RESUMEN

Poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)] is a highly promising valuable biodegradable material with good biocompatibility and degradability. Vibrio natriegens, owing to its fast-growth, wide substrate spectrum characteristics, was selected to produce P(3HB-co-LA). Herein, the crucial role of acetyltransferase PN96-18060 for PHB synthesis in V. natriegens was identified. Heterologous pathway of P(3HB-co-LA) was introduced into V. natriegens successfully, in addition, overexpression of the dldh gene led to 1.84 fold enhancement of the lactate content in P(3HB-co-LA). Finally, the production of P(3HB-co-LA) was characterized under different carbon sources. The lactate fraction in P(3HB-co-LA) was increased to 28.3 mol% by the modification, about 1.84 times of that of the control. This is the first successful case of producing the P(3HB-co-LA) in V. natriegens. Collectively, this study showed that V. natriegens is an attractive host organism for producing P(3HB-co-LA) and has great potential to produce other co-polymers.

RESUMEN

A series of rare earth alkoxides bearing amine-bridged bis(phenolato) ligands were synthesized through sequential reactions of RE(C5H5)3(THF) (RE = Y, Lu) or Nd[N(SiMe3)2]3 with bis(phenols) LH2 and CF3CH2OH. Complexes REL(OCH2CF3)(THF)n (1-6) bearing different aryl-substituents were obtained in good yields of 59-70%. They were applied in the ring-opening polymerization (ROP) of rac-ß-butyrolactone (rac-BBL), which showed good activity (TOF up to 27,300 h-1), resulting in syndiotactically enriched poly(3-hydroxybutyrate) (PHB) (Pr up to 0.86) with narrow polydispersities (PDI ≤ 1.27). The yttrium complex 3 bearing bulky o-1,1-diphenylethyl substituents outperformed other complexes, suggesting that the smaller ionic radii of metal centers and bulky ortho substituents of ancillary ligands play crucial roles in controlling the activity and stereoselectivity in ROP of rac-BBL. Kinetics of the polymerization of rac-BBL initiated by complex 3 was investigated, which revealed first order dependences on the monomer and initiator concentrations, respectively.

RESUMEN

Addition of statistically optimized concentration of electron acceptor, propionic acid (1.2 g/L) at different cultivation times (0 h, 14.86 h and 19 h) during batch cultivation of B. thuringiensis in mixed substrate (glucose and glycerol) featured production of 8 g/L of biomass and 3.57 g/L of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) containing 0.805 g/L of 3-hydroxyvalerate concentration. Successful scale up of batch cultivation from 7 L to a 70 L bioreactor was, thereafter, achieved using power/volume (P/V) criteria with maximum PHBV and biomass concentration of 3.57 g/L and 7.15 g/L respectively. Characterization of PHBV so produced was carried out using NMR, FTIR, DSC and TGA to elucidate its structure, thermal properties and stability to map their applications in society. These findings highlight the potential of the optimized batch cultivation and scale-up process in producing PHBV emphasizing its relevance in sustainable biopolymer production.

Asunto(s)

Bacillus thuringiensis , Biomasa , Reactores Biológicos , Poliésteres , Poliésteres/metabolismo , Poliésteres/química , Bacillus thuringiensis/metabolismo , Espectroscopía Infrarroja por Transformada de Fourier , Técnicas de Cultivo Celular por Lotes , Rastreo Diferencial de Calorimetría , Termogravimetría , Polihidroxibutiratos

