Understanding the effects of metal pre-exposure on the sensitivity of zebrafish larvae to metal toxicity: A toxicokinetics-toxicodynamics approach.

Organisms are increasingly tolerant to metal toxicity in the natural ecosystems, which did not match the results of the environmental risk assessment (ERA) of metals based on toxicity data from organisms in the laboratory. Studies have described the effects of pre-exposure to metals on metal toxicity tolerance in terms of the toxicokinetic (TK) process; however, the toxicodynamic (TD) process may be more susceptible to metal pre-exposure. Therefore, to determine whether pre-exposure to low concentrations of silver (Ag) or cadmium (Cd) affects the metal TK and TD processes of zebrafish (Danio rerio) larvae, we investigated four TK-TD model parameters that control tolerance and sensitivity to metal toxicity on the survival. Our results showed that the killing rate (ks) of larvae exposed to high Cd concentrations was significantly lower following pre-exposure to 10 µg/L Cd than that of larvaenot pre-exposed. However, the ks for high Ag concentrations was significantly higher in zebrafish larvae following pre-exposure to 2 µg/L Ag than in larvae not pre-exposed. In other words, a one-day pre-exposure to 2 µg/L Ag rendered the larvae more sensitive to Ag during a subsequent 4-day exposure to higher Ag concentrations, whereas a one-day pre-exposure to 10 µg/L Cd rendered the larvae more tolerance to Cd during a subsequent 4-day exposure to higher Cd concentrations. Our results further the current understanding of toxic metal tolerance mechanisms, both in TK and TD processes, and they will guide future laboratory studies to assess actual pre-exposure scenarios that occur in natural environments. Thus, our study can help reduce uncertainty in testing and improve ecological management concerning metal risk assessments.

Notoginsenoside R1 protects oxygen and glucose deprivation-induced injury by upregulation of miR-21 in cardiomyocytes.

Notoginsenoside R1 (NG-R1) is a major component of Panax notoginseng, which has been used clinically for the treatment of diabetic nephropathy for centuries in China. This study aimed to reveal the functional impacts and the underlying mechanisms of NG-R1 on oxygen-glucose deprivation (OGD)-injured cardiomyocytes. Rat cardiomyocyte line H9c2 and primary cardiomyocytes were subjected to OGD with or without NG-R1 treatment. The expression levels of miR-21 and phosphatase and tensin homolog (PTEN) in the cell were altered by microRNA, vector or short-hairpin RNA transfections. Thereafter, changes in cell viability, apoptosis, and PI3K/AKT signaling were monitored. NG-R1 with low concentrations had no impact on H9c2 cells viability, but 80 µM of NG-R1 significantly reduced cell viability. NG-R1 (20 µM) protected H9c2 cells and primary cardiomyocytes against OGD-induced cell damage, as cell viability was increased, apoptotic cell rate was reduced, and Bax, cleaved caspase-3 and -9 were downregulated by addition of NG-R1. MiR-21 was low expressed in response to OGD exposure, while was highly expressed by NG-R1 treatment. PTEN was a direct target of miR-21. More interestingly, OGD-induced cell damage could be recovered by miR-21 overexpression or PTEN silence. Furthermore, PTEN silence recovered OGD-blocked PI3K/AKT signaling pathway. To conclude, this study demonstrated that NG-R1 exerted remarkable benefits in reduction of OGD-induced cardiomyocyte loss. The cardioprotective actions of NG-R1 possibly via upregulation of miR-21, repressing the expression of miR-21's target PTEN and thereby preventing the blockage of PI3K/AKT signaling pathway.

Referred Somatic Hyperalgesia Mediates Cardiac Regulation by the Activation of Sympathetic Nerves in a Rat Model of Myocardial Ischemia.

Myocardial ischemia (MI) causes somatic referred pain and sympathetic hyperactivity, and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear. Here, in a rat model, we showed that MI not only led to referred mechanical hypersensitivity on the forelimbs and upper back, but also elicited sympathetic sprouting in the skin of the referred area and C8-T6 dorsal root ganglia, and increased cardiac sympathetic tone, indicating sympathetic-sensory coupling. Moreover, intensifying referred hyperalgesic inputs with noxious mechanical, thermal, and electro-stimulation (ES) of the forearm augmented sympathetic hyperactivity and regulated cardiac function, whereas deafferentation of the left brachial plexus diminished sympathoexcitation. Intradermal injection of the α2 adrenoceptor (α2AR) antagonist yohimbine and agonist dexmedetomidine in the forearm attenuated the cardiac adjustment by ES. Overall, these findings suggest that sensory inputs from the referred pain area contribute to cardiac functional adjustment via peripheral α2AR-mediated sympathetic-sensory coupling.

[Electroacupuncture at "Neiguan"(PC6) decreased cardiac sympathetic hyperactivity and improved cardiac function in chronic myocardial ischemia model rats].

OBJECTIVE: To investigate the autonomic nervous mechanism of acupuncture therapy in the treatment of ischemic cardiomyopathy by observing the influence of electroacupuncture (EA) at "Neiguan"(PC6) on the superior cervical cardiac nerve activity and cardiac function in chronic myocardial ischemia (CMI) rats. METHODS: Male SD rats were randomly divided into control, model and EA groups (n＝8 in each group). The CMI model was established by ligating the anterior descending branch of the left coronary artery. EA (15 Hz, 1.5 mA) was applied to bilateral PC6 for 20 min, once a day for 28 consecutive days. Cardiac sympathetic nerve electrical activities (CSNEA), electrocardiogram (ECG) of the standard limb lead Ⅱ and ultrasonic cardiogram (UCG) were recorded for observing changes of ST segment height, left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS)．. RESULTS: The CSNEA was significantly increased(P<0.001), and the hight of ECG-STⅡ， LVEF and LVFS were considerably decreased in the model group relevant to the control group (P<0.01, P<0.001), while after the intervention, modeling induced increase of CSNEA and decrease of ECG-STⅡ， LVEF and LVFS were obviously suppressed in the EA group in comparison with the model group (P<0.01, P<0.05, P<0.001). CONCLUSION: EA of PC6 can improve cardiac function and myocardial ischemia in CMI rats, which is possibly related to its effect in decreasing cardiac sympathetic hyperactivity.

Adsorption of arsenic, phosphorus and chromium by bismuth impregnated biochar: Adsorption mechanism and depleted adsorbent utilization.

Bismuth impregnated biochar were synthesized to deal with wastewater pollution. Nitrogen adsorption-desorption isotherms, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) were used to determine the characteristics of adsorbents and explore the main adsorption mechanism. Results showed that bismuth particle was carried successfully within the biochar matrix, making contributions to creating micropore and boost specific surface area. The loaded bismuth, served as the adsorption site, rather than the specific surface area played an important role in arsenic and phosphorus adsorption. Batch adsorption experiments demonstrated a fit Langmuir model for arsenic (As) and phosphorus (P) and a suitable Freundlich model for chromium (Cr). Thermodynamic parameters depicted the endothermic nature and the spontaneous process for phosphate and arsenic adsorption. Besides, this contaminant-loaded carbon adsorbent was further applied for the removal of methylene blue from aqueous solution.