Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.226
Filtrar
1.
Appl Microbiol Biotechnol ; 108(1): 265, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498113

RESUMO

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a type of polyhydroxyalkanoates (PHA) that exhibits numerous outstanding properties and is naturally synthesized and elaborately regulated in various microorganisms. However, the regulatory mechanism involving the specific regulator PhaR in Haloferax mediterranei, a major PHBV production model among Haloarchaea, is not well understood. In our previous study, we showed that deletion of the phosphoenolpyruvate (PEP) synthetase-like (pps-like) gene activates the cryptic phaC genes in H. mediterranei, resulting in enhanced PHBV accumulation. In this study, we demonstrated the specific function of the PPS-like protein as a negative regulator of phaR gene expression and PHBV synthesis. Chromatin immunoprecipitation (ChIP), in situ fluorescence reporting system, and in vitro electrophoretic mobility shift assay (EMSA) showed that the PPS-like protein can bind to the promoter region of phaRP. Computational modeling revealed a high structural similarity between the rifampin phosphotransferase (RPH) protein and the PPS-like protein, which has a conserved ATP-binding domain, a His domain, and a predicted DNA-binding domain. Key residues within this unique DNA-binding domain were subsequently validated through point mutation and functional evaluations. Based on these findings, we concluded that PPS-like protein, which we now renamed as PspR, has evolved into a repressor capable of regulating the key regulator PhaR, and thereby modulating PHBV synthesis. This regulatory network (PspR-PhaR) for PHA biosynthesis is likely widespread among haloarchaea, providing a novel approach to manipulate haloarchaea as a production platform for high-yielding PHA. KEY POINTS: • The repressive mechanism of a novel inhibitor PspR in the PHBV biosynthesis was demonstrated • PspR is widespread among the PHA accumulating haloarchaea • It is the first report of functional conversion from an enzyme to a trans-acting regulator in haloarchaea.


Assuntos
Poli-Hidroxialcanoatos , Poli-Hidroxialcanoatos/metabolismo , Hidroxibutiratos , DNA , Poliésteres/metabolismo
2.
PLoS One ; 19(3): e0300708, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38517926

RESUMO

Researchers are increasingly using insights derived from large-scale, electronic healthcare data to inform drug development and provide human validation of novel treatment pathways and aid in drug repurposing/repositioning. The objective of this study was to determine whether treatment of patients with multiple sclerosis with dimethyl fumarate, an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, results in a change in incidence of type 2 diabetes and its complications. This retrospective cohort study used administrative claims data to derive four cohorts of adults with multiple sclerosis initiating dimethyl fumarate, teriflunomide, glatiramer acetate or fingolimod between January 2013 and December 2018. A causal inference frequentist model averaging framework based on machine learning was used to compare the time to first occurrence of a composite endpoint of type 2 diabetes, cardiovascular disease or chronic kidney disease, as well as each individual outcome, across the four treatment cohorts. There was a statistically significantly lower risk of incidence for dimethyl fumarate versus teriflunomide for the composite endpoint (restricted hazard ratio [95% confidence interval] 0.70 [0.55, 0.90]) and type 2 diabetes (0.65 [0.49, 0.98]), myocardial infarction (0.59 [0.35, 0.97]) and chronic kidney disease (0.52 [0.28, 0.86]). No differences for other individual outcomes or for dimethyl fumarate versus the other two cohorts were observed. This study effectively demonstrated the use of an innovative statistical methodology to test a clinical hypothesis using real-world data to perform early target validation for drug discovery. Although there was a trend among patients treated with dimethyl fumarate towards a decreased incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease relative to other disease-modifying therapies-which was statistically significant for the comparison with teriflunomide-this study did not definitively support the hypothesis that Nrf2 activation provided additional metabolic disease benefit in patients with multiple sclerosis.


