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Objective To explore the relationship among serum vitamin D,calcium ion,blood lipid lev-els and preeclampsia in pregnant women,and analyze the pregnancy outcomes of pregnant women with pre-eclampsia.Methods A total of 166 pregnant women with preeclampsia who underwent pregnancy examina-tion and delivered in Urumqi Municipal Maternal and Child Health Care Hospital from January 1,2021 to Jan-uary 1,2023 were selected as the observation group,and 200 healthy pregnant women during the same period were selected as the control group.The levels of serum vitamin D,calcium ion,phosphorus ion,blood lipid in-dicators,uric acid,and creatinine were detected in the two groups,and the pregnancy complications and preg-nancy outcomes were observed.The influencing factors of preeclampsia were analyzed by using multivariate logistic regression model.Results The levels of serum vitamin D,calcium ion,and high density lipoprotein in the observation group were lower than those in the control group,and the levels of serum uric acid and creati-nine were higher than those in the control group,with statistical significance(P＜0.05).The incidence of fetal growth retardation,placental abruption,oligohydramnios,cesarean section,low birth weight infants,premature delivery,and postpartum hemorrhage in the observation group were significantly higher than those in the con-trol group(P＜0.05).Multivariate logistic regression analysis showed that serum vitamin D(OR=15.141,95％CI:1.831-125.204,P=0.012),calcium ion(OR=4.625,95％CI:2.654-8.059,P＜0.001),high-den-sit y lipoprotein(OR=0.395,95％CI:0.235-0.666,P＜0.001),creatinine(OR=1.034,95％CI:1.005-1.063,P=0.020)and uric acid(OR=1.006,95％CI:1.003-1.010,P＜0.001)were independent factors for the occurrence of preeclampsia in pregnant women.Conclusion The levels of serum vitamin D,calcium ions,blood lipids,uric acid and creatinine may be correlated with the occurrence of preeclampsia.
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AIM:To investigate the mechanism of Piezo1 channel activation promoting the increase in intra-cellular Ca2+ concentration([Ca2+]i)of rat coronary artery smooth muscle cells(CASMCs).METHODS:The primary CASMCs of SD rats were cultured,and the expression and subcellular localization of Piezo1 in the cells were observed by immunofluorescence staining.The Piezo1 and stromal interaction molecule 1(STIM1)in CASMCs were knocked down by siRNA transfection,and the expression levels of the proteins were detected by Western blot.Utilizing laser confocal mi-croscopy,the change of[Ca2+]i in CASMCs was detected by Fluo-4 AM fluorescent probes.RESULTS:It was confirmed by immunofluorescence staining that the expression of Piezo1 existed in primary rat CASMCs.Immunofluorescence staining also showed that Piezo1 was co-located with sarco-/endoplasmic reticulum Ca2+-ATPase 2(SERCA2),mitochondrial outer membrane protein TOM20 and nuclear membrane protein lamin B1.Western blot results showed that the protein expres-sion levels of STIM1 and Piezo1 were significantly down-regulated by siRNA transfection(P<0.05).Compared with con-trol group,Yoda1,the agonist of Piezo1,could increase the extracellular Ca2+ influx of CASMCs(P<0.01).However,the Ca2+ influx mediated by Yoda1 was not affected by the inhibition of L-type calcium channels.Treatment with Yoda1 in-creased the intracellular Ca2+ release of CASMCs(P<0.01).However,inhibition of calcium channels on endoplasmic re-ticulum,ryanodine receptor and inositol 1,4,5-triphosphate receptor,did not affect intracellular Ca2+ release mediated by Yoda1.After the Ca2+ in endoplasmic reticulum was emptied using thapsigargin(TG),Yoda1 also mediated the Ca2+ re-lease of other organelles in CASMCs(P<0.01).After inhibition of L-type calcium channels,treatment with store-operated calcium channel(SOCC)inhibitor BTP2 or knockdown of STIM1 led to the decrease in extracellular Ca2+ influx of CASMCs mediated by Yoda1(P<0.01).Treatment with TG increased the release of Ca2+ from the endoplasmic reticulum of CASMCs after knockdown of Piezo1(P<0.05),but the extracellular Ca2+ influx mediated by TG was not affected.After inhibition of L-type calcium channels and SOCC,knockdown of Piezo1 led to the decreases in intracellular Ca2+ release and extracellular Ca2+ influx induced by Yoda1(P<0.01).CONCLUSION:The Piezo1 agonist orchestrates the influx of extracellular Ca2+ by activating Piezo1 channels on the cell membrane and inducing the indirect activation of SOCC.More-over,it facilitates the release of Ca2+ from organelles.Consequently,these pathways synergistically elevate the[Ca2+]i of rat CASMCs.