RESUMEN

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality in patients with type 2 diabetes (T2DM). Acute increases in circulating levels of ketone body 3-hydroxybutyrate have beneficial acute hemodynamic effects in patients without T2DM with chronic heart failure with reduced ejection fraction. However, the cardiovascular effects of prolonged oral ketone ester (KE) treatment in patients with T2DM and HFpEF remain unknown. METHODS: A total of 24 patients with T2DM and HFpEF completed a 6-week randomized, double-blind crossover study. All patients received 2 weeks of KE treatment (25 g D-ß-hydroxybutyrate-(R)-1,3-butanediol × 4 daily) and isocaloric and isovolumic placebo, separated by a 2-week washout period. At the end of each treatment period, patients underwent right heart catheterization, echocardiography, and blood samples at trough levels of intervention, and then during a 4-hour resting period after a single dose. A subsequent second dose was administered, followed by an exercise test. The primary end point was cardiac output during the 4-hour rest period. RESULTS: During the 4-hour resting period, circulating 3-hydroxybutyrate levels were 10-fold higher after KE treatment (1010±56 µmol/L; P<0.001) compared with placebo (91±55 µmol/L). Compared with placebo, KE treatment increased cardiac output by 0.2 L/min (95% CI, 0.1 to 0.3) during the 4-hour period and decreased pulmonary capillary wedge pressure at rest by 1 mm Hg (95% CI, -2 to 0) and at peak exercise by 5 mm Hg (95% CI, -9 to -1). KE treatment decreased the pressure-flow relationship (∆ pulmonary capillary wedge pressure/∆ cardiac output) significantly during exercise (P<0.001) and increased stroke volume by 10 mL (95% CI, 0 to 20) at peak exercise. KE right-shifted the left ventricular end-diastolic pressure-volume relationship, suggestive of reduced left ventricular stiffness and improved compliance. Favorable hemodynamic responses of KE treatment were also observed in patients treated with sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 analogs. CONCLUSIONS: In patients with T2DM and HFpEF, a 2-week oral KE treatment increased cardiac output and reduced cardiac filling pressures and ventricular stiffness. At peak exercise, KE treatment markedly decreased pulmonary capillary wedge pressure and improved pressure-flow relationship. Modulation of circulating ketone levels is a potential new treatment modality for patients with T2DM and HFpEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05236335.

RESUMEN

The present study aimed to fabricate innovative fibrous materials with various biological activities from poly(3-hydroxybutyrate), sodium hyaluronate (HA), chitosan (Ch), Melissa officinalis (MO), Hypericum perforatum (HP) extract, or a combination of both extracts. Electrospinning or electrospinning followed by dip coating and the subsequent formation of a polyelectrolyte complex were the methods used to prepare these materials. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) were applied for investigating the morphology of materials, their thermal characteristics, and their surface chemical composition. The composition and design of the mats had an influence on the in vitro release behavior of the main bioactive compounds present in the MO and HP extracts incorporated in the materials. It was found that as-created materials comprising a combination of both extracts and a Ch/HA complex exerted higher antioxidant activity than that of (non-)coated MO-containing mats and Ch/HA-coated mats containing HP. The novel materials manifested antibacterial efficacy towards the pathogenic bacteria S. aureus and E. coli, as evidenced by the performed microbiological screening. Furthermore, the mats possessed a great growth inhibitory effect on HeLa cancer cells but had a less pronounced effect on the growth of normal mouse BALB/3T3 fibroblasts. The loading of both extracts in the mats and the formation of coating led to the enhancement of the in vitro anticancer and antibacterial activities of the materials. Thus, the novel materials have potential for use in local cancer therapy as well as for use as wound dressings.

