(P<0.05).The structure and morphology of intestinal mucosa were improved in the GPX group,the probiotic group and the combination group,and the structure of colonic crypt and goblet cell number were increased.Compared with the probiotic group and the GPX group,the colon wall thickness,colon wet mass index and tumor number were decreased,the protein expression levels of TGF-β1 and Smad4 were increased,and levels of IL-6 and TNF-α were decreased in the combination group(P<0.05).Conclusion GPX combined with probiotics could inhibit the transformation of colon inflammation-tumor,and the mechanism may be related to the regulation of TGF-β1/Smads pathway and the inhibition of pro-inflammatory factors of IL-6 and TNF-α.
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Tralokinumab is a selective interleukin-13 inhibitor developed by LEO Pharma in Denmark. It was granted approval by the US Food and Drug Administration on December 27, 2021, for the treatment of patients aged 18 years or older with moderate to severe atopic dermatitis whose disease is refractory to or cannot be fully controlled by local prescription therapy. This article presents a comprehensive review of the recent research progress in the treatment of moderate to severe atopic dermatitis with tralokinumab.
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Agricultural production is largely based on the use of agrochemicals in order to minimize pests, pathogens, and undesirable weeds toward increase production. In the current situation, however, several threats are emerging that threaten food security, human and environmental health, ecological balance, and soil biodiversity. Agrochemicals may shift beneficial microorganisms in the community over time, with potentially dangerous consequences, such as the development of antibiotic resistance. Farming systems utilizing agrochemicals might adversely affect soil microorganisms responsible for nutrient cycling processes, such as: nitrogen fixation, phosphorus solubilizing, and others. Some agrochemicals reduce soil enzyme activity and biochemical reactions, which are key indicators of soil microbiology. In this review, we explore how applied agrochemicals affect soil microbes and biochemical health attributes under different cropping systems, as well as ways to overcome the negative impacts of agrochemicals.
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Synthetic plastics have been widely used in various fields of the national economy and are the pillar industry. However, irregular production, plastic product use, and plastic waste piling have caused long-term accumulation in the environment, contributing considerably to the global solid waste stream and environmental plastic pollution, which has become a global problem to be solved. Biodegradation has recently emerged as a viable disposal method for a circular plastic economy and has become a thriving research area. In recent years, important breakthroughs have been made in the screening, isolation, and identification of plastic-degrading microorganisms/enzyme resources and their further engineering, which provide new ideas and solutions for treating microplastics in the environment and the closed-loop bio-recycling of waste plastics. On the other hand, the use of microorganisms (pure cultures or consortia) to further transform different plastic degradants into biodegradable plastics and other compounds with high added value is of great significance, promoting the development of a plastic recycling economy and reducing the carbon emission of plastics in their life cycle. We edited a Special Issue on the topic of "Biotechnology of Plastic Waste Degradation and Valorization", focusing on the researches progress in three aspects: Mining microbial and enzyme resources for plastic biodegradation, Design and engineering of plastic depolymerase, and biological high-value transformation of plastic degradants. In total, 16 papers have been collected in this issue including reviews, comments, and research articles, which provide reference and guidance for further development of plastic waste degradation and valorization biotechnology.
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Plásticos Biodegradáveis , Biodegradação Ambiental , BiotecnologiaRESUMO
Ginsenoside Compound K(CK)is a kind of protopanaxadiol ginsenosides,which exerts antitumor effects on various cancers,such as lung cancer,liver cancer and breast cancer.Pharmacological studies have proved that CK induces tumor cell cycle arrest and apoptosis,as well as regulates tumor cell autophagy and inhibits tumor metastasis by regulating multiple signaling pathways(AMPK/mTOR and PI3K/Akt et cetera).However,as an intestinal metabolite of natural protopanaxadiol ginsenosides,CK cannot be directly extracted from the ginseng plant.Therefore,biotransformation from natural ginsenosides such as ginsenoside Rb1 or biosynthesis are utilized to obtain CK.Biotransformation of CK uses enzymes or microorganisms to transform different ginsenosides or their structural analogs into CK;biosynthesis of CK cultures cell factories and biosynthetic enzymes to synthesize glucose and other simple compounds into CK.In this review,we systematically summarized the research progress in biopreparation and antitumor mechanism of CK in recent years,with the aim of providing evidence for the future development of CK as a clinical anti-tumor candidate drug or an adjunctive drug.
