Metabolism In Human Body Research Articles

Effect of Astaxanthin Supplementation on Antioxidant Capacity, Blood Lactate and Blood Uric Acid Metabolism in Human Recovery Stage After Exercise

To study the effects of astaxanthin supplementation on serum antioxidant capacity, blood lactic acid and blood uric acid metabolism of human body in the 1h recovery period after acute high-intensity exercise. Sixteen male students grade 2016 from Physical Education Institution (age: 19.13±2.52, height: 179±4.21cm and weight 68.23±7.81kg) were randomly divided into two groups: group A (experimental) and B (control). Group A was given astaxanthin for 28 days at a moderate dose (12 mg/d) and placebo for 28 days at group B. 4 weeks later, all subjects underwent exercise on power bike. The antioxidant capacity and blood uric acid and the content of blood lactic acid was assayed using anti-oxidation Kit (FORD), blood lactic acid Kit (LACTIC ACID), blood uric acid Kit (URIC ACID). Results: 1) One hour after exercise, the antioxidant capacity in both A and B obviously increased without exception and the value of group A was obviously higher than B. The blood lactic acid in both groups dramatically declined and the value of group A was obviously lower than B. The blood uric acid rised in both groups and the value of A was obviously lower than B. Conclusions: Pre-supplement of astaxanthin can accelerate the recovery of antioxidant capacity, accelerate the clearance of blood lactate and delay the increase of blood uric acid in the body within 1 hour after exercise.

Klotho protein function among patients with type 1 diabetes.

The fibroblast growth factor 23 (FGF23) and Klotho system play a very important role in the regulation of the human body metabolism. On the one hand, they promote longevity, and on the other hand they promote insulin resistance. Nowadays, accelerated aging in diabetes as the main consequence of chronic complications of the disease is postulated. Signalling pathways induced by insulin, insulin-like growth factor (IGF-1), and their homologues play an important role in controlling the aging process. Because FGF23/Klotho system affects glucose metabolism and gene expression of antioxidant enzymes, changes in its concentration may be a marker of chronic complications of diabetes or a treatment option. Despite huge improvements in the treatment of diabetes, its chronic complications remain an important clinical problem. An interesting issue is the relationship between the concentration of FGF23/Klotho and management of the disease, duration, insulin resistance, and development of complications in type 1 diabetes.

Useful Influence of Ear & Body Acupuncture Treatment on the Significant Reduction of Body Weight of Obesity and its Relationship with Oxidant-Antioxidant System

333 Acupuncture has been used in treating obesity even before 1975. Effect mechanism and beneficial effects of acupuncture treatment are unclear. Reactive oxygen species (ROS) are harmful by-products of human body metabolism. The oxidative effects of ROS are neutralized by the antioxidant capacity. Thiols are substantial antioxidant agents and found in cysteine amino acid. Cysteine residues form disulfide bridges, predictor of oxidant stress. Thiol-disulfide homeostasis is an important parameter associated with several disorders such as cardiac, endocrine, neurologic diseases. To date, the effect of acupuncture on oxidative stress and thiol–disulfide homeostasis in obese individuals has not yet been examined. Therefore, in this study, we aimed to investigate the effect of acupuncture for weight control on dynamic thiol–disulfide homeostasis. A total of 101 subjects who were being treated for weight control at our center (89 women and 12 men, body mass index (BMI) ≥22.48) were randomly enrolled in this study, and treated with ear & body acupuncture. Body acupuncture is given manually. Ear acupuncture is given with a needle embedded within adhesive tape through performing acupressure by the patients three times per day. We measured the levels of thiol, any organic compound containing –SH group. Reduced thiol was represented with native thiol (-SH). Oxidized thiol (-S-S) was represented by disulfide. Total thiol was composed of sum of the native thiol and disulfide levels. We analyzed the differences between baseline BMI, blood native thiol, total thiol, and disulfide levels, and those after 10 weeks of acupuncture treatment. After acupuncture treatment, significant body weight and BMI reductions were observed. Mean body weight decreased significantly from 78.66±12.66 kg before treatment to 74.46±11.29 kg after treatment (p<0.001) and mean BMI decreased from 29.54±3.99 kg/m2 before treatment to 27.98±3.68 kg/m2 after treatment (p<0.001). Mean native thiol and total thiol levels increased significantly after acupuncture compared to before acupuncture. Disulfide levels insignificantly decreased. This is the first study to demonstrate that the beneficial effects of acupuncture in treating obesity are associated with improvements in thiol–disulfide homeostasis, an imbalance in which is associated with oxidative stress. Additional studies are warranted to investigate the mechanism or signaling pathways involved in the effect of acupuncture on obesity.

