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Modeling and optimization of lipase-catalyzed production of succinic acid ester using central composite design analysis

Abdul Rahman MB, Jarmi NI, Chaibakhsh N, Basri M

J Ind Microbiol Biotechnol, 2011 Jan;38(1):229-34.
PMID: 20803246 DOI: 10.1007/s10295-010-0817-3

Esterification of succinic acid with oleyl alcohol catalyzed by immobilized Candida antarctica lipase B (Novozym 435) was investigated in this study. Response surface methodology (RSM) based on a five-level, four-variable central composite design (CCD) was used to model and analyze the reaction. A total of 21 experiments representing different combinations of the four parameters including temperature (35-65°C), time (30-450 min), enzyme amount (20-400 mg), and alcohol:acid molar ratio (1:1-8:1) were generated. A partial cubic equation could accurately model the response surface with a R(2) of 0.9853. The effect and interactions of the variables on the ester synthesis were also studied. Temperature was found to be the most significant parameter that influenced the succinate ester synthesis. At the optimal conditions of 41.1°C, 272.8 min, 20 mg enzyme amount and 7.8:1 alcohol:acid molar ratio, the esterification percentage was 85.0%. The model can present a rapid means for estimating the conversion yield of succinate ester within the selected ranges.

Matched MeSH terms: Succinates/metabolism*
Fulltext Reconstruction options following wide excision of basal cell carcinoma of the face

Khoo, Hau Chun, Enda Gerard, Kelly, Mohd Ali Mat Zain, Farrah-Hani Imran

Journal of Surgical Academia, 2015;5(2):70-74.
MyJurnal

Basal cell carcinoma is the commonest skin malignancy diagnosed in Malaysia. Surgery is the recommended treatment of choice with the lowest failure rate provided a clear margin is obtained. However, the defect may be too large to be repaired primarily. Formal reconstruction using grafts and flaps should be done to achieve the optimal aim of maintaining the integrity, function and cosmetic patient outcome. Three reconstructive methods are described in this series to restore the facial defect following the wide local excision. The procedures described were peri-alar crescentic advancement flap, nasolabial rotational flap and full thickness skin graft using supraclavicular skin. This series highlights the usage of the procedures based on solid foundation and principles, without compromising the desired outcomes for the patient.

Matched MeSH terms: Succinates
Microscopic study of AOT and CTAB anionic-rich catanionic phase

Chun YT, Kok SK, Shahidan Radiman, Irman Abdul Rahman, Nur Farhana Amari

Sains Malaysiana, 2014;43:623-628.

Catanionic system using anionic sodium bis-(2ethylhexyl)sulfosuccinate (Am) and cationic cetyltrimethylammonium bromide (cTAB) is studied. The system is prepared by addition of CTAB solution to a prepared AOT solution until slight anionic-rich catanionic phase is produced. Catanionic system consists of the mixture of different types of surfactants and counterion due to electrostatic interaction between the oppositely charged surfactant. Both of these products affect the in surface activity of the surfactant. Hydrodynamic diameters decrease and clearer solution were seen with the increase of CTAB concentration in solution mixture. As a result, mixed surfactant with larger hydrophobic region and the presence of counterion will induce smaller vesicle to form in catanionic system.

Matched MeSH terms: Succinates
Comparative pharmacokinetic study of oral and rectal formulations of artesunic acid in healthy volunteers

Navaratnam V, Mansor SM, Mordi MN, Akbar A, Abdullah MN

Eur J Clin Pharmacol, 1998 Jul;54(5):411-4.
PMID: 9754985

OBJECTIVE: A single cross-over, comparative pharmacokinetic study of oral and rectal formulations of 200 mg artesunic acid in 12 healthy Malaysian volunteers is reported.
METHODS: Plasma concentrations of artesunic acid and dihydroartemisinin were determined simultaneously by HPLC with electrochemical detection. The test drug was well tolerated and no undesirable adverse effects were observed.
RESULTS: Comparison of pharmacokinetic parameters of artesunic acid after oral and rectal administration showed statistically significant differences in t(max) and AUC, with no changes for Cmax and t1/2. As for dihydroartemisinin, differences were observed for t(max) and Cmax but not for AUC.
CONCLUSION: There appear to be pharmacokinetic differences between oral and rectal modes of administration. The significance of these findings should be explored in malaria patients before appropriate therapeutic regimens are devised.