Assuntos
Doenças Cardiovasculares , Crotonatos , Diabetes Mellitus Tipo 2 , Hidroxibutiratos , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Nitrilas , Insuficiência Renal Crônica , Toluidinas , Adulto , Humanos , Imunossupressores/uso terapêutico , Fumarato de Dimetilo/uso terapêutico , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Estudos Retrospectivos , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Incidência , Fator 2 Relacionado a NF-E2 , Cloridrato de Fingolimode/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico
3.
Int J Biol Macromol ; 263(Pt 1): 130188, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38373562

RESUMO

Plastic pollution is the biggest environmental concern of our time. Breakdown products like micro- and nano-plastics inevitably enter the food chain and pose unprecedented health risks. In this scenario, bio-based and biodegradable plastic alternatives have been given a momentum aiming to bridge a transition towards a more sustainable future. Polyhydroxyalkanoates (PHAs) are one of the few thermoplastic polymers synthesized 100 % via biotechnological routes which fully biodegrade in common natural environments. Poly(hydroxybutyrate-co-hydroxyhexanoate) [P(HB-co-HHx)] is a PHA copolymer with great potential for the commodity polymers industry, as its mechanical properties can be tailored through fine-tuning of its molar HHx content. We have recently developed a strategy that enables for reliable tailoring of the monomer content of P(HB-co-HHx). Nevertheless, there is often a lack of comprehensive investigation of the material properties of PHAs to evaluate whether they actually mimic the functionalities of conventional plastics. We present a detailed study of P(HB-co-HHx) copolymers with low to moderate hydroxyhexanoate content to understand how the HHx monomer content influences the thermal and mechanical properties and to link those to their abiotic degradation. By increasing the HHx fractions in the range of 2 - 14 mol%, we impart an extension of the processing window and application range as the melting temperature (Tm) and glass temperature (Tg) of the copolymers decrease from Tm 165 °C to 126 °C, Tg 4 °C to -5.9 °C, accompanied by reduced crystallinity from 54 % to 20 %. Elongation at break was increased from 5.7 % up to 703 % at 14 mol% HHx content, confirming that the range examined was sufficiently large to obtain ductile and brittle copolymers, while tensile strength was maintained throughout the studied range. Finally, accelerated abiotic degradation was shown to be slowed down with an increasing HHx fraction decreasing from 70 % to 55 % in 12 h.


Assuntos
Caproatos , Poli-Hidroxialcanoatos , Ácido 3-Hidroxibutírico/metabolismo , Hidroxibutiratos , Biotecnologia
4.
J Hazard Mater ; 466: 133573, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38306834

RESUMO

Biosourced and biodegradable plastics offer a promising solution to reduce environmental impacts of plastics for specific applications. Here, we report a novel bacterium named Alteromonas plasticoclasticus MED1 isolated from the marine plastisphere that forms biofilms on foils of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). Experiments of degradation halo, plastic matrix weight loss, bacterial oxygen consumption and heterotrophic biosynthetic activity showed that the bacterial isolate MED1 is able to degrade PHBV and to use it as carbon and energy source. The likely entire metabolic pathway specifically expressed by this bacterium grown on PHBV matrices was shown by further genomic and transcriptomic analysis. In addition to a gene coding for a probable secreted depolymerase, a gene cluster was located that encodes characteristic enzymes involved in the complete depolymerization of PHBV, the transport of oligomers, and in the conversion of the monomers into intermediates of central carbon metabolism. The transcriptomic experiments showed the activation of the glyoxylate shunt during PHBV degradation, setting the isocitrate dehydrogenase activity as regulated branching point of the carbon flow entering the tricarboxylic acid cycle. Our study also shows the potential of exploring the natural plastisphere to discover new bacteria with promising metabolic capabilities.


Assuntos
Bactérias , Poliésteres , Bactérias/genética , Bactérias/metabolismo , Hidroxibutiratos , Biopolímeros , Carbono/metabolismo
5.
Microb Cell Fact ; 23(1): 56, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368375