Therapeutic tactics with violations of the menstrual cycle caused by ovulative dysfunction

Purpose: presentation of modern data on the pathogenesis of menstrual cycle disorders (NMCs) associated with ovulatory dysfunction, and the effectiveness of their treatment with medication.Basic provisions. It is shown that NMC is the result of violations of the cyclic production of gonadotropic and sex hormones. Among the hormonal drugs for the treatment of NMCs, combined estrogen-progestational oral contraceptives (COCs), especially those with drospirenone (DRSP), are advantageous. The introduction of calcium levomefolate - biologically active form of folatein the composition of COCs containing 30 μg of ethinylestradiol and DRSP has a potentiating effect associated with their noncontraceptive effects due to antiandrogenic and antimineralocorticoid activity. It was shown that calcium levomefolate, which participates in human body metabolism, as a component of COC, has a protective effect on the cardiovascular system (due to a decrease in the level of homocysteinemia) in the syndrome of polycystic ovaries, contributes to reducing obesity.Conclusion. The combination of 30EE/DRSP promotes the normalization of the menstrual cycle and has non-contraceptive effects associated with antiandrogenic and antimineralcorticoid action, and fortification with calcium levomefolate also has a positive effect on the hormonal profile and lipid metabolism, has a protective effect on cardiovascular diseases in women with the metabolic syndrome in polycystic ovaries, contributes to the normalization of weight.

Integrated Bio/Nano/CMOS interfaces for electrochemical molecular sensing

Integrated bio/nano/Complementary Metal‐Oxide‐Semiconductor (CMOS) interfaces for electrochemical molecular sensing are becoming more and more common in the literature, especially for developing new electronic biochips for smart and intelligent Internet‐of‐Things (IoT) applications in remote monitoring of human body metabolism. The need for a bio interface is to specifically recognize the sensing of target molecules. The need for a nano interface is to address issues related to device sensitivity with respect to the envisaged medical application. Finally, the need for a CMOS interface comes from the modern approach to wearable and personal electronics, now also thought as an entry gate for monitoring people in their daily lives (e.g., sportsmen during competitions or trainings, chronic patients at home, etc.). Therefore, this paper reviews some of the most advanced approaches and methods published in the literature over the last decade related to the co‐design of integrated bio/nano/CMOS interfaces for electrochemical sensing of molecules related to human metabolism. Several approaches for realizing nanostructures directly on top of CMOS dies are introduced as well, and the related applications in biosensing are described. © 2018 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

Study on the thermal-moisture comfort of knitted upper fabric with the foot model

PurposeThe purpose of this paper is to measure the thermal and moisture resistance of the knitted upper fabrics with the foot model, which provided basis for designing and producing sports shoes with thermal-moisture comfort.Design/methodology/approachIn this paper, different yarn materials and fabric stitches were selected as the changing factors. The three kinds of yarn materials and the three kinds of fabric stitches were combined to design and weave eight pieces of knitted upper fabrics. Human sweating was simulated by the thermal-moisture comfort foot model, and then tested the thermal and moisture resistance of eight pieces of fabrics in different parts of the foot. Finally, the relationship between yarn material, fabric stitch, and the thermal and moisture resistance in different parts of the foot was analyzed by data.FindingsThe composition of the yarn material and fabric stitch has certain effect on the thermal-moisture comfort in different sections of the foot. When the yarn material of the four parts of the lateral arch, medial arch, ankle and heel is composed of 31.1tex moisture wicking polyester/33.3tex spandex coated yarn, the yarn material of the instep and toes is composed of 31.1tex ordinary polyester/33.3tex spandex coated yarn, and all parts of fabric stitch choose single-sided loop transfer stitch, the knitted sports shoes have the best thermal-moisture comfort.Originality/valueThe study used the thermal-moisture comfort foot model to simulate the human body metabolism and sweating system. Through the quantitative analyze of the thermal and moisture resistance of knitted upper fabrics to provide basis for the producers to design and product knitted sports shoes with good thermal-moisture comfort.

