Research Progress on the Molecular Mechanisms of Toxicology of Ethanol-Aconitine Induced Arrhythmia.

ABSTRACT: Aconitum is one of the most widely used Chinese herbal medicines, and aconitine is the major toxic component in it. Aconitine can induce a variety of arrhythmias, resulting in death. Acute ethanol consumption causes arrhythmia as well. Poisoning cases caused by aconitum medicinal liquor are frequently encountered in the practice of forensic medicine. The molecular mechanisms of myocardial toxicity of these two drugs have much in common, and both of them affect the sodium channel, calcium channel and potassium channel of myocardial cell membrane and so on. This paper analyzes and discusses the possible co-effects of ethanol-aconitine on cardiomyocyte channel proteins, by reviewing researches on the mechanism of cardiotoxicity of ethanol and aconitine in recent years, in order to provide ideas and references for the research on the molecular mechanism of arrhythmia caused by combined poisoning.

[Research advances on the roles of exosomes derived from vascular endothelial progenitor cells in wound repair].

Angiogenesis is the core step of wound repair, and vascular endothelial progenitor cells (EPC) play an extremely important role during wound repair. Recent studies have shown that vascular EPC-derived exosomes (EPC-Exo) can protect vessels, promote the proliferation and migration of vascular endothelial cells, and have anti-inflammatory, anti-oxidant and anti-apoptotic effects on vascular endothelial cells. This article reviews the mechanism of vascular EPC-Exo in angiogenesis and its potential applications in wound repair in recent years.

[Effects of allogeneic skin fibroblasts on promoting wound healing of diabetic mice and the mechanism].

