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1.
J Pharm Biomed Anal ; 207: 114421, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34710729

RESUMO

Cintirorgon (LYC-55716) is a promising first-in-class antitumor agent as a RORγ agonist in the treatment against various types of cancer. To support preclinical mouse studies, a bioanalytical method was developed and successfully applied for quantification of cintirorgon in mouse plasma and tissue homogenates using LC-MS/MS. The method was fully validated in mouse plasma and partial validation was performed in eight different homogenates originating from brain, kidney, liver, lung, small intestine, small intestine content, spleen, and testis. Sample preparation was performed using 96-well plates for fast and efficient analysis. Protein precipitation was done by addition of 20 µL acetonitrile containing monensin as internal standard to 10 µL sample. Chromatographic separation was achieved on a Polaris 3 C18-A column using gradient elution with 0.2% (v/v) formic acid and 0.2% (v/v) ammonium hydroxide in water (A) and methanol (B) as eluents. The total run time was 3 min. Detection was carried out with a triple quadrupole mass spectrometer with electrospray ionization operated in the positive ion-mode. Quantification could be accomplished within a linear validated concentration range of 5-4,000 ng/mL (10-4,000 ng/mL in brain homogenates) with an intra- and inter-day precision between 4.6-14.7% and 5.1-15.6% (including the LLOQ), respectively, and accuracies between 89.1%-111.2%. The method was successfully applied to a preclinical study with cintirorgon in mice.


Assuntos
Plasma , Espectrometria de Massas em Tandem , Animais , Benzoxazinas , Cromatografia Líquida , Masculino , Camundongos , Propionatos , Reprodutibilidade dos Testes
2.
Chemosphere ; 287(Pt 1): 131979, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34450368

RESUMO

With an increasing number of health-related impacts of per- and polyfluoroalkyl substances (PFAS) being reported, there is a pressing need to understand PFAS transport within both the human body and the environment. As proteins can serve as a primary transport mechanism for PFAS, understanding PFAS binding to proteins is essential for predictive physiological models where accurate values of protein binding constants are vital. In this work we present a critical analysis of three common models for analyzing PFAS binding to bovine serum albumin (BSA) based on fluorescence quenching: the Stern-Volmer model, the modified Stern-Volmer model, and the Hill equation. The PFAS examined include perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorobutanesulfonic acid (PFBS), perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), and the replacement compound 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate (HFPO-DA or GenX). While all three models capture the general effects of hydrophobicity and steric limitations to PFAS binding, the Hill equation highlighted a unique relationship between binding cooperativity and the number of fluorinated carbons, with PFOA exhibiting the greatest binding cooperativity. The significance of steric limitations was confirmed by comparing results obtained by fluorescence quenching, which is an indirect method based on specific binding, to those obtained by equilibrium dialysis where PFAS binding directly correlated with traditional measures of hydrophobicity. Finally, the binding constants were correlated with PFAS physicochemical properties where van der Waals volume best described the steric limitations observed by fluorescence quenching.


Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorcarbonetos , Albuminas , Fluorcarbonetos/análise , Humanos , Propionatos
3.
J Agric Food Chem ; 69(46): 13895-13903, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34757739

RESUMO

Bio-based propionate is widely welcome in the food additive industry. The current anaerobic process by Propionibacteria endures low titers and a long fermentation time. In this study, a new route for propionate production from l-threonine was designed. 2-Ketobutyrate, deaminated from l-threonine, is cleaved into propionaldehyde and CO2 and then be oxidized into propionic acid, which is neutralized by ammonia released from the first deamination step. This CoA-independent pathway with only CO2 as a byproduct boosts propionate production from l-threonine with high productivity and purity. The key enzyme for 2-ketobutyrate decarboxylation was selected, and its expression was optimized. The engineered Pseudomonas putida strain, harboring 2-ketoisovalerate decarboxylase from Lactococcus lactis could produce 580 mM (43 g/L) pure propionic acid from 600 mM l-threonine in 24 h in the batch biotransformation process. Furthermore, a high titer of 62 g/L propionic acid with a productivity of 1.07 g/L/h and a molar yield of >0.98 was achieved in the fed-batch pattern. Finally, an efficient sequential fermentation-biotransformation process was demonstrated to produce propionate directly from the fermentation broth containing l-threonine, which further reduces the costs since no l-threonine purification step is required.


