Understanding the Coupling Mechanism of Intercalation and Conversion Hybrid Storage in Lithium-Graphite Anode.

Anodes with high capacity and long lifespan play an important role in the advanced batteries. However, none of the existing anodes can meet these two requirements simultaneously. Lithium (Li)-graphite composite anode presents great potential in balancing these two requirements. Herein, the working mechanism of Li-graphite composite anode is comprehensively investigated. The capacity decay features of the composite anode are different from those of Li ion intercalation in Li ion batteries and Li metal deposition in Li metal batteries. An intercalation and conversion hybrid storage mechanism are proposed by analyzing the capacity decay ratios in the composite anode with different initial specific capacities. The capacity decay models can be divided into four stages including Capacity Retention Stage, Relatively Independent Operation Stage, Intercalation & Conversion Coupling Stage, Pure Li Intercalation Stage. When the specific capacity is between 340 and 450 mAh g-1, its capacity decay ratio is between that of pure intercalation and conversion model. These results intensify the comprehensive understandings on the working principles in Li-graphite composite anode and present novel insights in the design of high-capacity and long-lifespan anode materials for the next-generation batteries.

Dendrobium officinale phenolic extract maintains proteostasis by regulating autophagy in a Caenorhabditis elegans model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and accumulating evidence suggested that proteostatic imbalance is a key feature of the disease. Traditional Chinese medicine exhibits a multi-target therapeutic effect, making it highly suitable for addressing protein homeostasis imbalance in AD. Dendrobium officinale is a traditional Chinese herbs commonly used as tonic agent in China. In this study, we investigated protection effects of D. officinale phenolic extract (SH-F) and examined its underlying mechanisms by using transgenic Caenorhabditis elegans models. We found that treatment with SH-F (50 µg/mL) alleviated Aß and tau protein toxicity in worms, and also reduced aggregation of polyglutamine proteins to help maintain proteostasis. RNA sequencing results showed that SH-F treatment significantly affected the proteolytic process and autophagy-lysosomal pathway. Furthermore, we confirmed that SH-F showing maintainance of proteostasis was dependent on bec-1 by qRT-PCR analysis and RNAi methods. Finally, we identified active components of SH-F by LC-MS method, and found the five major compounds including koaburaside, tyramine dihydroferulate, N-p-trans-coumaroyltyramine, naringenin and isolariciresinol are the main bioactive components responsible for the anti-AD activity of SH-F. Our findings provide new insights to develop a treatment strategy for AD by targeting proteostasis, and SH-F could be an alternative drug for the treatment of AD.

Electrochemically and Thermally Stable Inorganics-Rich Solid Electrolyte Interphase for Robust Lithium Metal Batteries.

Severe dendrite growth and high-level activity of the lithium metal anode lead to a short life span and poor safety, seriously hindering the practical applications of lithium metal batteries. With a trisalt electrolyte design, an F-/N-containing inorganics-rich solid electrolyte interphase on a lithium anode is constructed, which is electrochemically and thermally stable over long-term cycles and safety abuse conditions. As a result, its Coulombic efficiency can be maintained over 98.98% for 400 cycles. An 85.0% capacity can be retained for coin-type full cells with a 3.14 mAh cm-2 LiNi0.5 Co0.2 Mn0.3 O2 cathode after 200 cycles and 1.0 Ah pouch-type full cells with a 4.0 mAh cm-2 cathode after 72 cycles. During the thermal runaway tests of a cycled 1.0 Ah pouch cell, the onset and triggering temperatures were increased from 70.8 °C and 117.4 °C to 100.6 °C and 153.1 °C, respectively, indicating a greatly enhanced safety performance. This work gives novel insights into electrolyte and interface design, potentially paving the way for high-energy-density, long-life-span, and thermally safe lithium metal batteries.

Robotic versus laparoscopic surgery for sporadic benign insulinoma: Short- and long-term outcomes.

