Advances on the production of organic acids by yeast / 生物工程学报

Organic acids are organic compounds that can be synthesized using biological systems. They often contain one or more low molecular weight acidic groups, such as carboxyl group and sulphonic group. Organic acids are widely used in food, agriculture, medicine, bio-based materials industry and other fields. Yeast has unique advantages of biosafety, strong stress resistance, wide substrate spectrum, convenient genetic transformation, and mature large-scale culture technology. Therefore, it is appealing to produce organic acids by yeast. However, challenges such as low concentration, many by-products and low fermentation efficiency still exist. With the development of yeast metabolic engineering and synthetic biology technology, rapid progress has been made in this field recently. Here we summarize the progress of biosynthesis of 11 organic acids by yeast. These organic acids include bulk carboxylic acids and high-value organic acids that can be produced naturally or heterologously. Finally, future prospects in this field were proposed.

Ácido L-poliláctico (PLA) y na-notubos de carbono de pared múltiple (NTCPM) con potenciales aplicaciones industriales / L-polylactic acid (PLA) and multi-walled carbon nano-tubes (CNTMW) with potential industrial applications / Ácido L-polilático (PLA) e na-notubos de carbono de paredes múltiplas (NTCPM) com possíveis aplicações industriais

Resumen En términos generales, es bien conocida la cualidad que poseen algunos polímeros de cambiar sus propiedades físicas y químicas finales mediante la adición de nanopartículas a la matriz polimérica para producir un material compuesto (MC). Esta investigación está basada en la obtención de un MC a partir de ácido poliláctico (PLA) y nanotubos de carbono de pared múltiple (NTCPM), muy empleado en la industria del envasado y dispositivos biomédicos, con el fin de ampliar su perfil industrial. Se desarrollaron cuatro mezclas de PLA y NTCPM, y se empleó polietilenglicol (PEG) como plastificante. Se evaluaron sus propiedades morfológicas, térmicas, mecánicas, termo-mecánicas, espectroscópicas, ángulo de contacto y cristalográficas. Se observó que los MCs presentaron degradación térmica a temperaturas inferiores a la matriz sin NTCPM, así como un aumento en el módulo de flexión y tensión en algunas de las muestras. Así mismo, se observó que los NTCPM pueden aumentar la cristalinidad del material y que, en algunos casos, se incrementa su rigidez, actuando como un aditivo útil para aplicaciones de mayor esfuerzo mecánico que la matriz. Del efecto de agregar PEG en los MC, se determinó que los NTCPM no restringen la movilidad de las cadenas poliméricas y se da un efecto plastificante, lo que permite mayor movilidad de la zona amorfa de las cadenas de polímero, como indica la literatura consultada. Finalmente, se concluyó que a mayores contenidos de NTCPM, se generan mejores valores en el módulo de flexión, esfuerzo máximo de flexión, módulo de elongación, esfuerzo de carga máxima y esfuerzo de ruptura, entre otras propiedades evaluadas.

Abstract The quality of some polymers to change their final physical and chemical properties by adding nanoparticles to the polymer matrix to produce a composite material (MC) is well known. This research is based on obtaining a MC from polylactic acid (PLA) and multi-walled carbon nanotubes (CNTMW), widely used in the packaging industry and biomedical devices, in order to expand its industrial profile. Four mixtures of PLA and CNTMW were developed, and polyethylene glycol (PEG) was used as a plasticizer. Their morphological, thermal, mechanical, thermo-mechanical, spectroscopic, contact angle, and crystallographic properties were evaluated. It was observed that the composites showed thermal degradation at temperatures below the matrix without CNTMW, as well as an increase in the modulus of flexion and tension in some of the samples. Likewise, it was observed that the CNTMW can increase the crystallinity of the material and that, in some cases, its rigidity is increased, acting as a useful additive for applications of greater mechanical stress than the matrix. From the effect of adding PEG in the composites, the CNTMW do not restrict the mobility of the polymer chains and a plasticizing effect occurs, which allows greater mobility of the amorphous zone of the polymer chains. In general terms, it was concluded that at higher CNTMW contents, better values were generated in the flexural modulus, maximum flexural stress, elongation modulus, maximum load stress and rupture stress, among other evaluated properties.

