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Biomedical subjects

Yichun Sun

Publications and source records attributed to Yichun Sun.

8 recordsLinked to original sources

Insights into the mechanism of enhanced tetramethylpyrazine production in dehulled adlay fermented by Bacillus subtilis BJ3-2.

Tetramethylpyrazine (TTMP) is a vital bioactive alkaloid and characteristic flavor compound in fermented foods. Our previous study found that fermentation of adlay by Bacillus subtilis BJ3-2 efficiently accumulates TTMP, whereas the underlying high-yield mechanism remains unclear. This study investigated the fermentation characteristics, gene transcription and protein expression of B. subtilis BJ3-2 in dehulled adlay (BDA) and soybean (BSB), respectively, and elucidated the mechanism responsible for high-yield TTMP production. The results showed that glutamate, leucine and phenylalanine were major free amino acids in BDA. The TTMP yield in BDA at 48 h (6.11 mg/g dry weight) was 360-fold higher than that in BSB. Transcriptomic and proteomic analysis demonstrated that compared with the soybean substrate, dehulled adlay substrate significantly up-regulated the expression of alsSD and ilvBH genes and their encoding proteins in B. subtilis BJ3-2, which were involved in C5-branched dibasic acid metabolism, 2-oxocarboxylic acid metabolism, and valine, leucine and isoleucine biosynthesis. Meanwhile, acetoin degradation was inhibited by down-regulating acetoin dehydrogenase complex (acoABCL) in citrate cycle, glycolysis/gluconeogenesis and carbon metabolism. Additionally, nitrogen metabolism pathway was transcriptionally enhanced to guarantee sufficient ammonium supply. Notably, protein-protein interaction and molecular docking analyses revealed that acetohydroxyacid synthase (ilvBH) interacted tightly with α-acetolactate decarboxylase (alsD), potentially forming a metabolic channel for acetoin synthesis. In conclusion, the efficient synthesis of TTMP in BDA was primarily attributed to the high synthesis and low degradation of acetoin, and the moderate synthesis of ammonium/ammonia. This study provided a theoretical basis for the targeted and efficient biosynthesis of TTMP.

Bacillus subtilis↗

Assessment of right ventricular diastolic suction in dogs with the use of wave intensity analysis.

Diastolic suction (DS) can be defined as that property of the ventricle by means of which it tends to refill itself during early diastole, independent of any force from the atrium. Although thought to be significant in the left ventricle (LV), DS in the right ventricle (RV) has received little attention, probably because of RV geometry. Our recent LV studies have shown that DS is related to both decreased elastance (i.e., tau, the relaxation time constant) and end-systolic volume (V(LVES)), thus reconciling the two mechanisms that have been used to explain the concept of DS. We hypothesized that RV DS would similarly depend on tau and V(RVES). In six anesthetized open-chest dogs, aortic, RV, right atrial (RA), pulmonary arterial (PA), and RV pericardial pressure, tricuspid velocity, and PA flow were measured. V(RVES) was calculated by measuring distances between eight ultrasonic crystals. An empirical index of relaxation, tau', and V(RVES) were manipulated by volume loading/caval constriction and isoproterenol/esmolol. We calculated the total energy (I(W-)) of the backward expansion wave generated during RV relaxation and that component causing DS [I(W-(DS))]; i.e., the energy remaining after tricuspid valve opening. I(W-) [I(W-(DS)) also] was found to be inversely related to tau' and to V(RVES) {i.e., I(W-) = -8.85.e((-0.0423tau')).e([-0.0665(%V(RVES))])}. Thus, as for the LV, the energy of the backward-going wave generated by the RV during relaxation depends on both the rate at which elastance decreases and the completeness of ejection. Despite the thin wall and nonspherical shape of the RV, DS appears to be an important mechanism.

Animals↗

Prediction of dissolution profiles of acetaminophen beads using artificial neural networks.

Immediate release acetaminophen (APAP) beads with 40% drug loading were prepared using the extrusion-spheronization process. Eighteen batches of beads were prepared based on a full factorial design by varying process variables such as extruder type, extruder screw speed, spheronization speed, and spheronization time. An in vitro dissolution test was carried out using the USP 27 Apparatus II (paddle) method. Artificial Neural Network (ANN) models were developed based on the aforementioned process variables and dissolution data. The trained ANN models were used to predict the dissolution profiles of APAP from the beads, which were prepared with various processing conditions. For training the ANN models, process variables were used as inputs, and percent drug released from APAP beads was used as the output. The dissolution data from one out of 18 batches of APAP beads was selected as the validation data set. The dissolution data of other 17 batches were used to train the ANN models using the ANN software (AI Trilogy) with two different training strategies, namely, neural and genetic. The validation results showed that the ANN model trained with the genetic strategy had better predictability than the one trained with the neural strategy. The ANN model trained with the genetic strategy was then used to predict the drug release profiles of two new batches of APAP beads, which were prepared with process variables that were not used during the ANN model training process. However, the process variables used to prepare the two new batches of APAP beads were within the confines of the process variables used to prepare the 18 batches. The actual drug release profile of these two batches of APAP beads was similar to the ones predicted by the trained and validated ANN model, as indicated by the high f2 values. Furthermore, the ANN model trained with genetic strategy was also used to optimize process variables to achieve the desired dissolution profiles. These batches of APAP beads were then actually prepared using the process variables predicted by the trained and validated ANN model. The dissolution results showed that the actual dissolution profiles of the APAP beads prepared from the predicted process variables were similar to the desired dissolution profiles.