Assuntos
Propionatos , Pseudomonas putida , Biotransformação , Fermentação , Pseudomonas putida/metabolismo , Treonina/metabolismo
4.
Plant Sci ; 313: 111097, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34763850

RESUMO

Safeners are chemical compounds used to improve selectivity and safety of herbicides in crops by activating genes that enhance herbicide metabolic detoxification. The genes activated by safeners in crops are similar to the genes causing herbicide resistance through increased metabolism in weeds. This work investigated the effect of the safener isoxadifen-ethyl (IS) in combination with fenoxaprop-p-ethyl (FE) on the evolution of herbicide resistance in Echinochloa crus-galli under recurrent selection. Reduced susceptibility was observed in the progeny after recurrent selection with both FE alone and with FE + IS for two generations (G2) compared to the parental population (G0). The resistance index found in G2 after FE + IS selection was similar as when FE was used alone, demonstrating that the safener did not increase the rate or magnitude of herbicide resistance evolution. G2 progeny selected with FE alone and the combination of FE + IS had increased survival to herbicides from other mechanisms of action relative to the parental G0 population. One biotype of G2 progeny had increased constitutive expression of glutathione-S-transferase (GST1) after recurrent selection with FE + IS. G2 progeny had increased expression of two P450 genes (CYP71AK2 and CYP72A122) following treatment with FE, while G2 progeny had increased expression of five P450 genes (CYP71AK2, CYP72A258, CYP81A12, CYP81A14 and CYP81A21) after treatment with FE + IS. Repeated selection with low doses of FE with or without the safener IS decreased E. crus-galli control and showed potential for cross-resistance evolution. Addition of safener did not further decrease herbicide sensitivity in second generation progeny; however, the recurrent use of safener in combination with FE resulted in safener-induced increased expression of several CYP genes. This is the first report using safener as an additional factor to study herbicide resistance evolution in weeds under experimental recurrent selection.


Assuntos
Echinochloa/genética , Echinochloa/fisiologia , Resistência a Herbicidas/genética , Resistência a Herbicidas/fisiologia , Herbicidas/metabolismo , Oxazóis/metabolismo , Propionatos/metabolismo , Brasil , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo , Controle de Plantas Daninhas
5.
Trop Anim Health Prod ; 53(5): 496, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34608511

RESUMO

The objective of the current experiment was to determine the effects of sodium bicarbonate (SBC) and chromium propionate (Cr) supplementation on dry matter intake (DMI), growth performance, blood indices, feed sorting behavior, and digestibility of nutrients during the hot and humid condition in Beetal bucks. Twenty-eight Beetal bucks were randomly assigned to four concentrates treatments (n = 7 bucks/treatment) under 2 × 2 factorial arrangements. The factors were (1) chromium supplementation, basal diet without any supplementation (C) and basal diet with Cr @ 1.5 mg Cr/head/day (Cr), and (2) sodium bircbonate supplementation, basal diet supplemented with SBC @15 g/kg of DM (SBC) and diet containing SBC @ 15 g/kg of DM) and Cr @ 1.5 mg/day/animal (SBC + Cr). Chromium was drenched to each animal during the morning feeding. The average daily noon temperature-humidity index (THI) was 86.37 ± 4.01. The daily DMI and ADG was higher (P < .0001) in the SBC, and trend for daily DMI was observed (P < 0.01) for the Cr. The feed to gain ratio was tended to improve (P = 0.056) by the supplementation of Cr. Plasma glucose, cholesterol, and catalase concentration were lower (P < 0.05) in the Cr supplemented, whereas plasma BUN and TPP were not influenced (P > 0.05) by the Cr or the SBC supplementation. The feed selection index indicated that supplementation of Cr and SBC had no effects on selection or rejection of feed particles. In Cr-supplemented bucks, there was a trend for higher ADF digestibility. Digestibility of dry matter, organic matter, NDF, and ADF were not affected by Cr or SBC supplementation. In conclusion, co supplementation of Cr @ 1.5 mg/d and SBC @ 15 g/kg resulted in highest DMI, ADG and improved the feed efficiency in heat-stressed fattening bucks by alleviating negative impacts of HS.