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Objective:To study the effects of different calcium ion concentrations on epithelial mesenchymal transformation (EMT) of human peritoneal mesothelial cell (HPMC) via endoplasmic reticulum stress (ERS).Methods:HPMC cell line HMrSV5 was cultured in vitro and treated in groups. The cells in the control group, high calcium group 1, and high calcium group 2 were treated with medium containing calcium ion concentrations of 1.25, 1.75, and 2.25 mmol/L, respectively. The solvent control group was treated with medium containing 1.25 mmol/L physiological calcium ion concentration and 0.1% dimethyl sulfoxide (DMSO), the high calcium+solvent group was treated with medium containing 2.25 mmol/L calcium ion concentration and 0.1% DMSO, the high calcium+4-phenylbutyric acid (4-PBA) group was treated with medium containing 2.25 mmol/L calcium ion concentration and 1 mmol/L ERS inhibitor 4-PBA, and each group was treated for 48 hours. Morphological changes of cells in each group were observed under light microscope. The expressions of epithelial cell phenotype marker zonula occluden-1 (ZO-1) and mesenchymal cell phenotype marker α-smooth muscle actin (α-SMA) in the cells were observed by immunofluorescence staining. The expressions of EMT marker genes E-cadherin, ZO-1, α-SMA and Vimentin were detected by fluorescence quantitative polymerase chain reaction (PCR). The expressions of ERS marker proteins phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), transcription activating factor 4 (ATF4) and C/EBP homologous protein (CHOP) were detected by Western blotting. Results:Compared with the control group, the morphology of HMrSV5 cells became slender and fibrotic, the fluorescence intensity of ZO-1 increased, and the fluorescence intensity of α-SMA decreased in high calcium 1 and high calcium 2 groups, indicating that the cells transformed from epithelial cells to mesenchyme cells. The mRNA expressions of E-cadherin and ZO-1 were significantly decreased, while the mRNA expressions of α-SMA and Vimentin and the protein expressions of p-PERK, p-eIF2α, ATF4 and CHOP were significantly increased, moreover, the expressions of the above marker genes or proteins in the high calcium 2 group was more obvious than those in the high calcium 1 group [E-cadherin mRNA (2 -ΔΔCt): 0.53±0.05 vs. 0.75±0.09, ZO-1 mRNA (2 -ΔΔCt): 0.42±0.06 vs. 0.69±0.06, α-SMA mRNA (2 -ΔΔCt): 1.81±0.16 vs. 1.32±0.14, Vimentin mRNA (2 -ΔΔCt): 2.05±0.22 vs. 1.48±0.16, p-PERK protein (p-PERK/β-actin): 0.81±0.09 vs. 0.59±0.06, p-eIF2α protein (p-eIF2α/β-actin): 0.87±0.10 vs. 0.50±0.06, ATF4 protein (ATF4/β-actin): 0.93±0.10 vs. 0.72±0.06, CHOP protein (CHOP/β-actin): 0.79±0.09 vs. 0.46±0.04, all P < 0.05]. Compared with the solvent control group, the morphological changes of cells, the expressions of EMT marker genes and ERS marker proteins after high calcium ion concentration of 2.25 mmol/L were consistent with those in the high calcium 2 group than control group. Compared with the high calcium+solvent group, the cell morphology recovered the characteristics of polygonal and pebble-like epithelial cells in the high calcium+4-PBA group, the fluorescence intensity of ZO-1 increased, the fluorescence intensity of α-SMA decreased, and the mRNA expressions of E-cadherin and ZO-1 in the cells were significantly increased [E-cadherin mRNA (2 -ΔΔCt): 0.86±0.09 vs. 0.57±0.04, ZO-1 mRNA (2 -ΔΔCt): 0.81±0.06 vs. 0.48±0.05, both P < 0.05], the mRNA expressions of α-SMA and Vimentin and the protein expressions of p-PERK, p-eIF2α, ATF4 and CHOP were significantly decreased [α-SMA mRNA (2 -ΔΔCt): 1.21±0.13 vs. 1.77±0.15, Vimentin mRNA (2 -ΔΔCt): 1.30±0.14 vs. 1.94±0.20, p-PERK protein (p-PERK/β-actin): 0.38±0.04 vs. 0.92±0.11, p-eIF2α protein (p-eIF2α/β-actin): 0.34±0.05 vs. 1.05±0.13, ATF4 protein (ATF4/β-actin): 0.57±0.06 vs. 0.97±0.11, CHOP protein (CHOP/β-actin): 0.51±0.04 vs. 0.90±0.12, all P < 0.05]. Conclusion:High calcium ion concentrations of 1.75 mmol/L and 2.25 mmol/L promote EMT of HPMC via activating ERS.