RESUMEN

In this investigation, the electrospun nanocomposite scaffolds were developed utilizing poly-3-hydroxybutyrate (PHB), zein, and multiwalled carbon nanotubes (MWCNTs) at varying concentrations of MWCNTs including 0.5 and 1 wt%. Based on the SEM evaluations, the scaffold containing 1 wt% MWCNTs (PZ-1C) exhibited the lowest fiber diameter (384 ± 99 nm) alongside a suitable porosity percentage. The presence of zein and MWCNT in the chemical structure of the scaffold was evaluated by FTIR. Furthermore, TEM images revealed the alignment of MWCNTs with the fibers. Adding 1 % MWCNTs to the PHB-zein scaffold significantly enhanced tensile strength by about 69 % and reduced elongation by about 31 %. Hydrophilicity, surface roughness, crystallinity, and biomineralization were increased by incorporating 1 wt% MWCNTs, while weight loss after in vitro degradation was decreased. The MG-63 cells exhibited enhanced attachment, viability, ALP secretion, calcium deposition, and gene expression (COLI, RUNX2, and OCN) when cultivated on the scaffold containing MWCNTs compared to the scaffolds lacking MWCNTs. Moreover, the study found that MWCNTs significantly reduced platelet adhesion and hemolysis rates below 4 %, indicating their favorable anti-hemolysis properties. Regarding the aforementioned results, the PZ-1C electrospun composite scaffold is a promising scaffold with osteogenic properties for bone tissue engineering applications.

Asunto(s)

Hidroxibutiratos , Nanotubos de Carbono , Osteogénesis , Poliésteres , Ingeniería de Tejidos , Andamios del Tejido , Zeína , Nanotubos de Carbono/química , Zeína/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Osteogénesis/efectos de los fármacos , Humanos , Poliésteres/química , Hidroxibutiratos/química , Hidroxibutiratos/farmacología , Huesos/efectos de los fármacos , Huesos/metabolismo , Hemólisis/efectos de los fármacos , Prohibitinas , Supervivencia Celular/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Nanocompuestos/química , Adhesión Celular/efectos de los fármacos , Adhesividad Plaquetaria/efectos de los fármacos , Resistencia a la Tracción , Osteoblastos/efectos de los fármacos , Osteoblastos/citología , Porosidad , Polihidroxibutiratos

RESUMEN

Poly(3-hydroxybutyrate) (P(3HB)) is an attractive biodegradable plastic alternative to petroleum-based plastic. However, the cost of microbial-based bioplastic production mainly lies in the cultivation medium. In this study, we screened the isolates capable of synthesizing P(3HB) using sugarcane bagasse (SCB) waste as a carbon source from 79 Bacillus isolates that had previously shown P(3HB) production using a commercial medium. The results revealed that isolate S356, identified as Bacillus cereus using 16S rDNA and gyrB gene analysis, had the highest P(3HB) accumulation. The highest P(3HB) yield (5.16 g/L, 85.3% of dry cell weight) was achieved by cultivating B. cereus S356 in an optimal medium with 1.5% total reducing sugar with SCB hydrolysate as the carbon source and 0.25% yeast extract as the nitrogen source. Transmission electron microscopy analysis showed the accumulation of approximately 3-5 P(3HB) granules in each B. cereus S356 cell. Proton nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy analyses confirmed that the polymer extracted from B. cereus S356 was P(3HB). Notably, during cultivation for P(3HB) plastic production, B. cereus S356 also secreted bacteriocin, which had high antibacterial activity against the same species (Bacillus cereus). Overall, this work demonstrated the possibility of co-producing eco-friendly biodegradable plastic P(3HB) and bacteriocin from renewable resources using the potential of B. cereus S356.

RESUMEN

Bio-based and biodegradable polyhydroxyalkanoates (PHAs) have great potential as sustainable packaging materials. The incorporation of zinc oxide nanoparticles (ZnO NPs) could further improve their functional properties by providing enhanced barrier and antimicrobial properties, although current literature lacks details on how the characteristics of ZnO influence the structure-property relationships in PHA/ZnO nanocomposites. Therefore, commercial ZnO NPs with different morphologies (rod-like, spherical) and silane surface modification are incorporated into poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) via extrusion and compression molding. All ZnO NPs are homogeneously distributed in the PHBHHx matrix at 1, 3 and 5 wt.%, but finer dispersion is achieved with modified ZnO. No chemical interactions between ZnO and PHBHHx are observed due to a lack of hydroxyl groups on ZnO. The fabricated nanocomposite films retain the flexible properties of PHBHHx with minimal impact of ZnO NPs on crystallization kinetics and the degree of crystallinity (53 to 56%). The opacity gradually increases with ZnO loading, while remaining translucent up to 5 wt.% ZnO and providing an effective UV barrier. Improved oxygen barrier and antibacterial effects against S. aureus are dependent on the intrinsic characteristics of ZnO rather than its morphology. We conclude that PHBHHx retains its favorable processing properties while producing nanocomposite films that are suitable as flexible active packaging materials.