BACKGROUND: Minimally invasive surgery is the optimal treatment for insulinoma. The present study aimed to compare short- and long-term outcomes of laparoscopic and robotic surgery for sporadic benign insulinoma. METHODS: A retrospective analysis of patients who underwent laparoscopic or robotic surgery for insulinoma at our center between September 2007 and December 2019 was conducted. The demographic, perioperative and postoperative follow-up results were compared between the laparoscopic and robotic groups. RESULTS: A total of 85 patients were enrolled, including 36 with laparoscopic approach and 49 with robotic approach. Enucleation was the preferred surgical procedure. Fifty-nine patients (69.4%) underwent enucleation; among them, 26 and 33 patients underwent laparoscopic and robotic surgery, respectively. Robotic enucleation had a lower conversion rate to laparotomy (0 vs. 19.2%, P = 0.013), shorter operative time (102.0 vs. 145.5 min, P = 0.008) and shorter postoperative hospital stay (6.0 vs. 8.5 d, P = 0.002) than laparoscopic enucleation. There were no differences between the groups in terms of intraoperative blood loss, the rates of postoperative pancreatic fistula and complications. After a median follow-up of 65 months, two patients in the laparoscopic group developed a functional recurrence and none of the patients in the robotic group had a recurrence. CONCLUSIONS: Robotic enucleation can reduce the conversion rate to laparotomy and shorten operative time, which might lead to a reduction in postoperative hospital stay.

Adjuvant nab-paclitaxel plus gemcitabine vs gemcitabine alone for resected pancreatic ductal adenocarcinoma: A single center experience in China.

BACKGROUND: Nab-paclitaxel plus gemcitabine (AG) has resulted in higher tumor response and survival rates for metastatic or advanced pancreatic ductal adenocarcinoma (PDAC) compared with gemcitabine (GEM) alone. AIM: To examine the feasibility and safety of AG adjuvant chemotherapy of resectable PDAC. METHODS: We retrospectively analyzed patients with resected PDAC who received AG or GEM as postoperative adjuvant treatment between January 2013 and December 2016 at the Chinese People's Liberation Army General Hospital, Beijing, China. The patients adopted combined nab-paclitaxel (125 mg/m2) and GEM (1 g/m2) or GEM (1 g/m2) alone treatment, on days 1 and 8 every 3 wk for six cycles, unless intolerable adverse events or disease progression occurred. The disease-free survival, overall survival (OS) and adverse events of the two groups were statistically analyzed. RESULTS: Compared with GEM, median disease-free survival (12.2 mo vs 15.8 mo, P = 0.039) and OS (20.6 mo vs 28.3 mo, P = 0.028) were significantly improved in the AG group. The 2-year OS rates were 63.3% and 43.3% in the AG and GEM groups, respectively. However, the incidence of sensory neuropathy was increased significantly in the AG than the GEM group (53.3% vs 23.3%, P < 0.001). CONCLUSION: In our initial experience, AG significantly improved disease-free survival and OS of patients with resected PDAC. AG may be a potential option for postoperative adjuvant chemotherapy of resectable PDAC.

Robotic vs laparoscopic hemihepatectomy: A comparative study from a single center.

BACKGROUND: Robotic surgery is increasingly being used in hepatectomy. Previous studies comparing the robotic and laparoscopic minor hepatectomy have been documented, but comparative studies on robotic and laparoscopic hemihepatectomy (LH) involving a large patient cohort are rare. The objective of this study was to compare perioperative outcomes between robotic and LH. METHODS: Data on the demographics, clinicopathologic characteristics, and perioperative outcomes of consecutive patients who underwent robotic or LH in a single center between November 2011 and July 2017 were analyzed. RESULTS: A total of 92 patients underwent robotic and 48 LH. Multiple linear regression analysis showed no significant difference in perioperative outcomes including operative time, postoperative hospital stay, postoperative complications, and mortality between the groups. Compared to the laparoscopic cohort, the robotic cohort had a significantly less estimated blood loss (120.24 mL; 95% confidence interval, 53.72-186.76) and a significantly lower conversation rate (1.09% vs 10.42%; P = .034). Stratified and interaction analyses demonstrated that disease type had an interaction effect on the association between the operative approach and the estimated blood loss. CONCLUSIONS: Robotic hemihepatectomy was safe and feasible in selected patients. It had similar perioperative outcomes as LH and was better than LH regarding estimated blood loss and open conversion.

A Rapid Detection Method for Morphological Characteristics of Biological Cells Based on Phase Imaging.

This paper presents a rapid label-free method for the identification of morphological characteristics of biological cells. Based on quantitative phase microscopy as well as the connotation of phase value, the gradient operator of phase and the associated analytic processing are employed to determine the edge of different parts of the samples. A heterogeneous biological cell model is established by simulation to show the mechanism of this method and a polystyrene bead is selected as a sample to confirm its validity by optical experiment. The result agrees well with the actual situation and this approach is proved to have good antinoise ability. Furthermore, a neutrophil is investigated by this method. Based on the optical experiment and the related analysis, the basic structure characteristics of the cell are obtained. It is indicated that the method presented in this paper could be applied to rapid identification and classification of living cells.