Assuntos
Dieta , Bicarbonato de Sódio , Ração Animal/análise , Animais , Cromo , Dieta/veterinária , Suplementos Nutricionais , Cabras , Resposta ao Choque Térmico , Masculino , Propionatos , Bicarbonato de Sódio/farmacologia
6.
Life Sci ; 285: 120003, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34599936

RESUMO

AIMS: Indole-3-propionic acid (IPA) is a natural product from human microbiota, exhibiting diverse biological activities. The study focused on investigating the antibacterial mode of action(s) triggered by IPA in Escherichia coli. Separate influence of nitric oxide (NO) and each reactive oxygen species, including superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH-), was specifically analyzed throughout the process. MAIN METHODS: The generation of respective reactive oxygen species (ROS), NO, and ONOO- was conducted using flow cytometer using different dyes. Further analysis of separate influences was held based on usage of each scavenger: sodium pyruvate, thiourea, tiron, and L-NAME. Oxidative cell damage was observed through the detection of glutathione depletion and lipid peroxidation. DNA fragmentation and membrane depolarization were observed by TUNEL and DiBAC4(3) staining agent. Finally, Annexin V/PI and FITC-VAD-FMK were applied to detect apoptosis-like death. KEY FINDINGS: IPA exhibited antibacterial activity in E. coli through the accumulation of ROS, NO, ONOO-, and DNA damage, eventually leading to apoptosis-like death. NO and O2- exerted the most potent influence on oxidative damage of E. coli, whereas H2O2 accounts for the least impact. Moreover, the results reveal the major contribution of ONOO- in IPA-induced apoptosis-like death in E. coli. SIGNIFICANCE: This is the first study that introduces the antibacterial activity and apoptosis-like death induced by IPA and suggests the possibility of being an alternative for current antibiotics. Furthermore, the distinct influence of each ROS and NO was analyzed to investigate their contribution to oxidative damage leading to bacterial apoptosis-like death.


Assuntos
Antibiose , Apoptose , Escherichia coli/fisiologia , Indóis/metabolismo , Microbiota/fisiologia , Óxido Nítrico/fisiologia , Propionatos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fragmentação do DNA , Escherichia coli/efeitos dos fármacos , Glutationa/metabolismo , Indóis/farmacologia , Peroxidação de Lipídeos , Microbiota/efeitos dos fármacos , Propionatos/farmacologia
7.
Environ Sci Technol ; 55(20): 14051-14058, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34618444

RESUMO

3-(3,5-Di-tert-butyl-4-hydroxyphenyl)propionate antioxidants, a family of synthetic phenolic antioxidants (SPAs) widely used in polymers, have recently been identified in indoor and outdoor environments. However, limited information is available concerning human exposure to these novel contaminants. In the present study, seven 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate antioxidants were analyzed in human urine samples of donors from the United States. None of the target SPAs were initially detected in the urine samples either before or after hydrolysis by ß-glucuronidase, prompting us to probe the major metabolites of these SPAs. We conducted rat metabolism studies with two representative congeners, tetrakis(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate) (AO1010) and N,N'-bis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionyl]hydrazine (AO1024). Neither AO1010 nor AO1024 was detected in rat urine, while 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionic acid (fenozan acid) was identified as a urinary biomarker for these 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate antioxidants. Surprisingly, fenozan acid was detected in 88% of the human urine samples before hydrolysis (geometric mean: 0.69 ng/mL) and 98% of the samples after hydrolysis (geometric mean: 10.2 ng/mL), indicating prevalent human exposure to 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate antioxidants. To our knowledge, this is the first study reporting the occurrence of fenozan acid in urine, where it can act as a potential biomarker of human exposure to 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate antioxidants.