Objective: To explore effects of allogeneic skin fibroblast (Fb) on promoting wound healing of diabetic mice and the mechanism. Methods: (1) Experiment 1. Ten diabetic mice and ten normal mice were chosen and sacrificed to collect back skin tissue. Suspension of the fourth generation of normal skin Fb and diabetic skin Fb were made. Another 27 diabetic mice were collected and divided into phosphate buffered saline (PBS) group, normal skin Fb group, and diabetic skin Fb group with random number table, with 9 mice in each group. Full-thickness skin defect wounds with area of 1 cm×1 cm were made on back of each mouse. Immediately after injury, 4 corners of wound of mice in normal skin Fb group and diabetic skin Fb group were injected with normal skin Fb and diabetic skin Fb suspension of 200 µL, respectively. Mice in PBS group were injected with the same amount of PBS at the same position. On post injury day (PID) 3, 7, 10, 14, and 17, surviving mice in the three groups were collected for gross wound observation and wound healing rate was calculated. On PID 7 and 14, 3 mice in each group were taken after gross wound observation to collect wound skin tissue. Percentage of Ki67 positive cell in wound tissue was detected by immunofluorescence method. Microvessel density (MVD) of wound tissue was detected by immunohistochemistry. Collagen fiber deposition of wound tissue was detected by Masson staining. (2) Experiment 2. Ten diabetic mice and ten normal mice were collected to make primary and the fourth generation normal skin Fb, and primary and the fourth generation diabetic skin Fb with the same method as in experiment 1. Apoptosis rate of Fb was detected by flow cytometry. The mRNA expressions and protein expressions of transforming growth factor ß(1) (TGF-ß(1)), advanced glycation end products (AGE), matrix metalloproteinase 9 (MMP-9), and neurokinin 1 (NK-1) of Fb were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Data were processed with analysis of variance of factorial design, one-way analysis of variance, and LSD-t test. Results: (1) The drying and scab growing speeds of wounds of mice in normal skin Fb group and diabetic skin Fb group at each time point post injury were faster than those of mice in PBS group. On PID 17, wound healing rate of mice in normal skin Fb group was close to that of mice in PBS group (t=3.45, P>0.05). At other time points, wound healing rate of mice in normal skin Fb group and diabetic skin Fb group was significantly higher than that of mice in PBS group, respectively (t=9.15, 10.25, 35.28, 6.79, 8.37, 10.69, 22.53, 6.70, 4.47, P<0.05 or P<0.01). On PID 7 and 14, wound healing rate of mice in normal skin Fb group was significantly higher than that of mice in diabetic skin Fb group (t=4.41, 4.16, P<0.05). On PID 7 and 14, percentages of Ki67 positive cells in wound tissue of mice in normal skin Fb group and diabetic skin Fb group were significantly higher than that of mice in PBS group (t=20.89, 31.82, 4.86, 29.53, P<0.05 or P<0.01); percentages of Ki67 positive cells in wound tissue of mice in normal skin Fb group were significantly higher than those of mice in diabetic skin Fb group (t=8.78, 13.51, P<0.05 or P<0.01). On PID 7 and 14, MVD of wound tissue of mice in normal skin Fb group and diabetic skin Fb group was significantly higher than that of mice in PBS group (t=26.92, 56.42, 10.36, 26.85, P<0.01). On PID 14, MVD of wound tissue of mice in normal skin Fb group was significantly higher than that of mice in diabetic skin Fb group (t=8.61, P<0.01). On PID 7 and 14, the amount of collagen fiber deposition of wound tissue of mice in normal skin Fb group was significantly higher than that of mice in diabetic skin Fb group and PBS group, respectively (t=10.09, 5.48, 4.77, 3.14, P<0.05 or P<0.01). (2) Apoptosis rate of primary normal skin Fb was (5.61±0.18)%, which was close to that of normal skin Fb of the fourth generation [(6.48±0.16)%, t=1.44, P=0.06]. Apoptosis rate of primary diabetic skin Fb was (26.25±0.56)%, which was significantly higher than that of primary normal skin Fb (t=36.61, P<0.01) and close to that of diabetic skin Fb of the fourth generation [(25.68±0.93)%, t=0.91, P=0.41]. The mRNA expressions of TGF-ß(1) and NK-1 of primary normal skin Fb were significantly higher than those of primary diabetic skin Fb (t=25.25, 273.30, P<0.01). The mRNA expressions of AGE and MMP-9 of primary normal skin Fb were significantly lower than those of primary diabetic skin Fb (t=23.01, 8.84, P<0.05 or P<0.01). The mRNA expressions of TGF-ß(1), AGE, and NK-1 in primary diabetic skin Fb were significantly higher than those of diabetic skin Fb of the fourth generation (t=4.34, 22.84, 12.10, P<0.05 or P<0.01). The protein expression of TGF-ß(1) and NK-1 of primary normal skin Fb were significantly higher than those of primary diabetic skin Fb (t=4.61, 8.53, P<0.05). The protein expressions of AGE and MMP-9 of primary normal skin Fb were significantly lower than those of primary diabetic skin Fb (t=10.22, 29.90, P<0.01). The protein expressions of AGE and NK-1 of primary diabetic skin Fb were significantly higher than those of diabetic skin Fb of the fourth generation (t=8.09, 4.36, P<0.05 or P<0.01). Conclusions: Allogeneic skin Fb can promote wound healing through promoting Fb proliferation, angiogenesis, collagen fiber deposition in wound of diabetic mice. When diabetic skin Fb of mice is cultured in vitro away from diabetic microenvironment, cell activity can't return to normal levels, and the effects of diabetic skin Fb on promoting wound healing is not as good as normal skin Fb.

[Novel affinity membrane used for bilirubin removal].

Bilirubin is a toxic substance. In order to effectively remove it from the hepatic patients' blood, two novel affinity membranes were prepared. These were prepared by chemically grafting on cellulose and immobilized with different ligands. One kind of ligand was poly-D-lysine, the other one was quaternary ammonium salt. Both affinity membranes were used for removal bilirubin from phosphate buffer and HSA solutions, and the effects of temperature, HSA concentration, adsorption time in static state experiment and flow rate in dynamic state experiment have been investigated. The results indicated that the membranes could remove over 70% bilirubin from phosphate buffer and at least 50% from low concentration HSA solutions. The results also indicated that the removal efficiency was better at higher temperature. In the static state experiment, four hours can be selected as adsorption time. In the dynamic state experiment, the flow rate can be properly increased.