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Objective To explore the effects of electromagnetic field(EMF)on thechange of Ca2+ in osteolbast from the qualitative and quantitative perspectives,and try to identify the role of Ca2+in EMF regulation on osteoblast proliferation and differentiation.Methods A platform was established for generating sine EMF with a frequency of 38.7 Hz and a strength of 1.5 mT.The MC3T3-E1 osteoblasts were randomly divided into control group and experimental group(EMF intervention for 8 h per day).CCK8 was used to detect osteoblast proliferation,ALP staining to detect osteoblast differentiation,and Ca2+fluorescence probes and flow cytometer to detect the Ca2+concentration in osteoblasts.Results CCK8 result showed that EMF intervention for 48,72,96 and 120 h could significantly promote osteoblast proliferation.After 14 days of EMF intervention,the positive expression of ALP was significantly higher in EMF group than in control group.Ca2+fluorescent staining and flow cytometry results revealed that EMF intervention could increase the Ca2+in osteoblasts.Conclusion The EMF-induced upregulation of Ca2+ signal in osteoblasts may be closely related to the promotions of osteoblast proliferation and differentiation by EMF,but which Ca2+-related biosignaling pathways are involved in the EMF promoting osteoblast proliferation and differentiation remains to be further investigated.
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Objective To observe the effects of Shengxue Tongbian Granules on colonic myoelectricity and Ca2+/CaM/MLCK signaling pathway in rats with slow transit constipation(STC)of blood deficiency and intestinal dryness syndrome;To explore its mechanism for the treatment of STC.Methods The STC model of blood deficiency and intestinal dryness syndrome was established by intragastric administration of loperamide combined with tail bloodletting.The rats were divided into control group,model group,mosapride citrate group and Shengxue Tongbian Granules group,with 8 rats in each group.The administration group was given corresponding drugs by gavage for 14 days.The general condition of rats before and after treatment was observed,the fecal water content was detected,the slow wave frequency,amplitude,and coefficient of variation of colonic electromyography were detected using a biological function experimental system,and intestinal propulsion rate was detected.HE staining was used to observe the pathological changes of colon tissue,the concentration of Ca2+ in colonic smooth muscle cells was detected by colorimetry,the expression of Cx43,calmodulin(CaM),myosin light chain kinase(MLCK)and p-MLC20 in smooth muscle tissue were detected by Western blot.Results Compared with the control group,the body mass,fecal water content and intestinal propulsion rate of rats in the model group decreased(P<0.01),the slow wave frequency of colonic electromyography slowed down,the coefficient of variation of frequency increased(P<0.01),and the amplitude and coefficient of variation of slow wave increased(P<0.01);colonic mucosal structure was damaged,with visible inflammatory changes and significant erosion,and the concentration of Ca2+ and the expressions of Cx43,CaM,MLCK,p-MLC20 proteins in colonic smooth muscle cells were significantly decreased(P<0.01).Compared with the model group,the body mass,fecal water content and intestinal propulsion rate of the rats in the mosapride citrate group and the Shengxue Tongbian Granules group significantly increased(P<0.05,P<0.01),the slow wave frequency of colonic electromyography increased and the coefficient of variation of frequency decreased(P<0.01),and the slow wave amplitude and amplitude variation coefficient decreased(P<0.05,P<0.01);the colonic mucosal structure was relatively intact,the erosion situation was improved,and the Ca2+ concentration,Cx43,CaM,MLCK and p-MLC20 protein expressions in colonic smooth muscle cells significantly increased(P<0.01).Conclusion Shengxue Tongbian Granules can improve defecation symptoms and promote colonic motility in STC rats with blood deficiency and intestinal dryness syndrome,which may be related to regulating colonic myoelectric rhythm and activating Ca2+/CaM/MLCK signaling pathway.
