Pharmacokinetics and pharmacodynamic interaction of bergamottin with atorvastatin in rats.

1. The pharmacokinetics and pharmacodynamic of concomitant administration of atorvastatin with bergamottin were investigated perspectives to reveal the potential herb-drug interaction between these two drugs.2. The hyperlipidaemia-induced Wistar rats received atorvastatin with or without bergamottin (2.5 mg/kg). The concentration of atorvastatin in the rats' serum was determined using an established HPLC/MS/MS method. The pharmacokinetic parameters were calculated using DAS software. Lipid levels were determined.3. Bergamottin increases the Cmax (from 48 ± 5 ng/mL to 89 ± 7 ng/mL), AUC0-∞ (from 176 ± 27 to 552 ± 131 h∗µg/L), and the elimination half-life of atorvastatin (t1/2) of atorvastatin. Co-administration of atorvastatin with bergamottin decreased total cholesterol (by 14%), low-density lipoproteins-cholesterol (by 20%), and triglyceride (by 12%), but increased thigh-density lipoprotein-cholesterol, when compared with atorvastatin alone.4. Co-administration of bergamottin and atorvastatin alters both pharmacokinetics and pharmacodynamics of atorvastatin. This study provides pre-clinical information evidence that bergamottin could potentiate the therapeutic efficacy of atorvastatin or increase its accumulation and adverse effects.

Reverse genetics construction and pathogenicity of a novel recombinant NADC30-like PRRSV isolated in China.

China has the largest pig herd in the world which accounts for more than 50% of the global pig population. Over the past three decades, the porcine reproductive and respiratory syndrome virus (PRRSV) has caused significant economic loss to the Chinese swine industry. Currently, the prevalent PRRSV strains in the field are extremely complicated, and the NADC30-like strains, NADC34-like strains, and novel recombinant viruses have become a great concern to PRRS control in China. In this study, a novel NADC30-like PRRSV, named GS2022, was isolated from the lung of a dead pig collected from a farm that experienced a PRRS outbreak. The complete genome of GS2022 shares the highest identity with the NADC30 strain and contains a discontinuous deletion of 131 aa in nsp2. Novel deletion and insertion have been identified in ORF7 and 3'UTR. Recombination analysis revealed that the GS2022 is a potential recombinant of NADC30-like and JXA1-like strains. Both inter-lineage and intra-lineage recombination events were predicted to be involved in the generation of the GS2022. An infectious cDNA clone of GS2022 was assembled to generate the isogenic GS2022 (rGS2022). The growth kinetics of rGS2022 were almost identical to those of GS2022. The pathogenicity of the GS2022 and rGS2022 was evaluated using a nursery piglet model. In the infection groups, the piglets exhibited mild clinical symptoms, including short periods of fever and respiratory diseases. Both gross lesions and histopathological lesions were observed in the lungs and lymph nodes of the infected piglets. Therefore, we reported a novel recombinant NADC30-like PRRSV strain with moderate pathogenicity in piglets. These results provide new information on the genomic characteristics and pathogenicity of the NADC30-like PRRSV in China.

Evaluation of the genotype I Japanese encephalitis virus as a stable viral vector for foreign gene expression.

Manipulation of the flavivirus genome to accommodate and express a heterologous gene of interest has become an attractive approach for gene delivery and the development of viral-vectored vaccines. However, due to the inherent genetic instability of the flavivirus genomes, the construction of recombinant viruses carrying a foreign gene could be problematic and heavily resistant. In this study, the possibility of the Japanese encephalitis virus (JEV) as a stable flavivirus vector for the expression of a foreign gene was assessed using reverse genetics. The full-length cDNA genome of genotype I (GI) JEV inherently possessed excellent stability and manipulability in a bacterial host, while mutations and deletions accumulated in the cDNA genomes of genotype Ⅲ (GⅢ) JEV strains. Using the GI JEV as backbones, we generate a panel of recombinant viruses expressing various foreign genes. All recombinant viruses exhibited excellent genetic stability and efficiently express foreign genes for at least ten serial passages in vitro. In application, a convenient, rapid and reliable image-based assay for neutralizing antibody testing and antiviral drug discovery was established with a mCherry-reporter recombinant virus (rBJ-mCherry). Meanwhile, the recombinant viruses expressing the antigens of the African swine fever virus (ASFV) or Classical swine fever virus (CSFV) could effectively induce antibody responses to the JEV vector and foreign antigens in a mouse vaccination model. Therefore, GI JEV strains could serve as viral vectors accommodating the expression of large foreign genes.