Irisin levels increase after treatment in patients with newly diagnosed Hashimoto thyroiditis.

Irisin is a newly identified myokine secreted by skeletal muscle and has significant effects on body metabolism. Thyroidal functional state has a profound influence on the metabolism of human body. Therefore, the aim of this study was to investigate the possible changes in serum irisin concentrations before and after treatment in hypothyroid subjects. The study included 26 patients with overt hypothyroidism due to Hashimoto thyroiditis and 19 healthy subjects. Baseline serum thyroid function tests and presence of thyroid autoantibodies and levels of creatine kinase (CK) and irisin were measured in both groups. All measurements in the hypothyroid group were repeated after euthyroidism was achieved. Serum irisin levels were significantly lower in the hypothyroid groups than the control group (p < 0.001). Negative correlation between irisin and thyroid stimulating hormone and CK levels (r = - 0.623, p < 0.001 and r = - 0.389, p = 0.008, respectively) and a positive correlation between irisin and free thyroxine (fT4) levels (r = 0.570, p < 0.001) was found. Serum CK levels decreased significantly after treatment (p < 0.001). Serum irisin levels significantly increased (from 57.4 to 99.8U/L, p < 0.001) when the hypothyroid patients were treated to achieve euthyroidism. To the best of our knowledge, this is the first study providing insight that low serum irisin levels significantly increased following treatment to euthyroid state in overt hypothyroid patients with Hashimoto thyroiditis. Larger scale studies are needed to confirm these results and to ensure irisin as a possible biomarker of Hashimoto's thyroiditis.

Ultra-small CuS Nanoparticles as Peroxidase Mimetics for Sensitive and Colorimetric Detection of Uric Acid in Human Serum

Abstract As the main final products of the purine metabolism in human body, uric acid (UA) usually presents in serum and urine. Thus, the level of UA in biology is closely related to human health. In this work, the ultra-small CuS nanoparticles (NPs) were demonstrated to possess intrinsic peroxidase-like activity towards 3,3',5,5'-tetramethylbenzidine (TMB) substrate in the presence of H2O2, which yielded the blue oxidized TMB (oxTMB) with strong absorption at 653 nm. Furthermore, H2O2 could be produced by the enzymatic reaction between UA and uricase to yield the blue oxTMB with the peroxidase mimetics activity of CuS NPs, which provided a sensitive and colorimetric method for UA detection with a linear range from 1.0 × 10−6 M to 1.0 × 10−4 M and a detection limit of 1.0 × 10−7 M. Moreover, the proposed method was successfully applied to the determination of UA in human serum samples, which supplied a similar result to the clinical method.

A novel hybrid decision support system for thyroid disease forecasting

Diagnosis of thyroid disease requires proper interpretation of functional data of the thyroid gland, which produces hormones to regulate the metabolism of human body. The thyroid disorders are classified on the basis of quantity of hormones produced, i.e., hyperthyroidism the case in which more hormones are produced and hypothyroidism where less than the required number of hormones are produced. Thyroid disease is a critical issue in underdeveloped countries, due to lack of awareness and early diagnosis. The use of machine learning methods is increasing with the passage of time as an alternative approach for the early diagnosis of thyroid disease. In this article, we present a novel intelligent hybrid decision support system based on linear discriminant analysis (LDA), k nearest-neighbor (kNN) weighed preprocessing, and adaptive neurofuzzy inference system (ANFIS) for the diagnosis of thyroid disorders. In the first stage of the LDA–kNN–ANFIS technique, LDA reduces the dimensionality of the disease dataset and eliminates unnecessary features. In the second stage, selected attributes are preprocessed using kNN-based weighed preprocessor. In the last stage, preprocessed selected attributes are provided to adaptive neurofuzzy inference system as an input for diagnosis. The proposed approach experimented on thyroid disease dataset, retrieved from the University of California Irvin’s machine learning repository to validate the overall performance of the system. The computed classification analysis made by accuracy, sensitivity, and specificity values of this approach were 98.5, 94.7, and 99.7%, respectively. This approach can also be efficiently applied to the diagnosis of other deadly diseases to get maximum accuracy with minimum possible features of the dataset.