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Many natural products can be bio-converted by the gut microbiota to influence pertinent efficiency. Ginsenoside compound K (GCK) is a potential anti-type 2 diabetes (T2D) saponin, which is mainly bio-transformed into protopanaxadiol (PPD) by the gut microbiota. Studies have shown that the gut microbiota between diabetic patients and healthy subjects are significantly different. Herein, we aimed to characterize the biotransformation of GCK mediated by the gut microbiota from diabetic patients and healthy subjects. Based on 16S rRNA gene sequencing, the results indicated the bacterial profiles were considerably different between the two groups, especially Alistipes and Parabacteroides that increased in healthy subjects. The quantitative analysis of GCK and PPD showed that gut microbiota from the diabetic patients metabolized GCK slower than healthy subjects through liquid chromatography tandem mass spectrometry (LC-MS/MS). The selected strain A. finegoldii and P. merdae exhibited a different metabolic capability of GCK. In conclusion, the different biotransformation capacity for GCK may impact its anti-diabetic potency.
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Humanos , Microbioma Gastrointestinal/genética , Cromatografia Líquida/métodos , Voluntários Saudáveis , RNA Ribossômico 16S , Fezes/microbiologia , Espectrometria de Massas em Tandem , Biotransformação , Diabetes Mellitus Tipo 2/tratamento farmacológicoRESUMO
The solid-phase microextraction technique quantifies analytes without considerably affecting the sample composition.Herein,a proof-of-concept study was conducted to demonstrate the use of coated probe electrospray ionization(coated-PESI)and coated blade spray(CBS)as ambient mass spectrometry ap-proaches for monitoring drug biotransformation.The ability of these methods was investigated for monitoring the dephosphorylation of a prodrug,combretastatin A4 phosphate(CA4P),into its active form,combretastatin A4(CA4),in a cell culture medium supplemented with fetal bovine serum.The CBS spot analysis was modified to achieve the same extraction efficiency as protein precipitation and ob-tained results in 7 min.Because coated-PESI performs extraction without consuming any samples,it is the preferred technique in the case of a limited sample volume.Although coated-PESI only extracts small quantities of analytes,it uses the desorption solvent volume of 5-10 pL,resulting in high sensitivity,thus allowing the detection of compounds after only 1 min of extraction.The biotransformation of CA4P into CA4 via phosphatases occurs within the simple matrix,and the proposed sample preparation techniques are suitable for monitoring the biotransformation.
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Flavonoid glycosides are the main active constituents of Epimedii Folium and its related plants. They can be divided into polyglycosides and low glycosides according to the number of glycosyl group. The polyglycosides of Epimedii Folium can be transformed into low glycosides after biotransformation ;pharmacological activities of low glycosides in anti-tumor ,tonifying kidney yang and anti-osteoporosis are stronger than those of polyglycosides. In this paper , the research progress about biotransformation technology of flavonoid glycosides of Epimedii Folium was reviewed. It was found that the main biotransformation pathway of flavonoid glycosides of Epimedii Folium was to obtain low glycosides by removing glycosyl group ; related methods were mainly enzymatic hydrolysis and microbial transformation ,and also included plant cell transformation ,acid hydrolysis method and synthesis method.