Assuntos
Antioxidantes , Hidroxitolueno Butilado , Animais , Biomarcadores , Butanos , Humanos , Propionatos , Ratos
8.
Appl Microbiol Biotechnol ; 105(23): 8937-8949, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34694448

RESUMO

Methanogenesis is central to anaerobic digestion processes. The conversion of propionate as a key intermediate for methanogenesis requires syntrophic interactions between bacterial and archaeal partners. In this study, a series of methanogenic enrichments with propionate as the sole substrate were developed to identify microbial populations specifically involved in syntrophic propionate conversion. These rigorously controlled propionate enrichments exhibited functional stability with consistent propionate conversion and methane production; yet, the methanogenic microbial communities experienced substantial temporal dynamics, which has important implications on the understanding of mechanisms involved in microbial community assembly in anaerobic digestion. Syntrophobacter was identified as the most abundant and consistent bacterial partner in syntrophic propionate conversion regardless of the origin of the source culture, the concentration of propionate, or the temporal dynamics of the culture. In contrast, the methanogen partners involved in syntrophic propionate conversion lacked consistency, as the dominant methanogens varied as a function of process condition and temporal dynamics. Methanoculleus populations were specifically enriched as the syntrophic partner at inhibitory levels of propionate, likely due to the ability to function under unfavorable environmental conditions. Syntrophic propionate conversion was carried out exclusively via transformation of propionate into acetate and hydrogen in enrichments established in this study. Microbial populations highly tolerant of elevated propionate, represented by Syntrophobacter and Methanoculleus, are of great significance in understanding methanogenic activities during process perturbations when propionate accumulation is frequently encountered. Key points • Syntrophobacter was the most consistent bacterial partner in propionate metabolism. • Diverse hydrogenotrophic methanogen populations could serve as syntrophic partners. • Methanoculleus emerged as a methanogen partner tolerant of elevated propionate.


Assuntos
Euryarchaeota , Propionatos , Archaea , Metano , Methanomicrobiaceae
9.
Aging (Albany NY) ; 13(17): 20860-20885, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517343

RESUMO

Cancer patients are particularly susceptible to the development of severe Covid-19, prompting us to investigate the serum metabolome of 204 cancer patients enrolled in the ONCOVID trial. We previously described that the immunosuppressive tryptophan/kynurenine metabolite anthranilic acid correlates with poor prognosis in non-cancer patients. In cancer patients, we observed an elevation of anthranilic acid at baseline (without Covid-19 diagnosis) and no further increase with mild or severe Covid-19. We found that, in cancer patients, Covid-19 severity was associated with the depletion of two bacterial metabolites, indole-3-proprionate and 3-phenylproprionate, that both positively correlated with the levels of several inflammatory cytokines. Most importantly, we observed that the levels of acetylated polyamines (in particular N1-acetylspermidine, N1,N8-diacetylspermidine and N1,N12-diacetylspermine), alone or in aggregate, were elevated in severe Covid-19 cancer patients requiring hospitalization as compared to uninfected cancer patients or cancer patients with mild Covid-19. N1-acetylspermidine and N1,N8-diacetylspermidine were also increased in patients exhibiting prolonged viral shedding (>40 days). An abundant literature indicates that such acetylated polyamines increase in the serum from patients with cancer, cardiovascular disease or neurodegeneration, associated with poor prognosis. Our present work supports the contention that acetylated polyamines are associated with severe Covid-19, both in the general population and in patients with malignant disease. Severe Covid-19 is characterized by a specific metabolomic signature suggestive of the overactivation of spermine/spermidine N1-acetyl transferase-1 (SAT1), which catalyzes the first step of polyamine catabolism.