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Objective To explore the mechanism of the treatment of atrial fibrillation(AF)with traditional Chinese medicine compound of eliminating phlegm and removing blood stasis.Methods Sixty male SD rats were randomly divided into the blank group and the model group.Ach(66 μg·mL-1)-CaCl2(10 mg·mL-1)was injected into the tail vein for 7 consecutive days to establish the rat AF model.The rats with successful modeling were randomly divided into model group,high,medium and low dose groups of Chinese herbal compound and verapamil group.The high,medium and low dose groups of Chinese herbal compound were given 12.38 mg,6.18 mg and 3.10 mg·kg-1·d-1 Chinese herbal compound for removing phlegm and removing blood stasis solution by gavage,while the verapamil group was given 8.31 mg·kg-1·d-1 verapamil solution by gavage,and the blank group and model group were given equal volume distilled water by gavage.During this period,the rats were still given tail vein injection for 14 consecutive days.The duration of atrial fibrillation in lead Ⅱ of rats was measured by electrophysiological recorder,the ultrastructural changes of rat atrial muscle were observed by transmission electron microscope,the relative expression of CAV1.2,CaM,CaMKⅡ mRNA in rat atrial muscle was detected by RT-PCR,and the expression of CAV1.2,CaM,CaMKⅡ and downstream proteins RyR2,P-RyR2 in rat atrial muscle was detected by Western blot.Results Compared with the blank group,the rats in the model group showed typical atrial fibrillation ECG.Compared with the model group,the duration of atrial fibrillation in the compound Chinese medicine group decreased.The arrangement of myofilaments was relatively neat,and the structure of mitochondria was relatively complete;CAV1.2 mRNA and protein expression increased(P<0.05),CaM,CaMKⅡ mRNA and protein expression decreased(P<0.01),downstream protein P-RyR2 expression decreased(P<0.01),RyR2 protein expression had no difference(P>0.05).Conclusion The Chinese herbal compound for removing phlegm and removing blood stasis can shorten the duration of atrial fibrillation in rats,inhibit the ultrastructure damage of atrial myocytes,and its mechanism may be related to regulating the expression of CAV1.2/CaM/CaMKⅡ signal pathway and improving the disorder of calcium regulation.
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@#Inositol 1，4，5-trisphosphate receptor （IP3R），which is a calcium ion （Ca2+） channel in the endoplasmic reticulum，participates in cellular biological functions through regulating the Ca2+ signal，and it is a key molecule in maintaining the normal function of the central nervous system. In recent years，more and more studies have found that the structural and functional abnormalities of IP3Rs are closely related to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease，Parkinson disease，Huntington disease，and spinocerebellar ataxia. However，it remains unclear how these structural and functional abnormalities affect the function of IP3Rs and the related calcium signal as well as the pathogenesis and severity of neurodegenerative diseases. This paper reviews the role of IP3Rs in neurodegenerative diseases.