Repeatability of the "flash-replenishment" method in contrast-enhanced ultrasound for the quantitative assessment of hepatic microvascular perfusion.

This study aimed to evaluate the feasibility and repeatability of the flash-replenishment method in contrast-enhanced ultrasound (CEUS) perfusion imaging and assess quantitatively microvascular perfusion in the liver. Twenty healthy New Zealand rabbits were submitted to CEUS perfusion imaging with continuous intravenous infusion. Using flash-replenishment kinetics, the dynamic process of depletion and refilling of microbubble contrast agent was recorded. The hepatic microvascular perfusion parameters were calculated, including region of interest, peak intensity (PI), area under the curve (AUC), and hepatic artery to vein transit time (HA-HVTT). A consistency test was performed for multiple measurements by the same operator and blind measurements by two different operators. The hepatic perfusion imaging of 3×108 bubbles/min had minimal error and the best imaging effect and repeatability. The variability of the perfusion parameter measured at 3 cm depth under the liver capsule was at a minimum with coefficient of variation of 3.9%. The interclass correlation coefficient (ICC) of measurements taken by the same operator was 0.985, (95% confidence interval, CI=0.927-0.998). Measurements taken by two operators had good consistency and reliability, with the ICC of 0.948 (95%CI=0.853-0.982). The PI and AUC of liver parenchyma after reperfusion were lower than before blocking; and HA-HVTT was significantly longer than before blocking (P<0.05). The flash-replenishment method in CEUS perfusion imaging showed good stability and repeatability, which provide a valuable experimental basis for the quantitative assessment of hepatic microvascular perfusion in clinical practice.

[A single-team experience with robotic pancreatic surgery in 1010 cases].

OBJECTIVE: To assess the safety and advantages of robotic pancreatic surgery (RPS) based on the single-team experience with 1010 cases. METHODS: The clinical data of 1010 cases of RPS performed by a single team from November, 2011 to September, 2017 in our hospital were collected prospectively and analyzed. In most of cases the surgeries were performed using the third-generation da Vinci robotic surgical system. RESULTS: The 1010 cases receiving RPS included 417 cases of robotic pancreatoduodenectomy (RPD), 428 cases of robotic distal pancreatectomy, 60 cases of robotic central pancreatectomy, 53 cases of robotic pancreatic tumor enucleation, 3 cases of Appleby procedure, and 49 cases of other operations (including 4 cases of innovative robotic retroperitoneal laparoscopic surgery, 4 cases of robotic pancreatic tumor enucleation combined with main pancreatic duct bridging repair, 1 case of single incision robotic pancreatic tumor enucleation, and 2 cases of robotic central pancreatectomy combined with end-to-end anastomosis reconstruction). The median operative time was 210 min (30-720 min) with a median intraoperative blood loss of 80 mL (10-2000 mL), a conversion rate of 4.06% (41/1010), a blood transfusion rate of 6.7% (68/1010), a mean post-operative stay of 10.87∓6.70 days, a complication rate (beyond grade III according to Clavien-Dindo scoring system) of 8.0% (81/1010), and a pancreatic fistula rate (beyond) grade B of 9.21% (93/1010). The mortality rate of the patients was 0.69% (7/1010) in 30 days and 1.31% (12//934) in 90 days. The application of RPS in total pancreatectomy increased steadily from the rate of 10.44% in 2012 to 72.06% in 2017. CONCLUSION: This represents to our knowledge the world largest series of robotic pancreatic resections. RPS is expected to gradually replace open procedure and laparoscopic procedure to become the primary choice of approach for pancreatectomy. After the learning curve, RPS procedure including distal pancreatectomy, robotic Appleby procedure and other operations can be safely performed, and the experiences from other centers can be beneficial to reduce severe complications in the early stage of learning.

Quantitative Evaluation of Hepatic Microvascular Perfusion after Ischemia-Reperfusion Injury in Rabbits by Contrast-Enhanced Ultrasound Perfusion Imaging.