Assuntos
COVID-19/sangue , COVID-19/patologia , Neoplasias/sangue , Neoplasias/virologia , Poliaminas/sangue , Acetilação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/microbiologia , COVID-19/virologia , Estudos de Coortes , Citocinas/sangue , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Metaboloma , Pessoa de Meia-Idade , Propionatos/sangue , Índice de Gravidade de Doença , Adulto Jovem , ortoaminobenzoatos/sangue
11.
Bull Environ Contam Toxicol ; 107(5): 961-966, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34515822

RESUMO

The research portrays the fate of a new herbicide mixture of fomesafen and quizalofop-ethyl. The soil samples viz. red lateritic soil (A), coastal saline soil (B) and black soil (C) were fortified separately for fomesafen and quizalofop-ethyl at 0.5 (T1) and 1.0 mg kg-1 (T2) doses and incubated at 20, 30 and 40°C. A satisfactory mean recovery, precision and linearity proved that the methods were accurate. Both the herbicides followed first + first order kinetics. Higher persistence of fomesafen was observed in Soil C than Soil B and Soil A with 22.38-53.75 days half-life, whereas quizalofop-ethyl showed higher stability in Soil A than Soils B and C with half-life of 0.93-12.07 days. Both compounds showed faster rates of dissipation at increased temperature, irrespective of soil type. The current study will help to predict the effect of temperature on the dissipation of herbicides in different soil under real field scenario.


Assuntos
Herbicidas , Poluentes do Solo , Benzamidas , Herbicidas/análise , Cinética , Propionatos , Quinoxalinas , Solo , Poluentes do Solo/análise , Temperatura
12.
J Food Biochem ; 45(10): e13922, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34476820

RESUMO

This study was conducted to study lycopene efficacy in brain-behavior, pro-inflammatory and apoptotic markers, and antioxidant levels in a rodent model. Rats were administered with propionic acid (PPA) (500 mg/kg BW) to induce autism-like disorders, then treated with different lycopene (L) concentrations (5, 10, 20 mg kg-1  day-1 ) for 35 days. The groups were: (i);control, (ii);PPA, (iii);PPA + L5, (iv);PPA + L10, and (v);PPA + L20. In this study, serum and brain malondialdehyde (MDA) levels decreased with lycopene supplements compared to the PPA group, similarly to the brain levels of inflammatory factors (IL-1α, IL-8, NF-κB, TNF-α; p < .05). Besides, brain levels of anti-apoptotic Bcl-2 decreased, whereas pro-apoptotic Bax, antioxidant Nrf2, and HO-1 levels in brain increased compared with PPA (p < .05). This study showed that lycopene might have therapeutic value to improve the dysfunctions in learning and memory in a dose-dependent way, along with the antioxidant, anti-inflammatory, and antiapoptotic molecular responses in a rat model of ASD-like disorders. PRACTICAL APPLICATIONS: This study suggested that lycopene can reduce propionic acid (PPA)-induced learning and memory impairment and oxidative damage by participating in multiple biological activities such as antioxidant, and anti-inflammatory effects. Lycopene protects serum and brain tissues against PPA induced oxidative damage in rats. These effects may be realized through up-regulation of the brain Nrf2/HO-1 pathway and down-regulation of the IL-1α, IL-8, TNF-α, and NF-κB levels. Lycopene may also contribute to memory and learning function, apoptotic/antiapoptotic modulation, and antioxidant and possible therapeutic efficacy in PPA-induced- Autism spectrum disorder cases.


Assuntos
Transtorno do Espectro Autista , Animais , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/tratamento farmacológico , Inflamação/tratamento farmacológico , Licopeno , Estresse Oxidativo , Propionatos , Ratos
13.
Nat Commun ; 12(1): 4798, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376656

RESUMO

We describe the anaerobic conversion of inositol stereoisomers to propionate and acetate by the abundant intestinal genus Anaerostipes. A inositol pathway was elucidated by nuclear magnetic resonance using [13C]-inositols, mass spectrometry and proteogenomic analyses in A. rhamnosivorans, identifying 3-oxoacid CoA transferase as a key enzyme involved in both 3-oxopropionyl-CoA and propionate formation. This pathway also allowed conversion of phytate-derived inositol into propionate as shown with [13C]-phytate in fecal samples amended with A. rhamnosivorans. Metabolic and (meta)genomic analyses explained the adaptation of Anaerostipes spp. to inositol-containing substrates and identified a propionate-production gene cluster to be inversely associated with metabolic biomarkers in (pre)diabetes cohorts. Co-administration of myo-inositol with live A. rhamnosivorans in western-diet fed mice reduced fasting-glucose levels comparing to heat-killed A. rhamnosivorans after 6-weeks treatment. Altogether, these data suggest a potential beneficial role for intestinal Anaerostipes spp. in promoting host health.