A system of real-time neural recording and stimulation and its potential application in blood pressure modulation.

Hypertension is one of the most prevalent chronic diseases that affects more than 20% of the adult population worldwide, but fortunately, most of their blood pressure can be effectively controlled via drug treatment. However, there still remains 5-30% of patients clinically who do not respond well to conventional medication, while the non-drug treatments currently existing are struggling with major drawbacks like irreversible nerve damage, huge side effects, and even non-effectiveness. In this study, based on the physiological regulation mechanism of blood pressure and state-of-the-art neuromodulation technique, we worked along with the vagus nerve stimulation scheme, developed, and explored whether and how a real-time neural recording and stimulation system could provide an insight into self-adaptive modulation in the blood pressure, in the hope to crack a crevice in the closed-loop treatment for resistant hypertension. Unlike traditional neuromodulation devices, additional signal recording and real-time wireless transmission functions are added to the same device to realize the features of a dynamic monitor and modulator. The system is tested both in vitro and in vivo, showing decent electrical performance of 8 kHz sampling rate and flexible stimulation outputs which sufficiently covers our needs in manipulating neural activities of interest. A relatively stable drop in the blood pressure resulting from stimulation was observed and specific patterns in the vagus nerve signals relating to blood pressure could also be primarily identified. This laid a solid foundation for further studies on the final realization of closed-loop automatic adjustment for resistive hypertension treatment.

Discrimination and Recognition of Phantom Finger Sensation Through Transcutaneous Electrical Nerve Stimulation.

Tactile sensory feedback would make a significant contribution to the state-of-the-art prosthetic hands for achieving dexterous manipulation over objects. Phantom finger sensation, also called referred sensation of lost fingers, can be noninvasively evoked by transcutaneous electrical nerve stimulation (TENS) of the phantom finger territories (PFTs) near the stump for upper-limb amputees. As such, intuitive sensations pertaining to lost fingers could be non-invasively generated. However, the encoding of stimulation parameters into tactile sensations that can be intuitively interpreted by the users remains a significant challenge. Further, how discriminative such artificial tactile sensation with TENS of the PFTs is still unknown. In this study, we systematically characterized the tactile discrimination across different phantom fingers on the stump skin by TENS among six subjects. Charge-balanced and biphasic stimulating current pulses were adopted. The pulse amplitude (PA), the pulse frequency (PF) and the pulse width (PW) were modulated to evaluate the detection threshold, perceived touch intensity, and the just-noticeable difference (JND) of the phantom finger sensation. Particularly, the recognition of phantom fingers under simultaneous stimulation was assessed. The psychophysical experiments revealed that subjects could discern fine variations of stimuli with comfortable sensation of phantom fingers including D1 (phantom thumb), D2 (phantom index finger), D3 (Phantom middle finger), and D5 (Phantom pinky finger). With respect to PA, PF, and PW modulations, the detection thresholds across the four phantom fingers were achieved by the method of constant stimuli based on a two-alternative forced-choice (2AFC) paradigm. For each modulation, the perceived intensity, which was indexed by skin indentations on the contralateral intact finger pulp, reinforced gradually with enhancing stimuli within lower-intensity range. Particularly, the curve of the indentation depth vs. PF almost reached a plateau with PF more than 200 Hz. Moreover, the performance of phantom finger recognition deteriorated with the increasing number of phantom fingers under simultaneous TENS. For one, two and four stimulating channels, the corresponding recognition rate of an individual PFT were respective 85.83, 67.67, and 46.44%. The results of the present work would provide direct guidelines regarding the optimization of stimulating strategies to deliver artificial tactile sensation by TENS for clinical applications.

[Study on variation specificity of maize induced by colchicine].

After two years continuous self-pollination,the variated specificities of five kinds of variations of maize induced by colchicine were examined and measured. Experiments show that germination potential increased 3% - 46%, cell diameter of root tip meristem region is 6% - 15% less than original material, meanwhile, nucleus diameter increased 5% - 18%, percentage of chromosome variation is 25.25% - 38.35% in root tip meristem region,but variation range is mainly in 10 - 30 piece. However, chromosome numbers tend to be more than 20 in root tip of maize No.1 and No.16, the other material variation trend is unobvious.