Surface with well-defined components and structures possesses unique electronic,magnetic,optical and chemical properties.As a result,surface chemistry research plays a crucial role in various fields such as catalysis,...Surface with well-defined components and structures possesses unique electronic,magnetic,optical and chemical properties.As a result,surface chemistry research plays a crucial role in various fields such as catalysis,energy,materials,quantum,and microelectronics.Surface science mainly investigates the correspondence between surface property and functionality.Scanning probe microscopy(SPM)techniques are important tools to characterize surface properties because of the capability of atomic-scale imaging,spectroscopy and manipulation at the single-atom level.In this review,we summarize recent advances in surface electronic,magnetic and optical properties characterized mainly by SPM-based methods.We focus on elucidating theπ-magnetism in graphene-based nanostructures,construction of spin qubits on surfaces,topology properties of surface organic structures,STM-based light emission,tip-enhanced Raman spectroscopy and integration of machine learning in SPM studies.展开更多
Surface chemistry focuses on the investigation of the adsorption,migration,assembly,activation,reaction,and desorption of atoms and molecules at surfaces.Surface chemistry plays the pivotal roles in both fundamental s...Surface chemistry focuses on the investigation of the adsorption,migration,assembly,activation,reaction,and desorption of atoms and molecules at surfaces.Surface chemistry plays the pivotal roles in both fundamental science and applied technology.This review will summarize the recent progresses on surface assembly,synthesis and catalysis investigated mainly by scanning tunneling microscopy and atomic force microscopy.Surface assemblies of water and small biomolecules,construction of Sierpin′ski triangles and surface chirality are summarized.On-surface synthesis of conjugated carbo-and heterocycles and other kinds of carbon nanostructures are surveyed.Surface model catalysis,including single-atom catalysis and electrochemical catalysis,are discussed at the single-atom level.展开更多
AIM:Danshen's capability to induce salivary fluid secretion and its mechanisms were studied to determine if it could improve xerostomia.METHODS:Submandibular glands were isolated from male Wistar rats under system...AIM:Danshen's capability to induce salivary fluid secretion and its mechanisms were studied to determine if it could improve xerostomia.METHODS:Submandibular glands were isolated from male Wistar rats under systemic anesthesia with pentobarbital sodium.The artery was cannulated and vascularly perfused at a constant rate.The excretory duct was also cannulated and the secreted saliva was weighed in a cup on an electronic balance.The weight of the accumulated saliva was measured every 3 s and the salivary flow rate was calculated.In addition,the arterio-venous difference in the partial oxygen pressure was measured as an indicator of oxygen consumption.In order to assess the mechanism involved in Dansheninduced fluid secretion,either ouabain(an inhibitor of Na+/K+ ATPase) or bumetanide(an inhibitor of NKCC1) was additionally applied during the Danshen stimulation.In order to examine the involvement of the main membrane receptors,atropine was added to block the M3 muscarinic receptors,or phentolamine was added to block the α1 adrenergic receptors.In order to examine the requirement for extracellular Ca2+,Danshen was applied during the perfusion with nominal Ca2+ free solution.RESULTS:Although Danshen induced salivary fluid secretion,88.7 ± 12.8 μL/g-min,n = 9,(the highest value around 20 min from start of DS perfusion was significantly high vs 32.5 ± 5.3 μL/g-min by carbamylcholine,P = 0.00093 by t-test) in the submandibular glands,the time course of that secretion differed from that induced by carbamylcholine.There was a latency associated with the fluid secretion induced by Danshen,followed by a gradual increasein the secretion to its highest value,which was in turn followed by a slow decline to a near zero level.The application of either ouabain or bumetanide inhibited the fluid secretion by 85% or 93%,and suppressed the oxygen consumption by 49% or 66%,respectively.These results indicated that Danshen activates Na+/K+ ATPase and NKCC1 to maintain Cl- release and K+ release for fluid secretion.Neither atropine or phentolamine inhibited the fluid secretion induced by Danshen(263% ± 63% vs 309% ± 45%,227% ± 63% vs 309% ± 45%,P = 0.899,0.626 > 0.05 respectively,by ANOVA).Accordingly,Danshen does not bind with M3 or α1 receptors.These characteristics suggested that the mechanism involved in DS-induced salivary fluid secretion could be different from that induced by carbamylcholine.Carbamylcholine activates the M3 receptor to release inositol trisphosphate(IP3) and quickly releases Ca2+ from the calcium stores.The elevation of [Ca2+]i induces chloride release and quick osmosis,resulting in an onset of fluid secretion.An increase in [Ca2+]i is essential for the activation of the luminal Cl- and basolateral K+ channels.The nominal removal of extracellular Ca2+ totally abolished the fluid secretion induced by Danshen(1.8 ± 0.8 μL/g-min vs 101.9 ± 17.2 μL/g-min,P = 0.00023 < 0.01,by t-test),suggesting the involvement of Ca2+ in the activation of these channels.Therefore,IP3-store Ca2+ release signalling may not be involved in the secretion induced by Danshen,but rather,there may be a distinct signalling process.CONCLUSION:The present findings suggest that Danshen can be used in the treatment of xerostomia,to avoid the systemic side effects associated with muscarinic drugs.展开更多
A central objective in deciphering the nervous system in health and disease is to define the connections of neurons. The propensity of neurotropic viruses to spread among synaptically-linked neurons makes them ideal f...A central objective in deciphering the nervous system in health and disease is to define the connections of neurons. The propensity of neurotropic viruses to spread among synaptically-linked neurons makes them ideal for mapping neural circuits. So far, several classes of viral neuronal tracers have become available and provide a powerful toolbox for delineating neural networks. In this paper, we review the recent developments of neurotropic viral tracers and highlight their unique properties in revealing patterns of neuronal connections.展开更多
AIM: To systematically review pathological changes of gastric mucosa in gastric atrophy (GA) and intestinal metaplasia (IM) after Helicobacter pylori (H. pylori) eradication.