The aim of this study was to evaluate microvascular perfusion after liver ischemia-reperfusion injury (IRI) in rabbits using the "flash-replenishment" method of contrast-enhanced ultrasound (CEUS) perfusion imaging. Twenty-eight rabbits underwent either 30, 60 or 90 min of ischemia and 120 min of reperfusion. CEUS perfusion imaging was performed using the "flash-replenishment" model, and hepatic microvascular perfusion parameters, including peak intensity (PI), area under the curve (AUC), and hepatic artery-to-vein transit time (HA-HVTT), were calculated. Prolonged ischemia upregulated intracellular adhesion molecule-1 (ICAM-1), alanine transaminase (ALT) and aspartate transaminase (AST) levels. Longer ischemia decreased PI and AUC, but increased HA-HVTT. The perfusion parameters were significantly correlated with Suzuki's pathology scores and ALT and AST levels. The "flash-replenishment" method of CEUS perfusion imaging is an accurate and non-invasive method for evaluating hepatic microvascular perfusion and provides a valuable experimental basis for early prediction of liver IRI damage after liver transplantation or liver resection.

Repeatability of the "flash-replenishment" method in contrast-enhanced ultrasound for the quantitative assessment of hepatic microvascular perfusion

This study aimed to evaluate the feasibility and repeatability of the flash-replenishment method in contrast-enhanced ultrasound (CEUS) perfusion imaging and assess quantitatively microvascular perfusion in the liver. Twenty healthy New Zealand rabbits were submitted to CEUS perfusion imaging with continuous intravenous infusion. Using flash-replenishment kinetics, the dynamic process of depletion and refilling of microbubble contrast agent was recorded. The hepatic microvascular perfusion parameters were calculated, including region of interest, peak intensity (PI), area under the curve (AUC), and hepatic artery to vein transit time (HA-HVTT). A consistency test was performed for multiple measurements by the same operator and blind measurements by two different operators. The hepatic perfusion imaging of 3×108 bubbles/min had minimal error and the best imaging effect and repeatability. The variability of the perfusion parameter measured at 3 cm depth under the liver capsule was at a minimum with coefficient of variation of 3.9%. The interclass correlation coefficient (ICC) of measurements taken by the same operator was 0.985, (95% confidence interval, CI=0.927-0.998). Measurements taken by two operators had good consistency and reliability, with the ICC of 0.948 (95%CI=0.853-0.982). The PI and AUC of liver parenchyma after reperfusion were lower than before blocking; and HA-HVTT was significantly longer than before blocking (P<0.05). The flash-replenishment method in CEUS perfusion imaging showed good stability and repeatability, which provide a valuable experimental basis for the quantitative assessment of hepatic microvascular perfusion in clinical practice.

Evaluation of Liver Ischemia-Reperfusion Injury in Rabbits Using a Nanoscale Ultrasound Contrast Agent Targeting ICAM-1.

OBJECTIVE: To assess the feasibility of ultrasound molecular imaging in the early diagnosis of liver ischemia-reperfusion injury (IRI) using a nanoscale contrast agent targeting anti-intracellular adhesion molecule-1 (anti-ICAM-1). METHODS: The targeted nanobubbles containing anti-ICAM-1 antibody were prepared using the avidin-biotin binding method. Human hepatic sinusoidal endothelial cells (HHSECs) were cultured at the circumstances of hypoxia/reoxygenation (H/R) and low temperature. The rabbit liver IRI model (I/R group) was established using the Pringle's maneuver. The time-intensity curve of the liver contrast ultrasonographic images was plotted and the peak intensity, time to peak, and time of duration were calculated. RESULTS: The size of the targeted nanobubbles were 148.15 ± 39.75 nm and the concentration was 3.6-7.4 × 109/ml, and bound well with the H/R HHSECs. Animal contrast enhanced ultrasound images showed that the peak intensity and time of duration of the targeted nanobubbles were significantly higher than that of common nanobubbles in the I/R group, and the peak intensity and time of duration of the targeted nanobubbles in the I/R group were also significantly higher than that in the SO group. CONCLUSION: The targeted nanobubbles have small particle size, stable characteristic, and good targeting ability, which can assess hepatic ischemia-reperfusion injury specifically, noninvasively, and quantitatively at the molecular level.

Effect of Pressure on Liver Stiffness During the Development of Liver Fibrosis in Rabbits.

This study was designed to investigate whether hepatic arterial pressure and portal pressure have an effect on liver stiffness during the development of liver fibrosis. Liver fibrosis was induced in 50 healthy New Zealand white rabbits. Laparotomy was performed to measure liver stiffness, and the portal vein and hepatic artery were successively ligated to repeat the measurements. A significant difference was observed among liver stiffness values measured at different time points (F = 22.82, p < 0.001). Differences between original liver stiffness and liver stiffness measured after portal ligation were positively correlated with portal pressure (r = 0.801, p < 0.001). In animals with grade 4 liver fibrosis, the increase in liver stiffness caused by pressure was greater than that caused by extracellular matrix accumulation (p = 0.002). In conclusion, hepatic arterial pressure and portal pressure have a significant effect on liver stiffness during the development of liver fibrosis.