Resumo Alguns polímeros têm a propriedade de alterar suas propriedades físicas e químicas finais, adicionando nanopartículas à matriz polimérica para produzir um composto. Esta pesquisa baseia-se na obtenção de composto partir de ácido polilático (PLA) e nanotubos de carbono de paredes múltiplas (MWCNT), amplamente utilizado na indústria de embalagens e dispositivos biomédicos, a fim de expandir seu perfil industrial. Foram desenvolvidas quatro misturas de PLA e MWCNT e o polietilenoglicol (PEG) foi usado como plastificante. Foram avaliadas suas propriedades morfológicas, térmicas, mecânicas, termo-mecânicas, espectroscópicas, ângulo de contato e cristalográficas. Observou-se que os compostos apresentaram degradação térmica em temperaturas abaixo da matriz sem MWCNT, além de aumento no módulo de flexão e tensão em algumas das amostras. Da mesma forma, observou-se que o MWCNT pode aumentar a cristalinidade do material e que, em alguns casos, sua rigidez é aumentada, atuando como um aditivo útil para aplicações de maior tensão mecânica que a matriz. A partir do efeito da adição de PEG nos compostos, determinou-se que o MWCNT não restringe a mobilidade das cadeias poliméricas e ocorre um efeito plastificante, que permite maior mobilidade da zona amorfa das cadeias poliméricas. Em termos gerais, concluiu-se que, com maiores teores de MWCNT, melhores valores foram gerados no módulo de flexão, tensão máxima de flexão, módulo de alongamento, tensão de carga máxima e tensão de ruptura, entre outras propriedades avaliadas.

Twelve-month comparative analysis of clinical outcomes using biodegradable polymer–coated everolimus-eluting stents versus durable polymer–coated everolimus-eluting stents in all-comer patients

Aim The purpose of the present study was to examine whether clinical differences exist between the biodegradable polymer (BDP)–coated Tetrilimus everolimus-eluting stent (EES) and the durable polymer (DP)–coated Xience EES by comparing the major adverse cardiac event (MACE) rate at 12 months in all-comer patients. Methods This study was designed as a multicentre, observational, retrospective, investigator-initiated study between January 2016 and October 2016. Two hundred thirteen patients who underwent percutaneous coronary intervention (PCI) with the BDP-EES were compared with 204 patients who underwent PCI with the DP-EES, irrespective of lesion complexity, comorbidities and acute presentation. The primary end point was MACE defined as a composite of cardiac death, myocardial infarction and target lesion revascularization. Results Baseline clinical and lesion characteristics of both the groups were similar, although the BDP-EES group had a significantly higher number of patients with diabetes mellitus (39.9% vs. 30.4%; p = 0.042) and type C lesion (67.4% vs. 48.1%; p < 0.001) than the DP-EES group. The 12-month MACE rate was 4.2% for the BDP-EES group versus 4.9% for the DP-EES group (p = 0.740). Mortality was lower in the BDP-EES group than in the DP-EES group (0.9% vs. 2.0%; p = 0.441). Conclusion The present comparative analysis shows that the BDP-coated Tetrilimus EES was as safe and effective as the DP-coated Xience EES during the 12-month follow-up period despite complex lesion characteristics.