AIM: To investigate nicotinamide’s action on glucose metabolism, and the association between niacin consumption and obesity prevalence. METHODS: Dynamic nicotinamide’s effect on plasma hydrogen peroxide and glucose ...AIM: To investigate nicotinamide’s action on glucose metabolism, and the association between niacin consumption and obesity prevalence. METHODS: Dynamic nicotinamide’s effect on plasma hydrogen peroxide and glucose metabolism was in- vestigated using oral glucose tolerance tests with or without nicotinamide in the same five healthy subjects.Lag-regression analysis was used to examine the association between the niacin consumption and the obesity prevalence among US children using the data from the Economic Research Service of the US Department of Agriculture and from US Centers for Disease Control and Prevention, respectively. RESULTS: Compared with the control oral glucose tolerance test, the 1-h plasma hydrogen peroxide (1.4 ± 0.1 μmol/L vs 1.6 ± 0.1 μmol/L, P = 0.016) and insulin levels (247.1 ± 129.0 pmol/L vs 452.6 ± 181.8 pmol/L, P = 0.028) were signif icantly higher, and the 3-h blood glucose was signif icantly lower (5.8 ± 1.2 mmol/L vs 4.5 ± 1.1 mmol/L, P = 0.002) after coadministration of glucose and 300 mg nicotinamide. The obesity prevalence among American children increased with the increasing per capita niacin consumption, the increasing grain contribution to niacin due to niacin-fortification, and the increasing niacin-fortified ready-to-eat cereal consumption, with a 10-year lag. The regression analyses showed that the obesity prevalence in the US children of all age groups was determined by niacin consumption (R2 = 0.814, 0.961 and 0.94 for 2-5 years, 6-11 years and 12-19 years age groups, respectively). CONCLUSION: The appetite-stimulating effect of nicotinamide appears to involve oxidative stress. Excess niacin consumption may be a major factor in the increased obesity prevalence in US children.展开更多
AIM： TO determine whether Chinese herbs （CHs） relieve xerostomia （dry mouth） by increasing salivary secretion. METHODS： The submandibular glands of Wistar rats were surgically isolated and perfused arterially wi...AIM： TO determine whether Chinese herbs （CHs） relieve xerostomia （dry mouth） by increasing salivary secretion. METHODS： The submandibular glands of Wistar rats were surgically isolated and perfused arterially with buffered salt solution. After control perfusion, recording started 5 min prior to the start of stimulation. After fluid secretion was induced by 0.2 μmol/L carbamylcholine （CCh） in the perfusate for 10 min, Chinese herb （CH） was added in the perfusion for 5 min. CCh was then overloaded at 0.2 μmol/L in the perfusion for 20 min. The volume of salivary fluid secretion was recorded by a computer-controlled balance system. RESULTS： Saliva secretion formed an initial ephemeral peak at 30 s followed by a gradual increase to a sustained level. CH alone induced no or little saliva in all types of CH selected. During perfusion with CH,overloading of CCh promoted fluid secretion in 1S of 20 CHs. This promotion was classified into four patterns, which were eventually related to the categories of CH： Overall sustained phase was continuously raised （Yin-nourishing, fluid production-promoting and heatclearing agents）; The sustained secretion rose to reach a maximum then decreased （Qi-enhancing agent）; Sustained secretion rose to reach the highest maximum and was then sustained with a slight decline （swelling-reducing, phlegm-resolving and pus-expelling agents）; Stimulation of salivary secretion without any added stimulants. Addition of CCh raised the fluid secretion to reach the highest maximum then sharply decreased to a lower sustained level （blood activating agent）. CONCLUSION： The present findings lead to the conclusion that various CHs have different promotional effects directly on the salivary gland.展开更多
Over the past few decades,food fortification and infant formula supplementation with high levels of vitamins have led to a sharp increase in vitamin intake among infants,children and adults.This is followed by a sharp...Over the past few decades,food fortification and infant formula supplementation with high levels of vitamins have led to a sharp increase in vitamin intake among infants,children and adults.This is followed by a sharp increase in the prevalence of obesity and related diseases,with significant disparities among countries and different groups within a country.It has long been known that B vitamins at doses below their toxicity threshold strongly promote body fat gain.Studies have demonstrated that formulas,which have very high levels of vitamins,significantly promote infant weight gain,especially fat mass gain,a known risk factor for children developing obesity.Furthermore,ecological studies have shown that increased B vitamin consumption is strongly correlated with the prevalence of obesity and diabetes.We therefore hypothesize that excess vitamins may play a causal role in the increased prevalence of obesity.This review will discuss:(1)the causes of increased vitamin intake;(2)the non-monotonic effect of excess vitamin intake on weight and fat gain;and(3)the role of vitamin fortification in obesity disparities among countries and different groups within a country.展开更多
AIM： To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS： Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of...AIM： To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS： Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N^1-methylnicotinamide on glucose metabolism, plasma HzO2 levels and tissue nicotinamide adenine dinucleotide （NAD） contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively. RESULTS： Diabetic subjects had significantly higher plasma N^1-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects （0.89 ± 0.13 μmol/L vs 0.6 ± 0.13 μmol/L, P 〈 0.001）. Cumulative doses of nicotinamide （2 g/kg） significantly increased rat plasma Nl-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by Nl-methy-Inicotinamide. Moreover, cumulative exposure to N^1- methylnicotinamide （2 g/kg） markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/ NADH ratio, and increased plasma H2O2 levels. Decrease in NAD/NADH ratio and increase in H2O2 generation were also observed in human erythrocytes after exposure to N^1-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide （5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load）. Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N^1- methylnicotinamide clearance. CONCLUSION： These findings suggest that nicotinamide overload, which induced an increase in plasma N^1- methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.展开更多