Acetaminophen↗

Pharmacokinetics of buprenorphine after intravenous administration in the mouse.

Buprenorphine is a potent partial m-opioid agonist that is used as an analgesic in animals and humans to ameliorate moderate to severe pain and in the treatment of opiate addiction as an alternative to methadone maintenance. The purpose of this study was to characterize the pharmacokinetics of buprenorphine after intravenous administration in mice. Mice (n=48) were given 2.4 mg/kg buprenorphine (HCl salt) by intravenous bolus injection, and groups of 4 mice were euthanized at 5, 15, and 30 min and 1, 2, 3, 5, 7, 9, 12, 18, and 24 h after drug administration. Plasma concentrations of buprenorphine and norbuprenorphine were determined using liquid chromatography-tandem mass spectrometry. By using the mean concentrations at each time point (n=4), pharmacokinetic parameters were estimated for buprenorphine using a 3-compartment model with the reciprocal of the predicted concentration as the weight factor. The estimated values for the exponents of the 1st, 2nd, and terminal compartments; volume of distribution at steady state; clearance; and area under the concentration-time curve were 12.8/h, 2.13/h, 0.239/h, 6.5 l/kg, 4.3 l/h/kg, and 559 microg/lxh, respectively. In addition, we compare the pharmacokinetic disposition of buprenorphine in the mouse with that previously reported for other species.

Analgesics, Opioid↗

Issues and challenges in developing long-acting veterinary antibiotic formulations.

Antibiotics are an important class of therapeutic agents, which are used for the treatment of bacterial infectious diseases in a variety of animal species. Antibiotic therapy varies from treatment period to administration routes, depending on the animal species or the type of the disease being treated. Despite the fact that there are a wide variety of commercially available antibiotics, difficulties and problems associated with the administration of antibiotics to animals still exist. Thus, there is a great need and tremendous opportunity to develop long-acting antibiotic formulations for veterinary applications. In this review article, common approaches used to develop long-acting antibiotic formulations are summarized. The challenges and issues related to the development of these long-acting formulations are also discussed.

Animals↗

Application of artificial neural networks in the design of controlled release drug delivery systems.

Controlled release drug delivery systems offer great advantages over the conventional dosage forms. However, there are great challenges to efficiently develop controlled release drug delivery systems due to the complexity of these delivery systems. Traditional statistic response surface methodology (RSM) is one of the techniques that has been employed to develop and formulate controlled release dosage forms. However, there are some limitations to the RSM technique. Hence, another technique called artificial neural networks (ANN) has recently gained wide popularity in the development of controlled release dosage forms. In this review, the basic ANN structure, the development of the ANN model and an explanation of how to use ANN to design and develop controlled release drug delivery systems are discussed. In addition, the applications of ANN in the design and development of controlled release dosage forms are also summarized in this review.

Delayed-Action Preparations↗

Controlled release of oxytetracycline in sheep.

A novel biodegradable injectable formulation of oxytetracycline (OTC) was administered subcutaneously to sheep at a dose of 40 mg/kg. Blood samples were collected from the jugular vein at predetermined time intervals. The concentration of OTC in plasma was analyzed by an HPLC method. The concentrations of OTC in plasma were maintained at or above 0.5 microg/ml (minimum inhibitory concentration) for approximately 6 days. The pharmacokinetic parameters of OTC in sheep were also determined by monitoring the plasma concentration of OTC after a single intravenous injection of a commercially available OTC formulation at 10 mg/kg body weight. The in vivo release profiles of OTC from the biodegradable injectable formulations in sheep were determined from the plasma concentration time profiles by the deconvolution method using PCDCON software. The in vitro release of OTC from the biodegradable injectable formulation was tested in phosphate buffer (pH 7.4), containing 0.686% w/v of sodium sulfite as antioxidant. The correlation between the in vitro and in vivo release of OTC from the injectable formulation was also evaluated. The results of the in vivo evaluation of the formulation in sheep indicated that a controlled release biodegradable injectable dosage form of OTC for food animals is feasible.

Animals↗

Relationship between right ventricular wave speed and elastance in dogs.

Wave speed (c) must be known to separate forward- and backward-going waves during wave-intensity analysis, which measures the energy transported by the waves in the circulation. c is related to elastance; the present study was performed to measure right ventricular (RV) c during the cardiac cycle and to compare c with RV elastance. In 7 dogs, we measured right atrial, pulmonary arterial, pericardial and 2 RV pressures, and pulmonary arterial flow. A pulse generator was connected to the RV apex, and c was measured by determining the transit time between the 2 high-fidelity RV pressure transducers; the distance was measured roentgenographically. Eight sonomicrometry crystals were implanted in the RV endocardium to calculate RV volume and, thereby, elastance. RV c ranged from approximately 1 m/s during diastole to approximately 4 m/s during systole. Log-log plots of c vs. elastance were linear. These slopes represent the power relationships between c and elastance and ranged from 0.30 to 0.56; for the combined data, it was 0.31. Given knowledge of c, forward- and backward-going waves can be identified and their energy quantitated. In the canine RV, c is approximately proportional to 1/3 the power of elastance: log c = 0.31.log E - 2.05.

Animals↗