Matched MeSH terms: Succinates/administration & dosage; Succinates/blood; Succinates/pharmacokinetics*
Biotechnological route for sustainable succinate production utilizing oil palm frond and kenaf as potential carbon sources

Luthfi AAI, Manaf SFA, Illias RM, Harun S, Mohammad AW, Jahim JM

Appl Microbiol Biotechnol, 2017 Apr;101(8):3055-3075.
PMID: 28280869 DOI: 10.1007/s00253-017-8210-z

Due to the world's dwindling energy supplies, greater thrust has been placed on the utilization of renewable resources for global succinate production. Exploration of such biotechnological route could be seen as an act of counterbalance to the continued fossil fuel dominance. Malaysia being a tropical country stands out among many other nations for its plenty of resources in the form of lignocellulosic biomass. To date, oil palm frond (OPF) contributes to the largest fraction of agricultural residues in Malaysia, while kenaf, a newly introduced fiber crop with relatively high growth rate, holds great potential for developing sustainable succinate production, apart from OPF. Utilization of non-food, inexhaustible, and low-cost derived biomass in the form of OPF and kenaf for bio-based succinate production remains largely untapped. Owing to the richness of carbohydrates in OPF and kenaf, bio-succinate commercialization using these sources appears as an attractive proposition for future sustainable developments. The aim of this paper was to review some research efforts in developing a biorefinery system based on OPF and kenaf as processing inputs. It presents the importance of the current progress in bio-succinate commercialization, in addition to describing the potential use of different succinate production hosts and various pretreatments-saccharifications under development for OPF and kenaf. Evaluations on the feasibility of OPF and kenaf as fermentation substrates are also discussed.

Matched MeSH terms: Succinates/economics; Succinates/metabolism*
Co-encapsulation of gemcitabine and tocotrienols in nanovesicles enhanced efficacy in pancreatic cancer

Maniam G, Mai CW, Zulkefeli M, Fu JY

Nanomedicine (Lond), 2021 02;16(5):373-389.
PMID: 33543651 DOI: 10.2217/nnm-2020-0374

Aim: To synthesize niosomes co-encapsulating gemcitabine (GEM) and tocotrienols, and physicochemically characterize and evaluate the antipancreatic effects of the nanoformulation on Panc 10.05, SW 1990, AsPC-1 and BxPC-3 cells. Materials & methods: Niosomes-entrapping GEM and tocotrienols composed of Span 60, cholesterol and D-α-tocopheryl polyethylene glycol 1000 succinate were produced by Handjani-Vila and film hydration methods. Results: The film hydration produced vesicles measuring 161.9 ± 0.5 nm, approximately 50% smaller in size than Handjani-Vila method, with maximum entrapment efficiencies of 20.07 ± 0.22% for GEM and 34.52 ± 0.10% for tocotrienols. In Panc 10.05 cells, GEM's antiproliferative effect was enhanced 2.78-fold in combination with tocotrienols. Niosomes produced a significant ninefold enhancement in cytotoxicity of the combination, supported by significantly higher cellular uptake of GEM in the cells. Conclusion: This study is a proof of concept on the synthesis of dual-drug niosomes and their efficacy on pancreatic cancer cells in vitro.

Matched MeSH terms: Succinates
Enhanced dispersion of multiwall carbon nanotubes in natural rubber latex nanocomposites by surfactants bearing phenyl groups

Mohamed A, Anas AK, Bakar SA, Ardyani T, Zin WM, Ibrahim S, et al.

J Colloid Interface Sci, 2015 Oct 1;455:179-87.
PMID: 26070188 DOI: 10.1016/j.jcis.2015.05.054

Here is presented a systematic study of the dispersibility of multiwall carbon nanotubes (MWCNTs) in natural rubber latex (NR-latex) assisted by a series of single-, double-, and triple-sulfosuccinate anionic surfactants containing phenyl ring moieties. Optical polarising microscopy, field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and Raman spectroscopy have been performed to obtain the dispersion-level profiles of the MWCNTs in the nanocomposites. Interestingly, a triple-chain, phenyl-containing surfactant, namely sodium 1,5-dioxo-1,5-bis(3-phenylpropoxy)-3-((3-phenylpropoxy)carbonyl) pentane-2-sulfonate (TCPh), has a greater capacity the stabilisation of MWCNTs than a commercially available single-chain sodium dodecylbenzenesulfonate (SDBS) surfactant. TCPh provides significant enhancements in the electrical conductivity of nanocomposites, up to ∼10(-2) S cm(-1), as measured by a four-point probe instrument. These results have allowed compilation of a road map for the design of surfactant architectures capable of providing the homogeneous dispersion of MWCNTs required for the next generation of polymer-carbon-nanotube materials, specifically those used in aerospace technology.