We describe a 77-year-old man with refractory gastric ulcer that worsened after Helicobacter pylori eradication therapy.Pathology showed marked infiltration of IgG4-positive plasma cells in the gastric lesions,which l...We describe a 77-year-old man with refractory gastric ulcer that worsened after Helicobacter pylori eradication therapy.Pathology showed marked infiltration of IgG4-positive plasma cells in the gastric lesions,which led us to suspect IgG4-related sclerosing disease.To the best of our knowledge,this is the first report of IgG4-related gastric ulcer without the main manifestation of autoimmune pancreatitis.展开更多
AIM: To explore the expression of transient receptor potential vanilloid 4(TRPV4) and its physiological meaning in mouse and rat gastric epithelia. METHODS: RT-PCR and immunochemistry were used to detect TRPV4 m RNA a...AIM: To explore the expression of transient receptor potential vanilloid 4(TRPV4) and its physiological meaning in mouse and rat gastric epithelia. METHODS: RT-PCR and immunochemistry were used to detect TRPV4 m RNA and protein expression in mouse stomach and a rat normal gastric epithelial cell line(RGE1-01), while Ca2+-imaging and electrophysiology were used to evaluate TRPV4 channel activity. ATP release was measured by a luciferin-luciferase assay. Gastric emptying was also compared between WT and TRPV4 knockout mice. RESULTS: TRPV4 m RNA and protein were detected in mouse tissues and RGE1-01 cells. A TRPV4-specific agonist(GSK1016790A) increased intracellular Ca2+ concentrations and/or evoked TRPV4-like current activities in WT mouse gastric epithelial cells andRGE1-01 cells, but not TRPV4 KO cells. GSK1016790 A or mechanical stimuli induced ATP release from RGE1-01 cells while TRPV4 knockout mice displayed delayed gastric emptying in vivo. CONCLUSION: TRPV4 is expressed in mouse and rat gastric epithelium and contributes to ATP release and gastric emptying.展开更多
In the present study, we aimed to evaluate the pathways contributing to ATP release from mouse astrocytes during hypoosmotic stress. We first examined the expression of mRNAs for proteins constituting possible ATP- re...In the present study, we aimed to evaluate the pathways contributing to ATP release from mouse astrocytes during hypoosmotic stress. We first examined the expression of mRNAs for proteins constituting possible ATP- releasing pathways that have been suggested over the past several years. In RT-PCR analysis using both control and osmotically swollen astrocytes, amplification of cDNA fragments of expected size was seen for connexins （Cx32, Cx37, Cx43）, pannexin 1 （Pxl）, the P2X7 receptor, MRP1 and MDR1, but not CFTR. Inhibitors of exocytotic vesicular release, gap junction hemi-channels, CFTR, MRP1, MDR1, the P2X7 receptor, and volume-sensitive outwardly rectifying chloride channels had no significant effects on the massive ATP release from astrocytes. In contrast, the hypotonicity-induced ATP release from astrocytes was most effectively inhibited by gadolinium （50 μM）, an inhibitor of the maxi-anion channel, which has recently been shown to serve as a pathway for ATP release from several other cell types. Thus, we propose that the maxi-anion channel constitutes a major pathway for swelling-induced ATP release from cultured mouse astrocytes as well.展开更多
AIM To evaluate the prognostic significance of perioperative carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)levels in stageⅡ/Ⅲgastric cancer.METHODS From a multi-institutional retrospective databa...AIM To evaluate the prognostic significance of perioperative carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)levels in stageⅡ/Ⅲgastric cancer.METHODS From a multi-institutional retrospective database compiled by integrating clinical data from nine institutions,data of 998 patients who underwent curative resection for stageⅡ/Ⅲgastric cancer between 2010 and 2014 were retrieved and analyzed.The prognostic impact of the preoperative and postoperative levels and chronological changes in CEA,CA19-9 and their combination were evaluated.To test whether postoperative adjuvant chemotherapy alters the prognostic impact of perioperative CEA and CA19-9 levels,the hazard ratios for mortality were compared between patients who underwent surgery alone and patients who underwent surgery followed by adjuvant chemotherapy.RESULTS The prognostic impact of postoperative CEA and CA19-9 was superior to that of the preoperative levels.Multivariable analysis identified high postoperative CEA and CA19-9 levels as independent prognostic factors for overall survival.Disease-free survival rates clearly decreased in a stepwise manner in association with postoperative CEA and CA19-9 levels,and patients with high levels of both markers showed significantly poorer prognosis than other patient groups.When we analyzed perioperative changes in serum CEA and CA19-9 levels,patients with high levels before and after surgery had the worst disease-free survival rates among all patient groups.Patients with normalized CEA levels after surgery had a significantly lower disease-free survival rate than those with normal perioperative levels,whereas patients with normalized CA19-9 levels after surgery had equivalent survival to those with normal perioperative levels.The prognostic impact of high CEA levels was observably smaller in patients who underwent adjuvant chemotherapy than in patients who underwent surgery alone,whereas that of high CA19-9 was greater in patients who underwent adjuvant chemotherapy.High postoperative CEA levels were significantly associated with an increased prevalence of liver,lung and bone recurrences,and high postoperative CA19-9 levels were significantly associated with increased frequencies of lymph node and liver recurrences.CONCLUSION The evaluation of serum CEA and CA 19-9 levels both before and after surgery provides useful information for precise risk stratification after curative gastrectomy.展开更多