RESUMEN

The increasing need for biodegradable polymers demands efficient and environmentally friendly extraction methods. In this study, a simple and sustainable method for extracting polyhydroxybutyrate (PHB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate (PHB-co-HV) from Methylocystis hirsuta and a mixed methanotrophic consortium with different biopolymer contents was presented. The extraction of biopolymers with 1,3-dioxolane was initially investigated by varying the biomass-to-solvent ratio (i.e., 1:2 w v-1, 1:4 w v-1, 1:6 w v-1, 1:8 w v-1 and 1:10 w v-1) and extraction time (6, 8 and 10 h) at the boiling point of the solvent and atmospheric pressure. Based on the results of the preliminary tests, and only for the most efficient biomass-to-solvent ratio, the extraction kinetics were also studied over a time interval ranging from 30 min to 6 h. For Methylocystis hirsuta, the investigation of the extraction time showed that the maximum extraction was reached after 30 min, with recovery yields of 87% and 75% and purities of 98.7% and 94% for PHB and PHB-co-HV, respectively. Similarly, the extraction of PHB and PHB-co-HV from a mixed methanotrophic strain yielded 88% w w-1 and 70% w w-1 recovery, respectively, with 98% w w-1 purity, at a biomass-to-solvent ratio of 6 in 30 min.

RESUMEN

BACKGROUND: Microbial biopolymers such as poly-3-hydroxybutyrate (PHB) are emerging as promising alternatives for sustainable production of biodegradable bioplastics. Their promise is heightened by the potential utilisation of photosynthetic organisms, thus exploiting sunlight and carbon dioxide as source of energy and carbon, respectively. The cyanobacterium Synechocystis sp. B12 is an attractive candidate for its superior ability to accumulate high amounts of PHB as well as for its high-light tolerance, which makes it extremely suitable for large-scale cultivation. Beyond its practical applications, B12 serves as an intriguing model for unravelling the molecular mechanisms behind PHB accumulation. RESULTS: Through a multifaceted approach, integrating physiological, genomic and transcriptomic analyses, this work identified genes involved in the upregulation of chlorophyll biosynthesis and phycobilisome degradation as the possible candidates providing Synechocystis sp. B12 an advantage in growth under high-light conditions. Gene expression differences in pentose phosphate pathway and acetyl-CoA metabolism were instead recognised as mainly responsible for the increased Synechocystis sp. B12 PHB production during nitrogen starvation. In both response to strong illumination and PHB accumulation, Synechocystis sp. B12 showed a metabolic modulation similar but more pronounced than the reference strain, yielding in better performances. CONCLUSIONS: Our findings shed light on the molecular mechanisms of PHB biosynthesis, providing valuable insights for optimising the use of Synechocystis in economically viable and sustainable PHB production. In addition, this work supplies crucial knowledge about the metabolic processes involved in production and accumulation of these molecules, which can be seminal for the application to other microorganisms as well.