Roles of acoustic radiation force impulse and two-dimensional shearwave elastography in grading liver fibrosis in rabbits.

OBJECTIVE: To explore the difference between acoustic radiation force impulse (ARFI) and two-dimensional shearwave elastography (2D-SWE) in grading liver fibrosis (LF). METHODS: Sixty New Zealand rabbits were divided into control group (n=10; without any treatment) and LF group (n=50; treated with CCl4 to induce LF at different degrees). Liver stiffness (LS) were measured in all the animals using ARFI and 2D-SWE, and liver tissues in the same sites were collected for pathological analysis. Spearman's rank-correlation coefficient was used for analysis between LF and LS,and the receiver operating characteristic curve was constructed to analyze the difference of the diagnostic performance of the two techniques. RESULTS: Data were obtained from 37 animals, among which 14 sites was at F0,11 sites at F1,12 sites at F3,and 22 sites at F4.All the LS measurements were successfully performed.A significant correlation between LS and ARFI results (r=0.802,P<0.01)as well as a significant correlation between LF and 2D-SWE results (r=0.892, P<0.01)were found. The receiver operating characteristic curves were successfully constructed. The area under the curve for diagnosing LF higher than F0, F1, F2 and F3 were 0.809,0.916,0.938, and 0.934, respectively, for ARFI, and those were 0.917,0.935,0.976, and 0.974, respectively,for 2D-SWE. CONCLUSION: ARFI and 2D-SWE can accurately grade LF,and 2D-SWE has a better diagnostic performance than ARFI.

A novel hemostatic sealant composed of gelatin, transglutaminase and thrombin effectively controls liver trauma-induced bleeding in dogs.

AIM: novel hemostatic sealant based on the in situ gel formation of gelatin catalyzed by thrombin and crosslinked by transglutaminase was designed. The aim of this study was to investigate the efficacy of the hemostatic sealant in control of bleeding caused by liver trauma in dogs. METHODS: Hepatic trauma that mimicked the grade III-IV rupture of liver was made in 20 dogs. The traumatic lesion was topically administered the hemostatic sealant (treatment group, n=10), or a thrombin solution (control group, n=10). The time to achieve hemostasis and the blood loss were measured. Contrast-enhanced ultrasound (CEUS) examination was performed in each animal on d 3, d 7, and d 10 d postoperatively to study the healing of the lesions. RESULTS: The mean time to achieve hemostasis in the treatment group was significantly shorter than that in the control group (1.20±0.33 vs 6.70±0.64 min, P<0.05). The mean blood loss in the treatment group was significantly less than that in the control group (47.22±8.61 vs 79.29±11.97 mL, P<0.05). In CEUS examination, the traumatic lesions in the treatment group became significantly smaller on d 3, and disappeared on d 7, whereas the lesions in the control group still existed on d 10. Ascites were never found during 10 d follow-up in the treatment group but were observed on d 3 and d 7 in the control group. CONCLUSION: Compared with thrombin, the novel hemostatic sealant shows much better efficacy in hemostasis and may promote wound healing in dog liver trauma.

[Liver stiffness measured by acoustic radiation force impulse imaging in assessing hepatic functional reserve in patients with space-occupying lesions in the liver].

OBJECTIVE: To investigate the value of liver stiffness measured by acoustic radiation force impulse imaging(ARFI) in assessing hepatic functional reserve in patients with space-occupying lesions in the liver. METHODS: Sixty-three patients with space-occupying lesions in the liver were enrolled. Liver stiffness (LS) measurements with ARFI and indocyanine green(ICG) retention test were performed in the same day, and plasma clearance rate of indocyanine green(ICG-K), ICG retention at 15 minutes(ICGR15) as well as 10 effective values of LS were recorded. The correlation between Child-Pugh score, ICGR15, ICG-K, and LS were evaluated. RESULTS: The LS measurements with ARFI failed in one patient. A strong correlation between LS and ICGR15(r=0.789, P<0.01) and an inverse correlation between LS and ICG-K(r=-0.738, P<0.01) were observed. Besides, there was a significant correlation between LS measurements and Child-Pugh score(r=0.929, P<0.01) . The LS significantly differed among patients with Child-Pugh class A, B, and C(P<0.01) . CONCLUSION: ARFI is a simple, feasible and non-invasive method for assessing hepatic functional reserve in patients with space-occupying lesions in the liver.