North American lake cress, Rorippa aquatica (Eaton) EJ Palmer & Steyermark (Brassicaceae), is listed as an endangered or threatened species. Lake cress shows heterophyllic changes in leaf form in response to the s...North American lake cress, Rorippa aquatica (Eaton) EJ Palmer & Steyermark (Brassicaceae), is listed as an endangered or threatened species. Lake cress shows heterophyllic changes in leaf form in response to the surrounding environment. Therefore, this species has received considerable attention from ecological and morphological perspectives. However, its phylogenetic position and taxonomic status have long been a subject of debate. To analyze the phylogenetic relationship of lake cress, we investigated chloroplast DNA sequences from 17 plant species. The results of phylogenetic reconstruction performed using trnL intron, trnG (GCC)-trnM (CAU), and psbC-trnS (UGA) indicated that lake cress is a member of Rorippa. Moreover, we found that the chromosome number of lake cress is 2n = 30. This result indicated that lake cress might have originated from aneuploidy of triploid species or via intergeneric crossing. Taken together, our results suggest an affinity between lake cress and Rorippa at the molecular level, indicating that lake cress should be treated as Rorippa aquatica (Eaton) EJ Palmer & Steyermark.展开更多
Some large-conductance Ca^2＋ and voltage-activated K^＋（BK） channels are activated by membrane stretch. However, the mechanism of mechano-gating of the BK channels is still not well understood. Previous studies hav...Some large-conductance Ca^2＋ and voltage-activated K^＋（BK） channels are activated by membrane stretch. However, the mechanism of mechano-gating of the BK channels is still not well understood. Previous studies have led to the proposal that the linker-gating ring complex functions as a passive spring, transducing the force generated by intracellular Ca^2＋ to the gate to open the channel. This raises the question as to whether membrane stretch is also transmitted to the gate of mechanosensitive （MS） BK channels via the linker-gating complex. To study this, we changed the linker length in the stretch-activated BK channel （SAKCaC）, and examined the effect of membrane stretch on the gating of the resultant mutant channels. Shortening the linker increased, whereas extending the linker reduced, the channel mechanosensitivity both in the presence and in the absence of intracellular Ca^2＋. However, the voltage and Ca^2＋ sensitivities were not significantly altered by membrane stretch. Furthermore, the SAKCaC became less sensitive to membrane stretch at relatively high intracellular Ca^2＋ concentrations or membrane depolarization. These observations suggest that once the channel is in the open-state conformation, tension on the spring is partially released and membrane stretch is less effective. Our results are consistent with the idea that membrane stretch is transferred to the gate via the linker-gating ring complex of the MS BK channels.展开更多
We previously investigated the physiological effect of an ethanol extract of fermented soymilk on rats and clarified that this extract modulated their hepatic lipid metabolism. Although the soy isoflavones and oligope...We previously investigated the physiological effect of an ethanol extract of fermented soymilk on rats and clarified that this extract modulated their hepatic lipid metabolism. Although the soy isoflavones and oligopeptides are representative functional components of the ethanol extract, it remained unclear whether these substances share a role in lipid metabolism modulation. Therefore, we attempted to clarify the effects of isoflavones and oligopeptides in lactic acid-fermented soymilk on lipid metabolism-related gene expression in rats and HepG2 cells. The fermented soymilk extract had a higher isoflavone aglycone content than the soymilk extract. Sevenweek-old male Sprague-Dawley rats were fed an AIN-93G diet, a diet plus 70% soymilk ethanol extract, or a diet plus 70% fermented soymilk ethanol extract for 5 weeks. Although both the soymilk and fermented soymilk ethanol extracts did not significantly affect plasma and hepatic lipid profiles, the expression levels of the genes encoding CYP7a1 and SREBP-2 were significantly upregulated in the livers of rats fed with the fermented soymilk extract. Whereas isoflavone aglycones upregulated CYP7a1-encoding gene expression in HepG2, oligopeptides in soymilk and fermented soymilk downregulated this expression. Oligopeptides in fermented soymilk downregulated the expression stronger than that observed with soymilk. On the other hand, no significant change in FAS expression was observed in the livers of rats fed the fermented soymilk extract. Although isoflavone aglycones did not affect FAS expression in HepG2 cells, oligopeptides in fermented soymilk downregulated FAS expression. The downregulation of FAS with oligopeptides from fermented soymilk was stronger than that from soymilk. In the present animal experiment, the effect on reduction of fat synthesis was not found because of insufficient amount of peptides derived from digestion of soy protein. These results suggest that isoflavone aglycones increase CYP7a1 gene expression, whereas oligopeptides decrease FAS expression. Isoflavone glycosides and proteins in soymilk were converted to isoflavone aglycones and oligopeptides by lactic acid fermentation, respectively, and these functional components independently improved the lipid metabolism. In the present study, it was found that isoflavone aglycones and oligopeptides in fermented soymilk differentially regulate hepatic lipid metabolism-related gene expression. Therefore, the consumption of fermented soymilk containing isoflavone aglycones and soy oligopeptides might prevent dyslipidemia more effectively than that of any other soy food. Fermented soymilk is a superior functional food modulating lipid metabolism.展开更多
文摘Surface with well-defined components and structures possesses unique electronic,magnetic,optical and chemical properties.As a result,surface chemistry research plays a crucial role in various fields such as catalysis,energy,materials,quantum,and microelectronics.Surface science mainly investigates the correspondence between surface property and functionality.Scanning probe microscopy(SPM)techniques are important tools to characterize surface properties because of the capability of atomic-scale imaging,spectroscopy and manipulation at the single-atom level.In this review,we summarize recent advances in surface electronic,magnetic and optical properties characterized mainly by SPM-based methods.We focus on elucidating theπ-magnetism in graphene-based nanostructures,construction of spin qubits on surfaces,topology properties of surface organic structures,STM-based light emission,tip-enhanced Raman spectroscopy and integration of machine learning in SPM studies.