RESUMEN

Poly-3-hydroxybutyrate (P3HB) is a biodegradable polyester produced mainly by bacterial fermentation in an isotactic configuration. Its high crystallinity (about 70%) and brittle behavior have limited the process window and the application of this polymer in different sectors. Atactic poly-3-hydroxybutyrate (a-P3HB) is an amorphous polymer that can be synthesized chemically and blended with the isotactic P3HB to reduce its crystallinity and improve its processability Ring-opening polymerization (ROP) is the most cited synthesis route for this polymer in the literature. In this work, a new synthesis route of a-P3HB by self-polycondensation of racemic ethyl 3-hydroxybutyrate will be demonstrated. Different catalysts were tested regarding their effectiveness, and the reaction parameters were optimized using titanium isopropoxide as the catalyst. The resulting polymers were compared by self-polycondensation for their properties with those of a-P3HB obtained by the ROP and characterized by Fourier transform infrared spectroscopy (FTIR) and gel permeation chromatography (GPC), and the double bond content (DBC) was determined by UV-VIS spectroscopy by using 3-butenoic acid as a standard. Additionally, a life cycle analysis (LCA) of the new method of synthesizing has been carried out to assess the environmental impact of a-P3HB.

RESUMEN

While the brittle polylactide (PLA) has a high durability among bioplastics, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBH) with certain ductility exhibits facile compostability. The addition of polybutylene adipate terephthalate (PBAT) may also be used to improve the ductility and toughness of brittle bioplastics. Binary and ternary blends of PLA/PBAT/PHBH based on either PLA or PHBH as the matrix have been manufactured using a twin-screw extruder. The melt rheological, mechanical, and morphological properties of the processed samples were examined. Binary blends of PLA/PHBH show superior strength, with the PLA75/PHBH25 blend exhibiting a tensile strength of 35.2 ± 3.0 MPa, which may be attributed to miscible-like morphology. In contrast, blends of PLA with PBAT demonstrate low strength, with the PLA50/PBAT50 blend exhibits a tensile strength of 9.5 ± 2.0 MPa due to the presence of large droplets in the matrix. PBAT-containing blends exhibit lower impact strengths compared to PHBH-containing blends. For instance, a PLA75/PBAT25 blend displays an impact strength of 1.76 ± 0.1 kJ/m2, whereas the PHBH75/PBAT25 blend displays an impact strength of 2.61 ± 0.3 kJ/m2, which may be attributed to uniformly dispersed PBAT droplets.

RESUMEN

Previously, we biosynthesized an evolved version of a bio-based polylactide (PLA) on microbial platforms using our engineered lactate-polymerizing enzyme (LPE). This lactate (LA)-based copolyester, LAHB, has advantages over PLA, including improved flexibility and biodegradability, and its properties can be regulated through the LA fraction. To expand the LA-incorporation capacity and improve polymer properties, in the state of in vivo LAHB production, propionyl-CoA transferases (PCTs) that exhibited enhanced production of LA-CoA than the conventional PCTs were selected. Here, the present study has demonstrated that the LA fraction of LAHB could be altered using various PCTs. Enhanced PCT performance was achieved by balancing polymer production and cell growth. Both events are governed by the use of acetyl-CoA, a commonly shared key metabolite. This could be attributed to the different reactivities of individual PCTs towards acetyl-CoA, which serves both as a CoA donor and a leading compound in the TCA cycle. Interestingly, we found complete sequence randomness in the LAHB copolymers, independent of the LA fraction. The mechanism of LA fraction-independent sequence randomness is discussed. This new PCT-based strategy synergistically combines with the evolution of LPE to advance the LAHB project, and enables us to perform advanced applications other than LAHB production utilizing CoA-linked substrates.

Asunto(s)

Coenzima A Transferasas , Ácido Láctico , Ácido Láctico/química , Coenzima A Transferasas/metabolismo , Coenzima A Transferasas/genética , Coenzima A Transferasas/química , Poliésteres/química , Acilcoenzima A/metabolismo , Acilcoenzima A/química , Polímeros/química , Acetilcoenzima A/metabolismo , Acetilcoenzima A/química

