ABSTRACT
Purposes: Since the role of store-operated calcium entry (SOCE) in endothelium-dependent hyperpolarization (EDH)-mediated vasorelaxation of mesenteric arteries in health and colitis is not fully understood, cyclopiazonic acid (CPA), a specific inhibitor of the sarco(endo) plasmic reticulum calcium-ATPases (SERCA), was used as a SOCE activator to investigate its role in normal mice and its alteration in colitis mice. Methods: The changes in Ca2+ signaling in vascular endothelial cells (VEC) were examined by single cell Ca2+ imaging and tension of mesenteric arteries in response to CPA were examined using Danish DMT520A microvascular measuring system. Results: CPA activated the SOCE through depletion of the endoplasmic reticulum (ER) Ca2+ in endothelial cells. CPA had a concentration-dependent vasorelaxing effect in endothelium-intact mesenteric arteries, which was lost after endothelial removal. Both nitric oxide (NO) and prostacyclin (PGI2) inhibitors did not affect CPA-induced vasorelaxation; however, after both NO and PGI2 were inhibited, KCa channel blocker [10 mM tetraethylammonium chloride (TEA)] inhibited CPA-induced vasorelaxation while KCa channel activator (0.3 µM SKA-31) promoted it. Two SOCE blockers [30 µM SKF96365 and 100 µM flufenamic acid (FFA)], and an Orai channel blocker (30 µM GSK-7975A) inhibited this vasorelaxation. The inhibition of both Na+/K+-ATPase (NKA) and Na+/Ca2+-exchange (NCX) also inhibited CPA-induced vasorelaxation. Finally, the CPA involved in EDH-induced vasorelaxation by the depletion of ER Ca2+ of mesenteric arteries was impaired in colitis mice. Conclusion: Depletion of ER Ca2+ by CPA induces a vasorelaxation of mesenteric arteries that is mediated through EDH mechanism and invokes the activation of SOCE. The CPA-induced endothelium-dependent dilation is impaired in colitis which may limit blood perfusion to the intestinal mucosa.
ABSTRACT
Wheat straw biochar (BC) was modified by KOH and magnetics to generate composited modified biochar (FKC). Based on characterization by scanning electron microscopy-energy dispersive spectrometry (SEM-EDS), Brunauer-Emmett-Teller (BET), Fourier transform infrared (FT-IR), X-ray diffraction (XRD), and magnetic (VSM) techniques, the adsorption characteristics and mechanisms of Cd2+ in water and the effects of temperature, pH value, and dosage on the adsorption characteristics of FKC were studied. The results showed that the modified biochar was loose and porous. The specific surface area of FKC increased by 19.11 times, the number of aromatic and oxygen-containing functional groups such as O-H, C=O, and C=C increased, and a new functional group Fe-O formed compared to the BC. FKC is magnetic, and its magnetization is 8.43 emu·g-1, which can be recycled and reused. The adsorption of Cd2+ by FKC fitted well with the pseudo-second-order kinetic model and the Langmuir model, indicating that chemical adsorption is the main adsorption mechanism. The theoretical maximum equilibrium adsorption capacity of FKC is 23.44 mg·g-1, which is 1.47 times that of BC. The thermodynamic parameters suggested the adsorption of Cd2+ by FKC was a spontaneous and endothermic process. The adsorption capacity increased with an increase of pH in the region 2-8, and a biochar dosage of 10 g·L-1 was used. After three cycles of adsorption-desorption-adsorption, the adsorption capacity of Cd2+ by FKC still reached 17.71 mg·g-1, indicating that FKC has good reusability. These results can provide a theoretical basis for the application of KOH and magnet-modified biochar from wheat straw to remove heavy metals from contaminated wastewater.
ABSTRACT
5-Isoproyl-3,8-dimethylazulene derivatives were synthesized and evaluated for antigastric ulcer activity in vivo. Some of them possess the best activity against gastric ulcer with ulcer index values lower than the drug reference (omeprazole). The structure-activity relationship (SAR) shows that the lipophilic flat structure contributes to quite potent antigastric ulcer activity.