基金supported by the National Natural Science Foundation of China(Nos.22225202,92356309,22132007,21991132,22172002)。
文摘Surface chemistry focuses on the investigation of the adsorption,migration,assembly,activation,reaction,and desorption of atoms and molecules at surfaces.Surface chemistry plays the pivotal roles in both fundamental science and applied technology.This review will summarize the recent progresses on surface assembly,synthesis and catalysis investigated mainly by scanning tunneling microscopy and atomic force microscopy.Surface assemblies of water and small biomolecules,construction of Sierpin′ski triangles and surface chirality are summarized.On-surface synthesis of conjugated carbo-and heterocycles and other kinds of carbon nanostructures are surveyed.Surface model catalysis,including single-atom catalysis and electrochemical catalysis,are discussed at the single-atom level.
基金Supported by Grants from The National Institute for Physiological Sciences and Graduate University for Advanced Studies
文摘AIM:Danshen's capability to induce salivary fluid secretion and its mechanisms were studied to determine if it could improve xerostomia.METHODS:Submandibular glands were isolated from male Wistar rats under systemic anesthesia with pentobarbital sodium.The artery was cannulated and vascularly perfused at a constant rate.The excretory duct was also cannulated and the secreted saliva was weighed in a cup on an electronic balance.The weight of the accumulated saliva was measured every 3 s and the salivary flow rate was calculated.In addition,the arterio-venous difference in the partial oxygen pressure was measured as an indicator of oxygen consumption.In order to assess the mechanism involved in Dansheninduced fluid secretion,either ouabain(an inhibitor of Na+/K+ ATPase) or bumetanide(an inhibitor of NKCC1) was additionally applied during the Danshen stimulation.In order to examine the involvement of the main membrane receptors,atropine was added to block the M3 muscarinic receptors,or phentolamine was added to block the α1 adrenergic receptors.In order to examine the requirement for extracellular Ca2+,Danshen was applied during the perfusion with nominal Ca2+ free solution.RESULTS:Although Danshen induced salivary fluid secretion,88.7 ± 12.8 μL/g-min,n = 9,(the highest value around 20 min from start of DS perfusion was significantly high vs 32.5 ± 5.3 μL/g-min by carbamylcholine,P = 0.00093 by t-test) in the submandibular glands,the time course of that secretion differed from that induced by carbamylcholine.There was a latency associated with the fluid secretion induced by Danshen,followed by a gradual increasein the secretion to its highest value,which was in turn followed by a slow decline to a near zero level.The application of either ouabain or bumetanide inhibited the fluid secretion by 85% or 93%,and suppressed the oxygen consumption by 49% or 66%,respectively.These results indicated that Danshen activates Na+/K+ ATPase and NKCC1 to maintain Cl- release and K+ release for fluid secretion.Neither atropine or phentolamine inhibited the fluid secretion induced by Danshen(263% ± 63% vs 309% ± 45%,227% ± 63% vs 309% ± 45%,P = 0.899,0.626 > 0.05 respectively,by ANOVA).Accordingly,Danshen does not bind with M3 or α1 receptors.These characteristics suggested that the mechanism involved in DS-induced salivary fluid secretion could be different from that induced by carbamylcholine.Carbamylcholine activates the M3 receptor to release inositol trisphosphate(IP3) and quickly releases Ca2+ from the calcium stores.The elevation of [Ca2+]i induces chloride release and quick osmosis,resulting in an onset of fluid secretion.An increase in [Ca2+]i is essential for the activation of the luminal Cl- and basolateral K+ channels.The nominal removal of extracellular Ca2+ totally abolished the fluid secretion induced by Danshen(1.8 ± 0.8 μL/g-min vs 101.9 ± 17.2 μL/g-min,P = 0.00023 < 0.01,by t-test),suggesting the involvement of Ca2+ in the activation of these channels.Therefore,IP3-store Ca2+ release signalling may not be involved in the secretion induced by Danshen,but rather,there may be a distinct signalling process.CONCLUSION:The present findings suggest that Danshen can be used in the treatment of xerostomia,to avoid the systemic side effects associated with muscarinic drugs.