RESUMO

BACKGROUND: Polyhydroxybutyrate (PHB) has emerged as a promising eco-friendly alternative to traditional petrochemical-based plastics. In the present study, we isolated and characterized a new strain of Salinicola salarius, a halophilic bacterium, from the New Suez Canal in Egypt and characterized exclusively as a potential PHB producer. Further genome analysis of the isolated strain, ES021, was conducted to identify and elucidate the genes involved in PHB production. RESULTS: Different PHB-producing marine bacteria were isolated from the New Suez Canal and characterized as PHB producers. Among the 17 bacterial isolates, Salinicola salarius ES021 strain showed the capability to accumulate the highest amount of PHB. Whole genome analysis was implemented to identify the PHB-related genes in Salinicola salarius ES021 strain. Putative genes were identified that can function as phaCAB genes to produce PHB in this strain. These genes include fadA, fabG, and P3W43_16340 (encoding acyl-CoA thioesterase II) for PHB production from glucose. Additionally, phaJ and fadB were identified as key genes involved in PHB production from fatty acids. Optimization of environmental factors such as shaking rate and incubation temperature, resulted in the highest PHB productivity when growing Salinicola salarius ES021 strain at 30°C on a shaker incubator (110 rpm) for 48 h. To maximize PHB production economically, different raw materials i.e., salted whey and sugarcane molasses were examined as cost-effective carbon sources. The PHB productivity increased two-fold (13.34 g/L) when using molasses (5% sucrose) as a fermentation media. This molasses medium was used to upscale PHB production in a 20 L stirred-tank bioreactor yielding a biomass of 25.12 g/L, and PHB of 12.88 g/L. Furthermore, the produced polymer was confirmed as PHB using Fourier-transform infrared spectroscopy (FTIR), gas chromatography-mass spectroscopy (GC-MS), and nuclear magnetic resonance spectroscopy (NMR) analyses. CONCLUSIONS: Herein, Salinicola salarius ES021 strain was demonstrated as a robust natural producer of PHB from agro-industrial wastes. The detailed genome characterization of the ES021 strain presented in this study identifies potential PHB-related genes. However, further metabolic engineering is warranted to confirm the gene networks required for PHB production in this strain. Overall, this study contributes to the development of sustainable and cost-effective PHB production strategies.


Assuntos
Halomonadaceae , Resíduos Industriais , Poli-Hidroxibutiratos , Plásticos , Polímeros , Hidroxibutiratos/metabolismo , Poliésteres/metabolismo
6.
Sci Rep ; 14(1): 3627, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351089

RESUMO

The study aimed to assess the metabolomic profile of the synovial fluid (SF) of dogs affected by spontaneous osteoarthritis (OA) and compare any differences based on disease progression. Sixty client-owned dogs affected by spontaneous OA underwent clinical, radiographic, and cytologic evaluations to confirm the diagnosis. The affected joints were divided into four study groups based on the Kallgreen-Lawrence classification: OA1 (mild), OA2 (moderate), OA3 (severe), and OA4 (extremely severe/deforming). The osteoarthritic joint's SF was subjected to cytologic examination and 1H-NMR analysis. The metabolomic profiles of the study groups' SF samples were statistically compared using one-way ANOVA. Sixty osteoarthritic joints (45 stifles, 10 shoulders and 5 elbows) were included in the study. Fourteen, 28, and 18 joints were included in the OA1, OA2, and OA3 groups, respectively (0 joints in the OA4 group). Metabolomic analysis identified 48 metabolites, five of which were significantly different between study groups: Mannose and betaine were elevated in the OA1 group compared with the OA2 group, and the 2-hydroxyisobutyrate concentration decreased with OA progression; in contrast, isoleucine was less concentrated in mild vs. moderate OA, and lactate increased in severe OA. This study identified different 1H-NMR metabolomic profiles of canine SF in patients with progressive degrees of spontaneous OA, suggesting 1H-NMR metabolomic analysis as a potential alternative method for monitoring OA progression. In addition, the results suggest the therapeutic potentials of the metabolomic pathways that involve mannose, betaine, 2-hydroxyisobutyrate, isoleucine, and lactate.