RESUMEN

BACKGROUND: The microbial chiral product (R)-3-hydroxybutyrate (3-HB) is a gateway to several industrial and medical compounds. Acetyl-CoA is the key precursor for 3-HB, and several native pathways compete with 3-HB production. The principal competing pathway in wild-type Escherichia coli for acetyl-CoA is mediated by citrate synthase (coded by gltA), which directs over 60% of the acetyl-CoA into the tricarboxylic acid cycle. Eliminating citrate synthase activity (deletion of gltA) prevents growth on glucose as the sole carbon source. In this study, an alternative approach is used to generate an increased yield of 3-HB: citrate synthase activity is reduced but not eliminated by targeted substitutions in the chromosomally expressed enzyme. RESULTS: Five E. coli GltA variants were examined for 3-HB production via heterologous overexpression of a thiolase (phaA) and NADPH-dependent acetoacetyl-CoA reductase (phaB) from Cupriavidus necator. In shake flask studies, four variants showed nearly 5-fold greater 3-HB yield compared to the wild-type, although pyruvate accumulated. Overexpression of either native thioesterases TesB or YciA eliminated pyruvate formation, but diverted acetyl-CoA towards acetate formation. Overexpression of pantothenate kinase similarly decreased pyruvate formation but did not improve 3-HB yield. Controlled batch studies at the 1.25 L scale demonstrated that the GltA[A267T] variant produced the greatest 3-HB titer of 4.9 g/L with a yield of 0.17 g/g. In a phosphate-starved repeated batch process, E. coli ldhA poxB pta-ackA gltA::gltA[A267T] generated 15.9 g/L 3-HB (effective concentration of 21.3 g/L with dilution) with yield of 0.16 g/g from glucose as the sole carbon source. CONCLUSIONS: This study demonstrates that GltA variants offer a means to affect the generation of acetyl-CoA derived products. This approach should benefit a wide range of acetyl-CoA derived biochemical products in E. coli and other microbes. Enhancing substrate affinity of the introduced pathway genes like thiolase towards acetyl-CoA will likely further increase the flux towards 3-HB while reducing pyruvate and acetate accumulation.

Asunto(s)

Ácido 3-Hidroxibutírico , Acetilcoenzima A , Citrato (si)-Sintasa , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Acetilcoenzima A/metabolismo , Citrato (si)-Sintasa/metabolismo , Citrato (si)-Sintasa/genética , Ácido 3-Hidroxibutírico/metabolismo , Ácido 3-Hidroxibutírico/biosíntesis , Ingeniería Metabólica/métodos , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Cetona Oxidorreductasas/metabolismo , Cetona Oxidorreductasas/genética , Oxidorreductasas de Alcohol

RESUMEN

Dental implant success is threatened by peri-implantitis, an inflammation leading to implant failure. Conventional treatments struggle with the intricate microbial and host factors involved. Antibacterial membranes, acting as barriers and delivering antimicrobials, may offer a promising solution. Thus, this study highlights the potential of developing antibacterial membranes of poly-3-hydroxybutyrate and silver nanoparticles (Ag Nps) to address peri-implantitis challenges, discussing design and efficacy against potential pathogens. Electrospun membranes composed of PHB microfibers and Ag Nps were synthesized in a blend of DMF/chloroform at three different concentrations. Various studies were conducted on the characterization and antimicrobial activity of the membranes. The synthesized Ag Nps ranged from 4 to 8 nm in size. Furthermore, Young's modulus decreased, reducing from 13.308 MPa in PHB membranes without Ag Nps to 0.983 MPa in PHB membranes containing higher concentrations of Ag Nps. This demonstrates that adding Ag Nps results in a less stiff membrane. An increase in elongation at break was noted with the rise in Ag Nps concentration, from 23.597 % in PHB membranes to 60.136 % in PHB membranes loaded with Ag Nps. The antibiotic and antibiofilm activity of the membranes were evaluated against Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus mutans, and Candida albicans. The results indicated that all PHB membranes containing Ag Nps exhibited potent antibacterial activity by inhibiting the growth of biofilms and planktonic bacteria. However, inhibition of C. albicans occurred only with the PHB-Ag Nps C membrane. These findings emphasize the versatility and potential of Ag Nps-incorporated membranes as a multifunctional approach for preventing and addressing microbial infections associated with peri-implantitis. The combination of antibacterial and antibiofilm properties in these membranes holds promise for improving the management and treatment of peri-implantitis-related complications.