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{L-End}Objective To analyze the local muscle response under continuous ergonomic workload by simulating manual lifting, and to screen the sensitive metabolic biomarkers during fatigue process. {L-End}Methods A total of 13 healthy male volunteers were selected as the study subjects using simple random sampling method. Study subjects underwent repetitive simulated manual lifting for four periods (T1 to T4), each lasting 12 minutes. The degree of work-related fatigue in the forearm, upper arm, shoulder, back, and leg muscles, and the whole body was accessed using Borg 6-20 Rating of Perceived Exertion (RPE) Scale. The venous blood samples were collected from elbow between each two periods to detect the levels of eight metabolic biomarkers: ammonia, lactate, creatine kinase, lactate dehydrogenase (LDH), C-terminal telopeptide of type Ⅰ collagen (CTX-Ⅰ), C-terminal telopeptide of type Ⅱ collagen (CTX-Ⅱ), cartilage oligomeric matrix protein (COMP), and calcium ions. {L-End}Results The RPE scores of the study subjects for the muscles of five body parts and the whole body increased with the increasing lifting periods (all P<0.01). Fatigue was observed in all target muscles, with overall body fatigue occurring in the T2 period. The levels of ammonia, lactate, creatine kinase, LDH, COMP, and calcium ions in the serum of study subjects were higher in the T1 to T4 periods than in the T0 period (all P<0.05). The serum CTX-Ⅰ level was higher in the T1 and T3 periods than that in the T0 period (all P<0.05) , and the serum CTX-Ⅱ level was higher in the T1, T2 and T4 periods than that in the T0 period (all P<0.05). The level of these eight serum metabolic biomarkers fluctuated during the T1 to T4 periods. The serum creatine kinase level increased with the period of lifting (all P<0.05). The serum lactate level was higher in the T3 period than those in the T1 and T2 periods (all P<0.05). The serum LDH and calcium ion levels were higher in the T2 to T4 periods than that in the T1 period (all P<0.05). The serum COMP level was higher in the T2 and T3 periods than that in the T1 period (all P<0.05). Except for CTX-Ⅰ, the levels of other seven metabolic markers in serum were higher in individuals after fatigue than before fatigue (all P<0.05). {L-End}Conclusion Serum metabolic biomarkers such as ammonia, lactate, creatine kinase, calcium ions, LDH, CTX-Ⅱ, and COMP exhibit significant changes before and after fatigue. These metabolic biomarkers could be used as sensitive biomarkers for evaluating muscle fatigue during repetitive works.
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Aim To evaluate the flow, pH and calcium release of white MTA (WMTA), salicylate-based resin root canal sealer (Sealapex; SEAL) and SEAL containing 10 (SE10) or 20% (SE20) (w/w) of MTA. Methodology Flow test was realized according to ISO 6876 specification. The sealers samples (n= 10) were placed in polyethylene tubes and immersed in deionized water. After 24 hours and 7, 14, and 28 days, the water pH was determined with a pH meter, and calcium release was assessed by atomic absorption spectrophotometry. Results SEAL and WMTA showed respectively the highest and lowest flow rate when compared with the other materials (P<0.05). SE20 showed the highest pH value only in 24h and 7 days periods (p<0.05). In 14- and 28-days periods, SEAL showed the lowest pH value (p<0.05), but there are no differences between other groups (p>0.05). In all periods, WMTA and SEAL respectively showed the highest and lowest calcium release (p<0.05). Conclusions SE20 proves to be an association with better flow and handling than WMTA, with satisfactory potential for alkalinization and calcium release.
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Skeletal muscle is an important organ for development and metabolism and its metabolic disor⁃ ders will induce a series of muscle diseases. As an important regulator of the muscle contraction process, Ca
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Aim To investigate the protective effect of cyclovirobuxine D(CVB-D) on aldosterone (ALD)-induced primary neonatal rat cardiac myocytes (PNRC-Ms) injury and the possible mechanism. Methods PNRCMs were extracted by trypsin, and the PNRCMs injury model was established by ALD (10 μmol · L
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Objective To explore the effect of S100 calcium ion binding protein A6 (S100A6) on proliferation and migration of esophageal adenocarcinoma SK-GT-4 cells. Methods Lenti viruses were used to construct stable transfected cell lines (shNC and shS100A6). Real-time PCR was used to detect the mRNA expression of S100A6. The inverted microscope and MTT were used to detect cell proliferation. The Transwell assay was used to detect cell migration. Western blotting was used to detect the expression of S100A6, p-ERK, p-Akt and its downstream molecular involved in proliferation and migration. Using U0126 ( inhibitor of MER1/2) and LY294002 ( inhibitor of PI3K) to detect the effect of these two inhibitors on cell proliferation and migration and the expression of p-ERK, p-Akt and its downstream molecular involved in proliferation and migration in shS100A6 cells. Results Stable cell lines of knockdown S100A6 were constructed. Knockdown S100A6 promoted cell proliferation and migration. Western blotting result displayed that in shS100A6 cells, the levels of p-Akt and p-ERK increased, p21 decreased, cyclinDl increased, and the expression of β-catenin and vimentin, increased. U0126 and LY294002 inhibited the migration of shS100A6 cells. U0126 had no effect on the proliferation of shS100A6 cells, however LY294002 could inhibit the proliferation of shS100A6 cells. U0126 treatment on shS100A6 cells could decrease p-ERK and β-catenin expression. After shS100A6 cells treated with LY294002, p-Akt and β-catenin expression decreased, p21 expression increased and the expression of cyclinDl decreased. Conclusion Low expression of S100A6 promotes cell proliferation and migration, which may be mediated by activation of p-Akt regulating cell cycle progression to promote cell proliferation and by activation of p-Akt/p-ERK to regulate β-catenin to promote cell migration.