Assuntos
Hidroxibutiratos , Osteoartrite , Líquido Sinovial , Humanos , Cães , Animais , Líquido Sinovial/metabolismo , Betaína/metabolismo , Manose/metabolismo , Isoleucina/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Osteoartrite/diagnóstico , Osteoartrite/veterinária , Osteoartrite/metabolismo , Lactatos/metabolismo
7.
Microb Cell Fact ; 23(1): 52, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360657

RESUMO

BACKGROUND: Among the polyhydroxyalkanoate (PHA), poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate] [P(3HB-co-3HHx)] is reported to closely resemble polypropylene and low-density polyethylene. Studies have shown that PHA synthase (PhaC) from mangrove soil (PhaCBP-M-CPF4) is an efficient PhaC for P(3HB-co-3HHx) production and N-termini of PhaCs influence its substrate specificity, dimerization, granule morphology, and molecular weights of PHA produced. This study aims to further improve PhaCBP-M-CPF4 through N-terminal truncation. RESULTS: The N-terminal truncated mutants of PhaCBP-M-CPF4 were constructed based on the information of the predicted secondary and tertiary structures using PSIPRED server and AlphaFold2 program, respectively. The N-terminal truncated PhaCBP-M-CPF4 mutants were evaluated in C. necator mutant PHB-4 based on the cell dry weight, PHA content, 3HHx molar composition, molecular weights, and granule morphology of the PHA granules. The results showed that most transformants harbouring the N-terminal truncated PhaCBP-M-CPF4 showed a reduction in PHA content and cell dry weight except for PhaCBP-M-CPF4 G8. PhaCBP-M-CPF4 G8 and A27 showed an improved weight-average molecular weight (Mw) of PHA produced due to lower expression of the truncated PhaCBP-M-CPF4. Transformants harbouring PhaCBP-M-CPF4 G8, A27, and T74 showed a reduction in the number of granules. PhaCBP-M-CPF4 G8 produced higher Mw PHA in mostly single larger PHA granules with comparable production as the full-length PhaCBP-M-CPF4. CONCLUSION: This research showed that N-terminal truncation had effects on PHA accumulation, substrate specificity, Mw, and granule morphology. This study also showed that N-terminal truncation of the amino acids that did not adopt any secondary structure can be an alternative to improve PhaCs for the production of PHA with higher Mw in mostly single larger granules.


Assuntos
Cupriavidus necator , Poli-Hidroxialcanoatos , Poli-Hidroxialcanoatos/metabolismo , Ácido 3-Hidroxibutírico , Caproatos/metabolismo , Hidroxibutiratos/metabolismo , Aciltransferases/genética , Aciltransferases/metabolismo , Grânulos Citoplasmáticos , Cupriavidus necator/genética , Cupriavidus necator/metabolismo
8.
Sci Total Environ ; 918: 170678, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38316313

RESUMO

BACKGROUND: Exposure to persistent organic pollutants (POPs) has been related to the risk of endometriosis however the mechanisms remain unclear. The objective of the present study was to characterize the metabolic profiles underpinning the associations between POPs and endometriosis risk. METHODOLOGY: A hospital-based case-control study was conducted in France to recruit women with and without surgically confirmed deep endometriosis. Women's serum was analyzed using gas and liquid chromatography coupled to high-resolution mass spectrometry (HRMS) to measure the levels of polychlorinated biphenyls (PCBs), organochlorinated pesticides (OCPs) and per-/polyfluoroalkyl substances (PFAS). A comprehensive metabolomic profiling was conducted using targeted HRMS and 1H nuclear magnetic resonance (1H NMR) to cover polar and non-polar fractions. A "meet-in-the-middle" statistical framework was applied to identify the metabolites related to endometriosis and POP levels, using multivariate linear and logistic regressions adjusting for confounding variables. RESULTS: Fourteen PCBs, six OCPs and six PFAS were widely found in almost all serum samples. The pesticide trans-nonachlor was the POP most strongly and positively associated with deep endometriosis risk, with odds ratio (95 % confidence interval) of 2.42 (1.49; 4.12), followed by PCB180 and 167. Women with endometriosis exhibited a distinctive metabolic profile, with elevated serum levels of lactate, ketone bodies and multiple amino acids and lower levels of bile acids, phosphatidylcholines (PCs), cortisol and hippuric acid. The metabolite 2-hydroxybutyrate was simultaneously associated to endometriosis risk and exposure to trans-nonachlor. CONCLUSIONS: To the best of our knowledge, this is the first comprehensive metabolome-wide association study of endometriosis, integrating ultra-trace profiling of POPs. The results confirmed a metabolic alteration among women with deep endometriosis that could be also associated to the exposure to POPs. Further observational and experimental studies will be required to delineate the causal ordering of those associations and gain insight on the underlying mechanisms.