Assessment of Public Knowledge regarding the Differences between Hyperthyroidism and Hypothyroidism

Background: Thyroid hormones play a pivotal role in the metabolism of human body. Changes of the thyroid gland activity manifest in nearly all body systems. Appropriate knowledge of the public about thyroid disorders and their manifestations is essential for early detection. Objective: The aim of this study was to assess public knowledge regarding the differences between hyperthyroidism and hypothyroidism in Tabuk city, Saudi Arabia. Methods: A cross sectional study was conducted on 300 randomly selected adult residents in Tabuk city. An Arabic self-administered questionnaire was filled by the participants through a link or softcopy. The questionnaire included questions about socio-demographic data of the respondents and other questions to assess knowledge about the type and functions of thyroid gland, its disorders, factors affecting thyroid disorders, and their common manifestations. Results: Respondents with good knowledge of thyroid gland and its disorders constituted 52%, while 45% had poor knowledge. Good knowledge was demonstrated in questions about the type of thyroid gland (71.4%), and the most susceptible individuals to have the disorder (90.4%). Manifestations of hypothyroidism were also recognized by most respondents, particularly weight gain (76%) as well as fatigability and sleepiness (74.9%). Inadequate and poor knowledge was found as regards the functions of thyroid gland, causes of thyroid hormonal disturbances, and symptoms of hyperthyroidism. Conclusion: The knowledge of respondents about thyroid disorders is poor. Inadequate knowledge can result in increased number of undetected cases. Health education should be launched by the health authorities and distributed through all available channels of information. Good knowledge of the general population about thyroid disorders is expected to decrease the incidence of preventable disorders and increase the detection of subtle undiagnosed cases.

Serum fatty acid patterns in patients with schizophrenia: a targeted metabonomics study

Previous studies have indicated that schizophrenia is linked to abnormal lipid metabolism. Free fatty acids (FFAs) in peripheral blood can reflect the status of lipid metabolism in human body. The purpose of this study was to scan the FFA pattern and elucidate the characteristics of lipid metabolic abnormality in schizophrenia patients. One hundred and ten patients with schizophrenia (SCZs) and 109 healthy controls (HCs) were included in the study and divided into a discovery set and a validation set. Forty-seven serum FFAs were detected by UPLC-QTOF-MS and 39 of them were absolutely quantified by establishing standard curves. Monounsaturated fatty acids (MUFAs) and ω-6 polyunsaturated fatty acids (ω-6 PUFAs) were significantly increased in SCZs compared with HCs. Desaturation from saturated fatty acids to MUFAs and β-oxidation were enhanced, as estimated by the ratios of products to precursors. These results suggest that lipolysis and β-oxidation are upregulated in SCZ, presumably resulting from insufficient brain energy supply.