Effect of interleukin-6 (IL-6) on the vascular smooth muscle contraction in abdominal aorta of rats with streptozotocin-induced diabetes.

Patients with type 1 diabetes are at a risk of hypertension. However, the mechanisms behind the findings are not completely known. The aim of the present study was to investigate involvement of interleukin-6 (IL-6) on the contraction of abdominal aorta in rats with type 1 diabetes. IL-6 levels in the plasma of rats with streptozotocin (STZ)-induced diabetes were determined by ELISA. The abdominal aorta was dissected free of fat and connective tissues and then cut into spiral rings. The endothelium-denuded strip was vertically suspended in tissue chambers containing 5 ml Krebs solution at 37 degrees C and bubbled continuously with 95% O2-5% CO2. The effects of phenylephrine (Phe) on the contractile responses of abdominal aorta were recorded. The effects of IL-6 and anti-rat IL-6 antibody on the Phe-induced response were also examined. Plasma levels of IL-6 increased time-dependently in rats with STZ-induced diabetes. Phe caused concentration-dependent contraction in aortic rings. Phe-induced contractions were higher in vascular strips of STZ-induced diabetic rats than that of control rats. Pretreatment of vascular strips with IL-6 for 1 h did not cause contraction but enhanced the contraction in response to Phe. Treatment of the vascular strips with an anti-IL-6 antibody for 1 h decreased the Phe-induced contractions. These results suggest that IL-6 causes vascular smooth muscle contraction in abdominal aorta of rats with type 1 diabetes.

Angiotensin-converting enzyme 2 attenuates atherosclerotic lesions by targeting vascular cells.

Angiotensin-converting enzyme 2 (ACE2) is a newly discovered homolog of ACE whose actions oppose those of angiotensin II (AngII). However, the underlying mechanisms by which ACE2 effectively suppresses early atherosclerotic lesions remain poorly understood. Here, we show, both in vitro and in vivo, that ACE2 inhibited the development of early atherosclerotic lesions by suppressing the growth of vascular smooth muscle cells (VSMCs) and improving endothelial function. In a relatively large cohort animal study (66 rabbits), aortic segments transfected by Ad-ACE2 showed significantly attenuated fatty streak formation, neointimal macrophage infiltration, and alleviation of impaired endothelial function. Segments also showed decreased expression of monocyte chemoattractant protein 1, lectin-like oxidized low-density lipoprotein receptor 1, and proliferating cell nuclear antigen, which led to the delayed onset of atherosclerotic lesions. At the cellular level, ACE2 significantly modulated AngII-induced growth and migration in human umbilical vein endothelial cells and VSMCs. The antiatherosclerotic effect of ACE2 involved down-regulation of the ERK-p38, JAK-STAT, and AngII-ROS-NF-kappaB signaling pathways and up-regulation of the PI3K-Akt pathway. These findings revealed the molecular mechanisms of the antiatherosclerotic activity of ACE2 and suggested that modulation of ACE2 could offer a therapeutic option for treating atherosclerosis.

Arecoline excites the contraction of distal colonic smooth muscle strips in rats via the M3 receptor-extracellular Ca2+ influx - Ca2+ store release pathway.

Areca is a Chinese herbal medicine that is widely used for constipation. However the mechanisms of its action are not clear. We investigated the effects of arecoline, the most active component of areca, on the motility of rat distal colonic smooth muscle strips. In longitudinal muscle of distal colon (LMDC) and circular muscle of distal colon (CMDC), arecoline increased the contraction in a dose-dependent manner. Tetrodotoxin (TTX) did not inhibit the effects of arecoline. The contractile response to arecoline was completely antagonized by atropine. 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) strongly depressed the response to arecoline, but gallamine and methoctramine did not. Nifedipine, 2-aminoethoxydiphenyl borate (2-APB), and Ca2+-free Krebs solution with EGTA partly inhibited the effects of arecoline. The sum of Ca2+-free Krebs solution, EGTA, and 2-APB completely inhibited the effects of arecoline. The results show that arecoline stimulates distal colonic contraction in rats via the muscarinic (M3) receptor - extracellular Ca2+ influx - Ca2+ store release pathway. It is likely that the action of areca in relieving constipation is due to its stimulation of muscle contraction.