基金supported by the National Natural Science Foundation of China (31671119 and 31871090)the Shenzhen Science and Technology Innovation Commission (JCYJ20160428164440255, JCYJ20170413162938668, JCYJ20170818155056369, and JCYJ20170307170742519)+3 种基金the Shenzhen Discipline Construction Project for Neurobiology (DRCSM [2016]1379)the Japan Society for the Promotion of Science KAKENHI (JP18K08494) the Japan Science and Technology Agency PRESTO (JPMJPR1784)the Ono Medical Research Foundation, and the Novartis Foundation (Japan) for the Promotion of Science
文摘A central objective in deciphering the nervous system in health and disease is to define the connections of neurons. The propensity of neurotropic viruses to spread among synaptically-linked neurons makes them ideal for mapping neural circuits. So far, several classes of viral neuronal tracers have become available and provide a powerful toolbox for delineating neural networks. In this paper, we review the recent developments of neurotropic viral tracers and highlight their unique properties in revealing patterns of neuronal connections.
文摘AIM: To systematically review pathological changes of gastric mucosa in gastric atrophy (GA) and intestinal metaplasia (IM) after Helicobacter pylori (H. pylori) eradication.
基金Supported by National Natural Science Foundation of China, No. 30570665the Foundation of Dalian Technology Bureau, No. 2008E13SF182the Foundation of Key Laboratory of Education Department of Liaoning Province, No. 2009S005
文摘AIM: To investigate nicotinamide’s action on glucose metabolism, and the association between niacin consumption and obesity prevalence. METHODS: Dynamic nicotinamide’s effect on plasma hydrogen peroxide and glucose metabolism was in- vestigated using oral glucose tolerance tests with or without nicotinamide in the same five healthy subjects.Lag-regression analysis was used to examine the association between the niacin consumption and the obesity prevalence among US children using the data from the Economic Research Service of the US Department of Agriculture and from US Centers for Disease Control and Prevention, respectively. RESULTS: Compared with the control oral glucose tolerance test, the 1-h plasma hydrogen peroxide (1.4 ± 0.1 μmol/L vs 1.6 ± 0.1 μmol/L, P = 0.016) and insulin levels (247.1 ± 129.0 pmol/L vs 452.6 ± 181.8 pmol/L, P = 0.028) were signif icantly higher, and the 3-h blood glucose was signif icantly lower (5.8 ± 1.2 mmol/L vs 4.5 ± 1.1 mmol/L, P = 0.002) after coadministration of glucose and 300 mg nicotinamide. The obesity prevalence among American children increased with the increasing per capita niacin consumption, the increasing grain contribution to niacin due to niacin-fortification, and the increasing niacin-fortified ready-to-eat cereal consumption, with a 10-year lag. The regression analyses showed that the obesity prevalence in the US children of all age groups was determined by niacin consumption (R2 = 0.814, 0.961 and 0.94 for 2-5 years, 6-11 years and 12-19 years age groups, respectively). CONCLUSION: The appetite-stimulating effect of nicotinamide appears to involve oxidative stress. Excess niacin consumption may be a major factor in the increased obesity prevalence in US children.
基金Supported by Cooperation survey and research project of the Nippon Foundation of the Japan-China Medical Association (2006-12)the International cooperation project (BZ2006058) of Bureau of Science and Technology of Jiangsu Province,China
文摘AIM： TO determine whether Chinese herbs （CHs） relieve xerostomia （dry mouth） by increasing salivary secretion. METHODS： The submandibular glands of Wistar rats were surgically isolated and perfused arterially with buffered salt solution. After control perfusion, recording started 5 min prior to the start of stimulation. After fluid secretion was induced by 0.2 μmol/L carbamylcholine （CCh） in the perfusate for 10 min, Chinese herb （CH） was added in the perfusion for 5 min. CCh was then overloaded at 0.2 μmol/L in the perfusion for 20 min. The volume of salivary fluid secretion was recorded by a computer-controlled balance system. RESULTS： Saliva secretion formed an initial ephemeral peak at 30 s followed by a gradual increase to a sustained level. CH alone induced no or little saliva in all types of CH selected. During perfusion with CH,overloading of CCh promoted fluid secretion in 1S of 20 CHs. This promotion was classified into four patterns, which were eventually related to the categories of CH： Overall sustained phase was continuously raised （Yin-nourishing, fluid production-promoting and heatclearing agents）; The sustained secretion rose to reach a maximum then decreased （Qi-enhancing agent）; Sustained secretion rose to reach the highest maximum and was then sustained with a slight decline （swelling-reducing, phlegm-resolving and pus-expelling agents）; Stimulation of salivary secretion without any added stimulants. Addition of CCh raised the fluid secretion to reach the highest maximum then sharply decreased to a lower sustained level （blood activating agent）. CONCLUSION： The present findings lead to the conclusion that various CHs have different promotional effects directly on the salivary gland.
文摘Over the past few decades,food fortification and infant formula supplementation with high levels of vitamins have led to a sharp increase in vitamin intake among infants,children and adults.This is followed by a sharp increase in the prevalence of obesity and related diseases,with significant disparities among countries and different groups within a country.It has long been known that B vitamins at doses below their toxicity threshold strongly promote body fat gain.Studies have demonstrated that formulas,which have very high levels of vitamins,significantly promote infant weight gain,especially fat mass gain,a known risk factor for children developing obesity.Furthermore,ecological studies have shown that increased B vitamin consumption is strongly correlated with the prevalence of obesity and diabetes.We therefore hypothesize that excess vitamins may play a causal role in the increased prevalence of obesity.This review will discuss:(1)the causes of increased vitamin intake;(2)the non-monotonic effect of excess vitamin intake on weight and fat gain;and(3)the role of vitamin fortification in obesity disparities among countries and different groups within a country.