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Berberine(BBR)is an isoquinoline alkaloid extracted from Coptis chinensis that improves diabetes,hyperlipidemia and inflammation.Due to the low oral bioavailability of BBR,its mechanism of action is closely related to the gut microbiota.This study focused on the CYP51 enzyme of intestinal bacteria to elucidate a new mechanism of BBR transformation by demethylation in the gut microbiota through multiple analytical techniques.First,the docking of BBR and CYP51 was performed;then,the pharma-cokinetics of BBR was determined in ICR mice in vivo,and the metabolism of BBR in the liver,kidney,gut microbiota and single bacterial strains was examined in vitro.Moreover,16S rRNA analysis of ICR mouse feces indicated the relationship between BBR and the gut microbiota.Finally,recombinant E.coli con-taining cyp51 gene was constructed and the CYP51 enzyme lysate was induced to express.The metabolic characteristics of BBR were analyzed in the CYP51 enzyme lysate system.The results showed that CYP51 in the gut microbiota could bind stably with BBR,and the addition of voriconazole(a specific inhibitor of CYP51)slowed down the metabolism of BBR,which prevented the production of the demethylated metabolites thalifendine and berberrubine.This study demonstrated that CYP51 promoted the deme-thylation of BBR and enhanced its intestinal absorption,providing a new method for studying the metabolic transformation mechanism of isoquinoline alkaloids in vivo.
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OBJECTIVE Epimedium is rich in a variety of beneficial active ingredients, and has been widely used in the ethnopharmacological practices, however, its biotransformation in gastrointestinal digestions remain unclear. This study aimed to investigate the dynamic changes of components and biological activity of Epimedium in the in vitro simu? lated digestion and subsequent human faecal fermentation. METHODS The models of in vitro simulated saliva, gastric and intestinal digestion, as well as colonic fermentation were constructed to simulate the digestion process of Epimedium. The dynamic changes of components of Epimedium during the simulated digestions in vitro and subsequent human faecal fermentation were investigated by UPLC-MS, HPLC-DAD combined with principal component analysis (PCA) and multi-ingredient quantitative analysis. RESULTS A variety of metabolites with high contents were produced after 0.5 h of intestinal digestion and colonic fermentation 0.5 h. Application of PCA to HPLC data showed the obvious separation of colonic fermentation 0.5 h stage samples from other colonic fermentation stages samples (24, 48 and 72 h). Addition? ally, non-digestion and saliva digestion stage samples clustered together, and there was obvious separation between intestinal digestion samples and gastric digestion samples. The contents of epimedium C, icariin and baohuside I all increased significantly after intestinal digestion [58.70 ± 7.08, 47.15 ± 5.68 and (12.78 ± 0.55) mg · g-1] compared with gastric digestion [29.00 ± 5.65, 17.40 ± 4.55 and (2.77 ± 0.19) mg·g-1]. There were significant differences between sample after 0.5 h of colonic fermentation [64.22 ± 9.32, 51.26 ± 6.33 and (16.68 ± 3.19) mg·g-1] and other time points (24, 48 and 72 h) in components and the contents of active ingredient, and the content of these components all decreased with the fermentation time. The ability of scavenging ABTS free radicals [IC50=(0.29 ± 0.02) g · L-1] increased significantly compared with gastric digestion [(1.57 ± 0.02) g·L-1], and after 0.5 h of colonic fermentation, the ability also increased significantly. CONCLUSION Gastrointestinal digestion had a significant impact on the contents of active components in Epimedium, and the metabolism of these components mainly occurred in the colon. The intestinal digestion and colonic fermentation significantly improved the anti-ABTS activity of epimedium.
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5-Aminolevulinic acid (5-ALA) has been approved for clinical photodynamic therapy (PDT) due to its negligible photosensitive toxicity. However, the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells. Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair, a liposomal nanomedicine (MFLs@5-ALA/DFO) with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA, which was prepared by co-encapsulating 5-ALA and DFO (deferoxamine, a special iron chelator) into the membrane fusion liposomes (MFLs). MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery. MFLs@5-ALA/DFO could efficiently reduce iron ion, thus blocking the biotransformation of photosensitive protoporphyrin IX (PpIX) to heme, realizing significant accumulation of photosensitivity. Meanwhile, the activity of DNA repair enzyme was also inhibited with the reduction of iron ion, resulting in the aggravated DNA damage in tumor cells. Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.