Total arsenic and speciation analysis of saliva and urine samples from individuals living in a chronic arsenicosis area in China

BackgroundIt is generally acknowledged that the determination of harmful chemical compounds excreted into saliva is useful for assessing their exposure levels. The aim of the present study was to compare the total arsenic and its species in saliva and urine samples collected from the people residing in an arsenic-contaminated area of China and to further verify the feasibility of using salivary arsenic as a new biomarker of arsenic exposure.MethodsTotal arsenic and speciation analyses in urine and saliva samples among 70 residents exposed to arsenic from drinking water in Shanxi, China were carried out by high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP/MS).ResultsThe result showed that, total arsenic concentration in saliva was relatively lower than in urine samples, but it existed a strong positive correlation with total urinary arsenic, drinking water arsenic and different skin lesions. For arsenic metabolism analyses, AsIII, AsV, MMA, and DMA were detected in all of the urine samples with the dominating species of DMA (73.2%). Different with urinary arsenic species, most arsenic species in saliva were not methylated. The major species in saliva was iAs (AsIII + AsV, 76.18%), followed by DMA (13.08%) and MMA (9.13%). And the primary methylation index (PMI), second methylation index (SMI) and proportion of the four different species (AsIII, AsV, MMA, and DMA) in saliva showed no significant positive relationship with that of in urine.ConclusionsThese findings indicated saliva may be used as a useful tool for biological monitoring of total arsenic exposure in the crowd rather than an efficient tool for assessing arsenic metabolism in human body after exposed to arsenic.

Identification of Thiazoloquin(az)olin(on)es Derivatives as CD38 Inhibitors Through 3D-QSAR and Molecular Docking Simulations

CD38 is regarded as a potential target. Inhibitors against CD38 can regulate calcium metabolism in human body to impede the occurrence of disease, including diabetes and myeloma. In this work, 47 thiazoloquin(az)olin(on)es analogues with high pIC50 values in the micromolar ranges are studied by three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular docking. The comparative molecule field analysis (i.e., CoMFA q2 = 0.790; r2 = 0.967; rpred 2 = 0.872) and comparative molecular similarity indices analysis (i.e., CoMSIA q2 = 0.723; r2 = 0.969; rpred 2 = 0.815) are applied. Then, the Topomer CoMFA method is performed to validate these models, and the results show that this model has q2 = 0.662, r2 = 0.915 and rpred 2 = 0.704. These results indicate that the three models have good predictive abilities. Subsequently, molecular docking highlights the important interactions between the ligand and the CD38 receptor protein. Keywords: 3D-QDAR, docking, CD38 inhibitor, Topomer CoMFA, CoMFA, CoMSIA

New insights into disruption of iron homeostasis by environmental pollutants

Among the numerous health conditions environmental pollutants can cause, chronic exposure to pollutants including persistent organic pollutants (POPs) and heavy metals has been shown to disturb a specific biological homeostatic process, the iron metabolism in human body. Disorders of iron metabolism are among the common diseases of humans and encompass a broad spectrum of diseases with different clinical manifestations, ranging from anemia to iron overload, and possibly to neurodegenerative diseases and cancer. Hepcidin–ferroportin (FPN) signaling is one of the key mechanisms responsible for iron supply, utilization, recycling, and storage, and recent studies demonstrated that exposure to environmental pollutants including POPs and heavy metals could lead to disruption of the hepcidin–FPN axis along with disordered systemic iron homeostasis and diseases. This article introduces and highlights the accompanying review article by Drs. Xu and Liu in this journal, which elaborates in detail the adverse effects of environmental pollutants on iron metabolism, and the mechanisms responsible for these toxicological outcomes. It also points out the knowledge gaps still existing in this subject matter. Research that will fill these gaps will improve our understanding of the issue and provide useful information to prevent or treat diseases induced by environmental pollutants.

Hepatic inflammatory biomarkers and its link with obesity and chronic diseases.