Matched MeSH terms: Succinates/chemistry*
In silico deletion of PtsG gene in Escherichia coli genome-scale model predicts increased succinate production from glycerol

Mienda BS, Shamsir MS

J Biomol Struct Dyn, 2015;33(11):2380-9.
PMID: 25921851 DOI: 10.1080/07391102.2015.1036461

Systems metabolic engineering and in silico analyses are necessary to study gene knockout candidate for enhanced succinic acid production by Escherichia coli. Metabolically engineered E. coli has been reported to produce succinate from glucose and glycerol. However, investigation on in silico deletion of ptsG/b1101 gene in E. coli from glycerol using minimization of metabolic adjustment algorithm with the OptFlux software platform has not yet been elucidated. Herein we report what is to our knowledge the first direct predicted increase in succinate production following in silico deletion of the ptsG gene in E. coli GEM from glycerol with the OptFlux software platform. The result indicates that the deletion of this gene in E. coli GEM predicts increased succinate production that is 20% higher than the wild-type control model. Hence, the mutant model maintained a growth rate that is 77% of the wild-type parent model. It was established that knocking out of the ptsG/b1101 gene in E. coli using glucose as substrate enhanced succinate production, but the exact mechanism of this effect is still obscure. This study informs other studies that the deletion of ptsG/b1101 gene in E. coli GEM predicted increased succinate production, enabling a model-driven experimental inquiry and/or novel biological discovery on the underground metabolic role of this gene in E. coli central metabolism in relation to increasing succinate production when glycerol is the substrate.

Matched MeSH terms: Succinates
Fulltext Morphological, Structural, Thermal, Permeability, and Antimicrobial Activity of PBS and PBS/TPS Films Incorporated with Biomaster-Silver for Food Packaging Application

Aziman N, Kian LK, Jawaid M, Sanny M, Alamery S

Polymers (Basel), 2021 Jan 27;13(3).
PMID: 33513665 DOI: 10.3390/polym13030391

The development of antimicrobial film for food packaging application had become the focus for researchers and scientists. This research aims to study the characteristics and antimicrobial activity of novel biofilms made of poly (butylene succinate) (PBS) and tapioca starch (TPS) added with 1.5% or 3% of Biomaster-silver (BM) particle. In morphological examination, the incorporation of 3% BM particle was considerably good in forming well-structured PBS film. Meanwhile, the functional groups analysis revealed the 3% BM particle was effectively interacted with PBS molecular chains. The flame retard behavior of BM metal particle also helped in enhancing the thermal stability for pure PBS and PBS/TPS films. The nucleating effect of BM particles had improved the films crystallinity. Small pore size features with high barrier property for gas permeability was obtained for BM filled PBS/TPS films. From antimicrobial analysis, the BM particles possessed antimicrobial activity against three bacteria Staphylococcus aureus, Escherichia coli, and Salmonella Typhimurium in which PBS/TPS 3% BM film exhibited strong antimicrobial activity against all tested bacteria, however, PBS/TPS 1.5% BM film exhibited strong antimicrobial activity against E. coli only. Hence, the incorporation of BM into PBS/TPS film could be a sustainable way for developing packaging films to preserve food products.

Matched MeSH terms: Succinates
Fulltext Stability of β-carotene in carrot powder and sugar confection as affected by resistant maltodextrin and octenyl succinate anhydride (OSA) starches

Shaaruddin S, Mahmood Z, Ismail H, Mohd Ghazali H, Hamzah MY, Muhammad K

J Food Sci Technol, 2019 Jul;56(7):3461-3470.
PMID: 31274914 DOI: 10.1007/s13197-019-03832-4

Encapsulation has been used to overcome the problem of instability of functional pigments such as carotenoids from natural sources. In this study, β-carotene in carrot juice was spray dried with four different wall materials namely maltodextrin, resistant maltodextrin, octenyl succinate anhydride (OSA) starches Capsul (CAP) and HICAP-100 (HCAP). The objective of this research was to study the effects of various wall materials on physicochemical properties and stability of β-carotene powders along with its stability after incorporation into sugar confection. All four wall materials produced powders of acceptable quality in terms of moisture content, water activity, hygroscopicity, solubility as well as onset glass transition temperature. OSA starches exhibited better pigment retention post spray drying where juices encapsulated with HCAP showed the highest retention (94.34%). This was also represented in more orange Hue values (H°) in powders produced with CAP (53.93) and HCAP (53.33). Powders produced with HCAP also showed the longest half-life after storage at 4 °C, 25 °C, and 40 °C, as well as under exposure to light. Similarly, carrot powders produced with OSA starches also exhibited better β-carotene retention after production of hard candy confection. Though candies with HCAP encapsulated juices showed the highest β-carotene retention post candy processing, candies with CAP encapsulated carrot juices exhibited better long term stability after storage at 25 °C and 40 °C as well as under exposure to light.