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Podophyllotoxin (PTOX) is an aryl-tetralin lignan of plant origin found in some species of Podophyllum such as Dysosma versipellis, Diphylleia sinensis, and Sinopodophyllum hexandrum. Etoposide and teniposide are produced semisynthetically from PTOX and used clinically to treat several forms of cancer. As a typical representative of new drug discovery from natural products, the production of PTOX solely depends on extraction from plants, resulting in severe contradiction between supply and demand. With the advantages of unconstrained resources and eco-friendly reaction conditions, biosynthesis method has become a trend in the production of PTOX and its derivatives. In this review, we summarize the research progress of PTOX biosynthesis in plants and expound the functions of the key enzymes as well as their subcellular location. The synthetic biology for production of PTOX intermediates in a tobacco chassis is also introduced. Finally, the heterologous expression and biotransformation of PTOX in microorganisms is summarized, which sets the foundation for the efficient microbial production of PTOX using cell factories.
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Genes de Plantas , Podofilotoxina/biossíntese , Podophyllum/genéticaRESUMO
Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans, (+) (7S, 8S, 7'S, 8'R) iso-magnosalicin (1a)/(-) (7R, 8R, 7'R, 8'S) iso-magnosalicin (1b) and (+) (7R, 8R, 7'S, 8'R) magnosalicin (2a)/(-) (7S, 8S, 7'R, 8'S) magnosalicin (2b), and four known metabolites, (±) acoraminol A (3), (±) acoraminol B (4), asaraldehyde (5), and 2, 4, 5-trimethoxybenzoic acid (6). Their structures, including absolute configurations, were determined by extensive analysis of NMR spectra, X-ray crystallography, and quantum chemical ECD calculations. The cytotoxic activity and Aβ
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Methylotrophic yeasts are considered as promising cell factories for bio-manufacturing due to their several advantages such as tolerance to low pH and high temperature. In particular, their methanol utilization ability may help to establish a methanol biotransformation process, which will expand the substrate resource for bio-refinery and the product portfolio from methanol. This review summarize current progress on engineering methylotrophic yeasts for production of proteins and chemicals, and compare the strengths and weaknesses with the model yeast Saccharomyces cerevisiae. The challenges and possible solutions in metabolic engineering of methylotrophic yeasts are also discussed. With the developing efficient genetic tools and systems biology, the methylotrophic yeasts should play more important roles in future green bio-manufacturing.
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Engenharia Metabólica , Metanol , Saccharomyces cerevisiae/genética , LevedurasRESUMO
Resumen El SARS-CoV-2 es un virus de la familia Coronaviridae, subfamilia coronavirus (CoV) y género β. Este se ha convertido en una amenaza inminente para toda la humanidad por ser el agente causal de la pandemia COVID-19, la cual llevó, por un lado, a la declaratoria de emergencia sanitaria a nivel mundial por parte de la Organización Mundial de la Salud (OMS) y, por otro, a instituir estrictas medidas de control para prevenir su contagio por parte de muchos gobiernos. En cuanto a la fisiopatología presentada en esta entidad, aunque las lesiones pulmonares han sido consideradas como las principales consecuencias de esta infección, a medida que avanza el conocimiento sobre el virus se han identificado también lesiones a nivel cardiaco, hepático y renal, que potencian la severidad de la infección y generan un mayor deterioro de los pacientes, su ingreso a las Unidades de Cuidados Intensivos y un mayor riesgo de mortalidad. Con base en esto, diversas investigaciones se han encaminado a determinar aquellos hallazgos clínicos y paraclínicos que puedan ser relevantes frente al pronóstico de los pacientes. Por lo anterior, la presente revisión aborda literatura disponible sobre los principales biomarcadores bioquímicos reportados por su asociación a daños cardiaco, hepático y renal, los cuales presentan mayor significancia para evaluar el curso, severidad, manejo y pronóstico de la infección, y cuya alteración conlleva finalmente a un mayor riesgo de mortalidad en pacientes hospitalizados que presentan COVID-19.