基金Supported by National Natural Science Foundation of China, No. 30570665the Foundation of Dalian Technology Bureau, No. 2008E13SF182the Foundation of Key Laboratory of Education Department of Liaoning Province,No. 2009S005
文摘AIM： To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS： Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N^1-methylnicotinamide on glucose metabolism, plasma HzO2 levels and tissue nicotinamide adenine dinucleotide （NAD） contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively. RESULTS： Diabetic subjects had significantly higher plasma N^1-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects （0.89 ± 0.13 μmol/L vs 0.6 ± 0.13 μmol/L, P 〈 0.001）. Cumulative doses of nicotinamide （2 g/kg） significantly increased rat plasma Nl-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by Nl-methy-Inicotinamide. Moreover, cumulative exposure to N^1- methylnicotinamide （2 g/kg） markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/ NADH ratio, and increased plasma H2O2 levels. Decrease in NAD/NADH ratio and increase in H2O2 generation were also observed in human erythrocytes after exposure to N^1-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide （5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load）. Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N^1- methylnicotinamide clearance. CONCLUSION： These findings suggest that nicotinamide overload, which induced an increase in plasma N^1- methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.
文摘We describe a 77-year-old man with refractory gastric ulcer that worsened after Helicobacter pylori eradication therapy.Pathology showed marked infiltration of IgG4-positive plasma cells in the gastric lesions,which led us to suspect IgG4-related sclerosing disease.To the best of our knowledge,this is the first report of IgG4-related gastric ulcer without the main manifestation of autoimmune pancreatitis.
基金Supported by Grants from the University of Toyama and JSPS KAKENHI to Mihara H,No.26870214
文摘AIM: To explore the expression of transient receptor potential vanilloid 4(TRPV4) and its physiological meaning in mouse and rat gastric epithelia. METHODS: RT-PCR and immunochemistry were used to detect TRPV4 m RNA and protein expression in mouse stomach and a rat normal gastric epithelial cell line(RGE1-01), while Ca2+-imaging and electrophysiology were used to evaluate TRPV4 channel activity. ATP release was measured by a luciferin-luciferase assay. Gastric emptying was also compared between WT and TRPV4 knockout mice. RESULTS: TRPV4 m RNA and protein were detected in mouse tissues and RGE1-01 cells. A TRPV4-specific agonist(GSK1016790A) increased intracellular Ca2+ concentrations and/or evoked TRPV4-like current activities in WT mouse gastric epithelial cells andRGE1-01 cells, but not TRPV4 KO cells. GSK1016790 A or mechanical stimuli induced ATP release from RGE1-01 cells while TRPV4 knockout mice displayed delayed gastric emptying in vivo. CONCLUSION: TRPV4 is expressed in mouse and rat gastric epithelium and contributes to ATP release and gastric emptying.
文摘In the present study, we aimed to evaluate the pathways contributing to ATP release from mouse astrocytes during hypoosmotic stress. We first examined the expression of mRNAs for proteins constituting possible ATP- releasing pathways that have been suggested over the past several years. In RT-PCR analysis using both control and osmotically swollen astrocytes, amplification of cDNA fragments of expected size was seen for connexins （Cx32, Cx37, Cx43）, pannexin 1 （Pxl）, the P2X7 receptor, MRP1 and MDR1, but not CFTR. Inhibitors of exocytotic vesicular release, gap junction hemi-channels, CFTR, MRP1, MDR1, the P2X7 receptor, and volume-sensitive outwardly rectifying chloride channels had no significant effects on the massive ATP release from astrocytes. In contrast, the hypotonicity-induced ATP release from astrocytes was most effectively inhibited by gadolinium （50 μM）, an inhibitor of the maxi-anion channel, which has recently been shown to serve as a pathway for ATP release from several other cell types. Thus, we propose that the maxi-anion channel constitutes a major pathway for swelling-induced ATP release from cultured mouse astrocytes as well.
文摘AIM To evaluate the prognostic significance of perioperative carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)levels in stageⅡ/Ⅲgastric cancer.METHODS From a multi-institutional retrospective database compiled by integrating clinical data from nine institutions,data of 998 patients who underwent curative resection for stageⅡ/Ⅲgastric cancer between 2010 and 2014 were retrieved and analyzed.The prognostic impact of the preoperative and postoperative levels and chronological changes in CEA,CA19-9 and their combination were evaluated.To test whether postoperative adjuvant chemotherapy alters the prognostic impact of perioperative CEA and CA19-9 levels,the hazard ratios for mortality were compared between patients who underwent surgery alone and patients who underwent surgery followed by adjuvant chemotherapy.RESULTS The prognostic impact of postoperative CEA and CA19-9 was superior to that of the preoperative levels.Multivariable analysis identified high postoperative CEA and CA19-9 levels as independent prognostic factors for overall survival.Disease-free survival rates clearly decreased in a stepwise manner in association with postoperative CEA and CA19-9 levels,and patients with high levels of both markers showed significantly poorer prognosis than other patient groups.When we analyzed perioperative changes in serum CEA and CA19-9 levels,patients with high levels before and after surgery had the worst disease-free survival rates among all patient groups.Patients with normalized CEA levels after surgery had a significantly lower disease-free survival rate than those with normal perioperative levels,whereas patients with normalized CA19-9 levels after surgery had equivalent survival to those with normal perioperative levels.The prognostic impact of high CEA levels was observably smaller in patients who underwent adjuvant chemotherapy than in patients who underwent surgery alone,whereas that of high CA19-9 was greater in patients who underwent adjuvant chemotherapy.High postoperative CEA levels were significantly associated with an increased prevalence of liver,lung and bone recurrences,and high postoperative CA19-9 levels were significantly associated with increased frequencies of lymph node and liver recurrences.CONCLUSION The evaluation of serum CEA and CA 19-9 levels both before and after surgery provides useful information for precise risk stratification after curative gastrectomy.