Assuntos
Endometriose , Poluentes Ambientais , Fluorocarbonos , Hidrocarbonetos Clorados , Praguicidas , Bifenilos Policlorados , Humanos , Feminino , Bifenilos Policlorados/análise , Praguicidas/análise , Endometriose/induzido quimicamente , Estudos de Casos e Controles , Hidrocarbonetos Clorados/análise , Poluentes Ambientais/análise , Hidroxibutiratos , Fluorocarbonos/análise
9.
Molecules ; 29(4)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38398551

RESUMO

Bis(acetylacetonato)oxidovanadium(IV) [(VO(acac)2], generally known as vanadyl acetylacetonate, has been shown to be preferentially sequestered in malignant tissue. Vanadium-48 (48V) generated with a compact medical cyclotron has been used to label VO(acac)2 as a potential radiotracer in positron emission tomography (PET) imaging for the detection of cancer, but requires lengthy synthesis. Current literature protocols for the characterization of VO(acac)2 require macroscale quantities of reactants and solvents to identify products by color and to enable crystallization that are not readily adaptable to the needs of radiotracer synthesis. We present an improved method to produce vanadium-48-labeled VO(acac)2, [48V]VO(acac)2, and characterize it using high-performance liquid chromatography (HPLC) with radiation detection in combination with UV detection. The approach is suitable for radiotracer-level quantities of material. These methods are readily applicable for production of [48V]VO(acac)2. Preliminary results of preclinical, small-animal PET studies are presented.


Assuntos
Hidroxibutiratos , Neoplasias , Pentanonas , Radioisótopos , Vanádio , Animais , Cromatografia Líquida de Alta Pressão , Vanádio/química , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons
10.
Science ; 383(6685): 911-918, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38386754

RESUMO

Coenzyme A (CoA) is essential to all life on Earth, and its functional subunit, pantetheine, is important in many origin-of-life scenarios, but how pantetheine emerged on the early Earth remains a mystery. Earlier attempts to selectively synthesize pantetheine failed, leading to suggestions that "simpler" thiols must have preceded pantetheine at the origin of life. In this work, we report high-yielding and selective prebiotic syntheses of pantetheine in water. Chemoselective multicomponent aldol, iminolactone, and aminonitrile reactions delivered spontaneous differentiation of pantoic acid and proteinogenic amino acid syntheses, as well as the dihydroxyl, gem-dimethyl, and ß-alanine-amide moieties of pantetheine in dilute water. Our results are consistent with a role for canonical pantetheine at the outset of life on Earth.


Assuntos
Coenzima A , Origem da Vida , Panteteína , Coenzima A/química , Panteteína/síntese química , Água/química , Nitrilas/química , Hidroxibutiratos/síntese química , 4-Butirolactona/síntese química , Aminoácidos/síntese química
11.
Psychopharmacology (Berl) ; 241(3): 613-625, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38334790

RESUMO

BACKGROUND AND PURPOSE: The use of the recreational drug gamma-hydroxybutyric acid (GHB) has increased over the past decade, concomitantly leading to a higher incidence of GHB use disorder. Evidence-based treatment interventions are hardly available and cognitive effects of long-term GHB use remain elusive. In order to study the development of GUD and the causal effects of chronic GHB consumption, a GHB self-administration model is required. EXPERIMENTAL APPROACH: Long Evans rats had access to GHB in their home cage according to a two-bottle choice procedure for 3 months. Intoxication and withdrawal symptoms were assessed using an automated sensor-based setup for longitudinal behavioral monitoring. Rats were trained in an operant environment according to a fixed ratio (FR) 1, 2, and 4 schedule of reinforcement. Addiction-like behaviors were assessed through progressive ratio-, non-reinforced-, and quinine-adulterated operant tests. In addition, the novel object recognition test and elevated plus maze test were performed before and after GHB self-administration to assess memory performance and anxiety-like behavior, respectively. KEY RESULTS: All rats consumed pharmacologically relevant levels of GHB in their home cage, and their intake remained stable over a period of 3 months. No clear withdrawal symptoms were observed following abstinence. Responding under operant conditions was characterized by strong inter-individual differences, where only a subset of rats showed high motivation for GHB, habitual GHB-seeking, and/or continued responding for GHB despite an aversive taste. Male rats showed a reduction in long-term memory performance 3 months after home-cage GHB self-administration. Anxiety-like behavior was not affected by GHB self-administration. CONCLUSION AND IMPLICATIONS: The GHB self-administration model was able to reflect individual susceptibility for addiction-like behavior. The reduction in long-term memory performance upon GHB self-administration calls for further research into the cognitive effects of chronic GHB use in humans.