The low-grade inflammation and insulin resistance are two events that could be present in varying degrees, on obesity and chronic diseases. The degree of subclinical inflammation can be gauged by measuring the concentrations of some inflammatory biomarkers, including the hepatic origin ones. Some of those biomarkers are sialic acid, α1-antitrypsin and the C-terminal fragment of alpha1-antitrypsin, ceruloplasmin, fibrinogen, haptoglobin, homocystein and plasminogen activator inhibitor-1. To approach the relation between adiposity and hepatic inflammatory markers, and to assess the possible associations between hepatic inflammatory biomarkers and obesity, as well as their capacity of predicting chronic diseases such as type 2 diabetes and atherotrombotic cardiovascular diseases. We used electronic scientific databases to select articles without restricting publication year. The sialic acid predicts the chance increase to become type 2 diabetic independently of BMI. Moreover, the α1-antitripsin, ceruloplasmin, fibrinogen and haptoglobulin biomarkers, seem predict the chance increase to become type 2 diabetic, dependently, of BMI. So, this process could be aggravated by obesity. The concentrations of fibrinogen, homocystein and PAI-1 increase proportionally to insulin resistance, showing its relation with metabolic syndrome (insulin resistance state) and with type 2 diabetes. In relation to cardiovascular diseases, every biomarkers reported in this review seem to increase the risk, becoming useful in add important prognostic. This review integrates the knowledge concerning the possible interactions of inflammatory mediators, in isolation or in conjunction, with obesity and chronic diseases, since these biomarkers play different functions and follow diverse biochemical routes in human body metabolism.

Electro-generated reactive oxygen species at Au surface as an indicator to explore glutathione redox chemistry and quantification

Abstract The thiol to disulfide inter-conversion plays vital role in the glutathione (GSH) metabolism in human body. Mimicking the GSH conversion to disulfide by electro-generated reactive oxygen species at gold electrode interface and the use of electro-reduction of the produced disulfides for the electro-analysis of low levels of GSH is reported.

An "enigmatic" L-carnosine (β-alanyl-L-histidine)? Cell proliferative activity as a fundamental property of a natural dipeptide inherent to traditional antioxidant, anti-aging biological activities: balancing and a hormonally correct agent, novel patented oral therapy dosage formulation for mobility, skeletal muscle power and functional performance, hypothalamic-pituitary- brain relationship in health, aging and stress studies.

Hypothalamic releasing and inhibiting hormones are major neuroendocrine regulators of human body metabolism being driven directly to the anterior pituitary gland via hypothalamic-hypophyseal portal veins. The alternative physiological or therapeutic interventions utilizing the pharmaco-nutritional boost of imidazole-containing dipeptides (non-hydrolized oral form of carnosine, carcinine, N-acetylcarnosine lubricant eye drops) can maintain health, enhance physical exercise performance and prevent ageing. Carnosine (β-alanyl-L-histidine) is synthesized in mammalian skeletal muscle. There is an evidence that the release of carnosine from the skeletal muscle sarcomeres moieties during physical exercise affects autonomic neurotransmission and physiological functions. Carnosine released from skeletal muscle during exercise acts as a powerful afferent physiological signaling stimulus for hypothalamus, may be transported into the hypothalamic tuberomammillary nucleus (TMN), specifically to TMN-histamine neurons and hydrolyzed herewith via activities of carnosine-degrading enzyme (carnosinase 2) localized in situ. Through the colocalized enzymatic activity of Histidine decarboxylase in the histaminergic neurons, the resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and physiological function. Carnosine and its imidazole-containing dipeptide derivatives are renowned for their anti-aging, antioxidant, membrane protective, metal ion chelating, buffering, anti-glycation/ transglycating activities used to prevent and treat a spectrum of age-related and metabolic diseases, such as neurodegenerative disease, sight threatening eye diseases, Diabetes mellitus and its complications, cancers and other disorders due to their wide spectrum biological activities. The precursor of carnosine (and related imidazole containing compounds) synthesis in skeletal muscles beta-alanine is used as the oral supplement by athletes to achieve the fine sporting art results due to the buffering activities of carnosine and its related imidazole- containing compounds which contribute to the maintenance of the acid-base balance in the acting muscles. This work originally emphasizes that overall data indicate the signaling activities of carnosine in skeletal and cardiac muscles switching on the mechanisms of exercise-induced telomere protection and point to the stress response and growth/cellular proliferation pathways as high-priority candidates for the ongoing studies and therapeutic concepts. The therapeutic interventions utilizing the specific oral formulation (Can-C Plus), timing dosing and pharmaco-nutritional boost of imidazolecontaining dipeptides can maintain health, enhance physical exercise performance and prevent aging. The patented therapeutic concept protects the existence of the interesting physiological major activities, better controls and therapeutic treatments for aging/age-related disorders (including age-related loss of muscle mass and muscle function) using carnosine dipeptide for cellular rejuvenation and manipulating telomeres and enzyme telomerase activity that may reduce some of the physiological declines that accompany aging.