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Mineral medicine is an indispensable part of traditional Chinese medicine and has a long history of application. Among them， mineral-based hemostatics have been widely applied for the treatment of various hemorrhagic diseases with extensive clinical experience and established efficacy. Gypsum Fibrosum （GF）， a commonly used mineral medicine in clinical， can clear away heat， and relieve anxiety and thirst. Gypsum Ustum （GU） is the processed product of GF after calcining at high temperature. It is mainly composed of anhydrous calcium sulfate （CaSO4） with the functions of moisturizing， promoting muscle growth， astringent sores and hemostasis. GU is often used externally to treat ulcer， itching， eczema， water and fire scalds， trauma bleeding， etc. Studies on the mechanism of hemostasis have shown that Ca2+ （coagulation factor Ⅳ） is involved in many key processes of the internal and external coagulation cascades and can prevent bleeding by regulating platelet activation and aggregation， and promoting the production of insoluble fibrin and the ultimate formation of a blood clot. GF and GU both contain Ca2+ which provide an important material basis of hemostatic effect for both compounds， but GU has a significant hemostatic effect， while GF has no hemostatic effect. After processing， the taste and efficacy of the GF have been obviously changed which reflects the characteristics of processing， but the processing mechanism of GU has not been fully clarified. Therefore， based on studies of GF before and after calcining， this paper focused on these aspects including calcining process， crystal form comparison， element content， efficacy comparison， and summarized various aspects of Ca2+ involved in hemostasis. In addition， the hemostatic properties of other calcium-containing mineral medicines and new calcium-containing hemostatic materials such as calcium alginate， mesoporous calcium silicate and nanogel hemostatic materials were also discussed. The paper aimed to provide a reference for elucidating processing mechanism and clinical dialectical use of GU， also to promote development of new calcium-containing hemostatic materials.
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OBJECTIVE@#To observe the clinical effect of moxibustion combined with western medication for rheumatoid arthritis (RA) of liver-kidney deficiency, and explore the mechanism of moxibustion for RA.@*METHODS@#A total of 60 patients with RA of liver-kidney deficiency were randomly divided into an observation group and a control group, 30 cases in each group. In the control group，leflunomide tablets were taken orally, once a day. On the base of the treatment as the control group, moxibustion was applied at Sanyinjiao (SP 6), Shenshu (BL 23), Zusanli (ST 36) and @*RESULTS@#After treatment, the TCM syndrome scores, HAQ scores and DAS-28 scores were decreased in the two groups (@*CONCLUSION@#Moxibustion combined with western medication can effectively relieve clinical symptoms, improve quality of life in RA patients, the curative effect is better than simple western medication. And its mechanism may be related to the regulation of serum level of Ca
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Humans , Acupuncture Points , Arthritis, Rheumatoid/drug therapy , Kidney , Liver , Moxibustion , Quality of LifeABSTRACT
To research the auditory nerve transduction effects under multi-wavelength pulsed laser stimulations within a safe and acceptable signal range. The real-time detection of intracellular calcium concentration was adopted by specific fluorescent indicator staining based on calcium imager. The spiral ganglion cells of mice were cultured in vitro. After fluorescent indicating, morphologic observation under optical microscope, Fura-2 calcium ion fluorescence excitation, intact morphology cells selection, fixing the optical fiber, the spiral ganglion cells were irradiated by different wavelength laser, including visible light (450 nm) and near infrared light (808 nm,1 065 nm). The intracellular calcium concentration was monitored by calcium ion imaging. When 450 nm laser stimulated spiral ganglion cells, the intracellular calcium concentration was strongly increased, however, for other wavelength laser stimulation, there was no obvious relative response. And the sensitivity expression of the nerve cells under laser was related with the location of laser fiber. Cells closer to the fiber produced more obvious changes in calcium ion concentration, while for cells farther away from the fiber, the change amplitudes were weaker although the number of changes in calcium ion concentration was consistent. The spiral ganglion cells of mice can induce a signal transduction response under the action of laser, and the response has laser wavelength selectivity.