Asunto(s)

Antibacterianos , Biopelículas , Hidroxibutiratos , Membranas Artificiales , Nanopartículas del Metal , Periimplantitis , Plata , Plata/química , Plata/farmacología , Biopelículas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Nanopartículas del Metal/química , Periimplantitis/tratamiento farmacológico , Periimplantitis/microbiología , Hidroxibutiratos/química , Hidroxibutiratos/farmacología , Poliésteres/química , Pruebas de Sensibilidad Microbiana , Humanos , Staphylococcus aureus/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Streptococcus mutans/efectos de los fármacos , Polihidroxibutiratos

RESUMEN

BACKGROUND: In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization. MATERIALS AND METHODS: We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately. RESULTS: The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta. CONCLUSION: Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.

Asunto(s)

Ácido 3-Hidroxibutírico , Aneurisma de la Aorta , Disección Aórtica , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , Disección Aórtica/genética , Disección Aórtica/epidemiología , Disección Aórtica/etiología , Ácido 3-Hidroxibutírico/sangre , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Factores de Riesgo , Aneurisma de la Aorta/genética , Aneurisma de la Aorta/epidemiología , Aneurisma de la Aorta/etiología , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Medición de Riesgo , Factores Protectores , Fenotipo , Biomarcadores/sangre , Análisis de Mediación

RESUMEN

INTRODUCTION: The prevention and control of hospital-acquired infections remain a significant challenge worldwide, as textiles used in hospital wards are highly involved in transmission processes. This paper reports a new antibacterial medical fabric used to prepare hospital pillowcases, bottom sheets and quilt covers for controlling and reducing hospital-acquired infections. METHOD: The medical fabric was composed of blended yarns of staple polyester (PET) and degradable poly(3-hydroxybutyrate co-3-hydroxyvalerate) (PHBV)/polylactic acid (PLA) fibres, which were coated with polylactide oligomers (PLAO), which are environmentally friendly and safe antimicrobial agents with excellent thermal stability in high-temperature laundry. A clinical trial was conducted, with emphasis on the bacterial species that were closely related to the infection cases in the study hospital. RESULT: After 7 days of use, 94% of PET/PHBV/PLA-PLAO fabric retained <20 colony-forming units/100 cm2 of the total bacterial amount, meeting hygiene and cleanliness standards. CONCLUSION: This study demonstrates the potential of fabrics containing polyhydroxyalkanoate oligomers as highly effective, safe and long-lasting antimicrobial medical textiles that can effectively reduce the incidence of hospital-acquired infections.

Asunto(s)

Antibacterianos , Infección Hospitalaria , Polihidroxialcanoatos , Textiles , Humanos , Textiles/microbiología , Infección Hospitalaria/prevención & control , Antibacterianos/farmacología , Polihidroxialcanoatos/farmacología , Polihidroxialcanoatos/química , Poliésteres/química , Bacterias/efectos de los fármacos

RESUMEN

While in nature, molecular chirality enables the formation of chiral macroscopic structures through crystallization and self-organization, such a transfer of molecular information to higher hierarchical levels is rarely observed in vitro. Here, the study reports on single crystals of microbially synthesized polyester poly[(R)-3-hydroxybutyrate], which have chiral habits when grown at the air-water interface, in analogy to the 2D crystallization of chiral lipids such as DPPC. Depending on the crystallization conditions, the chiral single crystals either undergo a transition into fiber-like structures, orassemble into larger superstructures with a uniform sense of rotation.