Assuntos
Hidroxibutiratos , Oxibato de Sódio , Síndrome de Abstinência a Substâncias , Humanos , Ratos , Masculino , Animais , Ratos Long-Evans , Individualidade , Condicionamento Operante , Autoadministração
12.
Microb Cell Fact ; 23(1): 59, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388436

RESUMO

BACKGROUND: Polyhydroxybutyrate is a biopolymer produced by bacteria and archaea under nitrogen-limiting conditions. PHB is an essential polymer in the bioplastic sector because of its biodegradability, eco-friendliness, and adaptability. The characterization of PHB is a multifaceted process for studying the structure and its properties. This entire aspect can assure the long-term viability and performance attributes of the PHB. The characteristics of PHB extracted from the halophile Brachybacterium paraconglomeratum were investigated with the objective of making films for application in healthcare. RESULTS: This was the first characterization study on PHB produced by a rare halophile, Brachybacterium paraconglomeratum (MTCC 13074). In this study, the strain produced 2.72 g/l of PHB for.5.1 g/l of biomass under optimal conditions. Methods are described for the determination of the physicochemical properties of PHB. The prominent functional groups CH3 and C = O were observed by FT-IR and the actual chemical structure of the PHB was deduced by NMR. GCMS detects the confirmation of four methyl ester derivatives of the extracted PHB in the sample. Mass spectrometry revealed the molecular weight of methyl 3-hydroxybutyric acid (3HB) present in the extract. The air-dried PHB films were exposed to TGA, DSC and a universal testing machine to determine the thermal profile and mechanical stability. Additionally, the essential property of biopolymers like viscosity was also assessed for the extracted PHB. CONCLUSIONS: The current study demonstrated the consistency and quality of B. paraconglomeratum PHB. Therefore, Brachybacterium sps are also a considerable source of PHB with desired characteristics for industrial production.


Assuntos
Actinobacteria , Actinomycetales , Poli-Hidroxibutiratos , Espectroscopia de Infravermelho com Transformada de Fourier , Polímeros , Biopolímeros , Hidroxibutiratos/química
13.
Appl Environ Microbiol ; 90(2): e0155723, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38299815

RESUMO

Using dissolved inorganic carbon (DIC) as a major carbon source, as autotrophs do, is complicated by the bedeviling nature of this substance. Autotrophs using the Calvin-Benson-Bassham cycle (CBB) are known to make use of a toolkit comprised of DIC transporters and carbonic anhydrase enzymes (CA) to facilitate DIC fixation. This minireview provides a brief overview of the current understanding of how toolkit function facilitates DIC fixation in Cyanobacteria and some Proteobacteria using the CBB and continues with a survey of the DIC toolkit gene presence in organisms using different versions of the CBB and other autotrophic pathways (reductive citric acid cycle, Wood-Ljungdahl pathway, hydroxypropionate bicycle, hydroxypropionate-hydroxybutyrate cycle, and dicarboxylate-hydroxybutyrate cycle). The potential function of toolkit gene products in these organisms is discussed in terms of CO2 and HCO3- supply from the environment and demand by the autotrophic pathway. The presence of DIC toolkit genes in autotrophic organisms beyond those using the CBB suggests the relevance of DIC metabolism to these organisms and provides a basis for better engineering of these organisms for industrial and agricultural purposes.