Assuntos
Acetatos/metabolismo , Clostridiales/metabolismo , Inositol/metabolismo , Intestinos/química , Propionatos/metabolismo , Animais , Clostridiales/classificação , Clostridiales/fisiologia , Dieta , Fezes/microbiologia , Interações entre Hospedeiro e Microrganismos , Humanos , Intestinos/microbiologia , Espectroscopia de Ressonância Magnética/métodos , Masculino , Camundongos Endogâmicos C57BL , Ácido Fítico/metabolismo , Espectrometria de Massas em Tandem/métodos
14.
BMC Res Notes ; 14(1): 335, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454571

RESUMO

OBJECTIVE: We previously identified propionic acid as a microbially-produced volatile organic compound with fungicidal activity against several pathogenic fungi. The purpose of this work is to better understand how propionic acid affects fungi by examining some of the effects of this compound on the yeast cell. RESULTS: We show that propionic acid causes a dramatic increase in the uptake of lucifer yellow in yeast cells, which is consistent with enhanced endocytosis. Additionally, using a propidium iodide assay, we show that propionic acid treatment causes a significant increase in the proportion of yeast cells in G1 and a significant decrease in the proportion of cells in G2, suggesting that propionic acid causes a cell cycle arrest in yeast. Finally, we show that the reduction of MTT is attenuated in yeast cells treated with propionic acid, indicating that propionic acid disrupts cellular respiration. Understanding the effects of propionic acid on the yeast cell may aid in assessing the broader utility of this compound.


Assuntos
Respiração Celular , Saccharomyces cerevisiae , Ciclo Celular , Endocitose , Propionatos
15.
Appl Microbiol Biotechnol ; 105(16-17): 6199-6213, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34410439

RESUMO

Propionic acid is an important organic acid with wide industrial applications, especially in the food industry. It is currently produced from petrochemicals via chemical routes. Increasing concerns about greenhouse gas emissions from fossil fuels and a growing consumer preference for bio-based products have led to interest in fermentative production of propionic acid, but it is not yet competitive with chemical production. To improve the economic feasibility and sustainability of bio-propionic acid, fermentation performance in terms of concentration, yield, and productivity must be improved and the cost of raw materials must be reduced. These goals require robust microbial producers and inexpensive renewable feedstocks, so the present review focuses on bacterial producers of propionic acid and promising sources of substrates as carbon sources. Emphasis is placed on assessing the capacity of propionibacteria and the various approaches pursued in an effort to improve their performance through metabolic engineering. A wide range of substrates employed in propionic acid fermentation is analyzed with particular interest in the prospects of inexpensive renewable feedstocks, such as cellulosic biomass and industrial residues, to produce cost-competitive bio-propionic acid. KEY POINTS: • Fermentative propionic acid production emerges as competitor to chemical synthesis. • Various bacteria synthesize propionic acid, but propionibacteria are the best producers. • Biomass substrates hold promise to reduce propionic acid fermentation cost.


Assuntos
Propionatos , Propionibacterium , Fermentação , Engenharia Metabólica
16.
J Phys Chem B ; 125(34): 9668-9677, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34427096

RESUMO

Cytochrome c oxidase (CcO) pumps protons from the N-side to the P-side and consumes electrons from the P-side of the mitochondrial membrane driven by energy gained from reduction of dioxygen to water. ATP synthesis uses the resulting proton gradient and electrostatic potential difference. Since the distance a proton travels through CcO is too large for a one-step transfer process, proton-loading sites (PLS) that can carry protons transiently are necessary. One specific pump-active PLS couples to the redox reaction, thus energizing the proton to move across the membrane against electric potential and proton gradient. The PLS should also prevent proton backflow. Therefore, the propionates of the two redox-active hemes in CcO were suggested as PLS candidates although, according to CcO crystal structures, none of the four propionates can be protonated on account of strong H-bonds. Here, we show that modeling the local structure around heme a3 propionates enhances significantly their capability of carrying a proton jointly. This was not possible for the propionates of heme a. The modeled structures are stable in molecular dynamics simulations (MDS) and are energetically similar to the crystal structure. Precise electrostatic energy computations of MDS data are used to estimate the pKA values of all titratable residues in CcO. For the modeled structures, the heme a3 propionates have pKA values high enough to host a proton transiently but not too high to fix the proton permanently. The change in pKA throughout the redox reaction is sufficient to push the proton to the P-side of the membrane and to provide the protons with the necessary amount of energy for ATP synthesis.