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Objective@#To research the auditory nerve transduction effects under multi-wavelength pulsed laser stimulations within a safe and acceptable signal range.@*Methods@#The real-time detection of intracellular calcium concentration was adopted by specific fluorescent indicator staining based on calcium imager. The spiral ganglion cells of mice were cultured in vitro. After fluorescent indicating, morphologic observation under optical microscope, Fura-2 calcium ion fluorescence excitation, intact morphology cells selection, fixing the optical fiber, the spiral ganglion cells were irradiated by different wavelength laser, including visible light (450 nm) and near infrared light (808 nm,1 065 nm). The intracellular calcium concentration was monitored by calcium ion imaging.@*Results@#When 450 nm laser stimulated spiral ganglion cells, the intracellular calcium concentration was strongly increased, however, for other wavelength laser stimulation, there was no obvious relative response. And the sensitivity expression of the nerve cells under laser was related with the location of laser fiber. Cells closer to the fiber produced more obvious changes in calcium ion concentration, while for cells farther away from the fiber, the change amplitudes were weaker although the number of changes in calcium ion concentration was consistent.@*Conclusion@#The spiral ganglion cells of mice can induce a signal transduction response under the action of laser, and the response has laser wavelength selectivity.
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Objective: To explore the mechanism of Salvia miltiorrhiza in treatment of microcirculatory disturbance based on network pharmacology. Methods: The targets of S. miltiorrhiza’s active components for treatment of microcirculatory disturbance were screened and predicted by utilizing TCMSP, PubChem Search, Genecards database and Swiss target prediction online tool. Cytoscape 3.3.0 software was adopted to construct an active component-microcirculatory disturbance target network. The protein-protein interaction (PPI) network was established by using STRING database. DAVID database was used to analyze metabolism pathway in target gene ontology (GO) biological process, Kyoto encyclopedia of genes and gnomes (KEGG). Results: Totally 65 active components of S. miltiorrhiza and nine related targets were screened. GO and KEGG pathway enrichment analysis revealed that active components of S. miltiorrhiza participated in oxidation-reduction process, cellular calcium ion homeostasis and other biological processes, and S. miltiorrhiza may regulate VEGF signaling pathway, cholinergic synapse signal transduction, oxytocin signaling pathway, aldosterone-regulated sodium reabsorption pathway and so on. Conclusion: This study reflects the characteristics of multi-components, multi-targets, and multi-pathways of S. miltiorrhiza in the treatment of microcirculation disturbance, which may provide new ideas and methodology for further research on the treatment of microcirculatory disturbance using S. miltiorrhiza.