Assuntos
Archaea , Bactérias , Archaea/genética , Archaea/metabolismo , Bactérias/genética , Bactérias/metabolismo , Processos Autotróficos/genética , Carbono/metabolismo , Hidroxibutiratos/metabolismo , Dióxido de Carbono/metabolismo , Ciclo do Carbono/genética
14.
J Neurol Sci ; 458: 122910, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38309248

RESUMO

BACKGROUND: Teriflunomide is administered orally to treat relapsing-remitting multiple sclerosis. In this prospective pilot study, the free and total serum concentrations of teriflunomide obtained during routine health care were measured and their relationship with disease activity was evaluated. METHODS: Eighty-nine patients were included in this study. Blood samples were collected from April 2021 to February 2022, and free and total teriflunomide serum concentrations were measured. Patient assessment involved monitoring of blood counts and potential adverse effects of teriflunomide. RESULTS: In the steady-state group, total teriflunomide concentrations ranged from 14.7 to 144.2 mg/L, while free concentrations from 31.1 to 389.7 µg/L. In the non-steady-state group, the total concentration ranged from 2.2 to 59.3 mg/L, with free concentrations ranging from 6.8 to 143.5 µg/L. In the steady-state group, a significant inverse correlation was found between absolute peripheral blood lymphocyte count and both total and free teriflunomide serum concentrations. CONCLUSION: Although all patients were treated with the same dose, up to a 10-fold difference in total and free teriflunomide serum concentrations, and up to a 5-fold difference in steady-state trough concentrations were observed. This vast interindividual variability can potentially lead to toxicity or, conversely, to suboptimal therapeutic concentrations of teriflunomide, with the risk of further worsening of multiple sclerosis compensation.


Assuntos
Crotonatos , Hidroxibutiratos , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Nitrilas , Toluidinas , Humanos , Esclerose Múltipla/tratamento farmacológico , Projetos Piloto , Estudos Prospectivos , Estudos Transversais , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
15.
Int J Biol Macromol ; 261(Pt 2): 129838, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38307428

RESUMO

A novel α-amylase Amy03713 was screened and cloned from the starch utilization strain Vibrio alginolyticus LHF01. When heterologously expressed in Escherichia coli, Amy03713 exhibited the highest enzyme activity at 45 °C and pH 7, maintained >50 % of the enzyme activity in the range of 25-75 °C and pH 5-9, and sustained >80 % of the enzyme activity in 25 % (w/v) of NaCl solution, thus showing a wide range of adapted temperatures, pH, and salt concentrations. Halomonas bluephagenesis harboring amy03713 gene was able to directly utilize starch. With optimized amylase expression, H. bluephagenesis could produce poly(3-hydroxybutyrate) (PHB), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB). When cultured for PHB production, recombinant H. bluephagenesis was able to grow up to a cell dry weight of 11.26 g/L, achieving a PHB titer of 6.32 g/L, which is the highest titer that has been reported for PHB production from starch in shake flasks. This study suggests that Amy03713 is an ideal amylase for PHA production using starch as the carbon source in H. bluephagenesis.


Assuntos
Halomonas , Ácidos Pentanoicos , Poli-Hidroxialcanoatos , Halomonas/genética , Halomonas/metabolismo , Carbono/metabolismo , Amido/metabolismo , Hidroxibutiratos/metabolismo , alfa-Amilases/genética , alfa-Amilases/metabolismo , Poliésteres/metabolismo
16.
Chemosphere ; 352: 141300, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286312

RESUMO

The search for eco-friendly substitutes for traditional plastics has led to the production of biodegradable bioplastics. However, concerns have been raised about the impact of bioplastic biodegradation on soil health. Despite these concerns, the potential negative consequences of bioplastics during various stages of biodegradation remain underexplored. Therefore, this study aims to investigate the impact of micro-bioplastics made of poly-3-hydroxybutyrate (P3HB) on the properties of three different soils. In our ten-month experiment, we investigated the impact of poly-3-hydroxybutyrate (P3HB) on Chernozem, Cambisol, and Phaeozem soils. Our study focused on changes in soil organic matter (SOM), microbial activity, and the level of soil carbon and nitrogen. The observed changes indicated an excessive level of biodegradation of SOM after the soils were enriched with micro-particles of P3HB, with concentrations ranging from 0.1% to 3%. The thermogravimetric analysis confirmed the presence of residual P3HB (particularly in the 3% treatment) and underscored the heightened biodegradation of SOM, especially in the more stable SOM fractions. This was notably evident in Phaeozem soils, where even the stable SOM pool was affected. Elemental analysis revealed changes in soil organic carbon content following P3HB degradation, although nitrogen levels remained constant. Enzymatic activity was found to vary with soil type and responded differently across P3HB concentration levels. Our findings confirmed that P3HB acts as a bioavailable carbon source. Its biodegradation stimulates the production of enzymes, which in turn affects various soil elements, indicating complex interactions within the soil ecosystem.