Assuntos
Complexo IV da Cadeia de Transporte de Elétrons , Prótons , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Heme/análogos & derivados , Heme/metabolismo , Oxirredução , Propionatos , Bombas de Próton/metabolismo
17.
Anim Sci J ; 92(1): e13614, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34405934

RESUMO

The methane-mitigating potency of cashew nutshell liquid (CNSL) was evaluated by investigating gas production from batch cultures using feces from Thai native ruminants that had been incubated for different periods. Feces was obtained from four Thai native cattle and four swamp buffaloes reared under practical feeding conditions at the Kasetsart University farm, Thailand. Fecal slurry from the same farm was also included in the analysis. CNSL addition successfully suppressed the methane production potential of feces from both ruminants by shifting short chain fatty acid profiles towards propionate production. Methane mitigation continued for almost 150 days, although the degree of mitigation was more apparent from Day 0 to Day 30. Bacterial and archaeal community shifts with CNSL addition were observed in feces from both ruminants; specifically, Bacteroides increased, whereas Lachnospiraceae and Ruminococcaceae decreased in feces to which CNSL was added. Fecal slurry did not show marked changes in gas production with CNSL addition. The findings showed that the addition of CNSL to the feces of ruminants native to the Southeast Asian region can suppress methane emission. Because CNSL can be easily obtained as a byproduct of the local cashew industry in this region, its on-site application might be ideal.


Assuntos
Anacardium/química , Fezes/microbiologia , Gases/metabolismo , Microbioma Gastrointestinal/fisiologia , Metano/metabolismo , Extratos Vegetais/farmacologia , Animais , Búfalos , Bovinos , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Microbiota , Propionatos/metabolismo , Tailândia
18.
Free Radic Biol Med ; 175: 1-17, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34425189

RESUMO

The aim of present study was to investigate the anticancer mechanisms of 3,3'-diselenodipropionic acid (DSePA), a redox-active organodiselenide in human lung cancer cells. DSePA elicited a significant concentration and time-dependent cytotoxicity in human lung cancer cell line A549 than in normal WI38 cells. The cytotoxic effect of DSePA was preceded by an acute decrease in the level of basal reactive oxygen species (ROS) and a concurrent increase in levels of reducing equivalents (like GSH/GSSG and NADH/NAD) within cells. Further, a series of experiments were performed to measure the markers of intrinsic (Bax, cytochrome c and caspase-9), extrinsic (TNFR, FADR and caspase-8) and endoplasmic reticulum (ER) stress (protein ubiquitylation, calcium flux, Bip, CHOP and caspase-12) pathways in DSePA treated cells. DSePA treatment significantly increased the levels of all the above markers. Moreover, DSePA did not alter the expression and phosphorylation (Ser15) of p53 but caused a significant damage to mitochondria. Pharmacological modulation of GSH level by BSO and NAC in DSePA treated cells led to partial abrogation and augmentation of cell kill respectively. This established the role of reductive stress as a trigger for the apoptosis induced by DSePA treatment. Finally, in vitro anticancer activity of DSePA was also corroborated by its in vivo efficacy of suppressing the growth of A549 derived xenograft tumor in SCID mice. In conclusion, above results suggest that DSePA induces apoptosis in a p53 independent manner by involving extrinsic and intrinsic pathways together with ER stress which can an interesting strategy for lung cancer therapy.