Abstract SARS-CoV-2 is a virus from the coronaviridae family, coronavirus (CoV) subfamily and genus β, it has become an imminent threat to all humanity as it is the causal agent of the COVID-19 pandemic, which led to On the one hand, the World Health Organization (WHO) declares a worldwide health emergency, and on the other, to institute strict control measures to prevent its spread by many governments. Regarding the pathophysiology presented in this entity, although lung lesions have been considered the main consequences of this infection, as knowledge about the virus progresses, cardiac, hepatic, and renal lesions have also been identified that enhance severity of the infection generating greater deterioration of the patients, their admission to the Intensive Care Units and a higher risk of mortality; Based on this, various investigations have aimed to determine those clinical and paraclinical findings that may be relevant to the prognosis of the patients. Therefore, this review addresses available literature on the main biochemical biomarkers reported for their association with cardiac, liver and kidney damage, which are more significant in evaluating the course, severity, management and prognosis of the infection and whose alteration ultimately leads to an increased risk of mortality in hospitalized patients presenting with COVID-19.
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Humanos , SARS-CoV-2 , Biomarcadores , Coronaviridae , COVID-19 , Unidades de Terapia IntensivaRESUMO
Resumo A farmacogenômica (FGx) investiga a interação entre genes e medicamentos. Através da análise de regiões específicas do DNA, informações sobre o perfil de metabolização do paciente para um determinado fármaco podem ser descritas, assim como o perfil esperado de resposta ao tratamento. Objetivamente, esse tipo de teste pode ter impacto no tratamento de pacientes que não estão respondendo adequadamente a um determinado medicamento, seja pela ausência dos efeitos esperados ou em virtude do aparecimento de efeitos adversos. Neste cenário, o objetivo desta revisão é o de informar o cardiologista clínico sobre esta importante área do conhecimento e atualizá-lo sobre o tema, procurando preencher as lacunas no que diz respeito à relação custo-benefício da aplicação da FGx nas doenças cardiovasculares, além de fornecer informações para a implementação da terapia guiada pela FGx na prática clínica.
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Humanos , Farmacogenética , Doenças Cardiovasculares/genéticaRESUMO
Recently, with the rapid development of new drug research in China, the human mass balance and biotransformation (MBB) studies on innovative drugs are on a track to become indispensable during new drug application. However, traditional analysis method, e.g. mass spectrum, is insufficient to elaborately explain the mass balance and the relative biotransformation of the investigated drugs in human bodies. This problem could be solved by applying radiolabelled technique into these MBB studies, which are more and more popular nowadays. The authors' hospital is one of the first a few organizations to conduct the MBB studies, and has completed almost 20 trials. This review mainly focused on the study design from the investigators' viewpoints, involving the related rules and regulations, both at home and abroad, and the protocol design, so as to provide our thinkings for references and benefit to the new drug clinical trial in the future.
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Protoberberine alkaloids belong to the quaternary ammonium isoquinoline alkaloids, and are the main active ingredients in traditional Chinese herbal medicines, like Coptis chinensis. They have been widely used to treat such diseases as gastroenteritis, intestinal infections, and conjunctivitis. Studies have shown that structural modification of the protoberberine alkaloids could produce derivative compounds with new pharmacological effects and biological activities, but the transformation mechanism is not clear yet. This article mainly summarizes the researches on the biotransformation and structure modification of protoberberine alkaloids mainly based on berberine, so as to provide background basis and new ideas for studies relating to the mechanism of protoberberine alkaloids and the pharmacological activity and application of new compounds.
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Alcaloides , Berberina , Alcaloides de Berberina , Biotransformação , CoptisRESUMO
The number of emerging organic and inorganic substances, which are called xenobiotic, is increasing day after day. The potential hazards of these substances are being tested since they are used as drugs and food additives. According to the data obtained from these tests, the harmless ones are released for use. However, it should be noted that these compounds, which are taken as drugs or food additives, are mostly biotransformed with cytochrome P450 in the liver. A large portion of different xenobiotic molecular structures that were biotransformed in the liver can be emptied into the small intestine by a biliary duct and can reenter the organism in their transformed molecular structure. Therefore, it should be accepted that the effects of transformed molecular structures of food additives, especially bread additives, to human must be researched.