Assuntos
Ecossistema , Poli-Hidroxibutiratos , Solo , Carbono/análise , Poliésteres , Hidroxibutiratos , Biopolímeros , Nitrogênio/análise
17.
Bioresour Technol ; 394: 130277, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176596

RESUMO

Traditional Chinese medicine residue (TCMR) was utilized as an inexpensive carbon source for the production of poly(3-hydroxybutyrate) (PHB) using the newly isolated Bacillus altitudinis HBU-SI7. The results showed that Yu Ping Feng TCMR could be directly hydrolysed by cellulase to obtain a high proportion of glucose (99 % of total sugar) without pretreatment, achieving an enzymatic hydrolysis rate of up to 89.2 %. B. altitudinis could grow and produce PHB when using enzymatically hydrolysed TCMR in a 5-L fermenter. After 20 h of fermentation, the maximum concentration of PHB was 11.2 g/L, and the highest cell dry weight (CDW) was 15.4 g/L, with 72.7 % of the PHB fraction in CDW. Moreover, this strain could utilize enzymatic hydrolysates from various herbal formulas to produce high levels of PHB. This novel approach aims to accumulate PHB from TCMR hydrolysates, offering an effective and environmentally friendly method to reduce production costs and achieve mass production.


Assuntos
Bacillus , Poli-Hidroxialcanoatos , Hidroxibutiratos/química , Medicina Tradicional Chinesa , Bacillus/metabolismo , Fermentação , Poliésteres/metabolismo
18.
Mult Scler Relat Disord ; 82: 105395, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38184909

RESUMO

The EVOLUTION trials comparing evobrutinib and teriflunomide in multiple sclerosis revealed unexpected negative results, challenging the choice of the annualized relapse rate (ARR) as the primary outcome. While monoclonal antibodies effectively control inflammation, the focus on ARR may not capture the long-term disability progression addressed by Bruton's tyrosine kinase inhibitors (BTKi). This letter questions the suitability of teriflunomide as a comparator due to low relapse rates in the control group, possibly stemming from patient selection bias. The author advocates for a reevaluation of study design, outcomes, and comparators in multiple sclerosis research, emphasizing the need for new approaches to address disease activity and disability progression. It is time to rethink clinical trials on Bruton's tyrosine kinase inhibitors in multiple sclerosis.


Assuntos
Crotonatos , Hidroxibutiratos , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Nitrilas , Toluidinas , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Recidiva
19.
Bioresour Technol ; 394: 130297, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38185449

RESUMO

Bioplastic production using cyanobacteria can be an effective strategy to cope with environmental problems caused by using petroleum-based plastics. Synechococcus elongatus UTEX 2973 with heterogeneous phaCAB can produce bioplastic polyhydroxybutyrate (PHB) with a high CO2 uptake rate. For cost-effective production of PHB in S. elongatus UTEX 2973, phaCAB was expressed by the constitutive Pcpc560, resulting in the production of 226 mg/L of PHB by only photoautotrophic cultivation without the addition of inducer. Several culture conditions were applied to increase PHB productivity, and when acetate was supplied at a concentration of 1 g/L as an organic carbon source, productivity significantly increased resulting in 607.2 mg/L of PHB and additive cost reduction of more than 300 times was achieved compared to IPTG. Consequently, these results suggest the possibility of cyanobacteria as an agent that can economically produce PHB and as a solution to the problem of petroleum-based plastics.


Assuntos
Petróleo , Poli-Hidroxibutiratos , Acetilcoenzima A , Análise Custo-Benefício , Plásticos , Biopolímeros , Hidroxibutiratos , Poliésteres
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...