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BACKGROUND: Opioids can regulate the changes of membrane potential and Ca2+ current in cardiomyocytes, but whether diacetylmorphine can induce the changes of cardiac rhythm, cell action potential and Ca2+ current has not been reported. OBJECTIVE: To explore the effect of diacetylmorphine on action potential and calcium current of isolated cardiomyocytes from neonatal Sprague-Dawley rats. METHODS: Five concentrations of diacetylmorphine (0, 10-2, 10-3, 10-4, 10-5 mol/L) and 20 mol/L verapamil were used to treat the cardiomyocytes of neonatal Sprague-Dawley rats cultured in vitro. The cells were divided into control group, diacetylmorphine group, diacetylmorphine+verapamil group. The latter two groups were treated with diacetylmorphine and diacetylmorphine+verapamil (20 μmol/L), respectively, while the control group was treated with the same amount of PBS. The study protocol was approved by the Animal Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University on May 21, 2018 with approval No. IACUC201805-K1. RESULTS AND CONCLUSION: At 24 hours of culture with different concentrations of diacetylmorphine, the number of cardiomyocytes with abnormal morphology increased significantly in a dose-dependent manner. When the concentration of diacetylmorphine increased, the number of survived cells decreased, with a reduction in the size of cytoplasm and number of pseudopods, the cell membrane was shrunk and the nuclear structure was blurred. Compared with the control group, when diacetylmorphine was added to intervene with the cardiomyocytes, there was a significant difference in the spontaneous beating frequency and rhythm of cardiomyocytes. The negative value of resting membrane potential decreased, while the time course of action potential increased significantly, and the amplitude of action potential decreased significantly. Compared with the control group, the number of cells with changes in the membrane potential significantly increased in the diacetylmorphine group. The addition of verapamil reduced the number of cells with changes in the membrane potential. Compared with the control group, the number of cells with variation of membrane potential was increased to some extents. These findings suggest that diacetylmorphine can induce cardiomyocyte morphological abnormality, increase the spontaneous beating frequency and rhythm of cardiomyocytes, and change the membrane potential and action potential of cardiomyocytes. Verapamil acts as a calcium channel blocker that can improve the rhythm abnormality of cardiomyocytes induced by diacetylmorphine.
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BACKGROUND: When regional citrate anticoagulation (RCA) is used in continuous renal replacement therapy (CRRT), one of the key aspects to achieve safe and effective extracorporeal circulation is the management of calcium ions. For calcium-free RCA-CRRT, there are generally two ways to do this: The deep vein and the venous line. The anticoagulant effects of different calcium supplementation pathways have not yet been explored. OBJECTIVE: In this trial, we would test our hypothesis that compared with the subclavian vein, when calcium was infused through the venous line of blood filter catheter, the arterial iCa2+ was lower. METHODS: This was a prospective, single-center, randomized crossover trial. From December 2018 to December 2019, 48 patients with RCA-CRRT at the Department of Intensive Care Unit of the First Hospital of Lanzhou University were selected. According to the different calcium sites, the patients were randomly divided into two groups. The calcium supplementation order of group A (n=24) was the venous line of the blood filter catheter-subclavian vein. Group B (n=24) was supplemented with subclavian vein-the venous line. Blood gas analysis results were compared using blood gas analyzers before and after replacement of the calcium supplementation route in all cases. The primary measurement outcome was the differences between arterial iCa2+ and post-filtration iCa2+ with different calcium supplementation pathways, and the simultaneous recording of pH, K+, and total hemoglobin. The secondary measurement outcomes were the incidences of catheter dysfunction and hypocalcemia during the intervention. The trial was approved by the Ethics Committee of the First Hospital of Lanzhou University (approval No. LDYYLL2018-165) in December 2018. The study was registered on the China Clinical Trial Registration Center (ChiCTRI 800020046) in December 2018. Sample and data collection time is from December 2018 to November 2019, data analysis time and test completion time is December 2019. DISCUSSION: This is the first trial on the anticoagulant effects of calcium-free RCA-CRRT through different calcium supplement routes. We will confirm that the arterial iCa2+ level is slightly lower when calcium is infused in the venous line of blood filter catheter than in the subclavian vein, and the incidence rates of catheter dysfunction and hypocalcemia will help us to determine which site is safer.
ABSTRACT
Stromal interaction molecule 1 (STIM1) is a transmembrane protein of the endoplasmic reticulum (ER) , a Ca2+ transducer in ER that activates the store-operated calcium channel.Through Orai1 protein, STIM1 adjusts the intracellular and extracellular calcium concentration.This way is called a store-operated Ca2+ entry.STIM1 plays a key role in phenotypic transformation of vascular smooth muscle cells, proliferation of endothelial cells, myocardial hypertrophy and myocardial fibrosis to regulate lots of cardiovascular diseases, such as atherosclerosis, congestive heart failure and systemic hypertension.STIM1 is closely related to cardiovascular diseases through calcium signal.The research progress of STIM1 in cardiovascular diseases is mainly discussed in this article.