Effect of nonionic surfactants in release media on accelerated in-vitro release profile of sirolimus eluting stents with biodegradable polymeric coating / 药物分析学报

It is a well-known fact that sirolimus (SRL) undergoes degradation process via hydrolysis in aqueous media, leading to incorrect assessment of drug amount and thus release characteristics of formulations. The main objective of the present study was to evaluate the effect of nonionic surfactants in media on in-vitro release profiles for sirolimus eluting stents (SES) coated with biodegradable polymeric matrix. Phosphate buffer and acetate buffer incorporating nonionic surfactants with varying concentrations were examined for adequate solubility and stability (by RP-HPLC). Good sink condition was achieved in phosphate buffer (at pH 4.0) with 1.0%Tween 20, 1.0%Brij 35%and 0.5%Brij 58. Hydrodynamic size (by DLS) and the micelle-water partition coefficient (P) with standard free energy of solubilization (?Gs°) of drug were evaluated to get some understanding about the solubilization phenomena. About 80%of drug release during the period of 48 h was achieved in optimized drug release media which was 1.0%Tween 20 in phosphate buffer pH 4.0. The obtained accelerated SRL release profile in optimized medium cor-related well with the real time in-vitro release in phosphate buffer (pH 7.4). Surface morphology changes (by SEM), changes in gravimetric weights and molecular weight change (by GPC) were examined before and after drug release to understand the drug release mechanism which explains that the polymer did not undergo degradation during the drug release.

Separation of polyhydroxyalkanoates-producing bacterial strains using PHA synthase gene and their evaluation for PHA deposition

In this study, a variety of samples were screened for the presence of PHA synthase gene. Results showed that 16 out of 102 isolated were positive for PHA respective genes. The highest prevalence was observed in Pseudomonas aeruginosa. The capability of PHA production was also shown by growing these strains on the defined medium and subsequent analysis using intracellular granules staining and Fourier transform infrared spectroscopy (FT-IR). The microscopic analysis showed that the positive strains accumulated PHA in the cell. The FT-IR analysis showed the presence of PHA peaks in the dried cells as well as in extraction product. P aeruginosa strain P7 showed higher concentration of PHA compared to the others as demonstrated by the highest respective peaks in FT-IR.

Biodegradation of blend films PVA/PVC, PVA/PCL in soil and soil with landfill leachate

This study investigated the biodegradation of blends films of poly(vinyl alcohol)/poly(vinyl chloride) (PVA/PVC) and poly(vinyl alcohol)/poly(caprolactone) (PVA/PCL) blends films prepared with dimethylformamide under a variety of conditions by respirometry, spectrophotometry (FTIR), scanning electron microscopy (SEM), and contact angle. The films were buried in the garden soil and in the soil mixed with the landfill leachate for 120 days at 28ºC. Significant levels of biodegradation were achieved in fairly short incubation times in the soil. The results indicated that PVA was the most biodegradable film in the soil and in the soil with the leachate.

Degranulação de neutrófilos ex-vivo por ação do polímero de amido de mandioca / Degranulation of neutrophils ex-vivo by the action of polymer cassava's starch

Os neutrófilos têm papel essencial na defesa do hospedeiro contra infecções. Quando estimulados respondem com aumento do consumo de oxigênio denominado "explosão respiratória", que gera grande quantidade de ânion superóxido e peróxido de hidrogênio, os quais desempenham importante função antimicrobiana, e subsequente degranulação de neutrófilos. Os polímeros são materiais amplamente utilizados em medicina veterinária. Vários estudos vêm sendo realizados na busca de novos polímeros e sua biocompatibilidade para uso médico. Um polímero de amido de mandioca (Manihot esculenta crantz) foi produzido no Laboratório de Química da Universidade Paranaense - Campus Umuarama, com objetivo de analisar a possibilidade de ocorrer degranulação de neutrófilos quando expostos ao amido. Os resultados iniciais mostraram uma ação bioinerte do polímero de amido de mandioca em diferentes concentrações quando colocado junto com neutrófilos. Dessa forma, este material tem aplicação potencial em biomateriais.

The neutrophils play an essential role in host defenses against infection. When stimulated it responds with an increase of consumption of oxygen known as 'respiratory burst', so generating a great quantity of superoxide anion and hydrogen peroxide, which play an important function antimicrobial, and subsequent degranulation of neutrophils. Polymers are materials largely used in veterinary medicine. Several studies have been carried out to find new polymers and their biocompatibility to medical use. One polymer of cassava's starch (Manihot esculenta crantz) was developed at the Paranaense University's Laboratory of Chemistry - Campus Umuarama City, aiming to analyze the neutrophils degranulation after exposition to this starch. The early results showed a bioinert action of the polymer of cassava's starch on different concentrations when it was in contact with neutrophils. Thus, this material is potentially indicated as biomaterial.