CypRules: a rule-based P450 inhibition prediction server.

Cytochrome P450 (CYPs) are the major enzymes involved in drug metabolism and bioactivation. Inhibition models were constructed for five of the most popular enzymes from the CYP superfamily in human liver. The five enzymes chosen for this study, namely CYP1A2, CYP2D6, CYP2C19, CYP2C9 and CYP3A4, account for 90% of the xenobiotic and drug metabolism in human body. CYP enzymes can be inhibited or induced by various drugs or chemical compounds. In this work, a rule-based CYP inhibition prediction online server, CypRules, was created based on predictive models generated by the rule-based C5.0 algorithm. CypRules can predict and provide structural rulesets for CYP inhibition for each compound uploaded to the server. Capable of fast execution performance, it can be used for virtual high-throughput screening (VHTS) of a large set of testing compounds. CypRules is freely accessible at http://cyprules.cmdm.tw/ and models, descriptor and program files for all compounds are publically available at http://cyprules.cmdm.tw/sources/sources.rar.

Benchmarking of Force Fields for Molecule-Membrane Interactions.

Studies of drug-membrane interactions witness an ever-growing interest, as penetration, accumulation, and positioning of drugs play a crucial role in drug delivery and metabolism in human body. Molecular dynamics simulations complement nicely experimental measurements and provide us with new insight into drug-membrane interactions; however, the quality of the theoretical data dramatically depends on the quality of the force field used. We calculated the free energy profiles of 11 molecules through a model dimyristoylphosphatidylcholine (DMPC) membrane bilayer using five force fields, namely Berger, Slipids, CHARMM36, GAFFlipids, and GROMOS 43A1-S3. For the sake of comparison, we also employed the semicontinuous tool COSMOmic. High correlation was observed between theoretical and experimental partition coefficients (log K). Partition coefficients calculated by all-atomic force fields (Slipids, CHARMM36, and GAFFlipids) and COSMOmic differed by less than 0.75 log units from the experiment and Slipids emerged as the best performing force field. This work provides the following recommendations (i) for a global, systematic and high throughput thermodynamic evaluations (e.g., log K) of drugs COSMOmic is a tool of choice due to low computational costs; (ii) for studies of the hydrophilic molecules CHARMM36 should be considered; and (iii) for studies of more complex systems, taking into account all pros and cons, Slipids is the force field of choice.

Design and synthesis of 1,3‐dicapryloyl‐2‐acetylglycerol as molecular probe for triacylglycerol metabolism study

AbstractThe increasing number of health issues caused by obesity and lack of healthy and efficient fat substitutes require development on new fat substitute. This study proposes a new potential reduced‐calorie structured triacylglycerol (TAG) of “1,3‐medium‐chain, 2‐short‐chain triglycerides (MSM)” configuration, and the fat substitution method is based on the suppression of 2‐monoacylglycerol absorption into intestinal cells, which would decrease the recombination of TAG and reduce lipid absorption in the digestive tract. A molecular probe, 1,3‐dicapryloyl‐2‐acetylglycerol, is offered for nutritionists to conduct further study on its metabolism in human body. The synthesis method for this structured TAG starts from the lipase‐catalyzed esterification between glycerol and caprylic acid, yielding 1,3‐dicapryloylglycerol, and is followed by direct esterification with acetic anhydride to form 1,3‐dicapryloyl‐2‐acetylglycerol. Its structure is characterized by FTIR,1H NMR,13C NMR, and LC‐ESI‐MS.Practical application: This kind of pure structured triglyceride can function as a molecular probe for nutritionists to test its metabolism in human body and conduct further evaluation on their fat substitute potential. The synthesis method can also be easily adopted by food industry since it involves only two simple reaction steps.