Assuntos
Apoptose , Proteína Supressora de Tumor p53 , Células A549 , Animais , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático , Humanos , Camundongos , Camundongos SCID , Propionatos , Espécies Reativas de Oxigênio/metabolismo , Compostos de Selênio , Proteína Supressora de Tumor p53/genética
19.
Molecules ; 26(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34443543

RESUMO

The thermodynamic, kinetic, and structural properties of Ln3+ complexes with the bifunctional DO3A-ACE4- ligand and its amide derivative DO3A-BACE4- (modelling the case where DO3A-ACE4- ligand binds to vector molecules) have been studied in order to confirm the usefulness of the corresponding Gd3+ complexes as relaxation labels of targeted MRI contrast agents. The stability constants of the Mg2+ and Ca2+ complexes of DO3A-ACE4- and DO3A-BACE4- complexes are lower than for DOTA4- and DO3A3-, while the Zn2+ and Cu2+ complexes have similar and higher stability than for DOTA4- and DO3A3- complexes. The stability constants of the Ln(DO3A-BACE)- complexes increase from Ce3+ to Gd3+ but remain practically constant for the late Ln3+ ions (represented by Yb3+). The stability constants of the Ln(DO3A-ACE)4- and Ln(DO3A-BACE)4- complexes are several orders of magnitude lower than those of the corresponding DOTA4- and DO3A3- complexes. The formation rate of Eu(DO3A-ACE)- is one order of magnitude slower than for Eu(DOTA)-, due to the presence of the protonated amine group, which destabilizes the protonated intermediate complex. This protonated group causes the Ln(DO3A-ACE)- complexes to dissociate several orders of magnitude faster than Ln(DOTA)- and its absence in the Ln(DO3A-BACE)- complexes results in inertness similar to Ln(DOTA)- (as judged by the rate constants of acid assisted dissociation). The 1H NMR spectra of the diamagnetic Y(DO3A-ACE)- and Y(DO3A-BACE)- reflect the slow dynamics at low temperatures of the intramolecular isomerization process between the SA pair of enantiomers, R-Λ(λλλλ) and S-Δ(δδδδ). The conformation of the Cα-substituted pendant arm is different in the two complexes, where the bulky substituent is further away from the macrocyclic ring in Y(DO3A-BACE)- than the amino group in Y(DO3A-ACE)- to minimize steric hindrance. The temperature dependence of the spectra reflects slower ring motions than pendant arms rearrangements in both complexes. Although losing some thermodynamic stability relative to Gd(DOTA)-, Gd(DO3A-BACE)- is still quite inert, indicating the usefulness of the bifunctional DO3A-ACE4- in the design of GBCAs and Ln3+-based tags for protein structural NMR analysis.


Assuntos
Complexos de Coordenação/química , Espectroscopia de Ressonância Magnética , Propionatos/química , Ácidos/química , Catálise , Íons , Cinética , Ligantes , Prótons , Soluções , Termodinâmica
20.
Molecules ; 26(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34443546

RESUMO

Recent studies found that short-chain fatty acids (SCFAs), which are produced through bacterial fermentation in the gastrointestinal tract, have oncoprotective effects against cervical cancer. The most common SCFAs that are well known include acetic acid, butyric acid, and propionic acid, among which propionic acid (PA) has been reported to induce apoptosis in HeLa cells. However, the mechanism in which SCFAs suppress HeLa cell viability remain poorly understood. Our study aims to provide a more detailed look into the mechanism of PA in HeLa cells. Flow cytometry analysis revealed that PA induces reactive oxygen species (ROS), leading to the dysfunction of the mitochondrial membrane. Moreover, PA inhibits NF-κB and AKT/mTOR signaling pathways and induces LC3B protein levels, resulting in autophagy. PA also increased the sub-G1 cell population that is characteristic of cell death. Therefore, the results of this study propose that PA inhibits HeLa cell viability through a mechanism mediated by the induction of autophagy. The study also suggests a new approach for cervical cancer therapeutics.


Assuntos
Antineoplásicos/farmacologia , Propionatos/farmacologia , Neoplasias do Colo do Útero/patologia , Antineoplásicos/química , Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/metabolismo , NF-kappa B/metabolismo , Propionatos/química , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/metabolismo
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