文摘North American lake cress, Rorippa aquatica (Eaton) EJ Palmer & Steyermark (Brassicaceae), is listed as an endangered or threatened species. Lake cress shows heterophyllic changes in leaf form in response to the surrounding environment. Therefore, this species has received considerable attention from ecological and morphological perspectives. However, its phylogenetic position and taxonomic status have long been a subject of debate. To analyze the phylogenetic relationship of lake cress, we investigated chloroplast DNA sequences from 17 plant species. The results of phylogenetic reconstruction performed using trnL intron, trnG (GCC)-trnM (CAU), and psbC-trnS (UGA) indicated that lake cress is a member of Rorippa. Moreover, we found that the chromosome number of lake cress is 2n = 30. This result indicated that lake cress might have originated from aneuploidy of triploid species or via intergeneric crossing. Taken together, our results suggest an affinity between lake cress and Rorippa at the molecular level, indicating that lake cress should be treated as Rorippa aquatica (Eaton) EJ Palmer & Steyermark.
基金Acknowledgments We thank Ms Mekie Takahashi, Ms Ritsuko Kanda （Nagaya University, Japan）, Dr Changliang Fu and Dr Shouqing Lu （Institute of Mechanics, Chinese Academy of Sciences） for technical assistance. This work was partly supported by research grants from the National Natural Science Foundation of China （10602031） and Grants-in-aid for Scientific Research on Priority Areas （#15086270 to M.S.） and Creative Research （# 16GS0308 to M.S.） from the Ministry of Education Science Sports and Culture, Japan.
文摘Some large-conductance Ca^2＋ and voltage-activated K^＋（BK） channels are activated by membrane stretch. However, the mechanism of mechano-gating of the BK channels is still not well understood. Previous studies have led to the proposal that the linker-gating ring complex functions as a passive spring, transducing the force generated by intracellular Ca^2＋ to the gate to open the channel. This raises the question as to whether membrane stretch is also transmitted to the gate of mechanosensitive （MS） BK channels via the linker-gating complex. To study this, we changed the linker length in the stretch-activated BK channel （SAKCaC）, and examined the effect of membrane stretch on the gating of the resultant mutant channels. Shortening the linker increased, whereas extending the linker reduced, the channel mechanosensitivity both in the presence and in the absence of intracellular Ca^2＋. However, the voltage and Ca^2＋ sensitivities were not significantly altered by membrane stretch. Furthermore, the SAKCaC became less sensitive to membrane stretch at relatively high intracellular Ca^2＋ concentrations or membrane depolarization. These observations suggest that once the channel is in the open-state conformation, tension on the spring is partially released and membrane stretch is less effective. Our results are consistent with the idea that membrane stretch is transferred to the gate via the linker-gating ring complex of the MS BK channels.
文摘We previously investigated the physiological effect of an ethanol extract of fermented soymilk on rats and clarified that this extract modulated their hepatic lipid metabolism. Although the soy isoflavones and oligopeptides are representative functional components of the ethanol extract, it remained unclear whether these substances share a role in lipid metabolism modulation. Therefore, we attempted to clarify the effects of isoflavones and oligopeptides in lactic acid-fermented soymilk on lipid metabolism-related gene expression in rats and HepG2 cells. The fermented soymilk extract had a higher isoflavone aglycone content than the soymilk extract. Sevenweek-old male Sprague-Dawley rats were fed an AIN-93G diet, a diet plus 70% soymilk ethanol extract, or a diet plus 70% fermented soymilk ethanol extract for 5 weeks. Although both the soymilk and fermented soymilk ethanol extracts did not significantly affect plasma and hepatic lipid profiles, the expression levels of the genes encoding CYP7a1 and SREBP-2 were significantly upregulated in the livers of rats fed with the fermented soymilk extract. Whereas isoflavone aglycones upregulated CYP7a1-encoding gene expression in HepG2, oligopeptides in soymilk and fermented soymilk downregulated this expression. Oligopeptides in fermented soymilk downregulated the expression stronger than that observed with soymilk. On the other hand, no significant change in FAS expression was observed in the livers of rats fed the fermented soymilk extract. Although isoflavone aglycones did not affect FAS expression in HepG2 cells, oligopeptides in fermented soymilk downregulated FAS expression. The downregulation of FAS with oligopeptides from fermented soymilk was stronger than that from soymilk. In the present animal experiment, the effect on reduction of fat synthesis was not found because of insufficient amount of peptides derived from digestion of soy protein. These results suggest that isoflavone aglycones increase CYP7a1 gene expression, whereas oligopeptides decrease FAS expression. Isoflavone glycosides and proteins in soymilk were converted to isoflavone aglycones and oligopeptides by lactic acid fermentation, respectively, and these functional components independently improved the lipid metabolism. In the present study, it was found that isoflavone aglycones and oligopeptides in fermented soymilk differentially regulate hepatic lipid metabolism-related gene expression. Therefore, the consumption of fermented soymilk containing isoflavone aglycones and soy oligopeptides might prevent dyslipidemia more effectively than that of any other soy food. Fermented soymilk is a superior functional food modulating lipid metabolism.