RESUMEN

The persistence of conventional fossil fuel-derived plastics in marine ecosystems has raised significant environmental concerns. Biodegradable plastics are being explored as an alternative. This study investigates the biodegradation behaviour in two marine environments of melt-extruded sheets of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) bioplastic as well as blends of PHBV with a non-toxic plasticiser (triethyl citrate, TEC) and composites of PHBV with wood flour. Samples were submerged for up to 35 weeks in two subtropical marine conditions: on the sandy seabed in the sublittoral benthic zone and the sandy seabed of an open air mesocosm with pumped seawater. Rates of biodegradation, lag times and times to 95 % mass loss (T95) were determined through mass loss data and Gompertz modelling. Mechanisms of biodegradation were studied through changes in molecular weight, mechanical properties and surface features. Results reveal a rapid biodegradation rate for all PHBV samples, demonstrating a range of specific biodegradation rates relative to exposed surface area of 0.03 ± 0.01 to 0.09 ± 0.04 mg.d-1.cm-2. This rapid rate of biodegradation meant that the subtle variations in biodegradation mechanisms across different sample thicknesses and additive compositions had little effect on overall lifetimes, with the T95 for most samples being around 250-350 days, regardless of site, highlighting the robust biodegradability of PHBV in seawater. It was only the PHBV-wood flour composite that showed faster biodegradation, and that was only in the exposed ocean site. The mesocosm site was otherwise shown to be a good model for the open ocean, with very comparable biodegradation rates and changes in mechanical properties over time.

Asunto(s)

Biodegradación Ambiental , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/análisis , Polihidroxialcanoatos/metabolismo , Agua de Mar/química , Poliésteres/metabolismo , Plásticos Biodegradables/metabolismo , Polihidroxibutiratos

RESUMEN

BACKGROUND: The ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output (CO) by 35% to 40% in healthy people and people with heart failure. The mechanisms underlying the effects of 3-OHB on myocardial contractility and loading conditions as well as the cardiovascular effects of its enantiomeric forms, D-3-OHB and L-3-OHB, remain undetermined. METHODS AND RESULTS: Three groups of 8 pigs each underwent a randomized, crossover study. The groups received 3-hour infusions of either D/L-3-OHB (racemic mixture), 100% L-3-OHB, 100% D-3-OHB, versus an isovolumic control. The animals were monitored with pulmonary artery catheter, left ventricle pressure-volume catheter, and arterial and coronary sinus blood samples. Myocardial biopsies were evaluated with high-resolution respirometry, coronary arteries with isometric myography, and myocardial kinetics with D-[11C]3-OHB and L-[11C]3-OHB positron emission tomography. All three 3-OHB infusions increased 3-OHB levels (P<0.001). D/L-3-OHB and L-3-OHB increased CO by 2.7 L/min (P<0.003). D-3-OHB increased CO nonsignificantly (P=0.2). Circulating 3-OHB levels correlated with CO for both enantiomers (P<0.001). The CO increase was mediated through arterial elastance (afterload) reduction, whereas contractility and preload were unchanged. Ex vivo, D- and L-3-OHB dilated coronary arteries equally. The mitochondrial respiratory capacity remained unaffected. The myocardial 3-OHB extraction increased only during the D- and D/L-3-OHB infusions. D-[11C]3-OHB showed rapid cardiac uptake and metabolism, whereas L-[11C]3-OHB demonstrated much slower pharmacokinetics. CONCLUSIONS: 3-OHB increased CO by reducing afterload. L-3-OHB exerted a stronger hemodynamic response than D-3-OHB due to higher circulating 3-OHB levels. There was a dissocitation between the myocardial metabolism and hemodynamic effects of the enantiomers, highlighting L-3-OHB as a potent cardiovascular agent with strong hemodynamic effects.

Asunto(s)

Hidroxibutiratos , Tomografía Computarizada por Rayos X , Humanos , Porcinos , Animales , Ácido 3-Hidroxibutírico/farmacología , Estudios Cruzados , Hidroxibutiratos/farmacología , Corazón , Cuerpos Cetónicos/metabolismo