Método para la bbtención de lacturo de alta purza a partir de la depolimerizacción de poli(ácido láctico) / A methd to obtaiin high purity lactide by the depolymerization of poly(lactic acid)

Se sintetizó lacturo por medio de la policondensación de ácido láctico a 180 °C y 5,3 kPa durante 120 minutos, y una posterior depolimerización a 220 °C y 5,3 kPa durante 40 minutos usando cloruro de estaño dihidratado como catalizador. Se utilizó un sistema novedoso de reacción y separación, recolectando el lacturo sólido y dejando en fase vapor el agua y el ácido láctico, garantizando así una alta pureza del producto y evitando reacciones reversibles.

Lactide was synthesized by polycondenzation of lactic acid at 180 °C and a 5.3 kPa for 120 minutes, and a subsequent depolymerization at 220 °C and 5.3 kPa for 40 minutes using dehydrated tin chloride as catalyst. A new reaction separation system was used, collecting the lactide in solid form and leaving water and lactic acid as vapor. This guarantees a high purity product and avoids any reversible reaction of lactide.

Development of biodegradable polymers as drug carriers / 国际生物医学工程杂志

Biodegradable polymers as drug delivery systems have attracted investigators. They degrade in biological fluids to produce biocompatible and nontoxic products, which could be removed from the body by normal physiological pathways without extra surgical removal. In this article, literatures on biodegradable polymers mainly served as matrix in controlled release systems are analyzed and reviewed.

Osteogenic Differentiation of Human Mesenchymal Stem Cells: Effects of the compositions of biodegradable polymers and the initial cell-seeding density / 대한정형외과학회잡지

PURPOSE: To investigate the effects of initial cell-seeding density and the compositions of biodegradable polymer scaffolds on the osteogenic differentiation of human mesenchymal stem cells. MATERIALS AND METHODS: Human mesenchymal stem cells (hBMSCs) were cultured three-dimensionally onto biodegradable polymers with three different compositions (65/35 PLGA, 85/15 PLGA, PLLA), and osteogenic differentiation was studied by; histology, immuno-histochemistry, and transmision/scanning electron microscopy. RESULTS: In terms of the amount of extracellular matrix (ECM) produced, the 65/35 PLGA (23% of the whole volume) was found to produce more ECM than 85/15 PLGA (21%) and PLLA (13%). Osteoblastic differentiation of hBMSCs was induced in all scaffolds examined and the deposition of ECM with calcifications started after 2 weeks of culture. The amount of calcium deposited on the 65/35 PLGA dramatically increased at 4 weeks. On comparing low cell-seeding density with the high cell-seeding density on 65/35 PLGA, calcium deposits reached similar levels at 6 weeks. CONCLUSION: Three-dimensional culture of hBMSCs on biodegrable polymer scaffolds induced bone formation, which was dependent on the compositions of the scaffolds and the initial cell-seeding density.

Biodegradable poly (lactic acid) microspheres for drug delivery systems

In connection with aim of maximizing the bio-availability of conventional drugs with minimum side-effects, new drug delivery systems (DDS) continue to attracted much attention. The controlled or sustained release of drugs represents one such approach, and in this regard report upon a study of DDS using biodegradable polymers which include poly (lactic acid) (PLA), poly (glycolic acid), and their copolymers (PLGA). Much attention is being paid to the controlled release of bio-active agents from microcapsules and microspheres made of biodegradable polymers, such as lactic acid homopolymers, as well as copolymers of glycolic acid. (11-21) Microcapsules or microspheres are injectable and able to provide pre-programmed durations of action, offering several advantages over the conventional dosage forms. This article reviews the results of a work program conducted in collaboration with a medical doctor upon DDS using biodegradable microspheres, such as PLA and PLGA.