Matched MeSH terms: Succinates
1H NMR-Based Metabolic Profiles Delineate the Anticancer Effect of Vitamin C and Oxaliplatin on Hepatocellular Carcinoma Cells

Lin C, Dong J, Wei Z, Cheng KK, Li J, You S, et al.

J Proteome Res, 2020 02 07;19(2):781-793.
PMID: 31916767 DOI: 10.1021/acs.jproteome.9b00635

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Because of its high recurrence rate and heterogeneity, effective treatment for advanced stage of HCC is currently lacking. There are accumulating evidences showing the therapeutic potential of pharmacologic vitamin C (VC) on HCC. However, the metabolic basis underlying the anticancer property of VC remains to be elucidated. In this study, we used a high-resolution proton nuclear magnetic resonance-based metabolomics technique to assess the global metabolic changes in HCC cells following VC treatment. In addition, the HCC cells were also treated with oxaliplatin (OXA) to explore the potential synergistic effect induced by the combined VC and OXA treatment. The current metabolomics data suggested different mechanisms of OXA and VC in modulating cell growth and metabolism. In general, VC treatment led to inhibition of energy metabolism via NAD+ depletion and amino acid deprivation. On the other hand, OXA caused significant perturbation in phospholipid biosynthesis and phosphatidylcholine biosynthesis pathways. The current results highlighted glutathione metabolism, and pathways related to succinate and choline may play central roles in conferring the combined effect between OXA and VC. Taken together, this study provided metabolic evidence of VC and OXA in treating HCC and may contribute toward the potential application of combined VC and OXA as complementary HCC therapies.

Matched MeSH terms: Succinates
Fulltext Long-term xeno-free culture of human pluripotent stem cells on hydrogels with optimal elasticity

Higuchi A, Kao SH, Ling QD, Chen YM, Li HF, Alarfaj AA, et al.

Sci Rep, 2015 Dec 14;5:18136.
PMID: 26656754 DOI: 10.1038/srep18136

The tentative clinical application of human pluripotent stem cells (hPSCs), such as human embryonic stem cells and human induced pluripotent stem cells, is restricted by the possibility of xenogenic contamination resulting from the use of mouse embryonic fibroblasts (MEFs) as a feeder layer. Therefore, we investigated hPSC cultures on biomaterials with different elasticities that were grafted with different nanosegments. We prepared dishes coated with polyvinylalcohol-co-itaconic acid hydrogels grafted with an oligopeptide derived from vitronectin (KGGPQVTRGDVFTMP) with elasticities ranging from 10.3 to 30.4 kPa storage moduli by controlling the crosslinking time. The hPSCs cultured on the stiffest substrates (30.4 kPa) tended to differentiate after five days of culture, whereas the hPSCs cultured on the optimal elastic substrates (25 kPa) maintained their pluripotency for over 20 passages under xeno-free conditions. These results indicate that cell culture matrices with optimal elasticity can maintain the pluripotency of hPSCs in culture.

Matched MeSH terms: Succinates/chemistry
Fulltext Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluation

Mudassir J, Darwis Y, Muhamad S, Khan AA

Int J Nanomedicine, 2019;14:4895-4909.
PMID: 31456636 DOI: 10.2147/IJN.S199507

Introduction: Insulin is given by injection, because when administered orally, it would be destroyed by enzymes in the digestive system, hence only about 0.1% reaches blood circulation. The purpose of the present study was to use pH sensitive polyelectrolyte methyl methacrylate (MMA)/itaconic acid (IA) nanogels as carriers in an attempt to improve absorption of insulin administered orally. Methods: Insulin (Ins) was incorporated into the MMA/IA nanogels (NGs) using the polyelectrolyte complexation (PEC) method to form Ins/NGs-PEC. Several parameters, including Ins:NGs ratio, pH, incubation time and stirring rate were optimized during preparation of InsNGs-PEC. The prepared formulations were characterized in terms of particle size (PS), polydispersity index (PdI), zeta potential (ZP) and percent entrapment efficiency (% EE). Results: The optimized InF12 nanogels had a PS, PdI, ZP and %EE of 190.43 nm, 0.186, -16.70 mV and 85.20%, respectively. The InF12 nanogels were lyophilized in the presence of different concentrations of trehalose as cryoprotectant. The lyophilized InF12 containing 2%w/v trahalose (InF12-Tre2 nanogels) was chosen as final formulation which had a PS, PdI, ZP and %EE of 430.50 nm, 0.588, -16.50 mv and 82.10, respectively. The in vitro release of insulin from InF12-Tre2 nanogels in the SGF and SIF were 28.71% and 96.53%, respectively. The stability study conducted at 5±3°C for 3 months showed that lnF12-Tre2 nanogels were stable. The SDS-PAGE assay indicated that the primary structure of insulin in the lnF12-Tre2 nanogels was intact. The in-vivo study in the diabetic rats following oral administration of InF12-Tre2 nanogels at a dose of 100 IU/kg body weight reduced blood glucose level significantly to 51.10% after 6 hours compared to the control groups. Conclusions: The pH sensitive MMA/IA nanogels are potential carriers for oral delivery of insulin as they enhanced the absorption of the drug.

Matched MeSH terms: Succinates
Fulltext Morphology, Structural, Thermal, and Tensile Properties of Bamboo Microcrystalline Cellulose/Poly(Lactic Acid)/Poly(Butylene Succinate) Composites

Rasheed M, Jawaid M, Parveez B, Hussain Bhat A, Alamery S

Polymers (Basel), 2021 Feb 01;13(3).
PMID: 33535490 DOI: 10.3390/polym13030465

The present study aims to develop a biodegradable polymer blend that is environmentally friendly and has comparable tensile and thermal properties with synthetic plastics. In this work, microcrystalline cellulose (MCC) extracted from bamboo-chips-reinforced poly (lactic acid) (PLA) and poly (butylene succinate) (PBS) blend composites were fabricated by melt-mixing at 180 °C and then hot pressing at 180 °C. PBS and MCC (0.5, 1, 1.5 wt%) were added to improve the brittle nature of PLA. Field emission scanning electron microscopy (FESEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscope (FTIR), thermogravimetric analysis (TGA), differential thermogravimetry (DTG), differential scanning calorimetry (DSC)), and universal testing machine were used to analyze morphology, crystallinity, physiochemical, thermal, and tensile properties, respectively. The thermal stability of the PLA-PBS blends enhanced on addition of MCC up to 1wt % due to their uniform dispersion in the polymer matrix. Tensile properties declined on addition of PBS and increased with MCC above (0.5 wt%) however except elongation at break increased on addition of PBS then decreased insignificantly on addition of MCC. Thus, PBS and MCC addition in PLA matrix decreases the brittleness, making it a potential contender that could be considered to replace plastics that are used for food packaging.

Matched MeSH terms: Succinates
Is 6% hydroxyethyl starch 130/0.4 safe in coronary artery bypass graft surgery?

Ooi JS, Ramzisham AR, Zamrin MD

Asian Cardiovasc Thorac Ann, 2009 Aug;17(4):368-72.
PMID: 19713332 DOI: 10.1177/0218492309338101

The aim of this study was to compare 6% hydroxyethyl starch 130/0.4 with 4% succinylated gelatin for priming the cardiopulmonary bypass circuit and as volume replacement in patients undergoing coronary artery bypass, in terms of postoperative bleeding, blood transfusion requirements, renal function, and outcome after surgery. Forty-five patients received 6% hydroxyethyl starch 130/0.4 (Voluven) and another 45 were given 4% succinylated gelatin (Gelofusine) as the priming solution for the cardiopulmonary bypass circuit as well as for volume replacement. Postoperative bleeding was quantified from the hourly chest drainage in the first 4 h and at 24 h postoperatively. The baseline characteristics of both groups were similar. In the hydroxyethyl starch group, the total amount of colloid used was 1.9 +/- 1.0 L, while the gelatin group had 2.0 +/- 0.7 L. There was no significant difference in hourly chest drainage between groups. Blood transfusion requirements, estimated glomerular filtration rate, extubation time, intensive care unit and hospital stay were similar in both groups. It was concluded that 6% hydroxyethyl starch 130/0.4 is a safe alternative colloid for priming the cardiopulmonary bypass circuit and volume replacement in patients undergoing coronary artery bypass surgery.

Matched MeSH terms: Succinates/adverse effects*

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